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Results for “Leukoencephalopathy, Progressive Multifocal”

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PubMed1994

In situ polymerase chain reaction demonstration of JC virus in progressive multifocal leukoencephalopathy, including an index case.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that is caused by JC papovavirus. The virus can be demonstrated in brains with PML using a variety of techniques. In situ polymerase chain reaction (PCR) is a new method that combines the sensitivity of PCR with the histological localization of in situ hybridization. We here show that in situ PCR can detect JC virus in archival tissue sections of 3 cases of PML, including 1 of the original cases described in 1958 and 1 case that was fixed in formalin for 7 weeks. JC virus DNA was amplified directly on tissue and demonstrated in the characteristic enlarged oligodendrocytes and bizarre astrocytes. These data illustrate the utility of the in situ PCR technique in detecting JC virus in archival sections, including those fixed for prolonged periods, and provide a historical footnote to the original report of PML.

Adult↗

PubMed1999

Progressive multifocal leukoencephalopathy.

Before the AIDS epidemic, progressive multifocal leukoencephalopathy (PML) was a rare disorder occurring most often in association with leukemia and lymphoma. Current estimates indicate that PML ultimately develops in up to 5% of all patients with AIDS. This demyelinating disease results from infection with JC virus, a papova virus, that most of the world's population is exposed to prior to adulthood. Although PML commonly occurs in the setting of advanced immunosuppression, it may be observed in patients with CD4 lymphocyte counts in excess of 200 cells/mm3. Focal neurological symptoms and signs coupled with hyperintense signals abnormalities of the white matter on T2-weighted cranial magnetic resonance imaging are highly suggestive of the disease. In this setting, a positive CSF polymerase chain reaction for JCV DNA has been felt to be sufficiently diagnostic to eliminate the need for brain biopsy. Survival of AIDS-associated PML is poor with median survivals averaging just 6 months. However, as many as 10% of AIDS patients with PML will have prolonged (>12 months) survival and partial recovery. Highly active antiretroviral therapy (HAART) has been demonstrated to have a salutary effect on survival.

Humans↗

PubMed2000

JC virus genotypes in France: molecular epidemiology and potential significance for progressive multifocal leukoencephalopathy.

JC virus (JCV) induces progressive multifocal leukoencephalopathy (PML), especially in human immunodeficiency virus (HIV)-infected patients. Although JCV genotypes have primarily been associated with geographic patterns, a distinctive neuropathogenicity was recently attributed to genotype 2. A multicenter study was conducted to describe the distribution of JCV genotypes in France and to investigate correlations between genotypes and PML. Genotypes were determined by sequencing 494 bp in the VP1 capsid gene. Peripheral JCV was studied in 65 urine samples from 43 HIV-infected patients and from 22 control subjects. Genotypes 1, 4, 2, and 3 were detected in 52.3%, 30.8%, 12.3%, and 4.6% of the samples, respectively. In 56 brain or cerebrospinal fluid samples, PML-associated JCV of genotypes 1, 2, 4, and 3 was found in 66%, 19.7%, 8.9%, and 5.4%, respectively. Infection with JCV genotypes 1 or 2 was correlated with PML (odds ratio, 3.29). On the other hand, infection with JCV genotype 4 could represent a lower risk for PML.

AIDS-Related Opportunistic Infections↗

PubMed1994

[Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome].

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection in HIV-infected persons. We present the characteristics of seven cases of PML, which represent 3.1% of our patients with AIDS. In six cases, was the "marker" disease for AIDS. The most common clinical manifestation was a slowly evolving focal neurological syndrome (average time of pre-hospitalization symptoms was 64 days). The number of T4 lymphocytes at the moment of diagnosis varied between 14 and 121 cel/mm3 (median: 51). Computerized tomography (CT) and cranial nuclear magnetic resonance (NMR) showed images of single (4 cases) or multiple white substance involvement without contrast uptake or mass-effect. The definitive diagnosis was made by cerebral biopsy. Four died within 20 to 90 days of diagnosis. Three of the five who received antiretrovirals survived with apparent stabilization of the process at 2, 13, and 23 months of diagnosis. PML can be an initial diagnostic disease for AIDS. Its symptoms and the CT/NMR should arouse suspicion. However, given that clinicoradiological data are often insufficient, it is advisable to conduct cerebral biopsies. Antiretrovirals may have a favorable effect on diseases course.

Acquired Immunodeficiency Syndrome↗

PubMed2005

New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy.

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.

Adult↗

PubMed1997

Diagnostic criteria and clinical procedures in HIV-1 associated progressive multifocal leukoencephalopathy.

The diagnosis of definite progressive multifocal leukoencephalopathy (PML) has been a neuropathological domain. We reviewed all Human Immunodeficiency Virus Type 1 (HIV-1) seropositive patients in our institution between 01.01.1989 and 31.12.1994 and identified 20/823 cases with PML by clinical and imaging criteria. Diagnosis was neuropathologically confirmed in 5 cases. Diagnostic criteria included rapid onset (< 2 weeks) of multifocal neurological signs and symptoms, advanced immunosuppression and asymmetric uni- or multifocal white matter lesions without mass effect, contrast enhancement or cortical atrophy in magnetic resonance imaging (MRI). The overall incidence of PML was stable over the observation period (approximately equal to 2.5%). The mean age at onset (41.7 years) was significantly lower compared to HIV-1 seronegative PML patients (peak in the sixth decade of life), male patients prevailed (100%). Mean survival (3.9 months) was extremely short. Human polyoma virus JC (JCV) polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) demonstrated a considerable rate of possible cerebral co-infection with HIV-1 and JCV as well as subclinical infection with JCV. Therefore demonstration of JCV deoxyribonucleic acid by PCR in the CSF alone is not sufficient for clinical PML diagnosis. We present diagnostic criteria on the basis of epidemiological, neuroradiological and CSF parameters that allow us to make the clinical diagnosis of PML. Although quick and safe, routine stereotactic brain biopsy is not necessary to confirm the diagnosis.

AIDS-Related Opportunistic Infections↗

PubMed2006

Progressive multifocal leukoencephalopathy in purine nucleoside phosphorylase deficiency.

Progressive multifocal leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine nucleoside phosphorylase is an enzyme in the purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with progressive multifocal leukoencephalopathy.

Child↗

PubMed2003

Progressive multifocal leukoencephalopathy in a lung transplant recipient.

Progressive multifocal leukoencephalopathy (PML) is a sub-acute, demyelinating disease of the brain caused by a human polyomavirus. We describe a patient with the onset of PML 7 months after lung transplantation. The patient was treated with immunosuppressive modulation and cidofovir, a new anti-viral therapy for PML, with stabilization of the symptoms. We also review the 4 additional reports in the literature of PML after heart and lung transplantation. Progressive multifocal leukoencephalopathy may become more prevalent as the population of heart and lung transplantation recipients increases.

Humans↗

PubMed1984

Progressive multifocal leukoencephalopathy.

PML is a progressive opportunistic infection of the CNS caused by a commonly occurring virus that may become manifest in the context of reduced host resistance in persons of any age. The authors review the disease and its causes, including a discussion of treatment attempts and differential diagnoses.

Adolescent↗

PubMed2000

[Progressive multifocal leukoencephalopathy an chronic lymphocytic leukemia].

INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease resulting from an opportunistic infection of the central nervous system by JC papovavirus. It mostly occurs in patients with an underlying immunosuppressive disorder. In the era of acquired immunodeficiency syndrome it is observed with increasing frequency. EXEGESIS: We report the case of a non-HIV-infected patient who presented chronic lymphocytic leukemia with progressive multifocal leukoencephalopathy uncovered by both imaging and the presence of JC virus in the cerebrospinal fluid. CONCLUSION: Due to the lack of specific treatment, the disease is still rapidly progressive and fatal.

Aged↗

PubMed2001

[Sarcoidosis and progressive multifocal leukoencephalopathy].

A 70-year-old woman treated for sarcoidosis complained of progressive cognitive impairment and gait disability. Magnetic resonance imaging of the brain revealed a nonenhancing lesion in T1-weighted imaging in the left parieto-occipital region and sarcoidosis of the central nervous system was evoked. However, she rapidly deteriorated with posterior and cerebellar extension of the lesions, suggesting of progressive multifocal leukoencephalopathy (PML). DNA of the JC virus (JCV) was detected in the cerebrospinal fluid (CSF) by a polymerase chain reaction. Despite antiviral therapy, she died nine months after the first neurological signs. This case illustrates the possible association between sarcoidosis and PML, and underlines the interest to detect the presence of JCV in the CSF when the diagnosis of neurosarcoidosis appeared uncertain.

Aged↗

PubMed1995

Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare.

Progressive multifocal leukoencephalopathy, a formerly rare disease that chiefly occurred in persons with underlying lymphoma and chronic lymphocytic leukemia, is now seen with increasing frequency in the era of acquired immunodeficiency syndrome. Progressive multifocal leukoencephalopathy is currently estimated to arise in 5% of all human immunodeficiency virus-infected individuals. The clinical features of the disorder in patients with acquired immunodeficiency syndrome do not appear to be significantly different from progressive multifocal leukoencephalopathy occurring in association with other immunosuppressive disorders. Radiographically, the appearance of HIV dementia on magnetic resonance imaging is sometimes confused with that of progressive multifocal leukoencephalopathy. Among the characteristics that are helpful in distinguishing between the two disorders are the presence of focal findings, the rate of disease progression, the specific magnetic resonance imaging attributes, including the location of the lesions, and certain cerebrospinal fluid parameters, including surrogate markers for human immunodeficiency virus dementia and the presence of myelin basic protein. The remarkable increase in the burden of progressive multifocal leukoencephalopathy has provided a vital impetus for its study, particularly with respect to diagnosis and therapy. Establishing an unequivocal diagnosis of progressive multifocal leukoencephalopathy currently requires brain biopsy. The application of polymerase chain reaction for JC virus amplification to cerebrospinal fluid samples suggests that it may provide an alternative means of diagnosis. Recent in vitro studies of cytosine arabinoside and camptothecin suggest that they, or similar agents, may prove useful in the treatment of this illness and well-designed clinical trials are underway.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Akinetic-rigid syndrome in a 13-year-old girl with HIV-related progressive multifocal leukoencephalopathy.

A 13-year-old HIV-infected girl presented with a rapidly progressive akinetic-rigid syndrome. Cranial magnetic resonance imaging revealed bilateral centrum semiovale lesions extending into the basal ganglia. Detailed histopathological study of a biopsy specimen from the involved regions resulted in a diagnosis of progressive multifocal leukoencephalopathy (PML). This case illustrates that an akinetic-rigid syndrome may be a rare presentation of PML. HIV-related PML may have unusual radiological features. Brain biopsy may be necessary to confirm PML in cases associated with atypical clinical and radiological presentations.

AIDS-Related Opportunistic Infections↗

PubMed1993

Visual loss due to progressive multifocal leukoencephalopathy in a heart transplant patient.

A 59-year-old male heart transplant recipient experienced progressive visual loss following routine cataract surgery with intraocular lens implantation. Cranial magnetic resonance (MR) imaging suggested and brain biopsy confirmed the cause to be progressive multifocal leukoencephalopathy (PML). The patient died 2 months following cataract surgery. This case illustrates that visual failure may be the initial manifestation of PML, and the ophthalmologist should be aware of this central demyelinating disorder when dealing with immunocompromised patients.

Blindness↗

PubMed1996

Primary progressive multifocal leukoencephalopathy presenting as an extrapyramidal syndrome.

We report a 63-year-old woman with a progressive illness which began as a parkinsonian syndrome with bilateral rest tremor, limb rigidity and a gait disorder followed by cognitive decline, visuomotor apraxia and visual agnosia. She died 10 years after the onset of the illness and at autopsy the brain showed characteristic changes of progressive multifocal leukoencephalopathy (PML) with the presence of the JC virus confirmed by in situ hybridisation. Neuropathology also showed some unusual features in the form of atypical linear lesions at the cortico-white matter junction. Some of these lesions were active while others were inactive and similar to the rarely described "burnt out" lesions of PML. PML can in rare cases occur without an underlying immune disorder or malignancy (primary PML) and a parkinsonian syndrome can be produced by a predominantly white matter disorder.

Basal Ganglia Diseases↗

PubMed1983

Multiple malignant astrocytomas in a patient with spontaneous progressive multifocal leukoencephalopathy.

A 67-year-old man with a four-year history of horizontal and vertical nystagmus and progressive cerebellar dysfunction later developed profound dementia and died of bronchopneumonia. Neuropathological examination revealed numerous active and inactive progressive multifocal leukoencephalopathy (PML) lesions in the cerebrum and cerebellum. Active lesions showed marked perivascular lymphocytic cuffing. Papovaviruses were identified ultrastructurally in both oligodendrocytes and astrocytes. Multiple malignant astrocytomas were documented, originating from PML lesions. No viruses could be demonstrated in neoplastic astrocytes. An immune-deficient state was not revealed clinically or at postmortem examination.

Aged↗

PubMed1995

Evaluation of the role of cytokine activation in the multiplication of JC virus (JCV) in human fetal glial cells.

The human polyomavirus, JCV, is the etiologic agent of the fatal central nervous system demyelinating disease, progressive multifocal leukoencephalopathy. Progressive multifocal leukoencephalopathy occurs most frequently in patients with underlying immunosuppressive disorders and is the direct result of virus multiplication in oligodendrocytes, the myelin producing cell in the central nervous system. In this report we test the ability of cellular activation signals to modulate expression of the JCV genome in either transfected or infected human fetal glial cells. In addition, we analyze the binding of nuclear proteins isolated from untreated and cytokine treated human fetal glial cells to transcription factor binding sites in the JCV regulatory region. In contrast to the effects of cellular activation on the expression of the HIV-1 promoter in these cells, none of the cellular activators tested increased expression of JCV. The cytokine, TNF-alpha, increased binding of NF kappa B (p50/p65) to a JC NF kappa B site but did not modulate the binding of nuclear proteins to the overlapping NF-1/AP1 region of the JCV enhancer. When taken together these results suggest that the response of JCV to cellular activation signals may be fundamentally different from the response of HIV-1 to these signals in human fetal glial cells and that the JC NF kappa B site may not be required for JCV gene expression or multiplication in vivo.

Antibody Specificity↗

PubMed1993

[Progressive multifocal leukoencephalopathy in a patient with acquired immunodeficiency syndrome].

We report a 28 year old heterosexual male with AIDS that presented with progressive motor disturbances and malaise. Light and transmission electron microscopy of a stereotaxic brain biopsy demonstrated a progressive multifocal leukoencephalopathy. This is a demyelinating infectious cerebral disease attributed to JC virus and must be considered in the differential diagnosis of central nervous system disturbances in AIDS patients.

Acquired Immunodeficiency Syndrome↗