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OBJECTIVE: Although autoantibodies targeted against voltage-gated potassium channel (VGKC)-associated proteins have been identified in limbic encephalitis (LE) and acquired neuromyotonia (aNMT), the role of these antibodies in disease pathophysiology has not been elucidated. The present study investigated axonal function across the spectrum of VGKC-complex antibody associated disorders. METHODS: Peripheral axonal excitability studies were undertaken in a cohort of patients with LE (N=6) and aNMT (N=11), compared to healthy controls (HC; N=20). RESULTS: Patients with LE demonstrated prominent abnormalities in peripheral axonal excitability during the acute phase, with reduced threshold change in threshold electrotonus (depolarizing 10-20 LE: 58.5±3.1%; HC: 67.4±0.9%; P<.005; S2 accommodation LE: 17.2±1.4%; HC: 22.2±0.6%; P≤.005) and in recovery cycle parameters (superexcitability LE: -16.0±0.9%; HC: -23.4±1.1%; P<.01; subexcitability LE: 8.5±1.2%; HC: 13.8±0.7%; P≤.005). The pattern of change in LE patients was dissimilar to the effects of antiepileptic medications, suggesting that these factors did not underlie excitability changes in LE. Normalization of excitability parameters was associated with recovery (TEd peak correlation coefficient=.868; P=.002), suggesting that peripheral excitability studies may provide a marker associated with clinical improvement. In contrast, patients with aNMT demonstrated no significant changes at the site of stimulation. CONCLUSIONS: The lack of prominent excitability abnormalities in patients with aNMT likely reflects a distal origin of hyperexcitability, expected to be at the motor nerve terminal, while the prominent changes observed in patients with LE likely represent a complex disturbance at the level of the axonal membrane, combined with electrolyte imbalance and adaptive change.

Original publication

DOI

10.1016/j.expneurol.2014.06.002

Type

Journal article

Journal

Exp Neurol

Publication Date

11/2014

Volume

261

Pages

337 - 342

Keywords

Axonal excitability, Leucine-rich glioma inactivated 1, Limbic encephalitis, Neuromyotonia, Voltage gated potassium channels, Adult, Aged, Antibodies, Cohort Studies, Electromyography, Female, Humans, Immunoglobulins, Intravenous, Isaacs Syndrome, Limbic Encephalitis, Male, Membrane Proteins, Middle Aged, Nerve Tissue Proteins, Neural Conduction, Peripheral Nerves, Potassium Channels, Voltage-Gated, Sodium