Introduction: Paraneoplastic neurological syndromes (PNSs) are severely disabling conditions that are associated with cancer. Well-characterized onconeural antibodies (Abs) are, by definition, virtually exclusively present in patients with cancer and include anti-Hu, Yo, CV2, Ri, Ma2, amphiphysin and anti-delta/notch-like epidermal growth factor-related receptor (DNER;Tr). More recently, a second group of antineuronal Abs has been described that are found in both patients with and without cancer. Areas covered: This review is focused on putative T-cell-mediated immunopathogenetic mechanisms and treatment of PNS associated with well-characterized onconeural Abs. As of December 2013, only uncontrolled open-label clinical trials, retrospective case series and case reports were detected in the literature. Six clinical studies in Hu-PNS reported the effect of immunotherapy on functional outcome. Expert opinion: When taken together, these six studies showed an improvement of one point or more on the modified Rankin scale (mRS) in 11% (7/61) of patients. In Yo-PNS, 8% (2/26) of patients improved on the mRS. PNS with other well-characterized onconeural Abs also responded poorly to immunotherapies. Potential new immunotherapies include natalizumab, fingolimod, alemtuzumab and a combination of rituximab with cyclophosphamide.

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Expert Opinion on Orphan Drugs
Department of Neurology