A 62-year-old right-handed French Caucasian woman was diagnosed in October 2007 for an ASS and treated by corticosteroids (methylprednisolone 40 mg/week and prednisolone 20 mg/day) and mycophenolate mofetil (3 g/day). In March 2010 white blood cell count showed profound lymphopenia (486/mm 3, normal range 1,500 to 4,000/mm 3, Figure 1). Because the ASS was controlled, methylprednisolone was stopped and prednisolone was progressively tapered to 7.5 mg/day. In May 2010 she presented progressive cognitive impairment, followed by a brisk worsening in July 2010 with dizziness and falls. At admission on July 8 th 2010 neurological examination revealed mental slowness, attention and memory troubles, and paresis of the left lower limb. Brain axial T2-WI MRI revealed confluent subcortical white matter hyperintensities of the right frontal and parietal region ( Figure 2A). Axial T1-WI MRI displayed hypointensities with multiple foci of gadolinium enhancement ( Figure 2B). Prednisolone and mycophenolate mofetil were stopped. The differential diagnoses were viral encephalitis, tuberculosis, cerebral lymphoma, paraneoplastic disorder and CNS involvement of a connective tissue disorder. General examination did not demonstrate any activity of the ASS. Blood cell count showed 750 lymphocytes/mm 3 ( Figure 1). Cerebrospinal fluid (CSF) examination on day 2 was normal, and in-house PCR ( Herpesviridae, enterovirus, JCV, BK virus, Toxoplasma gondii and Mycobacterium tuberculosis), and serologies (HIV, Borrelia and syphilis), were negative, as well as direct staining and cultures for bacteria and fungi. Blood immunophenotyping showed 673 CD4 + T cells/mm 3 (normal range 500-1,500), 82 CD8 + T cells/mm 3 (normal range 250-950) and 37 CD19 + B cells/mm 3 (normal range 100-600) ( Figure 1). The level of anti-Jo1 antibodies previously detected (Nov 2009, 7.4 AI (normal range 0-0.9) was decreasing (5.9 AI) and a screening for anti-neutrophil cytoplasmic and onconeuronal antibodies was negative. A computed tomography scan showed steady lung interstitial infiltrates, and no evidence for sarcoidosis, tuberculosis or cancer. A stereotactic brain biopsy of the right parietal lobe was performed on July 16 th 2010. Neuropathological examination showed demyelinated lesions with axonal loss and a severe inflammatory reaction with a vasculitic component and endothelial damage ( Figure 2D-E). Perivascular and parenchymal inflammatory infiltrates showed a pronounced CD3 + T cell infiltrate ( Figure 2F) composed mostly by CD4 + T cells, in association with a few CD68 + macrophages/microglial cells and CD138 + plasma cells. Anti-Simian virus 40 (SV40) immunohistochemistry (cross-reacting with the JCV) was positive, and a second aliquot of the CSF taken on day 2, sent to Dr. Major's laboratory at the NIH, was positive for JCV by Real-time TaqMan PCR at a low level (23 copies/ml) , both firmly establishing the diagnosis of PML. A diagnosis of simultaneous PML-IRIS with vasculitis was made. As in the meantime her neurological status had stabilized, the patient did not receive corticosteroids. When followed up in November 2010, mental slowness and paresis of the left lower limb had completely recovered, and repeated MRI showed improvement of previous lesions. In parallel, blood immunophenotyping showed partial normalization ( Figure 1). However, concomitantly she presented with a severe flare of the ASS, with myositis, polyarthritis and active interstitial pneumonitis. A one-week course of oral corticosteroids was initiated together with monthly intravenous polyclonal immunoglobulin therapy (IVIg). By December 2012 the ASS was considered under control with IVIg alone. The patient was fully independent without any neurological abnormalities, while MRI showed sequellar lesions ( Figure 2C).