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Biomedical subjects

S K Shankar

Publications and source records attributed to S K Shankar.

At least 37 records · Page 2Linked to original sources

Subependymal giant cell astrocytoma: a clinicopathological study of 23 cases with special emphasis on proliferative markers and expression of p53 and retinoblastoma gene proteins.

AIMS: To gain a better insight into the biological behaviour of subependymal giant cell astrocytoma (SEGA), tumour suppressor gene protein expression and various proliferative indices were studied in these tumours and correlated with histological features and clinical outcome. METHODS: We studied 23 cases of SEGA, 19 from our own Institute and four from the National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore, India. Immunohistochemical staining for various glial and neuronal markers, proliferative markers (MIB-1, Topoisomerase II alpha PCNA) and tumour suppressor gene protein expression of p53 and retinoblastoma (Rb) were performed. RESULTS: Nineteen cases of SEGA were collected over a period of 23 years (January 1978-December 2001), which accounted for 0.16% of all intracranial tumours and 0.51% of all gliomas reported at this centre. Ages ranged from 4 to 37 years (mean 13.2 years) with a male preponderance. Nine of the 23 cases were associated with tuberous sclerosis (TS), six at the time of diagnosis, while three developed TS during the follow-up period. Treatment consisted of surgical resection (total in nine cases and subtotal in 14 cases) followed by radiotherapy in seven cases. Except for two patients who died in the immediate post-operative period of surgical complications, the remaining patients were all alive in the follow-up period (mean 37.1 months). One patient experienced recurrence 22 years after the first surgery and a second patient after 2 years. Necrosis and/or mitoses were observed in five cases. Immunohistochemically, tumours were positive for both glial and neuronal markers. Interspersed inflammatory cells were a mixture of mast cells and lymphocytes of T immunophenotype. The MIB-1 labelling index (LI) ranged from 0 to 8% (mean 3.0%), topoisomerase II alpha (topo II alpha) LI from 0 to 9.5% (mean 2.9%) and PCNA LI from 10 to 59% (mean 32.5%). The difference in the labelling indices of tumours with and without mitoses and/or necrosis was not statistically significant. None of the tumours revealed loss of Rb gene protein expression. p53 immunopositivity was seen in 14 cases (labelling indices ranged from 1 to 7.3% with a mean of 2.4%). The correlation between the MIB-1 LI and topo II alpha LI, and topo II alpha LI and PCNA LI was significant (P<0.05) but not so with other parameters like p53 protein expression, duration of survival and morphological features such as mitoses and necrosis. CONCLUSIONS: SEGAs are rare intraventricular tumours associated with TS and express both neuronal and glial markers. They have a low proliferative potential. Mitoses and necrosis are not associated with a worse prognosis. In view of the low proliferative indices and long survival of these patients without recurrence, the role of post-operative radiotherapy is questionable. These patients should be followed up closely as many of them develop stigmata of tuberous sclerosis at a later stage.

Adolescent↗

Tangier disease--a diagnostic challenge in countries endemic for leprosy.

A case of Tangier disease (TD) is reported from India. The patient had presented with indolent mononeuritis multiplex and trophic ulcers of 16 years duration mimicking Hansen's disease. He received antileprosy treatment for one and a half years. Nerve conduction studies revealed features of demyelinating neuropathy. Biopsies of the sural nerve and skin showed striking vacuolation of Schwann cells and myelin sheaths, and foamy vacuolated fibroblasts, respectively, and no evidence of Hansen's disease. Low levels of apolipoprotein A1 (ApoA1) and cholesterol in the serum and undetectable levels of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in the blood confirmed the diagnosis of TD. This is the first reported case of TD from a tropical country-India. An attempt to establish a correct diagnosis should be made by demonstrating the histopathological and lipoprotein abnormality to avoid long term medications that are chosen empirically and are unnecessary. The importance of recognising this disease in a country where Hansen's disease is highly endemic cannot be overemphasised.

Adult↗

Subarachnoid spread of germinoma mimicking tuberculous meningitis.

A case of pineal germinaoma spreading along the basal subarachnoid space, clinically and macroscopically at autopsy, resembling tuberculous basal arachnoiditis is reported. Need to carry out CSF cytology of even hemorrhagic CSF is stressed, to diagnose the condition.

Adult↗

Carcinomatous meningitis mimicking Creutzfeldt-Jakob disease.

We report a case of carcinomatous meningitis diagnosed at autopsy that was clinically diagnosed as a case of Creutzfeldt-Jakob disease (CJD) because of rapidly evolving dementia. Pathological study revealed diffusely spreading carcinomatous meningitis, infiltrating into cortex along Virchow Robin space. Immunostaining for Prion protein was negative. Despite advances in clinical diagnosis, tissue diagnosis remains a pre-requisite for confirmation of CJD.

Creutzfeldt-Jakob Syndrome↗

Medulloblastoma with extensive nodularity: a variant occurring in the very young-clinicopathological and immunohistochemical study of four cases.

CASE REPORT: Four cases of medulloblastoma with extensive nodularity (MBEN) are described. The patients were 3 years of age or younger at diagnosis. Cranial CT scan disclosed multiple coalescing nodules with peculiar 'grape-like' architecture in three patients. A near total excision of the tumour was performed in all four patients. The patients are currently receiving radiation and chemotherapy. Histologically, the tumours were characterized by extreme nodularity with intranodular uniformity and low proliferative index. The internodular zones were extremely cellular, composed of undifferentiated, mitotically active cells. Bcl-2 protein expression was observed in the cellular zones but was distinctly absent within nodules. DISCUSSION: MBEN represents a variant that occurs in very young children but has a good prognosis. The favourable outcome is probably related to its spontaneous neurocytic differentiation. The pattern of Bcl-2 immunoreactivity in MBENs indicates that this protein could be a key player in the regulation of neuronal differentiation in medulloblastomas.

Cerebellar Neoplasms↗

MRI and in vivo proton MR spectroscopy in a racemose cysticercal cyst of the brain.

Racemose cysticercal cyst is the subarachnoid manifestation of the larvae of Taenia solium. On MRI the cysts may resemble other cystic masses. We report the magnetic resonance spectroscopy (MRS) features of a case on in vivo proton spectroscopy and discuss its role in the diagnosis of intracranial cysts of parasitic aetiology.

Brain Diseases↗

Low prevalence of progressive multifocal leukoencephalopathy in India and Africa: is there a biological explanation?

Infection with human immunodeficiency virus (HIV) clade C virus is the most common form of HIV infection in the world. It largely infects populations in Africa and Asia and not much is known about the neurological complications associated with the virus. Cases of progressive multifocal leukoencephalopathy (PML) have been rarely reported in the literature in the acquired immunodeficiency syndrome (AIDS) or non-AIDS populations from these regions. In this article, the authors present three recently diagnosed patients with AIDS and PML from one neurological center in India, review the diagnostic challenges faced, and speculate on the possible biological reasons, including viral strain differences as well as HIV and JC virus interactions, that may account for the low incidence.

Acquired Immunodeficiency Syndrome↗

T helper responses to Japanese encephalitis virus infection are dependent on the route of inoculation and the strain of mouse used.

T helper cytokine and IgG subtype responses were studied in three strains of mice (C57BL/6J, Swiss albino, BALB/c; n=90 per strain) immunized with live Japanese encephalitis virus (JEV) by intraperitoneal (IP), subcutaneous (SC) and peroral (PO) routes. Lymphocytes obtained from the spleens of immunized and control mice were stimulated in vitro with JEV for 48 h and the supernatants were assayed for the presence of the cytokines IL-4 and IFN-gamma. JEV-specific IgG isotypes were also measured in the sera of immunized mice. T helper cytokine responses in mice immunized with JEV were found to be strain- and route-specific in the three species tested. Moreover, they were also dependent on the type of immunogen used (live vs killed virus), as well as the number of doses administered. C57BL/6J and BALB/c mice were more uniform in their T helper responses compared with the outbred Swiss albino mice and induced a good Th1 response (P<0.001). Among the three routes evaluated, the IP and SC routes consistently elicited a Th1 response compared with the PO route (P<0.001), where an initial Th2-type response reverted to a Th1 response after repeated immunization. Live JEV induced a Th1 response while the commercial killed vaccine induced a predominant Th2 profile.

Administration, Oral↗

Association of primary central nervous system lymphomas with the Epstein-Barr virus.

The incidence of primary central nervous system lymphoma (PCNSL), previously a rare tumor, has increased significantly over the past few decades, partly due to the AIDS epidemic but also in immunocompetent individuals. Studies from Western countries have shown a consistent association of tumors occurring in immunocompromised individuals with the Epstein-Barr virus (EBV) suggesting an important role for the virus in the pathogenesis of these tumors, but an infrequent association of the virus with PCNSL in the immunocompetent host has also been noted. We studied 11 patients with PCNSL who had no evidence of an immunocompromised state. All the tumors were aggressive B cell lymphomas. EBV association was studied using EBER in-situ hybridization. 10 out of the 11 tumors were negative for EBV, indicating that tumors in immunocompetent individuals in developing countries are also infrequently EBV associated and that a different pathogenetic mechanism is operative in the evolution of these tumors.

Adult↗

Epithelioid and retiform hemangioendothelioma of the skull bone--report of four cases.

Hemangioendothelioma (HE) is a borderline or intermediate type of vascular neoplasm. We report clinical and histopathological characteristics of four cases of HE arising from the skull bones because of its extreme rarity in this location. The age of the patients ranged from 6-45 years. Three patients presented with a painless swelling over the head and one case had sphenoid wing mass with dimness of vision and proptosis. Radiographic images showed a well-demarcated, osteolytic lesion in the skull bone in all the four, one case in addition had sclerotic edges and another had specks of calcification. Grossly, the tumour was very vascular with hemorrhagic areas. Histologically, three cases showed features of an epithelioid variant of HE, with short strands and solid nests of rounded to slightly spindled, eosinophilic endothelial cells, some of them having small intracellular vacuoles. The stroma was myxoid--hyalinised with focal mixed inflammatory infiltrate. One case had features of a 'retiform' histological variant composed of numerous elongated vessels lined by a single layer of hobnail endothelial cells, focal lymphocytic infiltrate and papillae with hyaline collagenous cores. The tumour cells in all the four were immuno-labelled by antibody to factor VIII-associated protein. The tumour cells lacked cytological atypia and mitosis was sparse. These features were important in prognostication as low-grade tumours can be cured by complete wide-resection.

Adult↗

Desmoplastic infantile ganglioglioma--clinicopathological and immunohistochemical study of four cases.

CASE REPORTS: Four cases of desmoplastic infantile ganglioglioma (DIG) seen in India are described. These patients presented with large, supratentorial, superficially situated cystic tumours that showed glial and ganglionic differentiation; accompanied by a severe desmoplastic reaction. MIB-1 labelling was rare, despite foci of apparently primitive neuroepithelial cells. There was lacking p53 protein expression by tumour cells in all cases. The prognosis was good following either partial or complete tumour resection. DIGs are a distinct form of developmental neuroepithelial tumour, probably arising from neural progenitor cells in subcortical zone along with mature subpial astrocytes. CONCLUSIONS: In view of its favourable prognosis, this tumour has to be diagnosed accurately by immunohistochemical techniques using glial and neuronal markers. The absence of p53 protein expression suggests that DIG probably has different molecular genetic pathways from other supratentorial astrocytomas.

Brain Neoplasms↗

Brain biopsy in Creutzfeldt-Jakob disease: evolution of pathological changes by prion protein immunohistochemistry.

The formation of protease-resistant prion protein (PrPsc) is considered to be an early event in the pathogenesis of Creutzfeldt-Jakob disease (CJD) and hence its demonstration in brain biopsies by immunohistochemistry is considered diagnostic. We analysed eight brain biopsies from the frontal cortex collected from different parts of India from cases diagnosed as CJD on clinical and pathological grounds for the expression of prion protein (PrP). The duration of illness in these cases varied from 2 months to 1 year. Immunohistochemistry was carried out on paraffin sections using two different clones (KG9 and 3F4) of monoclonal antibodies to PrP. Although all eight cases showed classical features of spongiform encephalopathy of varying severity, only five of the eight cases revealed PrP(sc) in the brain tissue. The immunolabelling was focal and all areas with spongiform change were not labelled. A temporal evolution in the staining pattern was evident - particulate diffuse labelling (synaptic type) in early stages (2 months), perivacuolar deposits in intermediate stages (5-6 months), and dense plaques in late stages (12 months).

Adult↗

Cryptococcal choroid plexitis as a mass lesion: MR imaging and histopathologic correlation.

Cryptococcosis is a relatively common mycotic infection of the CNS caused by a ubiquitous saprophytic fungus. We present an unusual case of CNS cryptococcosis in an immunocompetent patient. Florid choroid plexitis resulted in the formation of intraventricular enhancing mass lesions that filled the ventricles and were hyperintense to associated periventricular edema on T2-weighted MR images. We also noted lesions corresponding to microcystic, dilated Virchow-Robin spaces in the basal ganglia that were characteristic of cryptococcal infection.

Basal Ganglia↗

Glioneuronal migration and development disorders: histological and immunohistochemical study with a comment on evolution.

Glioneuronal migration disorders of the brain evolve primarily due to aberration in neuronal migration, maturation and programming in the development of various topographic zones in the brain, following pathological alterations in glial and neuronal interactions. These are broadly referred as cortical dysplastic conditions. While these dysplastic conditions involving cerebral cortex present as drug resistant seizure disorder, those involving cerebellum present as mass lesions or slowly progressing vertigo. We report 17 cases, representing the histological spectrum of dysplastic, glioneuronal migration disorders which include, hemimegalencephaly (1), tuberous sclerosis (4), Sturge Weber Syndrome with focal dysplasia (1), Dysembryoplastic neuroepithelial tumor (7) and Lhermitte Ductos disease of cerebellum (2). The dysplastic neurons in varied stages of maturation showed neuronal cytoskeletal pathology similar to that in neuro degenerative diseases, especially when associated with cytomegaly. Similarly, cells exhibiting dual expression of glial and neuronal markers were noted in the cerebral dysplastic lesions. The dysplastic glial elements probably form the subependymal giant cell astrocytomas. Dysplastic neuronal elements form the nidus for DNT. When localized, surgical resection ameliorate the symptoms in many of these condition. Study of these conditions provide better insight into glioneuronal interaction and maturation of the brain.

Adolescent↗

Spinal intramedullary tuberculoma and abscess: a rare cause of paraparesis.

Five cases of spinal intramedullary tuberculomas (IMT) and one case of spinal intramedullary tuberculous abscess (ITA) are presented. Gd enhanced MRI revealed ring enhancing lesion with central hypodensity, suggesting granulomatous pathology. Surgical excision of the intramedullary lesions was carried out in four cases, while two patients received presumptive anti-tuberculous chemotherapy only. Repeat MRI after completion of anti-tuberculous therapy showed total resolution of the lesion. In other cases following surgical excision, the patients improved significantly. The management of these rare lesions is discussed and the literature reviewed.

Adult↗

Stroke in a young man with fibromuscular dysplasia of the cranial vessels with anticardiolipin antibodies: a case report.

A case of fibromuscular dysplasia (FMD), presenting with a non-hemorrhagic infarct is reported. Positivity of anticardiolipin antibodies suggested an immune response. A 40-year-old man presented with sudden onset of stroke, preceded by similar ischemic attacks. Computed tomography (CT) of the brain showed a recent non-hemorrhagic infarct in the left middle cerebral artery (MCA) territory and an old right MCA territory infarct. Serum was positive for anticardiolipin antibodies. These above findings were confirmed at autopsy. A portion of the internal carotid artery and the middle cerebral arteries on both sides revealed features of FMD, with thrombosis. This case suggests an immune mechanism for FMD, hitherto unobserved in the cerebral circulation.

Adult↗