mdl-100907 and Leukoencephalopathy--Progressive-Multifocal

Progressive multifocal leukoencephalopathy (PML) is a severe encephalic demyelinating disease associated with JC virus (JCV) reactivation that occurs mostly in patients with immune disorders. Patients affected by sarcoidosis are at risk for developing PML both for leukocyte dysfunction and for receiving immunosuppressive medications: delayed diagnosis and high-dose corticosteroids are associated with a reduced survival. Although no specific treatment for PML exists, several therapeutic possibilities have been assessed with uncertain benefits (5HT2a receptor inhibitors are active in vitro against JCV): the cornerstone of sarcoidosis-associated PML is immunosuppressants withdrawal.We report the case of a female patient affected by systemic sarcoidosis for 30 years receiving low-dose corticosteroids (5 mg every other day). Due to memory impairment an MRI was performed showing three T2 hyperintense lesions involving white matter. Cerebrospinal fluid JCV PCR (845 copies/ml), neuropathological examination and immunohistochemistry (SV40 protein and JCV DNA positivity) on brain biopsy confirmed PML. Mirtazapine 15 mg was started while prednisone treatment was continued. 3 and 6 months later cognitive performances improved and brain MRIs were stable while cerebrospinal fluid JCV DNA was undetectable (6 months later). In conclusion the diagnosis of PML in patients with sarcoidosis is challenging given the overlapping presentation; the use of 5HT2a receptor antagonists deserves further studying in patients needing immunosuppressant drugs to control their dysimmune disease.

Topics: Aged; DNA, Viral; Female; Humans; Immunosuppressive Agents; JC Virus; Leukoencephalopathy, Progressive Multifocal; Mianserin; Mirtazapine; Sarcoidosis; Serotonin 5-HT2 Receptor Antagonists

We studied the susceptibility of human embryonic stem cell-derived oligodendrocyte progenitor cells to infection with JC virus, the causative agent of progressive multifocal leukoencephalopathy (PML). A human embryonic stem cell line, H7, was used to derive an enriched population of cells expressing the oligodendrocyte progenitor cell-specific marker NG2. These cells expressed the 5HT2a receptor (5HT2aR) for JC virus and were highly susceptible to infection. Infection was reduced by treatment with anti-5HT2aR antibodies and by the 5HT2aR antagonists ritanserin and ketanserin. This is the first demonstration that human embryonic stem cell-derived oligodendrocyte progenitor cells are susceptible to JC virus infection and indicates that cells poised to replenish mature oligodendrocytes in PML lesions may also be a target of viral infection.

Topics: Antibodies, Monoclonal; Antigens; Biomarkers; Cell Line; Embryonic Stem Cells; Fetus; Humans; JC Virus; Ketanserin; Leukoencephalopathy, Progressive Multifocal; Oligodendroglia; Proteoglycans; Receptor, Serotonin, 5-HT2A; Ritanserin; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists

Topics: Adult; Female; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Male; Mianserin; Middle Aged; Mirtazapine; Polycythemia Vera; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT2 Receptor Antagonists

Topics: Adult; Female; Humans; Leukoencephalopathy, Progressive Multifocal; Piperazines; Risperidone; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Thiazoles

Topics: Astrocytes; Cell Line; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Oligodendroglia; Receptor, Serotonin, 5-HT2A; Receptors, Virus; Serotonin 5-HT2 Receptor Antagonists