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.

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.

La biopsia estereotáctica en el diagnóstico de las lesiones cerebrales focales en sida / Stereotactic brain biopsy in the diagnosis of focal brain lesions in AIDS

Las lesiones cerebrales focales constituyen una complicación frecuente en los pacientes con infección por el virus de la inmunodeficiencia humana (HIV) y síndrome de inmunodeficiencia adquirida (sida). Durante el período comprendido entre enero de 1999 y mayo de 2007 se realizaron un total de 83 biopsias en pacientes con sida y lesiones cerebrales. Se incluyeron aquellos pacientes que no hubiesen respondido al algoritmo habitual de enfoque diagnóstico-terapéutico de estas lesiones. Todas las muestras obtenidas fueron sometidas a evaluación intraoperatoria para asegurar la obtención de material patológico y posterior análisis histopatológico y exámenes microbiológicos. De los 41 pacientes con lesiones cerebrales múltiples, 62 tenían localización supratentorial, en 4 eran infratentoriales y 17 mostraron ambas localizaciones. Cincuenta y un lesiones seleccionadas como blanco estereotáctico tuvieron refuerzo periférico del contraste. Se obtuvo material histopatológico en el 100% de los procedimientos. El diagnóstico más frecuente fue el de leucoencefalopatía multifocal progresiva (LEMP) con 24 casos (29%), seguido del linfoma primario del sistema nervioso central (LPSNC) con 19 diagnósticos (23%) y de toxoplasmosis en 13 pacientes (15.7%). Se comprobó una relación significativa entre los diagnósticos histopatológicos y la localización de las lesiones y entre los diagnósticos histopatológicos y el comportamiento de las imágenes luego de la administración de la sustancia de contraste. El rédito diagnóstico alcanzó el 90.3% (75 biopsias). La morbiletalidad en esta serie fue de 2.4%. La biopsia cerebral estereotáctica permitió alcanzar el diagnóstico etiológico y adecuar el enfoque terapéutico en la mayoría de los pacientes de esta serie.

Focal brain lesions are frequent complications among HIV/AIDS patients. Between January 1999 and May 2007, 83 procedures of stereotactic brain biopsies in HIV/AIDS patients with focal cerebral lesions were carried out. The inclusion criteria were lack of response to current diagnostic and therapeutic guidelines for brain lesions. All the samples underwent microscopic evaluation during surgery to assert valid material and delayed histopathological and microbiological examination. Forty one patient images demonstrated multiple brain lesions. Sixty two cases had supratentorial localization, 4 lesions were located beneath the tentorium and 17 showed both settings. Fifty one lesions presented peripheral enhancement after contrast computed tomography (CT) or magnetic resonance imaging (MRI). A 100% of useful samples recovery was achieved. Progressive multifocal leucoencephalopathy (PML) was the most frequent diagnosis (29%), followed by primary central nervous system lymphoma (PCNSL) (23%), and toxoplasmosis (15.7%). Statistically significant association was observed between histopathological diagnosis and lesion location and between those and peripheral ring enhancement images. The positive diagnostic rate of the invasive procedure was 90.3%. The morbidity/mortality rate was 2.4% in this series. In conclusion, the stereotactic brain biopsy ordered early during the patient’s evolution showed a good performance in order to achieve a prompt and accurate diagnosis and to guide the therapeutic scheme in these AIDS patients with focal brain lesions.

Leucoencefalopatía multifocal progresiva en paciente con SIDA. Presentación de un caso / Progressive multifocal leucoencephalopaty in a patient with aids

Progressive Multifocal Leucoencephalopaty (PML) is an untreatable viral infection of the brain white matter, seen in persons with very advanced HIV infection.

Leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate: report of three brazilian patients

A novel leukoencephalopathy was recently identified based on magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (¹H-MRS) findings. Leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL) is an autosomal recessive disorder characterized by early onset of symptoms and slowly progressive cerebellar, pyramidal and spinal cord dorsal column dysfunction. MRI and ¹H-MRS typically show abnormalities within cerebral and cerebellar white matter, a characteristic involvement of brainstem and spinal cord tracts and elevated lactate in the abnormal white matter. We present three cases with characteristic clinical and neuroimaging findings of this disorder. Some additional unique findings of our patients are discussed, like distal motor neuropathy and elevated creatine kinase in the serum.

Uma nova leucoencefalopatia foi recentemente descrita com base em achados característicos de ressonância magnética e espectroscopia de prótons por ressonância magnética. Leucoencefalopatia com envolvimento do tronco cerebral e da medula espinal e elevação do lactato cerebral é uma doença autossômica recessiva de aparecimento precoce e evolução lenta, caracterizada por disfunção cerebelar, piramidal e das colunas dorsais da medula. Ressonância magnética e espectroscopia de prótons tipicamente demonstram anormalidades na substância branca cerebral e cerebelar, com envolvimento característico de tratos no tronco encefálico e na medula espinhal e aumento de lactato na substância branca cerebral anormal. Relatamos três casos com achados clínicos e de neuroimagem característicos. Achados adicionais peculiares aos nossos pacientes são discutidos, como a elevação da creatina-quinase sérica e a presença de neuropatia motora distal.

Meningitis linfomatosa como sitio de recaída en la enfermedad de Hodgkin / Limphomatous meningitis as recurrence site in Hodgkin's disease

Intracraneal manifestations of Hodgkin's Disease (HD) are extremely rare, with an estimated incidence rate of approximately 0.5%. They can be classified as: 1) treatment-related leucoencephalopathy, 2) central nervous system infections, 3) paraneoplasic syndromes and 4) intracraneal lymphomas, which could be sub-classified into intraparenchymal or intradural masses. We describe a case of a 40 year-old male with mixed cellularity type HD who developed neurological manifestations as relapsed disease. Magnetic resonance imaging suggested leptomeningeal metastases and atypical cells were found in cerebrospinal fluid. The patient died from progressive disease refractory to third line chemotherapy. There are less than 50 similar cases reported in the literature. We review the clinical features and differential diagnosis of leptomeningeal metastases in Hodgkin's disease.

Head tremor and progressive multifocal leukoencephalopathy in AIDS patients: report of two cases

A leucoencefalopatia multifocal progressiva (LMP) é causada pela replicação do vírus JC em oligodendrócitos de pacientes imunocomprometidos. As manifestações mais comuns incluem déficits motores e sensitivos, alterações da marcha, da fala e da linguagem, cefaléia e distúrbios visuais e cognitivos. Embora a presença de distúrbios do movimento não seja tão freqüente na LMP, bradicinesia, rigidez, abalos mioclônicos e ataxia mioclônica já foram descritos. Nós relatamos dois casos de LMP associados com tremor cefálico.

Leucoencefalopatia multifocal progressiva como manifestação inicial da síndrome da imunodeficiência adquirida / Progressive multifocal leukoencephalopathy as initial manifestation of acquired immunodeficiency

This is a report of a man with acquired immunodeficiency syndrome (AIDS) who presented acutely ill with severe progressive multifocal leukoencephalopathy (PML) as the first manifestation of AIDS. PML was diagnosed in the brain after gross and microscopical examination as well as by immunohistochemistry with an antibody against JC virus.

Relata-se caso de homem portador da Síndrome da Imunodeficiência Adquirida que apresentou quadro agudo e grave de Leucoencefalopatia Multifocal Progressiva (LMP) como primeira manifestação da Síndrome. A LMP foi caracterizada macro e microscopicamente e através de estudo imuno-histoquímico utilizando o anticorpo antivírus JC.

Biópsia cerebral estereotáxica em pacientes com Aids com sintomas neurológicos / Stereotaxic brain biopsy in AIDS patients with neurological manifestations

Estudo prospectivo mostrando a importância da biópsia cerebral estereotáxica no manuseio do paciente com AIDS e que apresenta sintomatologia neurológica confirmada através de imagens. Todos estes pacientes obedecem a escalonamento terapêutico e, depois de terem sido dados os passos prévios, a biópsia passa a ser indicada visando ao diagnóstico etiológico adequado. O protocolo foi iniciado em agosto-1995 e concluído em dezembro-1996. Vinte pacientes foram biopsiados. Nosso protocolo é semelhante ao descrito por Levy e col. (Chicago IL, USA). Linfoma primário foi o diagnóstico predominante, seguido de leucoencefalopatia multifocal progressiva, toxoplasmose e leucoencefalopatia pelo HIV. Um caso de linfoma de células gigantes diplóico foi incluído. Nossa morbi/mortalidade foi nula. Por esta amostragem é possível concluir que a biópsia cerebral estereotáxica é um procedimento seguro e eficaz em pacientes com AIDS.

Sudden appearance of multiple brain lesions in Aids after a cerebral biopsy. Case report

A unique case of cerebral toxoplasmosis which had an acute appearance of multiple discrete lesions following a biopsy and its neuroradiological findings are reported in detail. Possible pathophysiological mechanism are presented

Escanografia en las enfermedades de la sustancia blanca / CT scan in the diagnosis of the white matter diseases

La escanografia cerebral ha permitido visualizar las lesiones producidas por enfermedades de la sustancia blanca, lo cual ayuda al clinico a confirmar el diagnostico y a establecer el pronostico. En este articulo se analizan las enfermedades mas importantes en las cuales la escanografia juega un papel fundamental en el diagnostico.