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Original Investigation |

Responses to and Outcomes of Treatment of Autoimmune Cerebellar Ataxia in Adults

Amy L. Jones, MD1; Eoin P. Flanagan, MD1; Sean J. Pittock, MD1,2; Jay N. Mandrekar, PhD3; Scott D. Eggers, MD1; J. Eric Ahlskog, PhD, MD1; Andrew McKeon, MD1,2
[+] Author Affiliations
1Department of Neurology, College of Medicine, Mayo Clinic, Rochester, Minnesota
2Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, Minnesota
3Department of Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, Minnesota
JAMA Neurol. 2015;72(11):1304-1312. doi:10.1001/jamaneurol.2015.2378.
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Importance  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.

Objectives  To investigate treatment responses and outcomes in adults with autoimmune cerebellar ataxia.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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 and Relevance  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.

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Figure 1.
Kaplan-Meier Curves Estimating Time to Wheelchair Dependence in Patients With Autoimmune Cerebellar Ataxia and Subgroups

Fifty-seven patients (50%) were expected to be wheelchair dependent by 25.5 months. Progression to wheelchair dependence was faster among patients with paraneoplastic compared with nonparaneoplastic autoimmune ataxia and among those with positivity for neuronal nuclear and cytoplasmic antibodies (NNC Abs+) only (vs positivity for plasma membrane protein Abs [PMP Abs+] only).

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Figure 2.
Kaplan-Meier Curves Estimating Time to Wheelchair Dependence in Patients With Further Antibody Subgroups of Autoimmune Cerebellar Ataxia

Progression to wheelchair dependence was faster among patients with Purkinje cell cytoplasmic antibody type 1 (PCA-1) seropositivity and glutamic acid decarboxylase 65-kDa autoantibody (GAD65) seronegativity. Patients with GAD65 seropositivity and patients with plasma membrane protein (PMP) seropositivity progressed to wheelchair dependence at similar rates. Abs indicates antibodies; superscript minus sign, seronegativity; and superscript plus sign, seropositivity.

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