Assuntos
Imunossupressores/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/psicologia , Natalizumab/efeitos adversos , Adulto , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Diagnóstico Precoce , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Masculino , Memória , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/psicologia , Natalizumab/uso terapêutico , Testes Neuropsicológicos , Desempenho Psicomotor , Curva ROC , Estudos RetrospectivosRESUMO
The introduction of highly active antiretroviral therapy does not seem to have altered the incidence of progressive multifocal leukoencephalopathy (PML) in HIV infection. Moreover, the occurrence of a HIV-related leukoencephalopathy, called not determined leukoencephalopaties (NDLE), has been reported. As neuropsychological impairment remains highly prevalent in HIV infection, the aim of this study is to describe the neuropsychological profile of PML and NDLE patients, analyzing the time-related changes. Clinical and neuropsychological data from 32 patients (17 PML, 15 NDLE) were compared with two control groups: (1) asymptomatic HIV+ patients without magnetic resonance imaging evidence of leukoencephalopathy; (2) age-/gender-/education-matched healthy subjects. Patients with rapidly worsening PML were significantly impaired on all neuropsychological tests, while PML with more benign course and NDLE groups showed a dysexecutive pattern of impairment. Asymptomatic HIV+ subjects showed mild and isolated cognitive deficits, without functional impact. Cognitive impairment should therefore be considered a key feature from HIV infection diagnosis.
Assuntos
Infecções por HIV/psicologia , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/psicologia , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/virologia , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus infection and with a frequent lethal outcome. PML usually occurs in immunocompromised subjects, such as HIV-positive individuals, as well as in other conditions characterized by depletion of cellular immunity, including hematological malignancies, autoimmune diseases, and immunomodulatory therapies. We describe the case of a 76-year-old man affected by advanced non-small cell lung cancer who developed PML after six cycles of carboplatin/gemcitabine therapy, during which a transitory leucopenia developed. The patient deceased a few months after the onset of the symptoms. Chemotherapy appears to be uncommon, but definite condition associated to PML.
Assuntos
Adenocarcinoma/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Neoplasias Pulmonares/complicações , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/psicologia , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , GencitabinaAssuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Confusão/etiologia , Dermatomicoses/diagnóstico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Dermatopatias Papuloescamosas/etiologia , Tinha do Couro Cabeludo/diagnóstico , Complexo AIDS Demência/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Atrofia , Edema Encefálico/etiologia , Candidíase Bucal/complicações , Córtex Cerebral/patologia , Dermatomicoses/patologia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Vírus JC , Leucoencefalopatia Multifocal Progressiva/psicologia , Microsporum/isolamento & purificação , Tinha do Couro Cabeludo/microbiologiaRESUMO
OBJECTIVE: To report a new American family with hereditary diffuse leukoencephalopathy with spheroids (HDLS), including serial, presymptomatic and symptomatic, cranial MRIs from the proband. METHODS: We report clinical and genealogic investigations of an HDLS family, sequential brain MRIs of the proband, and autopsy slides of brain tissue from the proband's father. RESULTS: We identified seven affected family members (five deceased). The mean age at symptomatic disease onset was 35 years (range: 20-57), and the mean disease duration was 16 years (range: 3-46). Five affected individuals initially manifested memory disturbance and behavioral changes, whereas two experienced a mood disorder as their presenting symptom. Our proband's father had been diagnosed clinically with vascular dementia, but his brain autopsy was consistent with HDLS. The proband had a cranial MRI prior to symptom onset, with two subsequent MRIs performed during follow-up. These serial images reveal a progressive, confluent, frontal-predominant leukoencephalopathy with symmetric cortical atrophy. CONCLUSIONS: The proband of our newly identified hereditary diffuse leukoencephalopathy with spheroids (HDLS) kindred had subtle evidence of an incipient leukoencephalopathy on a presymptomatic cranial MRI. Conceivably, MRI may facilitate identifying affected presymptomatic individuals within known HDLS kindreds, increasing the likelihood of isolating the causative genes.
Assuntos
Axônios/patologia , Encéfalo/patologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/genética , Adulto , Idoso , Evolução Fatal , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/psicologia , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , LinhagemRESUMO
PURPOSE OF REVIEW: Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. RECENT FINDINGS: Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. SUMMARY: With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/psicologia , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/psicologia , NatalizumabRESUMO
After the introduction of highly active antiretroviral therapy (HAART) in 1996 the neurological manifestations of human immunodeficiency virus (HIV-1)-infection did not decline in incidence and prevalence like the other complications of immunodeficiency; in contrast, due to the longer survival times of HAART treated HIV-1-positive individuals, prevalence of virus associated neurological disease increased during the last years, as international studies underline. Therefore, clinicians and HIV-therapists should be able to diagnose HIV-1-associated neurological disease even in early stages. This article describes symptoms and signs, neuro-imaging and cerebrospinal fluid findings as well as therapy options in primary HIV-1-associated neurological disease like encephalo- and myelopathy and polyneuropathy. Furthermore, those opportunistic infections, caused by bacteria, viruses other than HIV and parasites emerging with manifest immunodeficiency and remaining to be relevant in the HAART era are presented from diagnostic, differential-diagnostic and therapeutic points of view. An extra paragraph describes the interaction of HAART with neurological/psychiatric standard therapies.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Doenças do Sistema Nervoso/etiologia , Complexo AIDS Demência/psicologia , Complexo AIDS Demência/terapia , Criptococose/etiologia , Criptococose/psicologia , Diagnóstico Diferencial , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos , Leucoencefalopatia Multifocal Progressiva/etiologia , Leucoencefalopatia Multifocal Progressiva/psicologia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/psicologia , Testes Neuropsicológicos , Toxoplasmose Cerebral/etiologia , Toxoplasmose Cerebral/psicologiaRESUMO
Progressive multifocal leukoencephalopathy is a progressive and ultimately fatal white-matter disease of the brain that is associated with polyomavirus infection. It is uncommon in the general population, and even in the immunosuppressed patient, who is inherently at greatest risk for active infection with the virus, it is rare. The causative agent in progressive multifocal leukoencephalopathy, JC virus, has become increasingly important in recent years as its role in nephropathy in the renal transplant recipient has become better understood. We present a young renal transplant patient who developed nephropathy with renal biopsy changes consistent with polyomavirus lesions and then developed mental status changes and was diagnosed with progressive multifocal leukoencephalopathy.
Assuntos
Transplante de Rim/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções por Polyomavirus/diagnóstico , Polyomavirus , Infecções Tumorais por Vírus/diagnóstico , Adolescente , Anticorpos Antivirais/sangue , Nitrogênio da Ureia Sanguínea , Encéfalo/patologia , Creatina Quinase/sangue , Eletroencefalografia , Evolução Fatal , Hematócrito , Hemoglobinas/análise , Humanos , Vírus JC/genética , Vírus JC/imunologia , Vírus JC/isolamento & purificação , Transplante de Rim/patologia , Leucoencefalopatia Multifocal Progressiva/complicações , Leucoencefalopatia Multifocal Progressiva/psicologia , Leucoencefalopatia Multifocal Progressiva/virologia , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/psicologia , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/psicologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/psicologia , Infecções Tumorais por Vírus/virologiaAssuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Abuso de Substâncias por Via Intravenosa/complicações , Infecções Oportunistas Relacionadas com a AIDS/psicologia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Leucoencefalopatia Multifocal Progressiva/psicologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Transtornos Cognitivos/etiologia , Leucoencefalopatia Multifocal Progressiva/patologia , Idoso , Feminino , Humanos , Imuno-Histoquímica , Leucoencefalopatia Multifocal Progressiva/complicações , Leucoencefalopatia Multifocal Progressiva/psicologia , Imageamento por Ressonância Magnética , Microscopia Eletrônica , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: Although numerous families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported, our understanding of the disease remains incomplete. Thus, we performed this study to investigate the phenotypic range and natural history of CADASIL. METHODS: We performed a pooled analysis of previously published cases. RESULTS: We identified 105 symptomatic patients in 33 families. Vascular risk factors were uncommon, with hypertension reported in only 8 patients. The mean age of symptom onset was 36. 7+/-12.9 years. Stroke or transient ischemic attack was an initial symptom in 45 patients, with a mean age of onset of 41.2+/-9.2 years. Migraine was also a common initial symptom, reported by 42 patients at a younger mean age of 28.3+/-11.7 years. Other initial symptoms included depression in 9 patients, cognitive impairment in 6 patients, and seizures in 3 patients. Regarding clinical course, 71 patients experienced a stroke or transient ischemic attack, and 52 of those patients had 1 or more recurrent ischemic events. Dementia was reported in 44 patients. Only 3 additional patients experienced migraine at a later time, while 13 additional patients developed depression. Six patients had seizures. Twenty-two of the 105 patients had died, with a mean age of death of 54.8+/-10.6 years. Nineteen of those 22 patients had experienced a stroke or transient ischemic attack and 19 patients were demented. CONCLUSIONS: CADASIL typically becomes evident in early or middle adulthood with migraine or an ischemic event, later manifests itself through recurrent subcortical ischemic strokes leading to a stepwise decline and dementia, and results in reduced survival.
Assuntos
Artérias Cerebrais , Infarto Cerebral/fisiopatologia , Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/fisiopatologia , Genes Dominantes , Leucoencefalopatia Multifocal Progressiva/fisiopatologia , Adolescente , Adulto , Idade de Início , Artérias Cerebrais/fisiopatologia , Infarto Cerebral/epidemiologia , Infarto Cerebral/psicologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/psicologia , Criança , Demência/etiologia , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Leucoencefalopatia Multifocal Progressiva/psicologia , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Mortalidade , SíndromeRESUMO
Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia.
Assuntos
Doenças Arteriais Cerebrais/psicologia , Infarto Cerebral/psicologia , Demência por Múltiplos Infartos/psicologia , Leucoencefalopatia Multifocal Progressiva/psicologia , Encéfalo/patologia , Doenças Arteriais Cerebrais/genética , Doenças Arteriais Cerebrais/patologia , Infarto Cerebral/genética , Infarto Cerebral/patologia , Mapeamento Cromossômico , Cromossomos Humanos Par 19 , Transtornos Cognitivos , Demência por Múltiplos Infartos/genética , Demência por Múltiplos Infartos/patologia , Fator de Crescimento Epidérmico/genética , Humanos , Deficiências da Aprendizagem , Leucoencefalopatia Multifocal Progressiva/genética , Leucoencefalopatia Multifocal Progressiva/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Pele/patologiaRESUMO
OBJECTIVE: To study correlations between total lesion load on brain MRI and clinical features, and to evaluate the influence of demographic variables on quantitative MRI variables in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: CADASIL is a hereditary form of small-vessel disease caused by mutations within the Notch3 gene. MRI abnormalities have been found both in asymptomatic and symptomatic CADASIL individuals. METHODS: Quantitative measurements on cerebral MRI were performed in 64 CADASIL individuals. MRI lesions were quantified using a semi-automated segmentation technique based on local thresholds. RESULTS: MRI total lesion volume correlated significantly with disability (Rankin Scale) on both T1- and proton density (PD)-weighted images. There was a significant inverse correlation between total lesion volume and overall cognitive performance as determined by the Mini-Mental State Examination. Age but not sex was correlated with lesion load both on T1- and PD-weighted images. There was no detectable influence of the Notch3 genotype on quantitative MRI variables. CONCLUSIONS: This study demonstrates correlations between MRI lesion volume and clinical characteristics in CADASIL. Longitudinal studies are now warranted to investigate whether quantitative MRI could be used as an adjunct outcome measure in future therapeutic trials in CADASIL.
Assuntos
Doenças Arteriais Cerebrais/patologia , Infarto Cerebral/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Encéfalo/patologia , Encéfalo/fisiopatologia , Doenças Arteriais Cerebrais/psicologia , Infarto Cerebral/psicologia , Cognição/fisiologia , Avaliação da Deficiência , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/psicologia , Masculino , Pessoa de Meia-IdadeRESUMO
A 43 year-old man with presumed progressive multifocal leukoencephalopathy developed difficulty recognizing objects and faces in the presence of adequate visual acuity and visual fields. His copying and matching of line drawings was intact, suggesting that his agnosia was associative. However, he had difficulty perceiving overlapping forms and drawings of single objects as integrated wholes. Unlike control subjects, he made fewer errors identifying silhouettes compared to line drawings with internal details. These alterations, together with his feature-by-feature descriptions of objects and copying, suggest that his agnosia was due to a disturbance in integrating local form features, as described by Riddoch and Humphreys (1987). This interpretation is supported by the findings that his tactile recognition and semantic and structural knowledge of the objects he could not identify visually were intact. Furthermore, his deficient performance in categorical matching of photographs to objects was dependent upon the perceptual complexity of the photographs. Similar deficits in early form processing described by other investigators are discussed.
Assuntos
Complexo AIDS Demência/fisiopatologia , Agnosia/fisiopatologia , Leucoencefalopatia Multifocal Progressiva/fisiopatologia , Rememoração Mental/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Desempenho Psicomotor/fisiologia , Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/psicologia , Adulto , Agnosia/diagnóstico , Agnosia/psicologia , Anomia/diagnóstico , Anomia/fisiopatologia , Anomia/psicologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Dominância Cerebral/fisiologia , Área de Dependência-Independência , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/psicologia , Masculino , Testes Neuropsicológicos , Orientação/fisiologiaRESUMO
Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.
Assuntos
Adenocarcinoma/secundário , Antineoplásicos , Fluoruracila/análogos & derivados , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Neoplasias Pulmonares/secundário , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adenocarcinoma/tratamento farmacológico , Adulto , Eletroencefalografia/efeitos dos fármacos , Feminino , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/psicologia , Neoplasias Pulmonares/tratamento farmacológico , Testes Neuropsicológicos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tomografia Computadorizada por Raios XRESUMO
A particular semiologic feature of a case of progressive multifocal leukoencephalopathy was the existence of utilization behavior as described by Lhermitte. The affection developed in a patient with myeloid leukemia treated by cytotoxic drugs. Multifocal low density areas were shown by CT Scan examination. The course of the disease was not altered by isoprinozine therapy.