Leucoencefalopatía multifocal progresiva, manifestación inicial en paciente con VIH

RESUMEN La leucoencefalopatía multifocal progresiva es una enfermedad desmielinizante del sistema nervioso central producido por un virus del género Polyomavirus. Las manifestaciones clínicas pueden ser motoras, sensitivas o cognitivas. Se presenta el caso de un paciente masculino de 32 años de edad con un cuadro de 24 horas de evolución de debilidad de miembro superior e inferior izquierdos que inició de manera insidiosa y progresiva, acompañada de disartria y confusión. Por sospecha de vasculitis cerebral versus enfermedad desmielinizante se inicia bolos de corticoides con lo cual mejora la debilidad. Se solicita estudios de laboratorio en la que se confirma sida. La resonancia magnética con Gadolinio en el que se observa lesiones compatibles con leucoencefalopatía multifocal progresiva. Se inicia tratamiento antirretroviral y es dado de alta sin otras complicaciones.

ABSTRACT Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by a virus of the Polyomavirus genus. The clinical manifestations can be motor, sensory or cognitive. We present the case of a 32-year-old male patient with a 24-hour evolution of weakness in the left upper and lower limb that began insidiously and progressively, accompanied by dysarthria and confusion. Due to suspicion of cerebral vasculitis versus demyelinating disease, corticosteroid boluses are started, which improves weakness. Laboratory studies are requested in which AIDS is confirmed. Gadolinium magnetic resonance imaging shows lesions compatible with progressive multifocal leukoencephalopathy. Antiretroviral treatment is started and he is discharged without other complications.

Importancia diagnóstica de leucoencefalopatía multifocal progresiva cerebelosa

RESUMEN Introducción: La leucoencefalopatía multifocal progresiva es una enfermedad desmielinizante del sistema nervioso central, de etiología viral. Se presenta en pacientes con enfermedades inmunosupresoras y la localización en fosa posterior es rara. Debido a sus formas clínicas inespecíficas se hace infrecuente su diagnóstico lo que conlleva a daño irreversible y/o a la muerte del paciente. Objetivo: Orientar sobre la posibilidad de leucoencefalopatía multifocal progresiva cerebelosa en pacientes inmunodeprimidos con manifestaciones neurológicas de daño en fosa posterior. Caso clínico: Paciente masculino, de 25 años de edad, sin antecedentes de enfermedades aparentes, que comienza con lenguaje escandido, temblor mixto dismetría y ataxia. Se diagnostica leucoencefalopatía multifocal progresiva cerebelosa por cuadro clínico, neuroimagen y presencia de virus JC en líquido cefalorraquídeo, además de una inmunosupresión severa causada por virus de inmunodeficiencia humana diagnosticado por pruebas serológicas. Conclusiones: Considerar leucoencefalopatía multifocal progresiva cerebelosa en todo paciente con manifestaciones neurológicas de afectación en fosa posterior y estudiar causas de inmunosupresión subyacente.

ABSTRACT Introduction: Progressive multifocal leukoencephalopathy is a demyelinating disease of viral etiology that affects the central nervous system. It presents in patients with immunosuppressive conditions and location in the posterior fossa is rare. Due to its unspecific clinical forms, its diagnosis is infrequent, leading to irreversible damage and/or the patient's death. Objective: Instruct about the possibility of cerebellar progressive multifocal leukoencephalopathy in immunocompromised patients with neurological manifestations of posterior fossa damage. Clinical case: A case is presented of a male 25-year-old patient without apparent pathological antecedents who started out with slurred speech, mixed tremor, dysmetria and ataxia. Cerebellar progressive multifocal leukoencephalopathy was diagnosed by clinical picture, neuroimaging and the presence of JC virus in the cerebrospinal fluid, alongside severe immunosuppression caused by human immunodeficiency virus diagnosed by serological testing.

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.

The latest progress on JC virus infection after renal transplantation / 器官移植

JC virus (JCV) is a member of polyomaviridae family that infects approximately 70% of the population worldwide. JCV constantly stays in a latent state after the primary infection. In immunosuppressed individuals, especially under the circumstances of low cellular immune function, JCV may be reactivated and lead to severe clinical manifestations. In recent years, the correlation between JCV and complications after renal transplantation has captivated widespread attention. JCV-associated nephropathy (JCVAN) has been reported. Here, latest research progresses on the epidemiology, molecular biology, in vivo infection process, JCV and complications after renal transplantation, and the relationship between JCV and BKV were reviewed, aiming to provide reference for the adjustment of immunosuppressive regimen following renal transplantation.

Leucoencefalopatía multifocal progresiva en mujer con SIDA

RESUMEN La leucoencefalopatía multifocal progresiva es una de las diversas entidades clínicas con compromiso del sistema nervioso central causada por el virus JC en pacientes con infección por VIH o en algún otro estado de inmunocompromiso. Es una enfermedad sin tratamiento específico efectivo demostrado. Se presenta el caso de una paciente de 33 años de edad con SIDA que desarrolló esta enfermedad con deterioro progresivo del estado general hasta que se produjo su deceso a los 7 días de internación.

ABSTRACT Progressive multifocal leukoencephalopathy is one of several clinical entities with compromise of the central nervous system caused by the JC virus in patients with HIV infection or in some other state of immunocompromise. It is a disease without proven effective specific treatment. We present the case of a 33-year-old patient with AIDS who developed this disease with progressive deterioration of the general condition until her death occurred 7 days after hospitalization.

High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE: The anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS. METHODS: The antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients. RESULTS: The overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52–4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years). CONCLUSIONS: The seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.

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)

Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica / 한국역학회지

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica / 한국역학회지

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

Difficult intubation of a patient with progressive multifocal leukoencephalopathy and muscle spasticity: A case report

Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease characterized by neurological deficits, including cognitive impairment, altered mental status, and muscle spasticity. Preoperative evaluation and intraoperative airway management of the airway is difficult in patients with this disease. In this report, the authors describe a 62-year-old man with PML and spastic hemiparesis, who was scheduled for video-assisted thoracic bullectomy under general anesthesia. A preoperative airway evaluation, including Mallampati classification, could not be performed due to lack of patient cooperation. Additionally, the anesthesiologist did not perform diverse physical assessments of the airway or prepare an adequate airway management strategy. During induction of general anesthesia, difficulty with intubation was encountered because of limited mouth opening. This case emphasizes that anesthesiologists should have thorough knowledge of airway assessment and management strategies, and perform a comprehensive assessment to implement appropriate airway management in patients with this disease.

Progressive Multifocal Leukoencephalopathy after Ibrutinib Therapy for Chronic Lymphocytic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.

Natalizumab-Related Progressive Multifocal Leukoencephalopathy-Immune Reconstitution Inflammatory Syndrome: A Case Report Highlighting Clinical and MRI Features

Multiple sclerosis (MS) patients treated with natalizumab often face the uncommon but severe complication of developing progressive multifocal leukoencephalopathy (PML). PML may be further complicated by immune reconstitution inflammatory syndrome (IRIS) after the removal of the drug. Since both PML and IRIS are associated with high morbidity and mortality rates, early clinical and radiological diagnosis of these complications is of paramount importance. Here, we report a case of an adult male patient who was diagnosed with PML after receiving natalizumab therapy for 6 years for the treatment of MS. Upon cessation of natalizumab, he presented with a paradoxical worsening of clinical and radiological findings consistent with an inflammatory brain injury due to IRIS. He was treated with high dose corticosteroid therapy followed by a gradual improvement in clinical and imaging findings. This article illustrates the magnetic resonance imaging (MRI) features of natalizumab‑associated PML-IRIS, along with a brief overview of its clinical features, complications and management strategies.

Different methods for JC virus detection / 中华微生物学和免疫学杂志

John Cunningham virus(JCV)is a type of human polyomavirus. It was first isolated from the brain of a patient with progressive multifocal leukoencephalopathy(PML)in 1971 and named after that patient. The seroprevalence of JCV in the general population is 40% to 60% . The mortality rate among patients with AIDS complicated by PML was shown to be 50% . For immunocompromised patients and pa-tients with long-term use of immunosuppressive drugs,JCV would cause fatal polyomavirus associated ne-phropathy(PVAN),viremia and some other related diseases. While the pathogenesis of JCV has well stud-ied,there are no specific prevention and treatment measures for infected individuals. Therefore,reliable, specific and sensitive JCV detection methods in clinical settings are needed. This review describes the pros and cons of different methods for JCV detection with potentials for clinical applications.

Progressive multifocal leukoencephalopathy in non HIV, splenectomised, 66 years old male A rare case report.

Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive AIDS-defining disease of the central nervous system. PML affects up to 8% of patients with AIDS and in most cases is fatal within 3–5 months. We presented here a case of 66 years old male who is non HIV with past history of splenectomy, and diagnosed as progressive multifocal leukoencephalopathy which is very rare. Here, we presented this rare entity which may be difficult to diagnose although, histopathological examination helps greatly in the diagnosis of this condition but the specificity and sensitivity of JC virus DNA PCR in CSF are quite acceptable.

Leucoencefalopatía multifocal progresiva asociada al uso de Natalizumab en un paciente con esclerosis múltiple. Primer caso en Latinoamérica. Hospital de San José - Bogotá 2013 / Progressive Multifocal Leukoencephalopathy associated with the use of Natalizumab in Patient with Multiple Sclerosis. First Case Report in Latin America Hospital de San Jose - Bogota, 2013

La Leucoencefalopatía Multifocal Progresiva (LMP) es una condición grave secundaria a la infección por virusJohn Cunningham (VJC) derivada de la deficiencia de inmunidad celular innata o adquirida. Se presenta el primercaso reportado en Latinoamérica de (LMP) asociada a Natalizumab (NZB) en un paciente con diagnóstico deesclerosis múltiple recaída-remisión, quien ingresa a urgencias con cuadro clínico de deterioro cognoscitivo,comportamental, motor y de lenguaje de curso progresivo. Se realizaron neuroimágenes con resonancia magnéticacerebral sugestivas de LMP, estudios de reacción en cadena de polimerasa en líquido cefalorraquídeopara virus JC, que resultaron negativos en dos oportunidades; el diagnóstico se confirmó mediante la técnica dehibridación in situ en biopsia cerebral. Se realiza este reporte con el fin de resaltar la importancia de la vigilanciaclínica y paraclínica en los pacientes con esclerosis múltiple que reciben NZB...

Progressive Multifocal Leukoencephalopathy (PML) is a serious condition secondary to John Cunninghamvirus (JCV) infection derived from an innate or acquired cellular immunity deficiency. We present the firstreported case in Latin America of PML associated with Natalizumab (NZB) in a patient with a diagnostic ofrelapsing – remitting multiple sclerosis, who entered the emergency room with progressive cognitive, behavioral,motor and language impairment. Neuroimaging performed with magnetic resonance imaging was suggestiveof PML. Polymerase chain reactions in cerebrospinal fluid for JC virus were conducted twice with negativeresults. Finally the diagnosis was confirmed by in situ hybridization technique on brain biopsy. This reportis made in order to highlight the importance of clinical and paraclinical monitoring in patients with multiplesclerosis receiving NZB...

A Case of Progressive Multifocal Leukoencephalopathy in Acquired Immune Deficiency Syndrome Initially Presented with Early Onset Dementia

Progressive multifocal leukoencephalopathy (PML) is a very rare and often fatal demyelinating disease of central nervous system (CNS), which mostly occurs in patients with immunosuppression such as acquired immunodeficiency syndrome (AIDS) patients, transplant patients and patients receiving chemotherapy. PML usually manifests with acute or subacute neurologic deficit. and its late diagnosis may lead death or significant permanent disability. We report a 33-year old man diagnosed with PML in AIDS, who initially presented with gradual onset of dementia. Most symptoms of PML were progressed rapidly for several months, and characterized by focal neurological symptoms. On the other hand, we were experienced in patients without focal neurological symptoms and ongoing overall cognitive decline slowly. Patients with immunosuppression can be presented in a variety of neurological symptoms, detailed examinations for cognitive functions were needed in early stage of the disease.

Diagnosis of acquired leukoencephalopathies in children / 中华实用儿科临床杂志

Leukoencephalopathy is a group of heterogeneous disorders,which mainly affect the cerebral white matter.Both genetic and acquired etiology can lead to these disorders.The diagnosis of several acquired leukoencephalopathy was described,focused on new definitions in diagnosis of demyelination in central nervous system.

Leucoencefalopatía multifocal progresiva (LMP) con cd4 > 200 mm3 / Progressive multifocal leukoencephalopathy (PML) with cd4> 200 mm3

Introducción: La LMP es una enfermedad causada por el virus JC.Afecta la sustancia encefálica provocando desmielinización progresiva. La infección se produce en la infancia y es en general asintomática. En condiciones de inmunosupresión, adquiere potencial neuropatógeno destruyendo los oligodendrocitos. Generalmente se presenta en pacientes bajo tratamiento QMT o personas HIV + CD4<100 mm3. Objetivos:presentación de un caso clínico y revisión bibliográfica. Reporte de caso: Paciente de 37 años, con diagnóstico reciente HIV, en tratamiento con antirretrovirales, inicia cuadro clínico com impotencia funcional en miembro inferior izquierdo. En un mes, el paciente evolucionó con progresión del foco neurológico,desarrollando plejía FBC izquierda + plejía crural derecha, disartria, trastornos deglutorios, desorientación culminando finalmente condeterioro del sensorio. El paciente fallece a los dos meses derealizado el diagnóstico.Discusión: El diagnóstico de LMP debe plantearse ante um paciente inmunodeprimido, que presenta un cuadro de deterioro cognitivo o déficit neurológico de curso progresivo. La mayoría delos casos ocurre en HIV + con recuento de CD4 muy bajos. Aunque no existe tratamiento específico para LMP, las terapias antirretrovirales de alta potencia (HAART) parecen influir en la supervivência.

Introduction: PML is a disease caused by the JC virus. It affects the brain substance causing progressive demyelination. The infection occurs in childhood and is generally asymptomatic. Under conditions of immunosuppression, acquired destroying oligodendrocytes neuropathogenic potential. It usually occurs in patients receiving QMT or HIV + CD4 <100 mm3. Objectives: clinical case report and literature review. Case report: Patient 35 years old, with newly diagnosed HIV in antiretroviral therapy, clinical starts with loss of function of the left lower limb. In one month, the patient developed focal neurologic progression, developing hemiplegia FBC crural left + right crural pegia, dysarthria, swallowing disorders, disorientation, culminating with sensory impairment. The patient died two months after the diagnosis. Discussion: The diagnosis of PML should be raised in an immunocompromised patient, presented symptoms of cognitive decline or neurological deficits progressive course. Most cases occur in HIV + with very low CD4 count. Although there is no specific treatment for PML, antiretroviral.

Nearly one-half of Brazilian patients with multiple sclerosis using natalizumab are DNA-JC virus positive / Cerca de metade dos pacientes brasileiros recebendo natalizumabe para tratamento de esclerose multipla tem DNA-JC virus positivo

Objective Natalizumab is a new and efficient treatment for multiple sclerosis (MS). The risk of developing progressive multifocal leukoencephalopathy (PML) during the use of this drug has created the need for better comprehension of JC virus (JCV) infection. The objective of the present study was to assess the prevalence of JCV-DNA in Brazilian patients using natalizumab. Method Qualitative detection of the JCV in the serum was performed with real-time polymerase chain reaction (PCR). Results In a group of 168 patients with MS who were undergoing treatment with natalizumab, JCV-DNA was detectable in 86 (51.2%) patients. Discussion Data on JCV-DNA in Brazil add to the worldwide assessment of the prevalence of the JCV in MS patients requiring treatment with natalizumab. .

Objetivo Natalizumabe é um tratamento novo e eficaz para esclerose múltipla (EM). O risco constatado de desenvolver leucoencefalopatia multifocal progressiva (LEMP) durante o uso desta droga criou a necessidade de melhor estudar a infecção pelo vírus JC (JCV). O objetivo do presente estudo foi avaliar a prevalência de DNA-JCV em paciente brasileiros usando natalizumabe. Método Detecção qualitativa de JCV no soro foi realizada através de reação em cadeia por polimerase (PCR) em tempo real. Resultados DNA-JCV foi detectado em 86 pacientes (51,2%) de um grupo de 168 pessoas com EM recebendo tratamento com natalizumabe,). Discussão Dados do DNA-JCV no Brasil complementam as avaliações mundiais sobre a prevalência de JCV em pacientes com EM que necessitam tratamento natalizumabe. .