A progressive multifocal leukoencephalopathy (PML) is caused by reactivation of the JC virus. The disease usually occurs in patients with impaired cell-mediated immunity, especially in patients with HIV infection. PML leads to a subacute and progressive demyelination in the CNS and multifocal neurological deficits, it runs, usually within a year, lethal. The diagnosis is made by MRI plus CSF-PCR. In AIDS patients, the highly active antiretroviral therapy can slow the progression, and patients receiving immunosuppressive drugs may improve once these drugs are discontinued. Treatment is otherwise symptomatic.
A progressive multifocal leukoencephalopathy (PML) is caused by reactivation of the JC virus. The disease usually occurs in patients with impaired cell-mediated immunity, especially in patients with HIV infection. PML leads to a subacute and progressive demyelination in the CNS and multifocal neurological deficits, it runs, usually within a year, lethal. The diagnosis is made by MRI plus CSF-PCR. In AIDS patients, the highly active antiretroviral therapy can slow the progression, and patients receiving immunosuppressive drugs may improve once these drugs are discontinued. Treatment is otherwise symptomatic. Etiology PML is caused by the reactivation of the JC virus, a ubiquitous papovavirus human, which is typically added in childhood and latent in the kidney, and possibly other tissues remains (z. B. mononuclear cells CNS). The reactivated virus shows a tropism to oligodendrocytes. Most patients who develop PML, have impaired cell-mediated immunity to AIDS (the most common risk factor), a disease of the reticuloendothelial system (eg., Leukemia, lymphoma) or other disorders (eg. As Wiskott-Aldrich syndrome , organ transplantation). The risk in AIDS patients increases with increasing viral load. The prevalence of PML has fallen due to the widespread use of effective antiretroviral agents. appears increasingly PML as a complication of immunomodulatory therapy (eg., monoclonal antibodies such as Natalizumab, rituximab). Symptoms and complaints drowsiness may be the first symptom. Hemiparesis is the most common finding. Aphasia, dysarthria and hemianopia are also common. A multifocal cortical lesion leads to cognitive impairment in two thirds of patients. Sensory, cerebellar and brainstem deficits may occur. Headaches and seizures are rare and usually occur in patients with AIDS. The gradual, inevitable progression leading to death, usually within 1-9 months after the onset of symptoms. Diagnosis MRI CSF testing for JC viral DNA A PML is likely in patients with unexplained progressive brain dysfunction, v. a. in patients with impaired cell-mediated immunity. A preliminary diagnosis is made based on a contrast-enhanced MRI, the one or more white matter lesions on T2-weighted images represents. A contrast media emphasizes 5-15% of the most poor and peripheral lesions. A CT can exhibit non-enhanced lesions with low density, but is considerably less sensitive than the MRT. The cerebrospinal fluid is examined by PCR for JC viral DNA; a positive result with matching findings in imaging is almost pathognomonic. Routine cerebrospinal fluid are usually normal. Serological tests are not helpful. A stereotactic biopsy can provide a definitive diagnosis, but is rarely applied. Symptomatic treatment Treatment Treatment is mainly supportive. The experimental use of drugs such as cidofovir and other antiviral substances is of no use. The antiretroviral therapy (ART) in AIDS patients has improved the output of PML, increasing the 1-year survival rate has risen from 10% to 50%. Patients may, however an inflammatory immune reconstitution syndrome (IRIS human immunodeficiency virus infection (HIV) infection: Immunrekonstitutionelles inflammatory syndrome (IRIS)) by aggressive antiretroviral therapy develop; the IRIS generates the recovering immune system an intense inflammatory reaction against the JC virus, thereby deteriorating the symptoms. An imaging after development of IRIS shows a greater increase in contrast of lesions and can be a significant cerebral edema. Glucocorticoids can help. Depending on the severity of IRIS and AIDS clinicians can decide to discontinue ART. The discontinuation of immunosuppressive drugs can lead to clinical improvement. However, patients who stop taking this medication, even at risk to develop an IRIS. If a PML develops in patients who natalizumab, another immunomodulatory substance or get an immunosuppressant, the drug should be discontinued and plasma exchange are performed to remove remnants of the circulating drug. Conclusion The reactivation of the ubiquitous JC virus, which goes back usually a disturbed zellvermittlete immunity, leading to PML. PML often causes clumsiness, hemiparesis, aphasia, dysarthria, hemianopia, and cognitive impairment. Perform an MRI and a Liquortest on JC virus DNA in patients who have an impaired cell-mediated immunity and an unexplained progressive brain dysfunction. The treatment of patients is carried supportive, and the interference underlying as stated treated (eg., By stopping natalizumab, other immunomodulatory drug or an immunosuppressant or by initiating antiretroviral therapy, has to very precisely on the development of an inflammatory Immunrekonstitutionssyndroms be respected).