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1/157. Virus-cell interaction in oligodendroglia, astroglia and phagocyte in progressive multifocal leukoencephalopathy. An electron microscopic study.

    A 46-year-old female, with an 11 year history of malignant lymphoreticular disease, developed a neurological illness clinically manifested by a focal mass lesion in the left frontal lobe. In biopsied tissue, immunofluorescence study revealed the presence of JC antigen in the glial cells. Histologically, the lesion was characteristic of PML consisting of PML consisting of focal necrosis in the subcortical white matter, numerous fat laden macrophages and marked hypertrophy of oligodendrocytes and astrocytes. By electron microscopy, hypertrophic astrocytes contained intranuclear viral particles consistent with papova virions and aggregates of intracytoplasmic viral particles consisting of a single to several virions tightly surrounded by a single membrane. The membrane appeared to have been derived from that of the cellular vesicles. Fusion of the virus-associated membrane to the astroglial plasmalemma occurred when the virions appeared to shift towards extracellular space. The virioncontaining astrocytes showed cytoplasmic "fibrillar hypertrophy" similar to the characteristic gigantic astroglias of PML. This fact would provide an additional evidence that these gigantic cells, although lacking identifiable viral structures, were the result of anaplastic transformation by jc virus. Many virus-bearing astroglias were noted to be in the early stage of cellular necrosis, of "edematous degeneration". This further indicates that the jc virus is capable of inducing both lytic and abortive astroglial infections. Many oligodendroglias were hypertrophic due to the presence of intranuclear viral particles and markedly increased numbers of microtubules and free ribosomes in the cytoplasm. Membrane-bound intracytoplasmic viral particles were also noted in the oligodendroglias. Some fat laden macrophages contained large intracytoplasmic viral bodies, presumably originating from phagocytized virus-bearing cells.
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ranking = 1
keywords = neurologic
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2/157. 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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ranking = 13.894306095506
keywords = nervous system
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3/157. 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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ranking = 13.894306095506
keywords = nervous system
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4/157. Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus.

    We describe a patient with longstanding systemic lupus erythematosus (SLE) in remission who presented with recent onset neurological symptoms. magnetic resonance imaging, followed by a brain biopsy and in situ hybridization, confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). The clinical findings in this patient emphasize the importance of considering PML in an individual with SLE and neurological abnormalities.
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ranking = 2
keywords = neurologic
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5/157. Successful intrathecal ethanol block for intractable spasticity of AIDS-related progressive multifocal leukoencephalopathy.

    OBJECTIVE: To study the efficacy of intrathecal ethanol block to relieve intractable spasticity in AIDS-related progressive multifocal leukoencephalopathy (PML) when long-term intrathecal baclofen infusion cannot be used. methods: A 33-year-old man with AIDS-related PML developed very severe spastic paraparesis (Ashworth rigidity score, 4) and painful muscle spasms. The patient was unable to sit in his wheelchair and remained bed bound. Combined oral baclofen and tizanidine at therapeutical doses were used without any effect on the spasticity. The patient refused the placement of an intrathecal catheter for long-term baclofen infusion. A single intrathecal ethanol (6 ml) injection in the L2-L3 intervertebral space with the patient placed in a lateral Trendelenburg (40 C) position was performed. RESULTS: The procedure was very effective in improving the stiffness (Ashworth rigidity score. 2, after the technique) and the muscle spasms disappeared. No side effects during or after the injection were observed. CONCLUSION: Intrathecal ethanol block is a last but very useful choice for treatment of intractable spasticity in PML and other neurologic disorders in AIDS patients when other oral treatments have failed and intrathecal baclofen infusion is not suitable.
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ranking = 1
keywords = neurologic
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6/157. 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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ranking = 13.894306095506
keywords = nervous system
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7/157. chorea in patients with AIDS.

    OBJECTIVE: To describe differing etiologies and possible anatomoclinical correlates of choreic movements in a series of AIDS patients. methods: We analyzed the clinical records and neuroimaging data of 5 consecutive AIDS patients who developed choreic movements at our center from January, 1994 to December, 1996. RESULTS: There were 2 cases of focal choreic dyskinesias, 1 of right hemichorea, and 2 of generalized chorea. Onset was acute and febrile in 1 case, and subacute in the other 4. In 1 patient the chorea was the AIDS onset symptom; in another choreic movements were the first neurological symptom following AIDS diagnosis; in 2 patients AIDS had a neurological onset other than chorea; and in the fifth patient buccofacial dyskinesias appeared following the development of bacterial encephalitis. CONCLUSION: chorea was associated with cerebral toxoplasmosis in 2 patients, progressive multifocal leukoencephalopathy in 1, subacute hiv encephalopathy in another, and was probably iatrogenic in the last. chorea is not unusual in AIDS, however the causes are variable and careful neuroradiological and clinical evaluation is required to identify them. AIDS-related disease should be considered in young patients presenting with chorea without a family history of movement disorders.
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ranking = 2
keywords = neurologic
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8/157. Progressive multifocal leukoencephalitis (PML) in three patients treated with standard-dose fludarabine (FAMP).

    Since 1990 we have treated 60 patients with standard-dose fludarabine for chronic lymphocytic leukemia (B-CLL), on a compassionate basis. Three patients developed grade IV neurologic complications after treatment, with demyelination of white matter on magnetic resonance imaging (MRI) in patient # 1, diffuse demyelination, abnormal oligodendroglia and enlarged astrocytes at brain biopsy in patient no 2, and progressive multifocal leukoencephalitis (PML) with jc virus on brain biopsy in patient # 3. The neurotoxicity of fludarabine was often observed after administration of high doses (90-120 mg/m2). At standard doses (18-25 mg/m2) neurologic complications were observed in very few cases (0.2%). PML was observed in only 0.52% of patients with chronic lymphocytic leukemia (CLL), particularly those with advanced CLL. Our findings are consistent with the results of published studies and show an increase in neurologic complications in patients with advanced CLL treated with fludarabine. This increased vulnerability is probably multifactorial, but may be secondary to the immunodeficiency.
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ranking = 4.1662034455863
keywords = neurotoxicity, neurologic, toxicity
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9/157. Progressive multifocal leukoencephalopathy demonstrating contrast enhancement on MRI and uptake of thallium-201: a case report.

    We describe a patient with AIDS who presented with focal neurological symptoms, and who had contrast-enhancing brain lesions on MRI which demonstrated increased thallium-201 uptake on SPECT. These findings were consistent with lymphoma; however, brain biopsy established a diagnosis of progressive multifocal leukoencephalopathy (PML). To our knowledge, this is the first reported case of PML with increased thallium-201 uptake on brain SPECT.
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ranking = 1
keywords = neurologic
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10/157. Leukoencephalopathy in multiple myeloma: two case reports.

    BACKGROUND: No case of leukoencephalopathy has been reported associated with multiple myeloma. patients: We report on two patients with a very rare association of leukoencephalopathy and multiple myeloma revealed by cognitive impairment. RESULTS: Chemotherapy has improved neurological and biological signs. Radiological abnormalities have been stabilized. CONCLUSION: The authors suggest that leukoencephalopathy is probably a direct cerebral expression of malignant gammopathy.
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ranking = 1
keywords = neurologic
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