Neuropsychological Profiles Of Voltage-Gated Potassium Channel Complex And Other Autoimmune Encephalopathies; More Than Memory Impairment (S18.005)

Objective: To evaluate cognitive function and imaging findings in patients with voltage-gated potassium channel complex antibody (VGKCC-Abs) associated encephalopathy . We compared indices of memory, visuospatial, language, and executive functions to deficits in patients with other antibody-associated autoimmune encephalopathies (AEs). Background: AEs represent a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly reported, few reports of AE assess all cognitive domains in detail. Methods: We assessed subjects (n=12) with AE who tested positive for VGKCC-Abs with a comprehensive neuropsychological protocol and compared their profiles to subjects with antibodies against intracellular (GAD, n=2) or another cell-surface protein (AMPAR, n=3), relative to a normative sample. Clinical MRI data were available for 10/12 VGKCC-Abs patients and evaluated descriptively. Four VGKCC-Abs subjects had serial cognitive testing available, permitting description of longitudinal change. Results: Patients with VGKCC-Abs demonstrated particular impairment in memory (mean Z=-1.9) and executive functions (mean Z=-1.5), with isolated difficulties in language (mean Z=-1.4) and sparing of visuospatial skills. By contrast, AMPAR-antibody positive subjects displayed striking executive dysfunction, whereas GAD-antibody positive subjects displayed less severe impairments across all domains. Longitudinal testing of four VGKCC-Abs AE subjects revealed heterogeneity in cognitive change over time; whereas most subjects improved in one domain, residual impairments or cognitive plateaus were observed. MRI findings in the VGKCc-Ab patients nearest to time of cognitive testing showed atrophy (5 of 10), and subtle or obvious hyperintensities in medial temporal lobe (MTL) structures (9 of 10). Conclusions: This study offers one of the first comprehensive evaluations of cognitive functioning in VGKCC associated AE and other antibody-mediated AE’s, and highlights the importance of domain-specific tests of cognition to parse out their complex clinical phenotypes. Delineating the relative strengths and weaknesses for AE subtypes remains critical for differential diagnosis, and has implications for development of focused cognitive therapies. Study supported by NIH/NIA R01 AG31189/K23021989, and the Michael J. Homer Family Fund Disclosure: Dr. Geschwind has received personal compensation for activities with Lundbeck, Inc., MedaCorp, The Council of Advisors, and Neurophage. Dr. Geschwind has received research support from NIH/NIA, the Tau Consortium and CurePSP. Dr. Gelfand has received personal compensation for activities with the National Multiple Sclerosis Society. Dr. Gelfand has received personal compensation in an editorial capacity for Watch Neurology. Dr. Irani has nothing to disclose. Dr. Neuhaus has nothing to disclose. Dr. Forner has nothing to disclose. Dr. Bettcher has nothing to disclose.