title: A prospective open-label study of sirolimus for the treatment of anti-Hu associated paraneoplastic neurological syndromes.
abstract: BACKGROUND
  Several lines of evidence suggest a T cell-mediated immune response in paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS). In order to investigate whether suppression of T cell-mediated immune responses in Hu-PNS patients improved their neurological outcome, we performed a prospective open-label, single-arm study on sirolimus.
  
  
  METHODS
  Seventeen progressive Hu-PNS patients were treated with sirolimus with an intended treatment duration of 8 weeks. Primary outcome measures were (i) functional improvement, defined as a decrease of one or more points on the modified Rankin Scale (mRS), and (ii) improvement of neurological impairment, defined as an increase of one or more points on the Edinburgh Functional Impairment Tests (EFIT).
  
  
  RESULTS
  One patient showed improvement on both clinical scales (mRS and EFIT). This patient presented with limbic encephalitis and improved dramatically from an mRS score of 3 to mRS 1. Another patient, with subacute sensory neuronopathy, remained stable at mRS 2 and improved one point on the EFIT scale. The other patients showed no improvement on the primary outcome measures. Median survival was 21 months.
  
  
  CONCLUSIONS
  We conclude that treatment of Hu-PNS patients with sirolimus may improve or stabilize their functional disabilities and neurological impairments. However, the effects of this T cell-targeted therapy were not better than reported in trials on other immunotherapies for Hu-PNS. Trial Registration https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-000793-20/NL.
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Adriaan H
authors.initials: AH
authors.lastname: de Jongste
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Jacoline E
authors.initials: JE
authors.lastname: Bromberg
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Marieke T
authors.initials: MT
authors.lastname: de Graaf
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Jan W
authors.initials: JW
authors.lastname: Gratama
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Marco W
authors.initials: MW
authors.lastname: Schreurs
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Herbert
authors.initials: H
authors.lastname: Hooijkaas
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.E.B., M.T.d.G., P.A.S.S.); Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands (A.H.d.J., J.W.G); Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands (T.v.G.); Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands (M.W.S., H.H.).
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D051959:ELAV Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020361:Paraneoplastic Syndromes, Nervous System / Q000188:drug therapy* / Q000276:immunology*; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D051959:ELAV Proteins; D020123:Sirolimus
keywords: paraneoplastic neurological syndromes; sirolimus; treatment