Acquired Toxoplasmosis Presenting with a Brainstem Granuloma in an Immunocompetent Adolescent.

Background: Toxoplasmosis is an uncommon disease in immunocompetent people. Case characteristics: We report an adolescent boy with central nervous system toxoplasmosis who presented with progressive lower cranial nerve palsies and a ring-enhancing lesion on neuroimaging. Intervention: Diagnosis of toxoplasmosis was confirmed on histopathology of the excised lesion. Message: Toxoplasmosis should be considered in the differential diagnosis of focal brain lesions irrespective of immune status.

Central nervous system norcardiosis with granulomatous pachymeningitis and osteomyelitis of skull vault.

A 34-year-old immunocompetent man weighing 95 kg was operated for a small left parietal scalp swelling in the year 2002. He was well until 2008, when he developed chronic diffuse headache, vomiting and drowsiness. The left parietal dura and overlying vault biopsy showed evidence of granulomatous pachymeningitis with osteomyelitis secondary to nocardiosis. He had responded well to inadequate antibiotic therapy. After a dormant period of 3 years, there was recrudescence of severe raised intracranial tension symptoms in 2011. Magnetic resonance imaging showed diffuse pachymeningeal thickening mainly involving the occipital dura, posterior falx, and tentorium cerebelli. In addition, well-defi ned small nodules with hypointense signals on both T1- and T2-weighted images were seen in occipital lobes. Patient was treated with three drug regime with good recovery at 3 months follow-up. This is a rare case of central nervous system nocardiosis with skull vault osteomyelitis and a protracted clinical course.

Absence of anaplastic lymphoma kinase-1 expression in inflammatory myofibroblastic tumors of the central nervous system: Does it signify a different nosologic entity from its systemic counterpart.

Background and Aim: Infl ammatory myofi broblastic tumors (IMFTs) are uncommon neoplasms of the central nervous system (CNS) of intermediate grade biologic potential. Anaplastic lymphoma kinase (ALK-1), a diagnostic marker of anaplastic large cell lymphoma, is also expressed in a subset of IMFTs and appears to have prognostic signifi cance. Though, few studies have evaluated expression of ALK-1 in IMFTs of the CNS. This retrospective study was undertaken to evaluate the expression of ALK-1 expression in IMFT of CNS by immunohistochemistry and correlate with the clinical, radiological and pathologic features. Materials and Methods: Five cases diagnosed as IMFT/ infl ammatory pseudotumour/plasma cell granuloma, diagnosed in CNS over 10 year period (1998-2007) were retrieved from the archives of Department of Neuropathology of a tertiary referralcenter. The clinical profi le and imaging features were collected from the case records. Hematoxylin and eosin stained sections were reviewed with immunohistochemistry for smooth muscle actin (SMA), vimentin, desmin, ALK-1, p53, MIB-1, CD68, leukocyte common antigen, CD3, and CD20. Results: All fi ve cases of IMFTs presented as duralbased space occupying or en-plaque lesions. Histologically, four cases had combined plasma cell granuloma-fi brous histiocytoma morphology, and one had fi brous histiocytoma-like morphology. Immunohistochemically, SMA was strongly positive in spindle cell component of the tumors confi rming diagnosis. ALK-1 expression could not be detected by immunohistochemistry in any of the cases. Conclusion: Further studies analyzing ALK-1 gene mutation and rearrangements are required to determine pathogenetic role, if any, in CNS IMFTs.

Hemorrhagic Pericarditis in a child with primary varicella infection (chickenpox).

Chickenpox (Varicella) representing the primary infection by Varicella zoster virus is a common benign and self-limited infectious disease of childhood. Although the disease can be associated with complications, they are generally mild and tend to occur in adults and immunocompromised children. Severe and life-threatening complications are extremely rare, particularly those involving the cardiovascular system. We report a malnourished 5-year-old girl with chicken pox complicated by hemorrhagic pericarditis and deep vein thrombosis leading to fatal pulmonary thromboembolism. Though varicella infection runs a benign self-limiting course, it continues to cause significant morbidity and mortality when associated with complications, particularly in malnourished children. Hence, the importance of vaccination and early recognition of complications is emphasized.

Biochemical analysis of protein stability in human brain collected at different post-mortem intervals.

BACKGROUND & OBJECTIVES: Rising prevalence of neurodegenerative disorders with a steady increase in aged-population necessitates studies of the human brain to understand their pathophysiology. As animal models are not available, medical centers have established "brain banks" to provide autopsy brain samples for such research. Frozen tissues must be of optimal quality to permit molecular and protein studies. Post-mortem interval (PMI) is an important factor affecting tissue quality although its effects on brain physiology are unclear. We undertook this study to analyze the biochemical effects of PMI on protein stability in human brains collected at autopsy and stored at the brain bank of a tertiary care neurosciences institute in south India. METHODS: Different neuroanatomical areas including frontal cortex (FC), cerebellum (CB), caudate nucleus (CD) and substantia nigra (SN) from autopsy human brains (n=9) with varying PMI (4-18 h) were analyzed for pH, protein insolubility, protein oxidation/ nitration and protein expression of glial fibrillary acidic protein (GFAP), synatophysin and neurofilament (NF). Histological changes at different PMI were also assessed. RESULTS: An increase in tissue pH was noted with increasing PMI. Although there was no significant alteration in solubility of proteins, SN showed increased protein oxidation/nitration events, GFAP and NF expression with increasing PMI. No major abnormalities in cell morphology or tissue integrity were noted. Immunohistochemistry with GFAP and NF did not show any significant increase in signal in FC at high PMI. INTERPRETATION & CONCLUSION: In post-mortem human brains, although there were no gross structural changes at the tissue level with increasing PMI, biochemical events such as oxidative and nitrosative damage of cellular proteins, tissue pH could be considered as markers of tissue quality for biochemical research. Further, SN was found to be most susceptible to PMI related changes.

Expression of nestin--a stem cell associated intermediate filament in human CNS tumours.

BACKGROUND & OBJECTIVES: Nestin is an intermediate filament protein expressed in undifferentiated cells during the development of brain and is considered as a marker for neuroepithelial stem cells. Expression of this protein in various CNS tumour cells suggests the possibility of existence of tumour stem cell modulating the evolution. We carried out an immunohistochemical study to demonstrate the expression of nestin and its co-expression with neuronal and glial intermediate filament and correlate with the grade of malignancy. METHODS: Formalin fixed, paraffin processed sections from two human foetuses, 16 brain tumours of both neuronal and glial lineage and two metastatic tumours were immunostained with polyclonal antibody to nestin. Serial sections from primary brain tumours were also stained with monoclonal antibody to neurofilament (NF) and glial fibrillary acidic protein (GFAP). Fluorescent double labeling was carried out on four cases using laser confocal microscopy, to document co-localization of nestin with other intermediate filaments in the tumour cells. RESULTS: Nestin expression was observed along the paraventricular zone of human foetuses and in brain tumours of both glial and neuronal lineage, of both high and low grades of malignancy. In addition, mature dysplastic spinal motor neurons adjacent to tumour and cerebellar Purkinje cells also expressed nestin along with neurofilament. INTERPRETATION & CONCLUSION: Nestin expression was noted in both low and high grade brain tumours and dysplastic neurons and did not parallel the malignant grade of the tumour. The expression of nestin in tumour cells and dysplastic neurons suggests aberrant expression of antigenically primitive proteins in cells to facilitate remodelling of the cell and migration. More studies are needed to elucidate the concept.

Tuberculous skin ulcer following needle-prick injury in a health care professional.

A case of cutaneous inoculation tuberculosis in a 25-year old health care professional is reported. The diagnosis was confirmed by histopathology and isolation of Mycobacterium tuberculosis by BACTEC 460TB radiometric method. Rapid healing of the ulcer was noted in response to surgical debridement and specific anti-tuberculous therapy.

Neuropathology of HIV/AIDS with an overview of the Indian scene.

Neurological manifestations of HIV infection and AIDS are being recognized with a frequency that parallels the increasing number of AIDS cases. Next to sub-Saharan Africa, India has the second largest burden of HIV related pathology, essentially caused by HIV-1 clade C in both the geographic locales, in contrast to USA and Europe. But the true prevalence of HIV related neuroinfections and pathology is not available due to inadequate medical facilities, social stigma and ignorance that lead to underdiagnosis. Neurotuberculosis, followed by cryptococcosis and toxoplasmosis in various combinations are the major neuropathologies reflecting the endemicity and manifesting clinically by reactivation of latent infection. Discordance in the clinical prevalence of various infections, when compared to pathological studies highlight similarities in clinical, radiological modalities of diagnosis and inherent problems in establishing definitive diagnosis. Viral infections appear to be relatively rare. Inspite of heavy burden of HIV/AIDS, HIV associated neoplasia is infrequent, including primary CNS lymphomas. HIV encephalitis and HIV associated dementia are considered infrequent, though systematic studies have just been initiated in various centres. Peripheral neuropathy characteristically manifests with vasculitic neuropathy while diffuse infiltrative lymphocytosis syndrome (DILS) involving nerves has not been reported from India. Spinal cord pathology including vacuolar myelopathy is rare, even in asymptomatic cases. Till now the AIDS cases in India were drug naive but a new cohort of cases following initiation of HAART therapy as a national policy is soon emerging, altering the biology and evolution of HIV/AIDS in India. Lacunae in the epidemiology, diagnosis and study of biology of HIV/AIDS are outlined for future research.

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.