Expert Commentary on “The Broad Field of Neuropathology” 1000 Brain “Tumours'', B. The Encephalitides, C. Wilson's Disease in India by Darab K. Dastur
Citation of the Original Article: Dastur K Darab. The Broad Field of Neuropathology. 1967; 15: 51-69.
It is an honor to offer a historical perspective and a commentary on a landmark article of Dr. Darab K Dastur, arguably the Father of Neuropathology in India. The events span over half a century from the late sixties across to the current era. His article “The Broad Field of Neuropathology” appeared in print in Neurology India (Vol. 15, No. 2, April–June 1967, Pg. 51–69) after being delivered as a Presidential Address at the XVI Annual Conference of the NSI at Bangalore in 1966. He was the second neuropathologist to be the President of the NSI after Dr. CGS Iyer (1961) and only four have graced the office till date!
Reading through the article and reviewing the happenings in the infantile field of neuropathology during the sixties, one is struck by several emerging facts and coincidences. I shall briefly discuss the connotations and the content of the article below.
The mooring of Neuropathology to General Pathology is evident in the article and the publications in contemporary world literature. The role, scope of work, and expertise of the neuropathologist was getting defined;, a similar, concurrent evolution was happening in the fields of neurochemistry, neurogenetics, and psychiatry., The International Society of Neuropathology had embraced a diverse scope of the discipline. Its proclamation stated that it dealt with “genesis and character of changes in the nervous tissue under pathological conditions.” Dr. Dastur justifies that a neuropathologist could stem from allied broad specialties of pathology/internal medicine or super-specialties of clinical neurology/neurosurgery or psychiatry. Even though such movement of academics is relatively common in the West compared to India, in retrospect, not many neuropathologists seem to have originated from the allied fields.
It is interesting to find an acknowledgment of various neurosurgeon colleagues with reference to particular cases described in the article in the text itself (e.g. a case of Dr. G Sinh), or with respect to new techniques (e.g. thankful to Dr. Bhagwati for undertaking the brain biopsies), indicating close cooperation and mutual interdependence between the surgeon and the pathologist in patient care as well as growth of neuropathology as a subspecialty. The style of writing is informal at places and largely a narrative, almost a verbatim transcription of the Presidential Address.
Several countries such as Great Britain, the United States, Soviet Union, and Germany had already begun to take stock of their historical milestones and have published national reviews on the progress.,,,, The fraternity had started to delve into the study of a variety of individual entities (e.g., phenylketonuria, psychoses, acute poisonings, rabies, lupus erythematous, trauma, degenerative disorders),,,,,,, and experimental situations, in some detail.
The teaching of neuropathology was being debated in premier medical schools of the world in the late sixties., The quantum of content for undergraduate teaching was the focus,,,, and the curriculum for postgraduate neuropathology was not conceived. In India, there were a handful of centers that were driven by pathologists who were trained abroad and had decided to focus their energies on the subspecialty. Dr. Dastur, Officer In-Charge ICMR, at the Neuropathology Unit of the JJ Group of Hospitals, Bombay, was one such; Dr. S Sriramachari at the Institute of Pathology, ICMR, Delhi, was another. I had joined Dr. Sriramachari as an ICMR fellow in 1966 to begin my journey. Deliberations on the instructive content for undergraduate and postgraduate teaching do not feature in published Indian literature. From a sporadic training of interested pathologists in the field to the initiation of Post Doctoral Certificate Course (PDCC) (Neuropathology, NIMHANS) in 2000 and Doctor of Medicine (DM) (Neuropathology, NIMHANS) in 2015, curricular streamlining has indeed come a long way. On a similar note, the formation of the Neuropathology Society of India in 2015 marks a milestone.
Deliberately enough, Dr Dastur has chosen three illustrative pathologies from the vista of neuropathology to interest a wide readership.
The first section of the article dwells on “one thousand” intracranial space-occupying lesions (ICSOLs) rather than just neoplasia – “one thousand” being a strikingly large number accumulated at a center by a dedicated team. The spectrum was evident only after histopathological examination in this era.
Despite available antituberculous medications, tuberculous etiology accounted for a fifth (21%) of the ICSOLs overall; the figure was even higher (46%) in children. Excluding the tuberculous cases, the distribution of tumors was similar to that reported from elsewhere in the world, both in adults and children. In India, an ICSOL in the pre-computed tomographic (CT) era was generally considered tubercular unless proved otherwise. Cystic tuberculous lesions were being recognized as distinct from caseous lesions and the mechanism of cavitation is expounded. Besides Indian publications,,,, occasional ones from the West, testify to the space-occupying nature of tuberculosis in the brain and spine.
There is an emphasis on histogenetic classification of brain tumors and avoidance of confusing terms reflecting morphologic attributes of neoplastic cells. Dr. Dastur goes on to describe various tumors in the narrative highlighting specific clinical features and histological correlates. The primacy of special stains in identifying the tissue type and histogenesis is evident in the elaborate description. The WHO Classification of Tumours of the Central Nervous System incorporating histochemistry first appeared in 2007 and has been subsequently revised in 2016 incorporating features of molecular biology and cytogenetics. Significantly, the latter means have allowed for diagnosis on comparatively smaller biopsy specimens and more accurate prognostication.
He does not make a distinction between “congenital” (detected prenatally or up to 60 days of life) and developmental neoplasia. Although the youngest child was 3 months old, the percentage of congenital tumors in the series is significant, 8.6%.
The section on encephalitides dwells on the indulgence of obtaining a brain biopsy and the justification thereof. Fortunately, opinion from 20 neurosurgeons and neurologists stationed across the Atlantic concurred on the fact that it was imperative for a diagnosis in a serious patient where all other noninvasive investigations had failed. In the absence of CT/magnetic resonance imaging (MRI) and immunological tests, derivations from cerebrospinal fluid examination were limited and the diagnosis depended on a biopsy or autopsy. The specimen had to be a generous wedge biopsy from the cortical surface to down almost to the ventricle! The neurosurgeons' contribution and the lack of a gross deficit when the site was restricted to the nondominant frontal lobe are documented. Noticeably, 25% of the biopsies turned out “tuberculous.” The subsequent decades would see a change with the advent of advanced imaging (CT - 1970s, MRI - 1980s), electrophysiology, and immunological studies.
Dastur elaborates on the findings in two entities – subacute progressive encephalitis and subacute sclerosing leukoencephalitis, which seem to be the points in a continuum of pathology of the white matter. Despite an adjunctive array of special stains, changes at the gray–white junction were largely a nonspecific response to a variety of stimuli – inflammatory, degenerative, or traumatic. While simultaneously appearing publications suspect a viral etiology,, several have documented ultrastructural details on electron microscopy from across the world., The relative occurrence of these and other (viral including HIV, parasitic, metabolic, and immunological) etiologies has changed with times. Yet, the entity of 'encephalitis, not otherwise specified' continues to vex the neuropathologist today with the final diagnosis becoming evident after years of diligent follow-up.
During this period, the inheritance and clinical features of Wilson disease were being elucidated. The publication mentions about investigations in 105 sibships (25 patients and 80 unaffected) from 18 families – the pedigree analysis of several cases is displayed reiterating the recessive inheritance, especially in families where consanguineous marriages were common. Besides hepatic and neurological forms, Dastur describes a late indolent “osseomuscular” form with radiological osteoporosis akin to rickets. This form debuted in the world literature here and is sparsely discussed later too. The late presenting osseomuscular form accounts for 2% of an impressive series of 282 cases from NIMHANS, probably the largest compilation from India. The observation that the disease is more common in South India is further borne out by the comparatively small numbers reported from the Post graduate Institute at Chandigarh.
The bulk of discussion speculates on clinical biochemistry - serum copper, serum ceruloplasmin, and the cupriruria with copper-chelating agents - BAL or penicillamine. However, no clear correlation with urinary calcium or phosphate is documented. Later, Dastur and Manghani have described low serum copper oxidase and high serum direct copper as constant accompaniments of the disease. The deliberations of a neuropathologist on laboratory medicine are noteworthy. The transition of diagnostic tests from this nebulous state to conclusive parameters - serum ceruloplasmin (decreased in 93%) and 24-h urinary copper excretion (increased in 70%) - has materialized over decades.
Dastur acknowledges a lack of autopsy material for comment. Anecdotal publications in later years have recognized that the pathological changes in Wilson's disease extend beyond the lenticular nucleus to a more diffuse distribution in the pons, midbrain, thalamus, dentate nucleus, and less frequently, corpus callosum and cortex–subcortex. In the largest autopsy series from India, Opalski cells and pontine myelinolysis have been singled out as specific to the neurological form of WD.
The author provides a kaleidoscopic peek at the future foreseeing the contribution of genetic studies in specific diagnosis. The stress on research and experimentation in human and animal models is apportioned a parallel importance. Not surprising, both these paths of scientific investigation have revolutionized much of our knowledge of basic neuropathology and its translation to diagnostics.
Dr. Dastur's article in the sixties is significant from several fronts - the tangible presence of neuropathological expertise in India, the presentation of unique facets of Indian disease to the world literature, and the spawning of research into the nascent field. We owe a lot to this pioneering perspective from Dr. Darab K Dastur.
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