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Year : 2022  |  Volume : 65  |  Issue : 5  |  Page : 122-124
Non-neoplastic disorders of the nervous system: Emerging from the shadows

1 Department of Neuropathology, NIMHANS, Bangalore, Karnataka, India
2 Department of Pathology, NIMS, Hyderabad, Telangana, India
3 Department of Pathology, AIIMS, New Delhi, India

Click here for correspondence address and email

Date of Web Publication11-May-2022

How to cite this article:
Mahadevan A, Uppin M, Sarkar C. Non-neoplastic disorders of the nervous system: Emerging from the shadows. Indian J Pathol Microbiol 2022;65, Suppl S1:122-4

How to cite this URL:
Mahadevan A, Uppin M, Sarkar C. Non-neoplastic disorders of the nervous system: Emerging from the shadows. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 May 28];65, Suppl S1:122-4. Available from: https://www.ijpmonline.org/text.asp?2022/65/5/122/345064

The field of non-neoplastic neuropathology is not as glamorous as oncology among pathologists. However, communicable as well as non-communicable diseases like infections, epilepsy, neuromuscular and autoimmune disorders constitute a large burden with high prevalence in our society. The first comprehensive disease burden estimate of neurological disorders in India was published in The Lancet Global Health by the India State-Level Disease Burden Initiative.[1]

The last decade has witnessed rapid advances in the diagnosis of neoplastic disorders of the central nervous system (CNS), but non-neoplastic disorders continue to pose a formidable challenge, both for diagnosis and treatment. In contrast to cancer, survival rates are considerably higher but unless diagnosed early and treated, can cause significant morbidity and neurological sequelae, constituting a heavy burden on family and society. This imposes a greater responsibility on the pathologist, both for accurate diagnosis and to decipher the basic pathomechanisms of disease, to facilitate the development of novel strategies to ameliorate post-infectious sequelae.

This Special Issue is a compilation of 11 reviews that provide the reader with concise updates on three core areas that populate the pathologists' platter-neuro infections, epilepsy, and, more recently, autoimmune encephalitides. These are authoritative reviews written by experts in the field, who share their perspectives and experience to provide practical tips for the practicing pathologist. We believe that this will be an important resource for all clinicians who care for patients with non-neoplastic disorders of the CNS. The issue also includes two important articles-fetal neuropathology and Brain Banking for neuroscience to enthuse young pathologists to revive the dying science of autopsies and its vital importance to drive today's research-oriented pathology.

Emerging and reemerging new infections and the heavy burden they impose on the health care system makes it essential for pathologists to be knowledgeable in this field. Pathologists employ pattern recognition for the diagnosis of CNS infections. The most frequently encountered histologic patterns in clinical practice include granulomatous and non-granulomatous inflammation that has a multitude of causes. The histological patterns do not just provide a clue to the agent but are dictated by the immunological response of the host to specific agents.[2],[3],[4] Accurate identification of the causative agent is critical, as it directly impacts treatment, prognosis, and neurological sequelae. Both articles in this issue, “Diagnostic approach to granulomatous lesions of the CNS” by C Sundaram and “Non-granulomatous inflammatory lesions of CNS: Approach to diagnosis” authored by Nandeesh and colleagues, cover the pathological spectrum of bacterial, viral, protozoal, and parasitic diseases of CNS, and provide the reader a simple, practical algorithmic approach and are richly illustrated. Interpretation of findings in the context of clinical, imaging features, and risk factors is emphasized.

The Coronavirus disease 2019 COVID19 pandemic that gripped the world taught us a lot about the epidemiology of disease outbreaks. It also brought into the limelight the crucial role of pathologists in patient care. The insights into the pathology of COVID-19 derived from autopsies conducted by pathologists guided treatment.[5] The well-written review on “Neuropathology of Covid 19: conclusions and controversies” by Hefti and colleagues provides comprehensive information on the neuropathology of COVID19 and also discusses the serious lacunae in the available literature, limited by the lack of suitable controls. The complex relationship between COVID19 and neurodegeneration and the potential effects of “longCOVID” are discussed. Answers to this enigmatic question will only come from long-term follow-ups of COVID19 survivors and brain donations, as our current understanding of COVID19's effects on the brain is perfunctory at best.

The past few decades have witnessed a significant rise in immunosuppressive treatment for autoimmune disorders and transplantation, resulting in a large pool of immunocompromised patients susceptible to a wide variety of opportunistic infections. The altered immune response changes the clinical presentation, neuroimaging features, as well as pathology, posing a serious dilemma in diagnosis. Laboratory diagnosis plays a very crucial role, and it is imperative for the pathologist to be aware of the alternate methods of confirmation of diagnosis, including serological and molecular tests.[6] In this edition, Jayshree and colleagues present a valuable update on the “Non-invasive tests for diagnosis of parasitic infections of CNS” for the diagnosis of three common parasitic infections-cerebral toxoplasmosis, neurocysticercosis, and cerebral malaria. However, the appropriate selection and interpretation of laboratory tests requires close interaction between the clinician and the laboratory.

In the current era, knowledge of neuroimaging findings has become quintessential for the pathologist to guide diagnosis.[3] Sharath and colleagues in this issue outline the radiologists' approach to the diagnosis of CNS infections, the ideal Magnetic resonance (MR) sequences, the unique imaging characteristics that help differentiate etiologic agents, the regional predilection in viral encephalitides (e.g., medial temporal in Herpes simplex virus (HSV), thalamus in flaviviral encephalitis), which are well-illustrated, providing a simple but valuable ready reckoner for the pathologist. This is a most useful review on “Role of neuroimaging in CNS infections,” and a must-know for every pathologist involved in the diagnosis of CNS infections.

The report by the India State-Level Disease Burden Initiative found that non-communicable and traumatic brain injuries have doubled in India in the last decade.[1] Of the non-communicable disorders, epilepsy ranks third after stroke and headache. Surgically resected tissues are increasingly encountered by the pathologist for diagnosis, making it essential to be familiar with the neuropathology of focal epilepsies. Of these, hippocampal sclerosis and focal cortical dysplasias are among the most common pathologies encountered in India. The International League Against Epilepsy (ILAE) has put forth a refined classification system for these disorders, enhancing precision in diagnosis and uniformity in reporting.[7],[8] Proper handling of surgical specimens and accurate selection of a panel of immunohistochemical stains are extremely important for diagnosis. The diagnostic approach and updates in the classification of hippocampal sclerosis are presented in this issue by Rajalakshmi P in her article “Pathology of surgically remediable epilepsy: how to evaluate”. Honavar and colleagues review the recent “Updates in focal cortical dysplasias,” including the emerging molecular pathogenesis in these disorders and the proposal for a revised classification.

The pathologist is increasingly called upon to diagnose autoimmune encephalitis, a newly recognized group of noninfectious immunemediated inflammatory disorders manifesting with epilepsy and encephalitis syndromes that can closely mimic infective causes.[9] Pathogenic autoantibodies have been discovered against intracellular onconeural antigens, surface neuronal, or synaptic antigens that cause a plethora of dramatic clinical manifestations. The emerging “Role of the pathologist in the diagnosis of autoimmune encephalitis” and the various testing modalities are reviewed by Mahadevan et al. Early diagnosis is crucial for instituting treatment and preventing morbidity and mortality.

We watch in growing dismay as the science and art of autopsies fade away, relegated to the back shelves of pathology. What was once a great seat of learning is summarily removed from the curriculum of pathology training, and the trainee pathologist is happy to settle behind a microscope admiring a cancer cell and tirelessly counting mitosis! It will be anathema to the branch of pathology if autopsies completely vanish, as their role in learning morbid pathology can never be replaced by any other means. As of now, fetal and perinatal autopsies continue to be performed as they have a role in identifying developmental malformations for counseling for future pregnancies.[10] The article on “Perinatal and Fetal autopsies in Neuropathology” by Chatterjee et al. in this issue presents a well-illustrated series of the common CNS abnormalities of the fetus and the newborn detected by autopsy. The authors discuss some of the newer methods like a virtual autopsy.

The article on Brain Banking in Neuroscience by Shankar and Mahadevan illustrates how the future of neuropathology lies in tissue banking.[11] Drawing on their experience of more than two decades, they trace the evolution of brain banking, the rise of global networks, benefits as well as challenges faced. The scope, methods of donor recruitment, collection protocols, annotation, quality control, monitoring, accreditation, etc., are discussed, which would be valuable to those interested in initiating tissue banking. The ethics of biobanking, one of the most controversial issues in bioethics, and the key issues of consent, confidentiality, and commercialization are examined. The intriguing concept of converting otherwise “biological waste” into invaluable resources for neuroscience to serve as a “gift of hope” for future generations is proposed.

Advances in pathobiology and molecular techniques forced the reluctant pathologist to abandon traditional morphology to learn the alphanumeric language of molecular biology. Now, the invasion of information technology, computer programming, and artificial intelligence into the sacred field of medicine has mercilessly broken the barriers between medicine and technology, ushering in the new era of “computational or digital pathology”.[12] The article “Artificial intelligence in neuropathology: Current status and future perspectives” by Vikas V, a neurosurgeon who also has enormous expertise in the field of artificial intelligence and its application in neuroscience, attempts to explain in simple terms for pathologists to understand artificial neural network, machine learning, and artificial intelligence for computational pathology, and its application with reference to neuropathology. The principle behind neural networks and artificial intelligence that is essentially modeled on the neurobiological principles of learning in humans is explained in simple terms. The interesting parallel between digital pathology and machine learning and the approach of a traditional pathologist in diagnosis is well brought out! He highlights the importance of the pathologist in taking the lead in guiding this burgeoning field of digital pathology in the right direction to ensure clinical relevance. One can foresee that there will be a unique set of ethical and regulatory concerns that will emerge. It appears that in the coming century, the traditional pathologists' best friend-the microscope will be relegated to the backseat to make way for a computer! Change as we know it is constant, and we will have to unlearn and relearn several of our skills to embrace a new and better tomorrow in the interest of patient care.

Overall, this section on non-neoplastic diseases is a well-written and illustrated series that addresses various aspects of pathology and lab diagnosis of CNS infections, epilepsy, biobanking, autopsy neuropathology, and the emerging field of digital neuropathology. The goal of this special issue is to provide the practicing pathologist with essential and useful information for day-to-day practice assembled in one convenient volume. It is hoped that this compilation will prove a useful reference material for the clinician regardless of their specialty faced with challenging cases. The futuristic practice of medicine envisions a new generation of crossbreed between clinicians, basic scientists, and engineers working together for the betterment of patient care.

   References Top

India State-Level Disease Burden Initiative Neurological Disorders Collaborators. The burden of neurological disorders across the states of India: The Global Burden of Disease Study 1990–2019. Lancet Glob Health 2021;9:e1129-44.  Back to cited text no. 1
Shah KK, Pritt BS, Alexander MP. Histopathologic review of granulomatous inflammation. J Clin Tuberc Other Mycobact Dis 2017;7:112.  Back to cited text no. 2
Shih RY, Koeller KK. Bacterial, fungal, and parasitic infections of the central nervous system: Radiologic-pathologic correlation and historical perspectives: From the radiologic pathology archives. Radiographics 2015;35:1141-69.  Back to cited text no. 3
Shankar SK, Mahadevan A, Kovoor JM. Neuropathology of viral infections of the central nervous system. Neuroimaging Clin N Am 2008;18:19-39.  Back to cited text no. 4
Bryce C, Grimes Z, Pujadas E, Ahuja S, Beasley MB, Albrecht R, et al. Pathophysiology of SARS-CoV-2: The Mount Sinai COVID-19 autopsy experience. Mod Pathol 2021;34:1456-67.  Back to cited text no. 5
Garcia HH, Nath A, Del Brutto OH. Parasitic infections of the nervous system. Semin Neurol 2019;39:35868.  Back to cited text no. 6
Blümcke I, Aronica E, Miyata H, Sarnat HB, Thom M, Roessler K, et al. International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia 2016;57:34858.  Back to cited text no. 7
Blümcke I, Coras R, Busch RM, MoritaSherman M, Lal D, Prayson R, et al. Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial. Epilepsia 2021;62:141628.  Back to cited text no. 8
Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M, et al. Autoimmune encephalitis: Proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 2021;92:757–68.  Back to cited text no. 9
Andola US, Am A, Ahuja M, Andola SK. Congenital malformations in perinatal autopsies 387-A study of 100 cases. J Clin Diagn Res 2012;6:1726-30.  Back to cited text no. 10
The Lancet Neurology. Brain banking: More effective strategies needed. Lancet Neurol 2013;12:1035.  Back to cited text no. 11
Deng S, Zhang X, Yan W, Chang EIC, Fan Y, Lai M, et al. Deep learning in digital pathology image analysis: A survey. Front Med 2020;14:470-87.  Back to cited text no. 12

Correspondence Address:
Anita Mahadevan
Department of Neuropathology, NIMHANS, Bangalore, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.345064

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