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1.
Emerg Infect Dis ; 25(11): 2145-2147, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31625858

RESUMO

Antibodies against PD1 have been used to treat progressive multifocal leukoencephalopathy (PML), a rare brain disease caused by JC virus. We used these antibodies (nivolumab) to treat PML in 3 kidney transplant recipients. All died within 8 weeks of diagnosis. Hence, nivolumab did not improve PML outcome after solid organ transplantation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Imunomodulação/efeitos dos fármacos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/imunologia , Transplantados , Antineoplásicos Imunológicos/farmacologia , Humanos , Vírus JC , Transplante de Rim , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/virologia , Nivolumabe/uso terapêutico , Nivolumabe/ultraestrutura , Resultado do Tratamento
2.
BMC Neurol ; 19(1): 252, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653203

RESUMO

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by JC virus (JCV). Although detecting JCV DNA in the cerebrospinal fluid (CSF) by real-time polymerase chain reaction (PCR) is useful, diagnosis is difficult when JCV concentrations are low. We therefore aimed to lower the detection limit of real-time PCR testing by enriching JCV in the CSF via ultrafiltration. METHODS: Virus suspensions and CSF specimens from 20 untreated patients with suspected PML were collected and total DNAs were extracted. The JCV large T gene was detected by quantitative real-time PCR under condition with and without prior centrifugal ultrafiltration. RESULTS: The JCV DNA was reliably detected to a lower limit of 10 copies/mL of virus suspension by real-time PCR with ultrafiltration. When using this method, the quantity of JCV DNA per PCR reaction increased 3.2- to 8.7-fold compared with the standard procedure. Seven patients were positive for JCV when using the standard procedure, and an additional patient was positive when using ultrafiltration. All JCV-positive patients had neurological features and magnetic resonance imaging findings compatible with PML. CONCLUSIONS: The detection limit of JCV DNA by real-time PCR can be lowered by viral enrichment using ultrafiltration. Our simple protocol offers a valuable tool for PML diagnosis when extremely low copy numbers of JCV are released into the CSF or when brain biopsy is not feasible.


Assuntos
DNA Viral/líquido cefalorraquidiano , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Ultrafiltração/métodos , Adulto , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade
4.
Fluids Barriers CNS ; 16(1): 28, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484537

RESUMO

Progressive multifocal leukoencephalopathy (PML), caused by infection with John Cunningham polyoma virus (JCPyV) in immune-compromised patients, is a serious demyelinating disease of the central nervous system. This disease often leads to major neurological impairments and consecutive disability. No effective treatment for PML has been found as yet. As JCPyV-PCR of the cerebrospinal fluid (CSF) may be negative in some cases, a reliable diagnosis might prove to be difficult as well. So far, two case reports suggested CSF-tau to be a promising biomarker for PML. Our study included 10 patients with assured diagnosis of PML and varying underlying diseases. In all but one the CSF-tau concentration was normal. Our results indicate that CSF-tau is not an appropriate biomarker for PML.


Assuntos
Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Semin Neurol ; 39(3): 383-390, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31378873

RESUMO

Opportunistic infections of the central nervous system are classically associated with immunosuppression arising from infection with human immunodeficiency virus and with various hematologic malignancies. However, over the past few years, they are increasingly associated with transplantation and various immunosuppressive treatments used to treat autoimmune diseases. They cause significant morbidity and mortality and remain a diagnostic challenge due to the absence of typical signs and symptoms of infection and mimicry by various noninfectious causes. The pathogens associated with these infections are often commonly found pathogens of low virulence in immunocompetent hosts and include various bacteria, parasites, fungi, or viruses. These infections can present as various clinical syndromes, including meningitis, encephalitis, space-occupying lesions, stroke-like presentations, or even neoplastic manifestations. Progressive multifocal leukoencephalopathy can be seen in patients with multiple sclerosis on various new immunomodulatory drugs in addition to patients with human immunodeficiency virus, transplantation, or hematologic malignancies, and is characterized by multifocal white matter lesions. Human herpesvirus-6 causes severe encephalitis in transplant recipients, known as posttransplantation acute limbic encephalitis. Neoplastic manifestations like Epstein-Barr virus-associated primary central nervous system lymphoma and posttransplantation lymphoproliferative disorders are particularly challenging to diagnose and manage. Modern diagnostic techniques, including advanced imaging techniques like magnetic resonance spectroscopy, use of polymerase chain reaction, and metagenomic sequencing, can be helpful in early recognition of pathogens. Treatment of most of these involves lowering of immunosuppression when possible and use of specific antimicrobial agents when available. Improved outcomes can be seen when early diagnosis is made.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções Oportunistas/diagnóstico , Infecções por Roseolovirus/diagnóstico , Anti-Infecciosos/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Herpesvirus Humano 6/isolamento & purificação , Humanos , Infecções Oportunistas/tratamento farmacológico
7.
Diagn Microbiol Infect Dis ; 95(3): 114859, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31320237

RESUMO

OBJECTIVE: To assess the predictive value of JC virus (JCV) PCR in cerebrospinal fluid (CSF) in the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a retrospective database query to identify patients with positive CSF JCV PCR. Clinical features, final diagnosis and quantitative PCR results were obtained. RESULTS: A positive CSF JCV PCR had a PPV of 10.4% for the diagnosis of PML. A weakly positive PCR had a PPV of 1.6%, whereas a moderately to highly positive PCR had a PPV of 92.3%. A PPV of 0.0% was observed in immunocompetent patients and in patients without compatible clinical or radiological features. CONCLUSIONS: A false-positive CSF JCV PCR is highly prevalent in our clinical practice. This test should be reserved for patients with a clinical suspicion of PML and the quantitative result of the PCR should be taken into account when making the diagnosis of PML.


Assuntos
Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Reação em Cadeia da Polimerase , Carga Viral/métodos , DNA Viral/sangue , DNA Viral/líquido cefalorraquidiano , DNA Viral/urina , Reações Falso-Positivas , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/sangue , Leucoencefalopatia Multifocal Progressiva/urina , Infecções por Polyomavirus/líquido cefalorraquidiano , Infecções por Polyomavirus/diagnóstico , Valor Preditivo dos Testes , Estudos Retrospectivos
8.
J Clin Neurosci ; 67: 261-263, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278051

RESUMO

A case of progressive multifocal leukoencephalopathy (PML) occurring on low dose immunosuppression for systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS) is presented. Neurologic changes in patients with SLE or SS should not be assumed to be a disease manifestation. Importantly, serious opportunistic infections such as PML can occur in minimally immunosuppressed rheumatic patients. Early diagnosis, facilitated by scrutiny of MRI findings, should trigger measures to reconstitute immunity in an otherwise fatal disease.


Assuntos
Leucoencefalopatia Multifocal Progressiva/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome de Sjogren/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/complicações , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico por imagem
11.
J Coll Physicians Surg Pak ; 29(6): S18-S19, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142409

RESUMO

John Cunningham virus (JCV), a member of polyomaviridae family, has been described as a cause of the progressive multifocal leukoencephalopathy (PML). It is a potentially fatal, disabling demyelinating infection of the brain occurring mostly in the setting of immunosuppression. A few cases of JCV-associated meningitis and encephalitis have been described in literature. We report a case presenting with laboured breathing and reduced conscious level, who after thorough investigations was diagnosed to be a case of PML.


Assuntos
Encéfalo/patologia , Líquido Cefalorraquidiano/virologia , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Adulto , Evolução Fatal , Feminino , Hormônio Foliculoestimulante , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/virologia , Reação em Cadeia da Polimerase
13.
Saudi J Kidney Dis Transpl ; 30(2): 526-530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031391

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease that affects immunocompromised hosts. Most often the disease is reported in association with leukemia, lymphoma, and AIDS. With recent advancements in immunosuppressive medications and subsequent rise in solid organ transplantations, it is becoming more prevalent in this population. Both the diagnosis and treatment of PML remains a challenge to the transplant community. The disease remains mostly underreported and undertreated. The diagnostic uncertainty in a renal transplant patient leads us to do the brain biopsy for suspicion and confirmation of PML.


Assuntos
Imunossupressão/efeitos adversos , Transplante de Rim , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/patologia , Biópsia , Encéfalo/patologia , Humanos , Leucoencefalopatia Multifocal Progressiva/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
15.
Autops. Case Rep ; 9(1): e2018063, Jan.-Mar. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-986756

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms due to the physicians' unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.


Assuntos
Humanos , Masculino , Adulto , Síndrome de Imunodeficiência Adquirida/complicações , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Autopsia , Leucoencefalopatia Multifocal Progressiva/patologia , Evolução Fatal , Vírus JC
18.
Am J Case Rep ; 20: 101-105, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30674865

RESUMO

BACKGROUND Progressive multifocal leukoencephalopathy (PML) is a serious opportunistic infectious disease with high morbidity and mortality. Its incidence in multiple sclerosis (MS) patients has risen since the introduction of disease modifying drugs. In the absence of a specific treatment, the outcome depends heavily on early diagnosis, which illustrates the importance of the role of characteristic brain magnetic resonance imaging (MRI). However, when relying mainly on MRI, the diagnosis of cases with atypical radiological changes may be missed or delayed. CASE REPORT A 32-year-old female diagnosed with elapsing remitting MS in 2009 was started on interferon-beta-1b that was escalated to natalizumab due to progression of the disease. Later, she was shifted to fingolimod as testing for John Cunningham polyoma virus (JCV) antibodies was positive. Three years later, she presented with a 3-week history of progressive walking impairment associated with twitching of her facial muscles and abnormal sensation all over her body that was associated with left hemi-paresis and sensory changes, in addition to truncal ataxia, which was treated with steroids as a relapse of MS. However, the patient continued to deteriorate and developed significant cognitive and behavioral changes. In view of this clinical picture, the diagnosis of PML was raised in spite of her atypical brain MRI features. Treatment with fingolimod was stopped and a sample of her cerebrospinal fluid was sent for JCV DNA analysis, which came back positive at 11 copies/mL. Treatment with mirtazepine and mefloquine was started, but the patient deteriorated further, and MRI showed severe changes consistent with immune reconstitution inflammatory syndrome. Intravenous steroids and intravenous immunoglobulin were given, and within a few weeks, the patient was stabilized and started to gradually improve. CONCLUSIONS In patients at risk for developing PML who present with typical clinical features, testing for JCV DNA is recommended even in the absence of typical radiological findings in order to prevent any delay in the diagnosis.


Assuntos
Leucoencefalopatia Multifocal Progressiva/diagnóstico , Esclerose Múltipla Recidivante-Remitente/complicações , Adulto , Encéfalo/diagnóstico por imagem , DNA Viral/isolamento & purificação , Feminino , Cloridrato de Fingolimode/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Vírus JC/genética , Imagem por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
19.
Leuk Lymphoma ; 60(2): 395-401, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29969336

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a life-threatening opportunistic infection of immunomodulatory therapies. PML cases reported in PubMed (1995-2017) following stem-cell transplantation (HSCT) or chemoimmunotherapy (CIT) for hematologic malignancies were reviewed. We found 107 cases, 40% were HSCT recipients (32 allogeneic, 11 autologous) and 40% indolent lymphomas receiving monoclonal antibodies (mAbs). HSCT cases had longer time to PML diagnosis (10.8 vs. 4 months, p < .001), higher proportion of PML therapy response (58% vs. 25%, p = .019), lower mortality rate (56% vs. 88%, p < .001), and longer median survival (8 vs. 2 months, p < .001). Outcome differences might be caused by selection bias as HSCT patients are most likely treated aggressively; however, time-dependent immune reconstitution might also contribute to their better prognosis. Increased use of mAbs and HSCT are associated with rising PML incidence in hematological malignancies, currently constituting the second largest vulnerable population after HIV-infected patients; further research is needed for its optimal treatment.


Assuntos
Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/mortalidade , Idoso , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucoencefalopatia Multifocal Progressiva/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico
20.
J Neurol Neurosurg Psychiatry ; 90(1): 44-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30100552

RESUMO

OBJECTIVE: To test the current progressive multifocal leukoencephalopathy (PML) diagnostic criteria by applying them to patients previously diagnosed with natalizumab (NTZ)-associated PML in a real-world clinical setting. METHODS: Patients from the Dutch-Belgian NTZ-PML cohort (n=28) were reviewed at the time of first diagnostic work-up and during follow-up, using the PML diagnostic criteria as proposed in a consensus statement from the American Academy of Neurology. RESULTS: At first diagnostic work-up, 18 patients (64.3%) met the criteria for high diagnostic certainty for PML ('definite PML' or 'probable PML'). During follow-up, this increased to 20 patients (71.4%) as JC virus DNA was detected in cerebrospinal fluid of two additional patients. Nonetheless, 28.6% of patients were still classified as 'possible PML' or 'not PML' (6 (21.5%) and 2 (7.1%) patients, respectively) despite a very high suspicion for PML based on lesion evolution and signs of PML-immune reconstitution inflammatory syndrome on MRI, and development of compatible symptoms. CONCLUSIONS: The current case definition of PML has low sensitivity for diagnosis of NTZ-PML in a real-world clinical setting in which MRI is frequently used for PML screening. This may delay diagnosis and appropriate management of PML, and may complicate a valid estimation of PML incidence during NTZ therapy.


Assuntos
Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Natalizumab/efeitos adversos , Adulto , Bélgica , Encéfalo/diagnóstico por imagem , Estudos de Coortes , DNA Viral/líquido cefalorraquidiano , Diagnóstico Precoce , Feminino , Humanos , Vírus JC/genética , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Países Baixos , Farmacovigilância , Reação em Cadeia da Polimerase , Ativação Viral
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