case series report study

Get new issue alerts Get alerts
Submit a Manuscript

Secondary Logo

Journal logo.

Colleague's E-mail is Invalid

Your message has been successfully sent to your colleague.

Save my selection

How to Write Case Reports and Case Series

Ganesan, Prasanth

Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Address for correspondence: Dr. Prasanth Ganesan, Medical Oncology, 3 rd Floor, SSB, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Puducherry - 605006, India. E-mail: [email protected]

Received March 13, 2022

Received in revised form April 10, 2022

Accepted April 10, 2022

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Case reports are considered the smallest units of descriptive studies. They serve an important function in bringing out information regarding presentation, management, and/or outcomes of rare diseases. They can also be a starting point in understanding unique associations in clinical medicine and can introduce very effective treatment paradigms. Preparing the manuscript for a case report may be the first exposure to scientific writing for a budding clinician/researcher. This manuscript describes the steps of writing a case report and essential considerations when publishing these articles. Individual components of a case report and the “dos and don'ts” while preparing these components are detailed.

INTRODUCTION

A case report describes several aspects of an individual patient's presentation, investigations, management decisions, and/or outcomes. This is a type of observational study and has been described as the smallest publishable unit in medical literature.[ 1 ] A case series involves a group of patients with similar presentations or treatments. In modern medicine [ Figure 1 ], these publications are categorized as the “lowest level of evidence”.[ 2 ] However, they serve several essential functions. For example, there are rare diseases where large, randomized trials, or even observational studies may not be possible. Medical practice, in these conditions, is often guided by well-presented case reports or series. There are situations where a single case report has heralded an important therapy change.[ 3 ] Further, case reports are often a student's first exposure to manuscript writing. Hence, these serve as training for budding scholars to understand scientific writing, learn the process of manuscript submission, and receive and respond to reviewer comments. This article explains the reasons why case reports are published and provides guidance for writing such type of articles.

WHY ARE CASE REPORTS PUBLISHED?

A case report is often published to highlight the rarity of a particular presentation. However, it may be of much more value if it also informs some aspects of management. This could be in the form of rare expressions of a common disease so that clinicians who read will be aware and can consider additional possibilities and differential diagnoses when encountering similar situations. A new form of evaluation of a patient, either to facilitate the diagnostics or to improve understanding of the disease condition, may stimulate a case report. Novel treatments may be tried, and the results might be necessary to disseminate. This may be encountered either in rare diseases or conditions where treatment options are exhausted. Moreover, randomized trials report outcomes of a group and often do not inform about the individual patient. [ Table 1 ] describes a few examples of case reports/case series which have had a remarkable impact on medical practice.

ETHICAL ISSUES

If there is a possibility of patient identification from the report, it is mandatory to obtain informed consent from the patient while approval from the institutional ethics committee (IEC) may also be needed depending on institutional policies.[ 7 ] If identifying information is absent (or if suitable steps are taken to remove identifying information or hide the identity, (such as by covering the eyes), it may still be required by some journals to obtain ethics committee approval for certain types of case reports. If a case series involves retrospective chart review, “waiver-of-consent” may be sought from the ethics committee. Indian Ethical Guidelines do not separately address this issue in case reports.[ 8 ] The Committee on Publication Ethics has described best practices for journals when publishing case reports which also gives links to model consent forms.[ 9 ]

HOW TO START?

If you are a beginner and you have identified an interesting case which you want to report, the first step would be to sit with your team and discuss the aspects of the case you want to highlight in your publication.[ 10 ] Do a literature search and try to summarize available information before writing the draft. It would also be a good idea to understand which journal you are targeting; this will assist in determining the number of figures, the word limits, and ethical requirements (such as informed consent). Discussions with senior faculty about the authors and their order should also be done at this point to avoid issues later. For a beginner, it would be a good practice to present the case in the department or in an institutional scientific forum before writing up the manuscript.

COMPONENTS OF a CASE REPORT

A case report usually has the following sections: an abstract, a brief introduction, the actual description of the case, and finally, the discussion which highlights the uniqueness of the case and includes a conclusion statement. Many journals these days publish case reports only as a letter to editor; in such cases, an abstract is not usually required.

The title must be informative about the problem being reported. It may refer to the particular issue being highlighted in the report, or it may refer to the educational aspect of that particular report. Catchy titles are often used by authors to trigger interest among the readers and make them want to read the article. Authors may remember to use titles which will help people locate the article when searching the literature.

When writing a title, it may be best to avoid terms such as “case report,” “review of literature,” “unique,” “rare,” “first-report”; these do not add value to the presentation.

Introduction

This must introduce the condition and clearly state why the case report is worth reading. It may also contain a brief mention of the current status of the problem being described with supporting references.

Describing the case

The case must be presented succinctly, in a chronological order, clearly highlighting the salient aspects of the case being reported. Relevant negative findings may be provided. For example, if a case is being reported for elaborating a new type of treatment, then more attention must be given to treatment aspects (e.g., name of the drug, dosage, schedule, dose modifications, or the type of surgery, duration, and type of anesthesia) after briefly describing the presentation and diagnostics. The idea is that the reader must be able to apply the treatment in his/her practice if required.

However, if the case is being presented for diagnostic rarity/unusual clinical features/pathological aspects, then more attention must be given to these aspects. For example, if the emphasis is on tissue pathology, then the description must include details about tissue processing, types of stains, and immunohistochemistry details.

Figures and tables

Figures, as in any publication, should be self-explanatory. A properly constructed figure legend can be used for describing certain aspects of the case much better than long-winded text in the main manuscript. This will also help to reduce the word count in the main manuscript. If there are multiple figures (e.g., follow-up radiology series and response to treatment images), these can be combined as [ Figure 1 ]a, [ Figure 1 ]b, [ Figure 1c ] or [ Figure 1 ]a, [ Figure 1 ]b, [ Figure 1 ]c, [ Figure 1d ]. This will help conform to the figure number limits prescribed by the journal. While preparing the figures, one must ensure that the quality of the art/photograph is not compromised. Further, patient identifying features must be masked, unless necessary to show.

Tables are usually not part of case reports but may be used. One example is presenting the baseline investigations in a tabular format which can facilitate assimilation as well as reduce the word count. Tables are more often used in case series. The most common is a type of table where the features of all the cases included are summarized with each row referring to an individual patient. This usually works for a series of up to ten patients; beyond that, the table may become crowded and difficult to understand. Tables may also be used in the discussion section to summarize related, published reports to date.

Discussion including review

A case report may help to alter the approach to patient management in the clinic or it may even stimulate original research evaluating a new treatment. Thus, the discussion must summarize the unique aspects of the case (why is the case different?) and the essential learning points/implications (how will it change management?/What further research needs to be done?). In addition to stating the differences from existing literature, the discussion should also attempt to explain these differences.

If the condition or treatment approach being focused on is sufficiently rare, reviewing all available cases published until that point is critical. This review may be presented in a table with each case described briefly. A more nuanced study might attempt to summarize the relevant demographics and clinical details of the various cases published to date in the form of a table (e.g., median age, gender distribution, and survival outcomes).

CASE SERIES - WHAT IS DIFFERENT?

There is no formal definition as to what is case series and what would be considered a retrospective cohort study. In general, a case series comprises <10 cases; beyond that, it may be feasible to apply formal statistics and may be considered a cohort study.

Both case reports and case series are descriptive studies. Case series must have similar cases and hence the inclusion must be clearly defined. The interventions must be documented in a way that is reproducible and follow-up of each individual in the report must be available. Although formal statistical analyses are usually not a part of case series, authors may attempt to summarize baseline demographic parameters using descriptive statistics.

ABSTRACT OF a CASE REPORT

As explained earlier, a few journals do not require abstracts for case report submissions. When required, one should try to highlight the salient aspects of the case presented and the reason for the publication within the abstract word limit, which may be as short as 100–200 words. Spend time and effort in writing a good abstract as this is a portion which is usually read by the editor during manuscript screening and may have implications for whether the article progresses to the next stage of editorial processing.

REFERENCES IN a CASE REPORT

One may only cite key references in a case report or series as there is limited scope for elaborate literature search. Most journals have a limit of 10–15 references for case reports; when publishing as a letter to editor (or correspondence), the allowed reference limit may be even lower (five or less for some journals).

CHOOSING THE RIGHT JOURNAL

Many journals have recently stopped publishing case reports and series. This is often an attempt by journals to optimize their resources (space and reviewer time) to attain the highest possible impact. Although this is unfortunate, it is a reality which must be acknowledged. Nonetheless, the advent of online-only journals has led to more options for aspiring authors. Some journals accept case series, whereas others have “sister” journals created to accept case reports and other, less definitive, contributions to the literature.[ 11 ] It is an important exercise to study all available journals accepting case reports of the type being written. The case report must be tailored to the journal's requirements. Many journals may charge an article processing fee; author(s) must consider whether they are willing to pay and publish. Some of these may be predatory journals; authors must be wary of them and scrupulously avoid publishing in such journals as they can permanently stain the publication records of a researcher.

PUBLISHING THE CASE REPORT/SERIES AS a LETTER TO EDITOR/IMAGE SERIES

When the matter to be conveyed is very minimal or is being published mainly for its rarity, letters to editor may be an alternate route to publish case report data. Interesting images may be published in the form of “images” series which is now a part of many journals. The flexibility of web-based publishing also allows interesting videos to be published online.

GUIDELINES FOR CASE REPORTS

There are guidelines which help authors in the preparation and submission of case reports. The CAse REports (CARE) checklist is one such popular guideline. It provides a “checklist” and other resources for authors that can help navigate the process of writing a case report, especially when a person is doing it for the first time.[ 12 ]

AUTHORSHIP IN CASE REPORTS

Although there are no separate guidelines for authorship in “case reports,” general authorship rules follow that for any manuscript. “Gift” authorship must be avoided. All authors must have contributed to the creation of the manuscript in addition to being involved in some aspect of care of the patient being reported. Authorship order should be ideally predecided based on mutual consensus.

CONCLUSIONS

A case report is a useful starting point for one's scientific writing career. There are useful online resources which describe the steps for a newbie writer.[ 13 14 ] [ Table 2 ] summarizes the important components to follow and understand when writing case reports. Although many frontline journals have reduced their acceptance of case reports, these publications continue to serve an essential scientific and academic role.

Financial support and sponsorship

Conflicts of interest.

There are no conflicts of interest.

Case reports; manuscript writing; case series; references

+ Favorites
View in Gallery

Readers Of this Article Also Read

How to revise and resubmit the manuscript after a favorable peer review, glossopharyngeal neuralgia following coronavirus disease 2019 infection, polymorphous adenocarcinoma of the parotid – an uncommon site of occurrence, primary vulval mucinous adenocarcinoma of intestinal type masquerading as..., detection of rare blood group ax phenotype in blood donor.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Publications
Account settings
My Bibliography
Collections
Citation manager

Save citation to file

Email citation, add to collections.

Create a new collection
Add to an existing collection

Add to My Bibliography

Your saved search, create a file for external citation management software, your rss feed.

Search in PubMed
Search in NLM Catalog
Add to Search

A critical guide to case series reports

PMID: 12897483
DOI: 10.1097/01.BRS.0000083174.84050.E5

Objective: Provide guidance to investigators and authors regarding appropriate conduct and reporting of case-series studies.

Summary of background data: Evidence-based practice has provided a substantial contribution to advancing clinical science. Many study designs have been critically examined, and the quality of the research literature has improved. A common study design in musculoskeletal medicine is the case series: a description of the course of patients over time. Case series can provide valuable information as to: case definition, trend analyses regarding outcomes, and clues as to causation. Case series cannot be used to draw inferences regarding treatment effect.

Methods: Examination of previous work on identification of characteristics of high quality study designs such as cohort studies; extending this work to case series.

Results: We identified draft characteristics that good case series studies should address: clearly defined study question; well- described study population; well-described intervention; use of validated outcome measures; appropriate statistical analyses; well-described results; discussion/conclusions supported by the data presented; funding sources acknowledged.

Conclusions: We propose these measures to authors and journal editors as one mechanism to improve the quality of the case series study.

PubMed Disclaimer

Publication types

Search in MeSH

Related information

Cited in Books

LinkOut - more resources

Full text sources.

Ovid Technologies, Inc.
Wolters Kluwer

Research Materials

NCI CPTC Antibody Characterization Program

Citation Manager

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Case Reports and Case Series

First Online: 12 October 2018

Cite this chapter

Bryan Kestenbaum MD, MS 2

4585 Accesses

Case reports and case series represent the most basic types of observational study designs. These studies describe the experiences of a single person ( case report ) or a group of people ( case series ) who have a specific disease or condition. Case reports and case series typically describe previously unrecognized diseases or unusual variants of a known disease process. Consequently, data from these studies are particularly useful for alerting the health community to the presence of a new disease and for generating hypotheses regarding possible causes. For example, initial case reports of opportunistic infections among previously healthy homosexual men alerted the health community to the presence of the human immunodeficiency virus (HIV) epidemic. The initial case series describing patients with nephrogenic systemic fibrosis (NSF) raised awareness of this previously unknown condition and motivated subsequent studies that ultimately led to the discovery of gadolinium contrast as the causal agent (Chap. 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save.

Get 10 units per month
Download Article/Chapter or Ebook
1 Unit = 1 Article or 1 Chapter
Cancel anytime
Available as PDF
Read on any device
Instant download
Own it forever
Available as EPUB and PDF
Compact, lightweight edition
Dispatched in 3 to 5 business days
Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Henley DV, Lipson N, Korach KS, Bloch CA. Prepubertal gynecomastia linked to lavender and tea tree oils. N Engl J Med. 2007;356(5):479–85.

Article CAS Google Scholar

Centers for Disease C, Prevention. Intussusception among recipients of rotavirus vaccine–United States, 1998–1999. MMWR Morb Mortal Wkly Rep. 1999;48(27):577–81.

Google Scholar

Download references

Author information

Authors and affiliations.

Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA

Bryan Kestenbaum MD, MS

You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

About this chapter

Kestenbaum, B. (2019). Case Reports and Case Series. In: Epidemiology and Biostatistics. Springer, Cham. https://doi.org/10.1007/978-3-319-96644-1_4

Download citation

DOI : https://doi.org/10.1007/978-3-319-96644-1_4

Published : 12 October 2018

Publisher Name : Springer, Cham

Print ISBN : 978-3-319-96642-7

Online ISBN : 978-3-319-96644-1

eBook Packages : Medicine Medicine (R0)

Share this chapter

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Publish with us

Policies and ethics

Find a journal
Track your research

Study Design 101: Case Report

Case Report
Case Control Study
Cohort Study
Randomized Controlled Trial
Practice Guideline
Systematic Review
Meta-Analysis
Helpful Formulas
Finding Specific Study Types
Case Reports

An article that describes and interprets an individual case, often written in the form of a detailed story. Case reports often describe:

Unique cases that cannot be explained by known diseases or syndromes
Cases that show an important variation of a disease or condition
Cases that show unexpected events that may yield new or useful information
Cases in which one patient has two or more unexpected diseases or disorders

Case reports are considered the lowest level of evidence, but they are also the first line of evidence, because they are where new issues and ideas emerge. This is why they form the base of our pyramid. A good case report will be clear about the importance of the observation being reported.

If multiple case reports show something similar, the next step might be a case-control study to determine if there is a relationship between the relevant variables.

Can help in the identification of new trends or diseases
Can help detect new drug side effects and potential uses (adverse or beneficial)
Educational - a way of sharing lessons learned
Identifies rare manifestations of a disease

Disadvantages

Cases may not be generalizable
Not based on systematic studies
Causes or associations may have other explanations
Can be seen as emphasizing the bizarre or focusing on misleading elements

Design pitfalls to look out for

The patient should be described in detail, allowing others to identify patients with similar characteristics.

Does the case report provide information about the patient's age, sex, ethnicity, race, employment status, social situation, medical history, diagnosis, prognosis, previous treatments, past and current diagnostic test results, medications, psychological tests, clinical and functional assessments, and current intervention?

Case reports should include carefully recorded, unbiased observations.

Does the case report include measurements and/or recorded observations of the case? Does it show a bias?

Case reports should explore and infer, not confirm, deduce, or prove. They cannot demonstrate causality or argue for the adoption of a new treatment approach.

Does the case report present a hypothesis that can be confirmed by another type of study?

Fictitious Example

A physician treated a young and otherwise healthy patient who came to her office reporting numbness all over her body. The physician could not determine any reason for this numbness and had never seen anything like it. After taking an extensive history the physician discovered that the patient had recently been to the beach for a vacation and had used a very new type of spray sunscreen. The patient had stored the sunscreen in her cooler at the beach because she liked the feel of the cool spray in the hot sun. The physician suspected that the spray sunscreen had undergone a chemical reaction from the coldness which caused the numbness. She also suspected that because this is a new type of sunscreen other physicians may soon be seeing patients with this numbness.

The physician wrote up a case report describing how the numbness presented, how and why she concluded it was the spray sunscreen, and how she treated the patient. Later, when other doctors began seeing patients with this numbness, they found this case report helpful as a starting point in treating their patients.

Real-life Examples

Hymes KB. Cheung T. Greene JB. Prose NS. Marcus A. Ballard H. William DC. Laubenstein LJ. (1981). Kaposi's sarcoma in homosexual men-a report of eight cases. Lancet. 2 (8247),598-600.

This case report was published by eight physicians in New York city who had unexpectedly seen eight male patients with Kaposi's sarcoma (KS). Prior to this, KS was very rare in the U.S. and occurred primarily in the lower extremities of older patients. These cases were decades younger, had generalized KS, and a much lower rate of survival. This was before the discovery of HIV or the use of the term AIDS and this case report was one of the first published items about AIDS patients.

Wu, E. B., & Sung, J. J. Y. (2003). Haemorrhagic-fever-like changes and normal chest radiograph in a doctor with SARS. Lancet, 361 (9368), 1520-1521.

This case report is written by the patient, a physician who contracted SARS, and his colleague who treated him, during the 2003 outbreak of SARS in Hong Kong. They describe how the disease progressed in Dr. Wu and based on Dr. Wu's case, advised that a chest CT showed hidden pneumonic changes and facilitate a rapid diagnosis.

Related Terms

Case Series

A report about a small group of similar cases.

Preplanned Case-Observation

A case in which symptoms are elicited to study disease mechanisms. (Ex. Having a patient sleep in a lab to do brain imaging for a sleep disorder).

Now test yourself!

1. Case studies are not considered evidence-based even though the authors have studied the case in great depth.

2. When are Case reports most useful?

When you encounter common cases and need more information When new symptoms or outcomes are unidentified When developing practice guidelines When the population being studied is very large

Evidence Pyramid - Navigation

Meta- Analysis
<< Previous: Welcome to Study Design 101
Next: Case Control Study >>

Last Updated: Sep 25, 2023 10:59 AM
URL: https://guides.himmelfarb.gwu.edu/studydesign101

Himmelfarb Intranet
Privacy Notice
Terms of Use
GW is committed to digital accessibility. If you experience a barrier that affects your ability to access content on this page, let us know via the Accessibility Feedback Form .
Himmelfarb Health Sciences Library
2300 Eye St., NW, Washington, DC 20037
Phone: (202) 994-2850
[email protected]
https://himmelfarb.gwu.edu

Quantitative study designs: Case Studies/ Case Report/ Case Series

Quantitative study designs.

Introduction
Cohort Studies
Randomised Controlled Trial
Case Control
Cross-Sectional Studies
Study Designs Home

Case Study / Case Report / Case Series

Some famous examples of case studies are John Martin Marlow’s case study on Phineas Gage (the man who had a railway spike through his head) and Sigmund Freud’s case studies, Little Hans and The Rat Man. Case studies are widely used in psychology to provide insight into unusual conditions.

A case study, also known as a case report, is an in depth or intensive study of a single individual or specific group, while a case series is a grouping of similar case studies / case reports together.

A case study / case report can be used in the following instances:

where there is atypical or abnormal behaviour or development
an unexplained outcome to treatment
an emerging disease or condition

The stages of a Case Study / Case Report / Case Series

Which clinical questions does Case Study / Case Report / Case Series best answer?

Emerging conditions, adverse reactions to treatments, atypical / abnormal behaviour, new programs or methods of treatment – all of these can be answered with case studies /case reports / case series. They are generally descriptive studies based on qualitative data e.g. observations, interviews, questionnaires, diaries, personal notes or clinical notes.

What are the advantages and disadvantages to consider when using Case Studies/ Case Reports and Case Series ?

What are the pitfalls to look for?

One pitfall that has occurred in some case studies is where two common conditions/treatments have been linked together with no comprehensive data backing up the conclusion. A hypothetical example could be where high rates of the common cold were associated with suicide when the cohort also suffered from depression.

Critical appraisal tools

To assist with critically appraising Case studies / Case reports / Case series there are some tools / checklists you can use.

JBI Critical Appraisal Checklist for Case Series

JBI Critical Appraisal Checklist for Case Reports

Real World Examples

Some Psychology case study / case report / case series examples

Capp, G. (2015). Our community, our schools : A case study of program design for school-based mental health services. Children & Schools, 37(4), 241–248. A pilot program to improve school based mental health services was instigated in one elementary school and one middle / high school. The case study followed the program from development through to implementation, documenting each step of the process.

Cowdrey, F. A. & Walz, L. (2015). Exposure therapy for fear of spiders in an adult with learning disabilities: A case report. British Journal of Learning Disabilities, 43(1), 75–82. One person was studied who had completed a pre- intervention and post- intervention questionnaire. From the results of this data the exposure therapy intervention was found to be effective in reducing the phobia. This case report highlighted a therapy that could be used to assist people with learning disabilities who also suffered from phobias.

Li, H. X., He, L., Zhang, C. C., Eisinger, R., Pan, Y. X., Wang, T., . . . Li, D. Y. (2019). Deep brain stimulation in post‐traumatic dystonia: A case series study. CNS Neuroscience & Therapeutics. 1-8. Five patients were included in the case series, all with the same condition. They all received deep brain stimulation but not in the same area of the brain. Baseline and last follow up visit were assessed with the same rating scale.

References and Further Reading

Greenhalgh, T. (2014). How to read a paper: the basics of evidence-based medicine. (5th ed.). New York: Wiley.

Heale, R. & Twycross, A. (2018). What is a case study? Evidence Based Nursing, 21(1), 7-8.

Himmelfarb Health Sciences Library. (2019). Study design 101: case report. Retrieved from https://himmelfarb.gwu.edu/tutorials/studydesign101/casereports.cfm

Hoffmann T., Bennett S., Mar C. D. (2017). Evidence-based practice across the health professions. Chatswood, NSW: Elsevier.

Robinson, O. C., & McAdams, D. P. (2015). Four functional roles for case studies in emerging adulthood research. Emerging Adulthood, 3(6), 413-420.

<< Previous: Cross-Sectional Studies
Next: Study Designs Home >>
Last Updated: Jun 13, 2024 10:34 AM
URL: https://deakin.libguides.com/quantitative-study-designs

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
BMJ Journals

http://orcid.org/0000-0001-5502-5975 Mohammad Hassan Murad 1 ,
Shahnaz Sultan 2 ,
Samir Haffar 3 ,
Fateh Bazerbachi 4
1 Evidence-Based Practice Center, Mayo Clinic , Rochester , Minnesota , USA
2 Division of Gastroenterology, Hepatology, and Nutrition , University of Minnesota, Center for Chronic Diseases Outcomes Research, Minneapolis Veterans Affairs Healthcare System , Minneapolis , Minnesota , USA
3 Digestive Center for Diagnosis and Treatment , Damascus , Syrian Arab Republic
4 Department of Gastroenterology and Hepatology , Mayo Clinic , Rochester , Minnesota , USA
Correspondence to Dr Mohammad Hassan Murad, Evidence-Based Practice Center, Mayo Clinic, Rochester, MN 55905, USA; murad.mohammad{at}mayo.edu

https://doi.org/10.1136/bmjebm-2017-110853

Statistics from Altmetric.com

Request permissions.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

epidemiology

In 1904, Dr James Herrick evaluated a 20-year-old patient from Grenada who was studying in Chicago and suffered from anaemia and a multisystem illness. The patient was found to have ‘freakish’ elongated red cells that resembled a crescent or a sickle. Dr Herrick concluded that the red cells were not artefacts because the appearance of the cells was maintained regardless of how the smear slide was prepared. He followed the patient who had subsequently received care from other physicians until 1907 and questioned whether this was syphilis or a parasite from the tropics. Then in 1910, in a published case report, he concluded that this presentation strongly suggested a previously unrecognised change in the composition of the corpuscle itself. 1 Sickle cell disease became a diagnosis thereafter.

Case reports and case series have profoundly influenced the medical literature and continue to advance our knowledge in the present time. In 1985, the American Medical Association reprinted 51 papers from its journal that had significantly changed the science and practice of medicine over the past 150 years, and five of these papers were case reports. 2 However, concerns about weak inferences and the high likelihood of bias associated with such reports have resulted in minimal attention being devoted to developing frameworks for approaching, appraising, synthesising and applying evidence derived from case reports/series. Nevertheless, such observations remain the bread and butter of learning by pattern recognition and integral to advancing medical knowledge.

Guidance on how to write a case report is available (ie, a reporting guideline). The Case Report (CARE) guidelines 3 were developed following a three-phase consensus process and provide a 13-item checklist that can assist researchers in publishing complete and meaningful exposition of medical information. This checklist encourages the explicit presentation of patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes. 3 Yet, systematic reviewers appraising the evidence for decision-makers require tools to assess the methodological quality (risk of bias assessment) of this evidence.

In this guide, we present a framework to evaluate the methodological quality of case reports/series and synthesise their results, which is particularly important when conducting a systematic review of a body of evidence that consists primarily of uncontrolled clinical observations.

Definitions

In the biomedical published literature, a case report is the description of the clinical course of one individual, which may include particular exposures, symptoms, signs, interventions or outcomes. A case report is the smallest publishable unit in the literature, whereas case series report aggregates individual cases in one publication. 4

If a case series is prospective, differentiating it from a single-arm uncontrolled cohort study becomes difficult. In one clinical practice guideline, it was proposed that studies without internal comparisons can be labelled as case series unless they explicitly report having a protocol before commencement of data collection, a definition of inclusion and exclusion criteria, a standardised follow-up and clear reporting of the number of excluded patients and those lost to follow-up. 6

Evaluating methodological quality

Pierson 7 provided an approach to evaluate the validity of a case report based on five components: documentation, uniqueness, objectivity, interpretation and educational value, resulting in a score with a maximum of 10 (a score above 5 was suggested indicate a valid case report). This approach, however, was rarely used in subsequent work and seems to conflate methodological quality with other constructs. For case reports of adverse drug reactions, other systems classify an association as definite, probable, possible or doubtful based on leading questions. 8 9 These questions are derived from the causality criteria that was established in 1965 by the English epidemiologist Bradford Hills. 10 Lastly, we have adapted the Newcastle Ottawa scale 11 for cohort and case–control studies by removing items that relate to comparability and adjustment (which are not relevant to non-comparative studies) and retained items that focused on selection, representativeness of cases and ascertainment of outcomes and exposure. This tool was applied in several published systematic reviews with good inter-rater agreement. 12–16

Proposed tool

The previous criteria from Pierson, 7 Bradford Hills 10 and Newcastle Ottawa scale modifications 11 converge into eight items that can be categorised into four domains: selection, ascertainment, causality and reporting. The eight items with leading explanatory questions are summarised in table 1 .

View inline

Tool for evaluating the methodological quality of case reports and case series

For example, a study that explicitly describes all the cases who have presented to a medical centre over a certain period of time would satisfy the selection domain. In contrast, a study that reports on several individuals with unclear selection approach leaves the reader with uncertainty to whether this is the whole experience of the researchers and suggests possible selection bias. For the domain of ascertainment, self-report (of the exposure or the outcome) is less reliable than ascertainment using administrative and billing codes, which in turn is less reliable than clinical records. For the domain of causality, we would have stronger inference in a case report of an adverse drug reaction that has resolved with cessation of the drug and reoccurred after reintroduction of the drug. Lastly, for the domain of reporting, a case report that is described with sufficient details may allow readers to apply the evidence derived from the report in their practice. On the other hand, an inadequately reported case will likely be unhelpful in the course of clinical care.

We suggest using this tool in systematic reviews of case reports/series. One option to summarise the results of this tool is to sum the scores of the eight binary responses into an aggregate score. A better option is not to use an aggregate score because numeric representation of methodological quality may not be appropriate when one or two questions are deemed most critical to the validity of a report (compared with other questions). Therefore, we suggest making an overall judgement about methodological quality based on the questions deemed most critical in the specific clinical scenario.

Synthesis of case reports/series

A single patient case report does not allow the estimation of an effect size and would only provide descriptive or narrative results. Case series of more than one patient may allow narrative or quantitative synthesis.

Narrative synthesis

A systematic review of the cases with the rare syndrome of lipodystrophy was able to suggest core and supportive clinical features and narratively summarised data on available treatment approaches. 17 Another systematic review of 172 cases of the infrequently encountered glycogenic hepatopathy was able to characterise for the first time patterns of liver enzymes and hepatic injury in this disease. 18

Quantitative synthesis

Quantitative analysis of non-comparative series does not produce relative association measures such as ORs or relative risks but can provide estimates of prevalence or event rates in the form of a proportion (with associated precision). Proportions can be pooled using fixed or random effects models by means of the various available meta-analysis software. For example, a meta-analysis of case series of patients presenting with aortic transection showed that mortality was significantly lower in patients who underwent endovascular repair, followed by open repair and non-operative management (9%, 19% and 46%, respectively, P<0.01). 19

A common challenge, however, occurs when proportions are too large or too small (close to 0 or to 1). In this situation, the variance of the proportion becomes very small leading to an inappropriately large weight in meta-analysis. One way to overcome this challenge is to transform prevalence to a variable that is not constrained to the 0–1 range and has approximately normal distribution, conduct the meta-analysis and then transform the estimate back to a proportion. 20 This is done using logit transformation or using the Freeman-Tukey double arcsine transformation, 21 with the latter being often preferred. 20

Another type of quantitative analysis that may be utilised is regression. A meta-analysis of 47 published cases of hypocalcaemia and cardiac dysfunction used univariate linear regression analysis to demonstrate that both QT interval and left ventricular ejection fraction were significantly correlated with corrected total serum calcium level. 22 Meta-regression, which is a regression in which the unit of analysis is a study, not a patient, can also be used to synthesise case series and control for study-level confounders. A meta-regression analysis of uncontrolled series of patients with uveal melanoma treated with proton beam therapy has shown that this treatment was associated with better outcomes than brachytherapy. 23 It is very important, however, to recognise that meta-regression results can be severely affected by ecological bias.

From evidence to decision

Several authors have described various important reasons to publish case reports/series ( table 2 ). 7 24 25

Role of case reports/series in the medical literature

It is paramount to recognise that a systematic review and meta-analysis of case reports/series should not be placed at the top of the hierarchy in a pyramid that depicts validity. 26 The certainty of evidence derived from a meta-analysis is contingent on the design of included studies, their risk of bias, as well as other factors such as imprecision, indirectness, inconsistency and likelihood of publication bias. 27 Commonly, certainty in evidence derived from case series/reports will be very low. Nevertheless, inferences from such reports can be used for decision-making. In the example of case series of aortic transection showing lower mortality with endovascular repair, a guideline recommendation was made stating ‘We suggest that endovascular repair be performed preferentially over open surgical repair or non-operative management’. This was graded as a weak recommendation based on low certainty evidence. 28 The strength of this recommendation acknowledged that the recommendation might not universally apply to everyone and that variability in decision-making was expected. The certainty in evidence rating of this recommendation implied that future research would likely yield different results that may change the recommendation. 28

The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach clearly separates the certainty of evidence from the strength of recommendation. This separation allows decision-making based on lower levels of evidence. For example, despite low certainty evidence (derived from case series) regarding the association between aspirin and Reye’s syndrome in febrile children, a strong recommendation for using acetaminophen over aspirin is possible. 29 GRADE literature also describes five paradigmatic situations in which a strong recommendation can be made based on low quality evidence. 30 One of which is when the condition is life threatening. An example of which would be using hyperbaric oxygen therapy for purpura fulminans, which is only based on case reports. 31

Guideline developers and decision-makers often struggle when dealing with case reports/case series. On occasions, they ignore such evidence and focus the scope of guidelines on areas with higher quality evidence. Sometimes they label recommendations based on case reports as expert opinion. 32 We propose an approach to evaluate the methodological quality of case reports/series based on the domains of selection, ascertainment, causality and reporting and provide signalling questions to aid evidence-based practitioners and systematic reviewers in their assessment. We suggest the incorporation of case reports/series in decision-making based on the GRADE approach when no other higher level of evidence is available.

In this guide, we have made the case for publishing case reports/series and proposed synthesis of their results in systematic reviews to facilitate using this evidence in decision-making. We have proposed a tool that can be used to evaluate the methodological quality in systematic reviews that examine case reports and case series.

Gagnier JJ ,
Altman DG , et al
Grimes DA ,
Abu-Zidan FM ,
Schünemann HJ ,
Naranjo CA ,
Sellers EM , et al
9. ↵ The World health Organization-Uppsala Monitoring Centre . The use of the WHO-UMC system for standardised case causality assessment . https://www.who-umc.org/media/2768/standardised-case-causality-assessment.pdf ( accessed 20 Sep 2017 ).
O’Connell D , et al
Bazerbachi F ,
Prokop L , et al
Vargas EJ , et al
Watt KD , et al
Szarka LA , et al
Hussain MT , et al
Farah W , et al
Leise MD , et al
Malgor R , et al
Barendregt JJ ,
Lee YY , et al
Freeman MF ,
Newman DB ,
Fidahussein SS ,
Kashiwagi DT , et al
Schild SE , et al
Vandenbroucke JP
Alsawas M , et al
Matsumura JS ,
Mitchell RS , et al
Guyatt GH ,
Vist GE , et al
Domecq JP ,
Murad MH , et al
Mestrovic J , et al
Alvarez-Villalobos N ,
Shah R , et al
Conboy EE ,
Mounajjed T , et al
Gottlieb MS
Coodin FJ ,
Uchida IA ,
Goldfinger SE
Lennox BR ,
Jones PB , et al

Contributors MHM drafted the paper and all coauthors critically revised the manuscript. All the authors contributed to conceive the idea and approved the final submitted version.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Read the full text or download the PDF:

PH717 Module 1B - Descriptive Tools

Descriptive epidemiology & descriptive statistics.

Page:
1
| 2
| 3
| 4
| 5
| 6
| 7
| 8
| 9

Case Reports and Case Series

Case reports, case series, test yourself.

Categories of Descriptive Epidemiology

A case report is a detailed description of disease occurrence in a single person. Unusual features of the case may suggest a new hypothesis about the causes or mechanisms of disease.

Example: Acquired Immunodeficiency in an Infant; Possible Transmission by Means of Blood Products

In April 1983 it had not yet been shown that AIDS could be transmitted by blood or blood products. An infant born with Rh incompatibility; required blood products from 18 donors over 8 weeks and subsequently developed unusual recurrent infections with opportunistic agents such as Candida. The infant's T cell count was low, suggesting AIDS. There was no family history of immunodeficiency, but one of the blood donors was found to have died of AIDS. This led the investigators to hypothesize that AIDS could be transmitted by blood transfusion.

Link to article by Ammann AJ et al: Acquired immunodeficiency in an infant: possible transmission by means of blood products. The Lancet 1:956-958, 1983.

A case series is a report on the characteristics of a group of subjects who all have a particular disease or condition. Common features among the group may suggest hypotheses about disease causation. Note that the "series" may be small (as in the example below) or it may be large (hundreds or thousands of "cases"). However, the chief limitation is that there is no comparison group. Consequently, common features may suggest hypotheses, but these need to be tested with some sort of analytical study before an association can be accepted as valid.

Example: Discovery of HIV in the United States

This was an extraordinarily important case series (a detailed description of characteristics of a series of people who all have the same disease) that suggested that this new syndrome was associated with sexual activity in male homosexuals. Alerting the medical establishment and proposing a hypothesis was an important milestone in the AIDS epidemic.

Link to article by Gottlieb MS, et al: Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med 1981;305:1425-1431.

There had been a number of case reports of liver cancers in young women taking oral contraceptives. A study was undertaken by contacting all of the cancer registries collaborating with the American College of Surgeons. The investigators wanted to collect information on as many of these rare liver tumors as possible across the US.

Table - Oral Contraceptive Use Among Women Who Developed Liver Cancer


31%	43%	22%
20%	10%	29%
49%	48%	49%

What conclusions can you draw from these data regarding a possible increased risk of liver cancer in woman taking oral contraceptives? Think about it before you look at the answer.

The key to identifying a case series is that all of the subjects included in the study have the primary disease or outcome of interest. For example, an article reported on 239 people who got bird flu. The article might present tables and graphs that gave information about their age, occupation, where they lived, whether they lived or died, etc., but basically it is a detailed description of the characteristics and outcomes in a group of people who all had the same disease.

data

return to top | previous page | next page

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here .

Case series
Clinical research design
Get an email alert for Case series
Get the RSS feed for Case series

Showing 1 - 13 of 65

View by: Cover Page List Articles

Sort by: Recent Popular

Streptococcus pneumoniae in Latin America and the Caribbean: A systematic review and meta-analysis">Nasopharyngeal carriage of Streptococcus pneumoniae in Latin America and the Caribbean: A systematic review and meta-analysis

Martín Brizuela, María Carolina Palermo, [ ... ], Silvina Ruvinsky

Quantitative changes in the corneal endothelium and central corneal thickness during anterior chamber inflammation: A systematic review and meta-analysis

Germán Mejía-Salgado, Paula Tatiana Muñoz-Vargas, [ ... ], Alejandra de-la-Torre

Healthcare worker access to molnupiravir: A case series

Jessica C. O’Keeffe, Meg Constable, [ ... ], Daniel P. O’Brien

Hemoadsorption in the critically ill—Final results of the International CytoSorb Registry

Fatime Hawchar, Dana Tomescu, [ ... ], Frank Martin Brunkhorst

Iron deficiency and common neurodevelopmental disorders—A scoping review

Scout McWilliams, Ishmeet Singh, [ ... ], Osman S. Ipsiroglu

A novel quantitative computer-assisted drug-induced liver injury causality assessment tool (DILI-CAT)

Hans L. Tillmann, Ayako Suzuki, [ ... ], Don C. Rockey

Antifungal therapy in the management of fungal secondary infections in COVID-19 patients: A systematic review and meta-analysis

Sujit Kumar Sah, Atiqulla Shariff, [ ... ], Teggina Math Pramod Kumar

Transition approaches for autistic young adults: A case series study

Yosheen Pillay, Charlotte Brownlow, Sonja March

Environmental effect of air versus gas tamponade in the management of rhegmatogenous retinal detachment VR surgery: A multicentre study of 3,239 patients

George Moussa, Walter Andreatta, [ ... ], Dong Young Park

Recurrent SARS-CoV-2 infections and their potential risk to public health – a systematic review

Seth Kofi Abrokwa, Sophie Alice Müller, [ ... ], Charbel El Bcheraoui

Effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions: A scoping review

T. A. M. Oud, E. Lazzari, [ ... ], M. A. Brehm

COVID-19 and cause of pregnancy loss during the pandemic: A systematic review

Seyyedeh Neda Kazemi, Bahareh Hajikhani, [ ... ], Mohammad Javad Nasiri

Integrated care pathways in neurosurgery: A systematic review

Keng Siang Lee, Stefan Yordanov, [ ... ], Benjamin Davies

Connect with Us

PLOS ONE on Twitter
PLOS on Facebook

Case report
Open access
Published: 02 July 2024

Inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in susceptible pediatric patients: a case series

Neginsadat Hosseinikargar 1 ,
Hossein Zarrinfar ORCID: orcid.org/0000-0002-1449-4668 2 , 3 ,
Seyed Javad Seyedi 4 &
Seyedeh Sabereh Mojtahedi 1 , 5 , 6

Journal of Medical Case Reports volume 18 , Article number: 301 ( 2024 ) Cite this article

1 Altmetric

Metrics details

Pulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections.

Case presentation

The present study reports three cases of inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in two Iranian pediatric patients under investigation and one Afghan patient. Unfortunately, two of them died. The cases involved patients aged 9, 1.5, and 3 years. They had been diagnosed with pulmonary disorders, presenting nonspecific clinical signs and radiographic images suggestive of pneumonia. The identification of A . flavus was confirmed through DNA sequencing of the calmodulin ( CaM ) region.

A . flavus was the most prevalent cause of pulmonary aspergillosis in pediatric patients. Early diagnosis and accurate antifungal treatment of pulmonary aspergillosis could be crucial in reducing the mortality rate and also have significant potential for preventing other complications among children. Moreover, antifungal prophylaxis seems to be essential for enhancing survival in these patients.

Peer Review reports

Introduction

Aspergillus species are commonly found in the environment, and inhaling their conidia can lead to invasive diseases in immunocompromised individuals, especially in pediatric patients [ 1 ]. Aspergillus flavus is a major contributor to life-threatening invasive aspergillosis (IA) in the Middle East, primarily affecting immunocompromised patients [ 2 , 3 ]. Children and adults have similar disease presentations, distributions, patterns, and susceptibility to pulmonary aspergillosis (PA). However, there are variations in the pharmacology of antifungal medications, the epidemiology of underlying diseases, and the use of improved diagnostic methods [ 4 ]. Early diagnosis and treatment will enhance outcomes, particularly in neonates and pediatric patients [ 5 ]. Diagnosing pulmonary aspergillosis is challenging because recovering Aspergillus from respiratory specimens cannot differentiate between colonization and invasion [ 6 , 7 ]. In some forms of PA, such as chronic fibrosing PA (CFPA), bronchiectasis, and other associated changes in the lungs will occur. In patients with pulmonary issues, it is strongly recommended to perform chest computed tomography and bronchoscopy with bronchoalveolar lavage (BAL) [ 8 ]. BAL is also beneficial for evaluating pediatric lung diseases and can be essential for detecting respiratory infections, particularly PA [ 6 , 8 ]. It is strongly recommended that all clinically relevant Aspergillus isolates undergo pathogen identification at the species complex level [ 9 ]. Appropriate and timely treatment of PA can play an important role in reducing mortality among vulnerable patients [ 10 ]. This study describes three cases of inappropriate treatment of pulmonary aspergillosis caused by A . flavus in pediatric patients from Iran in the Middle East.

In April 2021, a 9-year-old Afghan boy was admitted to Sheikh Hospital in Mashhad. He presented with a fever, dyspnea, nonproductive cough, and respiratory distress. Additionally, he had previously received chemotherapy for Hodgkin’s lymphoma and tested negative for coronavirus disease 2019 (COVID-19) upon admission. Although he was treated with vancomycin and meropenem for antibiotic prophylaxis, he had not received any antifungal prophylaxis. Additionally, the patient received a blood transfusion. The radiography scans revealed the following outcomes: in the lung radiography scan (Fig. 1 ), an opacity patch was observed in the peripheral right hemothorax of the lungs. During his hospitalization, he also underwent a total gastrectomy and an intestinal biopsy. His hematological findings showed that his white blood cell (WBC) count was 0.5 × 10 3 /μl, red blood cell (RBC) count was 2.56 × 10 6 /μl, hemoglobin (Hb) was 6.9 g/dl, hematocrit (HCT) was 21.4%, platelet (PLT) count was 52 × 10 3 /μl, mean corpuscular volume (MCV) was 83.59 fl, mean corpuscular hemoglobin (MCH) was 26.95 pg, and mean corpuscular hemoglobin concentration (MCHC) was 32.24 g/dl. Moreover, other laboratory findings showed that the uric acid level was 4.2 mg/dl, and levels of calcium, phosphorus, urea, creatinine, sodium, and potassium were within the normal range. After the bronchoscopy, the secretions were sent to the medical mycology lab for additional diagnostic testing. The Pneumocystis jirovecii test result was negative for this patient. The clinical specimen was examined microscopically using 15% potassium hydroxide (KOH), and several hyaline septate hyphae were observed. In addition, the clinical specimen was also cultured on Sabouraud dextrose agar (SDA) and then incubated for 4–6 days at 35 °C. The colonies exhibited a yellowish-green appearance surrounded by a white circle that was eventually covered by conidia, as revealed by microscopic examination, indicating an Aspergillus species. The genomic DNA of Aspergillus was extracted, and polymerase chain reaction (PCR) and Sanger sequencing of the calmodulin ( CaM ) region were performed as described previously [ 11 ]. The closest match to the isolate in the CaM BLAST in GenBank was A . flavus . The genome sequence of the isolate has been deposited in GenBank with the accession number OQ538375. He had received imipenem, cefuroxime, and acyclovir for pulmonary pneumonia. Regrettably, owing to a delayed diagnosis of PA and a lack of prompt treatment with antifungal medication, the patient passed away after 22 days of hospitalization.

A chest radiograph showing an opaque patch in the peripheral right hemithorax of the lungs

In December 2021, a 1.5-year-old Iranian girl from Chenaran, located in Khorasan Razavi, was admitted to Sheikh Hospital in Mashhad. She had drowned in a pool for 10 minutes. Thereafter, she was resuscitated for 25 minutes, but her blood pressure and blood sugar levels were elevated. Additionally, she also received insulin. After her blood sugar levels returned to normal, she was administered dopamine. The patient was catheterized and intubated. Upon arrival at the hospital, she was unconscious and using an artificial manual breathing unit (Ambu) bag. She also experienced diarrhea, vomiting, and fever, and blood secretions were observed from the anus. However, she only received clindamycin for prophylaxis. Her hematological findings showed a WBC count of 2.7 × 10 3 /μl, RBC count of 4.47 × 10 6 /μl, Hb of 12.8 g/dl, HCT of 39.1%, PLT count of 152 × 10 3 /μl, MCV of 87.47 fl, MCH of 28.64 pg, and MCHC of 32.74 g/dl. The patient’s blood group was B+, and she received a transfusion. Her COVID-19 test result was negative. The radiography scan revealed consolidation in the middle zone of the right lung (Fig. 2 ). After a bronchoscopy, the BAL specimen was sent to the medical mycology laboratory for further analysis. The P . jirovecii test result was negative for this patient. The clinical specimen was examined microscopically using 15% KOH, which revealed septate hyphae similar to those in case 1. Another portion of the clinical specimen was also cultured on a SDA plate and then incubated at 35 °C for 4–6 days. The macroscopic and microscopic examination of the colonies revealed an Aspergillus species. The genomic DNA of Aspergillus was extracted, and PCR and Sanger sequencing of the CaM region were performed as previously described [ 11 ]. The closest match to the isolate in the CaM BLAST in GenBank was A . flavus . The genome sequence of the isolate has been deposited in GenBank with the accession number OQ538376. Furthermore, she was treated with ceftriaxone antibiotics. Regrettably, as a result of the delayed diagnosis and the severity of the PA infection, coupled with the absence of prompt treatment with antifungal medication, the patient passed away 3 days after being admitted to the hospital.

A chest radiograph showing consolidation in the middle zone of the right lung during a lung radiography scan

A 3-year-old Iranian girl was admitted to Sheikh Hospital in Mashhad in June 2021. She presented with fever, a nonproductive cough, convulsions, diarrhea, vomiting, lethargy, weakness, and signs of cerebral palsy (CP). She was diagnosed with pneumonia. However, the physician prescribed vancomycin and metronidazole as prophylaxis. The patient underwent catheterization and received a blood transfusion. Her COVID-19 test result was negative. The lung radiography scan revealed lung involvement in the right peripheral area (Fig. 3 ). Her hematological findings showed a WBC count of 9.8 × 10 3 /μl, RBC count of 3.64 × 10 6 /μl, Hb of 10 g/dl, HCT of 31%, PLT count of 331 × 10 3 /μl, MCV of 85 fl, MCH of 27 pg, MCHC of 32 g/dl, urea of 36 mg/dL, and high C-reactive protein (CRP) levels. Additionally, the levels of calcium, uric acid, creatinine, sodium, and potassium were within the normal range. After bronchoscopy, the BAL specimen was sent to the medical mycology laboratory for examination of fungal infections. The result of the P . jirovecii test, using real-time PCR, was positive for this patient. The septate hyphae were observed in a direct examination of the BAL specimen using 15% KOH. Additionally, another portion of the BAL specimen was cultured on a SDA plate and then incubated at 35 °C for 4–6 days. Aspergillus species were identified using PCR and sequencing, as previously described [ 11 ]. The PCR and Sanger sequencing of the CaM region of the isolate revealed that the closest match in the CaM BLAST in GenBank was A . flavus species. The genome sequence has been deposited in GenBank with the accession number OQ538374. The patient was prescribed seizure medication and amikacin. Despite only experiencing partial recovery and insisting on being discharged, the patient left the hospital without receiving antifungal drugs. Unfortunately, we were unable to follow up with this patient regarding the fungal infection.

A chest radiograph showing lung involvement in the right peripheral area

Aspergillus infections are a significant cause of morbidity and mortality, particularly among the growing population of immunocompromised patients [ 12 ]. Corticosteroids and prolonged neutropenia are known risk factors for this complication. Patients with PA usually present with fever, pleuritic chest pain, and hemoptysis [ 13 ]. Pneumothorax due to PA in children is extremely rare. However, it can be a devastating complication in children with hematological disorders [ 12 ]. Diagnosing invasive pulmonary aspergillosis (IPA) definitively remains challenging owing to its wide range of clinical features and the absence of approved laboratory methods. The type of clinical specimen, the sensitivity, and specificity of laboratory methods, as well as the availability of these techniques in medical centers, can significantly impact the diagnosis of this disease. Histopathological characteristics are considered the gold standard for diagnosing IPA. However, obtaining a tissue biopsy is often not feasible owing to the fragile condition of the patient, particularly in pediatric cases where invasive procedures may pose a risk. Therefore, the BAL fluid appears to be a relatively safe and useful specimen in high-risk patients suspected of having PA [ 6 ]. In contrast, traditional methods have much lower sensitivity compared with molecular and serological methods and cannot definitively diagnose IPA on their own. Yeoh et al . conducted a review study that demonstrated the inherent challenges in the timely diagnosis of IPA. They suggested that a combination of computed tomography (CT) imaging and microbiological testing can facilitate this process [ 14 ]. In the current study, CT scans were not performed. Instead, the initial diagnosis of these patients relied on chest X-rays and microbiological procedures. In CT and plain radiograph findings, most studies describe nodular opacities as most frequent, followed by wedge-shaped/lobar consolidations. Our cases showed consolidation and opacity patches in the chest X-ray without any wedge shape. However, radiographic images cannot specifically distinguish infections caused by Aspergillus from other microbial infections. Yeoh et al . also demonstrated that respiratory sampling through either BAL or lung biopsy is recommended, but it is not always feasible in pediatric patients.

Similarly, in our study, the BAL specimen could help identify fungal agents. However, it is important to distinguish cases of colonization from actual invasion of host tissues by fungal agents. Shah et al . reported three children who developed pneumothorax as a presenting feature of PA during induction chemotherapy for leukemia [ 1 ]. The diagnosis of PA was based on clinical manifestations, radiology findings, and a serum galactomannan test in two cases, and in one case, a specimen obtained by needle aspiration. In this report, we describe cases of pneumothorax in three children. One case had undergone chemotherapy, and the other had a coinfection with P . jirovecii . Unfortunately, galactomannan test on BAL or serum was not conducted in our cases owing to financial constraints. Crassard et al . conducted a 15-year review study in a pediatric hematology department and reported that 22 patients presented with lung involvement related to IPA [ 15 ]. The positive culture revealed the presence of various Aspergillus species, including A . fumigatus (18 cases), A . nidulans (3 cases), A . flavus (1 case), and A . terreus (1 case). Two species, A . fumigatus and A . nidulans , were isolated in a BAL culture from only one patient. Mark de mol et al . suggested that the galactomannan (GM) assay on BAL specimens is a valuable diagnostic tool for detecting IPA in children, with high sensitivity and specificity for the BAL GM index [ 7 ]. Several diagnostic studies have shown that the detection of BAL GM has better test performance than serum [ 16 , 17 ]. They found that 41 children suffered from IPA, diagnosed based on a GM test. During the direct examination, two specimens showed septate hyphae, and the culture results of seven specimens were positive for Aspergillus spp. The distribution of positive cultures was as follows: four A . fumigatus , two A . flavus , and one Aspergillus spp. Regrettably, in the current study, we were unable to conduct the GM test owing to several limitations. Children with IPA typically exhibit nonspecific radiographic findings, in contrast to the cavitary lesions frequently observed in adults [ 12 ]. We reported nonspecific radiographic findings, such as patches of opacity and consolidation. In a retrospective multicenter analysis of pediatric IPA, the most common diagnostic radiologic finding was nodules [ 8 ]. However, the German acute lymphocytic leukemia (ALL)-Berlin-Frankfurt-Muenster (BFM) study group reported that fungal infections accounted for one-fifth of fatal infections in pediatric patients with ALL [ 18 ]. Aspergillus was implicated in two-thirds of the cases of invasive fungal infections [ 18 ]. Despite the devastating complications and high mortality associated with IA, there is still no consensus on a prophylactic agent or treatment of choice for pediatric patients [ 19 ]. In our reports, regrettably, owing to the late diagnosis of PA, these patients did not receive appropriate and timely treatment. Timely diagnosis is crucial in pediatrics because of the potential severity and complications associated with PA. However, the challenges are associated with the nonspecific nature of symptoms and lower yields from microbiological procedures, which can lead to a high mortality rate among pediatric patients. This is because Aspergillus , a group of filamentous fungi, can destroy lung tissue and blood vessels. Regrettably, in the current study, it appears that two out of the three children studied passed away owing to a lack of timely diagnosis and treatment. Kashefi et al . reported the successful treatment of PA caused by A . fumigatus in a child with systemic lupus erythematosus using amphotericin B (50 mg/day) for 19 days [ 10 ]. Therefore, an accurate diagnosis of PA infection using paraclinical findings of the patient, such as radiographic images and laboratory results, can play a crucial role, especially in vulnerable children. Timely diagnosis and treatment of PA in children can reduce the risk of complications and mortality rates [ 14 ]. The present study has several novel findings, including the identification of three causative agents of PA by A . flavus in a specialized children’s hospital in Northeast Iran. This study is also the first research investigated in this region during the COVID-19 era. Furthermore, the present study examined the quantitative molecular diagnostic method for detecting P . jirovecii pneumonia (PJP) in pediatric patients. The present study has some limitations, including a relatively small sample size of children. Furthermore, we lacked comprehensive information about potential underlying diseases and the patients’ medical histories, including previous PA conditions and treatments, and access to serological methods for a more precise diagnosis of this disease.

Given that PA in pediatric patients has significant potential for morbidity and mortality complications, early diagnosis can be critical in decreasing the fatality rate. Furthermore, antifungal prophylaxis appears to be crucial for improving survival in these patients.

Data availability

Written informed consent was obtained from patient’s accompanying individual and are available for provision to the journal on demand.

Shah K, Kumar A, Kumar A, Kumar N, Kaushik P, Thumallapalli A, et al . Pulmonary aspergillosis silently presenting as pneumothorax in children with leukemia: a report of three cases. Indian J Med Paediatr Oncol. 2022;43(05):439–42.

Article Google Scholar

Zanganeh E, Zarrinfar H, Rezaeetalab F, Fata A, Tohidi M, Najafzadeh MJ, et al . Predominance of non-fumigatus Aspergillus species among patients suspected to pulmonary aspergillosis in a tropical and subtropical region of the Middle East. Microb Pathog. 2018;116:296–300.

Article PubMed Google Scholar

Nourizadeh N, Adabizadeh A, Zarrinfar H, Majidi M, Jafarian AH, Najafzadeh MJ. Fungal biofilms in sinonasal polyposis: the role of fungal agents is notable? J Oral Maxillofac Surg Med Pathol. 2019;31(4):295–8.

Dehghani R, Mohammadi S, Zarrinfar H, Jarahi L, Najafzadeh MJ, Salah H. The emergence of decreased activity of amphotericin B and voriconazole against clinical isolates of Aspergillus species: a subtropical region of the Middle East. J Popul Ther Clin Pharmacol. 2023;30(17):146–54.

Google Scholar

Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al . Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24:e1–38.

Zarrinfar H, Saber S, Kordbacheh P, Makimura K, Fata A, Geramishoar M, et al . Mycological microscopic and culture examination of 400 bronchoalveolar lavage (BAL) samples. Iran J Public Health. 2012;41(7):70.

CAS PubMed PubMed Central Google Scholar

de Mol M, de Jongste JC, van Westreenen M, Merkus PJ, de Vries AH, Hop WC, et al . Diagnosis of invasive pulmonary aspergillosis in children with bronchoalveolar lavage galactomannan. Pediatr Pulmonol. 2013;48(8):789–96.

Burgos A, Zaoutis TE, Dvorak CC, Hoffman JA, Knapp KM, Nania JJ, et al . Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases. Pediatrics. 2008;121(5):e1286–94.

Warris A, Lehrnbecher T, Roilides E, Castagnola E, Brüggemann R, Groll AH. ESCMID-ECMM guideline: diagnosis and management of invasive aspergillosis in neonates and children. Clin Microbiol Infect. 2019;25(9):1096–113.

Article CAS PubMed Google Scholar

Kashefi E, Seyedi SJ, Zomorodian K, ZareShahrabadi Z, Zarrinfar H. Successful treatment of pulmonary aspergillosis due to Aspergillus fumigatus in a child affected by systemic lupus erythematosus: a case report from Northeastern Iran. Clin Case Rep. 2021;9(5): e04248.

Article PubMed PubMed Central Google Scholar

Najafzadeh MJ, Dolatabadi S, Zarrinfar H, Houbraken J. Molecular diversity of aspergilli in two Iranian hospitals. Mycopathologia. 2021;186:519–33.

Pana ZD, Roilides E, Warris A, Groll AH, Zaoutis T. Epidemiology of invasive fungal disease in children. J Pediatr Infect Dis Soc. 2017;6(Suppl_1):S3–11.

Kousha M, Tadi R, Soubani A. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121):156–74.

Article CAS PubMed PubMed Central Google Scholar

Yeoh DK, McMullan BJ, Clark JE, Slavin MA, Haeusler GM, Blyth CC. The challenge of diagnosing invasive pulmonary aspergillosis in children: a review of existing and emerging tools. Mycopathologia. 2023;188(5):731–43.

Crassard N, Hadden H, Piens MA, Pondarre C, Hadden R, Galambrun C, et al . Invasive aspergillosis in a paediatric haematology department: a 15-year review. Mycoses. 2008;51(2):109–16.

Clancy CJ, Jaber RA, Leather HL, Wingard JR, Staley B, Wheat LJ, et al . Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol. 2007;45(6):1759–65.

Becker MJ, Lugtenburg EJ, Cornelissen JJ, Van Der Schee C, Hoogsteden HC, De Marie S. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J Haematol. 2003;121(3):448–57.

Grigull L, Beier R, Schrauder A, Kirschner P, Loening L, Jack T, et al . Invasive fungal infections are responsible for one-fifth of the infectious deaths in children with ALL. Mycoses. 2003;46(11–12):441–6.

Dvorak C, Steinbach W, Brown J, Agarwal R. Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2005;36(7):621–9.

Download references

Acknowledgements

We would like to thank the Food and Indoor Mycology—Houbraken group at The Westerdijk Fungal Biodiversity Institute in Utrecht, Netherlands, for identifying the Aspergillus isolates.

This study was financially supported by the Research Deputy (No. 991032) of Mashhad University of Medical Sciences.

Author information

Authors and affiliations.

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

Neginsadat Hosseinikargar & Seyedeh Sabereh Mojtahedi

Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Hossein Zarrinfar

Sinus and Surgical Endoscopic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Seyed Javad Seyedi

Department of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Seyedeh Sabereh Mojtahedi

Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran

You can also search for this author in PubMed Google Scholar

Contributions

NH performed routine laboratory examinations and contributed to writing the manuscript, HZ (corresponding author) collected information for the case report, SJS contributed to the patient’s care and initially diagnosed the patient, and SSM contributed to the editing of the manuscript and the required case information, images, and slides. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Hossein Zarrinfar .

Ethics declarations

Ethics approval and consent to participate.

These cases were derived from a section of grant No. 4000884 that was approved by the ethics committee (ethics code: IR.MUMS.MEDICAL.REC.1399.556). A signed informed consent form was obtained from the patient’s accompanying individual, granting permission to use the data for educational or research purposes before the procedure.

Consent for publication

Written informed consent was obtained from the patient’s next of kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Hosseinikargar, N., Zarrinfar, H., Seyedi, S.J. et al. Inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in susceptible pediatric patients: a case series. J Med Case Reports 18 , 301 (2024). https://doi.org/10.1186/s13256-024-04599-9

Download citation

Received : 29 November 2023

Accepted : 15 May 2024

Published : 02 July 2024

DOI : https://doi.org/10.1186/s13256-024-04599-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Pulmonary aspergillosis
Pediatric patients
Aspergillus

Journal of Medical Case Reports

ISSN: 1752-1947

Submission enquiries: Access here and click Contact Us
General enquiries: [email protected]

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

View all journals
Explore content
About the journal
Publish with us
Sign up for alerts
Open access
Published: 02 July 2024

Preoperative visualization of the greater occipital nerve with magnetic resonance imaging in candidates for occipital nerve decompression for headaches

Mariam Saad 1 na1 ,
Isaac V. Manzanera Esteve 1 na1 ,
Adam G. Evans 1 ,
Huseyin Karagoz 1 ,
Tigran Kesayan 2 ,
Krista Brooks-Horrar 3 ,
Saikat Sengupta 4 ,
Ryan Robison 4 , 5 ,
Brian Johnson 5 , 6 ,
Richard Dortch 7 ,
Wesley P. Thayer 1 ,
Patrick Assi 1 ,
Lisa Gfrerer 8 &
Salam Kassis 1

Scientific Reports volume 14 , Article number: 15248 ( 2024 ) Cite this article

Metrics details

Diagnostic markers
Peripheral nervous system

Occipital nerve decompression is effective in reducing headache symptoms in select patients with migraine and occipital neuralgia. Eligibility for surgery relies on subjective symptoms and responses to nerve blocks and Onabotulinum toxin A (Botox) injections. No validated objective method exists for detecting occipital headache pathologies. The purpose of the study is to explore the potential of high-resolution Magnetic Resolution Imaging (MRI) in identifying greater occipital nerve (GON) pathologies in chronic headache patients. The MRI protocol included three sequences targeting fat-suppressed fluid-sensitive T2-weighted signals. Visualization of the GON involved generating 2-D image slices with sequential rotation to track the nerve course. Twelve patients underwent pre-surgical MRI assessment. MRI identified four main pathologies that were validated against intra-operative examination: GON entanglement by the occipital artery, increased nerve thickness and hyperintensity suggesting inflammation compared to the non-symptomatic contralateral side, early GON branching with rejoining at a distal point, and a connection between the GON and the lesser occipital nerve. MRI possesses the ability to visualize the GON and identify suspected trigger points associated with headache symptoms. This case series highlights MRI's potential to provide objective evidence of nerve pathology. Further research is warranted to establish MRI as a gold standard for diagnosing extracranial contributors in headaches.

Introduction

The occipital nerves originating from the C2 and C3 spinal nerves provide sensation to the posterior head, encompassing the area beneath the occiput to the cranial vertex and extending laterally to the ear and the skin above the parotid gland 1 . Compression of the occipital nerves at specific points along their pathways can trigger occipital neuralgia and cervicogenic headache 2 . The relief of symptoms by local anesthetic blockade is a diagnostic criterion in both types of headaches as specified by the International Classification of Headache Disorders 3 rd Edition (ICDH-3) 3 . Migraines, however, have traditionally been attributed to have central nervous system origins, with more recent reports proposing a pathogenesis involving both central and peripheral mechanisms, including the role of pain from peripheral nerves of the head 4 , 5 , 6 , 7 . The ongoing debate centers on determining the primary site of the pathology within this complex interplay 4 .

Migraine headaches affect approximately 15–18% of the global population 8 , and rank as the second leading cause of disability worldwide 9 , 10 . In the United States, migraines are the most prevalent condition contributing to lost work hours, constituting a significant financial burden of $19.6 billion annually 11 . Symptomatic management with abortive and preventive medications remains the mainstay of migraine treatment 12 . Migraine prevention is recommended for patients experiencing more than four migraine episodes a month, yet less than half of these patients receive maintenance preventative therapy 13 . The range of medications used to treat migraines spans at least five different drug classes 14 , highlighting the multifaceted nature as well as the need for more definitive treatments for this disease. Individuals with symptoms refractory to medications and experiencing a characteristic headache in a distribution of peripheral nerves along the scalp could be suffering from headaches triggered by an external nerve compression 15 , 16 , 17 . Chronic headaches that meet diagnostic criteria for chronic migraine may also be accompanied by pain in a peripheral nerve distribution, such as the occipital nerve, due to a variety of etiologies. Although there are no reliable studies of how many patients with chronic migraine also have occipital neuralgia diagnosis, some estimates suggest that up to a quarter of patients presenting to a community headache clinic have a pain disorder associated with the occipital nerve 18 .

Furthermore, 85% of patients with occipital nerve area pain who present to a headache clinic are diagnosed with a second headache diagnosis, primarily migraine 18 . Chronic pain of a cranial nerve may lead to allodynia, which is known to lead to chronification of migraine headaches, and patients with painful neuropathy of the occipital nerve who also have chronic migraines may need additional treatment considerations. Patients in this category may find relief through treatments with peripheral nerve cascade effects, such as botulinum toxin injections, nerve blocks, transcutaneous nerve stimulation, implanted nerve stimulators, radiofrequency nerve ablation (RFA), and cryoneurolysis 19 , 20 , 21 , 22 . Yet these treatments are recognized for their short-lived temporary effects 23 .

Surgical decompression of the occipital nerves at their origin has been an established treatment for persistent cervicogenic headaches using dorsal C2 root decompression or anterior cervical decompression and fusion 24 , 25 , 26 . Additionally, surgical decompression along the distal tracks of occipital nerves, beyond their spinal origins, has shown significant improvement in patients with occipital neuralgia 27 , 28 . For migraines, studies have found extracranial nerve decompression surgery to be highly effective in reducing or eliminating symptoms in a subset of patients 29 , 30 , 31 , 32 , 33 , 34 . With careful patient selection, 50 to 85% experience complete symptom resolution, with an additional 8 to 30% report significant improvement 35 , 36 , 37 , 38 . Patient candidacy for decompression surgery relies on a comprehensive clinical evaluation, incorporating detailed history, headache characteristics, patient headache sketches, and response to injectables, with a lack of reliance on direct objective measures 37 .

In diseases related to the anatomic compression of peripheral nerves, such as neuropathies of the brachial and lumbosacral plexuses and carpal and cubital tunnel syndromes, specialized imaging modalities have been developed to identify the anatomic landmarks causing the entrapment of peripheral nerves and visualizing the compression points 39 , 40 , 41 , 42 , 43 , 44 . These techniques aid in diagnosis, particularly when clinical evaluation is insufficient or inconclusive and when nerve conduction studies are challenging 45 . In the case of occipital headaches, ultrasound imaging has been described to identify sites of occipital nerve entrapment in occipital neuralgia 46 , yet evaluation with ultrasound relies heavily on operator expertise in performing the test and analyzing the results, making it operator-dependent 2 . In cervicogenic headaches, MRI is used to detect structural changes of ligaments and membranes in the upper cervical spine that are postulated to be the sources of these headaches 47 , 48 . However, the diagnostic value of these changes is still controversial 49 .

High-resolution MRI can help identify peripheral nerve pathologies by detecting nerve signal abnormalities, recognizing muscle-related changes within a particular nerve region, displaying unexpected lesions that imitate symptoms of nerve damage, or ruling out neuropathy by revealing entirely normal imaging features in both muscles and nerves 50 . To our knowledge, no imaging technique has been identified that can successfully trace the occipital nerves and identify nerve pathologies with possible applicability for migraines and occipital neuralgia.

In this study, we aim to explore the potential of high-resolution MRI in identifying nerve pathologies in the GONs of patients with migraines undergoing occipital nerve decompression surgery. MRI findings are compared to operative observations, and patient-reported outcomes are collected to validate the observed pathologic findings.

Patients and methods

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board (IRB) of Vanderbilt University Medical Center. All participants were provided written informed consent before enrollment, and confidentiality of their data was strictly maintained throughout the study duration. Participants were assured of their right to withdraw from the study without repercussion. Individuals scheduled to undergo occipital nerve decompression surgery were approached for potential participation. The inclusion criteria encompassed males and females aged 18–85 who were capable of undergoing MRI scanning, with a diagnosis of chronic headache in the occipital region, and who could provide consent. Exclusion criteria included patients unable to recline in the MRI due to orthopedic, cardiac, or claustrophobic reasons, as well as children, patients in pregnancy, and individuals with metallic implants or previous exposure to metal fragments.

The occipital trigger site comprises three cranial sensory nerves that can be compressed by surrounding tissue: the GON, the lesser occipital nerve (LON), and the third occipital nerve (TON). The GON is thicker in caliber than the two other nerves and is characterized by radiation of the pain from the back of the head to the apex 37 . The LON is characterized by pain that starts posterolateral in the scalp and that can radiate towards the ear 37 . In this study, patients with headache characteristics congruent with compression of the GON are included.

All patients underwent comprehensive evaluation by a neurologist and a pain medicine physician and were given the ICHD-3 diagnosis of chronic migraine. Furthermore, all patients had pain of varying durations in the area of the occipital nerves, from frequent several-second episodes to constant baseline pain with superimposed episodes of worsening pain. All patients described this occipital pain as a contributor to their migraine headache episodes. Although the pain in some of these participants was not strictly brief and paroxysmal, which is typical for a ‘neuralgia’ diagnosis, their pain was neuralgiform in nature, severe, and they met all other diagnostic criteria for occipital neuralgia per the ICHD-3 3 . The patients were evaluated to distinguish occipital neuralgia from atlantooccipital, atlantoaxial joint, or cervical zygapophyseal joint etiologies. All patients had failed medical therapy and demonstrated temporary relief with nerve blocks or trigger point injections. Subsequently, patients were referred to the Department of Plastic Surgery and were deemed appropriate candidates for decompression surgery. Patients presented for MRI imaging of the occipital region on average three days prior to the scheduled surgery. All imaging was performed at Vanderbilt University Medical Center. The acquisition and subsequent analysis of all MRIs were conducted by the first author, I.M.E., who remained blinded to any patient-specific symptoms or complaints. All surgeries were performed at the same institution and video-recorded by the senior author, S.K., who described the operative pathologic findings, completely blinded from the MRI results. Additionally, two independent surgeons, H.K. and P.A., reviewed the video recordings to identify pathologic findings, blinded from the MRI results.

Patients were asked to complete a questionnaire via Research Electronic Data Capture (REDCap), a secure data collection tool that meets HIPAA compliance standards, to obtain average migraine pain severity, monthly migraine days, and headache duration when untreated with medication before surgery and at a 6-month post-operative timepoint. The percent change of these three factors between the pre- and post-operative settings was calculated 51 .

MRI Technique

MRI was performed using a research 3-Tesla Philips Healthcare MRI (Philips North America Corporation, Cambridge, MA, USA) and a 32-channel head coil. The protocol included three MRI sequences characterized by targeting fat-suppressed fluid-sensitive T2-weighted signal intensity to enhance nerve pathologies and perform a morphological assessment (nerve course caliber and size) 50 . The three MRI sequences are T2-FFE (3D PSIF), Fast inversion recovery (3D NerveView) and 3D mDixon TSE (3D BrainView). The sequence parameters are summarized in Table 1 .

MRI analysis

Nerve tracking was achieved using Connectome Workbench version 1.4.2. This tool overlays and reformats the images of the three sequences simultaneously in any plane, including the oblique plane, without loss of resolution, allowing the visualization of nerves with a chosen contrast regardless of location and orientation.

Analysis of the GON topography was performed by following and tracking the nerve distally in the subcutaneous tissue, then proximally at the trapezius muscle and fascia, the splenius capitis muscle, the semispinalis capitis muscle, and the obliquus capitis muscles until reaching the origin of the nerve proximally at the level of the C2 and C3 vertebrae. Diverse aspects such as nerve pathway variations, nerve caliber changes, and interactions between the nerve and adjacent structures were documented to identify pathologies linked to the GON. Such structures include the occipital artery (OA), the LON, and the muscles and fascia coursing along the track of the GON. Additionally, variations in nerve intensity signal at certain locations can be associated with nerve inflammation 52 .

Surgical technique and outcomes

Surgery is performed using a transverse occipital incision that allows access to the greater, lesser, and third occipital nerves. The LON is exposed laterally and tracked proximally to its exit from the posterior border of the sternocleidomastoid muscle and distally to the subcutaneous tissues, releasing all compression points. The GON is first identified at the third compression point as it exits the semispinalis capitis muscle and is tracked distally through the fourth compression point upon entry into the trapezius muscle fascial canal, followed by the fifth compression point at a potential intersection with the OA. Lastly, the sixth and most distal compression point is located at the trapezius fascia at the level of the nuchal ridge reaching into the subcutaneous tissue. The nerve is then tracked proximally within the semispinalis capitis muscle to the second compression point at the entry into the semispinalis capitis muscle, followed by the first and most proximal compression point at the junction of obliquus capitis inferior and the semispinalis capitis muscles 15 , 35 , 53 . The TON is identified caudally to the GON and decompressed as well.

Patient characteristics

Twelve patients were recruited to participate in this study. Ten were female and the average age was 49 ± 15. As a baseline, the average frequency of headaches was 16.5 ± 8.9 days/month, the mean headache duration was 20.0 ± 12.5 h/day, and the average pain level was 7.5 ± 1.4 on a scale from 1 to 10. All patients have had a previous trial of at least one injection with temporary relief of headache symptoms, with nerve blocks being the most commonly used (75%). Nausea (83%) and photophobia (83%) were the most prevalent symptoms associated with the headaches. A family history of migraine headaches was present in 58% of patients. All patients have had trials of many medications prior to undergoing surgery. Most notably, all patients have been on tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitor (100%). The majority have used calcitonin-gene related peptide inhibitors (91.7%), topiramate (75%), other anti-epileptic drugs (91.7%), and non-steroidal anti-inflammatory drugs (91.7%). Patient demographics, headache characteristics and, previous treatments are summarized in Table 2 .

The MRI protocol facilitated the visualization of the GON, covering its entire span from its most distal point in the subcutaneous tissue until its origin at the C2 and C3 vertebrae proximally. The nerve was traced using axial, parasagittal, and coronal slices, and rotated in a manner that enabled the visualization of both longitudinal and transverse sections at any stage of the analysis.

Continued reformatting of the three superimposed MR images in any desired plane while maintaining resolution enables comprehensive visualization of the nerve’s entire pathway. Additionally, the image overlay feature permits the selection of a preferred contrast for enhanced clarity. A representative 3-D visualization of the bilateral GONs’ course is shown in Fig. 1 -A of a patient with migraine and associated pain in bilateral areas of the occipital scalp. Performing transverse imaging and capturing both the left and right GONs in view facilitates a comparative analysis between the pathological side and its counterpart, as shown in Fig. 1 -B of the same patient.

Tracking of the GONs. ( A ) A representative 3D map of the left and right occipital nerves. ( B ) NerveView image of the GON bilaterally near the obliquus capitis muscle up to the trapezius muscle with yellow arrows pointing at the nerve path.

Among the twelve patients who underwent imaging, four MRI observations were particularly prominent and were also encountered intra-operatively and upon review of the video recordings. These observations are summarized in Table 3 .

In this paper, we will outline each of the four identified neuropathies on MRI scans that were confirmed by intra-operative examination. Some of the neuropathies were observed in patients intra-operatively but were not detected on pre-operative MRI. It should be emphasized that patients may have more than one of these neuropathies, but our focus will be on describing these individual findings comprehensively.

The most observed finding on the MRI that translated intra-operatively into a pathological compression point is the entanglement of the GON by the OA. This finding was identified in five patients on the MRI and confirmed in these same five patients intra-operatively, and seen again in additional two patients intra-operatively, yielding a successful detection rate of 71.4% by MRI compared to intra-operative findings. The OA was successfully managed by clipping and transecting the artery and detangling it from around the GON. MRI imaging and an operative photograph of a 51-year-old patient with migraines, predominantly in the left occipital region, depict the first pathology in Fig. 2 .

Coronal NerveView MRI tracking the left GON. ( A ) Two crossing structures with high intensity signals (red box). ( B ) Intraoperative image showing the GON (yellow dotted lines) and the OA being clipped and separated from the GON.

In four patients, sections of the GON at particular locations were identified on the MRI with higher signal intensity and increased thickness. These were interpreted as signs of inflammation (Fig. 3 ). Operative assessment of the GON and review of the video recording validated the finding as a thickened and edematous nerve with a yellowish discoloration that diminished upon decompression and was classified as inflammation by the surgeons in six patients. This neuropathy was successfully detected by MRI in 66.7% of cases. The findings of high signal intensity and increased thickness are shown in Fig. 3 , using images of a 48-year-old patient with symptoms predominantly on the left side. In some cases, the nerve is described intraoperatively as demonstrating an hourglass deformity. An MRI of another patient, who predominantly suffers from right-sided migraines, shows the same pathology in Fig. 4 . Yet in this patient, the right occipital nerve exhibits higher signal intensity compared to its counterpart on the left. The intraoperative photo corresponding to the MRI in Fig. 4 is shown in Fig. 6 -B, where only the right occipital region is being operated on, and where the patient is demonstrating two types of neuropathies.

( A ) Sagittal and ( B ) Transverse NerveView MRI tracking the left GON with high intensity signal as it courses through the trapezius fascia (red box). ( C ) Intraoperative thickened and yellowish GON at the level of a thick trapezius fascia (yellow arrow).

Transverse NerveView MRI tracking the right GON (yellow arrow) with high intensity signal as compared to the left GON (green arrow).

Anatomical variations of the GON can also represent possible points of neuropathy. Some variations can include early branching of the nerve and rejoining at a distal point with structures passing through the splitting. The branching was determined on the MRI and later observed again during surgery in two out of three patients, giving an MRI a detection rate of 66.7% for this neuropathy. Figure 5 demonstrates the early branching in a 53-year-old patient with predominant migraines on the right side.

( A ) Sagittal and ( B ) Transverse BrainView MRI showing a split structure suspected to be the GON (red box). ( C ) Intraoperative image showing the splitting in the left GON (yellow dotted lines) and the absence of splitting in the right GON.

The relationship of the GON relative to its surroundings is an important point that was being monitored on MRI. Two patients had images demonstrating a connection between the GON and LON. The relationship was seen again intraoperatively in these same two patients and is depicted in Fig. 6 with a 25-year-old patient having predominant migraines on the right side. The detection rate of the MRI of a connection between GON and LON in this series is 100%. It is important to mention that the MRI was capable of detecting both neuropathies along the course of the right GON in this patient: the high signal intensity signal at the level of the paraspinal muscles shown in Fig. 4 and the connection between the GON and the LON shown in Fig. 6 .

( A ) Transverse NerveView MRI showing connected structures (red box), appearing to depict the right GON and LON. ( B ) Intraoperative image showing the GON and the LON (yellow arrows) having a neural connection (yellow dotted lines).

Post-operative outcomes

Responses to the post-operative questionnaire were collected at 6 months and demonstrated a 64.2% decrease in monthly migraine days from an average of 16.5 ± 8.9 days to 5.9 ± 6.8 ( p < 0.0001). When headaches did occur, their mean duration decreased by 73.5%, from an average of 20.0 ± 12.5 h to a post-operative average of 5.3 ± 7.3 h ( p < 0.0001). Headache pain scores decreased by 18.7%, from an average of 7.5 ± 1.4 to a post-operative average of 6.1 ± 2.4 ( p = 0.004). The changes in patient outcomes are summarized in Table 4 .

In most patients, the pre-operative MRI was able to visualize and track the GON from its proximal origin at the C2 and C3 vertebrae to the subcutaneous tissue passing through the described six compression points 15 , 35 , 53 . In each MRI scan, abrupt changes in nerve thickness, nerve signal intensity, and variable relationships with nearby structures were being evaluated.

Among the twelve patients, several anatomic variations were noted. The OA was observed entangling the GON on the MRI in five patients. The OA compressing the GON is a previously established migraine trigger and compression point that would necessitate intervention to achieve symptomatic improvement 54 . In cadaveric studies, the relationship between the GON and OA appears intricate, as they might run in a parallel fashion at certain junctures and intersect at others. In a study involving 73 cadavers, the GON and OA had crossed once in 78% of cases, twice in 7%, and three times in 4% 55 . Additional research is needed to investigate whether interactions between the OA and the GON are associated with symptomatic improvement following surgery. Another four patients had a hyperintense signal emission on the MRI from their GON, especially when compared to the contralateral nerve in the case of unilateral headaches, hypothesized to represent inflammation. The nerves were seen intra-operatively as thickened, edematous, and yellowish. Hyperintensity on T2-weighted MRI aids in the identification of neural edema, particularly in instances of neural inflammation without compression, as seen in cases of cubital tunnel syndrome 56 .

The ability to detect inflammation surpasses the capabilities of the ultrasound which preferentially detects neural compressions, making MRI a superior choice in discerning neural inflammation in non-compressive pathologies 56 . While specific hourglass deformities were described in two cases by the operating surgeon, the precise findings of an abrupt change in nerve diameter along with an MRN signal change from hyper-, to hypo-, to hyperintensity characteristic of an hourglass constriction were not seen on an initial MRI evaluation of these two patients 57 . Early branching of the GON and distal rejoining was detected in the MRI of two patients. This splitting is seen on the MRI as a tracked single structured nerve that then forms a fork-like structure and downstream reconnection. In a cadaveric study, only two half-heads out of 40 cadavers demonstrated a division in the GON into two parts, each piercing the trapezius muscle aponeurosis separately and reuniting after passing it 58 . Two patients had the neuropathy of a connection between the GON and the LON. While this connection is described in cadaveric studies at the level of the occiput 58 , 59 , its visualization on MRI serves as a significant milestone highlighting the MRI’s capability to identify precise anatomical details. In cases where multiple neuropathies are detected in a patient, as illustrated in Figs. 4 and 6 , further investigation is warranted to determine whether these neuropathies are interrelated, consequential, or completely independent.

In other neuropathies, such as cubital and carpal tunnel syndromes, electrodiagnostic testing may be utilized to confirm and prognosticate the pathology 60 . However, electrodiagnostic testing is not possible in evaluating the occipital nerve due to its anatomical location. Imaging modalities, specifically MRI, have been explored in other neuropathies. MRI with multiplanar sequences, including high-resolution T1 and heavily T2-weighted fat-suppressed sequences, successfully detected abnormalities of the lumbosacral plexus and lower extremity nerves due to spinal and extraspinal compressions, malignancy, musculoskeletal disease, iatrogenesis, inflammation, and idiopathic diseases 45 . In a study of ulnar neuropathy at the elbow, an axial T2-weighted MRI sequence was evaluated in the detection of compression points associated with ulnar neuropathy. While achieving a perfect correlation in 66% of cases between MRI findings and intra-operative observations, the study also demonstrates a fair-to-moderate level of correlation on Cohen Kappa's measure 61 .

The MRI protocol utilized in our study is distinguished by its ability to concurrently reformat images from the three set sequences simultaneously in any plane, including the oblique plane, without compromising resolution. Additionally, aligning the nerve’s axial plane to be perpendicular to one of the three MRI planes is used to minimize potential morphological swelling artifacts. This combined approach facilitates the seamless tracking of small, tortuous nerves such as the GON.

The aim of this study is to identify and delineate GON-related MRI findings suggestive of compressive neuropathies or pathologies that would be amenable to surgical intervention. These observations were independently recorded intra-operatively and addressed surgically and were later reported upon review of the operative video, thereby validating the retrospective analysis of the MRI scans. While the study delineates MRI's capability to identify morphological features of the GON, it cannot definitively conclude the pathological nature of the observed findings in the current study design based on evaluations of twelve patients.

Despite most patients reporting significant reductions in migraine and headache frequency, duration, and pain severity following surgery, conclusive determination of specific neuropathies resulting from the observed findings post-surgery remains elusive. Future comparative investigations with at least 12 months follow-up between healthy individuals and those with pathology could enhance the understanding of GON-related neuropathies. Establishing a comprehensive database with nerve-tracking maps would significantly augment insights into potential neuropathies affecting the GON. The limited statistical analysis due to the small dataset derived from twelve patients is a study limitation. However, this series demonstrates the viability of utilizing MRI to assess the GON pre-operatively and explore the relationship between anatomical and surgical findings in migraine manifestations.

MRI can visualize the GON in patients with migraine headaches and occipital pain who are being considered for surgery and can detect anatomical features along the nerve, validated by comparison to intra-operative findings. Just as objective imaging modalities have been demonstrated to improve surgical outcomes in other nerve entrapment disorders such as carpal tunnel syndrome 62 , future research is needed to evaluate the diagnostic ability of high-resolution MRI in detecting migraine and occipital neuralgia-related nerve pathologies, decreasing false negatives and guiding surgical and extracranial interventions.

Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Kemp, W. J. 3rd., Tubbs, R. S. & Cohen-Gadol, A. A. The innervation of the scalp: A comprehensive review including anatomy, pathology, and neurosurgical correlates. Surg. Neurol. Int. 2 , 178. https://doi.org/10.4103/2152-7806.90699 (2011).

Article PubMed PubMed Central Google Scholar

Barmherzig, R. & Kingston, W. Occipital neuralgia and cervicogenic headache: Diagnosis and management. Curr. Neurol. Neurosci. Rep. 19 , 20. https://doi.org/10.1007/s11910-019-0937-8 (2019).

Article PubMed Google Scholar

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edn. Cephalalgia 38 , 1–211 (2018). https://doi.org/10.1177/0333102417738202

Do, T. P., Hougaard, A., Dussor, G., Brennan, K. C. & Amin, F. M. Migraine attacks are of peripheral origin: the debate goes on. J. Headache Pain. 24 , 3. https://doi.org/10.1186/s10194-022-01538-1 (2023).

Shevel, E. The extracranial vascular theory of migraine—A great story confirmed by the facts. Headache 51 , 409–417. https://doi.org/10.1111/j.1526-4610.2011.01844.x (2011).

Bartsch, T. & Goadsby, P. J. Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain 125 , 1496–1509. https://doi.org/10.1093/brain/awf166 (2002).

Bartsch, T. & Goadsby, P. J. The trigeminocervical complex and migraine: Current concepts and synthesis. Curr. Pain Headache Rep. 7 , 371–376. https://doi.org/10.1007/s11916-003-0036-y (2003).

Article CAS PubMed Google Scholar

Goadsby, P. J. et al. Pathophysiology of migraine: A disorder of sensory processing. Physiol. Rev. 97 , 553–622. https://doi.org/10.1152/physrev.00034.2015 (2017).

Steiner, T. J. & Stovner, L. J. Global epidemiology of migraine and its implications for public health and health policy. Nat. Rev. Neurol. 19 , 109–117. https://doi.org/10.1038/s41582-022-00763-1 (2023).

Steiner, T. J. et al. Migraine remains second among the world’s causes of disability, and first among young women: Findings from GBD2019. J. Headache Pain 21 , 137. https://doi.org/10.1186/s10194-020-01208-0 (2020).

Article CAS PubMed PubMed Central Google Scholar

Stewart, W. F., Ricci, J. A., Chee, E., Morganstein, D. & Lipton, R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA 290 , 2443–2454. https://doi.org/10.1001/jama.290.18.2443 (2003).

Robbins, M. S. Diagnosis and management of headache: A review. JAMA 325 , 1874–1885. https://doi.org/10.1001/jama.2021.1640 (2021).

Buse, D. C. et al. Barriers to care in episodic and chronic migraine: Results from the chronic migraine epidemiology and outcomes study. Headache 61 , 628–641. https://doi.org/10.1111/head.14103 (2021).

Zobdeh, F. et al. Pharmacological treatment of migraine: Drug classes, mechanisms of action, clinical trials and new treatments. Br. J. Pharmacol. 178 , 4588–4607. https://doi.org/10.1111/bph.15657 (2021).

Blake, P. & Burstein, R. Emerging evidence of occipital nerve compression in unremitting head and neck pain. J. Headache Pain 20 , 76. https://doi.org/10.1186/s10194-019-1023-y (2019).

Guyuron, B., Varghai, A., Michelow, B. J., Thomas, T. & Davis, J. Corrugator supercilii muscle resection and migraine headaches. Plast. Reconstr. Surg. 106 , 429–434. https://doi.org/10.1097/00006534-200008000-00030 (2000).

Perry, C. J. et al. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache. Ann. Neurol. 79 , 1000–1013. https://doi.org/10.1002/ana.24665 (2016).

Mathew, P. G., Najib, U., Khaled, S. & Krel, R. Prevalence of occipital neuralgia at a community hospital-based headache clinic. Neurol. Clin. Pract. 11 , 6–12. https://doi.org/10.1212/CPJ.0000000000000789 (2021).

Abd-Elsayed, A., Nguyen, S. & Fiala, K. Radiofrequency ablation for treating headache. Curr. Pain Headache Rep. 23 , 18. https://doi.org/10.1007/s11916-019-0755-3 (2019).

Evans, A. G. et al. Outcomes of transcutaneous nerve stimulation for migraine headaches: A systematic review and meta-analysis. J. Neurol. 269 , 4021–4029. https://doi.org/10.1007/s00415-022-11059-1 (2022).

Evans, A. G. et al. Nerve blocks for occipital headaches: A systematic review and meta-analysis. J. Anaesthesiol. Clin. Pharmacol. 39 , 170–180. https://doi.org/10.4103/joacp.JOACP_62_21 (2023).

Janis, J. E., Barker, J. C. & Palettas, M. Targeted peripheral nerve-directed onabotulinumtoxin a injection for effective long-term therapy for migraine headache. Plast. Reconstr. Surg. Glob. Open 5 , e1270. https://doi.org/10.1097/GOX.0000000000001270 (2017).

Chang, I. A., Wells, M. W., Wang, G. M., Tatsuoka, C. & Guyuron, B. Nonpharmacologic treatments for chronic and episodic migraine: A systematic review and meta-analysis. Plast. Reconstr. Surg. 152 , 1087–1098. https://doi.org/10.1097/PRS.0000000000010429 (2023).

Pang, X., Liu, C. & Peng, B. Anterior cervical surgery for the treatment of cervicogenic headache caused by cervical spondylosis. J. Pain. Res. 13 , 2783–2789. https://doi.org/10.2147/JPR.S275680 (2020).

Pikus, H. J. & Phillips, J. M. Characteristics of patients successfully treated for cervicogenic headache by surgical decompression of the second cervical root. Headache 35 , 621–629. https://doi.org/10.1111/j.1526-4610.1995.hed3510621.x (1995).

Yang, L. et al. Anterior cervical decompression and fusion surgery for cervicogenic headache: A multicenter prospective cohort study. Front. Neurol. 13 , 1064976. https://doi.org/10.3389/fneur.2022.1064976 (2022).

Jose, A., Nagori, S. A., Chattopadhyay, P. K. & Roychoudhury, A. Greater occipital nerve decompression for occipital neuralgia. J. Craniofac. Surg. 29 , e518–e521. https://doi.org/10.1097/SCS.0000000000004549 (2018).

Pietramaggiori, G. & Scherer, S. Minimally invasive nerve- and muscle-sparing surgical decompression for occipital neuralgia. Plast. Reconstr. Surg. 151 , 169–177. https://doi.org/10.1097/PRS.0000000000009777 (2023).

ElHawary, H., Barone, N., Baradaran, A. & Janis, J. E. Efficacy and safety of migraine surgery: a systematic review and meta-analysis of outcomes and complication rates. Ann. Surg. 275 , e315–e323. https://doi.org/10.1097/SLA.0000000000005057 (2022).

Evans, A. G. et al. Outcomes of surgical treatment of migraines: a systematic review & meta-analysis. Plast. Surg. (Oakv) 31 , 192–205. https://doi.org/10.1177/22925503211036701 (2023).

Guyuron, B., Kriegler, J. S., Davis, J. & Amini, S. B. Comprehensive surgical treatment of migraine headaches. Plast. Reconstr. Surg. 115 , 1–9 (2005).

Guyuron, B., Kriegler, J. S., Davis, J. & Amini, S. B. Five-year outcome of surgical treatment of migraine headaches. Plast. Reconstr. Surg. 127 , 603–608. https://doi.org/10.1097/PRS.0b013e3181fed456 (2011).

Guyuron, B. et al. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast. Reconstr. Surg. 124 , 461–468. https://doi.org/10.1097/PRS.0b013e3181adcf6a (2009).

Janis, J. E. et al. A review of current evidence in the surgical treatment of migraine headaches. Plast. Reconstr. Surg. 134 , 131S-141S. https://doi.org/10.1097/PRS.0000000000000661 (2014).

Ascha, M., Kurlander, D. E., Sattar, A., Gatherwright, J. & Guyuron, B. In-depth review of symptoms, triggers, and treatment of occipital migraine headaches (Site IV). Plast. Reconstr. Surg. 139 , 1333e–1342e. https://doi.org/10.1097/PRS.0000000000003395 (2017).

Ducic, I., Hartmann, E. C. & Larson, E. E. Indications and outcomes for surgical treatment of patients with chronic migraine headaches caused by occipital neuralgia. Plast. Reconstr. Surg. 123 , 1453–1461. https://doi.org/10.1097/PRS.0b013e3181a0720e (2009).

Gfrerer, L., Austen, W. G. Jr. & Janis, J. E. Migraine surgery. Plast. Reconstr. Surg. Glob. Open 7 , e2291. https://doi.org/10.1097/GOX.0000000000002291 (2019).

Raposio, E. & Bertozzi, N. Trigger site inactivation for the surgical therapy of occipital migraine and tension-type headache: Our experience and review of the literature. Plast. Reconstr. Surg. Glob. Open 7 , e2507. https://doi.org/10.1097/GOX.0000000000002507 (2019).

Bencardino, J. T. & Rosenberg, Z. S. Entrapment neuropathies of the shoulder and elbow in the athlete. Clin. Sports. Med. 25 (465–487), vi–vii. https://doi.org/10.1016/j.csm.2006.03.005 (2006).

Chirokikh, A. A. et al. Where does ultrasound fit in the diagnostic algorithm for cubital tunnel syndrome?. Hand (N Y) https://doi.org/10.1177/15589447231200645 (2023).

Du, R., Auguste, K. I., Chin, C. T., Engstrom, J. W. & Weinstein, P. R. Magnetic resonance neurography for the evaluation of peripheral nerve, brachial plexus, and nerve root disorders. J. Neurosurg. 112 , 362–371. https://doi.org/10.3171/2009.7.JNS09414 (2010).

Graf, A., Ahmed, A. S., Roundy, R., Gottschalk, M. B. & Dempsey, A. Modern treatment of cubital tunnel syndrome: Evidence and controversy. J. Hand Surg. Glob. Online 5 , 547–560. https://doi.org/10.1016/j.jhsg.2022.07.008 (2023).

Petrover, D. & Richette, P. Treatment of carpal tunnel syndrome: From ultrasonography to ultrasound guided carpal tunnel release. Joint Bone Spine 85 , 545–552. https://doi.org/10.1016/j.jbspin.2017.11.003 (2018).

Vo, N. Q. et al. Magnetic resonance imaging as a first-choice imaging modality in carpal tunnel syndrome: New evidence. Acta Radiol. 64 , 675–683. https://doi.org/10.1177/02841851221094227 (2023).

Robbins, N. M. et al. Magnetic resonance neurography in the diagnosis of neuropathies of the lumbosacral plexus: A pictorial review. Clin. Imaging 40 , 1118–1130. https://doi.org/10.1016/j.clinimag.2016.07.003 (2016).

Narouze, S. Occipital neuralgia diagnosis and treatment: The role of ultrasound. Headache 56 , 801–807. https://doi.org/10.1111/head.12790 (2016).

Krakenes, J. et al. MRI assessment of the alar ligaments in the late stage of whiplash injury–a study of structural abnormalities and observer agreement. Neuroradiology 44 , 617–624. https://doi.org/10.1007/s00234-002-0799-6 (2002).

Krakenes, J. & Kaale, B. R. Magnetic resonance imaging assessment of craniovertebral ligaments and membranes after whiplash trauma. Spine 31 , 2820–2826. https://doi.org/10.1097/01.brs.0000245871.15696.1f (2006).

Knackstedt, H., Krakenes, J., Bansevicius, D. & Russell, M. B. Magnetic resonance imaging of craniovertebral structures: Clinical significance in cervicogenic headaches. J. Headache Pain 13 , 39–44. https://doi.org/10.1007/s10194-011-0387-4 (2012).

Chhabra, A. et al. MR neurography: Past, present, and future. AJR Am. J. Roentgenol. 197 , 583–591. https://doi.org/10.2214/AJR.10.6012 (2011).

Diener, H. C. et al. Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults. Cephalalgia 40 , 1026–1044. https://doi.org/10.1177/0333102420941839 (2020).

Chen, Y., Haacke, E. M. & Li, J. Peripheral nerve magnetic resonance imaging. F1000Res https://doi.org/10.12688/f1000research.19695.1 (2019).

Janis, J. E. et al. The anatomy of the greater occipital nerve: Part II. Compression point topography. Plast. Reconstr. Surg. 126 , 1563–1572. https://doi.org/10.1097/PRS.0b013e3181ef7f0c (2010).

Chung, M., Lu, K. B., Sanniec, K. & Amirlak, B. The greater occipital nerve and its dynamic compression points: Implications in migraine surgery. Plast. Reconstr. Surg. 149 , 1321–1324. https://doi.org/10.1097/PRS.0000000000009094 (2022).

Saglam, L., Gayretli, O., Coskun, O. & Kale, A. Morphological features of the greater occipital nerve and its possible importance for interventional procedures. J. Anat. https://doi.org/10.1111/joa.13959 (2023).

Griffith, J. F. & Guggenberger, R. Diagnostic Imaging IDKD. In Musculoskeletal Diseases 2021–2024 (eds Hodler, J. et al. ) 259–268 (Springer, 2021).

Chapter Google Scholar

Sneag, D. B. et al. MRI bullseye sign: An indicator of peripheral nerve constriction in parsonage-turner syndrome. Muscle Nerve 56 , 99–106. https://doi.org/10.1002/mus.25480 (2017).

Natsis, K. et al. The course of the greater occipital nerve in the suboccipital region: A proposal for setting landmarks for local anesthesia in patients with occipital neuralgia. Clin. Anat. 19 , 332–336. https://doi.org/10.1002/ca.20190 (2006).

Choi, I. & Jeon, S. R. Neuralgias of the head: Occipital neuralgia. J. Korean Med. Sci. 31 , 479–488. https://doi.org/10.3346/jkms.2016.31.4.479 (2016).

American Association of Electrodiagnostic Medicine, A. A. o. N., American Academy of Physical, M. & Rehabilitation. Practice parameter for electrodiagnostic studies in carpal tunnel syndrome: summary statement. Muscle Nerve 25 , 918–922 (2002). https://doi.org/10.1002/mus.10185

Hold, A. et al. 3-Tesla MRI-assisted detection of compression points in ulnar neuropathy at the elbow in correlation with intraoperative findings. J. Plast. Reconstr. Aesthet. Surg. 71 , 1004–1009. https://doi.org/10.1016/j.bjps.2018.02.014 (2018).

Britz, G. W. et al. Carpal tunnel syndrome: Correlation of magnetic resonance imaging, clinical, electrodiagnostic, and intraoperative findings. Neurosurgery 37 , 1097–1103. https://doi.org/10.1227/00006123-199512000-00009 (1995).

Download references

Vanderbilt Institute for Clinical and Translational Research, VR60350, Plastic Surgery Foundation, 941171.

Author information

These authors contributed equally: Mariam Saad and Isaac V. Manzanera Esteve.

Authors and Affiliations

Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

Mariam Saad, Isaac V. Manzanera Esteve, Adam G. Evans, Huseyin Karagoz, Wesley P. Thayer, Patrick Assi & Salam Kassis

Department of Anesthesiology, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

Tigran Kesayan

Department of Neurology, Tennessee Valley Healthcare System, Nashville, TN, 37212, USA

Krista Brooks-Horrar

Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

Saikat Sengupta & Ryan Robison

Philips Healthcare, Nashville, TN, 37219, USA

Ryan Robison & Brian Johnson

University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

Brian Johnson

Barrow Neurological Institute, Phoenix, AZ, 85013, USA

Richard Dortch

Division of Plastic and Reconstructive Surgery, Weill Cornell, New York, NY, 10065, USA

Lisa Gfrerer

You can also search for this author in PubMed Google Scholar

Contributions

M.S. and I.V.M.E. are both first authors. M.S. has made substantial contributions in the analysis and interpretation of the data, have drafted the work, and revised it. I.V.M.E. has made substantial contributions to the conception and design of the work, in the data analysis and interpretation, and in the creation of a new software used in the work and have drafted and substantively revised it. A.G.E. have made substantial contributions in drafting the work. H.K. has made substantial contributions in analysis and interpretation of data, and revising the work. T.K. has made substantial contributions in revising the work. K.B.H. has made substantial contributions in revising the work. S.S. has made substantial contributions in the creation of a new software used in the work. R.R. has made substantial contributions in the creation of a new software used in the work. B.J. has made substantial contributions in the creation of a new software used in the work. R.D. has made substantial contributions in revising the work. W.P.T. has made substantial contributions in interpreting the data and revising the work. P.A. has made substantial contributions in data analysis and revising the work. L.G. has made substantial contributions in revising the work. S.K. has made substantial contributions in the conception and the design of the work, the acquisition, analysis, and interpretation of data, and revising the work.

Corresponding author

Correspondence to Salam Kassis .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Cite this article.

Saad, M., Manzanera Esteve, I.V., Evans, A.G. et al. Preoperative visualization of the greater occipital nerve with magnetic resonance imaging in candidates for occipital nerve decompression for headaches. Sci Rep 14 , 15248 (2024). https://doi.org/10.1038/s41598-024-65334-4

Download citation

Received : 28 March 2024

Accepted : 19 June 2024

Published : 02 July 2024

DOI : https://doi.org/10.1038/s41598-024-65334-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Headache surgery
Decompression surgery
Occipital nerve
Neuropathic pain
Migraine surgery
Nerve decompression

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

Explore articles by subject
Guide to authors
Editorial policies

2024 - WFP’s Support to Strengthening Social Protection Systems Around the Globe

https://docs.wfp.org/api/documents/WFP-0000159322/download/

This series of case studies draws from rapid literature reviews, interviews and consultations with WFP staff and key stakeholders. It evaluates WFP’s long-term contributions to supporting and strengthening national social protection systems across a range of different ‘building blocks’, examining its strategic objectives and role in each context and highlighting key successes, challenges, and lessons learned.

The series covers the following fifteen countries: Bangladesh, Cambodia, the Caribbean, Colombia, Djibouti, Ecuador, Ghana, Haiti, India, Iraq, Mauritania, Pakistan, Philippines, Uganda, and Zimbabwe.

The series of case studies was conducted by the Centre for Social Protection of the Institute of Development Studies (IDS) for WFP.

Publications

2024 - measuring the value of using social protection for emergency response: research programme.

2024 - Maximizing impact: the intersection of social protection and resilience. WFP Social Protection and Resilience Policy Brief

Regional Evaluation of WFP’s contribution to Shock-Responsive Social Protection in Latin America and the Caribbean (2015–2022)

Advanced search

Supported by

Corruption Law Allows Gifts to State and Local Officials, Supreme Court Rules

The court, which has limited the sweep of several anti-corruption laws, distinguished after-the-fact rewards from before-the-fact bribes.

Share full article

The Supreme Court building in Washington with several birds flying above it.

By Abbie VanSickle and Adam Liptak

Reporting from Washington

The Supreme Court limited the sweep of a federal law on Wednesday aimed at public corruption, ruling that it did not apply to gifts and payments meant to reward actions taken by state and local officials.

The 6-to-3 ruling , which split along ideological lines, was the latest in a series of decisions cutting back federal anti-corruption laws.

Justice Brett M. Kavanaugh, writing for a conservative majority, said that the question in the case was whether federal law makes it a crime for state and local officials to accept such gratuities after the fact. He wrote, “The answer is no.”

Federal prosecutors’ interpretation of the law created traps for public officials, leaving them to guess what gifts were allowed, he added. If they guessed wrong, the opinion continued, the officials could face up to a decade in prison.

The decision reflected a sharp divide on the court, with Justice Ketanji Brown Jackson, joined by Justices Elena Kagan and Sonia Sotomayor, dissenting. While the conservative wing asserted that the ruling gave discretion to state and local governments and protected officials from having to guess whether their behavior had crossed a criminal line, the liberals said the decision represented more chipping away of a statute aimed at protecting against graft.

“Officials who use their public positions for private gain threaten the integrity of our most important institutions,” Justice Jackson wrote. “Greed makes governments — at every level — less responsive, less efficient and less trustworthy from the perspective of the communities they serve.”

We are having trouble retrieving the article content.

Please enable JavaScript in your browser settings.

Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.

Thank you for your patience while we verify access.

Already a subscriber? Log in .

Want all of The Times? Subscribe .

Discover CALS

See how our current work and research is bringing new thinking and new solutions to some of today's biggest challenges.

Agriculture
Applied Economics
Climate Change
Communication
Environment
Global Development
Health + Nutrition

New report on conservation, land-use in the Hudson River Estuary Watershed

Department of Global Development
Natural Resources and the Environment
Natural Resources

The new report, Natural Resource Protection in the Hudson Valley: Municipal Conservation Stories , presents case studies from seven Hudson Valley towns and highlights the experiences, challenges, and successes of elected officials and municipal volunteers in pursuing conservation actions.

In New York State, municipal governments can play a vital role in conservation of biodiversity priorities, such as forest habitat and wildlife corridors; protection of water resources; and climate change adaptation through local plans and policies. For more than two decades, the New York State Department of Environmental Conservation’s (DEC) Hudson River Estuary Program and Cornell University’s Department of Natural Resources and the Environment (DNRE) have partnered to study the biodiversity of the estuary watershed and help municipalities and land trusts pursue conservation planning initiatives that consider local, regional, and state priorities.

The outreach publication evolved from Cornell research into municipal planning strategies that result in ecosystem protection outcomes. The research is led by Daria Ponstingel , a postdoctoral research associate at DNRE, with Shorna Allred , Adjunct Professor in DNRE and the Department of Global Development at Cornell University and Susan R. Wolf Professor at the University of North Carolina at Chapel Hill, and Laura Heady , the Conservation and Land Use Program Coordinator with Cornell DNRE at the NYSDEC Hudson River Estuary Program.

A key component of the research project was the development of a Municipal Conservation Efforts Index, which scored 256 watershed municipalities based on a set of 19 possible actions that support conservation. The index included a range of local practices, plans, and policies, such as adopting wetland protection, creating an open space plan, or having a conservation advisory council.

“These conservation actions build community resilience to flooding and drought, protect water quality, and preserve natural areas of unique significance, and include commitments to take action on climate change,” said Ponstingel.

“For the publication, we interviewed community leaders from towns that had high or medium index scores, and through their stories, share examples, insights, and lessons learned for other municipalities, conservation practitioners, and anyone else interested in locally-driven approaches to biodiversity conservation,” Ponstingel added.

“The estuary watershed is one of the most biologically rich parts of New York State,” said Heady, “which makes it a wonderful place to live. But with many, many local governments and landowners, the watershed is a ‘complex decision-making landscape’ where the impact of uncoordinated, individual decisions can have tremendous impacts on the larger ecosystem."

We’re fortunate to have many local leaders whose commitment to their communities and nature are making a very positive impact, and we hope their stories inspire others to follow their lead and contribute to a shared conservation vision for the Hudson Valley,” Heady added.

“It’s remarkable to look at the long history of engagement by these municipalities with our Conservation and Land Use Team at the Estuary Program,” said Allred. “This speaks to the importance of building long-term relationships and trust when entering the challenging arena of land-use planning—a sentiment also shared by our interviewees when discussing their own role in public outreach and community engagement. We’ve seen changes in how people receive news and information, and since the COVID-19 pandemic, the traditional, in-person ‘town hall’ meeting isn’t as effective. We’re glad to share how municipalities are addressing these challenges in inclusive community engagement.”

The communities profiled in the publication include the following, with brief highlights from their stories:

Town of Bedford (Westchester County). Bedford is building on its long history implementing conservation policies with a new initiative to preserve wildlife habitat connectivity.
Town of Beekman (Dutchess County). The chair of Beekman's Conservation Advisory Council (CAC) has served for 26 years; he recommended having diverse perspectives to be a successful CAC.
Town of Milan (Dutchess County). Milan’s recent natural resources inventory (NRI) helped the community understand its relationship to water that spans municipal boundaries.
Town of Nassau (Rensselaer County). Nassau’s supervisor pointed to the NRI and science as the underpinnings of the town's land-use ordinance.
Town of New Paltz (Ulster County). When federal regulations changed, New Paltz was able to pursue its wetland protection goals thanks to having a local law.
Town of Philipstown (Putnam County). By having a Natural Resources Officer/Wetlands Inspector, Philipstown is able to take a wholistic approach to conservation planning and enforcement.
Town of Woodstock (Ulster County). Woodstock leaders emphasized transparency and comprehensive outreach as keys to their successful adoption of a critical environmental area.

A limited number of hard copies of the 56-page Natural Resource Protection in the Hudson Valley: Municipal Conservation Stories have been distributed to county planning agencies and land trusts throughout New York State, municipalities in the estuary watershed, and program partners, and is available for viewing and download on the DEC website .

Funding for the research and publication was received from the New York State Water Resources Institute and the Hudson River Estuary Program . Learn more about the Conservation and Land Use Team’s work in the estuary watershed .

Keep Exploring

Development Sociology

Two individuals show dragon fruit banner

We openly share valuable knowledge.

an image, when javascript is unavailable

672 Wine Club
Motorcycles
Car of the Month
Destinations
Men’s Fashion
Watch Collector
Art & Collectibles
Vacation Homes
Celebrity Homes
New Construction
Home Design
Electronics
Fine Dining
Dubai Tourism
Gateway Bronco
On Location – Olympic Games Paris 2024
One&Only
The Ritz-Carlton, Kapalua
Saratoga Spring Water
Sports & Leisure
Health & Wellness
Best of the Best
The Ultimate Gift Guide
Food & Drink
Taste Test: Heaven Hill’s New Bourbon Proves Grain-to-Glass Whiskey Is More Than a Gimmick

This is a case study in how grains can affect a whiskey's flavor.

Jonah flicker, jonah flicker's most recent stories, this new 100-year-old cognac may be the oldest barrel-aged expression ever, buffalo trace just dropped a new barrel-proof rye whiskey for its colonel e.h. taylor, jr. line.

Share This Article

More Spirits

Hermitage Siècle d’Or 100 Year Old Cognac

How to Make a Fort Tilden Cooler, the Sophisticated Beachy Cocktail

Colonel E.H. Taylor, Jr Barrel Proof Rye Whiskey

Bowmore and Aston Martin Just Unveiled Their Final Whisky Collab

The Grand UK Debut

JULY 17 - 19, 2024 Head to the British countryside to test and evaluate the top luxury and performance vehicles of 2024.

Give the Gift of Luxury

Latest Galleries in Spirits

The 11 Best Gins to Drink Right Now, From Roku to Monkey 47

The 15 Best Whiskeys to Buy Now, From Bourbon to Scotch

More from our brands, top street-style trends from paris couture week: statement dressing, conversational bags and more, new york mets introduce $5 food and beverage promotion, skydance media and national amusements inc. reach new merger agreement for paramount global, wing luke museum to relocate show accused of ‘platforming zionist ideology’, the best yoga mats for any practice, according to instructors.

The Daily Show Fan Page

Explore the latest interviews, correspondent coverage, best-of moments and more from The Daily Show.

The Daily Show

S29 E68 • July 8, 2024

Host Jon Stewart returns to his place behind the desk for an unvarnished look at the 2024 election, with expert analysis from the Daily Show news team.

Extended Interviews

The Daily Show Tickets

Attend a Live Taping

Find out how you can see The Daily Show live and in-person as a member of the studio audience.

Best of Jon Stewart

The Weekly Show with Jon Stewart

New Episodes Thursdays

Jon Stewart and special guests tackle complex issues.

Powerful Politicos

The Daily Show Shop

Great Things Are in Store

Become the proud owner of exclusive gear, including clothing, drinkware and must-have accessories.

About The Daily Show

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Publications
Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

Advanced Search
Journal List
BMC Res Notes

The clinical case report: a review of its merits and limitations

Trygve nissen.

1 Department of Clinical Medicine, University of Tromsø, N-9038 Tromsø, Norway

2 Division of General Psychiatry, University Hospital of North Norway, N-9291 Tromsø, Norway

3 Division of Addictions and Specialized Psychiatry, University Hospital of North Norway, N-9291 Tromsø, Norway

The clinical case report has a long-standing tradition in the medical literature. While its scientific significance has become smaller as more advanced research methods have gained ground, case reports are still presented in many medical journals. Some scholars point to its limited value for medical progress, while others assert that the genre is undervalued. We aimed to present the various points of view regarding the merits and limitations of the case report genre. We searched Google Scholar, PubMed and select textbooks on epidemiology and medical research for articles and book-chapters discussing the merits and limitations of clinical case reports and case series.

The major merits of case reporting were these: Detecting novelties, generating hypotheses, pharmacovigilance, high applicability when other research designs are not possible to carry out, allowing emphasis on the narrative aspect (in-depth understanding), and educational value. The major limitations were: Lack of ability to generalize, no possibility to establish cause-effect relationship, danger of over-interpretation, publication bias, retrospective design, and distraction of reader when focusing on the unusual.

Conclusions

Despite having lost its central role in medical literature in the 20th century, the genre still appears popular. It is a valuable part of the various research methods, especially since it complements other approaches. Furthermore, it also contributes in areas of medicine that are not specifically research-related, e.g. as an educational tool. Revision of the case report genre has been attempted in order to integrate the biomedical model with the narrative approach, but without significant success. The future prospects of the case report could possibly be in new applications of the genre, i.e. exclusive case report databases available online, and open access for clinicians and researchers.

Throughout history the clinical case report and case report series have been integral components of medical literature [ 1 ]. The case report genre held a strong position until it was sidelined in the second half of the 20 th century [ 2 , 3 ]. New methodologies for research articles paved the way for evidence-based medicine. Editors had to make space for these research articles and at the same time signaled less enthusiasm for publishing case reports [ 4 ]. This spurred some heated debates in medical journals as readers were worried that the traditional case report was in jeopardy [ 5 , 6 ]. Those who welcomed the new trend with fewer case reports being published pointed mainly to their low quality and inclination to emphasize mere curiosa [ 7 - 9 ]. Some of the proponents of the genre claimed that the case report had been and still was indispensible for furthering medical knowledge and that it was unique in taking care of the detailed study of the individual patient as opposed to the new research methods with their “…nomothetic approach [taking] precedence…” [ 5 ]. Still, the case report got a low ranking on the evidence hierarchy. After a decline in popularity a new interest for the case report emerged, probably beginning in the late 1990s [ 2 ]. A peer-reviewed ‘Case reports’ section was introduced in the Lancet in 1995 [ 10 ]. In 2007, the first international, Pubmed-listed medical journal publishing only case reports was established [ 11 , 12 ]. In the following years, several similar journals, for the most part online and open-access, have been launched.

The present debate is not so much focused on whether case reporting is obsolete or not. Some of the discussions after the turn of the century have been about adapting the case report genre to new challenges. One example is the suggestion of incorporating the narrative, i.e. “… stressing the patient’s story”, in the case report [ 13 ]. The authors termed their initiative “The storied case report”. Their endeavor was not met with success. In analyzing the causes for this, they wondered if “… junior trainees find it too hard to determine what is relevant and senior trainees find it too hard to change their habits” [ 13 ]. A similar attempt was done when the editors of the Journal of Medical Case Reports in 2012 encouraged authors to include the patients’ perspectives by letting patients describe their own experiences [ 14 ].

Notwithstanding, we feel there is much to be gained from having an ongoing discussion highlighting the indications and contraindications for producing case reports. This can to some degree be facilitated by getting an understanding of the merits and limitations of the genre. The objective of this article is to present the merits and limitations of case reports and case series reports.

We adopted Taber’s Cyclopedic Medical Dictionary’s definition of the case report : “A formal summary of a unique patient and his or her illness, including the presenting signs and symptoms, diagnostic studies, treatment course and outcome” [ 15 ]. A case report consists of one or two cases, most often only one. The case series or case series report usually consists of three to ten cases [ 16 ]. (In the following we use the term case report to denote both case reports and case series report). Case reports are most often naturalistic and descriptive. Sometimes, however, they can be prospective and experimental.

As literature specifically dealing with the case report genre seemed harder to elicit from the databases than the vast amount of particular case reports, we performed iterative searches. We searched Google Scholar and PubMed using the search terms ‘case report(s)’, ‘case series’, ‘case series report(s)’, ‘case reporting’ in various combinations with ‘clinical’, ‘medical’, ‘anecdotal’, ‘methodology’, ‘review’, ‘overview’, ‘strengths’, ‘weaknesses’, ‘merits’, and ‘limitations’. Further references were identified by examining the literature found in the electronic searches. We also consulted major textbooks on epidemiology [ 17 , 18 ], some scholars of medical genres [ 19 , 20 ] and a monograph on case reporting by the epidemiologist M. Jenicek [ 16 ]. We delimited our review to the retrospective, naturalistic, and descriptive case report, also labeled the “traditional” or “classic” case report, and case series including such reports. Thus we excluded other types, such as the planned, qualitative case study approach [ 21 ] and simulated cases [ 22 - 24 ]. Finally, we extracted the relevant data and grouped the merits and limitations items in rank order with the items we judged to be the most important first.

New observations

The major advantage of case reporting is probably its ability to detect novelties [ 16 ]. It is the only way to present unusual, uncontrolled observations regarding symptoms, clinical findings, course of illness, complications of interventions, associations of diseases, side effects of drugs, etc. In short, anything that is rare or has never been observed previously might be important for the medical community and ought to be published. A case report might sensitize readers and thus facilitate detection of similar or identical cases.

Generating hypotheses

From a single, or preferably several single case reports or a case series, new hypotheses could be formulated. These could then be tested with formal research methods that are designed to refute or confirm the hypotheses, i.e. comparative (observational and experimental) studies.

There are numerous examples of new discoveries or major advancements in medicine that started with a case report or, in some cases, as humbly as a letter to the editor. The first concern from the medical community about the devastating side effect of thalidomide, i.e. the congenital abnormalities, appeared as a letter to the editor in the Lancet in 1961 [ 25 ]. Soon thereafter, several case reports and case series reports were published in various journals. Case reporting is thus indispensable in drug safety surveillance (pharmacovigilance) [ 26 ].

Sometimes significant advancements in knowledge have come not from what researchers were pursuing, but from “accidental discoveries”, i.e. by serendipity. The story of Alexander Fleming’s discovery of penicillin in 1928 is well known in the medical field [ 27 ]. Psychiatry has profited to a large degree from this mode of advancing medical science as many of the drugs used for mental disorders have been discovered serendipitously [ 27 ]. One notable example is the discovery of the effect of lithium on manic episodes in patients with manic-depressive disorder [ 28 ]. A more recent discovery is the successful treatment of infantile hemangiomas with systemic propranolol. This discovery was published, as a case series report, in the correspondence section in New England Journal of Medicine [ 29 ]. However, the evidence for the effect of this treatment is still preliminary, and several randomized trials are under way [ 30 , 31 ].

Clear and operational entities are prerequisites for doing medical research. Descriptions must come before understanding. Clinical observations that lead to new disorders being described are well suited for case reporting. The medical literature is replete with case-based articles describing new diseases and syndromes. One notable example is the first description of neurasthenia by G. Beard in Boston Medical and Surgical Journal in 1869 [ 32 ].

Researching rare disorders

For rare disorders randomized controlled trials (RCTs) can be impossible to run due to lack of patients to be enrolled. Research on drug treatment and other kinds of interventions must therefore be based on less rigorous methodologies, among them case series and case reports. This would be in accordance with the European Commission’s recommendation to its members to improve health care for those with rare disorders [ 33 ].

Solving ethical constraints

Case reporting can be valuable when ethical constraints prohibit experimental research. Take as an example the challenge of how to manage the side effects of accidental extravasation of cytotoxic drugs. As RCTs on humans seem unethical in this clinical situation the current guidelines rest on small observational studies, case reports and animal studies [ 34 ]. Or another example: Physical restraint is sometimes associated with sudden, unexpected death. The cause or causes for this are to some degree enigmatic, and it is hard to conceive of a controlled study that could be ethical [ 35 , 36 ]. Case reports and case series being “natural experiments” might be the only evidence available for guiding clinical practice.

In-depth narrative case studies

Case reporting can be a way of presenting research with an idiographic emphasis. As contrasted to nomothetic research, an idiographic approach aims at in-depth understanding of human phenomena, especially in the field of psychology and psychiatry. The objective is not generalizable knowledge, but an understanding of meaning and intentionality for an individual or individuals. Sigmund Freud’s case studies are relevant examples. This usage of case reports borders on qualitative research. Qualitative studies, although developed in the social sciences, have become a welcome contribution within health sciences in the last two decades.

Educational value

Clinical medical learning is to a large degree case-based. Typical case histories and vignettes are often presented in textbooks, in lectures, etc. Unusual observations presented as published case reports are important as part of doctors’ continuing medical education, especially as they demonstrate the diversity of manifestations both within and between medical diseases and syndromes [ 37 , 38 ]. Among the various medical texts, the case report is the only one that presents day-to-day clinical practice, clinicians’ diagnostic reasoning, disease management, and follow-up. We believe that some case reports that are written with the aim of contributing to medical knowledge turn out to be of most value educationally because the phenomena have already been described elsewhere. Other case reports are clearly primarily written for educational value [ 37 ]. Some journals have regular sections dedicated to educational case reports, e.g. The Case Records of the Massachusetts General Hospital in the New England Journal of Medicine and the Clinical Case Conference found in the American Journal of Psychiatry.

The cost of doing a case report is low compared to planned, formal studies. Most often the necessary work is probably done in the clinical setting without specific funding. Larger studies, for instance RCTs, will usually need an academic setting.

Fast publication

The time span from observation to publication can be much shorter than for other kinds of studies. This is obviously a great advantage as a case report can be an important alert to the medical community about a serious event. The unexpected side effects of the sedative-antinauseant thalidomide on newborn babies is a telling story. The drug had been prescribed during pregnancy to the babies’ mothers. After the first published observation of severe abnormalities in babies appeared as a letter to the editor of the Lancet in December 16 th , 1961 [ 25 ], several case reports and series followed [ 39 , 40 ]. It should be mentioned though that the drug company had announced on December 2 nd , 1961, i.e. two weeks before the letter from McBride [ 25 ], that it would withdraw the drug form the market immediately [ 41 ].

Flexible structure

Riaz Agha, editor of the International Journal of Surgery Case Reports suggests that the case report, with its less rigid structure is useful as it “… allows the surgeon(s) to discuss their diagnostic approach, the context, background, decision-making, reasoning and outcomes” [ 42 ]. Although the editor is commenting on the surgical case report, the argument can be applied for the whole field of clinical medicine. It should be mentioned though, that other commentators have argued for a more standardized, in effect more rigid, structure [ 43 ].

Clinical practice can be changed

Case reporting can lead to or contribute to a change in clinical practice. A drug might be withdrawn from the market. Or a relabeling might change the attitude to and treatment of a condition. During Word War I the shell shock syndrome was labeled and described thoroughly in several articles in the Lancet , the first of them appearing in February 1915 [ 44 ]. The author was the British captain and military doctor Charles S. Myers. Before his efforts to bring good care and treatment to afflicted soldiers there had been a common misconception that many of these dysfunctional soldiers were malingerers or cowards.

Exercise for novice researchers

The case report format is well suited for young doctors not yet trained as researchers. It can be an opportunity for a first exercise in authoring an article and a preparation for a scientific career [ 37 , 45 , 46 ].

Communication between the clinical and academic fields

Articles authored by clinicians can promote communication between practicing clinicians and academic researchers. Observations published can generate ideas and be a trigger for further studies. For instance, a case series consisting of several similar cases in a short period can make up the case-group for a case–control study [ 47 ]. Clinicians could do the observation and publish the case series while the case–control study could be left to the academics.

Entertainment

Some commentators find reading case reports fun. Although a rather weak argument in favor of case reporting, the value of being entertained should not be dismissed altogether. It might inspire physicians to spend more time browsing and reading scientific literature [ 48 ].

Studying the history of medicine

Finally, we present a note on a different and unintended aspect of the genre. The accumulated case reports from past eras are a rich resource for researching and understanding medical history [ 49 , 50 ]. A close study of old case reports can provide valuable information about how medicine has been practiced through the centuries [ 50 , 51 ].

Limitations

No epidemiological quantities.

As case reports are not chosen from representative population samples they cannot generate information on rates, ratios, incidences or prevalences. The case or cases being the numerator in the equation, has no denominator. However, if a case series report consists of a cluster of cases, it can signal an important and possibly causal association, e.g. an epidemic or a side effect of a newly marketed drug.

Causal inference not possible

Causality cannot be inferred from an uncontrolled observation. An association does not imply a cause-effect relationship. The observation or event in question could be a mere coincidence. This is a limitation shared by all the descriptive studies [ 47 ]. Take the thalidomide tragedy already mentioned as an example; Unusual events such as congenital malformations in some of the children born to mothers having taken a specific drug during pregnancy does not prove that the drug is the culprit. It is a mere hypothesis until further studies have either rejected or confirmed it. Cause-effect relationships require planned studies including control groups that to the extent possible control for chance, bias and confounders [ 52 ].

Generalization not possible

From the argument above, it follows that findings from case reports cannot be generalized. In order to generalize we need both a cause-effect relationship and a representative population for which the findings are valid. A single case report has neither. A case series, on the other hand, e.g. many “thalidomide babies” in a short time period, could strengthen the suspicion of a causal relationship, demanding further surveillance and research.

Publication bias could be a limiting factor. Journals in general favor positive-outcome findings [ 53 ]. One group of investigators studying case reports published in the Lancet found that only 5% of case reports and 10% of case series reported treatment failures [ 54 ]. A study of 435 case reports from the field of dentistry found that in 99.1%, the reports “…clearly [had] a positive outcome and the intervention was considered and described as successful by the authors” [ 55 ].

Overinterpretation

Overinterpretation or misinterpretation is the tendency or temptation to generalize when there is no justification for it. It has also been labeled “the anecdotal fallacy” [ 56 ]. This is not a shortcoming intrinsic to the method itself. Overinterpretation may be due to the phenomenon of case reports often having an emotional appeal on readers. The story implicitly makes a claim to truth. The reader might conclude prematurely that there is a causal connection. The phenomenon might be more clearly illustrated by the impact of the clinician’s load of personal cases on his or her practice. Here exemplified by a young doctor’s confession: “I often tell residents and medical students, ‘The only thing that actually changes practice is adverse anecdote.’” [ 57 ].

Emphasis on the rare

As case reporting often deals with the rare and atypical, it might divert the readers’ attention from common diseases and problems [ 58 ].

Confidentiality

Journals today require written informed consent from patients before publishing case reports. Both authors and publishers are responsible for securing confidentiality. A guarantee for full confidentiality is not always possible. Despite all possible measures taken to preserve confidentiality, sometimes the patient will be recognized by someone. This information should be given to the patient. An adequately informed patient might not consent to publication. In 1995 in an Editorial in the British Journal of Psychiatry one commentator, Isaac Marks, feared that written consent would discourage case reports being written [ 59 ]. Fortunately, judged form the large number of reports being published today, it seems unlikely that the demand for consent has impeded their publication.

Other methodological limitations

Case reports and series are written after the relevant event, i.e. the observation. Thus, the reports are produced retrospectively. The medical record might not contain all relevant data. Recall bias might prevent us from getting the necessary information from the patient or other informants such as family members and health professionals.

It has also been held against case reporting that it is subjective. The observer’s subjectivity might bias the quality and interpretation of the observation (i.e. information bias).

Finally, the falsification criterion within science, which is tested by repeating an experiment, cannot be applied for case reports. We cannot design another identical and uncontrolled observation. However, unplanned similar “experiments” of nature can be repeated. Several such observations can constitute a case series that represents stronger indicative evidence than the single case report.

The major advantages of case reporting are the ability to make new observations, generate hypotheses, accumulate scientific data about rare disorders, do in-depth narrative studies, and serve as a major educational tool. The method is deficient mainly in being unable to deliver quantitative data. Nor can it prove cause-effect relationship or allow generalizations. Furthermore, there is a risk of overinterpretation and publication bias.

The traditional case report does not fit easily into the qualitative-quantitative dichotomy of research methods. It certainly shares some characteristics with qualitative research [ 16 ], especially with regard to the idiographic, narrative perspective – the patient’s “interior world” [ 60 ] – that sometimes is attended to. Apart from “The storied case report” mentioned in the Background-section, other innovative modifications of the traditional case report have been tried: the “evidence-based case report” [ 61 ], the “interactive case report” [ 62 ] and the “integrated narrative and evidence based case report” [ 63 ]. These modifications of the format have not made a lasting impact on the way case reports in general are written today.

The method of case reporting is briefly dealt with in some textbooks on epidemiology [ 17 , 18 ]. Journals that welcome case reports often put more emphasis on style and design than on content in their ‘instruction to authors’ section [ 64 ]. As a consequence, Sorinola and coworkers argue for more consensus and more consistent guidance on writing case reports [ 64 ]. We feel that a satisfactory amount of guidance concerning both style and content now exists [ 12 , 16 , 65 , 66 ]. The latest contribution, “The CARE guidelines”, is an ambitious endeavor to improve completeness and transparency of reports [ 66 ]. These guidelines have included the “Patient perspective” as an item, apparently a bit half-heartedly as this item is placed after the Discussion section, thus not allowing this perspective to influence the Discussion and/or Conclusion section. We assume this is symptomatic of medicine’s problem with integrating the biomedical model with “narrative-based medicine”.

In recent years the medical community has taken an increased interest in case reports [ 2 ], especially after the surge of online, exclusive case report journals started in 2007 with the Journal of Medical Case Reports (which was the first international, Pubmed-listed medical journal publishing only case reports) as the first of this new brand. The climate of skepticism has been replaced by enthusiasm and demand for more case reports. A registry for case reports, Cases Database, was founded in 2012 [ 67 ]. On the condition that it succeeds in becoming a large, international database it could serve as a register being useful for clinicians at work as well as for medical research on various clinical issues. Assuming Pamela P. Powell’s assertion that “[a]lmost all practicing physicians eventually will encounter a case worthy of being reported” [ 60 ] is valid, there should be no shortage of potential cases waiting to be reported and filed in various databases, preferably online and open access.

Limitations of this review

There are several limitations to this study. It is a weakness that we have not been able to review all the relevant literature. The number of publications in some way related to case reports and case report series is enormous, and although we have attempted to identify those publications relevant for our purpose (i.e. those that describe the merits and limitations of the case report genre), we might have missed some. It was difficult to find good search terms for our objective. Still, after repeated electronic searches supplemented with manual searches in reference lists, we had a corpus of literature where essentially no new merits or limitations emerged.

As we point out above, the ranking of merits and limitations represents our subjective opinion and we acknowledge that others might rank the importance of the items differently.

The perspective on merits and limitations of case reporting has been strictly medical. As a consequence we have not analyzed or discussed the various non-medical factors affecting the publication of case reports in different medical journals [ 2 ]. For instance, case reports are cited less often than other kinds of medical research articles [ 68 ]. Thus they can lower a journal’s impact factor, potentially making the journal less attractive. This might lead some high-impact journals to publish few or no case reports, while other journals have chosen to specialize in this genre.

Before deciding on producing a case report or case series based on a particular patient or patients at hand, the observant clinician has to determine if the case report method is the appropriate article type. This review could hopefully assist in that judgment and perhaps be a stimulus to the continuing debate in the medical community on the value of case reporting.

Competing interests

The authors declare that there are no competing interests.

Authors’ contributions

TN contributed to the conception, drafting, and revision of the article. RW contributed to the conception, drafting, and revision of the article. Both authors approved the final manuscript.

Acknowledgements

There was no specific funding for this study.

Cabán-Martinez AJ, Beltrán WF. Advancing medicine one note at a time: the educational value in clinical case reports. BMC Res Notes. 2012; 5 :293. doi: 10.1186/1756-0500-5-293. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Nissen T, Wynn R. The recent history of the clinical case report: a narrative review. JRSM Sh Rep. 2012; 3 :87. doi: 10.1258/shorts.2012.012046. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Nissen T, Wynn R. The history of the case report: a selective review. JRSM Open. 2014; 5 :4. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Wilkinson G. Fare the well – the Editor’s last words. Br J Psychiatry. 2003; 182 :465–466. doi: 10.1192/bjp.182.6.465. [ CrossRef ] [ Google Scholar ]
Williams DDR. In defence of case of the case report (Letter) Br J Psychiatry. 2004; 184 :84. doi: 10.1192/bjp.184.1.84. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Enoch MD. Case reports (Letter) Br J Psychiatry. 2005; 185 :169. [ PubMed ] [ Google Scholar ]
Nahum AM. The clinical case report: “Pot boiler” or scientific literature? Head Neck Surg. 1979; 1 :291–292. doi: 10.1002/hed.2890010402. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Doherty M. What value case reports? (Editorial) Ann Rheum Dis. 1994; 53 :1–2. doi: 10.1136/ard.53.1.1. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Procopio M. Publication of case reports. Br J Psychiatry. 2005; 187 :91. [ PubMed ] [ Google Scholar ]
Bignall J, Horton R. Learning from stories – Lancet’s case reports. Lancet. 1995; 346 :1256. [ PubMed ] [ Google Scholar ]
Kidd M, Hubbard C. Introducing Journal of Medical Case Reports. J Med Case Rep. 2007; 1 :1. doi: 10.1186/1752-1947-1-1. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Rison RA. A guide to writing case reports for the Journal of Medical Case Reports and BioMed Central Research Notes. J Med Case Reports. 2013; 7 :239. doi: 10.1186/1752-1947-7-239. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Bayoumi AM, Kopplin PA. The storied case report. CMAJ. 2004; 171 :569–570. doi: 10.1503/cmaj.1031503. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Kidd MR, Saltman D. Case reports at the vanguard of the 21 st century medicine (Editorial) J Med Case Rep. 2012; 6 :156. doi: 10.1186/1752-1947-6-156. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Venes D. Taber’s Cyclopedic Medical Dictionary. 21. Philadelphia: F.A. Davis Company; 2009. [ Google Scholar ]
Jenicek M. Clinical case reporting in evidence-based medicine. Oxford: Butterworth Heinemann; 1999. [ Google Scholar ]
Fletcher RH, Fletcher SW. Clinical epidemiology: The essentials. 4. Philadelphia: Lippincott Williams & Wilkins; 2005. [ Google Scholar ]
Sackett DL, Brian Haynes R, Tugwell P. Clinical epidemiology. Boston: Little, Brown and Company; 1985. [ Google Scholar ]
Berkencotter C. Patient tales. Case histories and the uses of narrative in psychiatry. Columbia: University of South Carolina Press; 2008. [ Google Scholar ]
Hunter KM. Doctors’ stories. The narrative structure of medical knowledge. Princeton: Princeton University Press; 1991. [ Google Scholar ]
Crowe S, Cresswell K, Robertson A, Huby G, Avery A, Sheikh A. The case study approach. BMC Med Res Methodol. 2011; 11 :100. doi: 10.1186/1471-2288-11-100. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Wynn R, Kvalvik AM, Hynnekleiv T. Attitudes to coercion at two Norwegian psychiatric units. Nord J Psychiatry. 2011; 65 :133–137. doi: 10.3109/08039488.2010.513068. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Wynn R, Myklebust LH, Bratlid T. Psychologists and coercion: decisions regarding involuntary psychiatric admission and treatment in a group of Norwegian psychologists. Nord J Psychiatry. 2007; 61 :433–437. doi: 10.1080/08039480701773139. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Aaker E, Knudsen A, Wynn R, Lund A. General practitioners’ reactions to non-compliant patients. Scand J Prim Health Care. 2001; 19 :103–106. doi: 10.1080/028134301750235330. [ PubMed ] [ CrossRef ] [ Google Scholar ]
McBride WG. Thalidomide and congenital abnormalities. (Letter) Lancet. 1961; 278 :1358. [ Google Scholar ]
Chakra CAN, Pariente A, Pinet M, Nkeng L, Moore N, Moride Y. Case series in drug safety. A review to determine characteristics and quality. Drug Saf. 2010; 33 :1081–1088. doi: 10.2165/11539300-000000000-00000. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Ban TA. The role of serendipity in drug discovery. Dialogues Clin Neurosci. 2006; 8 :335–344. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust. 1949; 2 :349–352. [ PubMed ] [ Google Scholar ]
Léauté-Labrèze C, de la Roque Dumas E, Hubiche T, Boralevi F. Propranolol for severe hemangiomas of infancy. (Letter to the editor) N Engl J Med. 2008; 358 :2649–2651. doi: 10.1056/NEJMc0708819. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Fretheim A. Godt nok dokumentert? (Sufficiently documented?) (Editorial) Tidsskr Nor Legeforen. 2010; 130 :1806. [ PubMed ] [ Google Scholar ]
U.S. National Institutes of Health. Studies found for the search 'propanolol and hemangiomas' in the ClinicalTrials.gov database. Accessed on 22 April, 2014 at: http://www.clinicaltrials.gov/ct2/results?term=propanolol+and+hemangiomas&Search=Search .
Beard G. Neurasthenia, or nervous exhaustion. Boston Med Surg J. 1869; 80 :217–221. doi: 10.1056/NEJM186904290801301. [ CrossRef ] [ Google Scholar ]
Taylor DM. Developing a strategy for the management of rare disorders. BMJ. 2012; 344 :e2417. doi: 10.1136/bmj.e2417. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Bjånes TK. Lokale bivirkninger ved parenteral administrering av legemidler. (Localized side effects caused by parenteral administration of drugs) Tidsskr Nor Legeforen. 2011; 131 :472–474. [ PubMed ] [ Google Scholar ]
Nissen T, Rørvik P, Haugslett L, Wynn R. Physical restraint and near death of a psychiatric patient. J Forensic Sci. 2013; 58 :259–262. doi: 10.1111/j.1556-4029.2012.02290.x. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Wynn R. Coercion in psychiatric care: clinical, legal, and ethical controversies. Int J Psychiatry Clin Pract. 2006; 10 :247–251. doi: 10.1080/13651500600650026. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Lundh A, Christensen M, Jørgensen AW. International or national publication of case reports. Dan Med Bul. 2011; 58 :A4242. [ PubMed ] [ Google Scholar ]
Grønli O, Wynn R. Normocalcemic hyperparathyroidism and treatment resistant depression. Psychosomatics. 2013; 54 :493–497. doi: 10.1016/j.psym.2012.10.008. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Ward SP. Thalidomide and congenital abnormalities. BMJ. 1962; 2 (5305):646–647. doi: 10.1136/bmj.2.5305.646. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Coodin FJ, Uchida CM, Murphy CH. Phocomelia: report of three cases. CMAJ. 1962; 87 :735–739. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Heyman DJ. Managing director of the Destillers Company Ltd. (Letter) Lancet. 1961; 278 :1262. [ Google Scholar ]
Agha R, Rosin RD. Time for a new approach to case reports. (Editorial) Int J Surg Case Rep. 2010; 1 :1–3. doi: 10.1016/j.ijscr.2010.04.001. doi:10.1016/j.ijscr.2010.04.001. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Aronson JA. Anecdotes as evidence. (Editorial) BMJ. 2003; 326 :1346. doi: 10.1136/bmj.326.7403.1346. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Myers CS. A contribution to the study of the shell shock. Being an account of three cases of loss of memory, vision, smell and taste, admitted into the Duchess of Westminster’s War Hospital, Le Touquet. Lancet. 1915; 185 :316–320. doi: 10.1016/S0140-6736(00)52916-X. [ CrossRef ] [ Google Scholar ]
Morris BA. The importance of case reports. (Letter to the Editor) CMAJ. 1989; 141 :875–876. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Rison RA. Neurology case reports: a call for all. J Med Case Rep. 2011; 5 :113. doi: 10.1186/1752-1947-5-113. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Grimes DA, Schulz KF. Descriptive studies: what they can and cannot do. Lancet. 2002; 359 :145–149. doi: 10.1016/S0140-6736(02)07373-7. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Kang S. Anecdotes in medicine - 15 years of Lancet case reports. Lancet. 2010; 376 :1448–1449. doi: 10.1016/S0140-6736(10)60624-1. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Rose JC, Corn M. Dr. E. and other patients: new lessons from old case reports. J Hist Med Allied Sci. 1984; 39 :3–32. doi: 10.1093/jhmas/39.1.3. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Álvarez Millán C. Practice versus theory: tenth-century case histories from Islamic Middle East. Soc Hist Med. 2000; 13 :293–306. doi: 10.1093/shm/13.2.293. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Álvarez Millán C. The case history in Medieval Islamic medical literature: Tajarib and Mujarrabat as source. Med Hist. 2010; 54 :195–214. doi: 10.1017/S0025727300006712. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing clinical research. 3. Philadelphia: Lippincott Williams & Wilkins; 2007. [ Google Scholar ]
Easterbrook PJ, Gopalan R, Berlin JA, Matthews DR. Publication bias in clinical research. Lancet. 1991; 337 :867–872. doi: 10.1016/0140-6736(91)90201-Y. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Albrecht J, Meves A, Bigby M. Case reports and case series from the Lancet had significant impact on medical literature. J Clin Epidemiol. 2005; 58 :1227–1232. doi: 10.1016/j.jclinepi.2005.04.003. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Oliveira GJ, Leles CR. Critical appraisal and positive outcome bias in case reports published in Brazilian dental journals. J Dent Educ. 2006; 70 :869–874. [ PubMed ] [ Google Scholar ]
Charlton BG, Walston F. Individual case studies in clinical research. J Eval Clin Practice. 1998; 4 :147–155. doi: 10.1111/j.1365-2753.1998.tb00081.x. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Stuebe AM. Level IV evidence – adverse anecdote and clinical practice. N Engl J Med. 2011; 365 :8–9. doi: 10.1056/NEJMp1102632. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Hoffman JR. Rethinking case reports. West J Med. 1999; 170 :253–254. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Wilkinson G, Fahy T, Russell G, Healy D, Marks I, Tantam D, Dimond B. Case reports and confidentiality. (Editorial) Br J Psychiatry. 1995; 166 :555–558. doi: 10.1192/bjp.166.5.555. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Powell PP. The single-case report in medical literature: the ‘Elephant man’ serves as an exellent example. J Am Med Writers Assoc. 1990; 5 :9–12. [ Google Scholar ]
Glasziou P. Evidence based case report: twenty year cough in a non-smoker. BMJ. 1998; 316 :1660–1661. doi: 10.1136/bmj.316.7145.1660. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Harker N, Montgomery A, Fahey T. Interactive case report. Treating nausea and vomiting during pregnancy: case outcome. BMJ. 2004; 328 :276. doi: 10.1136/bmj.328.7434.276. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Reis S, Hermoni D, Livingstone P, Borkan J. Integrated narrative and evidence based case report: case report of paroxysmal atrial fibrillation and anticoagulation. BMJ. 2002; 325 :1018–1020. doi: 10.1136/bmj.325.7371.1018. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Sorinola O, Olufowobi O, Coomarasamy A, Khan KS. Instructions to authors for case reporting are limited: a review of a core journal list. BMC Med Educ. 2004; 4 :4. doi: 10.1186/1472-6920-4-4. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Rossor MN. In: How to write a paper. 4. Hall GM, editor. London: Blackwell Publishing; 2008. How to write a case report; pp. 71–75. [ Google Scholar ]
Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. CARE group. The CARE guidelines: consensus-based clinical case reporting guideline development. J Med Case Rep. 2013; 7 :223. doi: 10.1186/1752-1947-7-223. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
BioMed Central. Cases Database. Accessed on 22 April, 2014 at: http://www.casesdatabase.com .
Mason RA. The case report – an endangered species? (Editorial) Anesthesia. 2001; 56 :99–102. doi: 10.1046/j.1365-2044.2001.01919.x. [ PubMed ] [ CrossRef ] [ Google Scholar ]

IMAGES

PPT
What is a Case Report/Case Series?
Case Report: A Beginner’s Guide with Examples
2. Case study and case series
(PDF) Case report and case series
Case reports and case series in prehospital emergency care research

VIDEO

Case Report + Case Series
1-4- Case Report and Case Series
MBA SEM 4 CP REPORT (Study on Examining theimpact of BNPL onconsumer spendings)
Study design part 1 online session 29/7/2023
2024 ലെ വളരെ പ്രധാനപ്പെട്ട CURRENT AFFAIRS
Case Report Vs. Case Study: Explained!

COMMENTS

Case series: an essential study design to build knowledge and pose
In January of 2020, Chinese investigators published a detailed case series describing the characteristics and outcomes of 41 adults with confirmed COVID-19. 1 The study showed that 15% of those patients died during the study period. That case series 1 was extremely important because it was the first published description of the impact of the ...
Case Reports, Case Series
Editorial. Introduction. Case reports and case series or case study research are descriptive studies to present patients in their natural clinical setting. Case reports, which generally consist of three or fewer patients, are prepared to illustrate features in the practice of medicine and potentially create new research questions that may contribute to the acquisition of additional knowledge ...
How to Write Case Reports and Case Series
There is no formal definition as to what is case series and what would be considered a retrospective cohort study. In general, a case series comprises <10 cases; beyond that, it may be feasible to apply formal statistics and may be considered a cohort study. Both case reports and case series are descriptive studies. Case series must have ...
Case series
Case series. A case series (also known as a clinical series) is a type of medical research study that tracks subjects with a known exposure, such as patients who have received a similar treatment, [1] or examines their medical records for exposure and outcome. Case series may be consecutive [2] or non-consecutive, [3] depending on whether all ...
Case series: Design, measures, and classic example
A case series offers a larger group of patients than a case report, which follows a cohort of up to three patients. Case series are typically retrospective in nature with the investigator performing chart review on a specific set of patients with a common interventional procedure, medical condition, etc. ... Case series study design steps ...
Case series: design, measures, and classic example
Abstract. Case series are observational reports without analysis. They are uncontrolled, anecdotal reports of uncommon or novel cases in individuals or groups of patients. Although case series fall low on the hierarchy of evidence, they are clinically important as they can highlight an unrecognized outcome or a novel mechanism, diagnosis, or ...
Methodological quality and synthesis of case series and case reports
Abstract. Case reports and case series are uncontrolled study designs known for increased risk of bias but have profoundly influenced the medical literature and continue to advance our knowledge. In this guide, we present a framework for appraisal, synthesis and application of evidence derived from case reports and case series.
A critical guide to case series reports
Abstract. Objective: Provide guidance to investigators and authors regarding appropriate conduct and reporting of case-series studies. Summary of background data: Evidence-based practice has provided a substantial contribution to advancing clinical science. Many study designs have been critically examined, and the quality of the research ...
Case series: design, measures, and an example
Case series are included in the group of descriptive studies alongside case reports, cross-sectional studies, surveillance studies, and ecological correlational studies. Case series projects can commonly be confused with cohort studies. Cohort studies identify patients at a common point in their disease and follow them over time.
Case Reports and Case Series
Case reports and case series are observational studies that describe the experience of one or more people with a particular disease or condition. 4.2. Case reports and case series can be an important first step in recognizing a new disease. 4.3. Case reports and case series have specific limitations: 4.3.1. Lack of denominator data needed to ...
Case Report
Lancet. 2 (8247),598-600. This case report was published by eight physicians in New York city who had unexpectedly seen eight male patients with Kaposi's sarcoma (KS). Prior to this, KS was very rare in the U.S. and occurred primarily in the lower extremities of older patients. These cases were decades younger, had generalized KS, and a much ...
Case Studies/ Case Report/ Case Series
A case study, also known as a case report, is an in depth or intensive study of a single individual or specific group, while a case series is a grouping of similar case studies / case reports together. A case study / case report can be used in the following instances: where there is atypical or abnormal behaviour or development.
Case Reports, Case Series
Case reports and case series or case study research are descriptive studies that are prepared for illustrating novel, unusual, or atypical features identified in patients in medical practice, and they potentially generate new research questions. They are empirical inquiries or investigations of a patient or a group of patients in a natural, real-world clinical setting.
Methodological quality and synthesis of case series and case reports
If a case series is prospective, differentiating it from a single-arm uncontrolled cohort study becomes difficult. In one clinical practice guideline, it was proposed that studies without internal comparisons can be labelled as case series unless they explicitly report having a protocol before commencement of data collection, a definition of inclusion and exclusion criteria, a standardised ...
PDF 10. Guideline and Template for Writing a Case Report/Case Series
10. GUIDELINE AND TEMPLATE FOR WRITING A CASE REPORT/CASE SERIES ... Writing the core of your case report: clinical findings and outcome Step 1: state the obvious ... retrospective study in Zambia, TB was more commonly diagnosed among children with Kwashiorkor (47%) compared to Marasmus-Kwashiorkor (24%) and marasmus (29%) [7]. ...
(PDF) Case report and case series
Case reports are the most basic type of. descriptive studies that deal with individuals. Case series aggregate individual cases in one. report. 1 Case reports/series are uncontrolled. (non ...
Case Reports and Case Series
Key Concept: The key to identifying a case series is that all of the subjects included in the study have the primary disease or outcome of interest. For example, an article reported on 239 people who got bird flu. The article might present tables and graphs that gave information about their age, occupation, where they lived, whether they lived or died, etc., but basically it is a detailed ...
Case series
A novel quantitative computer-assisted drug-induced liver injury causality assessment tool (DILI-CAT) Hans L. Tillmann, Ayako Suzuki, [ ... ], Don C. Rockey. Antifungal therapy in the management of fungal secondary infections in COVID-19 patients: A systematic review and meta-analysis.
Aortic Thrombosis Associated with Three Types of COVID‐19 Vaccine
Aortic thrombosis has been reported little in patients with COVID-19, and an association with COVID-19 vaccines has been found. The aim of the present study was to report five cases of aortic thrombosis at our institution in a three-month period associated with the COVID-19 vaccine. 2. Case Series 2.1. Case 1
Case Report
An article that describes and interprets an individual case, often written in the form of a detailed story. Case reports often describe: Unique cases that cannot be explained by known diseases or syndromes. Cases that show an important variation of a disease or condition. Cases that show unexpected events that may yield new or useful information.
Inappropriate treatment of pulmonary aspergillosis caused by
Background Pulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections. Case presentation The present study reports three cases of inappropriate ...
Preoperative visualization of the greater occipital nerve with ...
Patient characteristics. Twelve patients were recruited to participate in this study. Ten were female and the average age was 49 ± 15. As a baseline, the average frequency of headaches was 16.5 ...
2024
This series of case studies draws from rapid literature reviews, interviews and consultations with WFP staff and key stakeholders. It evaluates WFP's long-term contributions to supporting and strengthening national social protection systems across a range of different 'building blocks', examining its strategic objectives and role in each context and highlighting key successes, challenges ...
Methodology: How to develop a case report or case series report
Abstract. Case reports or case series reports are descriptive studies, although their results are not used to make inferences, they are the first line of evidence for new therapies and a preamble to research with a stronger methodological design. This type of study is essential to describe new or unusual diseases, adverse events, or ...
Supreme Court Rules Public Corruption Law Allows Gifts to Officials
The case before the court, Snyder v. United States, No. 23-108, concerned James Snyder, a former mayor of Portage, Ind., a city of about 38,000 people near Lake Michigan.
New report on conservation, land-use in the Hudson River Estuary
The new report, Natural Resource Protection in the Hudson Valley: Municipal Conservation Stories, presents case studies from seven Hudson Valley towns and highlights the experiences, challenges, and successes of elected officials and municipal volunteers in pursuing conservation actions. In New York State, municipal governments can play a vital role in conservation of biodiversity priorities ...
Taste Test: Heaven Hill Grain to Glass Wheated Bourbon
Heaven Hill's Grain to Glass series started about eight years ago, when executive chairman Max Shapira worked with an Indiana company called Beck's Hybrids to choose a specific corn seed ...
The Daily Show Fan Page
The Daily Show. S29 E68 • July 8, 2024. Host Jon Stewart returns to his place behind the desk for an unvarnished look at the 2024 election, with expert analysis from the Daily Show news team.
The clinical case report: a review of its merits and limitations
Background. Throughout history the clinical case report and case report series have been integral components of medical literature [].The case report genre held a strong position until it was sidelined in the second half of the 20 th century [2,3].New methodologies for research articles paved the way for evidence-based medicine.
Inside the numbers from new study on Senate staff diversity
The study dissects racial representation in mid-level jobs in Senate offices, career pathways for Black staffers and confronts issues with data availability.

Secondary Logo

How to Write Case Reports and Case Series

INTRODUCTION

WHY ARE CASE REPORTS PUBLISHED?

ETHICAL ISSUES

HOW TO START?

COMPONENTS OF a CASE REPORT

Introduction

Describing the case

Figures and tables

Discussion including review

CASE SERIES - WHAT IS DIFFERENT?

ABSTRACT OF a CASE REPORT

REFERENCES IN a CASE REPORT

CHOOSING THE RIGHT JOURNAL

PUBLISHING THE CASE REPORT/SERIES AS a LETTER TO EDITOR/IMAGE SERIES

GUIDELINES FOR CASE REPORTS

AUTHORSHIP IN CASE REPORTS

CONCLUSIONS

Financial support and sponsorship

Readers Of this Article Also Read

Save citation to file

Add to My Bibliography

A critical guide to case series reports

Similar articles

Publication types

Related information

LinkOut - more resources

Research Materials

Case Reports and Case Series

Cite this chapter

Access this chapter

Author information

Rights and permissions

Copyright information

About this chapter

Download citation

Share this chapter

Study Design 101: Case Report

Disadvantages

Design pitfalls to look out for

Fictitious Example

Real-life Examples

Related Terms

Now test yourself!

Evidence Pyramid - Navigation

Quantitative study designs: Case Studies/ Case Report/ Case Series

Case Study / Case Report / Case Series

The stages of a Case Study / Case Report / Case Series

Which clinical questions does Case Study / Case Report / Case Series best answer?

What are the advantages and disadvantages to consider when using Case Studies/ Case Reports and Case Series ?

What are the pitfalls to look for?

Critical appraisal tools

Real World Examples

References and Further Reading

Log in using your username and password

You are here

Statistics from Altmetric.com

Definitions

Evaluating methodological quality

Proposed tool

Synthesis of case reports/series

Narrative synthesis

Quantitative synthesis

From evidence to decision

Read the full text or download the PDF:

PH717 Module 1B - Descriptive Tools

Case Reports and Case Series

Streptococcus pneumoniae in Latin America and the Caribbean: A systematic review and meta-analysis">Nasopharyngeal carriage of Streptococcus pneumoniae in Latin America and the Caribbean: A systematic review and meta-analysis

Quantitative changes in the corneal endothelium and central corneal thickness during anterior chamber inflammation: A systematic review and meta-analysis

Healthcare worker access to molnupiravir: A case series

Hemoadsorption in the critically ill—Final results of the International CytoSorb Registry

Iron deficiency and common neurodevelopmental disorders—A scoping review

A novel quantitative computer-assisted drug-induced liver injury causality assessment tool (DILI-CAT)

Antifungal therapy in the management of fungal secondary infections in COVID-19 patients: A systematic review and meta-analysis

Transition approaches for autistic young adults: A case series study

Environmental effect of air versus gas tamponade in the management of rhegmatogenous retinal detachment VR surgery: A multicentre study of 3,239 patients

Recurrent SARS-CoV-2 infections and their potential risk to public health – a systematic review

Effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions: A scoping review

COVID-19 and cause of pregnancy loss during the pandemic: A systematic review