Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 16 de 16
Filter
2.
Neurol Sci ; 32(5): 833-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21630038

ABSTRACT

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.


Subject(s)
HIV Infections/psychology , JC Virus/isolation & purification , Leukoencephalopathy, Progressive Multifocal/psychology , Adult , Aged , Antiretroviral Therapy, Highly Active , Female , HIV Infections/drug therapy , HIV Infections/virology , Humans , Leukoencephalopathy, Progressive Multifocal/drug therapy , Leukoencephalopathy, Progressive Multifocal/virology , Male , Middle Aged , Neuropsychological Tests
3.
Neurol Sci ; 32(4): 683-5, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21327396

ABSTRACT

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.


Subject(s)
Adenocarcinoma/complications , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukoencephalopathy, Progressive Multifocal/chemically induced , Lung Neoplasms/complications , Adenocarcinoma/drug therapy , Adenocarcinoma of Lung , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Fatal Outcome , Humans , Immunocompromised Host , Leukoencephalopathy, Progressive Multifocal/pathology , Leukoencephalopathy, Progressive Multifocal/psychology , Lung Neoplasms/drug therapy , Magnetic Resonance Imaging , Male , Tomography, X-Ray Computed , Gemcitabine
5.
Neurology ; 71(12): 925-9, 2008 Sep 16.
Article in English | MEDLINE | ID: mdl-18794495

ABSTRACT

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.


Subject(s)
Axons/pathology , Brain/pathology , Leukoencephalopathy, Progressive Multifocal/diagnosis , Leukoencephalopathy, Progressive Multifocal/genetics , Adult , Aged , Fatal Outcome , Female , Humans , Leukoencephalopathy, Progressive Multifocal/psychology , Magnetic Resonance Imaging , Male , Memory Disorders/etiology , Mental Disorders/etiology , Middle Aged , Pedigree
6.
Curr Opin Neurol ; 19(4): 341-9, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16914971

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Leukoencephalopathy, Progressive Multifocal/chemically induced , Multiple Sclerosis/drug therapy , Adult , Antibodies, Monoclonal, Humanized , Crohn Disease/complications , Crohn Disease/drug therapy , Female , Humans , Leukoencephalopathy, Progressive Multifocal/pathology , Leukoencephalopathy, Progressive Multifocal/psychology , Magnetic Resonance Imaging , Male , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/psychology , Natalizumab
7.
Fortschr Neurol Psychiatr ; 73(10): 577-86, 2005 Oct.
Article in German | MEDLINE | ID: mdl-16217698

ABSTRACT

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.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/complications , Nervous System Diseases/etiology , AIDS Dementia Complex/psychology , AIDS Dementia Complex/therapy , Cryptococcosis/etiology , Cryptococcosis/psychology , Diagnosis, Differential , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Leukoencephalopathy, Progressive Multifocal/etiology , Leukoencephalopathy, Progressive Multifocal/psychology , Nervous System Diseases/diagnosis , Nervous System Diseases/psychology , Neuropsychological Tests , Toxoplasmosis, Cerebral/etiology , Toxoplasmosis, Cerebral/psychology
8.
J Child Neurol ; 19(4): 301-4, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15163098

ABSTRACT

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.


Subject(s)
Kidney Transplantation/adverse effects , Leukoencephalopathy, Progressive Multifocal/diagnosis , Polyomavirus Infections/diagnosis , Polyomavirus , Tumor Virus Infections/diagnosis , Adolescent , Antibodies, Viral/blood , Blood Urea Nitrogen , Brain/pathology , Creatine Kinase/blood , Electroencephalography , Fatal Outcome , Hematocrit , Hemoglobins/analysis , Humans , JC Virus/genetics , JC Virus/immunology , JC Virus/isolation & purification , Kidney Transplantation/pathology , Leukoencephalopathy, Progressive Multifocal/complications , Leukoencephalopathy, Progressive Multifocal/psychology , Leukoencephalopathy, Progressive Multifocal/virology , Magnetic Resonance Imaging , Male , Mental Disorders/complications , Mental Disorders/psychology , Polymerase Chain Reaction , Polyomavirus Infections/complications , Polyomavirus Infections/psychology , Polyomavirus Infections/virology , Tumor Virus Infections/complications , Tumor Virus Infections/psychology , Tumor Virus Infections/virology
10.
Stroke ; 30(6): 1230-3, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10356105

ABSTRACT

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.


Subject(s)
Cerebral Arteries , Cerebral Infarction/physiopathology , Cerebrovascular Disorders/genetics , Cerebrovascular Disorders/physiopathology , Genes, Dominant , Leukoencephalopathy, Progressive Multifocal/physiopathology , Adolescent , Adult , Age of Onset , Cerebral Arteries/physiopathology , Cerebral Infarction/epidemiology , Cerebral Infarction/psychology , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/psychology , Child , Dementia/etiology , Female , Humans , Ischemic Attack, Transient/physiopathology , Leukoencephalopathy, Progressive Multifocal/psychology , Male , Middle Aged , Migraine Disorders/physiopathology , Mortality , Syndrome
11.
J Neurol Sci ; 163(2): 163-7, 1999 Mar 01.
Article in English | MEDLINE | ID: mdl-10371078

ABSTRACT

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.


Subject(s)
Cerebral Arterial Diseases/psychology , Cerebral Infarction/psychology , Dementia, Multi-Infarct/psychology , Leukoencephalopathy, Progressive Multifocal/psychology , Brain/pathology , Cerebral Arterial Diseases/genetics , Cerebral Arterial Diseases/pathology , Cerebral Infarction/genetics , Cerebral Infarction/pathology , Chromosome Mapping , Chromosomes, Human, Pair 19 , Cognition Disorders , Dementia, Multi-Infarct/genetics , Dementia, Multi-Infarct/pathology , Epidermal Growth Factor/genetics , Humans , Learning Disabilities , Leukoencephalopathy, Progressive Multifocal/genetics , Leukoencephalopathy, Progressive Multifocal/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Skin/pathology
12.
Clin Neuropathol ; 18(3): 113-23, 1999.
Article in English | MEDLINE | ID: mdl-10361995

ABSTRACT

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.


Subject(s)
Cognition Disorders/etiology , Leukoencephalopathy, Progressive Multifocal/pathology , Aged , Female , Humans , Immunohistochemistry , Leukoencephalopathy, Progressive Multifocal/complications , Leukoencephalopathy, Progressive Multifocal/psychology , Magnetic Resonance Imaging , Microscopy, Electron , Time Factors , Tomography, X-Ray Computed
13.
Neurology ; 52(7): 1361-7, 1999 Apr 22.
Article in English | MEDLINE | ID: mdl-10227618

ABSTRACT

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.


Subject(s)
Cerebral Arterial Diseases/pathology , Cerebral Infarction/pathology , Leukoencephalopathy, Progressive Multifocal/pathology , Magnetic Resonance Imaging/methods , Adult , Aged , Brain/pathology , Brain/physiopathology , Cerebral Arterial Diseases/psychology , Cerebral Infarction/psychology , Cognition/physiology , Disability Evaluation , Female , Humans , Leukoencephalopathy, Progressive Multifocal/psychology , Male , Middle Aged
14.
Cortex ; 30(1): 145-58, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8004984

ABSTRACT

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.


Subject(s)
AIDS Dementia Complex/physiopathology , Agnosia/physiopathology , Leukoencephalopathy, Progressive Multifocal/physiopathology , Mental Recall/physiology , Pattern Recognition, Visual/physiology , Psychomotor Performance/physiology , AIDS Dementia Complex/diagnosis , AIDS Dementia Complex/psychology , Adult , Agnosia/diagnosis , Agnosia/psychology , Anomia/diagnosis , Anomia/physiopathology , Anomia/psychology , Brain Mapping , Cerebral Cortex/physiopathology , Dominance, Cerebral/physiology , Field Dependence-Independence , Humans , Leukoencephalopathy, Progressive Multifocal/diagnosis , Leukoencephalopathy, Progressive Multifocal/psychology , Male , Neuropsychological Tests , Orientation/physiology
15.
Jpn J Psychiatry Neurol ; 44(4): 723-7, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2096243

ABSTRACT

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.


Subject(s)
Adenocarcinoma/secondary , Antineoplastic Agents , Fluorouracil/analogs & derivatives , Leukoencephalopathy, Progressive Multifocal/chemically induced , Lung Neoplasms/secondary , Substance-Related Disorders/etiology , Adenocarcinoma/drug therapy , Adult , Electroencephalography/drug effects , Female , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Leukoencephalopathy, Progressive Multifocal/diagnosis , Leukoencephalopathy, Progressive Multifocal/psychology , Lung Neoplasms/drug therapy , Neuropsychological Tests , Substance-Related Disorders/diagnosis , Substance-Related Disorders/psychology , Tomography, X-Ray Computed
16.
Rev Neurol (Paris) ; 139(4): 307-8, 1983.
Article in French | MEDLINE | ID: mdl-6577526

ABSTRACT

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.


Subject(s)
Impulsive Behavior , Leukoencephalopathy, Progressive Multifocal/psychology , Adult , Humans , Leukemia, Myeloid/complications , Leukoencephalopathy, Progressive Multifocal/complications , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...