The Value of Case Reports

Koen Santifort^1,2*Rodrigo Gutierrez-Quintana³Natasha J Olby⁴Björn Meij⁵Vicente Aige Gil⁶Kaspar Matiasek⁷John Henry Rossmeisl⁸Joao Miguel De Frias⁹Simone Spinillo¹⁰Bruno André Lopes^11,12Susana Monforte¹²Richard A. LeCouteur¹³Martí Pumarola¹⁴Brian A. Summers¹⁵

• ¹IVC Evidensia Small Animal Referral Hospital Arnhem, Neurology, Arnhem, Netherlands
• ²IVC Evidensia Small Animal Hospital Hart van Brabant, Waalwijk, Netherlands
• ³University of Glasgow School of Veterinary Medicine, Glasgow, United Kingdom
• ⁴Department of Clinical Sciences, North Carolina State University, Raleigh, United States
• ⁵Universiteit Utrecht Faculteit Diergeneeskunde, Utrecht, Netherlands
• ⁶Department of Sanitat i Anatomia Animal, Faculty of Veterinary Medicine, Universitat Autònoma de Barcelona Campus UAB, Travessera dels turons s/n, 08193 Bellaterra, Barcelona, Spain
• ⁷Section of Clinical & Comparative Neuropathology, Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
• ⁸Virginia-Maryland College of Veterinary Medicine Department of Small Animal Clinical Sciences, Blacksburg, United States
• ⁹Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Edinburgh, United Kingdom
• ¹⁰ChesterGates Veterinary Specialists, Chester, Cheshire, United Kingdom
• ¹¹Southfields Veterinary Specialists, Basildon, United Kingdom
• ¹²University of Cambridge Department of Veterinary Medicine, Cambridge, United Kingdom
• ¹³School of Veterinary Medicine, University of California, Davis, United States
• ¹⁴Mouse and Comparative Pathology Unit, Department of Animal Medicine and Surgery, Faculty of Veterinary Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
• ¹⁵Melbourne Veterinary School, University of Melbourne, Melbourne, Werribee, Victoria, Australia

The medical neurologists and neurosurgeons of the world constitute a huge professional body, focused on the disorders of the nervous system of a single species: humans. Subspecializations, such as in neonatal neurology, neuromuscular disorders, and geriatric neurology, have long evolved, given both the complexity of the conditions and the huge case numbers. Some neurological disorders (e.g. Alzheimer's and Parkinson's diseases) are of increasing importance globally. In striking contrast, veterinary neurology and neurosurgery is numerically a miniscule profession, yet tasked with investigating and treating conditions in several animal species, each with their own idiosyncrasies (cats are not small dogs). In many developed countries, there is now an expectation for sophisticated treatments for neurological disorders affecting beloved pets.Veterinary neurology, like its counterpart in human medicine, often deals with rare, unexpected, complex, or poorly understood conditions. Moreover, the clinical presentations can be daunting for general practitioners and students, possibly leading to a fear of having to manage neurological patients (a phenomenon referred to as neurophobia in human and veterinary medical literature ) (1)(2)(3)(4)(5)(6)(7).An extra factor contributing to this phenomenon in veterinary neurology, in comparison with its larger sister professions in humans, may be that scientific progress in veterinary neurology advances more slowly. Publications describe newly recognized disorders, superior imaging modalities, advances in neurosurgical procedures and improved therapeutic options, but case numbers are often small. Thus, while progress moves more slowly in the veterinary profession, case reports remain useful tools for documentation, education, and innovation. This article offers the collective opinion of 14 authors from the field of veterinary neurology on the contemporary value of case reports in veterinary neurology and neurosurgery. This paper resulted from the accumulated individual authors' opinions, which are provided in full in the Supplementary Material file. Case reports (Box 1) offer an opportunity to challenge and advance what is known. They can be key to solving difficult and rare cases or form the basis of endeavors to explore new therapies and management approaches. Such reports will interest and aid those in general practice, more so specialists engaged in neurology. N ovelty is often a factor of interest in these reports. However, not all case reports can, or need be novel and some will be justified if confirming or modifying findings in earlier communications, or describing the occurrence of syndromes in additional (different) animal breeds or global regions. Novelty is not the sole factor that comes into play when assessing the value of case reports. Even when similar diagnoses have been reported before, confirmation of earlier treatment results or rather contradictory outcomes can be of further value in the management of future cases. Surely, the conclusions in a few case reports may eventually prove to be erroneous but progress in medicine is always a work in progress.Case reports introduce something new, and it is novelty that often inspires a case report to be written, which then opens the door to future research. Indeed, a novel patient that inspires a case report may trigger decades of investigation in its wake. For example, the first description of Alzheimer's Disease was a modest case report (9,10). Few have such an exceptional and lasting impact. In veterinary neurology, a case report described the first case of 'neurogenic lameness', occurring in a pelvic limb due to a lateralized lumbar disc extrusion in a dog (11). This was important because it clarified a confusing clinical presentation. Another impactful case report led to the identification of Neospora caninum which hitherto had been masquerading as Toxoplasma gondii; nowadays, there is extensive literature about this protozoan and its impact in several species ( 12,13). A series of reports on pituitary surgery in dogs and cats have offered a revolutionary way to treat various pituitary diseases and have broadened the scope of these disorders (14)(15)(16). The introduction of additive manufacturing (e.g. personalized 3D-implants) in veterinary medicine for complex orthopedic, neurologic, and oncologic cases are recently also documented through case reports (17). Case reports can be classified based on the number of cases presented, their pattern of occurrence, or their focus (e.g. treatment protocol). Types include :- A type of single-patient trial using crossover comparisons (e.g., treatment vs. placebo) within the same individual. Designed to assess efficacy or tolerability in that specific patient and bridge the gap between clinical trials and individual care. First-in-man (or first-in-dog/cat/…) clinical case reports introduce a novel treatment in patients for which safety and efficacy was first tested in in vitro studies and/or experimental small animals (e.g. rodents).Standardized formats like CARE guidelines (8) can increase consistency and quality of case reports.Case reports can inform and reveal the necessary next step . They may explore and question the pathophysiology of diseases, raise potential toxicities, and warn about possible infectious disease outbreaks on the horizon. By presenting real-world clinical scenarios and challenges, they serve as excellent learning tools for students, practitioners, and researchers. They can illustrate clinical reasoning, disease management, and up -to-date techniques. Students and practitioners alike benefit from real clinical examples that reinforce diagnostic reasoning and elucidate anatomical-pathological correlations.For many young veterinarians, writing a case report is their first experience in the world of scientific publishing. It offers valuable lessons in precisely documenting clinical observations and investigations, presenting a meaningful discussion of findings, and responding to peer review critiques.For example, a case report describing a cat with myokymia and neuromyotonia was published in 2005 (19). Years later, one of the authors (NO) was contacted by a veterinarian about a cat with similar clinical signs. Treatment was guided by the previously published report and led to a positive outcome for the cat. While this does not constitute formal evidence for clinical decision -making, it nevertheless positively impacted the life of one cat-and that might make all the difference.Specifically for the field of neuro-oncology and neurosurgery, case reports sometimes provide the best level of knowledge and can give new insights into the occurrence and diagnostic characteristics (including histopathological examinations) of certain tumor types. Recent case reports that documented unusual tumor types affecting the central nervous system or tumors affecting the central nervous system in remarkable patients (e.g. young age) often include diagnostic imaging study characteristics in addition to detailed clinical findings that help clinicians and pathologists to make the most out of such rare cases (20)(21)(22).The language of case reports should reflect moderation and caution (23). With limited case numbers, broad generalizations are to be avoided but excessive reserve is unnecessary and might discourage further research. What is learned from a single case should not be generalized and conclusions drawn should recognize the limitations inherent in a single example. Gaps in knowledge should be clearly indicated. Much of the current knowledge in the field of veterinary neurology and neurosurgery relies on reports including small case numbers or observational studies that are inherently limited in determining causation or treatment efficacy . This is highlighted, for instance, by a recent review on the treatment of meningoencephalitis of unknown origin in dogs (2 4). Even when putting all the data of small case number-studies together, the ability to draw conclusions is limited. Indeed, the authors would encourage taking inspiration from case reports to collaborate in multi-center studies, especially in treatment case series or prospectively designed, randomized, blinded studies, in order to get a reasonable sample size allowing statistically meaningful analysis.In academic assessment, case reports generally carry less weight than original research articles, which are based on more robust methodologies and include studies conducted under defined conditions with treatment and control groups. However, case reports can reflect sharp observational skills or the ability to interpret seemingly contradictory clinical findings, which lead to an important breakthrough in medical knowledge, or in hypothesis generation. The best of case reports are major contributions. A study in the human medical literature showed that about 25% of case reports from The Lancet led to subsequent larger studies, illustrating that case reports can play a crucial role in generating hypotheses that can lead to larger studies (18).While case reports do not offer statistically significant proof in the way that large -scale studies or randomized controlled trials do, their value extends beyond mere statistical rigor. The argument that their low ranking in the evidence hierarchy diminishes their worth overlooks the critical role they play in medical knowledge and practice. Case reports sometimes serve as vital documentation for rare conditions that otherwise may be ignored in favor of major syndromes where a foundation of knowledge already exists. Case reports of the unusual can provide the breakthroughs that "get the ball rolling," acting as catalysts for larger and more comprehensive studies guided by the initial findings. Additionally, they provide insights into unusual treatment responses, adverse effects, and complications that may not yet be broadly recognized. What can be viewed as a case report is the 'Nof-1 clinical trial', a type of single -patient study that uses crossover comparisons of different treatments (e.g., treatment versus placebo) within the same individual. This type of trial may actually be one of the most reliable ways of determining the efficacy of treatment in that particular patient .Similarly, first-in-man and first-in-dog/cat case reports or series can serve as vital links between 'benchtop' and 'bedside' studies. These reports are essential for establishing the safety and feasibility (though not efficacy) of novel treatments, particularly when placebo -controlled studies are not feasible-such as with the introduction of a new surgical technique. Even when extensive preliminary work has been conducted in vitro, in silico, ex vivo in cadavers, and in vivo in animal models (e.g., mice, rats, or rabbits), transitioning to patient studies remains a major leap ; experimental animals with induced disease may not respond the same way as veterinary or human patients with naturally occurring disease. Ethically approved first-in-patient studies and case reports are therefore crucial early-stage contributions that pave the way for large -scale, prospective, randomized clinical trials aimed at evaluating efficacy and informing evidence -based practice. They can catalyze developments from bench top to bedside. In this context, veterinary patients also play a unique role as translational animal models for spontaneous diseases shared between humans, dogs, and cats. This growing field, known as One Health -One Medicine, has generated numerous case reports that have benefitted both humans and their companion animals in meaningful, bidirectional ways (25)(26)(27)(28)(29)(30)(31).The role of case reports as educational tools is also undeniable , both for the authors, who must use critical thinking and clinical reasoning skills, and for readers, who gain exposure to diagnostic and treatment challenges. Furthermore, in situations where more comprehensive studies are not feasible due to ethical or logistical constraints, case reports offer the best available evidence. As already stated, new diseases or syndromes often first emerge in the form of case reports with full comprehension only following additional interrogation. Perhaps most importantly, case reports inspire scientific curiosity by drawing attention to unique or unexpected cases ; they encourage deeper inquiry and innovation. Their value, therefore, should not be judged solely on their ability to present a case but rather on their broader contributions to medical progress, education, and discovery.Evaluating the value of a case report could benefit from a structured, quantitative approach. One example is the scoring system proposed by Pierson (32), although it is subject to variation between assessors. This method assesses reports based on their uniqueness, documentation quality, objectivity, interpretation, and educational value, each scored from 0 to 2, with a maximum of 10 points. A total score of 9-10 indicates a valuable contribution, 6 -8 warrants cautious interpretation, and 5 or less suggests the report may not meet publication standards. Such frameworks support both authors and reviewers in assessing the potential impact and quality of a case report, fostering consistency and transparency in evaluating their merit.The necessity of peer review of case reports has been questioned ( 33). Collectively, the authors of this opinion piece consider peer review to be of continued importance in case reports to verify the credibility of findings and conclusions. Reviewers play a crucial role in evaluating information and where needed, will request further investigations such as the examination of medical records or images or overlooked prior publications. Case reports have been compared with letters to the editor or website posts which can quickly disseminate clinical observations. However, these often lack rigorous peer review, and so again may be less credible and potentially ambiguous, leaving the reader to decide whether believable or not.Peer review of case reports extends beyond validating scientific claims; it also supports the refinement of clinical storytelling and encourages a balanced discussion of (the impact of) errors, uncertainties, and decision-making under pressure. Given that case reports may describe scenarios where standard protocols were not feasible or applicable, such as lack of access to advanced diagnostic testing modalities, reviewers with broad clinical experience are well positioned to recognize both the challenges and the ingenuity involved. Their feedback can enhance the informative value of the report and ensure that the lessons drawn are appropriately contextualized. When formal studies are not feasible, thoughtful peer review can convert anecdotal insights into useful clinical knowledge.In summary, the strengths and limitations of case reports (and ways to deal with them) are listed as follows:Strengths of case reports• Document unusual or new diseases, unexpected treatment responses, or novel complications. o For rare diseases, they may provide the best available evidence of the presentation, clinical signs and course of action. • Document the presence of known diseases in circumstances (e.g. geographical areas)previously not reported or thought exempt of disease (f.i. since a certain date) with legislative or One Health/zoonotic consequences (e.g. rabies).• Inspire further research.• Provide rich, in-depth descriptions of patient history, diagnostic workup, treatment course, and outcomes. • Trigger clinical innovation by proof-of-concept.• Describe safety and feasibility of novel treatments in first-in-man or first-in-dog/cat studies; serve as a translational link between 'benchtop' and 'bedside'. • Serve as excellent learning tools.• Highlight new therapeutic options.• Are associated with low costs compared to formal studies.• Can help detect and inform of new, rare, or late-onset adverse drug reactions (pharmacovigilance). • Are useful when ethical constraints prevent experimental research , or are inevitable when translating novel treatments from the 'benchtop' (in vitro, in silico, ex vivo cadaver studies) via in vivo experimental animals to the 'bedside' (human and veterinary patients). • Promote interdisciplinary collaboration which extends beyond patient care to a shared manuscript preparation. • Can serve as sentinels for domestic family violence as reflected by animal abuse causing nonaccidental injuries.• Provide a realistic view of the clinical context, including decision -making challenges and socioeconomic considerations (factors involving social dynamics and financial constraints that may influence decision -making or outcomes) that are often underrepresented in research articles. o Keep the rare case in perspective: atypical presentation of known disorders is more common than something brand new. Discuss how the case contributes to broader clinical knowledge, such as differential diagnosis approaches. o Avoid overemphasizing novelty when this is not the main point of the report, such as use of "this is the first…" type of sentences . In the context of veterinary neurology and neurosurgery, case reports are invaluable for documenting what is new, rare and novel, generating research questions, and providing educational insights ; they often make for interesting reading. They inspire and propel the field forward. Despite limitations, they remain an essential component of medical literature when interpreted with appropriate caution and scholarly rigor. They offer unique opportunities for specialists to share their insights and contribute to the collective knowledge, ultimately benefiting animal health. They serve the One Health -One Medicine field for humans and animals. If not immediately, eventually they will be helpful in some circumstance, somewhere, sometime. Their value lies not in statistical significance, but in their power to inform, share invaluable clinical experience, and provoke thought and inquiry.In conclusion, it is the collective opinion of the authors that while case reports have limitations, if these constraints are kept in mind, their contributions to clinical practice, education, and research are significant.