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Immune reconstitution inflammatory syndrome mimicking progressive multifocal leucoencephalopathy in a multiple sclerosis patient treated with natalizumab: a case report and review of the literature.

Natalizumab (NTM) represents an effective drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). Progressive multifocal le … eripheral enhancement. Visual fields showed scotomata mostly of the left eye. NTM was discontinued. JC virus (JCV) polymerase chain reaction (PCR) in cerebrospinal fluid was negative. The patient received IV corticosteroids for 5 days and then monthly for 2 months with subsequent clinical and MRI improvement. On month 4, she presented with a new relapse wi …

Clinical experience of natalizumab in Crohn's disease patients in a restricted distribution program.

BACKGROUND: Natalizumab (NAT) is a humanized monoclonal antibody against a4-integrin initially approved for the treatment of multiple sclero … ine sepsis while on NAT. Of the 5 patients on long-term maintenance therapy, 4 have a positive anti-JC virus antibody. No patients developed progressive multifocal leukoencephalopathy or other neurological complications. CONCLUSION: NAT remains a valuable alternative treatment option for patients with refractory Crohn's disease under a restricted distribu …

Уроки, извлеченные из смертельной прогрессирующей многофукальной лейкоэнцефалопатии у пациента с множественным склерозом, который лечился натализумбом.

ЦЕЛЬ: Описание клинических, радиологических и гистопатологических особенностей смертельного случая прогрессивной многофокальной лейкоэнцефалопатии (ПМЛ) у пациента с множественным склерозом, который лечится натализумабом. Мы воспользуемся этим случаем для анализа стратификации и диагноза риска PML. Отчет о деле. Лечение в специализированном центре третьего уровня. ПАТИЕНТ: 55-летний пациент с вирусом JC (JCV) с множественным склерозом, который умер от PML после 45 инъекций внутриутробного вируса. ОСНОВНЫЕ МЕРЫ ПО ИТОГАМ: Результаты цепной реакции мозгового магнитного резонанса и цереброспиново

Совпадение в аннотации оригинала
OBJECTIVE: To describe the clinical, radiological, and histopathological features of a fatal case of progressive multifocal leukoencephalopa … DESIGN: Case report. SETTING: Tertiary referral center hospitalized care. PATIENT: A 55-year-old, JC virus (JCV) antibody-positive patient with multiple sclerosis who died of PML after receiving 45 infusions of natalizumab. MAIN OUTCOME MEASURES: Brain magnetic resonance imaging and cerebrospinal fluid JCV DNA polymerase chain reaction results. RESULTS …

Characterization of JC human polyomavirus infection in a Portuguese population.

JC virus (JCV) is ubiquitous in the human population, infecting children asymptomatically. After primary infection, JCV persists in the host throughout life and is often excreted in the urine. Two hundred thirty-four urine samples and 78 serum samples, collected from 171 healthy individuals and 63 patients infected with HIV, were used to characterize JCV infection in a Portuguese population. Using PCR, JCV DNA was detected in 38% of the urine samples. A significant difference in the excretion rate was observed between patients infected with HIV (51%) and healthy individuals (33%). The frequenc…

Evidence for modulation of BAG3 by polyomavirus JC early protein.

Polyomavirus JC (JCV) infects oligodendrocytes and astrocytes in the brain and is the cause of the demyelinating disease progressive multifocal leukoencephalopathy (PML). In cell culture, JCV infection is characterized by severe damage to cellular DNA, which begins early in infection, and a viral cytopathic effect, which is observed late in infection. Nevertheless, these JCV-infected cells show a low level of apoptosis, at both the early and late stages of infection. This suggests that there is conflicting interplay between viral anti-apoptotic pathways that seek to optimize virus production,

Urine cytology findings of polyomavirus infections.

Polyomaviruses of the BK- and JC-strains often remain latent within the transitional cell layer of the bladder, ureters and the renal pelvis as well as in tubular epithelial cells of the kidney. Slight changes in the immune status and/or an immunocompromised condition can lead to the (re)activation of latent polyomaviruses, especially along the transitional cell layer, resulting in the shedding of viral particles and infected cells into the urine. A morphologic sign of the (re)activation of polyomaviruses is the detection of typical intranuclear viral inclusion bearing epithelial cells, so-cal

Molecular epidemiology of JC polyomavirus genotypes in PLWH from Turkey.

BACKGROUND: JC polyomavirus (JCPyV) is a globally prevalent human polyomavirus that establishes lifelong latency, primarily in renal tissue. Despite its global importance, molecular epidemiological data on JCPyV still remain limited. OBJECTIVES: This study aimed to investigate the prevalence, genotype distribution, and genetic variations of JCPyV in urine and plasma samples from people living with HIV (PLWH) in Turkey. Additionally, we explored the correlation between JCPyV presence, immunological parameters, and demographic factors, providing the first molecular epidemiological report of JCP

Single-Molecule Sequencing Revealing the Presence of Distinct JC Polyomavirus Populations in Patients With Progressive Multifocal Leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by reactivation of JC polyomavirus (JCPyV) in immunosuppressed individuals and lytic infection by neurotropic JCPyV in glial cells. The exact content of neurotropic mutations within individual JCPyV strains has not been studied to our knowledge. METHODS: We exploited the capacity of single-molecule real-time sequencing technology to determine the sequence of complete JCPyV genomes in single reads. The method was used to precisely characterize individual neurotropic JCPyV strains of 3 patients with PML witho

Anti-JCV antibody prevalence in a French cohort of MS patients under natalizumab therapy.

To measure the prevalence of JCV-specific antibodies in a French cohort of MS patients treated with natalizumab and to identify risk factor(s) of JCV seropositivity. Progressive multifocal leukoencephalopathy (PML) risk may be stratified by anti-JCV antibody status, duration of natalizumab therapy (≥24 months) and prior exposure to immunosuppressive (IS) drugs. No data are available in France on the prevalence of anti-JCV antibodies and distribution of PML risk factors in patients treated with natalizumab. Sera of 361 patients under natalizumab therapy in two MS centers were analyzed using a p

Progressive multifocal leukoencephalopathy and multiple sclerosis: lessons from natalizumab.

Three patients have developed progressive multifocal leukoencephalopathy while being treated with natalizumab for their autoimmune diseases. One patient had relapsing-remitting multiple sclerosis (RRMS), one had Crohn's disease, and one (who had been enrolled in an RRMS phase III trial) had no evidence of multiple sclerosis on autopsy. The patient with RRMS now has severe, permanent neurologic damage and the other two patients died. In this article, we recommend revised entry and diagnostic criteria to prevent enrollment of RRMS patients with a favorable prognosis or questionable diagnosis int

Infectious CNS disease as a differential diagnosis in systemic rheumatic diseases: three case reports and a review of the literature.

BACKGROUND: Immunosuppressive treatment of rheumatic diseases may be associated with several opportunistic infections of the brain. The differentiation between primary central nervous system (CNS) involvement and CNS infection may be difficult, leading to delayed diagnosis. OBJECTIVE: To differentiate between CNS involvement and CNS infection in systemic rheumatic diseases. METHODS AND RESULTS: Three patients with either longstanding or suspected systemic rheumatic diseases (systemic lupus erythematodes, Wegener's granulomatosis, and cerebral vasculitis) who presented with various neuropsych

Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses.

Progressive multifocal leukoencephalopathy (PML) is a lethal brain disease caused by uncontrolled replication of JC polyomavirus (JCV). JCV strains recovered from the brains of PML patients carry mutations that prevent the engagement of sialylated glycans, which are thought to serve as receptors for the infectious entry of wild-type JCV. In this report, we show that non-sialylated glycosaminoglycans (GAGs) can serve as alternative attachment receptors for the infectious entry of both wild-type and PML mutant JCV strains. After GAG-mediated attachment, PML mutant strains engage non-sialylated n

Role of NDUFS1 in mitochondrial dysfunction and oxidative stress in glaucomatous retinal ganglion cells.

This study investigates the role of NDUFS1, a subunit of mitochondrial complex I, in glaucomatous retinal ganglion cell (RGC) injury and determines whether it mediates RGC apoptosis through regulating mitochondrial dysfunction and oxidative stress (OS). A microbead-induced glaucoma mouse model was established. Intraocular pressure (IOP) measurements, retinal whole-mount immunofluorescence staining, TUNEL assay, and OS marker detection were conducted to assess RGC survival, apoptosis, and OS. In vitro, NDUFS1 was knocked down or overexpressed in R28 retinal cells. JC-1 staining, adenosine triph

Progressive Multifocal Leukoencephalopathy Mimicking a Cerebral Vasculitis Flare.

We report a case of a 68-year-old woman with a background of primary cerebral vasculitis, which was diagnosed two years ago. She appeared to have had a recurrence of her symptoms with new onset history of expressive dysphasia, right-sided upper limb weakness, and right-sided facial weakness during a rheumatology clinic visit. The patient was on maintenance azathioprine for her cerebral vasculitis at the time of presentation. She had received a total of 2 g of rituximab through intravenous infusion, with a two-week interval between doses. Additionally, she had undergone intravenous cyclophospha

[Prophylactic and therapeutic management of increased susceptibility to infection in patients with immunodeficiency].

Infections are an important warning sign for a weakened immune system. In the internal medical practice acquired (secondary), particularly drug-induced immunodeficiencies, are much more frequent than congenital (primary) immunodeficiencies. The management starts as early as the planning phase before initiation of immunosuppression. The risk of infection should be individually stratified and protective vaccinations should be completed. Depending on the immunosuppressive treatment, there can be a necessity for preventive treatment, e.g. for latent tuberculosis infection or hepatitis B. The serol

JCPyV-Induced MAPK Signaling Activates Transcription Factors during Infection.

JC polyomavirus (JCPyV), a ubiquitous human pathogen, is the etiological agent of the fatal neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Like most viruses, JCPyV infection requires the activation of host-cell signaling pathways in order to promote viral replication processes. Previous works have established the necessity of the extracellular signal-regulated kinase (ERK), the terminal core kinase of the mitogen-activated protein kinase (MAPK) cascade (MAPK-ERK) for facilitating transcription of the JCPyV genome. However, the underlying mechanisms by which the MAP

Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.

Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host, and their seroprevalence can reach 90% in healthy adults. Few studies have focused on the pediatric population, and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyV

Early diagnosis of progressive multifocal leucoencephalopathy: longitudinal lesion evolution.

OBJECTIVE: Early diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed … gnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.

Seroprevalence of Epstein-Barr Virus, Cytomegalovirus, and Polyomaviruses in Children with Inflammatory Bowel Disease.

BACKGROUND: Young age and thiopurine therapy are risk factors for lymphoproliferative disease among patients with inflammatory bowel disease (IBD). AIMS: The aims of this study were to evaluate the prevalence of seropositivity for the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) among children and adolescents with IBD, to assess the viral load of EBV, CMV, and BK and JC polyomaviruses (BKV, JCV) in these patients, and to assess the influence of different therapeutic regimens on seroprevalence and viral load. METHODS: Children who had been followed in our center were tested for EB