Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG–positive patients

Objective: To describe an expanded phenotypic spectrum and longitudinal outcome in 256 LGI1-IgG–seropositive and/or CASPR2-IgG–seropositive patients. Methods: Patients were identified through service neural autoantibody evaluation. Ninety-five had longitudinal follow-up (7–456 months; median = 35). Results: Among 3,910 patients tested, 196 were LGI1-IgG positive, 51 were CASPR2-IgG positive, and 9 were dual positive. Cerebrospinal fluid testing was less sensitive than serum testing, detecting only 24 of 38 (63%) LGI1-IgG–positive and 5 of 6 (83%) CASPR2-IgG–positive patients. LGI1-IgG–positive specimens had higher voltage-gated potassium channel–IgG immunoprecipitation values (0.33nmol/l, range = 0.02–5.14) than CASPR2-IgG–positive specimens (0.10nmol/l, range = 0.00–0.45, p < 0.001). Of patients presenting with pain or peripheral nervous system (PNS) manifestations, 39% were LGI1-IgG seropositive (7% had solely neuropathy or pain). Multivariate analysis identified age as the only significant predictor of central nervous system (CNS) versus PNS involvement (>50 years; odds ratio = 15, p < 0.001). Paroxysmal dizziness spells (PDS), a unique LGI1-IgG accompaniment (14% of patients), frequently delayed the diagnosis. T2-mesiotemporal hyperintensity was more common in LGI1-IgG–positive (41%) than in CASPR2-IgG–positive patients (p = 0.033). T1-bright basal ganglia were confined to LGI1-IgG–positive patients with faciobrachial–dystonic seizures (9 of 39, 31%). Cancer was found in 44% of LGI1-IgG/CASPR2-IgG dual seropositive patients (one-third thymoma). Response to initial immunotherapy was favorable in 97%; mean modified Rankin score was 3 (range = 1–5) at onset and 1.74 (range = 0–6) at last follow-up, with 9% having severe refractory disability, 20% being asymptomatic, 28% receiving immunotherapy, and 58% receiving antiepileptic medication. Interpretation: Older age is a strong predictor of CNS involvement in patients seropositive for CASPR2-IgG or LGI1-IgG. Pain, peripheral manifestations, and stereotypic paroxysmal dizziness spells are common with LGI1-IgG. Response to initial immunotherapy is often favorable, but some patients remain severely disabled, requiring long-term immunotherapy and/or antiepileptic medications. Ann Neurol 2017;82:79–92.