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Abstract Background Progressive multifocal leukoencephalopathy (PML) is a rare complication of patients treated with fingolimod. Case presentation Routine MRI eventually led to diagnosis of asymptomatic early PML that remained stable after discontinuation of fingolimod. As blood lymphocyte counts normalized, signs of immune reconstitution inflammatory syndrome (IRIS) and renewed MS activity developed. Both, advanced laboratory and ultrahigh field MRI findings elucidated differences between PML and MS. Conclusions In our case, early discontinuation of fingolimod yielded a good outcome, lymphocyte counts reflected immune system activity, and paraclinical findings helped to differentiate between PML-IRIS and MS.

In dieser Übersichtsarbeit werden typische bildgebende Befunde von Erkrankungen infolge immunmodulierender Therapien dargestellt. Ein typisches Bildmuster hat vor allem die progressive multifokale Leukoenzephalopathie (PML), eine subakute, durch Reaktivierung des JC-Virus hervorgerufene Infektion, an die bei einer Multiple-Sklerose(MS)-Therapie mit Natalizumab, Fingolimod, Rituximab und Fumarat, aber auch bei bestehenden lymphoproliferativen Erkrankungen oder sonstigen Immunsuppressionen gedacht werden sollte. Beim Wiederherstellen der Immunkompetenz kann es überlappend zu einer verstärkten Gewebeantwort in Form eines inflammatorischen Immunrekonstitutionssyndroms (IRIS) kommen. Andere, im Zusammenhang mit der Immunmodulation auftretende MRT-Befunde wie Methrotrexat-assoziierte Leukoenzephalopathie oder „posterior reversible encephalopathy syndrome“ (PRES) werden ebenfalls aufgrund typischer MRT-Veränderungen diagnostiziert. Bei Immuntherapien mit Aktivierung von T‑Lymphozyten sollte immer bedacht werden, dass sich diese auch gegen normales Hirngewebe richten. Bei der Vielzahl von Folgeerkrankungen in Zusammenhang mit Stammzell- oder Organtransplantationen überlappen ursprüngliche und durch immunmodulatorische Medikamente ausgelöste Erkrankungen. [ABSTRACT FROM AUTHOR]

In recent years, new insights into the immunological pathways in multiple sclerosis (MS) have been detected. This increasing knowledge has led to more distinct treatment options in modifying the disease course of MS. In 2006, natalizumab, an α4-integrin monoclonal antibody rituzimab, which depletes CD20+ cells, pre-B mature B cells. Rituximab is approved for the treatment of a number of autoimmune diseases other than MS, such as rheumatoid arthritis and non-Hodgkin's lymphoma. Early-phase trials in the autoimmune-driven disorders Sjögren's syndrome, vasculitis and thrombocytopenic purpura confirmed the use of rituximab in B-cell-mediated diseases. Another autoimmune disease affecting the CNS is neuromyelitis optica (NMO). NMO is characterized by having some similarities with MS and several studies demonstrated successful therapy of NMO using rituximab. In addition, numerous case reports in MS patients showed a stabilization of the course with a reduction of the relapse rate and MRI Pathologies in MS patients. To date, one Phase II clinical trial in MS patients confirmed the results from these case reports. In this article, we will focus on the role of B cells in MS and the immunomodulatory pathways of rituximab. Recent data from experimental and clinical trials, as well as safety aspects, are discussed. A future perspectives is given regarding the possible role rituximab, as well as possible other candidates for treating MS. [ABSTRACT FROM AUTHOR]

Background: Progressive multifocal leukoencephalopathy (PML) is a rare complication of patients treated with fingolimod.Case Presentation: Routine MRI eventually led to diagnosis of asymptomatic early PML that remained stable after discontinuation of fingolimod. As blood lymphocyte counts normalized, signs of immune reconstitution inflammatory syndrome (IRIS) and renewed MS activity developed. Both, advanced laboratory and ultrahigh field MRI findings elucidated differences between PML and MS.Conclusions: In our case, early discontinuation of fingolimod yielded a good outcome, lymphocyte counts reflected immune system activity, and paraclinical findings helped to differentiate between PML-IRIS and MS. [ABSTRACT FROM AUTHOR]