Biomedical subjects
Publications and source records attributed to V Santosh.
A colloid xanthogranuloma of the third ventricle is described. Presenting features were symptoms of raised intracranial tensions and two episodes of seizures. The pathogenesis, clinical and radiological features, differential diagnosis and treatment of this rare benign lesion are briefly discussed.
A case of cerebral abscess caused by Fonsecaea pedrosoi is reported in a nonimmunocompromised 15-year-old boy. In the absence of a primary cutaneous lesion, this fungus was considered to be a primary neuropathogen. The fungus was cultured and characterized from the abscess material obtained at surgery. Prompt therapy using amphotericin B and 5-flucytosine helped in the successful recovery of this patient.
Pathomorphological features of 10 HIV positive individuals studied at autopsy and biopsy are described. Nine patients had evidence of neuro-AIDS and eight of them succumbed to various opportunistic infections. One surviving patient underwent a diagnostic lymph node biopsy which revealed tuberculous lymphadenopathy. Cryptococcal meningitis was the commonest CNS opportunistic infection, seen in five cases, with disseminated systemic cryptococcosis in two. The other opportunistic infections included toxoplasma encephalitis in two, with acanthamoeba infection in one patient. Pulmonary tuberculosis was noted in three patients while other bacterial infections such as meningococcal meningitis, pseudomonas septicaemia were observed in three and pneumocystis carinii pneumonia in one. One seropositive individual was clinically asymptomatic but succumbed to a road traffic accident. The brain in this case showed features of HIV associated early leucoencephalopathy. Bacterial infections caused by organisms other than Mycobacterium tuberculosis associated with AIDS are often underdiagnosed and should be considered, especially in developing countries. In cases of cryptococcal and tuberculous meningitis or multiple parasitic infections, the patients should be screened for associated HIV infection.
A case of disseminated Burkitt's lymphoma with nervous system involvement in a HIV negative 35 year old lady is described. She primarily presented with multiple cranial nerve palsies. At autopsy, diffuse involvement of parenchymatous organs and lymphomatous meningitis with conspicuous sparing of gastrointestinal system was observed. In addition, there was an unusual feature of paraneoplastic demyelinating peripheral neuropathy. Incidentally, a large hydatid cyst was also seen in the left lobe in addition to the lymphomatous involvement of the liver.
Pediatric glioblastoma multiforme (GBM) tumors, which have been established as 'de novo' neoplasms, are known to differ from their adult counterparts in terms of biology, genetics and ultimately survival of patients. In order to evaluate the utility of markers of tumor biology for refining prognostic assessment, we retrospectively analyzed 54 pediatric GBMs (age range 9 months to 15 years) occurring at different anatomical sites in the brain, operated at our institute between 1995 and 2001. The expression of p53, epidermal growth factor receptor (EGFR), bcl-2 and retinoblastoma proteins (pRb) was analyzed by immunohistochemistry and the results were compared with the clinical profile, MIB-1 labeling index (LI) and patient survival. p53 immunoreactivity was noted in 53.7% of cases, predominantly in thalamic (75%) and cerebral lobar (62.2%), followed by brainstem tumors (30%). It was absent in cerebellar tumors. p53-positive tumors had a higher MIB-1 LI, compared to p53-negative tumors (p=0.003). EGFR and bcl-2 overexpression was observed in 25.9% and 33.3% of cases, respectively, and loss of pRb expression was evident in only 7.4% of cases, indicating that loss of this gene function is not significantly involved in pediatric GBMs. p53 and bcl-2 expression were maximally noted in patients with poorer outcome. Our results indicate that p53 expression status is noted in a significant number of pediatric supratentorial neoplasms. p53 with bcl-2 overexpression is more often associated with ominous prognosis. Further molecular characterization would provide newer insights into the biology of these neoplasms and form a basis for future therapeutic decision making.
Clinical, histological, immunohistochemical and ultrastructural features of 5 cases of inclusion body myositis -4 sporadic (s-IBM) and one hereditary (h-IBM) form are described. These patients (3 men, 2 women) had chronic progressive weakness of varying severity in all 4 extremities with sparing of cranial muscles. Elevation of CPK was noted in 2 patients. Electromyography revealed features of myopathy in 4 and additional neurogenic changes in 2 subjects. Clinical diagnosis was often other than inclusion body myositis. Presence of characteristic eosinophilic inclusions within the vacuoles established the diagnosis. The inclusions were congophilic and showed positivity to ubiquitin, beta-amyloid and SMI-31 in the sporadic cases while congophila was absent in the hereditary form. Immunostaining to hyperphosphorylated-tau was negative in both s-IBM and h-IBM. Membraneous whorls were observed at ultrastructural level. None of the patients improved with steroids and trial with other immunosuppressants was unsuccessful.
Giant axonal neuropathy (GAN) and infantile neuroaxonal dystrophy (INAD) are two progressive neurodegenerative disorders of childhood that have considerable clinical as well as histological overlap but are believed to be ultrastructurally distinct. The clinicopathological and ultrastructural features of three cases of INAD, two of whom are siblings and one case of GAN are described. The sural nerve biopsies in all four cases were essentially similar on light microscopy revealing giant axons. On electron microscopy, the findings in the case of GAN were typical with dense accumulation of neurofilaments within the giant axons. In the three cases of INAD, too, in addition to accumulation of mitochondria and organelles with vesiculotubular profiles, a similar increase in neurofilaments was evident. We, therefore, believe that these two disorders may represent a spectrum in evolution of intermediate filament pathology with various organelles participating in the temporal evolution of the disease process.
Schwannomas from cranial nerves and spinal roots are most often benign, malignant schwannomas being uncommon in this location. This report describes a unique case of multiple cellular and malignant schwannomas of the cranial and spinal nerves in a patient with features of neurofibromatosis 2. The tumors were arising from left optic, bilateral oculomotor, trochlear, abducent and vestibular nerves, the left facial and the spinal lumbar nerve roots. The tumor arising from the right trochlear nerve was seen excavating into the hippocampus and the left vestibular nerve into the medulla. In addition, the patient had nodular schwannomas adherent to the inferior surface of the optic chiasm and the cerebellum away from the cranial nerves. Hyperplastic schwannosis was noted in perivascular spaces of thalamus, cerebellum and hippocampus on both sides away from the main lesions. The immunohistochemical and ultrastructural profiles of the tumors suggest that neurofibromas and schwannomas are probably not distinct tumors but lie within a spectrum that differs histologically depending on the predominant cell type.
Cryptococcosis is increasing because of an ever rising population of immunocompromised individuals especially those with acquired immune deficiency syndrome (AIDS). Cryptococcal infection of the central nervous system (CNS) were diagnosed in 149 cases over a period of 19.5 years (January 1978-June 1998). Culture was positive in all cases except three who were already on antifungal therapy. India ink mounts of cerebrospinal fluid (CSF) revealed encapsulated cryptococci in 134, and cryptococcal antigen was detected in 111 of 114 patients tested. A comparison of laboratory and certain clinical parameters in patients with and without associated HIV infection showed that a poor CSF cell response and culture of cryptococci from extra-neural sites was more often associated with HIV infection and was statistically significant. Further, presence of concomitant infection especially tuberculosis, and mortality were higher in the HIV positive group.
In developing countries hydatidosis is both a medical and economic problem related to environmental hygiene and healthy veterinary practice. This cestode parasitic infestation, uncommonly involving the nervous system, presents with varied clinical manifestation, at times causing diagnostic dilemmas. Multiple intracranial and spinal hydatidosis is rare. A series of 29 histologically confirmed cases of hydatidosis of neuraxis (21 intracranial and 8 spinal) from South India are presented. Among the 21 cases of intracranial hydatidosis, 12 cases were in pediatric age, while only 1 spinal lesion was noted in a 5-year-old child. The clinical presentation of intracranial lesions was predominantly that of raised intracranial pressure and visual symptoms, while spinal hydatidosis manifested with severe back pain, weakness and sphincter disturbances. The cranial cysts were usually single and uniloculated (12 cases), multiple in 7 and single but multiloculated in 2. In spinal hydatidosis, the cysts are usually multiple and extradural, rare ones being intramedullary and intradural. Based on clinical features and imaging, the differential diagnosis for intracranial lesions were cystic tumors and arachnoid cyst while metastasis and tuberculosis were considered in cases of spinal hydatidosis because of vertebral bony involvement. The majority of the cysts could be surgically resected totally and some were aspirated under control suction and resected. None of the cases had anaphylactic reaction, with no significant post-operative morbidity and no mortality. One intracranial and 2 spinal lesions caused by fertile cysts recurred to undergo repeated surgery.
Hemimegalencephaly (HME), a rare congenital abnormality characterized by unilateral enlargement of the cerebral hemisphere, is one of the less common causes of intractable seizures. We report a 6-month-old infant with uncontrolled seizures who was diagnosed to have a large mass lesion based on a CT scan. Postmortem examination revealed left-sided HME with pachygyria, widened cortex, indistinct grey-white junction, and distorted deep nuclear masses. Histological features included loss of cortical lamination, large atypical neurons with argyrophilic accumulations, ballooned cells, neuronal heterotopia, and astrocytosis with dystrophic calcification. The heterotopic neurons in the white matter were present in a radial pattern suggestive of aberrant neuronal migration. Several large neurons were dystrophic with cytoskeletal abnormalities like phosphorylated high molecular weight neurofilament and ubiquitin in the cytoplasm. However, typical neurofibrillary tangles with Congo red and tau positivity were not observed. Synaptophysin labelling was found to be decreased in the cortex, but some of the abnormal neurons had dense perisomatic label. The majority of the balloon cells were astrocytic in origin, being positive for glial fibrillary acidic protein and negative for the neuronal markers. Although the etiology of HME is not known, it provides an opportunity to study anomalous development of the brain and neuronal developmental abnormalities.
Dysembryoplastic neuroepithelial tumor (DNT), a benign neoplasm, is now a well recognized clinicopathological entity. We report the second case of DNT in the cerebellum occurring in a 20-year-old male presenting with ataxia. He also had Arnold-Chiari malformation of the adult type. Histologically the tumor was a "simple" DNT having the specific "glioneuronal" element, namely oligodendrocyte-like cells (OLCs), mucoid change and floating neurons (Purkinje cells). A striking feature was the perpendicular arrangement of the neuropil columns extending from the pial surface to white matter similar to those seen in supratentorial examples. On immunstaining some of the OLCs were positive for synaptophysin and negative for glial fibrillary acidic protein (GFAP), glucocerebroside, tau and MAP-2. The neuropil was synaptophysin-positive and focally positive for MAP-2 and GFAP as well. The Purkinje cells were morphologically normal but malaligned and were positive for phosphorylated neurofilament suggesting secondary dysplastic changes. A transition of the lesion into relatively normal cerebellum preserving the folial architecture was observed. The histological and immunochemical features of the DNT in cerebellum suggests its possible origin from the pluripotential external granular layer.