Autoimmune Cerebellar Ataxia: Treatment Responses and Outcomes in 118 Patients (I4-4B)

OBJECTIVE: To investigate outcomes in autoimmune cerebellar ataxia. BACKGROUND: Autoimmune cerebellar degeneration is generally considered neurologically devastating. METHODS: A review of autoimmune cerebellar ataxia (Mayo Clinic, 1989-2012) included patients seropositive for 蠅1 neural autoantibodies, who received 蠅1 immunotherapy (102) or cancer therapy (42), and had neurologist-reported outcomes documented. Paraneoplastic and non-paraneoplastic autoimmune cases were compared. RESULTS: Inclusion criteria were met by 118 patients. Median neurologic symptom-onset age was 58 years (range, 27-83); 87 were women (73.7[percnt]). Median follow-up duration was 8 months (range, 1-220). Of 55 patients with a non-paraneoplastic cause, all were seropositive for 蠅1 autoantibodies targeting neuronal cytoplasmic GAD65 (33) or neural ion channels or receptors (N-type calcium channel, 9; P/Q-type calcium channel, 8; VGKC-complex, 6; muscle or neuronal acetylcholine receptors, 6). Of 63 patients with a paraneoplastic cause, 53 were seropositive for 蠅1 autoantibodies with high cancer-predictive value (neuronal cytoplasmic [PCA-1, 37; CRMP5-IgG, 7; other, 9] or nuclear [ANNA-1, 4; AGNA-1, 2; ANNA-3, 2]) and 10 were seropositive for 蠅1 antibodies with low cancer-predictive value only (targeting GAD65, neural ion channels or receptors), but also had cancer detected. Overall, 54/118 patients (45.8[percnt]) improved with immunotherapy (50) or cancer therapy (13). Final evaluations revealed: walker-dependency, 44; wheelchair-dependency, 37; independent ambulation, 24; bed-bound, 7 (caused by cancer [4], ataxia [2], infection [1]), and cane-dependency, 6. Neurologic improvements occurred more commonly among non-paraneoplastic patients (31/55 vs 23/63, p=0.04) and in patients seropositive for antibodies targeting neural ion channels or receptors only (14/21 versus 33/82 patients seropositive for neuronal nuclear/cytoplasmic antibodies only, p<0.001). The non-paraneoplastic patients were more likely ambulatory at last follow-up (44/55 versus 30/63, p<0.001). CONCLUSION: The autoantibody profile of autoimmune cerebellar ataxias is diverse. Though usually severe, improvements may occur, particularly in patients with non-paraneoplastic disorders and in those harboring autoantibodies directed against neural plasma membrane protein antigens. Disclosure: Dr. Jones has nothing to disclose. Dr. Pittock9s institution has received compensation for activities with Alexion Pharmaceuticals, Medimmune, and Chugai Pharma. Dr. Pittock and his institution stand to receive royalty payments in the technology entitled Neuromyelitis Optica Autoantibodie Dr. Lennon stands to receive royalty payments for commercial assays to detect of Aquaporin 4-specific Autoantibody. Dr. Eggers has nothing to disclose. Dr. Ahlskog has nothing to disclose. Research support from MedImmune for a laboratory diagnostics study.