title: Responses to and Outcomes of Treatment of Autoimmune Cerebellar Ataxia in Adults.
abstract: OBJECTIVE
  Classic Purkinje cell cytoplasmic antibody type 1 (PCA-1, or anti-Yo) paraneoplastic cerebellar ataxia has a poor prognosis, yet little has been published otherwise regarding treatment responses and outcomes among patients with autoimmune cerebellar ataxia.
  
  
  OBJECTIVE
  To investigate treatment responses and outcomes in adults with autoimmune cerebellar ataxia.
  
  
  METHODS
  A cohort study conducted at Mayo Clinic, Rochester, Minnesota, included 118 patients who had ataxia, were 18 years or older, were seropositive for at least 1 neural autoantibody, had received at least 1 immunotherapy or cancer therapy, and had neurologist-reported outcomes documented from January 1, 1989, through December 31, 2013. Data were collected from May 14, 2013, through August 9, 2014, and analyzed from August 9, 2014, through April 27, 2015. Responses to immunotherapy (corticosteroids, intravenous immunoglobulin, plasma exchange, and immunosuppressants) and ambulatory outcomes were compared between different subgroups. Subgroups were classified as paraneoplastic vs nonparaneoplastic disorders; neuronal nuclear and/or cytoplasmic (NNC) antibody positivity vs plasma membrane protein (PMP) antibody positivity; and glutamic acid decarboxylase 65-kDa isoform (GAD65) antibody positivity vs PMP antibody positivity.
  
  
  METHODS
  Response to therapy and ambulatory ability, with univariate logistic regression and Kaplan-Meier analyses.
  
  
  RESULTS
  Inclusion criteria were met by 118 patients. Median age at onset of neurologic symptoms was 58 (range, 27-83) years, and 87 patients (73.7%) were women. Median duration from symptom onset to last follow-up was 25 (range, 2-223) months. Sixty-three patients had paraneoplastic and 55 patients had nonparaneoplastic ataxic disorders. Eighty-one patients were seropositive for NNC antibodies (most commonly PCA-1 [anti-Yo], antineuronal nuclear antibody type 1 [anti-Hu], and GAD65 antibody); 22 patients, for neural PMP receptor or ion channel antibodies (most commonly targeting P/Q- or N-type voltage-gated calcium channels); and 15 patients, for antibodies from both categories. Neurologic improvements occurred in 54 patients (with a robust change in ambulatory ability in 22) attributable to immunotherapy; univariate regression analysis revealed that improvements were significantly more common among patients with nonparaneoplastic disorders (P = .03) and those with exclusively PMP antibodies (P = .02). Kaplan-Meier analyses revealed that progression to wheelchair dependence occurred significantly faster among patients with NNC antibody positivity only (P = .02), although those with GAD65 autoimmunity progressed to wheelchair dependence at a rate similar to those with PMP autoimmunity (P = .92).
  
  
  CONCLUSIONS
  Although autoimmune ataxia is usually severe, treatment responses can be gratifying, particularly in patients with nonparaneoplastic disorders and in those harboring autoantibodies directed against GAD65 or neural PMPs.
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Jones
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Flanagan
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota2Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: Department of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Mandrekar
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Eggers
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: J Eric
authors.initials: JE
authors.lastname: Ahlskog
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota2Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D002524:Cerebellar Ataxia / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D020362:Paraneoplastic Cerebellar Degeneration / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D011689:Purkinje Cells / Q000276:immunology
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2