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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

• An introductory paragraph that explains what your working topic and thesis is
• A forecast of key topics or texts that will appear in the review
• Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
• Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically Evaluate: Mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

• Summarize the key findings you have taken from the literature and emphasize their significance
• Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

• Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
• Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
• Qualitative versus quantitative research
• Empirical versus theoretical scholarship
• Divide the research by sociological, historical, or cultural sources
• Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

• It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
• Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
• Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
• Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

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• 04 December 2020
• Correction 09 December 2020

How to write a superb literature review

Andy Tay is a freelance writer based in Singapore.

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Literature reviews are important resources for scientists. They provide historical context for a field while offering opinions on its future trajectory. Creating them can provide inspiration for one’s own research, as well as some practice in writing. But few scientists are trained in how to write a review — or in what constitutes an excellent one. Even picking the appropriate software to use can be an involved decision (see ‘Tools and techniques’). So Nature asked editors and working scientists with well-cited reviews for their tips.

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Correction 09 December 2020 : An earlier version of the tables in this article included some incorrect details about the programs Zotero, Endnote and Manubot. These have now been corrected.

Hsing, I.-M., Xu, Y. & Zhao, W. Electroanalysis 19 , 755–768 (2007).

Article   Google Scholar  

Ledesma, H. A. et al. Nature Nanotechnol. 14 , 645–657 (2019).

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Brahlek, M., Koirala, N., Bansal, N. & Oh, S. Solid State Commun. 215–216 , 54–62 (2015).

Choi, Y. & Lee, S. Y. Nature Rev. Chem . https://doi.org/10.1038/s41570-020-00221-w (2020).

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• What is a Literature Review? | Guide, Template, & Examples

What is a Literature Review? | Guide, Template, & Examples

Published on 22 February 2022 by Shona McCombes . Revised on 7 June 2022.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research.

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarise sources – it analyses, synthesises, and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

Why write a literature review, examples of literature reviews, step 1: search for relevant literature, step 2: evaluate and select sources, step 3: identify themes, debates and gaps, step 4: outline your literature review’s structure, step 5: write your literature review, frequently asked questions about literature reviews, introduction.

• Quick Run-through
• Step 1 & 2

When you write a dissertation or thesis, you will have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and scholarly context
• Develop a theoretical framework and methodology for your research
• Position yourself in relation to other researchers and theorists
• Show how your dissertation addresses a gap or contributes to a debate

You might also have to write a literature review as a stand-alone assignment. In this case, the purpose is to evaluate the current state of research and demonstrate your knowledge of scholarly debates around a topic.

The content will look slightly different in each case, but the process of conducting a literature review follows the same steps. We’ve written a step-by-step guide that you can follow below.

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Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research objectives and questions .

If you are writing a literature review as a stand-alone assignment, you will have to choose a focus and develop a central question to direct your search. Unlike a dissertation research question, this question has to be answerable without collecting original data. You should be able to answer it based only on a review of existing publications.

Make a list of keywords

Start by creating a list of keywords related to your research topic. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list if you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can use boolean operators to help narrow down your search:

Read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

To identify the most important publications on your topic, take note of recurring citations. If the same authors, books or articles keep appearing in your reading, make sure to seek them out.

You probably won’t be able to read absolutely everything that has been written on the topic – you’ll have to evaluate which sources are most relevant to your questions.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models and methods? Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• How does the publication contribute to your understanding of the topic? What are its key insights and arguments?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible, and make sure you read any landmark studies and major theories in your field of research.

You can find out how many times an article has been cited on Google Scholar – a high citation count means the article has been influential in the field, and should certainly be included in your literature review.

The scope of your review will depend on your topic and discipline: in the sciences you usually only review recent literature, but in the humanities you might take a long historical perspective (for example, to trace how a concept has changed in meaning over time).

Remember that you can use our template to summarise and evaluate sources you’re thinking about using!

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It’s important to keep track of your sources with references to avoid plagiarism . It can be helpful to make an annotated bibliography, where you compile full reference information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

You can use our free APA Reference Generator for quick, correct, consistent citations.

To begin organising your literature review’s argument and structure, you need to understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly-visual platforms like Instagram and Snapchat – this is a gap that you could address in your own research.

There are various approaches to organising the body of a literature review. You should have a rough idea of your strategy before you start writing.

Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarising sources in order.

Try to analyse patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organise your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text, your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

If you are writing the literature review as part of your dissertation or thesis, reiterate your central problem or research question and give a brief summary of the scholarly context. You can emphasise the timeliness of the topic (“many recent studies have focused on the problem of x”) or highlight a gap in the literature (“while there has been much research on x, few researchers have taken y into consideration”).

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, make sure to follow these tips:

• Summarise and synthesise: give an overview of the main points of each source and combine them into a coherent whole.
• Analyse and interpret: don’t just paraphrase other researchers – add your own interpretations, discussing the significance of findings in relation to the literature as a whole.
• Critically evaluate: mention the strengths and weaknesses of your sources.
• Write in well-structured paragraphs: use transitions and topic sentences to draw connections, comparisons and contrasts.

In the conclusion, you should summarise the key findings you have taken from the literature and emphasise their significance.

If the literature review is part of your dissertation or thesis, reiterate how your research addresses gaps and contributes new knowledge, or discuss how you have drawn on existing theories and methods to build a framework for your research. This can lead directly into your methodology section.

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a dissertation , thesis, research paper , or proposal .

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarise yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your  dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the ‘Cite this Scribbr article’ button to automatically add the citation to our free Reference Generator.

McCombes, S. (2022, June 07). What is a Literature Review? | Guide, Template, & Examples. Scribbr. Retrieved 14 May 2024, from https://www.scribbr.co.uk/thesis-dissertation/literature-review/

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Literature Reviews

• What is a literature review?
• Steps in the Literature Review Process
• Define your research question
• Determine inclusion and exclusion criteria
• Choose databases and search
• Review Results
• Synthesize Results
• Analyze Results
• Librarian Support

What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

• Provide a comprehensive and updated review of the literature;
• Explain why this review has taken place;
• Articulate a position or hypothesis;
• Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

• Demonstrate how a study fills a gap in research
• Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

• Organizes or describes a topic
• Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

• It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
• It may be too focused. Some niche studies may miss the bigger picture.
• It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
• It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

Meryl Brodsky : Communication and Information Studies

Hannah Chapman Tripp : Biology, Neuroscience

Carolyn Cunningham : Human Development & Family Sciences, Psychology, Sociology

Larayne Dallas : Engineering

Janelle Hedstrom : Special Education, Curriculum & Instruction, Ed Leadership & Policy ​

Susan Macicak : Linguistics

Imelda Vetter : Dell Medical School

For help in other subject areas, please see the guide to library specialists by subject .

Periodically, UT Libraries runs a workshop covering the basics and library support for literature reviews. While we try to offer these once per academic year, we find providing the recording to be helpful to community members who have missed the session. Following is the most recent recording of the workshop, Conducting a Literature Review. To view the recording, a UT login is required.

• October 26, 2022 recording
• Last Updated: Oct 26, 2022 2:49 PM
• URL: https://guides.lib.utexas.edu/literaturereviews

• UConn Library
• Literature Review: The What, Why and How-to Guide
• Introduction

Literature Review: The What, Why and How-to Guide — Introduction

• Getting Started
• How to Pick a Topic
• Strategies to Find Sources
• Evaluating Sources & Lit. Reviews
• Tips for Writing Literature Reviews
• Writing Literature Review: Useful Sites
• Citation Resources
• Other Academic Writings

What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

• To develop a theory or evaluate an existing theory
• To summarize the historical or existing state of a research topic
• Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

• A research paper assigned in a course
• A thesis or dissertation
• A grant proposal
• An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

• Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

• Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

• Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

• Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

• UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
• << Previous: Getting Started
• Next: How to Pick a Topic >>
• Last Updated: Sep 21, 2022 2:16 PM
• URL: https://guides.lib.uconn.edu/literaturereview

Libraries | Research Guides

Literature reviews, what is a literature review, learning more about how to do a literature review.

• Planning the Review
• The Research Question
• Choosing Where to Search
• Organizing the Review
• Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

• Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

• Next: Planning the Review >>
• Last Updated: May 2, 2024 10:39 AM
• URL: https://libguides.northwestern.edu/literaturereviews

How to Write a Literature Review

What is a literature review.

• What Is the Literature
• Writing the Review

A literature review is much more than an annotated bibliography or a list of separate reviews of articles and books. It is a critical, analytical summary and synthesis of the current knowledge of a topic. Thus it should compare and relate different theories, findings, etc, rather than just summarize them individually. In addition, it should have a particular focus or theme to organize the review. It does not have to be an exhaustive account of everything published on the topic, but it should discuss all the significant academic literature and other relevant sources important for that focus.

This is meant to be a general guide to writing a literature review: ways to structure one, what to include, how it supplements other research. For more specific help on writing a review, and especially for help on finding the literature to review, sign up for a Personal Research Session .

The specific organization of a literature review depends on the type and purpose of the review, as well as on the specific field or topic being reviewed. But in general, it is a relatively brief but thorough exploration of past and current work on a topic. Rather than a chronological listing of previous work, though, literature reviews are usually organized thematically, such as different theoretical approaches, methodologies, or specific issues or concepts involved in the topic. A thematic organization makes it much easier to examine contrasting perspectives, theoretical approaches, methodologies, findings, etc, and to analyze the strengths and weaknesses of, and point out any gaps in, previous research. And this is the heart of what a literature review is about. A literature review may offer new interpretations, theoretical approaches, or other ideas; if it is part of a research proposal or report it should demonstrate the relationship of the proposed or reported research to others' work; but whatever else it does, it must provide a critical overview of the current state of research efforts. 

Literature reviews are common and very important in the sciences and social sciences. They are less common and have a less important role in the humanities, but they do have a place, especially stand-alone reviews.

Types of Literature Reviews

There are different types of literature reviews, and different purposes for writing a review, but the most common are:

• Stand-alone literature review articles . These provide an overview and analysis of the current state of research on a topic or question. The goal is to evaluate and compare previous research on a topic to provide an analysis of what is currently known, and also to reveal controversies, weaknesses, and gaps in current work, thus pointing to directions for future research. You can find examples published in any number of academic journals, but there is a series of Annual Reviews of *Subject* which are specifically devoted to literature review articles. Writing a stand-alone review is often an effective way to get a good handle on a topic and to develop ideas for your own research program. For example, contrasting theoretical approaches or conflicting interpretations of findings can be the basis of your research project: can you find evidence supporting one interpretation against another, or can you propose an alternative interpretation that overcomes their limitations?
• Part of a research proposal . This could be a proposal for a PhD dissertation, a senior thesis, or a class project. It could also be a submission for a grant. The literature review, by pointing out the current issues and questions concerning a topic, is a crucial part of demonstrating how your proposed research will contribute to the field, and thus of convincing your thesis committee to allow you to pursue the topic of your interest or a funding agency to pay for your research efforts.
• Part of a research report . When you finish your research and write your thesis or paper to present your findings, it should include a literature review to provide the context to which your work is a contribution. Your report, in addition to detailing the methods, results, etc. of your research, should show how your work relates to others' work.

A literature review for a research report is often a revision of the review for a research proposal, which can be a revision of a stand-alone review. Each revision should be a fairly extensive revision. With the increased knowledge of and experience in the topic as you proceed, your understanding of the topic will increase. Thus, you will be in a better position to analyze and critique the literature. In addition, your focus will change as you proceed in your research. Some areas of the literature you initially reviewed will be marginal or irrelevant for your eventual research, and you will need to explore other areas more thoroughly. 

Examples of Literature Reviews

See the series of Annual Reviews of *Subject* which are specifically devoted to literature review articles to find many examples of stand-alone literature reviews in the biomedical, physical, and social sciences. 

Research report articles vary in how they are organized, but a common general structure is to have sections such as:

• Abstract - Brief summary of the contents of the article
• Introduction - A explanation of the purpose of the study, a statement of the research question(s) the study intends to address
• Literature review - A critical assessment of the work done so far on this topic, to show how the current study relates to what has already been done
• Methods - How the study was carried out (e.g. instruments or equipment, procedures, methods to gather and analyze data)
• Results - What was found in the course of the study
• Discussion - What do the results mean
• Conclusion - State the conclusions and implications of the results, and discuss how it relates to the work reviewed in the literature review; also, point to directions for further work in the area

Here are some articles that illustrate variations on this theme. There is no need to read the entire articles (unless the contents interest you); just quickly browse through to see the sections, and see how each section is introduced and what is contained in them.

The Determinants of Undergraduate Grade Point Average: The Relative Importance of Family Background, High School Resources, and Peer Group Effects , in The Journal of Human Resources , v. 34 no. 2 (Spring 1999), p. 268-293.

This article has a standard breakdown of sections:

• Introduction
• Literature Review
• Some discussion sections

First Encounters of the Bureaucratic Kind: Early Freshman Experiences with a Campus Bureaucracy , in The Journal of Higher Education , v. 67 no. 6 (Nov-Dec 1996), p. 660-691.

This one does not have a section specifically labeled as a "literature review" or "review of the literature," but the first few sections cite a long list of other sources discussing previous research in the area before the authors present their own study they are reporting.

• Next: What Is the Literature >>
• Last Updated: Jan 11, 2024 9:48 AM
• URL: https://libguides.wesleyan.edu/litreview

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What is a Literature Review? How to Write It (with Examples)

A literature review is a critical analysis and synthesis of existing research on a particular topic. It provides an overview of the current state of knowledge, identifies gaps, and highlights key findings in the literature. 1 The purpose of a literature review is to situate your own research within the context of existing scholarship, demonstrating your understanding of the topic and showing how your work contributes to the ongoing conversation in the field. Learning how to write a literature review is a critical tool for successful research. Your ability to summarize and synthesize prior research pertaining to a certain topic demonstrates your grasp on the topic of study, and assists in the learning process. 

Table of Contents

• What is the purpose of literature review? 
• a. Habitat Loss and Species Extinction: 
• b. Range Shifts and Phenological Changes: 
• c. Ocean Acidification and Coral Reefs: 
• d. Adaptive Strategies and Conservation Efforts: 

How to write a good literature review 

• Choose a Topic and Define the Research Question: 
• Decide on the Scope of Your Review: 
• Select Databases for Searches: 
• Conduct Searches and Keep Track: 
• Review the Literature: 
• Organize and Write Your Literature Review: 
• How to write a literature review faster with Paperpal? 
• Frequently asked questions 

What is a literature review?

A well-conducted literature review demonstrates the researcher’s familiarity with the existing literature, establishes the context for their own research, and contributes to scholarly conversations on the topic. One of the purposes of a literature review is also to help researchers avoid duplicating previous work and ensure that their research is informed by and builds upon the existing body of knowledge.

What is the purpose of literature review?

A literature review serves several important purposes within academic and research contexts. Here are some key objectives and functions of a literature review: 2  

1. Contextualizing the Research Problem: The literature review provides a background and context for the research problem under investigation. It helps to situate the study within the existing body of knowledge. 

2. Identifying Gaps in Knowledge: By identifying gaps, contradictions, or areas requiring further research, the researcher can shape the research question and justify the significance of the study. This is crucial for ensuring that the new research contributes something novel to the field. 

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3. Understanding Theoretical and Conceptual Frameworks: Literature reviews help researchers gain an understanding of the theoretical and conceptual frameworks used in previous studies. This aids in the development of a theoretical framework for the current research. 

4. Providing Methodological Insights: Another purpose of literature reviews is that it allows researchers to learn about the methodologies employed in previous studies. This can help in choosing appropriate research methods for the current study and avoiding pitfalls that others may have encountered. 

5. Establishing Credibility: A well-conducted literature review demonstrates the researcher’s familiarity with existing scholarship, establishing their credibility and expertise in the field. It also helps in building a solid foundation for the new research. 

6. Informing Hypotheses or Research Questions: The literature review guides the formulation of hypotheses or research questions by highlighting relevant findings and areas of uncertainty in existing literature. 

Literature review example

Let’s delve deeper with a literature review example: Let’s say your literature review is about the impact of climate change on biodiversity. You might format your literature review into sections such as the effects of climate change on habitat loss and species extinction, phenological changes, and marine biodiversity. Each section would then summarize and analyze relevant studies in those areas, highlighting key findings and identifying gaps in the research. The review would conclude by emphasizing the need for further research on specific aspects of the relationship between climate change and biodiversity. The following literature review template provides a glimpse into the recommended literature review structure and content, demonstrating how research findings are organized around specific themes within a broader topic. 

Literature Review on Climate Change Impacts on Biodiversity:

Climate change is a global phenomenon with far-reaching consequences, including significant impacts on biodiversity. This literature review synthesizes key findings from various studies: 

a. Habitat Loss and Species Extinction:

Climate change-induced alterations in temperature and precipitation patterns contribute to habitat loss, affecting numerous species (Thomas et al., 2004). The review discusses how these changes increase the risk of extinction, particularly for species with specific habitat requirements. 

b. Range Shifts and Phenological Changes:

Observations of range shifts and changes in the timing of biological events (phenology) are documented in response to changing climatic conditions (Parmesan & Yohe, 2003). These shifts affect ecosystems and may lead to mismatches between species and their resources. 

c. Ocean Acidification and Coral Reefs:

The review explores the impact of climate change on marine biodiversity, emphasizing ocean acidification’s threat to coral reefs (Hoegh-Guldberg et al., 2007). Changes in pH levels negatively affect coral calcification, disrupting the delicate balance of marine ecosystems. 

d. Adaptive Strategies and Conservation Efforts:

Recognizing the urgency of the situation, the literature review discusses various adaptive strategies adopted by species and conservation efforts aimed at mitigating the impacts of climate change on biodiversity (Hannah et al., 2007). It emphasizes the importance of interdisciplinary approaches for effective conservation planning. 

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Writing a literature review involves summarizing and synthesizing existing research on a particular topic. A good literature review format should include the following elements. 

Introduction: The introduction sets the stage for your literature review, providing context and introducing the main focus of your review. 

• Opening Statement: Begin with a general statement about the broader topic and its significance in the field. 
• Scope and Purpose: Clearly define the scope of your literature review. Explain the specific research question or objective you aim to address. 
• Organizational Framework: Briefly outline the structure of your literature review, indicating how you will categorize and discuss the existing research. 
• Significance of the Study: Highlight why your literature review is important and how it contributes to the understanding of the chosen topic. 
• Thesis Statement: Conclude the introduction with a concise thesis statement that outlines the main argument or perspective you will develop in the body of the literature review. 

Body: The body of the literature review is where you provide a comprehensive analysis of existing literature, grouping studies based on themes, methodologies, or other relevant criteria. 

• Organize by Theme or Concept: Group studies that share common themes, concepts, or methodologies. Discuss each theme or concept in detail, summarizing key findings and identifying gaps or areas of disagreement. 
• Critical Analysis: Evaluate the strengths and weaknesses of each study. Discuss the methodologies used, the quality of evidence, and the overall contribution of each work to the understanding of the topic. 
• Synthesis of Findings: Synthesize the information from different studies to highlight trends, patterns, or areas of consensus in the literature. 
• Identification of Gaps: Discuss any gaps or limitations in the existing research and explain how your review contributes to filling these gaps. 
• Transition between Sections: Provide smooth transitions between different themes or concepts to maintain the flow of your literature review. 

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Conclusion: The conclusion of your literature review should summarize the main findings, highlight the contributions of the review, and suggest avenues for future research. 

• Summary of Key Findings: Recap the main findings from the literature and restate how they contribute to your research question or objective. 
• Contributions to the Field: Discuss the overall contribution of your literature review to the existing knowledge in the field. 
• Implications and Applications: Explore the practical implications of the findings and suggest how they might impact future research or practice. 
• Recommendations for Future Research: Identify areas that require further investigation and propose potential directions for future research in the field. 
• Final Thoughts: Conclude with a final reflection on the importance of your literature review and its relevance to the broader academic community. 

Conducting a literature review

Conducting a literature review is an essential step in research that involves reviewing and analyzing existing literature on a specific topic. It’s important to know how to do a literature review effectively, so here are the steps to follow: 1  

Choose a Topic and Define the Research Question:

• Select a topic that is relevant to your field of study. 
• Clearly define your research question or objective. Determine what specific aspect of the topic do you want to explore? 

Decide on the Scope of Your Review:

• Determine the timeframe for your literature review. Are you focusing on recent developments, or do you want a historical overview? 
• Consider the geographical scope. Is your review global, or are you focusing on a specific region? 
• Define the inclusion and exclusion criteria. What types of sources will you include? Are there specific types of studies or publications you will exclude? 

Select Databases for Searches:

• Identify relevant databases for your field. Examples include PubMed, IEEE Xplore, Scopus, Web of Science, and Google Scholar. 
• Consider searching in library catalogs, institutional repositories, and specialized databases related to your topic. 

Conduct Searches and Keep Track:

• Develop a systematic search strategy using keywords, Boolean operators (AND, OR, NOT), and other search techniques. 
• Record and document your search strategy for transparency and replicability. 
• Keep track of the articles, including publication details, abstracts, and links. Use citation management tools like EndNote, Zotero, or Mendeley to organize your references. 

Review the Literature:

• Evaluate the relevance and quality of each source. Consider the methodology, sample size, and results of studies. 
• Organize the literature by themes or key concepts. Identify patterns, trends, and gaps in the existing research. 
• Summarize key findings and arguments from each source. Compare and contrast different perspectives. 
• Identify areas where there is a consensus in the literature and where there are conflicting opinions. 
• Provide critical analysis and synthesis of the literature. What are the strengths and weaknesses of existing research? 

Organize and Write Your Literature Review:

• Literature review outline should be based on themes, chronological order, or methodological approaches. 
• Write a clear and coherent narrative that synthesizes the information gathered. 
• Use proper citations for each source and ensure consistency in your citation style (APA, MLA, Chicago, etc.). 
• Conclude your literature review by summarizing key findings, identifying gaps, and suggesting areas for future research. 

Whether you’re exploring a new research field or finding new angles to develop an existing topic, sifting through hundreds of papers can take more time than you have to spare. But what if you could find science-backed insights with verified citations in seconds? That’s the power of Paperpal’s new Research feature!  

How to write a literature review faster with Paperpal?

Paperpal, an AI writing assistant, integrates powerful academic search capabilities within its writing platform. With the Research feature, you get 100% factual insights, with citations backed by 250M+ verified research articles, directly within your writing interface with the option to save relevant references in your Citation Library. By eliminating the need to switch tabs to find answers to all your research questions, Paperpal saves time and helps you stay focused on your writing.   

Here’s how to use the Research feature:  

• Ask a question: Get started with a new document on paperpal.com. Click on the “Research” feature and type your question in plain English. Paperpal will scour over 250 million research articles, including conference papers and preprints, to provide you with accurate insights and citations. 
• Review and Save: Paperpal summarizes the information, while citing sources and listing relevant reads. You can quickly scan the results to identify relevant references and save these directly to your built-in citations library for later access. 
• Cite with Confidence: Paperpal makes it easy to incorporate relevant citations and references into your writing, ensuring your arguments are well-supported by credible sources. This translates to a polished, well-researched literature review. 

The literature review sample and detailed advice on writing and conducting a review will help you produce a well-structured report. But remember that a good literature review is an ongoing process, and it may be necessary to revisit and update it as your research progresses. By combining effortless research with an easy citation process, Paperpal Research streamlines the literature review process and empowers you to write faster and with more confidence. Try Paperpal Research now and see for yourself.  

Frequently asked questions

A literature review is a critical and comprehensive analysis of existing literature (published and unpublished works) on a specific topic or research question and provides a synthesis of the current state of knowledge in a particular field. A well-conducted literature review is crucial for researchers to build upon existing knowledge, avoid duplication of efforts, and contribute to the advancement of their field. It also helps researchers situate their work within a broader context and facilitates the development of a sound theoretical and conceptual framework for their studies.

Literature review is a crucial component of research writing, providing a solid background for a research paper’s investigation. The aim is to keep professionals up to date by providing an understanding of ongoing developments within a specific field, including research methods, and experimental techniques used in that field, and present that knowledge in the form of a written report. Also, the depth and breadth of the literature review emphasizes the credibility of the scholar in his or her field.  

Before writing a literature review, it’s essential to undertake several preparatory steps to ensure that your review is well-researched, organized, and focused. This includes choosing a topic of general interest to you and doing exploratory research on that topic, writing an annotated bibliography, and noting major points, especially those that relate to the position you have taken on the topic. 

Literature reviews and academic research papers are essential components of scholarly work but serve different purposes within the academic realm. 3 A literature review aims to provide a foundation for understanding the current state of research on a particular topic, identify gaps or controversies, and lay the groundwork for future research. Therefore, it draws heavily from existing academic sources, including books, journal articles, and other scholarly publications. In contrast, an academic research paper aims to present new knowledge, contribute to the academic discourse, and advance the understanding of a specific research question. Therefore, it involves a mix of existing literature (in the introduction and literature review sections) and original data or findings obtained through research methods. 

Literature reviews are essential components of academic and research papers, and various strategies can be employed to conduct them effectively. If you want to know how to write a literature review for a research paper, here are four common approaches that are often used by researchers.  Chronological Review: This strategy involves organizing the literature based on the chronological order of publication. It helps to trace the development of a topic over time, showing how ideas, theories, and research have evolved.  Thematic Review: Thematic reviews focus on identifying and analyzing themes or topics that cut across different studies. Instead of organizing the literature chronologically, it is grouped by key themes or concepts, allowing for a comprehensive exploration of various aspects of the topic.  Methodological Review: This strategy involves organizing the literature based on the research methods employed in different studies. It helps to highlight the strengths and weaknesses of various methodologies and allows the reader to evaluate the reliability and validity of the research findings.  Theoretical Review: A theoretical review examines the literature based on the theoretical frameworks used in different studies. This approach helps to identify the key theories that have been applied to the topic and assess their contributions to the understanding of the subject.  It’s important to note that these strategies are not mutually exclusive, and a literature review may combine elements of more than one approach. The choice of strategy depends on the research question, the nature of the literature available, and the goals of the review. Additionally, other strategies, such as integrative reviews or systematic reviews, may be employed depending on the specific requirements of the research.

The literature review format can vary depending on the specific publication guidelines. However, there are some common elements and structures that are often followed. Here is a general guideline for the format of a literature review:  Introduction:   Provide an overview of the topic.  Define the scope and purpose of the literature review.  State the research question or objective.  Body:   Organize the literature by themes, concepts, or chronology.  Critically analyze and evaluate each source.  Discuss the strengths and weaknesses of the studies.  Highlight any methodological limitations or biases.  Identify patterns, connections, or contradictions in the existing research.  Conclusion:   Summarize the key points discussed in the literature review.  Highlight the research gap.  Address the research question or objective stated in the introduction.  Highlight the contributions of the review and suggest directions for future research.

Both annotated bibliographies and literature reviews involve the examination of scholarly sources. While annotated bibliographies focus on individual sources with brief annotations, literature reviews provide a more in-depth, integrated, and comprehensive analysis of existing literature on a specific topic. The key differences are as follows: 

References 

• Denney, A. S., & Tewksbury, R. (2013). How to write a literature review.  Journal of criminal justice education ,  24 (2), 218-234. 
• Pan, M. L. (2016).  Preparing literature reviews: Qualitative and quantitative approaches . Taylor & Francis. 
• Cantero, C. (2019). How to write a literature review.  San José State University Writing Center . 

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How To Write An A-Grade Literature Review

3 straightforward steps (with examples) + free template.

By: Derek Jansen (MBA) | Expert Reviewed By: Dr. Eunice Rautenbach | October 2019

Quality research is about building onto the existing work of others , “standing on the shoulders of giants”, as Newton put it. The literature review chapter of your dissertation, thesis or research project is where you synthesise this prior work and lay the theoretical foundation for your own research.

Long story short, this chapter is a pretty big deal, which is why you want to make sure you get it right . In this post, I’ll show you exactly how to write a literature review in three straightforward steps, so you can conquer this vital chapter (the smart way).

Overview: The Literature Review Process

• Understanding the “ why “
• Finding the relevant literature
• Cataloguing and synthesising the information
• Outlining & writing up your literature review
• Example of a literature review

But first, the “why”…

Before we unpack how to write the literature review chapter, we’ve got to look at the why . To put it bluntly, if you don’t understand the function and purpose of the literature review process, there’s no way you can pull it off well. So, what exactly is the purpose of the literature review?

Well, there are (at least) four core functions:

• For you to gain an understanding (and demonstrate this understanding) of where the research is at currently, what the key arguments and disagreements are.
• For you to identify the gap(s) in the literature and then use this as justification for your own research topic.
• To help you build a conceptual framework for empirical testing (if applicable to your research topic).
• To inform your methodological choices and help you source tried and tested questionnaires (for interviews ) and measurement instruments (for surveys ).

Most students understand the first point but don’t give any thought to the rest. To get the most from the literature review process, you must keep all four points front of mind as you review the literature (more on this shortly), or you’ll land up with a wonky foundation.

Okay – with the why out the way, let’s move on to the how . As mentioned above, writing your literature review is a process, which I’ll break down into three steps:

• Finding the most suitable literature
• Understanding , distilling and organising the literature
• Planning and writing up your literature review chapter

Importantly, you must complete steps one and two before you start writing up your chapter. I know it’s very tempting, but don’t try to kill two birds with one stone and write as you read. You’ll invariably end up wasting huge amounts of time re-writing and re-shaping, or you’ll just land up with a disjointed, hard-to-digest mess . Instead, you need to read first and distil the information, then plan and execute the writing.

Step 1: Find the relevant literature

Naturally, the first step in the literature review journey is to hunt down the existing research that’s relevant to your topic. While you probably already have a decent base of this from your research proposal , you need to expand on this substantially in the dissertation or thesis itself.

Essentially, you need to be looking for any existing literature that potentially helps you answer your research question (or develop it, if that’s not yet pinned down). There are numerous ways to find relevant literature, but I’ll cover my top four tactics here. I’d suggest combining all four methods to ensure that nothing slips past you:

Method 1 – Google Scholar Scrubbing

Google’s academic search engine, Google Scholar , is a great starting point as it provides a good high-level view of the relevant journal articles for whatever keyword you throw at it. Most valuably, it tells you how many times each article has been cited, which gives you an idea of how credible (or at least, popular) it is. Some articles will be free to access, while others will require an account, which brings us to the next method.

Method 2 – University Database Scrounging

Generally, universities provide students with access to an online library, which provides access to many (but not all) of the major journals.

So, if you find an article using Google Scholar that requires paid access (which is quite likely), search for that article in your university’s database – if it’s listed there, you’ll have access. Note that, generally, the search engine capabilities of these databases are poor, so make sure you search for the exact article name, or you might not find it.

Method 3 – Journal Article Snowballing

At the end of every academic journal article, you’ll find a list of references. As with any academic writing, these references are the building blocks of the article, so if the article is relevant to your topic, there’s a good chance a portion of the referenced works will be too. Do a quick scan of the titles and see what seems relevant, then search for the relevant ones in your university’s database.

Method 4 – Dissertation Scavenging

Similar to Method 3 above, you can leverage other students’ dissertations. All you have to do is skim through literature review chapters of existing dissertations related to your topic and you’ll find a gold mine of potential literature. Usually, your university will provide you with access to previous students’ dissertations, but you can also find a much larger selection in the following databases:

• Open Access Theses & Dissertations
• Stanford SearchWorks

Keep in mind that dissertations and theses are not as academically sound as published, peer-reviewed journal articles (because they’re written by students, not professionals), so be sure to check the credibility of any sources you find using this method. You can do this by assessing the citation count of any given article in Google Scholar. If you need help with assessing the credibility of any article, or with finding relevant research in general, you can chat with one of our Research Specialists .

Alright – with a good base of literature firmly under your belt, it’s time to move onto the next step.

Need a helping hand?

Step 2: Log, catalogue and synthesise

Once you’ve built a little treasure trove of articles, it’s time to get reading and start digesting the information – what does it all mean?

While I present steps one and two (hunting and digesting) as sequential, in reality, it’s more of a back-and-forth tango – you’ll read a little , then have an idea, spot a new citation, or a new potential variable, and then go back to searching for articles. This is perfectly natural – through the reading process, your thoughts will develop , new avenues might crop up, and directional adjustments might arise. This is, after all, one of the main purposes of the literature review process (i.e. to familiarise yourself with the current state of research in your field).

As you’re working through your treasure chest, it’s essential that you simultaneously start organising the information. There are three aspects to this:

• Logging reference information
• Building an organised catalogue
• Distilling and synthesising the information

I’ll discuss each of these below:

2.1 – Log the reference information

As you read each article, you should add it to your reference management software. I usually recommend Mendeley for this purpose (see the Mendeley 101 video below), but you can use whichever software you’re comfortable with. Most importantly, make sure you load EVERY article you read into your reference manager, even if it doesn’t seem very relevant at the time.

2.2 – Build an organised catalogue

In the beginning, you might feel confident that you can remember who said what, where, and what their main arguments were. Trust me, you won’t. If you do a thorough review of the relevant literature (as you must!), you’re going to read many, many articles, and it’s simply impossible to remember who said what, when, and in what context . Also, without the bird’s eye view that a catalogue provides, you’ll miss connections between various articles, and have no view of how the research developed over time. Simply put, it’s essential to build your own catalogue of the literature.

I would suggest using Excel to build your catalogue, as it allows you to run filters, colour code and sort – all very useful when your list grows large (which it will). How you lay your spreadsheet out is up to you, but I’d suggest you have the following columns (at minimum):

• Author, date, title – Start with three columns containing this core information. This will make it easy for you to search for titles with certain words, order research by date, or group by author.
• Categories or keywords – You can either create multiple columns, one for each category/theme and then tick the relevant categories, or you can have one column with keywords.
• Key arguments/points – Use this column to succinctly convey the essence of the article, the key arguments and implications thereof for your research.
• Context – Note the socioeconomic context in which the research was undertaken. For example, US-based, respondents aged 25-35, lower- income, etc. This will be useful for making an argument about gaps in the research.
• Methodology – Note which methodology was used and why. Also, note any issues you feel arise due to the methodology. Again, you can use this to make an argument about gaps in the research.
• Quotations – Note down any quoteworthy lines you feel might be useful later.
• Notes – Make notes about anything not already covered. For example, linkages to or disagreements with other theories, questions raised but unanswered, shortcomings or limitations, and so forth.

If you’d like, you can try out our free catalog template here (see screenshot below).

2.3 – Digest and synthesise

Most importantly, as you work through the literature and build your catalogue, you need to synthesise all the information in your own mind – how does it all fit together? Look for links between the various articles and try to develop a bigger picture view of the state of the research. Some important questions to ask yourself are:

• What answers does the existing research provide to my own research questions ?
• Which points do the researchers agree (and disagree) on?
• How has the research developed over time?
• Where do the gaps in the current research lie?

To help you develop a big-picture view and synthesise all the information, you might find mind mapping software such as Freemind useful. Alternatively, if you’re a fan of physical note-taking, investing in a large whiteboard might work for you.

Step 3: Outline and write it up!

Once you’re satisfied that you have digested and distilled all the relevant literature in your mind, it’s time to put pen to paper (or rather, fingers to keyboard). There are two steps here – outlining and writing:

3.1 – Draw up your outline

Having spent so much time reading, it might be tempting to just start writing up without a clear structure in mind. However, it’s critically important to decide on your structure and develop a detailed outline before you write anything. Your literature review chapter needs to present a clear, logical and an easy to follow narrative – and that requires some planning. Don’t try to wing it!

Naturally, you won’t always follow the plan to the letter, but without a detailed outline, you’re more than likely going to end up with a disjointed pile of waffle , and then you’re going to spend a far greater amount of time re-writing, hacking and patching. The adage, “measure twice, cut once” is very suitable here.

In terms of structure, the first decision you’ll have to make is whether you’ll lay out your review thematically (into themes) or chronologically (by date/period). The right choice depends on your topic, research objectives and research questions, which we discuss in this article .

Once that’s decided, you need to draw up an outline of your entire chapter in bullet point format. Try to get as detailed as possible, so that you know exactly what you’ll cover where, how each section will connect to the next, and how your entire argument will develop throughout the chapter. Also, at this stage, it’s a good idea to allocate rough word count limits for each section, so that you can identify word count problems before you’ve spent weeks or months writing!

PS – check out our free literature review chapter template…

3.2 – Get writing

With a detailed outline at your side, it’s time to start writing up (finally!). At this stage, it’s common to feel a bit of writer’s block and find yourself procrastinating under the pressure of finally having to put something on paper. To help with this, remember that the objective of the first draft is not perfection – it’s simply to get your thoughts out of your head and onto paper, after which you can refine them. The structure might change a little, the word count allocations might shift and shuffle, and you might add or remove a section – that’s all okay. Don’t worry about all this on your first draft – just get your thoughts down on paper.

Once you’ve got a full first draft (however rough it may be), step away from it for a day or two (longer if you can) and then come back at it with fresh eyes. Pay particular attention to the flow and narrative – does it fall fit together and flow from one section to another smoothly? Now’s the time to try to improve the linkage from each section to the next, tighten up the writing to be more concise, trim down word count and sand it down into a more digestible read.

Once you’ve done that, give your writing to a friend or colleague who is not a subject matter expert and ask them if they understand the overall discussion. The best way to assess this is to ask them to explain the chapter back to you. This technique will give you a strong indication of which points were clearly communicated and which weren’t. If you’re working with Grad Coach, this is a good time to have your Research Specialist review your chapter.

Finally, tighten it up and send it off to your supervisor for comment. Some might argue that you should be sending your work to your supervisor sooner than this (indeed your university might formally require this), but in my experience, supervisors are extremely short on time (and often patience), so, the more refined your chapter is, the less time they’ll waste on addressing basic issues (which you know about already) and the more time they’ll spend on valuable feedback that will increase your mark-earning potential.

Literature Review Example

In the video below, we unpack an actual literature review so that you can see how all the core components come together in reality.

Let’s Recap

In this post, we’ve covered how to research and write up a high-quality literature review chapter. Let’s do a quick recap of the key takeaways:

• It is essential to understand the WHY of the literature review before you read or write anything. Make sure you understand the 4 core functions of the process.
• The first step is to hunt down the relevant literature . You can do this using Google Scholar, your university database, the snowballing technique and by reviewing other dissertations and theses.
• Next, you need to log all the articles in your reference manager , build your own catalogue of literature and synthesise all the research.
• Following that, you need to develop a detailed outline of your entire chapter – the more detail the better. Don’t start writing without a clear outline (on paper, not in your head!)
• Write up your first draft in rough form – don’t aim for perfection. Remember, done beats perfect.
• Refine your second draft and get a layman’s perspective on it . Then tighten it up and submit it to your supervisor.

Psst… there’s more!

This post is an extract from our bestselling short course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

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38 Comments

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• USC Libraries
• Research Guides

Organizing Your Social Sciences Research Paper

• 5. The Literature Review
• Purpose of Guide
• Design Flaws to Avoid
• Independent and Dependent Variables
• Glossary of Research Terms
• Reading Research Effectively
• Narrowing a Topic Idea
• Broadening a Topic Idea
• Extending the Timeliness of a Topic Idea
• Academic Writing Style
• Applying Critical Thinking
• Choosing a Title
• Making an Outline
• Paragraph Development
• Research Process Video Series
• Executive Summary
• The C.A.R.S. Model
• Background Information
• The Research Problem/Question
• Theoretical Framework
• Citation Tracking
• Content Alert Services
• Evaluating Sources
• Primary Sources
• Secondary Sources
• Tiertiary Sources
• Scholarly vs. Popular Publications
• Qualitative Methods
• Quantitative Methods
• Insiderness
• Using Non-Textual Elements
• Limitations of the Study
• Common Grammar Mistakes
• Writing Concisely
• Avoiding Plagiarism
• Footnotes or Endnotes?
• Further Readings
• Generative AI and Writing
• USC Libraries Tutorials and Other Guides
• Bibliography

A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

• Give a new interpretation of old material or combine new with old interpretations,
• Trace the intellectual progression of the field, including major debates,
• Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
• Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

• Place each work in the context of its contribution to understanding the research problem being studied.
• Describe the relationship of each work to the others under consideration.
• Identify new ways to interpret prior research.
• Reveal any gaps that exist in the literature.
• Resolve conflicts amongst seemingly contradictory previous studies.
• Identify areas of prior scholarship to prevent duplication of effort.
• Point the way in fulfilling a need for additional research.
• Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE : Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

• An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
• Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
• An explanation of how each work is similar to and how it varies from the others,
• Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

• Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
• Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
• Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
• Persuasiveness -- which of the author's theses are most convincing or least convincing?
• Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. By Publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from your organizational strategy. In other words, a chronological review would have subsections for each vital time period; a thematic review would have subtopics based upon factors that relate to the theme or issue. However, sometimes you may need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

• Current Situation : Information necessary to understand the current topic or focus of the literature review.
• Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
• History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
• Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
• Standards : Description of the way in which you present your information.
• Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates that what you are saying is valid. Be Selective Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. Use Caution When Paraphrasing When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

• Sources in your literature review do not clearly relate to the research problem;
• You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
• Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
• Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
• Does not describe the search procedures that were used in identifying the literature to review;
• Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
• Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

• How are they organizing their ideas?
• What methods have they used to study the problem?
• What theories have been used to explain, predict, or understand their research problem?
• What sources have they cited to support their conclusions?
• How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

• Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
• Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
• Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

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The first story in her first book evoked her father’s life. The last story in her last book evoked her mother’s death. In between, across 14 collections and more than 40 years, Alice Munro showed us in one dazzling short story after another that the humble facts of a single person’s experience, subjected to the alchemy of language and imagination and psychological insight, could provide the raw material for great literature.

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And not just any person, but a girl from the sticks. It mattered that Munro, who died on Monday night at the age of 92, hailed from rural southwestern Ontario, since so many of her stories, set in small towns on or around Lake Huron, were marked by the ambitions of a bright girl eager to leave, upon whom nothing is lost. There was the narrator of “Boys and Girls,” who tells herself bedtime stories about a world “that presented opportunities for courage, boldness and self-sacrifice, as mine never did.” There was Rose, from “The Beggar Maid,” who wins a college scholarship and leaves her working-class family behind. And there was Del Jordan, from “Lives of Girls and Women” — Munro’s second book, and the closest thing she ever wrote to a novel — who casts a jaundiced eye on her town’s provincial customs as she takes the first fateful steps toward becoming a writer.

Does it seem reductive or limiting to derive a kind of artist’s statement from the title of that early book? It shouldn’t. Munro was hardly a doctrinaire feminist, but with implacable authority and command she demonstrated throughout her career that the lives of girls and women were as rich, as tumultuous, as dramatic and as important as the lives of men and boys. Her plots were rife with incident: the threatened suicide in the barn, the actual murder at the lake, the ambivalent sexual encounter, the power dynamics of desire. For a writer whose book titles gestured repeatedly at love (“The Progress of Love,” “The Love of a Good Woman,” “Hateship, Friendship, Courtship, Loveship, Marriage”), her narratives recoiled from sentimentality. Tucked into the stately columns of The New Yorker, where she was a steady presence for decades, they were far likelier to depict the disruptions and snowballing consequences of petty grudges, careless cruelties and base impulses: the gossip that mattered.

Munro’s stories traveled not as the crow flies but as the mind does. You got the feeling that, if the GPS ever offered her a shorter route, she would decline. Capable of dizzying swerves in a line or a line break, her stories often spanned decades with intimacy and sweep; that’s partly what critics meant when they wrote of the novelistic scope she brought to short fiction.

Her sentences rarely strutted or flaunted or declared themselves; but they also never clanked or stumbled — she was an exacting and precise stylist rather than a showy one, who wrote with steely control and applied her ambitions not to language but to theme and structure. (This was a conscious choice on her part: “In my earlier days I was prone to a lot of flowery prose,” she told an interviewer when she won the Nobel Prize in 2013. “I gradually learned to take a lot of that out.”) In the middle of her career her stories started to grow roomier and more contemplative, even essayistic; they could feel aimless until you approached the final pages and recognized with a jolt that they had in fact been constructed all along as intricately and deviously as a Sudoku puzzle, every piece falling neatly into place.

There was a signature Munro tone: skeptical, ruminative, given to a crucial and artful ambiguity that could feel particularly Midwestern. Consider “The Bear Came Over the Mountain,” which — thanks in part to Sarah Polley’s Oscar-nominated film adaptation, “ Away From Her ” (2006) — may be Munro’s most famous story; it details a woman’s descent into senility and her philandering husband’s attempt to come to terms with her attachment to a male resident at her nursing home. Here the husband is on a visit, confronting the limits of his knowledge and the need to make peace with uncertainty, in a characteristically Munrovian passage:

She treated him with a distracted, social sort of kindness that was successful in holding him back from the most obvious, the most necessary question. He could not demand of her whether she did or did not remember him as her husband of nearly 50 years. He got the impression that she would be embarrassed by such a question — embarrassed not for herself but for him. She would have laughed in a fluttery way and mortified him with her politeness and bewilderment, and somehow she would have ended up not saying either yes or no. Or she would have said either one in a way that gave not the least satisfaction.

Like her contemporary Philip Roth — another realist who was comfortable blurring lines — Munro devised multilayered plots that were explicitly autobiographical and at the same time determined to deflect or undermine that impulse. This tension dovetailed happily with her frequent themes of the unreliability of memory and the gap between art and life. Her stories tracked the details of her lived experience both faithfully and cannily, cagily, so that any attempt at a dispassionate biography (notably, Robert Thacker’s scholarly and substantial “Alice Munro: Writing Her Lives,” from 2005) felt at once invasive and redundant. She had been in front of us all along.

Until, suddenly, she wasn’t. That she went silent after her book “Dear Life” was published in 2012, a year before she won the Nobel, makes her passing now seem all the more startling — a second death, in a way that calls to mind her habit of circling back to recognizable moments and images in her work. At least three times she revisited the death of her mother in fiction, first in “The Peace of Utrecht,” then in “Friend of My Youth” and again in the title story that concludes “Dear Life”: “The person I would really have liked to talk to then was my mother,” the narrator says near the end of that story, in an understated gut punch of an epitaph that now applies equally well to Munro herself, but she “was no longer available.”

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Audio produced by Sarah Diamond .

Gregory Cowles is the poetry editor of the Book Review and senior editor of the Books desk. More about Gregory Cowles

• Case Report
• Open access
• Published: 11 May 2024

Carbon monoxide poisoning with hippocampi lesions on MRI: cases report and literature review

• Wenxia Li 1   na1 ,
• Jun Meng 2   na1 ,
• Jing Lei 2 ,
• Cheng Li 2 &
• Wei Yue 1 , 2  

BMC Neurology volume  24 , Article number:  159 ( 2024 ) Cite this article

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Carbon monoxide (CO) poisoning is now one of the leading causes of poisoning-related mortality worldwide. The central nervous system is the most vulnerable structure in acute CO poisoning. MRI is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. The imaging features of CO poisoning are diverse. We report atypical hippocampal lesions observed on MRI in four patients after acute CO exposure.

Case presentations

We report four patients who presented to the emergency department with loss of consciousness. The diagnosis of CO poisoning was confirmed on the basis of their detailed history, physical examination and laboratory tests. Brain MRI in all of these patients revealed abnormal signal intensity in hippocampi bilaterally. They all received hyperbaric oxygen therapy. The prognosis of all four patients was poor.

Hippocampi, as a relatively rare lesion on MRI of CO poisoning, is of important significance both in the early and delayed stages of acute CO poisoning. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.

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Carbon monoxide (CO) is a colorless, tasteless, odorless gas that is imperceptible to human [ 1 ]. In several countries or regions, there is a high mortality rate due to CO poisoning. Of these, more patients die from unintentional CO poisoning than intentional reasons [ 2 ]. The central nervous system is the most vulnerable structure in acute CO poisoning due to its high energy demands [ 3 ]. MRI and related imaging modalities, the commonly used clinical imaging method, is important in assessing the severity of brain damage from CO poisoning and, to some extent, can predicts the prognosis of CO poisoning brain damage [ 4 ]. The imaging features of CO poisoning are diverse. It has been reported that the bilateral basal ganglia, especially the globus pallidus (GP), and the centrum semiovale are the most common sites of lesion in acute CO poisoning MRI, while cases involving the medial temporal lobe in the region of hippocampi are rare [ 4 , 5 ]. We herein report four patients with CO poisoning who were studied by MRI during the acute phase and all were found to have lesions in the hippocampal region (Table  1 ).

A 65-year-old male was found unconscious and unresponsive to verbal stimuli in the house on 1/27/2018. The house he was in had a coal stove and the coals were burning incompletely. According to the investigation, he had suffered accidental CO poisoning as a result of a fault in the household’s heating. He was exposed in CO for approximately 15 h. There was no vomit beside him and he was not experiencing seizures. Then, he was transported to the hospital. In the emergency room, His vital signs were normal with the Glasgow coma score (GCS) 12. He was drowsy with an intact pupillary light response. He did not respond to verbal stimuli. His arterial carboxyl hemoglobin (COHb) was measured at 39%. Doctors treated him with hyperbaric oxygen therapy (HBOT) on 3 times. The patient became conscious 17 h after admission, responding to painful stimuli, and was able to move his limbs as instructed with GCS ranging from 12 to 15. Although he could understand words correctly, he still could not express himself. The patient received continuous HBOT on 5 separate days after admission. After 10 days of admission, his neurological function was largely restored. However, around the 20th day of hospitalization, the patient suddenly developed new neurological symptoms. He exhibited increased muscle tone, severely impaired cognitive function, memory loss, and mixed aphasia. Doctors considered him to have delayed neurological syndrome caused by CO poisoning. The MRI scan of his brain approximately 48 h after exposure to CO showed the bilateral hippocampi abnormalities (Fig.  1 A).

DWI obtained from four patients with acute carbon monoxide poisoning. ( A ) A 65-year-old man (patient A, COHb: 39%) examined at 48 h post-exposure, with demonstration of restricted diffusion (arrows) in the bilateral hippocampi. ( B ) A 61-year-old man (patient B, COHb: 19.2%) examined at 24 h post-exposure, with demonstration of restricted diffusion (arrows) in the bilateral hippocampi and globus pallidus. ( C ) A 62-year-old man (patient C, COHb: 7.8%) examined at 72 h post-exposure, with demonstration of restricted diffusion (arrows) in the bilateral hippocampi. ( D ) A 24-year-old woman (patient D, COHb: 7%) examined at 12 h post-exposure, with demonstration of restricted diffusion (arrows) in the bilateral medial temporal lobe and cerebral peduncle

A 61-year-old male was found unconscious and unresponsive to verbal stimuli inside his house on 12/29/2021. The house he was staying in had a coal stove for heating. And the carbon in the coal stove was burning incompletely. It is found that he was suffered from accidental CO poisoning after falling asleep. He was in the CO filled house for at least 10 h. He suffered from vomiting, urinary and fecal incontinence. His arterial COHb was 19.2%. After admission, the patient’s respiratory rate and heart rate were unstable, unresponsive to dizzand pain stimuli. And the patient was coma with GCS of 10. The patient received continuous HBOT during his hospitalization for 8 continuous days. During the subsequent hospitalization, the patient remained comatose with GCS ranging from 10 to 8. At the time of discharge, the patient’s consciousness was still in coma, unresponsive to verbal stimuli, and responsive to heavy pain stimuli. The MRI scan of the brain approximately 24 h after his exposure to CO showed the abnormalities in the bilateral hippocampi and basal ganglia (Fig.  1 B).

A 62-year-old male was found unconscious and unresponsive to verbal stimuli in the house on 2/13/2023. He was beside a relatively large amount of vomit. He was unresponsive to painful stimuli. There were traces of burning charcoal in the house he was in and the person in the house with him was dead. This patient, along with the deceased in the same house, was accidentally poisoned with CO due to a house fire. His arterial COHb was 7.8%. The patient was comatose on admission with a GCS score of 8. His heart rate, respiratory rate and blood pressure were unstable. The patient’s pupillary light reflection was poor and his limbs did not respond to painful stimuli. The patient then received 2 HBO treatments. Twelve hours after admission, the patient’s mental state changed from coma to consciousness, but his cognitive function still did not recover, as exhibited by memory loss and unresponsiveness. The patient received continuous HBOT for 7 days. At the time of discharge, the patient’s consciousness shifted to conscious, with GCS ranging from 8 to 15, but he still had symptoms of memory loss. The MRI scan of the brain approximately 72 h after his exposure to CO showed abnormal signals in the bilateral hippocampi (Fig.  1 C).

A 24-year-old female was found unconscious and unresponsive to verbal stimuli in the house on 2/16/2023. Her perioral area had white frothy secretions. Her family stated that she had been inside the house with a coal stove burning for warmth and that she had said she was dizzy. The patient was depressed. And this time she attempted suicide by burning coal. Her arterial COHb was 7%. On admission, the patient remained in a comatose state with a GCS score of 7, and her vital signs were unstable. The patient was unresponsive to verbal and pain stimuli, but the pupillary light reflection was present. During her hospitalization, the patient received continuous hyperbaric oxygen therapy for 5 times. At the time of discharge, the consciousness of the patient changed from coma to lethargy with brief spontaneous eye opening. And GCS was ranging from 7 to 10. The MRI scan of the brain approximately 12 h after her exposure to CO showed abnormal signals in the medial temporal lobe and cerebral peduncle (Fig.  1 D).

Literature review and discussion

The pathophysiologic mechanism of CO poisoning involves the binding of CO to hemoglobin to form COHb [ 6 ]. CO shows a 250-fold higher affinity for hemoglobin than oxygen and competitively binds to it to form COHb. COHb has no ability to carry oxygen and is not easily dissociated, which also shifts the hemoglobin oxygenation curve to the left. In this case, blood oxygen is not easily released to the tissues, resulting in cellular hypoxia [ 7 , 8 ]. At the same time, CO affects mitochondrial metabolism, which can aggravate tissue hypoxia [ 9 ]. Furthermore, studies have shown that hypotension and cardiac dysfunction induced by CO also can lead to circulatory hypoxia in the body [ 10 , 11 ]. The pathological changes in the brain tissue of patients with CO poisoning are similar to those of hypoxic encephalopathy, like cerebral edema and varying degrees of necrosis. Cerebral edema and ischemia can be followed by cerebral circulatory disorders, causing ischemic cerebral necrosis and further aggravating cerebral hypoxia [ 4 ].

CO poisoning causes a wide variety of symptoms that exhibit an unspecific character. Patients often present with tachycardia, headache, vomiting, fainting, and seizures [ 12 ]. Studies have shown that approximately 20% of patients with CO poisoning experience a progression from acute to chronic symptoms, and approximately 10% develop delayed neurological syndrome [ 13 ]. Some scholars have categorized the degree of poisoning as mild, moderate, or severe based on COHb concentration [ 14 ]. Hence, concentration of COHb seems to be somewhat proportional to the severity of clinical symptoms, as seen in the four patients we reported. However, it has been found that concentration of COHb is closely related to that of CO in the air at the time of intoxication and the duration of exposure, whereas the degree of intoxication is not only related to the concentration of COHb, but also to the the clinical manifestations, especially the individual’s tolerance to hypoxia [ 15 ]. Therefore, COHb concentration cannot be used to determine the severity of the patient’s symptoms and prognosis.

MRI, one of the most commonly used imaging methods, is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. MRI can provide an objective assessment of brain damage [ 16 ]. Some researchers defined the time between CO exposure and MRI as the hyperacute phase within 24 h, the acute phase between 24 h and 7 days, the subacute phase between 8 and 21 days, and the chronic phase over 22 days [ 4 ]. The early stage of acute CO toxic encephalopathy on MRI mainly involves the cerebral white matte (CWM) and basal ganglia (especially the GP) [ 17 ]. Current conventional MRI studies have focused on some typical manifestations in the chronic phase, i.e., typical findings of bilateral high signal in basal ganglia and CWM on T2WI-weighted images [ 18 ]. Many studies have shown that magnetic resonance DWI can help to assess ischemic-hypoxic brain damage in both the hyperacute and acute phases of CO poisoning. DWI can characterize cell toxic edema in damaged CWM more sensitively and earlier than conventional MRI [ 15 ]. Moon et al. [ 19 ] found that DWI could reflect cytotoxic edema after CWM injury more sensitively than conventional MRI and may contribute to the prediction of long-term neurologic outcomes after discharge from the hospital.

With regard to damage to gray matter structures other than the GP during the acute phase of CO poisoning, few reports have described hippocampal lesions, and most of the cases were combined with other areas of abnormality. Of the 19 patients with acute CO poisoning reported by Donnell et al. [ 20 ], four patients exhibited abnormal signals in medial temporal lobe in the region of hippocampi, most of which were bilateral and combined with abnormalities in other locations. Kim et al. [ 15 ] reported the DWI imaging characteristics of 7 patients with acute phase of CO poisoning, of whom 2 had hippocampal lesions that showed limited diffusion of the lesion site on the DWI/ADC maps and their symptoms manifested as lethargy or coma. Henke et al. [ 21 ] reported a patient with CO poisoning who showed undefined high signal in the hippocampal lesions bilaterally on T2-weighted images 5 days after poisoning. His symptoms presented with severe amnesia and disorientation. There also have been previous reports describing damage to hippocampi in the chronic phase in patients with CO poisoning. Bastin et al. [ 22 ] performed brain MRI in a patient with CO poisoning 18 years after the event. The results showed that the hippocampal volume of this patient was reduced by more than 50% compared to a normal healthy population. The patient’s clinical presentation was characterized as severely impaired recall. Tamura et al. [ 23 ] examined MRI of a patient with acute CO poisoning 1 year after the event. The rate of hippocampal volume reduction in the first year after CO poisoning was approximately 4% compared to her previous MRI. Furthermore, in a report on hippocampal lesions revealed that acute phase hippocampal lesions may portend a very poor prognosis [ 20 ]. In all four patients we reported, the first MRI was performed within 72 h of the event, and DWI imaging showed that all patients presented with bilateral hippocampal lesions with or without abnormalities in other areas. The four patients we reported had clinical signs of impaired consciousness in the acute phase, two patients developed cognitive dysfunction with severe impairment of short-time memory in the acute phase, and two patients suffered from a persistent coma. All four patients were treated with hyperbaric oxygen, reduction of cerebral edema, and improvement of coronary flow, but the prognosis was not good, and one of them developed delayed neurological syndrome, which is similar to the report of Donnell et al [ 20 ].

Most of these patients with hippocampal lesions after CO poisoning reported above developed cognitive dysfunction during the recovery period, and most had a poor prognosis. The hippocampus is an important region for memory, learning, and emotional activities and has a high metabolic rate. Therefore, the hippocampus is very vulnerable to ischemia and hypoxia. In the animal model of acute CO poisoning, the hippocampal neurons of CO-poisoned rats were obviously damaged and hippocampal neurogenesis were significantly inhibited, which is consistent with the imaging performance of the cases reported in this study. Therefore, we conducted a systematic review of MRI of CO poisoning showing abnormal lesions in hippocampi (Table  2 ). The results found that, firstly, isolated bilateral hippocampal lesions are rare in the acute phase of poisoning, and most of them were reported as unilateral or bilateral hippocampal abnormalities combined with lesions in other parts of the brain, whereas the two patients reported in the present study had isolated bilateral hippocampal lesions; secondly, most of the patients with hippocampal lesions had cognitive dysfunctions in their clinical presentation, and two of the patients reported in the present study developed cognitive dysfunctions; finally, the hippocampal lesions in acute phase may portend a poor prognosis; in the present case, two patients had remaining cognitive dysfunction, and two patient was in lethargy or coma state.

Our cases illustrated that the hippocampi, as an atypical presentation, can be seen on MRI in a few patients with CO poisoning. Hippocampal lesions indicated by MRI are extremely significant in acute and subacute phases in patients with acute CO toxic brain injury. MRI is able to detect hippocampal lesions in acute injuries with sudden onset of neurologic deficits, and may also be able to predict, to some extent, brain injury in patients in the mid- to long-term, suggesting a prognosis for the patient. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

basal ganglia

carbon monoxide

carboxyl hemoglobin

cerebral white matte

globus pallidus

Glasgow coma score

hyperbaric oxygen therapy

medial temporal lobe

temporal white matter

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Acknowledgements

We thank the patients for agreeing to submit their cases.

This work was supported by Tianjin Key Medical Discipline (Specialty) Construction Project [grant number TJYXZDXK-052B].

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Wenxia Li and Jun Meng have contributed equally to this work and share first authorship.

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Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, 300070, China

Wenxia Li & Wei Yue

Tianjin Huanhu Hospital, Tianjin, 300350, China

Jun Meng, Jing Lei, Cheng Li & Wei Yue

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WL and JM analyzed and interpreted patient data. WL and CL gathered the materials, searched databases and conducted a literature review. JL interpreted the MRI of the brain. LW, JM, CL and WY were responsible for writing the manuscript. All authors critically revised the article for important intellectual content and approved the final manuscript.

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Correspondence to Wei Yue .

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Li, W., Meng, J., Lei, J. et al. Carbon monoxide poisoning with hippocampi lesions on MRI: cases report and literature review. BMC Neurol 24 , 159 (2024). https://doi.org/10.1186/s12883-024-03668-2

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CASE REPORT article

Eosinophilic granulomatous polyangiitis with central nervous system involvement in children: a case report and literature review.

• Department of Pediatric Nephrology, Rheumatology, and Immunology, The Affiliated Hospital of Qingdao University, Qingdao, China

Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition.

Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils.

Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

1 Introduction

Eosinophilic granulomatosis with polyangiitis is a rare autoimmune vasculitis that primarily affects small- to medium-sized blood vessels ( 1 ). The onset of EGPA is generally observed between the ages of 25 and 50, with a reported prevalence among adults ranging from 10 to 13 per million. Nevertheless, EGPA can also manifest during childhood, carrying a notable attendant morbidity and mortality ( 2 ). Characterized by eosinophilia, granulomatous inflammation, and necrotizing vasculitis, it typically manifests with a wide range of symptoms including asthma, eosinophilia, and systemic vasculitis. Furthermore, it has the potential to affect numerous organs, including the kidneys, heart, digestive tract, and nervous system. Notably, in EGPA, peripheral nervous system involvement is more prevalent, whereas central nervous system involvement occurs less frequently. The pathophysiology of EGPA involves the dysregulation of the immune system, specifically the activation of eosinophils, which trigger inflammation and tissue damage in affected organs. Recent studies have unequivocally established the significance of ANCA in tissue damage from a clinicopathological perspective ( 2 ). The diagnosis of the disease relies on a combination of clinical findings, laboratory tests, and histopathological examination. Treatment typically involves the use of immunosuppressive drugs and corticosteroids, aimed at suppressing the overactive immune system and reducing inflammation ( 3 ). In this study, we retrospectively analyzed the clinical characteristics of a pediatric case of EGPA complicated by CNS involvement.

2 Case presentations

A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital in June 2023. In January and March 2023, she was hospitalized at another hospital due to recurrent cough and asthma. During the period, multiple blood tests revealed a significant increase in eosinophil count and IgE levels. MPO-ANCA was positive while the antinuclear antibodies profile was negative. Allergen testing confirmed strong sensitization to dust mites. Chest CT scan reveals augmented thickness and density of the pulmonary trachea, numerous ground-glass opacities and nodular shadows scattered throughout the lungs, as well as enhanced bronchial wall thickness. Nasal sinus CT scan revealed acute sinusitis. Pulmonary function test indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology showed hyperplastic bone marrow with a notable increase in eosinophil proportion. Lung alveolar lavage fluid examination did not detect pathogenic bacteria. Genetic testing through whole exome sequencing did not identify any pathogenic mutations associated with the clinical phenotype. During the second hospitalization, a transient red rash appeared on her left wrist. Following treatment with anti-infective agents, glucocorticoids, nebulization, her eosinophil count normalized and the rash disappeared. After discharge, she was prescribed oral prednisone acetate, which was gradually tapered.

Eleven days prior to admission, she experienced unprovoked intermittent coughing, accompanied by yellowish and purulent sputum. The cough, which was particularly severe during the night, was accompanied by wheezing and dyspnea. Additional symptoms included nasal congestion and yellowish loose stools. Notably, the eosinophil count in the blood routine examination at another hospital was once again elevated. Despite treatment with azithromycin for anti-infection, the child’s condition did not improve. Five days prior to admission, she developed a fever accompanied by red rashes on the extensor surfaces of the feet and hands. The cough intensified, and there was hemoptysis, which was pinkish and streaky in nature. The hemoptysis episodes occurred at regular intervals of 10–20 minutes. The child had previously been in excellent health and had no significant personal history. Her father had a history of allergic rhinitis, and her mother had an allergic constitution.

On admission, she revealed a weight of 29kg (P25-P50), a height of 146cm (P75-P90), a temperature of 36.2°C, a heart rate of 135 beats per minute, a respiratory rate of 40 beats per minute, the blood pressure of 95/60mmHg, and the oxygen saturation (SP02) ranging between 93% and 94%. She was conscious but in a poor mental state. Spotted papules were visible on her hands and feet, which were partially ulcerated and scabbed, accompanied by pain ( Figure 1A ). Additionally, pulmonary rales were audible bilaterally. The abdomen was soft, with a 2cm indentation under the right rib cage of the liver. The cardiac and neurologic examinations were unremarkable.

Figure 1 (A) Foot rash, partially ulcerated and scabbed. (B, C) Before treatment, the HRCT scan of the chest showed multiple patchy and nodular lesions with unclear boundaries, indicating high-density shadows in both lungs. And multiple enlarged lymph nodes were observed in the mediastinum and bilateral hilar regions. (D) Before treatment, the CT plain scan of the paranasal sinuses revealed a notable thickening of the mucosa in the bilateral maxillary, ethmoid, sphenoid, and frontal sinuses. (E) Before treatment, the MRI scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex. (F) Before treatment, the MRA revealed moderate to severe stenosis in the middle cerebral artery segment M2 of the left middle cerebral artery.

The laboratory tests showed white blood cell count of 13.66×10 9 /L (4.3×10 9 -11.3×10 9 ), lymphocyte count of 1.27×10 9 /L (1.5×10 9 -4.6×10 9 ), eosinophil count of 4.11×10 9 /L (0.00×10 9 -0.68×10 9 ), platelet count of 314×10 9 /L (167×10 9 -453×10 9 ), hemoglobin of 118g/L (118–156), C-reactive protein of 67.68mg/L (0–5); erythrocyte sedimentation rate of 43.00mm/60min (0–20), procalcitonin of 0.181ng/mL (<0.05), albumin of 23.5g/L (39–54), D-dimer of 7310ng/mL (0–500), ferritin of 438ng/ml (13–84). The blood culture and sputum culture were negative, and the blood coagulation, liver function, kidney function, myocardial enzymes, urine, and stool samples were all within normal limits. The immunological assessment revealed that the immunoglobulin G level was 15.80g/L, while the immunoglobulin E level was significantly elevated at >2500.00IU/mL. Detailed lymphocyte subset analysis reveals lymphocytes constitute 3.98% (11.4%-57%) of white blood cells, and among lymphocytes, T lymphocytes represent 63.71% (53.7%-82.8%). Helper T lymphocytes, CD4+ naive T cells and CD4+ effector T cells account for 60.55% (46.2%-78%), 26.39% (7.2%-68.9%), 24.56% (0.44%-6.06%) of total T lymphocytes, respectively. Plasmablasts represent 0.29% (1.9%-23.7%) of B lymphocytes. Other lymphocyte subsets such as NK cells, CD4+ central memory T cells, regulatory T cells, CD8+ T cells, double negative T cells, B lymphocytes, and dendritic cells are generally normal. The tests for antinuclear antibody, complement, ASO and RF were all negative. The aetiological examination indicated that the five respiratory pathogens, Mycoplasma pneumoniae, fungal G test, fungal GM test, and tuberculosis infection T cell were all negative.

The high-resolution chest computed tomography (HRCT) imaging revealed multiple patchy and nodular lesions with unclear boundaries, indicating high-density shadows in both lungs ( Figure 1B ). Additionally, multiple enlarged lymph nodes were observed in the mediastinum and bilateral hilar regions ( Figure 1C ), and a small amount of pleural effusion was present on the right side. The CT plain scan of the paranasal sinuses revealed a notable thickening of the mucosa in the bilateral maxillary, ethmoid, sphenoid, and frontal sinuses ( Figure 1D ). Within the sinus cavities, there were scattered patches of low-density lesions, and no significant signs of bone destruction were detected in the sinus walls. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Electrocardiogram displayed sinus rhythm and irregular sinus rhythm. Echocardiogram revealed mild mitral and tricuspid valve regurgitation.

After admission, the child was given piperacillin sodium and tazobactam sodium for anti-infection, nebulized for cough and asthma. However, on the second day of hospitalization, she continued to experience fever, coughing, hemoptysis, and labored breathing. Even under oxygen inhalation, her oxygenation remained inadequate. Therefore, the child was transferred to the Pediatric Intensive Care Unit (PICU) for tracheal intubation and ventilator support treatment under sedation and analgesia. Meanwhile, meropenem was upgraded for anti-infection, etamsylate and hemocoagulase were given for hemostasis.

Then she underwent bronchoscopy, revealing significant inflammatory and nodular changes in the bronchial mucosa under microscopic examination. Lung lavage fluid metagenomic test came back negative, while the culture suggested EB virus infection. Cytological classification showed neutrophils at 23.00% (<2%) and eosinophils at 13.00% (<1%). Therefore, we enhanced the etiological examination of EB. The EB virus capsid antigen IgM was 8.19AU/mL (<3), and EB virus DNA was 2.03e+003 (≤5.0e+003). Subsequently, we added ganciclovir antiviral therapy to the treatment plan. Furthermore, the skin pathological examination of the left ankle showed a reticulated pattern of hyperkeratosis, accompanied by necrosis in the central epidermis. In the superficial and middle layers of the dermis, fibrinoid necrosis is observed in the blood vessel walls, concurrent with neutrophil infiltration. Numerous neutrophils and eosinophils are visible infiltrating the areas surrounding the blood vessels, while erythrocyte extravasation and nuclear dust are also apparent. Notably, no distinct granulomatous structure is evident, and the overall changes are indicative of leukocytoclastic vasculitis ( Figure 2A ). The pathological examination of the lung tissue biopsy indicated the presence of chronic suppurative inflammation, accompanied by fibrous tissue proliferation and fibrosis ( Figures 2B, C ).

Figure 2 (A) Before treatment, the skin pathological examination of the left ankle showed a reticulated pattern of hyperkeratosis, accompanied by necrosis in the central epidermis. In the superficial and middle layers of the dermis, fibrinoid necrosis is observed in the blood vessel walls, concurrent with neutrophil infiltration. Numerous neutrophils and eosinophils are visible infiltrating the areas surrounding the blood vessels, while erythrocyte extravasation and nuclear dust are also apparent. Notably, no distinct granulomatous structure is evident, and the overall changes are indicative of leukocytoclastic vasculitis. (B, C) Before treatment, the pathological examination of the lung tissue biopsy indicated the presence of chronic suppurative inflammation, accompanied by fibrous tissue proliferation and fibrosis.

The patient, a school-age girl, has a known history of recurrent asthma. Over the course of the illness, she has developed skin and lung involvement. Her peripheral blood eosinophil count has repeatedly been found to be more than 10%, and a sinus CT scan has demonstrated sinusitis. After using the clinical diagnostic criteria established by the American College of Rheumatology in 1990 ( 4 ), we confirmed the diagnosis of EGPA. After obtaining a clear diagnosis, we administered a methylprednisolone pulse therapy (500mg for 3 days followed by 750mg for 2 days) and cyclophosphamide (300mg for 2 days) to effectively treat the condition. In addition, we administered piperacillin tazobactam to combat infections. Following these treatments, her temperature normalized, coughing, wheezing, and hemoptysis symptoms resolved, and the rash showed signs of improvement.

On the seventh day of hospitalization, the child had a convulsion once, with both eyes exhibiting an upward gaze, and a blood pressure of 125/72mmHg. The child’s consciousness remains unknown while sedated. The EEG showed epileptic waves. We have perfected the lumbar puncture procedure and did not detect any abnormalities in the cerebrospinal fluid routine, biochemistry, immunoglobulin, bacterial culture, and smear. MRI scan of the brain showed multiple FLAIR hyperintensities in the bilateral cerebral cortex ( Figure 1E ). The magnetic resonance angiography (MRA) revealed moderate to severe stenosis in the middle cerebral artery segment M2 of the left middle cerebral artery ( Figure 1F ), while the magnetic resonance venography (MRV) showed no significant abnormalities. To control the epileptic seizures, she was administered levetiracetam. After treatment, the child no longer experienced seizures.

At the follow-up review conducted one month following discharge, her peripheral blood eosinophil count returned to normal levels. Chest CT scans revealed significant improvement in lung inflammation ( Figures 3A, B ), pulmonary function test showed mild ventilation-diffusion dysfunction. And the cranial MRI showed a reduction in the abnormal signal intensity in the bilateral cerebral cortex compared to the previous scan ( Figure 3C ) while the cranial MRA was unremarkable ( Figure 3D ). The patient continues to visit the outpatient department for regular follow-up appointments, adjust the dosage and frequency of drug administration based on laboratory and imaging test results. Currently, she is receiving maintenance treatment with 6 rounds of monthly intravenous cyclophosphamide already completed.

Figure 3 (A, B) After treatment, the chest CT scans revealed significant improvement in lung inflammation and no obvious enlarged lymph nodes were seen in the mediastinum and bilateral hilar. (C) After treatment, the cranial MRI showed a reduction in the abnormal signal intensity in the bilateral cerebral cortex compared to the previous scan. (D) After treatment, there were no markedly abnormal findings in cranial MRA.

Using the search terms “eosinophilic granulomatosis with polyangiitis (EGPA)/Churg-Strauss syndrome”, “central nervous system” and “child” to search the China National Knowledge Infrastructure (CNKI), Wanfang database, and Chinese Biomedical Literature Database (up to December 2023), no reports of children were found. All reported cases were adults and the common clinical manifestations of the CNS were cerebral infarction or ischemia, subarachnoid hemorrhage, and cerebral hemorrhage. When we searched the PubMed database using the same search terms, we retrieved one relevant case ( 5 ). The patient, a 14-year-old boy, presented with a protracted fever, weight loss, muscle pain, joint pain, and a purpuric rash. He subsequently developed finger numbness, sinusitis, testicular pain, lung infiltration, asthma, and pericardial effusion. Laboratory tests revealed that eosinophils accounted for 58% of his peripheral blood count. The skin biopsy results indicated eosinophilic granulocytic infiltration necrotizing vasculitis. Following initial treatment with glucocorticoids and cyclophosphamide, the patient’s condition improved. However, during the course of his illness, he developed cerebral vasculitis secondary to epilepsy, and ultimately, hypoxemia and cardiac arrest triggered by severe asthma led to his demise. The case we reported is the first known instance of pediatric CNS involvement in China to date.

3 Discussion

EGPA is a multifaceted disease characterized by chronic rhinosinusitis, chronic sinusitis, asthma, and elevated levels of eosinophils in the peripheral blood. It was first described by pathologists J.Churg and L.Strauss in 1951, also known as the Churg-Strauss syndrome. EGPA is a rare disorder, with an annual incidence rate ranging from 0.5 to 6.8 per million individuals ( 6 ). It can affect individuals of all ages, with the median age of onset typically ranging from 38 to 54. There are no significant racial, familial, or gender disparities associated with EGPA. Additionally, few cases have been reported in children ( 7 ).

The cause of EGPA remains unknown, but it is thought to be associated with environmental and genetic factors. The primary mechanism behind the development of EGPA is caused by EOS infiltration and ANCA-induced damage to the vascular endothelium. Notably, approximately 70% of patients have a history of allergic rhinitis, and the onset often linked to asthma. Comprehensive examinations reveal elevated levels of EOS in the peripheral blood and tissues, along with increased IgE levels, indicating that EGPA may be a form of allergic or hypersensitivity disease ( 8 ).

EGPA is distinguished by eosinophilic infiltration and vasculitis, presenting with a diverse array of vascular-related clinical symptoms. Vasculitis primarily targets small-to-medium-sized vessels, resulting in a spectrum of issues linked to blood vessel dysfunction. Respiratory involvement, particularly affecting the lungs, is a prominent feature of EGPA. Additionally, patients may exhibit cutaneous vasculitis due to inflammation and necrosis in skin vessels. Cardiovascular, gastrointestinal, and nervous system involvements are also possible ( 2 ). A significant proportion of EGPA patients, up to 75%, experience peripheral neuropathy, often manifesting as polyneuropathy. In some instances, cranial nerves may also be implicated, though central nervous system involvement remains comparatively uncommon. And in a recent systematic analysis of 33 children with EGPA by Zwerina, it was observed that female patients were in the majority ( 9 ). Notably, when compared to adults, children tend to have more severe involvement of the heart and lungs, while the peripheral nerves and skeletal muscles are less.

The clinical features of EGPA are typically divided into three distinct stages: the prodromal phase, the vasculitis phase, and the extravascular granuloma phase. During the prodromal phase, patients typically exhibit atopic diseases with eosinophilia being most prevalent in the peripheral blood, lung and gastrointestinal tract. The vasculitis phase is characterized by the presence of systemic small-to-medium vessel vasculitis. Skin involvement is a frequent feature of this phase, affecting between 1/2 and 2/3 of EGPA patients. This involvement typically manifests as tender subcutaneous nodules on the extensor surfaces of the arms, hands and legs, as well as petechial or ecchymotic skin lesions. The heart is also often observed during this phase and represents one of the severe manifestations. The extravascular granuloma phase is the final stage, during which patients may develop granulomatous lesions in the nose, lungs, and intestines.

The diagnostic criteria for EGPA primarily rely on the clinical diagnostic criteria established by the American College of Rheumatology in 1990 ( 4 ). It includes: (1) a history of asthma (2) peripheral blood eosinophilia with a proportion exceeding 10% of white blood cells (3) involvement of paranasal sinuses (4) transient pulmonary infiltrates (5) neuropathy affecting single or multiple nerves (6) pathological confirmation of extravascular eosinophil infiltration. A patient who meets four or more could be diagnosed with EGPA. The lung and the skin are most commonly affected while EGPA can impact any system, including the cardiovascular, gastrointestinal, renal, and central nervous system. In the case we are reporting, the patient demonstrated involvement of the lung, skin and CNS during the course of the illness. Her peripheral blood eosinophil counts repeatedly exceeded 10%, and cranial imaging indicated sinusitis, fulfilling the diagnostic criteria. The time from onset to diagnosis was 8 months, exhibiting characteristics such as recurrent illness, multiple affected organs, and a severe condition compared to many adult EGPA cases.

The involvement of the CNS in EGPA is characterized by clinical manifestations that cannot be attributed to metabolic encephalopathy or other causes. It is estimated that approximately 70% of adult EGPA patients experience neurological involvement, although the CNS is less commonly affected ( 10 ). The involvement of the CNS mainly manifests as ischemic lesions, intracranial hemorrhage or subarachnoid hemorrhage, cranial nerve palsy and vision loss ( 11 ). The pathogenesis may be associated with secondary cerebral vasculitis and eosinophilic infiltration. Suying Liu et al. conducted a study on 110 EGPA patients aged between 19 and 80, and found that 17.3% had involvement of the CNS. The most common manifestation was ischemic lesions (63.2%), followed by reversible posterior encephalopathy syndrome (PRES) (36.8%) ( 12 ). And age, disease duration, and fever are potential independent risk factors for CNS involvement.

EGPA-associated PRES is characterized by patients presenting with typical acute neurological symptoms, along with radiological abnormalities of reversible vasogenic brain edema. This condition is often accompanied by seizures, encephalopathy, headache, and visual disturbances in the context of EGPA. The precise mechanism of PRES remains unclear, and it may be caused by changes in brain autoregulation due to the involvement of two mechanisms: hypertension and endothelial injury ( 13 , 14 ). During the course of the patient’s illness, seizures occurred, blood pressure increased significantly compared to when the patient was admitted, cranial MR imaging demonstrated PRES manifestations, and MRA revealed cerebral artery stenosis. Consequently, a comprehensive evaluation encompassing the child’s clinical presentation, radiological findings, and response to therapy led to the conclusion that the patient was suffering from EGPA complicated by CNS involvement, manifesting as PRES and cerebrovascular stenosis.

At present, there are no confirmed laboratory indicators for EGPA. Some studies have shown that adults with EGPA who are ANCA-positive are more likely to exhibit clinical manifestations such as weight loss, ear, nose, and throat lesions, as well as peripheral neuropathy. While ANCA-negative individuals are more prone to tissue damage in the heart and lungs. In this particular case, the child was ANCA-positive and presented with symptoms such as fever, rash, involvement of the gastrointestinal tract, lungs, and nervous system. However, in Eleftheriou’s pediatric series of EGPA in the UK, none of the children tested positive for ANCA ( 15 ). Given the limited number of pediatric EGPA cases, it remains uncertain whether there is a correlation between clinical manifestations and ANCA in children.

The treatment of EGPA involves a multidisciplinary approach tailored to the specific needs of each patient. The main goals of therapy are to control inflammation, prevent organ damage, and improve quality of life. Systemic glucocorticoids continue to serve as the cornerstone of treatment, effectively suppressing inflammation and managing symptoms. Patients with severe disease require pulsed intravenous glucocorticoid treatment, typically administered as daily methylprednisolone pulses ranging from 500 to 1,000 mg each over a three-day period, with a maximum cumulative dose of 3 grams. Subsequently, high-dose oral glucocorticoids should be prescribed, such as 0.75 to 1 mg/kg per day, to maintain effective therapy ( 3 ). In severe cases, particularly when the central nervous system, heart, kidneys, or digestive tract are affected, immunosuppressive agents such as cyclophosphamide or methotrexate may be prescribed. These agents aim to modulate immune system activity and safeguard blood vessels and organs from further harm. For younger patients with involvement of the nervous system and myocardium, the use of high-dose intravenous immunoglobulin may be considered a viable alternative when standard treatment fails to produce satisfactory results. In select cases, biologic therapies, like rituximab, that target specific immune system components may also be explored ( 7 , 16 – 19 ). For patients with relapsing-refractory disease without organ or life-threatening manifestations, interleukin-5 receptor antagonist in combination with steroids is recommended ( 3 , 20 , 21 ). Which can help reduce the need for oral glucocorticoids and potentially delay the progression of the disease ( 22 – 24 ). Currently, there are few cases of pediatric EGPA, and there is a lack of long-term follow-up data on the treatment of these patients. During the hospitalization, the child we reported had a rapidly progressing condition and multiple organs affected. Therefore, methylprednisolone in combination with CTX was chosen as the treatment option.

Suying Liu et al. discovered that individuals with damage to the CNS are more prone to experiencing digestive tract involvement ( 12 ). The microbiota-gut-brain axis theory offers a potential explanation for this connection ( 25 ). Cyclophosphamide is more effective at crossing the blood-brain barrier than rituximab. Therefore, glucocorticoids combined with cyclophosphamide are often the preferred initial treatment for EGPA affecting the CNS ( 26 ). Suying Liu et al. observed that intrathecal injection therapy had a positive impact. Zhou Jiaxin reported on 73 EGPA patients, finding that 11% had CNS involvement ( 27 ). All patients received methylprednisolone pulse therapy, and cyclophosphamide was the preferred treatment option.

In clinical practice, the five-factor score (FFS), which was meticulously developed and refined by the French Vasculitis Study Group, is utilized to assess disease risk factors and predict prognosis ( 1 ). It includes: (1) involvement of the gastrointestinal tract (2) cardiac involvement (3) serum creatinine levels surpassing 150 μmol/L (4) age exceeding 65 years (5) absence of ear, nose, and throat involvement. Each factor is assigned a score of 1, and higher cumulative scores indicate a poorer prognosis. However it fails to provide clear guidance for other adverse outcomes in EGPA patients, such as disability due to peripheral nerve involvement ( 20 ).

The case we are reporting is an EGPA patient with CNS who exhibits PRES accompanied by cerebral artery stenosis. Both domestically and internationally, there have been no reports on this condition in children. This highlights the diverse nature of neurological symptoms in EGPA patients. If patients exhibit allergic diseases, including asthma, allergic rhinitis, urticaria, and have elevated eosinophil counts, they should be highly suspected of having EGPA. It is crucial to conduct cranial imaging and other tests to diagnose EGPA as soon as possible and establish a corresponding treatment plan to improve the prognosis for these children.

EGPA is a rare condition, even more so in children. The absence of distinctive clinical manifestations makes it prone to misdiagnosis and delayed diagnosis, leading to many patients not receiving early diagnosis and treatment. Therefore, it is crucial to have a thorough understanding of the clinical characteristics of EGPA, diagnose and treat the condition promptly and consistently before severe organ involvement occurs, and prevent irreversible organ damage to enhance patient prognosis and quality of life.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Ethics statement

The studies involving humans were approved by the Affiliated Hospital of Qingdao University. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.

Author contributions

NN: Conceptualization, Data curation, Formal Analysis, Writing – original draft. LL: Conceptualization, Data curation, Formal Analysis, Writing – original draft. CB: Data curation, Formal Analysis, Methodology, Writing – original draft. DW: Data curation, Supervision, Writing – original draft. SG: Data curation, Supervision, Writing – original draft. JL: Data curation, Writing – original draft. RZ: Formal Analysis, Investigation, Writing – original draft. YL: Data curation, Supervision, Writing – original draft. QZ: Data curation, Supervision, Writing – original draft. HC: Conceptualization, Investigation, Project administration, Writing – review & editing.

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Acknowledgments

The authors thank their colleagues at the Affiliated Hospital of Qingdao University for editorial support and comments.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Keywords: eosinophilic granulomatosis with polyangiitis, child, central nervous system, diagnosis, therapy

Citation: Nie N, Liu L, Bai C, Wang D, Gao S, Liu J, Zhang R, Lin Y, Zhang Q and Chang H (2024) Eosinophilic granulomatous polyangiitis with central nervous system involvement in children: a case report and literature review. Front. Immunol. 15:1406424. doi: 10.3389/fimmu.2024.1406424

Received: 26 March 2024; Accepted: 01 May 2024; Published: 15 May 2024.

Reviewed by:

Copyright © 2024 Nie, Liu, Bai, Wang, Gao, Liu, Zhang, Lin, Zhang and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Hong Chang, [email protected]

† These authors have contributed equally to this work and share first authorship

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Research Article

Financial hardship among patients suffering from neglected tropical diseases: A systematic review and meta-analysis of global literature

Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Visualization, Writing – original draft

Affiliations Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, United States of America, Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

Roles Conceptualization, Data curation, Formal analysis, Investigation, Validation, Writing – review & editing

Affiliations Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, United States of America, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea

Roles Investigation, Writing – review & editing

Affiliation Corvaxan Foundation, Villanova, Pennsylvania, United States of America

Roles Conceptualization, Writing – review & editing

Affiliation Department of Global Programme for Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland

Roles Conceptualization, Funding acquisition, Project administration, Writing – review & editing

* E-mail: [email protected]

Affiliations Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, United States of America, IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah, United States of America

• Chanthawat Patikorn, 
• Jeong-Yeon Cho, 
• Joshua Higashi, 
• Xiao Xian Huang, 
• Nathorn Chaiyakunapruk

• Published: May 13, 2024
• https://doi.org/10.1371/journal.pntd.0012086
• Peer Review
• Reader Comments

Introduction

Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs.

We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I 2 statistic.

Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0–11.0%), dengue (12.5%), and lymphatic filariasis (0.0–23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9–99.3%) and visceral leishmaniasis (24.6–91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65–80%, n = 2, I 2 = 0.00%). Costs of visceral leishmaniasis impoverished 20–26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare.

NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors.

Author summary

Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. We found that NTDs lead to a substantial number of households facing financial hardship. CHS risk due to direct OOP costs was relatively low among patients with leprosy (0.0–11.0%), dengue (12.5%), and lymphatic filariasis (0.0–23.0%), and relatively high among patients with Buruli ulcers (45.6%). CHS risk varied widely among patients with chikungunya (11.9–99.3%) and visceral leishmaniasis (24.6–91.8%). Costs of visceral leishmaniasis impoverished 20–26% of 61 households, depending on the costs captured. Nevertheless, financial hardship caused by NTDs was not comprehensively evaluated in the literature. Therefore, to develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors.

Citation: Patikorn C, Cho J-Y, Higashi J, Huang XX, Chaiyakunapruk N (2024) Financial hardship among patients suffering from neglected tropical diseases: A systematic review and meta-analysis of global literature. PLoS Negl Trop Dis 18(5): e0012086. https://doi.org/10.1371/journal.pntd.0012086

Editor: Yoel Lubell, Mahidol-Oxford Tropical Medicine Research Unit, THAILAND

Received: November 7, 2023; Accepted: March 20, 2024; Published: May 13, 2024

Copyright: © 2024 Patikorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

Funding: This study is funded by the Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland. XXH, as an employee of the World Health Organization, contributed to this study in terms of study design, data interpretation, and report writing.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:XXH works for the World Health Organization. The author alone is responsible for the views expressed in this publication and does not necessarily represent the decisions, policies, or views of the World Health Organization.

In 2021, the World Health Organization (WHO) reported that 1.65 billion people required treatment and care for neglected tropical diseases (NTDs) as they faced humanistic, social, and economic burdens incurred by the diseases. NTDs are a diverse group of diseases that mainly affect underprivileged communities in tropical and subtropical areas [ 1 ]. NTDs predominantly affect disadvantaged populations in low- and middle-income countries (LMICs) due to the lack of timely access to affordable care. It has been reported that every low-income country is affected by at least five NTDs [ 2 ]. Even worse, impoverishment serves as a structural determinant. At the same time, it is a consequence of NTDs due to the direct and indirect costs incurred [ 3 ]. Therefore, the WHO has advocated in their recent NTDs 2021–2023 roadmap that NTDs must be overcome to attain Sustainable Development Goals (SDGs) and ensure Universal Health Coverage (UHC). The NTDs 2021–2030 roadmap targets that 90% of the population at risk are protected against catastrophic out-of-pocket (OOP) health spending caused by NTDs [ 1 ].

Financial hardship is usually quantified as catastrophic health spending (CHS) (as known as catastrophic health expenditure) and impoverishment. CHS is the proportion of households with OOP costs incurred by a specific disease that exceed a specific threshold of the total household income or expenditure (budget share approach) or non-subsistent household expenditure (capacity-to-pay approach). Impoverishment is when the OOP costs push households below the poverty line [ 4 – 6 ]. CHS and impoverishment are well-established indicators for the financial risk protection of the healthcare system, which was an essential dimension of the UHC as indicated under the SDG 3.8.2 indicators [ 1 , 7 ].

Financial hardship poses a greater challenge for individuals affected by NTDs, as they frequently reside in poverty before the onset of the disease. To evaluate the long-term economic risk imposed by health spending on NTDs, it is important to understand the coping strategies of this population. Literature has shown that coping strategies, such as seeking financial assistance through loans or selling their assets, could push households into or further into poverty if it impacts their productivity [ 8 ]. Thus, providing coverage to these groups effectively strengthens the financial risk protection of the health system [ 7 ]. Since some types of NTD are closely related to financial hardship, improving their financial protection may help attain UHC, especially for LMICs [ 9 ].

Financial protection is an essential indicator for NTDs and UHC; however, there was limited research on the financial hardship of NTDs. Although many studies addressed the question of the economic burden of NTDs, there is no systematic review and meta-analysis summarizing the financial hardship faced by the population affected by NTDs. Therefore, to fill this knowledge gap and build a baseline for the NTDs roadmap’s financial risk protection indicator, this study aimed to summarize the prevalence and magnitude of financial hardship among patients suffering from NTDs. Additionally, we assessed the methodologies of quantifying CHS and impoverishment incurred by NTDs.

Scope of the review

The protocol of this systematic review was registered with PROSPERO (CRD42023385627) [ 10 ]. This study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline ( S1 PRISMA Checklist) [ 11 ]. Differences from the original review protocol are described with rationale ( S1 Table ).

This systematic literature review focused on 20 diseases selected as NTDs by WHO: Buruli ulcer, Chagas disease, dengue and chikungunya, dracunculiasis (Guinea-worm disease), echinococcosis, foodborne trematodiases, human African trypanosomiasis (sleeping sickness), leishmaniasis, leprosy (Hansen’s disease), lymphatic filariasis, mycetoma, chromoblastomycosis and other deep mycoses, onchocerciasis (river blindness), rabies, scabies and other ectoparasitoses, schistosomiasis, soil-transmitted helminthiases, snakebite envenoming, taeniasis/cysticercosis, trachoma, and yaws and other endemic treponematoses [ 12 ].

Outcomes of interest of this systematic review were the prevalence and magnitude of victims who faced financial hardship caused by NTDs, including CHS, impoverishment, and coping strategies.

Search strategy and selection process

We searched three bibliographic databases, PubMed, EMBASE, and EconLit, to identify articles reporting financial hardship among patients suffering from NTDs from any country indexed from database inception to January 1, 2023. We also searched for grey literature in two databases, OpenGrey and EBSCO Open Dissertations. The search terms used were ( Disease name and its synonyms ) AND (catastroph* OR impoverish* OR coping OR economic consequence* OR out-of-pocket OR "out of pocket" OR ((household OR family OR patient AND (cost* OR spending OR expen*))), that was adapted to match the search techniques of each database. A full search strategy is shown in S2 Table . There was no language restriction applied in this systematic review. A supplemental search was performed by tracking citation and snowballing the eligible articles’ reference list.

Two reviewers (CP and JYC) independently performed the study selection. They screened the titles and abstracts of identified articles from database searches for relevance. Potentially relevant articles were sought for full-text articles. We requested the authors for full-text articles or reports of highly relevant articles without full-text articles, such as conference abstracts. The retrieved full-text articles were selected based on the eligibility criteria. Discrepancies arising during study selection were resolved by discussion with the third reviewer (NC).

Eligibility criteria

We included empirical studies reporting CHS, impoverishment, or coping strategies incurred by NTDs using primary data collection.

Data extraction

We developed a data extraction sheet by performing a pilot test of extracting five randomly selected articles and refining it until finalization. Two reviewers (CP and JYC) independently performed data extraction. Another reviewer (JH) checked the extracted data for correctness. Any discrepancies were resolved by discussion among reviewers.

Study findings and methodological characteristics extracted from the eligible articles are as follows: first author, publication year, NTDs, study setting, study design, sample characteristics, sample size, data collection period, data collection methods, time horizon, a perspective of the analysis, discount rate, costing year, reported currency, cost units, the definition of CHS and impoverishment, prevalence and magnitude of CHS and impoverishment incurred, economic consequences and coping strategies of financial hardship. Corresponding authors of the eligible articles were contacted to request individual patient-level data. However, we received no response.

The financial risk protection metric is intended to capture only the OOP costs for medical services (e.g., treatment and diagnosis costs). However, some studies considered certain types of direct non-medical costs (e.g., transportation, food, and accommodation costs) and indirect costs (e.g., productivity and income losses) when quantifying financial hardship. Some studies also included informal care costs, such as traditional medicine, as OOP costs [ 6 ]. Thus, our systematic review categorized costs extracted from the eligible studies as direct costs (OOP costs) and indirect costs. Direct costs were further categorized as direct medical costs and direct non-medical costs. The combination of direct costs and indirect costs was categorized as total costs.

Quality assessment

Two reviewers independently assessed the eligible articles’ quality (CP and JYC). Any discrepancies were resolved by consensus among the reviewers. To the best of our knowledge, there is no risk-of-bias assessment tool for economic burden studies. Hence, we assessed the quality of the eligible articles using the cost-of-illness evaluation checklist by Larg and Moss [ 13 ].

Data synthesis

A narrative synthesis was performed to summarize study findings, methodological characteristics, and the quality of the eligible studies. The identified countries were categorized based on the World Bank’s income levels and regions [ 14 ].

Statistical analysis

We performed meta-analyses to calculate the pooled prevalence of households experiencing financial hardship. However, this was possible only for studies that quantified financial hardship using the same measurement definition for a particular NTD. For example, we performed a meta-analysis to calculate the pooled prevalence of households experiencing CHS due to visceral leishmaniasis based on two studies that defined CHS as direct costs exceeding 10% of annual household income [ 8 , 15 ]. The remaining studies were not meta-analyzed due to the differences in the definitions of CHS. We estimated the pooled prevalence of CHS and 95% confidence intervals (CI) using a random-effects model under the DerSimonian and Laird approach [ 16 ]. Effect sizes were computed using each study’s Freeman–Tukey double-arcsine-transformed proportion. This variance-stabilizing transformation is particularly preferable when the proportions are close to 0 or 1 [ 17 ]. p < .05 was considered statistically significant in 2-sided tests.

Heterogeneity was evaluated by observing the forest plots and using the I 2 statistic that estimated the proportion of variability in a meta-analysis that is explained by differences between the included trials rather than by sampling error. Subgroup analyses were performed to explore possible causes of heterogeneity among study results. Publication bias was assessed using the funnel plot asymmetry test and the Egger regression asymmetry test [ 18 ]. Statistical analyses were conducted using Stata version 18.0 (Stata Corporation).

Patient and public involvement

Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.

Overall characteristics of the included studies

A total of 1,768 articles were identified from the search, of which 10 studies were included ( Fig 1 ) [ 8 , 15 , 19 – 26 ]. A list of excluded studies with reasons is presented in S3 Table . These studies quantified financial hardship among 2,761 patients in five LMICs (India, Nepal, Nigeria, Sudan, and Vietnam) who had been diagnosed with six out of the WHO’s 20 NTDs, including Buruli ulcer [ 20 ], chikungunya [ 21 , 26 ], dengue [ 22 ], visceral leishmaniasis [ 8 , 15 , 25 ], leprosy [ 19 , 23 ], and lymphatic filariasis [ 24 ]. Table 1 provides a summary of the study characteristics. We found no major concern in the quality of the included studies ( S4 Table )

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Financial hardship caused by NTDs was quantified as CHS (10 studies) [ 8 , 15 , 19 – 26 ], and impoverishment (1 study) [ 8 ]. All studies were conducted in LMICs with a focus on South Asia (7 studies) [ 8 , 19 , 21 , 23 – 26 ], Sub-Saharan Africa (2 studies) [ 15 , 20 ], East Asia & Pacific (1 study) [ 22 ]. Patients were mostly identified using a hospital-based approach (7 studies) [ 8 , 15 , 19 , 20 , 22 , 23 , 25 ], with active case-finding intervention implemented in two of those studies [ 20 , 23 ]. Five studies reported that patients sought informal healthcare, such as traditional healers, ayurveda, and homeopathy [ 19 – 21 , 25 , 26 ].

Costs captured in the financial hardship were direct medical costs (10 studies, 100%) [ 8 , 15 , 19 – 26 ], direct non-medical costs (9 studies, 90%) [ 8 , 15 , 19 – 21 , 23 – 26 ], and indirect costs (7 studies, 70%) [ 8 , 15 , 19 , 21 , 23 , 25 , 26 ], as summarized in Table 2 . These costs were captured with a different timeframe, including during a disease episode [ 8 , 15 , 20 , 21 , 25 , 26 ], during hospitalization in an intensive care unit [ 22 ], monthly costs with a maximum recall period of 3 years [ 19 ], per one outpatient visit in the last 6 months [ 23 ], and per one hospitalization episode in the last year and per one outpatient visit in the last 15 days [ 24 ]. Abandonment of healthcare seeking due to financial burden was not reflected in the reported costs as the included studies captured only patients who sought healthcare.

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The health insurance systems or special programs covered some of the costs. The costs for diagnosis and treatment of visceral leishmaniasis were provided free of charge to patients under the publicly financed health insurance system in Nepal [ 8 , 25 ] and Sudan [ 15 ]. In Nigeria, international development partners funded a special program that provided free diagnosis and treatment of Buruli ulcers, as well as accommodation, school funding, and basic allowance [ 20 ]. Additionally, the Indian government had a special program that provides financial assistance to families of patients affected by leprosy [ 19 ]. However, patients in India had to pay high OOP costs for medical services for leprosy [ 19 , 23 ], chikungunya [ 21 , 26 ], and lymphatic filariasis [ 24 ]. Similarly, patients in Vietnam also paid high OOP costs for the medical treatment of dengue [ 22 ]. For more details, refer to Table 3 .

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Financial hardship among patients suffering from NTDs

Catastrophic health spending..

CHS was variedly defined across studies in terms of types of costs (medical costs, medical and transportation costs, direct costs, indirect costs, or total costs), thresholds (5%, 10%, 15%, 25%, 30%, 40%, or 100%), timeframe (monthly, quarterly, or annual), household resources (income, consumption expenditure, national average annual household expenditure, or international poverty line) and perspective (household or individual). All studies used the budget share approach to quantify CHS. The most commonly used definitions of CHS caused by NTDs were direct costs of a disease episode exceeding 10% of annual household income (3 studies) [ 8 , 15 , 20 ] and total costs of a disease episode exceeding 10% of annual household income (3 studies) [ 8 , 15 , 25 ]. CHS that included only the direct medical costs was reported in two studies [ 8 , 22 ].

We summarized the prevalence of households experiencing CHS and the magnitude of CHS, determined as the percentage of the costs of NTDs as a share of income, in Table 4 . The prevalence and magnitude of CHS varied depending on the definitions of CHS, disease duration (episodic or chronic), and thresholds used (≤10% or >10%). Overall, the direct costs of NTDs resulted in a wide range of households experiencing CHS. CHS was generally low among patients with leprosy (0.0–11.0%) [ 19 , 23 ], dengue (12.5%) [ 22 ], and lymphatic filariasis (0.0–23.0%) [ 24 ], and relatively high among patients with Buruli ulcers (45.6%) [ 20 ]. CHS varied widely among patients with chikungunya (11.9–99.3%) [ 21 , 26 ] and visceral leishmaniasis (24.6–91.8%) [ 8 , 15 , 25 ].

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Meta-analyses were performed to pool the prevalence of CHS in studies reporting CHS using the same measurement definition in a particular CHS. This was only possible for visceral leishmaniasis, in which CHS was quantified as direct costs of a disease episode exceeding 10% of annual household income in two studies [ 8 , 15 ], and total costs exceeding 10% of annual household income in three studies [ 8 , 15 , 25 ].

The pooled prevalence of CHS, defined as direct costs exceeding 10% of annual household income, was 73% (95% CI; 65–80%, n = 2, I 2 = 0.00%), as shown in Fig 2A . Egger’s test (P = 0.80) indicated no evidence of small-study effects. Visual inspection of the funnel plot indicated no evidence of publication bias ( S1A Fig ).

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The pooled prevalence of CHS, defined as total costs exceeding 10% of annual household income, was 74% (95% CI; 49–93%, n = 3, I 2 = 94.72%), as shown in S2 Fig . We explored the source of heterogeneity by visual inspection of the forest plot. We found that the source of heterogeneity was the differences in the treatment of visceral leishmaniasis, where sodium stibogluconate was used in two studies [ 8 , 15 ], and miltefosine in one study [ 25 ]. Therefore, we performed a subgroup meta-analysis based on different treatments, as shown in Fig 2B . We removed one study [ 25 ] from the meta-analysis to investigate the publication bias without the presence of heterogeneity. Egger’s test (P = 0.81) indicated no evidence of small-study effects. Visual inspection of the funnel plot indicated no evidence of publication bias ( S1B Fig ).

Impoverishment.

Impoverishment was investigated in one study in patients with visceral leishmaniasis, which defined impoverishment as annual household income falling below the poverty line after paying for treatment [ 8 ]. Costs of visceral leishmaniasis impoverished 20–26% of the 61 households investigated, depending on the costs captured (20% medical costs, 21% medical and transportation costs, 26% direct costs), as shown in Table 2 .

Coping strategies

Four studies reported coping strategies used by patients to pay the costs of NTDs. These strategies included using savings (71–100% of patients), taking out loans (32–80%), selling livestock or other assets (17–32%), or borrowing money (0–23%), as shown in Table 2 . However, these studies did not distinguish between coping strategies used by patients who experienced CHS and those who did not [ 8 , 19 , 24 , 25 ].

Cost drivers and determinants of financial hardship

To understand the cost drivers of financial hardship caused by NTDs, we analyzed the percentage share of types of costs captured in the direct costs. The findings are presented in Fig 3 . Direct medical costs were the primary cost driver in nine studies [ 8 , 19 – 21 , 23 – 26 ]. However, one study identified food and transportation costs as the main cost drivers [ 15 ].

Abbreviation: ENL–erythema nodosum leprosum. Tripathy et al, 2020 [ 24 ]; Tiwari et al, 2018 [ 23 ]; Chandler et al, 2015 [ 19 ]; Uranw et al, 2013 [ 25 ], Meheus et al, 2013 [ 15 ], Adhikari et al, 2009 [ 8 ], McBride et al, 2019[ 22 ], Vijayakumar et al, 2013 [ 26 ], Gopalan et al, 2009 [ 21 ], Chukwu et al, 2017 [ 20 ] .

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Determinants of CHS were assessed in one study among patients with Buruli ulcers. The study concluded that neither age, gender, rural/urban location, education, occupation, religion, nor patient income group was a determinant of CHS [ 20 ]. There was no study investigating determinants of impoverishment.

NTDs primarily impact populations with limited financial means, yet the literature addressing the financial hardship caused by NTDs is relatively scarce. Our systematic review revealed that there were only ten studies covering six NTDs. We discovered that many households are facing financial hardship as a result of NTDs, despite having access to publicly funded healthcare systems or special NTD programs. The costs related to NTDs resulted in significant financial hardship for these households, mainly due to the high OOP costs associated with medical treatment. Even in situations where drugs used to treat NTDs were provided free of charge, the costs for supportive care, medical procedures, transportation, and food were still high and could have a devastating financial impact on these households. Moreover, these financial hardship indicators might not fully reflect the financial risk of the population affected by NTDs because many live in poverty or even extreme poverty. Victims of NTDs are usually those who are socially disadvantaged. They need to make trade-offs between suffering from the disease and seeking healthcare because not all victims can afford the costs of NTDs, especially OOP costs for medical treatment and transportation, which could lead to the abandonment of healthcare [ 1 – 3 ].

The research findings have shown that merely providing funding for treatments of NTDs is insufficient for protecting those affected by NTDs from financial hardship. Therefore, it is crucial to strengthen the entire healthcare system to effectively address the challenges of NTDs and provide financial protection to the victims. Additionally, it is important to encourage and engage communities to change the behavior of those affected by NTDs so that they seek medical assistance at appropriate healthcare facilities instead of relying on traditional healers or not seeking care at all. Our research also supports the need for an economic framework to guide NTD investments [ 27 ]. The ability to prioritize investments, informed partially by economic parameters, may appeal to a broad set of stakeholders and help facilitate the process of building coalitions to achieve the WHO’s goal that 90% of the at-risk population is protected against financial hardship caused by NTDs [ 1 ].

Although there is no consensus regarding the estimation approach and thresholds in quantifying CHS, it is important to note that these differences can significantly impact the findings and consequently impact the applications and implications of the findings [ 6 , 28 ]. We found that CHS was variedly defined across studies in terms of estimation approach, types of costs, thresholds, timeframe, household resources, and perspective. Our review revealed that 90% of the included studies captured direct non-medical costs as part of the OOP costs [ 8 , 15 , 19 – 21 , 23 – 26 ]. Furthermore, Seventy percent of the included studies considered indirect costs in quantifying financial hardship [ 8 , 15 , 19 , 21 , 23 , 25 , 26 ]. This approach aligned with an indicator called “catastrophic costs” that has emerged in tuberculosis studies. Catastrophic costs occur when the total healthcare costs, including direct and indirect costs, exceed 20% of the annual household income [ 28 ]. This indicator could be a more comprehensive measure of the overall financial burden of NTDs on the household beyond just the OOP costs which will be useful when evaluating and monitoring different healthcare policies and interventions to mitigate financial hardship caused by NTDs.

The findings of this systematic review and meta-analysis should be interpreted under the following limitations. The included studies in our review only focused on patients who sought healthcare, so the financial burden of those who did not seek healthcare was not captured in the reported OOP costs. This means that people who could not afford healthcare may have been excluded from these studies. Moreover, we could not perform meta-analyses of the prevalence of CHS on all identified NTDs due to differences in how CHS was quantified across studies and lack of access to individual patient-level data.

Hence, we highlighted some methodological considerations to guide future studies on financial hardship among households suffering from NTDs to gain a better understanding of the neglected public health issues and to inform the development of strategies of what to address to tackle the financial burden of NTDs. Firstly, methods to quantify financial hardship should be coherent to allow comparability across studies. For instance, CHS and impoverishment should be defined and measured in a relevant manner to the nature of the NTD, including estimation approach, thresholds, types of costs, timeframe, household resources, and perspective. Secondly, subgroup analyses should be conducted to evaluate the determinants of financial hardship across household characteristics (e.g., income, socioeconomic status) or phases of disease (e.g., disease onset, treatment seeking, diagnosis, treatment, post-treatment). Lastly, coping strategies should be assessed among those who did and did not experience financial hardship to understand the economic consequences of financial hardship across subgroups.

NTDs can be a devastating burden on households, not only in terms of physical and mental health but also financially. NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. Furthermore, OOP costs represented only a partial picture of the financial hardship the population affected by NTDs faces. To mitigate this financial hardship, it is imperative to conduct thorough research to identify the factors contributing to it. Future research should consider various household characteristics, such as income, education level, and geographic location, as well as the different disease stages, from onset to treatment completion. Future studies should also investigate the hidden financial burden due to the abandonment of healthcare-seeking to capture the economic burden and opportunity costs of those who did not seek healthcare. By carefully examining these factors, researchers and decision-makers can gain insight into the specific challenges faced by households affected by NTDs and develop targeted interventions to alleviate financial hardships. Ultimately, these studies can help inform the development of strategies to reduce the burden of NTDs on households and improve overall health outcomes.

Supporting information

S1 prisma checklist. prisma checklist..

https://doi.org/10.1371/journal.pntd.0012086.s001

S1 Table. Differences from original review protocol.

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S2 Table. Full search strategy.

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S3 Table. Excluded studies with reasons.

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S4 Table. Quality assessment using Larg, A., and Moss, J. R. (2011) Cost-of-illness studies: a guide to critical evaluation.

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S1 Fig. Assessment of publication bias.

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S2 Fig. Forest plot of pooled proportion of catastrophic health spending defined as total costs exceeding 10% of annual household income.

https://doi.org/10.1371/journal.pntd.0012086.s007

Acknowledgments

The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

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Writing a Scientific Review Article: Comprehensive Insights for Beginners

Ayodeji amobonye.

1 Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, KwaZulu-Natal, Durban 4000, South Africa

2 Writing Centre, Durban University of Technology, P.O. Box 1334 KwaZulu-Natal, Durban 4000, South Africa

Japareng Lalung

3 School of Industrial Technology, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia

Santhosh Pillai

Associated data.

The data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

Review articles present comprehensive overview of relevant literature on specific themes and synthesise the studies related to these themes, with the aim of strengthening the foundation of knowledge and facilitating theory development. The significance of review articles in science is immeasurable as both students and researchers rely on these articles as the starting point for their research. Interestingly, many postgraduate students are expected to write review articles for journal publications as a way of demonstrating their ability to contribute to new knowledge in their respective fields. However, there is no comprehensive instructional framework to guide them on how to analyse and synthesise the literature in their niches into publishable review articles. The dearth of ample guidance or explicit training results in students having to learn all by themselves, usually by trial and error, which often leads to high rejection rates from publishing houses. Therefore, this article seeks to identify these challenges from a beginner's perspective and strives to plug the identified gaps and discrepancies. Thus, the purpose of this paper is to serve as a systematic guide for emerging scientists and to summarise the most important information on how to write and structure a publishable review article.

1. Introduction

Early scientists, spanning from the Ancient Egyptian civilization to the Scientific Revolution of the 16 th /17 th century, based their research on intuitions, personal observations, and personal insights. Thus, less time was spent on background reading as there was not much literature to refer to. This is well illustrated in the case of Sir Isaac Newton's apple tree and the theory of gravity, as well as Gregor Mendel's pea plants and the theory of inheritance. However, with the astronomical expansion in scientific knowledge and the emergence of the information age in the last century, new ideas are now being built on previously published works, thus the periodic need to appraise the huge amount of already published literature [ 1 ]. According to Birkle et al. [ 2 ], the Web of Science—an authoritative database of research publications and citations—covered more than 80 million scholarly materials. Hence, a critical review of prior and relevant literature is indispensable for any research endeavour as it provides the necessary framework needed for synthesising new knowledge and for highlighting new insights and perspectives [ 3 ].

Review papers are generally considered secondary research publications that sum up already existing works on a particular research topic or question and relate them to the current status of the topic. This makes review articles distinctly different from scientific research papers. While the primary aim of the latter is to develop new arguments by reporting original research, the former is focused on summarising and synthesising previous ideas, studies, and arguments, without adding new experimental contributions. Review articles basically describe the content and quality of knowledge that are currently available, with a special focus on the significance of the previous works. To this end, a review article cannot simply reiterate a subject matter, but it must contribute to the field of knowledge by synthesising available materials and offering a scholarly critique of theory [ 4 ]. Typically, these articles critically analyse both quantitative and qualitative studies by scrutinising experimental results, the discussion of the experimental data, and in some instances, previous review articles to propose new working theories. Thus, a review article is more than a mere exhaustive compilation of all that has been published on a topic; it must be a balanced, informative, perspective, and unbiased compendium of previous studies which may also include contrasting findings, inconsistencies, and conventional and current views on the subject [ 5 ].

Hence, the essence of a review article is measured by what is achieved, what is discovered, and how information is communicated to the reader [ 6 ]. According to Steward [ 7 ], a good literature review should be analytical, critical, comprehensive, selective, relevant, synthetic, and fully referenced. On the other hand, a review article is considered to be inadequate if it is lacking in focus or outcome, overgeneralised, opinionated, unbalanced, and uncritical [ 7 ]. Most review papers fail to meet these standards and thus can be viewed as mere summaries of previous works in a particular field of study. In one of the few studies that assessed the quality of review articles, none of the 50 papers that were analysed met the predefined criteria for a good review [ 8 ]. However, beginners must also realise that there is no bad writing in the true sense; there is only writing in evolution and under refinement. Literally, every piece of writing can be improved upon, right from the first draft until the final published manuscript. Hence, a paper can only be referred to as bad and unfixable when the author is not open to corrections or when the writer gives up on it.

According to Peat et al. [ 9 ], “everything is easy when you know how,” a maxim which applies to scientific writing in general and review writing in particular. In this regard, the authors emphasized that the writer should be open to learning and should also follow established rules instead of following a blind trial-and-error approach. In contrast to the popular belief that review articles should only be written by experienced scientists and researchers, recent trends have shown that many early-career scientists, especially postgraduate students, are currently expected to write review articles during the course of their studies. However, these scholars have little or no access to formal training on how to analyse and synthesise the research literature in their respective fields [ 10 ]. Consequently, students seeking guidance on how to write or improve their literature reviews are less likely to find published works on the subject, particularly in the science fields. Although various publications have dealt with the challenges of searching for literature, or writing literature reviews for dissertation/thesis purposes, there is little or no information on how to write a comprehensive review article for publication. In addition to the paucity of published information to guide the potential author, the lack of understanding of what constitutes a review paper compounds their challenges. Thus, the purpose of this paper is to serve as a guide for writing review papers for journal publishing. This work draws on the experience of the authors to assist early-career scientists/researchers in the “hard skill” of authoring review articles. Even though there is no single path to writing scientifically, or to writing reviews in particular, this paper attempts to simplify the process by looking at this subject from a beginner's perspective. Hence, this paper highlights the differences between the types of review articles in the sciences while also explaining the needs and purpose of writing review articles. Furthermore, it presents details on how to search for the literature as well as how to structure the manuscript to produce logical and coherent outputs. It is hoped that this work will ease prospective scientific writers into the challenging but rewarding art of writing review articles.

2. Benefits of Review Articles to the Author

Analysing literature gives an overview of the “WHs”: WHat has been reported in a particular field or topic, WHo the key writers are, WHat are the prevailing theories and hypotheses, WHat questions are being asked (and answered), and WHat methods and methodologies are appropriate and useful [ 11 ]. For new or aspiring researchers in a particular field, it can be quite challenging to get a comprehensive overview of their respective fields, especially the historical trends and what has been studied previously. As such, the importance of review articles to knowledge appraisal and contribution cannot be overemphasised, which is reflected in the constant demand for such articles in the research community. However, it is also important for the author, especially the first-time author, to recognise the importance of his/her investing time and effort into writing a quality review article.

Generally, literature reviews are undertaken for many reasons, mainly for publication and for dissertation purposes. The major purpose of literature reviews is to provide direction and information for the improvement of scientific knowledge. They also form a significant component in the research process and in academic assessment [ 12 ]. There may be, however, a thin line between a dissertation literature review and a published review article, given that with some modifications, a literature review can be transformed into a legitimate and publishable scholarly document. According to Gülpınar and Güçlü [ 6 ], the basic motivation for writing a review article is to make a comprehensive synthesis of the most appropriate literature on a specific research inquiry or topic. Thus, conducting a literature review assists in demonstrating the author's knowledge about a particular field of study, which may include but not be limited to its history, theories, key variables, vocabulary, phenomena, and methodologies [ 10 ]. Furthermore, publishing reviews is beneficial as it permits the researchers to examine different questions and, as a result, enhances the depth and diversity of their scientific reasoning [ 1 ]. In addition, writing review articles allows researchers to share insights with the scientific community while identifying knowledge gaps to be addressed in future research. The review writing process can also be a useful tool in training early-career scientists in leadership, coordination, project management, and other important soft skills necessary for success in the research world [ 13 ]. Another important reason for authoring reviews is that such publications have been observed to be remarkably influential, extending the reach of an author in multiple folds of what can be achieved by primary research papers [ 1 ]. The trend in science is for authors to receive more citations from their review articles than from their original research articles. According to Miranda and Garcia-Carpintero [ 14 ], review articles are, on average, three times more frequently cited than original research articles; they also asserted that a 20% increase in review authorship could result in a 40–80% increase in citations of the author. As a result, writing reviews can significantly impact a researcher's citation output and serve as a valuable channel to reach a wider scientific audience. In addition, the references cited in a review article also provide the reader with an opportunity to dig deeper into the topic of interest. Thus, review articles can serve as a valuable repository for consultation, increasing the visibility of the authors and resulting in more citations.

3. Types of Review Articles

The first step in writing a good literature review is to decide on the particular type of review to be written; hence, it is important to distinguish and understand the various types of review articles. Although scientific review articles have been classified according to various schemes, however, they are broadly categorised into narrative reviews, systematic reviews, and meta-analyses [ 15 ]. It was observed that more authors—as well as publishers—were leaning towards systematic reviews and meta-analysis while downplaying narrative reviews; however, the three serve different aims and should all be considered equally important in science [ 1 ]. Bibliometric reviews and patent reviews, which are closely related to meta-analysis, have also gained significant attention recently. However, from another angle, a review could also be of two types. In the first class, authors could deal with a widely studied topic where there is already an accumulated body of knowledge that requires analysis and synthesis [ 3 ]. At the other end of the spectrum, the authors may have to address an emerging issue that would benefit from exposure to potential theoretical foundations; hence, their contribution would arise from the fresh theoretical foundations proposed in developing a conceptual model [ 3 ].

3.1. Narrative Reviews

Narrative reviewers are mainly focused on providing clarification and critical analysis on a particular topic or body of literature through interpretative synthesis, creativity, and expert judgement. According to Green et al. [ 16 ], a narrative review can be in the form of editorials, commentaries, and narrative overviews. However, editorials and commentaries are usually expert opinions; hence, a beginner is more likely to write a narrative overview, which is more general and is also referred to as an unsystematic narrative review. Similarly, the literature review section of most dissertations and empirical papers is typically narrative in nature. Typically, narrative reviews combine results from studies that may have different methodologies to address different questions or to formulate a broad theoretical formulation [ 1 ]. They are largely integrative as strong focus is placed on the assimilation and synthesis of various aspects in the review, which may involve comparing and contrasting research findings or deriving structured implications [ 17 ]. In addition, they are also qualitative studies because they do not follow strict selection processes; hence, choosing publications is relatively more subjective and unsystematic [ 18 ]. However, despite their popularity, there are concerns about their inherent subjectivity. In many instances, when the supporting data for narrative reviews are examined more closely, the evaluations provided by the author(s) become quite questionable [ 19 ]. Nevertheless, if the goal of the author is to formulate a new theory that connects diverse strands of research, a narrative method is most appropriate.

3.2. Systematic Reviews

In contrast to narrative reviews, which are generally descriptive, systematic reviews employ a systematic approach to summarise evidence on research questions. Hence, systematic reviews make use of precise and rigorous criteria to identify, evaluate, and subsequently synthesise all relevant literature on a particular topic [ 12 , 20 ]. As a result, systematic reviews are more likely to inspire research ideas by identifying knowledge gaps or inconsistencies, thus helping the researcher to clearly define the research hypotheses or questions [ 21 ]. Furthermore, systematic reviews may serve as independent research projects in their own right, as they follow a defined methodology to search and combine reliable results to synthesise a new database that can be used for a variety of purposes [ 22 ]. Typically, the peculiarities of the individual reviewer, different search engines, and information databases used all ensure that no two searches will yield the same systematic results even if the searches are conducted simultaneously and under identical criteria [ 11 ]. Hence, attempts are made at standardising the exercise via specific methods that would limit bias and chance effects, prevent duplications, and provide more accurate results upon which conclusions and decisions can be made.

The most established of these methods is the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines which objectively defined statements, guidelines, reporting checklists, and flowcharts for undertaking systematic reviews as well as meta-analysis [ 23 ]. Though mainly designed for research in medical sciences, the PRISMA approach has gained wide acceptance in other fields of science and is based on eight fundamental propositions. These include the explicit definition of the review question, an unambiguous outline of the study protocol, an objective and exhaustive systematic review of reputable literature, and an unambiguous identification of included literature based on defined selection criteria [ 24 ]. Other considerations include an unbiased appraisal of the quality of the selected studies (literature), organic synthesis of the evidence of the study, preparation of the manuscript based on the reporting guidelines, and periodic update of the review as new data emerge [ 24 ]. Other methods such as PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), MOOSE (Meta-analysis Of Observational Studies in Epidemiology), and ROSES (Reporting Standards for Systematic Evidence Syntheses) have since been developed for systematic reviews (and meta-analysis), with most of them being derived from PRISMA.

Consequently, systematic reviews—unlike narrative reviews—must contain a methodology section which in addition to all that was highlighted above must fully describe the precise criteria used in formulating the research question and setting the inclusion or exclusion criteria used in selecting/accessing the literature. Similarly, the criteria for evaluating the quality of the literature included in the review as well as for analysing, synthesising, and disseminating the findings must be fully described in the methodology section.

3.3. Meta-Analysis

Meta-analyses are considered as more specialised forms of systematic reviews. Generally, they combine the results of many studies that use similar or closely related methods to address the same question or share a common quantitative evaluation method [ 25 ]. However, meta-analyses are also a step higher than other systematic reviews as they are focused on numerical data and involve the use of statistics in evaluating different studies and synthesising new knowledge. The major advantage of this type of review is the increased statistical power leading to more reliable results for inferring modest associations and a more comprehensive understanding of the true impact of a research study [ 26 ]. Unlike in traditional systematic reviews, research topics covered in meta-analyses must be mature enough to allow the inclusion of sufficient homogeneous empirical research in terms of subjects, interventions, and outcomes [ 27 , 28 ].

Being an advanced form of systematic review, meta-analyses must also have a distinct methodology section; hence, the standard procedures involved in the traditional systematic review (especially PRISMA) also apply in meta-analyses [ 23 ]. In addition to the common steps in formulating systematic reviews, meta-analyses are required to describe how nested and missing data are handled, the effect observed in each study, the confidence interval associated with each synthesised effect, and any potential for bias presented within the sample(s) [ 17 ]. According to Paul and Barari [ 28 ], a meta-analysis must also detail the final sample, the meta-analytic model, and the overall analysis, moderator analysis, and software employed. While the overall analysis involves the statistical characterization of the relationships between variables in the meta-analytic framework and their significance, the moderator analysis defines the different variables that may affect variations in the original studies [ 28 , 29 ]. It must also be noted that the accuracy and reliability of meta-analyses have both been significantly enhanced by the incorporation of statistical approaches such as Bayesian analysis [ 30 ], network analysis [ 31 ], and more recently, machine learning [ 32 ].

3.4. Bibliometric Review

A bibliometric review, commonly referred to as bibliometric analysis, is a systematic evaluation of published works within a specific field or discipline [ 33 ]. This bibliometric methodology involves the use of quantitative methods to analyse bibliometric data such as the characteristics and numbers of publications, units of citations, authorship, co-authorship, and journal impact factors [ 34 ]. Academics use bibliometric analysis with different objectives in mind, which includes uncovering emerging trends in article and journal performance, elaborating collaboration patterns and research constituents, evaluating the impact and influence of particular authors, publications, or research groups, and highlighting the intellectual framework of a certain field [ 35 ]. It is also used to inform policy and decision-making. Similarly to meta-analysis, bibliometric reviews rely upon quantitative techniques, thus avoiding the interpretation bias that could arise from the qualitative techniques of other types of reviews [ 36 ]. However, while bibliometric analysis synthesises the bibliometric and intellectual structure of a field by examining the social and structural linkages between various research parts, meta-analysis focuses on summarising empirical evidence by probing the direction and strength of effects and relationships among variables, especially in open research questions [ 37 , 38 ]. However, similarly to systematic review and meta-analysis, a bibliometric review also requires a well-detailed methodology section. The amount of data to be analysed in bibliometric analysis is quite massive, running to hundreds and tens of thousands in some cases. Although the data are objective in nature (e.g., number of citations and publications and occurrences of keywords and topics), the interpretation is usually carried out through both objective (e.g., performance analysis) and subjective (e.g., thematic analysis) evaluations [ 35 ]. However, the invention and availability of bibliometric software such as BibExcel, Gephi, Leximancer, and VOSviewer and scientific databases such as Dimensions, Web of Science, and Scopus have made this type of analysis more feasible.

3.5. Patent Review

Patent reviews provide a comprehensive analysis and critique of a specific patent or a group of related patents, thus presenting a concise understanding of the technology or innovation that is covered by the patent [ 39 ]. This type of article is useful for researchers as it also enhances their understanding of the legal, technical, and commercial aspects of an intellectual property/innovation; in addition, it is also important for stakeholders outside the research community including IP (intellectual property) specialists, legal professionals, and technology-transfer officers [ 40 ]. Typically, patent reviews encompass the scope, background, claims, legal implications, technical specifications, and potential commercial applications of the patent(s). The article may also include a discussion of the patent's strengths and weaknesses, as well as its potential impact on the industry or field in which it operates. Most times, reviews are time specified, they may be regionalised, and the data are usually retrieved via patent searches on databases such as that of the European Patent Office ( https://www.epo.org/searching.html ), United States Patent and Trademark Office ( https://patft.uspto.gov/ ), the World Intellectual Property Organization's PATENTSCOPE ( https://patentscope.wipo.int/search/en/structuredSearch.jsf ), Google Patent ( https://www.google.com/?tbm=pts ), and China National Intellectual Property Administration ( https://pss-system.cponline.cnipa.gov.cn/conventionalSearch ). According to Cerimi et al. [ 41 ], the retrieved data and analysed may include the patent number, patent status, filing date, application date, grant dates, inventor, assignee, and pending applications. While data analysis is usually carried out by general data software such as Microsoft Excel, an intelligence software solely dedicated to patent research and analysis, Orbit Intelligence has been found to be more efficient [ 39 ]. It is also mandatory to include a methodology section in a patent review, and this should be explicit, thorough, and precise to allow a clear understanding of how the analysis was carried out and how the conclusions were arrived at.

4. Searching Literature

One of the most challenging tasks in writing a review article on a subject is the search for relevant literature to populate the manuscript as the author is required to garner information from an endless number of sources. This is even more challenging as research outputs have been increasing astronomically, especially in the last decade, with thousands of new articles published annually in various fields. It is therefore imperative that the author must not only be aware of the overall trajectory in a field of investigation but must also be cognizant of recent studies so as not to publish outdated research or review articles. Basically, the search for the literature involves a coherent conceptual structuring of the topic itself and a thorough collation of evidence under the common themes which might reflect the histories, conflicts, standoffs, revolutions, and/or evolutions in the field [ 7 ]. To start the search process, the author must carefully identify and select broad keywords relevant to the subject; subsequently, the keywords should be developed to refine the search into specific subheadings that would facilitate the structure of the review.

Two main tactics have been identified for searching the literature, namely, systematic and snowballing [ 42 ]. The systematic approach involves searching literature with specific keywords (for example, cancer, antioxidant, and nanoparticles), which leads to an almost unmanageable and overwhelming list of possible sources [ 43 ]. The snowballing approach, however, involves the identification of a particular publication, followed by the compilation of a bibliography of articles based on the reference list of the identified publication [ 44 ]. Many times, it might be necessary to combine both approaches, but irrespective, the author must keep an accurate track and record of papers cited in the search. A simple and efficient strategy for populating the bibliography of review articles is to go through the abstract (and sometimes the conclusion) of a paper; if the abstract is related to the topic of discourse, the author might go ahead and read the entire article; otherwise, he/she is advised to move on [ 45 ]. Winchester and Salji [ 5 ] noted that to learn the background of the subject/topic to be reviewed, starting literature searches with academic textbooks or published review articles is imperative, especially for beginners. Furthermore, it would also assist in compiling the list of keywords, identifying areas of further exploration, and providing a glimpse of the current state of the research. However, past reviews ideally are not to serve as the foundation of a new review as they are written from someone else's viewpoint, which might have been tainted with some bias. Fortunately, the accessibility and search for the literature have been made relatively easier than they were a few decades ago as the current information age has placed an enormous volume of knowledge right at our fingertips [ 46 ]. Nevertheless, when gathering the literature from the Internet, authors should exercise utmost caution as much of the information may not be verified or peer-reviewed and thus may be unregulated and unreliable. For instance, Wikipedia, despite being a large repository of information with more than 6.7 million articles in the English language alone, is considered unreliable for scientific literature reviews, due to its openness to public editing [ 47 ]. However, in addition to peer-reviewed journal publications—which are most ideal—reviews can also be drawn from a wide range of other sources such as technical documents, in-house reports, conference abstracts, and conference proceedings. Similarly, “Google Scholar”—as against “Google” and other general search engines—is more appropriate as its searches are restricted to only academic articles produced by scholarly societies or/and publishers [ 48 ]. Furthermore, the various electronic databases, such as ScienceDirect, Web of Science, PubMed, and MEDLINE, many of which focus on specific fields of research, are also ideal options [ 49 ]. Advancement in computer indexing has remarkably expanded the ease and ability to search large databases for every potentially relevant article. In addition to searching by topic, literature search can be modified by time; however, there must be a balance between old papers and recent ones. The general consensus in science is that publications less than five years old are considered recent.

It is important, especially in systematic reviews and meta-analyses, that the specific method of running the computer searches be properly documented as there is the need to include this in the method (methodology) section of such papers. Typically, the method details the keywords, databases explored, search terms used, and the inclusion/exclusion criteria applied in the selection of data and any other specific decision/criteria. All of these will ensure the reproducibility and thoroughness of the search and the selection procedure. However, Randolph [ 10 ] noted that Internet searches might not give the exhaustive list of articles needed for a review article; hence, it is advised that authors search through the reference lists of articles that were obtained initially from the Internet search. After determining the relevant articles from the list, the author should read through the references of these articles and repeat the cycle until saturation is reached [ 10 ]. After populating the articles needed for the literature review, the next step is to analyse them individually and in their whole entirety. A systematic approach to this is to identify the key information within the papers, examine them in depth, and synthesise original perspectives by integrating the information and making inferences based on the findings. In this regard, it is imperative to link one source to the other in a logical manner, for instance, taking note of studies with similar methodologies, papers that agree, or results that are contradictory [ 42 ].

5. Structuring the Review Article

The title and abstract are the main selling points of a review article, as most readers will only peruse these two elements and usually go on to read the full paper if they are drawn in by either or both of the two. Tullu [ 50 ] recommends that the title of a scientific paper “should be descriptive, direct, accurate, appropriate, interesting, concise, precise, unique, and not be misleading.” In addition to providing “just enough details” to entice the reader, words in the titles are also used by electronic databases, journal websites, and search engines to index and retrieve a particular paper during a search [ 51 ]. Titles are of different types and must be chosen according to the topic under review. They are generally classified as descriptive, declarative, or interrogative and can also be grouped into compound, nominal, or full-sentence titles [ 50 ]. The subject of these categorisations has been extensively discussed in many articles; however, the reader must also be aware of the compound titles, which usually contain a main title and a subtitle. Typically, subtitles provide additional context—to the main title—and they may specify the geographic scope of the research, research methodology, or sample size [ 52 ].

Just like primary research articles, there are many debates about the optimum length of a review article's title. However, the general consensus is to keep the title as brief as possible while not being too general. A title length between 10 and 15 words is recommended, since longer titles can be more challenging to comprehend. Paiva et al. [ 53 ] observed that articles which contain 95 characters or less get more views and citations. However, emphasis must be placed on conciseness as the audience will be more satisfied if they can understand what exactly the review has contributed to the field, rather than just a hint about the general topic area. Authors should also endeavour to stick to the journal's specific requirements, especially regarding the length of the title and what they should or should not contain [ 9 ]. Thus, avoidance of filler words such as “a review on/of,” “an observation of,” or “a study of” is a very simple way to limit title length. In addition, abbreviations or acronyms should be avoided in the title, except the standard or commonly interpreted ones such as AIDS, DNA, HIV, and RNA. In summary, to write an effective title, the authors should consider the following points. What is the paper about? What was the methodology used? What were the highlights and major conclusions? Subsequently, the author should list all the keywords from these answers, construct a sentence from these keywords, and finally delete all redundant words from the sentence title. It is also possible to gain some ideas by scanning indices and article titles in major journals in the field. It is important to emphasise that a title is not chosen and set in stone, and the title is most likely to be continually revised and adjusted until the end of the writing process.

5.2. Abstract

The abstract, also referred to as the synopsis, is a summary of the full research paper; it is typically independent and can stand alone. For most readers, a publication does not exist beyond the abstract, partly because abstracts are often the only section of a paper that is made available to the readers at no cost, whereas the full paper may attract a payment or subscription [ 54 ]. Thus, the abstract is supposed to set the tone for the few readers who wish to read the rest of the paper. It has also been noted that the abstract gives the first impression of a research work to journal editors, conference scientific committees, or referees, who might outright reject the paper if the abstract is poorly written or inadequate [ 50 ]. Hence, it is imperative that the abstract succinctly represents the entire paper and projects it positively. Just like the title, abstracts have to be balanced, comprehensive, concise, functional, independent, precise, scholarly, and unbiased and not be misleading [ 55 ]. Basically, the abstract should be formulated using keywords from all the sections of the main manuscript. Thus, it is pertinent that the abstract conveys the focus, key message, rationale, and novelty of the paper without any compromise or exaggeration. Furthermore, the abstract must be consistent with the rest of the paper; as basic as this instruction might sound, it is not to be taken for granted. For example, a study by Vrijhoef and Steuten [ 56 ] revealed that 18–68% of 264 abstracts from some scientific journals contained information that was inconsistent with the main body of the publications.

Abstracts can either be structured or unstructured; in addition, they can further be classified as either descriptive or informative. Unstructured abstracts, which are used by many scientific journals, are free flowing with no predefined subheadings, while structured abstracts have specific subheadings/subsections under which the abstract needs to be composed. Structured abstracts have been noted to be more informative and are usually divided into subsections which include the study background/introduction, objectives, methodology design, results, and conclusions [ 57 ]. No matter the style chosen, the author must carefully conform to the instructions provided by the potential journal of submission, which may include but are not limited to the format, font size/style, word limit, and subheadings [ 58 ]. The word limit for abstracts in most scientific journals is typically between 150 and 300 words. It is also a general rule that abstracts do not contain any references whatsoever.

Typically, an abstract should be written in the active voice, and there is no such thing as a perfect abstract as it could always be improved on. It is advised that the author first makes an initial draft which would contain all the essential parts of the paper, which could then be polished subsequently. The draft should begin with a brief background which would lead to the research questions. It might also include a general overview of the methodology used (if applicable) and importantly, the major results/observations/highlights of the review paper. The abstract should end with one or few sentences about any implications, perspectives, or future research that may be developed from the review exercise. Finally, the authors should eliminate redundant words and edit the abstract to the correct word count permitted by the journal [ 59 ]. It is always beneficial to read previous abstracts published in the intended journal, related topics/subjects from other journals, and other reputable sources. Furthermore, the author should endeavour to get feedback on the abstract especially from peers and co-authors. As the abstract is the face of the whole paper, it is best that it is the last section to be finalised, as by this time, the author would have developed a clearer understanding of the findings and conclusions of the entire paper.

5.3. Graphical Abstracts

Since the mid-2000s, an increasing number of journals now require authors to provide a graphical abstract (GA) in addition to the traditional written abstract, to increase the accessibility of scientific publications to readers [ 60 ]. A study showed that publications with GA performed better than those without it, when the abstract views, total citations, and downloads were compared [ 61 ]. However, the GA should provide “a single, concise pictorial, and visual summary of the main findings of an article” [ 62 ]. Although they are meant to be a stand-alone summary of the whole paper, it has been noted that they are not so easily comprehensible without having read through the traditionally written abstract [ 63 ]. It is important to note that, like traditional abstracts, many reputable journals require GAs to adhere to certain specifications such as colour, dimension, quality, file size, and file format (usually JPEG/JPG, PDF, PNG, or TIFF). In addition, it is imperative to use engaging and accurate figures, all of which must be synthesised in order to accurately reflect the key message of the paper. Currently, there are various online or downloadable graphical tools that can be used for creating GAs, such as Microsoft Paint or PowerPoint, Mindthegraph, ChemDraw, CorelDraw, and BioRender.

5.4. Keywords

As a standard practice, journals require authors to select 4–8 keywords (or phrases), which are typically listed below the abstract. A good set of keywords will enable indexers and search engines to find relevant papers more easily and can be considered as a very concise abstract [ 64 ]. According to Dewan and Gupta [ 51 ], the selection of appropriate keywords will significantly enhance the retrieval, accession, and consequently, the citation of the review paper. Ideally, keywords can be variants of the terms/phrases used in the title, the abstract, and the main text, but they should ideally not be the exact words in the main title. Choosing the most appropriate keywords for a review article involves listing down the key terms and phrases in the article, including abbreviations. Subsequently, a quick review of the glossary/vocabulary/term list or indexing standard in the specific discipline will assist in selecting the best and most precise keywords that match those used in the databases from the list drawn. In addition, the keywords should not be broad or general terms (e.g., DNA, biology, and enzymes) but must be specific to the field or subfield of study as well as to the particular paper [ 65 ].

5.5. Introduction

The introduction of an article is the first major section of the manuscript, and it presents basic information to the reader without compelling them to study past publications. In addition, the introduction directs the reader to the main arguments and points developed in the main body of the article while clarifying the current state of knowledge in that particular area of research [ 12 ]. The introduction part of a review article is usually sectionalised into background information, a description of the main topic and finally a statement of the main purpose of the review [ 66 ]. Authors may begin the introduction with brief general statements—which provide background knowledge on the subject matter—that lead to more specific ones [ 67 ]. It is at this point that the reader's attention must be caught as the background knowledge must highlight the importance and justification for the subject being discussed, while also identifying the major problem to be addressed [ 68 ]. In addition, the background should be broad enough to attract even nonspecialists in the field to maximise the impact and widen the reach of the article. All of these should be done in the light of current literature; however, old references may also be used for historical purposes. A very important aspect of the introduction is clearly stating and establishing the research problem(s) and how a review of the particular topic contributes to those problem(s). Thus, the research gap which the paper intends to fill, the limitations of previous works and past reviews, if available, and the new knowledge to be contributed must all be highlighted. Inadequate information and the inability to clarify the problem will keep readers (who have the desire to obtain new information) from reading beyond the introduction [ 69 ]. It is also pertinent that the author establishes the purpose of reviewing the literature and defines the scope as well as the major synthesised point of view. Furthermore, a brief insight into the criteria used to select, evaluate, and analyse the literature, as well as the outline or sequence of the review, should be provided in the introduction. Subsequently, the specific objectives of the review article must be presented. The last part of the “introduction” section should focus on the solution, the way forward, the recommendations, and the further areas of research as deduced from the whole review process. According to DeMaria [ 70 ], clearly expressed or recommended solutions to an explicitly revealed problem are very important for the wholesomeness of the “introduction” section. It is believed that following these steps will give readers the opportunity to track the problems and the corresponding solution from their own perspective in the light of current literature. As against some suggestions that the introduction should be written only in present tenses, it is also believed that it could be done with other tenses in addition to the present tense. In this regard, general facts should be written in the present tense, specific research/work should be in the past tense, while the concluding statement should be in the past perfect or simple past. Furthermore, many of the abbreviations to be used in the rest of the manuscript and their explanations should be defined in this section.

5.6. Methodology

Writing a review article is equivalent to conducting a research study, with the information gathered by the author (reviewer) representing the data. Like all major studies, it involves conceptualisation, planning, implementation, and dissemination [ 71 ], all of which may be detailed in a methodology section, if necessary. Hence, the methodological section of a review paper (which can also be referred to as the review protocol) details how the relevant literature was selected and how it was analysed as well as summarised. The selection details may include, but are not limited to, the database consulted and the specific search terms used together with the inclusion/exclusion criteria. As earlier highlighted in Section 3 , a description of the methodology is required for all types of reviews except for narrative reviews. This is partly because unlike narrative reviews, all other review articles follow systematic approaches which must ensure significant reproducibility [ 72 ]. Therefore, where necessary, the methods of data extraction from the literature and data synthesis must also be highlighted as well. In some cases, it is important to show how data were combined by highlighting the statistical methods used, measures of effect, and tests performed, as well as demonstrating heterogeneity and publication bias [ 73 ].

The methodology should also detail the major databases consulted during the literature search, e.g., Dimensions, ScienceDirect, Web of Science, MEDLINE, and PubMed. For meta-analysis, it is imperative to highlight the software and/or package used, which could include Comprehensive Meta-Analysis, OpenMEE, Review Manager (RevMan), Stata, SAS, and R Studio. It is also necessary to state the mathematical methods used for the analysis; examples of these include the Bayesian analysis, the Mantel–Haenszel method, and the inverse variance method. The methodology should also state the number of authors that carried out the initial review stage of the study, as it has been recommended that at least two reviews should be done blindly and in parallel, especially when it comes to the acquisition and synthesis of data [ 74 ]. Finally, the quality and validity assessment of the publication used in the review must be stated and well clarified [ 73 ].

5.7. Main Body of the Review

Ideally, the main body of a publishable review should answer these questions: What is new (contribution)? Why so (logic)? So what (impact)? How well it is done (thoroughness)? The flow of the main body of a review article must be well organised to adequately maintain the attention of the readers as well as guide them through the section. It is recommended that the author should consider drawing a conceptual scheme of the main body first, using methods such as mind-mapping. This will help create a logical flow of thought and presentation, while also linking the various sections of the manuscript together. According to Moreira [ 75 ], “reports do not simply yield their findings, rather reviewers make them yield,” and thus, it is the author's responsibility to transform “resistant” texts into “docile” texts. Hence, after the search for the literature, the essential themes and key concepts of the review paper must be identified and synthesised together. This synthesis primarily involves creating hypotheses about the relationships between the concepts with the aim of increasing the understanding of the topic being reviewed. The important information from the various sources should not only be summarised, but the significance of studies must be related back to the initial question(s) posed by the review article. Furthermore, MacLure [ 76 ] stated that data are not just to be plainly “extracted intact” and “used exactly as extracted,” but must be modified, reconfigured, transformed, transposed, converted, tabulated, graphed, or manipulated to enable synthesis, combination, and comparison. Therefore, different pieces of information must be extracted from the reports in which they were previously deposited and then refined into the body of the new article [ 75 ]. To this end, adequate comparison and combination might require that “qualitative data be quantified” or/and “quantitative data may be qualitized” [ 77 ]. In order to accomplish all of these goals, the author may have to transform, paraphrase, generalize, specify, and reorder the text [ 78 ]. For comprehensiveness, the body paragraphs should be arranged in a similar order as it was initially stated in the abstract or/and introduction. Thus, the main body could be divided into thematic areas, each of which could be independently comprehensive and treated as a mini review. Similarly, the sections can also be arranged chronologically depending on the focus of the review. Furthermore, the abstractions should proceed from a wider general view of the literature being reviewed and then be narrowed down to the specifics. In the process, deep insights should also be provided between the topic of the review and the wider subject area, e.g., fungal enzymes and enzymes in general. The abstractions must also be discussed in more detail by presenting more specific information from the identified sources (with proper citations of course!). For example, it is important to identify and highlight contrary findings and rival interpretations as well as to point out areas of agreement or debate among different bodies of literature. Often, there are previous reviews on the same topic/concept; however, this does not prevent a new author from writing one on the same topic, especially if the previous reviews were written many years ago. However, it is important that the body of the new manuscript be written from a new angle that was not adequately covered in the past reviews and should also incorporate new studies that have accumulated since the last review(s). In addition, the new review might also highlight the approaches, limitations, and conclusions of the past studies. But the authors must not be excessively critical of the past reviews as this is regarded by many authors as a sign of poor professionalism [ 3 , 79 ]. Daft [ 79 ] emphasized that it is more important for a reviewer to state how their research builds on previous work instead of outright claiming that previous works are incompetent and inadequate. However, if a series of related papers on one topic have a common error or research flaw that needs rectification, the reviewer must point this out with the aim of moving the field forward [ 3 ]. Like every other scientific paper, the main body of a review article also needs to be consistent in style, for example, in the choice of passive vs. active voice and present vs. past tense. It is also important to note that tables and figures can serve as a powerful tool for highlighting key points in the body of the review, and they are now considered core elements of reviews. For more guidance and insights into what should make up the contents of a good review article, readers are also advised to get familiarised with the Boote and Beile [ 80 ] literature review scoring rubric as well as the review article checklist of Short [ 81 ].

5.8. Tables and Figures

An ideal review article should be logically structured and efficiently utilise illustrations, in the form of tables and figures, to convey the key findings and relationships in the study. According to Tay [ 13 ], illustrations often take a secondary role in review papers when compared to primary research papers which are focused on illustrations. However, illustrations are very important in review articles as they can serve as succinct means of communicating major findings and insights. Franzblau and Chung [ 82 ] pointed out that illustrations serve three major purposes in a scientific article: they simplify complex data and relationships for better understanding, they minimise reading time by summarising and bringing to focus on the key findings (or trends), and last, they help to reduce the overall word count. Hence, inserting and constructing illustrations in a review article is as meticulous as it is important. However, important decisions should be made on whether the charts, figures, or tables to be potentially inserted in the manuscript are indeed needed and how best to design them [ 83 ]. Illustrations should enhance the text while providing necessary information; thus, the information described in illustrations should not contradict that in the main text and should also not be a repetition of texts [ 84 ]. Furthermore, illustrations must be autonomous, meaning they ought to be intelligible without having to read the text portion of the manuscript; thus, the reader does not have to flip back and forth between the illustration and the main text in order to understand it [ 85 ]. It should be noted that tables or figures that directly reiterate the main text or contain extraneous information will only make a mess of the manuscript and discourage readers [ 86 ].

Kotz and Cals [ 87 ] recommend that the layout of tables and figures should be carefully designed in a clear manner with suitable layouts, which will allow them to be referred to logically and chronologically in the text. In addition, illustrations should only contain simple text, as lengthy details would contradict their initial objective, which was to provide simple examples or an overview. Furthermore, the use of abbreviations in illustrations, especially tables, should be avoided if possible. If not, the abbreviations should be defined explicitly in the footnotes or legends of the illustration [ 88 ]. Similarly, numerical values in tables and graphs should also be correctly approximated [ 84 ]. It is recommended that the number of tables and figures in the manuscript should not exceed the target journal's specification. According to Saver [ 89 ], they ideally should not account for more than one-third of the manuscript. Finally, the author(s) must seek permission and give credits for using an already published illustration when necessary. However, none of these are needed if the graphic is originally created by the author, but if it is a reproduced or an adapted illustration, the author must obtain permission from the copyright owner and include the necessary credit. One of the very important tools for designing illustrations is Creative Commons, a platform that provides a wide range of creative works which are available to the public for use and modification.

5.9. Conclusion/Future Perspectives

It has been observed that many reviews end abruptly with a short conclusion; however, a lot more can be included in this section in addition to what has been said in the major sections of the paper. Basically, the conclusion section of a review article should provide a summary of key findings from the main body of the manuscript. In this section, the author needs to revisit the critical points of the paper as well as highlight the accuracy, validity, and relevance of the inferences drawn in the article review. A good conclusion should highlight the relationship between the major points and the author's hypothesis as well as the relationship between the hypothesis and the broader discussion to demonstrate the significance of the review article in a larger context. In addition to giving a concise summary of the important findings that describe current knowledge, the conclusion must also offer a rationale for conducting future research [ 12 ]. Knowledge gaps should be identified, and themes should be logically developed in order to construct conceptual frameworks as well as present a way forward for future research in the field of study [ 11 ].

Furthermore, the author may have to justify the propositions made earlier in the manuscript, demonstrate how the paper extends past research works, and also suggest ways that the expounded theories can be empirically examined [ 3 ]. Unlike experimental studies which can only draw either a positive conclusion or ambiguous failure to reject the null hypothesis, four possible conclusions can be drawn from review articles [ 1 ]. First, the theory/hypothesis propounded may be correct after being proven from current evidence; second, the hypothesis may not be explicitly proven but is most probably the best guess. The third conclusion is that the currently available evidence does not permit a confident conclusion or a best guess, while the last conclusion is that the theory or hypothesis is false [ 1 ]. It is important not to present new information in the conclusion section which has link whatsoever with the rest of the manuscript. According to Harris et al. [ 90 ], the conclusions should, in essence, answer the question: if a reader were to remember one thing about the review, what would it be?

5.10. References

As it has been noted in different parts of this paper, authors must give the required credit to any work or source(s) of information that was included in the review article. This must include the in-text citations in the main body of the paper and the corresponding entries in the reference list. Ideally, this full bibliographical list is the last part of the review article, and it should contain all the books, book chapters, journal articles, reports, and other media, which were utilised in the manuscript. It has been noted that most journals and publishers have their own specific referencing styles which are all derived from the more popular styles such as the American Psychological Association (APA), Chicago, Harvard, Modern Language Association (MLA), and Vancouver styles. However, all these styles may be categorised into either the parenthetical or numerical referencing style. Although a few journals do not have strict referencing rules, it is the responsibility of the author to reference according to the style and instructions of the journal. Omissions and errors must be avoided at all costs, and this can be easily achieved by going over the references many times for due diligence [ 11 ]. According to Cronin et al. [ 12 ], a separate file for references can be created, and any work used in the manuscript can be added to this list immediately after being cited in the text [ 12 ]. In recent times, the emergence of various referencing management software applications such as Endnote, RefWorks, Mendeley, and Zotero has even made referencing easier. The majority of these software applications require little technical expertise, and many of them are free to use, while others may require a subscription. It is imperative, however, that even after using these software packages, the author must manually curate the references during the final draft, in order to avoid any errors, since these programs are not impervious to errors, particularly formatting errors.

6. Concluding Remarks

Writing a review article is a skill that needs to be learned; it is a rigorous but rewarding endeavour as it can provide a useful platform to project the emerging researcher or postgraduate student into the gratifying world of publishing. Thus, the reviewer must develop the ability to think critically, spot patterns in a large volume of information, and must be invested in writing without tiring. The prospective author must also be inspired and dedicated to the successful completion of the article while also ensuring that the review article is not just a mere list or summary of previous research. It is also important that the review process must be focused on the literature and not on the authors; thus, overt criticism of existing research and personal aspersions must be avoided at all costs. All ideas, sentences, words, and illustrations should be constructed in a way to avoid plagiarism; basically, this can be achieved by paraphrasing, summarising, and giving the necessary acknowledgments. Currently, there are many tools to track and detect plagiarism in manuscripts, ensuring that they fall within a reasonable similarity index (which is typically 15% or lower for most journals). Although the more popular of these tools, such as Turnitin and iThenticate, are subscription-based, there are many freely available web-based options as well. An ideal review article is supposed to motivate the research topic and describe its key concepts while delineating the boundaries of research. In this regard, experience-based information on how to methodologically develop acceptable and impactful review articles has been detailed in this paper. Furthermore, for a beginner, this guide has detailed “the why” and “the how” of authoring a good scientific review article. However, the information in this paper may as a whole or in parts be also applicable to other fields of research and to other writing endeavours such as writing literature review in theses, dissertations, and primary research articles. Finally, the intending authors must put all the basic rules of scientific writing and writing in general into cognizance. A comprehensive study of the articles cited within this paper and other related articles focused on scientific writing will further enhance the ability of the motivated beginner to deliver a good review article.

Acknowledgments

This work was supported by the National Research Foundation of South Africa under grant number UID 138097. The authors would like to thank the Durban University of Technology for funding the postdoctoral fellowship of the first author, Dr. Ayodeji Amobonye.

Data Availability

Conflicts of interest.

The authors declare that they have no conflicts of interest.

• Case Report
• Open access
• Published: 14 May 2024

Motor polyradiculoneuropathy as an unusual presentation of neurobrucellosis: a case report and literature review

• Ahmad Alikhani 1 ,
• Noushin Ahmadi 1 ,
• Mehran Frouzanian 2 &
• Amirsaleh Abdollahi 2  

BMC Infectious Diseases volume  24 , Article number:  491 ( 2024 ) Cite this article

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Brucellosis, a zoonotic disease caused by Brucella species, poses a significant global health concern. Among its diverse clinical manifestations, neurobrucellosis remains an infrequent yet debilitating complication. Here, we present a rare case of neurobrucellosis with unusual presentations in a 45-year-old woman. The patient’s clinical course included progressive lower extremity weakness, muscle wasting, and double vision, prompting a comprehensive diagnostic evaluation. Notable findings included polyneuropathy, elevated brucella agglutination titers in both cerebrospinal fluid and blood, abnormal EMG-NCV tests, and resolving symptoms with antibiotic therapy. The clinical presentation, diagnostic challenges, and differentiation from other neurological conditions are discussed. This case underscores the importance of considering neurobrucellosis in regions where brucellosis is prevalent and highlights this rare neurological complication’s distinctive clinical and radiological features. Early recognition and appropriate treatment are crucial to mitigate the significant morbidity associated with neurobrucellosis.

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Introduction

Brucellosis, caused by Brucella species, is an infectious ailment recognized by various names such as remitting, undulant, Mediterranean, Maltese, Crimean, and goat fever. Humans contract it through the consumption of unpasteurized milk and dairy products, undercooked meat, or skin contact with infected livestock [ 1 , 2 , 3 ]. Various Brucella species, including Brucella melitensis (primarily sourced from sheep and goats), Brucella abortus (found in cattle), Brucella suis (associated with pigs/hogs), and Brucella canis (linked to dogs), can lead to illness in humans [ 3 , 4 , 5 ]. While brucellosis in humans is rarely fatal, it can lead to disability [ 6 ]. Brucellosis ranks among the most prevalent zoonotic diseases, impacting approximately 500,000 individuals yearly [ 7 ]. The combined estimate for the prevalence of brucellosis was 15.53% [ 8 ].

Neurobrucellosis, a rare complication of systemic brucellosis, can occur in adult and pediatric cases [ 9 ], and can manifest at any stage of the disease. They can present in various clinical presentations such as meningitis, encephalitis, meningoencephalitis, myelitis, radiculopathy, polyneuropathy, stroke, cerebral venous thrombosis, and occasionally psychiatric symptoms [ 10 , 11 ]. Although the mortality rate is low, patients often experience persistent neurological issues following neurobrucellosis [ 12 ]. Studies suggest that around 20% of neurobrucellosis cases result in lasting neurological problems [ 13 ]. It is uncommonly considered in cases of meningoencephalitis or polyneuropathy, making it crucial for clinicians to have a high suspicion of it in patients displaying such symptoms, especially in endemic regions, to prevent severe clinical outcomes. In this study, we present a rare case of neurobrucellosis with unusual clinical presentations in a patient admitted to our center.

Case presentation

A 45-year-old female patient, with no prior medical history, presented to our center after enduring distal pain and weakness in her lower extremities for approximately 10 months. Over this period, the muscle weakness progressed, affecting proximal muscles of upper and lower limbs, and leading to a substantial weight loss of 25–30 kg despite maintaining appetite. Initially dismissive of the limb weakness and pain, the patient sought medical attention six months after symptom onset due to the worsening symptoms and gait impairment. Over the subsequent four months, she underwent multiple medical evaluations and tests, including a lumbar X-ray. Following these initial investigations and due to low serum vitamin D levels, vitamin D and calcium supplements were prescribed, and lumbar MRI were requested for further evaluation. (Table  1 )

Upon referral to an infectious disease specialist, the patient’s history of local dairy consumption and positive serologic test for brucellosis prompted treatment with rifampin and doxycycline. However, the patient’s condition deteriorated significantly five days after starting this treatment. She experienced severe gait disorder, lower extremity weakness, diplopia, and blurred vision that had gradually worsened over two weeks. Subsequently, she presented to our center for further assessment.

Upon admission, the patient was unable to stand even with assistance and exhibited diplopia. Cranial nerve examination revealed no abnormalities, except for the II, III, and IV cranial nerves, which could not be thoroughly examined due to the presence of diplopia. The patient tested negative for Kernig and Brudzinski signs. There were no palpable supraclavicular or inguinal lymph nodes. Physical examinations of the breast, axilla, lungs, heart, and abdomen were unremarkable. Muscle strength was reduced in the lower extremities, and deep tendon reflexes of the knee and Achilles were absent. The plantar reflex was non-responsive, and certain reflexes, including biceps, triceps, and brachioradialis, were absent despite normal movement of the upper extremities. Anorectal muscle tone and anal reflex were normal.

Further investigations included normal urinalysis and abdominal and pelvic ultrasound. Chest X-ray and brain CT were also ordered. Due to the patient’s refusal of lumbar puncture, a suspicion of neurobrucellosis led to the initiation of a three-drug regimen (Table  2 ); ceftriaxone 2 g IV twice daily, rifampin 600 mg PO daily, and doxycycline 100 mg PO twice daily. The ophthalmology consultation did not reveal any ocular pathology, and the neurologist ordered brain MRI and EMG-NCV tests. The patient’s brain MRI was unremarkable, but EMG-NCV showed sensory and motor polyneuropathy. Consequently, intravenous immunoglobulin (IVIG) therapy was initiated at a daily dose of 25 g. After five days, the patient consented to lumbar puncture, confirming the diagnosis of brucellosis. Co-trimoxazole 960 mg PO three times daily was added to her treatment regimen, and IVIG therapy continued for seven days. Following a 3-day course of IVIG treatment, the neuropathy symptoms showed significant improvement. By the seventh day, there was a notable enhancement in limb strength, particularly in the upper limbs, reaching a 2-point improvement. After undergoing three weeks of intravenous therapy, the patient transitioned to oral medication. Despite disagreement regarding the necessity of a second CSF examination, the patient was discharged with a prescription for doxycycline, rifampin, and cotrimoxazole. Upon discharge, the patient could walk with the aid of a walker. However, within a month, a slight limp persisted, and by the third-month post-discharge, all symptoms had resolved completely.

Brucellosis is widely spread globally, with more than half a million reported human cases annually [ 14 , 15 ]. Countries like Kenya, Yemen, Syria, Greece, and Eritrea have experienced high rates of brucellosis. The situation of brucellosis has shown signs of improvement in many epidemic regions. However, new areas with high occurrences of this disease continue to emerge, particularly in Africa and the Middle East, where the incidence of the disease varies [ 16 ]. Brucellosis is linked to various neurological complications collectively known as neurobrucellosis, which is an uncommon condition, and only a few cases have been reported globally [ 17 , 18 , 19 , 20 , 21 ]. Our patient exhibited muscle weakness, polyneuropathy, and inability to walk, which are often not regarded as indicative of a brucella infection by many physicians. While the diagnosis of neurobrucellosis can typically be confirmed through classical clinical signs, radiological examinations, and serological tests, patients might not always display typical symptoms, as observed in our case. Hence, in regions where the disease is prevalent, clinicians should maintain a high level of suspicion if patients do not show improvement with standard treatment. Additionally, the lack of awareness among healthcare professionals and limited access to advanced laboratory facilities can lead to misdiagnosis.

The frequent manifestations of neurobrucellosis include meningitis or meningoencephalitis. Typically, it starts with a sudden headache, vomiting, and altered mental state, which can progress to unconsciousness, with or without seizures [ 22 ]. Additionally, brucellosis can lead to several central nervous system issues such as inflammation of cerebral blood vessels, abscesses in the brain or epidural space, strokes, and cerebellar ataxia. Peripheral nerve problems may include nerve damage or radiculopathy, Guillain-Barré syndrome, and a syndrome resembling poliomyelitis [ 13 ]. Nevertheless, the patient exhibited no indications of seizures, brain hemorrhage, stroke, or focal neurological impairments. Instead, the observed symptoms were consistent with radiculopathy and muscular weakness.

In only 7% of neurobrucellosis cases, the peripheral nervous system is affected. Remarkably, our case falls within this rare category, adding to its unique and intriguing nature. Previous case studies have detailed polyradiculoneuropathies, manifesting as acute, subacute, or chronic forms [ 23 ]. Our patient’s condition aligns with chronic motor polyradiculopathy. Interestingly, some of these cases exhibit sensory deficits or resemble Guillain-Barré syndrome [ 23 , 24 ]. In a prior case study conducted by Abuzinadah and colleagues, a comparable case was described as a subacute motor polyradiculopathy. The patient exhibited gradual bilateral lower limb weakness over three weeks, eventually leading to loss of mobility within seven weeks. Brucella was isolated from the cerebrospinal fluid after a two-week incubation period, and high antibody titers were detected in the patient’s serum [ 23 ]. In another study led by Alanazi and colleagues, a 56-year-old man initially diagnosed with Guillain-Barré syndrome experienced worsening symptoms despite appropriate treatment. Following plasma exchange and antibiotics, his condition improved temporarily, only to relapse, raising suspicion of chronic inflammatory demyelinating polyneuropathy, and treatment with IVIG resulted in substantial improvement. Upon further investigation, he was diagnosed with brucellosis [ 24 ]. This highlights the importance of recognizing GBS-like symptoms in regions where brucellosis is prevalent, prompting clinicians to consider the possibility of brucellosis in their diagnosis.

While there are no established criteria for diagnosing neurobrucellosis [ 25 ], certain articles have suggested several methods for its diagnosis. These methods include the presence of symptoms aligning with neurobrucellosis, isolating brucella from cerebrospinal fluid (CSF) or detecting a positive brucella agglutination titer in CSF, observing lymphocytosis, elevated protein, and decreased glucose levels in CSF, or identifying specific diagnostic indicators in cranial imaging such as magnetic resonance imaging or computed tomography (MRI or CT) [ 13 , 26 , 27 , 28 ]. Neurobrucellosis does not present a distinct clinical profile or specific CSF characteristics. Imaging observations of neurobrucellosis fall into four categories: normal, inflammatory (indicated by granulomas and enhanced meninges, perivascular spaces, or lumbar nerve roots), alterations in white matter, and vascular changes [ 29 ]. We suspected neurobrucellosis based on the patient’s clinical symptoms, geographic correlation, high brucella agglutination test titers in both cerebrospinal fluid and blood, symptom resolution following treatment, and the exclusion of other common causes.

In Iran, one differential diagnosis often confused with brucellosis is tuberculosis, as both chronic granulomatous infectious diseases are prevalent here [ 30 , 31 ]. Neurobrucellosis and tuberculosis exhibit significant similarities in clinical symptoms, lab results, and neuroimaging findings. However, deep grey matter involvement and widespread white matter lesions seen in neuroimaging, resembling demyelinating disorders, appear to be distinctive to brucellosis [ 32 ]. There is a noticeable similarity in the clinical symptoms and laboratory findings of brucellosis and tuberculosis [ 33 ]. It is crucial to thoroughly eliminate the possibility of tuberculosis in any suspected or confirmed brucellosis cases before starting antibiotic treatment.

Due to the challenging nature of treating brucellosis and the likelihood of experiencing relapses, it is crucial to provide an extended course of treatment [ 27 ]. This treatment approach should involve a combination of antibiotics that can easily penetrate the cell wall and effectively reach the central nervous system [ 27 , 34 ]. Neurobrucellosis is treated with 3 to 6 months of combination therapy comprising doxycycline, rifampicin, and ceftriaxone or trimethoprim-sulfamethoxazole [ 35 ], similar to the treatment administered to our patient. For patients allergic to cephalosporins, quinolones are recommended, which are considered to be effective in treating brucellosis [ 36 , 37 ]. In complicated situations such as meningitis or endocarditis, streptomycin or gentamicin is administered in the initial 14 days of treatment, in addition to the previously mentioned regimen. Timely and proper treatment results in a positive prognosis, with a less than 1% fatality rate for such complex cases [ 17 , 38 ]. Our patient experienced a highly positive outcome following the prescribed therapy. Initially relying on a walker, a slight limp endured for a month, and by the third month after discharge, all symptoms completely disappeared.

The present study underscores the significance of considering neurobrucellosis as a potential diagnosis when evaluating muscle weakness and radiculopathy, especially in regions where the disease is prevalent. A comprehensive patient history, precise clinical examination, positive serology in blood or cerebrospinal fluid, imaging results, or cerebrospinal fluid analysis can contribute to establishing a conclusive diagnosis.

Data availability

The datasets generated and/or analysed during the current study are not publicly available due to our team’s privacy concerns but are available from the corresponding author on reasonable request.

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A.A oversaw and treated the case, including the entire revision process. N.A. contributed to the article’s composition. M.F. authored the discussion section, along with the complete revision. AS.A. played a role in crafting the case report discussion and participated in the entire revision process.

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Alikhani, A., Ahmadi, N., Frouzanian, M. et al. Motor polyradiculoneuropathy as an unusual presentation of neurobrucellosis: a case report and literature review. BMC Infect Dis 24 , 491 (2024). https://doi.org/10.1186/s12879-024-09365-2

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Received : 04 December 2023

Accepted : 29 April 2024

Published : 14 May 2024

DOI : https://doi.org/10.1186/s12879-024-09365-2

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• Neurobrucellosis
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