AIDS-related progressive multifocal leukoencephalopathy

Abstract INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of JC virus (JCV). METHODS: We described the profile of laboratory-confirmed PML cases among AIDS patients. RESULTS: A total of 43 HIV patients with clinical conditions compatible with PML were obtained; 5 cases were confirmed by JCV testing. The main clinical finding was mental confusion. Median CD4 count was 54 cells/mm³. CONCLUSIONS: Three of the five confirmed PML cases died; the time between diagnosis and death was 2, 5, and 6 months. It is important to consider JCV infection as a differential diagnosis.

Progressive multifocal leukoencephalopathy: a challenging diagnosis established at autopsy

Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms due to the physicians' unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.

Dementia and behavioral disorders in progressive multifocal leukoencephalopathy (PML) ­ case report / Demência e alterações comportamentais na leucoencefalopatia multifocal progressive (LEMP) ­ relato de caso

Psychiatric disturbances in Progressive Multifocal Leukoencephalopathy (PML) are rarely adressed and its study can offer insights into the neurobiology of psychosis. The authors report a case of male patient, 42 years old, HIV positive, with PML and psychotic symptoms. The present case shows the need for regular neurological and neuropsychological evaluations of HIV positive patients and the importance of studying diseases that cause lesions in the white matter,such as PML, to elucidate the neurobiology of psychosis.(AU)

Os distúrbios psiquiátricos na Leucoencefalopatia Multifocal Progressiva (LEMP) raramente são abordados e seu estudo pode oferecer insights sobre a neurobiologia da psicose. Os autores relatam caso de paciente do sexo masculino, 42 anos, HIV positivo, com LEMP e sintomas psicóticos. O caso apresentado evidencia a necessidade de realização regular de avaliações neurológicas e neuropsicológicas de pacientes HIV positivos e a importância de se estudar doenças que causam lesões na substância branca, como a LEMP, para elucidar a neurobiologia da psicose.(AU)

JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region

Abstract JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215 bp) and IG (610 bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4+/TCD8+ lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.

Use of John Cunningham virus polymerase chain reaction in the diagnosis of progressive multifocal leucoencephalopathy - A rare presenting manifestation in an HIV-positive patient.

John Cunningham virus infection is an important cause of progressive multifocal leucoencephalopathy (PML) in the context of advanced human immunodeficiency virus infection. Limited data are available regarding the true incidence of PML as a presenting manifestation of HIV. We report one such case and also highlight the effective use of polymerase chain reaction in confirming its diagnosis.

Progressive multifocal leukoencephalopathy restricted to the posterior fossa in a patient with systemic lupus erythematosus

Progressive multifocal leukoencephalopathy is a neurological infectious disease caused by the John Cunningham polyomavirus (JCV), an opportunistic agent with worldwide distribution. This disease is frequently seen in immunosuppresed patients and rarely associated with systemic lupus erythematosus. In the central nervous system PML demyelinating lesions occur in the supratentorial compartment. The authors describe a rare case of PML secondary to SLE treatment with atypical presentation restricted to the posterior fossa.

Progressive multifocal leukoencephalopathy as an AIDS-defining condition in a patient with high CD4+ T-lymphocyte count / Leucoencefalopatia multifocal progressiva como condição definidora de AIDS em paciente com contagem alta de linfócitos T CD4

We present the case of a 31-year-old man with acute manifestation of progressive multifocal leukoencephalopathy (PML) as an AIDS-defining disease. The patient presented with a three-day history of neurological disease, brain lesions without mass effect or contrast uptake and a slightly increased protein concentration in cerebrospinal fluid. A serological test for HIV was positive and the CD4+ T-cell count was 427/mm³. Histological examination of the brain tissue revealed abnormalities compatible with PML. The disease progressed despite antiretroviral therapy, and the patient died three months later. PML remains an important cause of morbidity and mortality among HIV-infected patients.

Apresentamos o caso de um homem de 31 anos com leucoencefalopatia multifocal progressiva (LMP) de manifestação aguda como doença definidora de AIDS. O paciente apresentou-se com doença neurológica com três dias de evolução, lesões encefálicas sem efeito de massa ou captação de contraste e leve aumento de proteínas no líquor. Sorologia para o HIV foi positiva e a contagem de linfócitos T CD4+ era de 427/mm³. O exame histológico de tecido cerebral revelou alterações compatíveis com LMP. A doença progrediu a despeito da terapia antirretroviral, e o paciente morreu após três meses. LMP permanece como causa relevante de mortalidade e morbidade em pacientes infectados pelo HIV.

Aids-related progressive multifocal leukoencephalopathy: a retrospective study in a referral center in São Paulo, Brazil / Leucoencefalopatia multifocal progressiva em pacientes com aids: estudo retrospectivo em um centro de referência de São Paulo, Brasil

Few data are available about progressive multifocal leukoencephalopathy (PML) in patients with acquired immunodeficiency syndrome (AIDS) from Brazil. The objectives of this study were to describe the main features of patients with PML and estimate its frequency among AIDS patients with central nervous system (CNS) opportunistic diseases admitted to the Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, from April 2003 to April 2004. A retrospective and descriptive study was performed. Twelve (6 percent) cases of PML were identified among 219 patients with neurological diseases. The median age of patients with PML was 36 years and nine (75 percent) were men. Nine (75 percent) patients were not on antiretroviral therapy at admission. The most common clinical manifestations were: focal weakness (75 percent), speech disturbances (58 percent), visual disturbances (42 percent), cognitive dysfunction (42 percent), and impaired coordination (42 percent). The median CD4+ T-cell count was 45 cells/µL. Eight (67 percent) of 12 patients were laboratory-confirmed with PML and four (33 percent) were possible cases. Eleven (92 percent) presented classic PML and only one case had immune reconstitution inflammatory syndrome (IRIS)-related PML. In four (33 percent) patients, PML was the first AIDS-defining illness. During hospitalization, three patients (25 percent) died as a result of nosocomial pneumonia and nine (75 percent) were discharged to home. Cases of PML were only exceeded by cases of cerebral toxoplasmosis, cryptococcal meningoencephalitis, and CNS tuberculosis, the three more frequent neurologic opportunistic infections in Brazil. The results of this study suggest that PML is not an uncommon HIV-related neurologic disorder in a referral center in Brazil.

Existe informação limitada sobre a presença da leucoencefalopatia multifocal progressiva (LEMP) em pacientes com aids no Brasil. Os objetivos do presente estudo foram descrever as principais características dos pacientes com LEMP e estimar a freqüência desta doença em pacientes com aids e doenças oportunistas do sistema nervoso central (SNC) internados em um centro de referência de São Paulo, Brasil. Neste estudo retrospectivo e descritivo, identificamos 12 (6 por cento) casos de LEMP entre 219 pacientes com doenças neurológicas oportunistas do SNC. A idade média dos pacientes com LEMP foi 36 anos e 9 (75 por cento) eram do sexo masculino. As manifestações clínicas mais freqüentes foram: déficits focais (75 por cento), alterações da fala (58 por cento), alterações visuais (42 por cento), alterações cognitivas (42 por cento), e problemas de coordenação (42 por cento). A média da contagem de células T-CD4+ foi 45 células/µL. Oito (67 por cento) dos 12 pacientes com LEMP tiveram diagnóstico confirmado laboratorialmente e em quatro (33 por cento) casos o diagnóstico foi possível. Onze (92 por cento) pacientes apresentaram LEMP clássica e um caso teve LEMP associada à síndrome de reconstituição imune. Em quatro (33 por cento) pacientes, a LEMP foi a primeira doença definidora de aids. Durante a internação, três pacientes (25 por cento) faleceram devido a pneumonia hospitalar e nove (75 por cento) tiveram alta. A LEMP foi apenas ultrapassada em freqüência pela toxoplasmose cerebral, a meningoencefalite criptococócica e a neurotuberculose, as três mais freqüentes doenças neurológicas oportunistas no Brasil. Os resultados deste estudo sugerem que a LEMP não é uma complicação neurológica incomum em pacientes com infecção pelo HIV no nosso meio.

Progressive multifocal leukoencephalopathy--as a presenting manifestation of AIDS.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic demyelinating disease caused by the ubiquitous, usually non pathogenic JC Polyomavirus. We report a case of PML as a presenting manifestation of AIDS in a forty five year old man on the basis of clinical features and neuroradiology.

Leucoencefalopatia multifocal progressiva em um paciente com leucemia linfoblástica aguda: relato de caso / Progressive multifocal leukoencephalopathy in a patient with acute lymphoblastic leukemia: case report

Leucoencefalopatia multifocal progressiva é uma patologia em que os oligodendrócitos são destruídos pelo Poliomavírus JC, um agente infeccioso comum na infância, que persiste na forma latente. O vírus pode ser ativado em indivíduos imunocomprometidos, particularmente em pacientes com síndrome de imunodeficiência adquirida, linfoma e doença mieloproliferativas crônicas. Relatamos um caso de um jovem portador de leucemia cujos pais queixaram-se de seu distúrbio comportamental há um mês. O diagnóstico foi estabelecido por critérios clínico-radiológicos. Não houve confirmação etiológica por meios anátomo-patológico. O presente estudo aborda aspectos relevantes da apresentação clínica e diagnóstico desta patologia rara, assim como sua associação com a leucemia.

Leucoencefalopatia multifocal progressiva confirmada por PCR para vírus JC no líquor: relato de caso / Progressive multifocal leukoencephalopathy confirmed by PCR for JC virus in cerebrospinal fluid: case report

Relatamos um caso de leucoencefalopatia multifocal progressiva, doença infecciosa desmielinizante do sistema nervoso central, seguido de revisão da literatura. Comenta-se a importância diagnóstica dos métodos de imagem, bem como da análise do líquor e da técnica de reação em cadeia da polimerase (PCR). Até o presente momento, não há terapia efetiva para a condição, com sobrevida média de 1-6 meses nos pacientes não tratados; evolução favorável pode ocorrer no subgrupo de pacientes que obtém melhora da imunidade com o uso de terapia anti-retroviral.

Leucoencefalopatía multifocal progresiva: a propósito de un caso clínico-patológico en un paciente infectado por VIH / Progressive multifocal leukoencephalopathy: a case report of a patient with HIV

Se presenta un caso clínico dee leucoencefalopatía multifocal progresiva (LMP) asociado a VIH, corroborando por estudio anatomopatológico. Se destaca la gran importancia de la introducción de las técnicas de biología molecular en el estudio cefalorraquídeo (LCR), en particular de la reacción en cadena de la polimerasa (PCR), determinando la presencia de JC virus, directamente ligado a la enfermedad, lo cual resuleve la enorme mayoría de los casos. Se expone la indicación precisa de la realización de biopsia cerebral por estereotaxia para el estudio anatomopatológico, por el cual se llega al diagnóstico definitivo de LMP.

Mutation of the Notch 3 gene in a Thai cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family.

The authors report the first Thai family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which the family members had a classical history of progressive vascular dementia. The proband was a 31-year old Thai male who presented with an acute stroke in the subcortical region. His past history revealed mental disturbance, including poor judgement and regressive behavior as well as mood changes for 1 year. He did not have a history of migraine or any other vascular risk factors except for a strong family history of ischemic stroke and progressive dementia. Magnetic resonance imaging demonstrated multiple small infarctions in the subcortical white matter of the bilateral frontal, parietal and occipital lobes with another small lesion in the pons. Genetic study demonstrated a Notch 3 mutation consisting of the substitution of a nucleotide at position 406 in exon 3 leading to the replacement of an Arginine by Cysteine at position 110 in the 2nd EGF motif, which is compatable with CADASIL.