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1/71. Progressive multifocal leukoencephalopathy (PML) and cerebral toxoplasmosis in an adult patient, with no symptoms of underlying immunosuppressing illness.

    We present a case of the coincidence of progressive multifocal leukoencephalopathy (PML) and central nervous system (CNS) toxoplasmosis in an adult patient, without a detectable cause of cell-mediated immunity impairment. The proper diagnosis was made postmortem on the basis of histological changes typical of both pathological processes. PML was characterized by the presence of subcortical focal demyelination, containing enlarged, densely basophilic oligodendrocyte nuclei, often with intranuclear inclusion, and bizarre astrocytes, mimicking neoplastic cells. PML was confirmed by detecting numerous papova virus particles in oligo- and astroglial nuclei by thin-section electron microscopy. Cerebral toxoplasmosis was characterized by the presence of multiple well-circumscribed necrotizing abscesses. Numerous toxoplasma gondii (T. gondii) cysts and free, non-encysted protozoan parasites were found among the inflammatory infiltrates. The diagnosis of cerebral toxoplasmosis was further confirmed by immunocytochemistry. In order to detect putative immunosuppressive background underlying both pathological processes, hiv infection was taken into consideration, however, no histopathological changes indicative of AIDS either in the CNS or in the peripheral organs were eventually found. Moreover no hiv provirus genome was identified in the formalin-fixed, paraffin embedded brain tissue by the polymerase chain reaction (PCR). Current view on the selected aspects of the pathogenesis of both disorders were discussed.
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2/71. Rapidly progressive multifocal leukoencephalopathy with substantial cell-mediated inflammatory response and with cognitive decline of non-Alzheimer type in a 75-year-old female patient.

    autopsy findings of rapidly progressive and widespread multifocal leukoencephalopathy (PML) in a 75-year-old woman with no known predisposing disease are demonstrated. Originally she was given a clinical working diagnosis of syndrome of progressive supranuclear palsy (PSP). The neuropathological investigation revealed widespread white and gray matter changes consistent with PML, and the jc virus was verified by EM, in situ hybridization and immunohistochemistry. In contrast to the few chronic inflammatory cells generally seen in PML in this case there was a substantial cell-mediated inflammatory response reflected in numerous T-helper and T-killer cells. The uncommon, widespread distribution of lesions and substantial cell-mediated response reported might indicate that the rearrangement of viral genome, previously suggested of importance for viral growth in the central nervous system (CNS), is also important for viral spread within the CNS, infectivity of glial cells and for the activation of cell-mediated immunity.
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keywords = nervous system
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3/71. hiv infection and seizures.

    New-onset seizures are frequent manifestations of central nervous system disorders in patients infected with human immunodeficiency virus (hiv). seizures are more common in advanced stages of the disease, although they may occur early in the course of illness. In the majority of patients, seizures are of the generalised type. status epilepticus is also frequent. Associated metabolic abnormalities increase the risk for status epilepticus. Cerebral mass lesions, cryptococcal meningitis, and hiv-encephalopathy are common causes of seizures. phenytoin is the most commonly prescribed anticonvulsant in this situation, although several patients may experience hypersensitivity reactions. The prognosis of seizure disorders in hiv-infected patients depends upon the underlying cause.
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4/71. Progressive multifocal leukoencephalopathy with concurrent Richter's syndrome.

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating infectious disease caused by the jc virus. It was originally described in patients with chronic lymphocytic leukemia (CLL). Richter's syndrome, or transformation to large cell lymphoma, occurs in approximately 3% of patients with CLL, and carries a poor prognosis. We report a patient with documented PML and concurrent Richter's transformation outside the central nervous system. Before establishing a definitive diagnosis of PML, radiation therapy to the presumed lymphomatous brain lesion had been considered, raising the issue of whether stereotactic brain biopsy should be considered in every patient in a similar situation. Although this is likely a rare occurrence, patients with Richter's transformation documented at an extra-neural site and a brain lesion may benefit from the establishment of an infectious diagnosis which would influence therapy.
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5/71. Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia.

    Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disorder of the central nervous system usually affecting immunocompromised individuals and is due to infection of the oligodendrocytes by the jc virus. A case of PML in a chronic lymphocytic leukemia (CLL) patient treated with fludarabine is reported, representing the second such instance in which the diagnosis of the neurological disorder was established by brain biopsy. A 61-year-old man with a 14-year history of B-cell type CLL, for which he had received chlorambucil therapy 10 years earlier, developed progressive paresis of both left extremities at 7 months of receiving low doses of oral fludarabine, when his CD4 count has decreased to 0.08 x 10(9)/l. Cranial magnetic resonance imaging revealed a subcortical focal lesion at the right precentral gyrus and a focal lesion at the right thalamus, and a stereotactic brain biopsy showed pathological findings consistent with PML, namely severe myelin breakdown, reactive astrocytosis, and abnormal, huge glial cells with large bizarre nuclei showing granular basophilic inclusions, whereas the presence of the jc virus was demonstrated by in situ hybridization. The present case, in addition to a few previously reported, calls attention to the possibility that severe neurological side effects can be associated with the immunosuppression provoked by the use of fludarabine in CLL patients.
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6/71. Progressive multifocal leukoencephalopathy (PML) in a patient with silicosis treated previously with steroids. A report of a case with jc virus infection confirmed immunohistochemically and by electron microscopy.

    We present a case of progressive multifocal leukoencephalopathy (PML) diagnosed at autopsy, in which jc virus infection of the central nervous system was confirmed by means of electron microscopy and immunohistochemistry. The patient had been receiving steroid hormones due to suspected sarcoidosis or pneumoconiosis. Diffuse silicosis in lungs and in hilar and mediastinal lymph nodes was diagnosed at autopsy. Intranuclear inclusions, ultrastructurally typical of jc virus were found in some oligodendrocytes in the white matter. However the strongest immunopositive viral deposits were found in the cerebellar cortex, also within purkinje cells. Numerous apparently apoptotic cells seen in white matter suggest that this mechanism of cell elimination plays an important role in PML pathogenesis and hence anti-apoptotic treatment may alleviate the symptoms and prolong survival.
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7/71. Progressive multifocal leukoencephalopathy presenting with an isolated focal movement disorder.

    Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus infection of the central nervous system predominantly affecting immunocompromised patients. Although the basal ganglia circuitry may be involved in the pathology of PML, movement disorders are exceedingly rare as presenting symptoms and have not been described as isolated features in such patients. We report a previously healthy, immunocompetent 24-year-old woman with histologically proven PML who presented with a focal movement disorder of the left arm as an isolated symptom for many months before diagnosis.
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8/71. Visual symptoms after lung transplantation: a case of progressive multifocal leukoencephalopathy.

    After solid organ transplantation, signs and symptoms of the central nervous system may present a diagnostic challenge. A 43-year-old patient developed a decrease in vision 15 months after bilateral lung transplantation. The initial diagnosis was a left posterior cataract, but left eye cataract extraction did not improve his vision. seizures led to investigation of a broader differential diagnosis (cyclosporine intoxication, post-transplant lymphoproliferative disorder, infectious disease, chronic lymphatic leukemia). The clinical diagnosis of progressive multifocal leukoencephalopathy (PML) was confirmed by demonstration of jc virus in the cerebrospinal fluid and by autopsy findings. Modulation of the immunosuppressive regimen was unsuccessful. This case illustrates that decreased vision in immunocompromised patients may be the first manifestation of PML.
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9/71. Concomitant progressive multifocal leucoencephalopathy and primary central nervous system lymphoma expressing jc virus oncogenic protein, large T antigen.

    This report describes the concomitant occurrence of the jc virus (JCV) induced demyelinating disease progressive multifocal leucoencephalopathy (PML) and a primary central nervous system lymphoma (PCNS-L) in a patient with AIDS. Postmortem neuropathological examination revealed characteristic features of PML including multiple lesions of demyelination, enlarged oligodendrocytes with hyperchromatic nuclei (many containing eosinophilic intranuclear inclusions), and enlarged astrocytes with bizarre hyperchromatic nuclei. Immunohistochemical analysis demonstrated the expression of the JCV capsid protein VP-1 in the nuclei of infected oligodendrocytes and astrocytes. The PCNS-L lesion located in the basal ganglia was highly cellular, distributed perivascularly, and consisted of large atypical plasmacytoid lymphocytes. Immunohistochemical examination of this neoplasm identified it to be of B cell origin. Moreover, expression of the JCV oncogenic protein, T antigen, was detected in the nuclei of the neoplastic lymphocytes. This study provides the first evidence for a possible association between JCV and PCNS-L.
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keywords = nervous system
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10/71. methotrexate leukoencephalopathy presenting as kluver-bucy syndrome and uncinate seizures.

    methotrexate causes several biochemical changes that impact the nervous system. The neurotoxicity usually affects the cerebral white matter, causing a leukoencephalopathy that can be chronic and progressive with cognitive decline. A 15-year-old male developed olfactory seizures and behavioral abnormalities (hypersexuality, placidity, and memory disturbances) compatible with partial kluver-bucy syndrome after treatment for central nervous system leukemia with intraventricular methotrexate. A magnetic resonance imaging study revealed evidence of white matter disease affecting both temporal lobes. A brain biopsy revealed a necrotizing encephalopathy compatible with methotrexate-related white matter injury. It may be prudent to verify normal cerebrospinal fluid dynamics before the administration of intraventricular methotrexate in children with a history of central nervous system leukemia.
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ranking = 3
keywords = nervous system
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