P256 Increased Barrett-Barrett conductance in motor axons of patients with anti-gad antibody

Objective Neurological disorders associated with anti-glutamic acid decarboxylase (GAD) antibody are diverse, including stiff-person syndrome, autoimmune cerebellar ataxia and epilepsy. To help understand the physiological actions of anti-GAD antibody, we examined the effects of the antibody on the excitability properties of peripheral motor axons. Methods Nine patients positive for anti-GAD antibody and without diabetic mellitus were studied. Multiple excitability measurements were made in the median nerve at the wrist, using computerized threshold-tracking (QTRACS with TRONDNF excitability protocol), and compared with normal control data. Subsequently we performed mathematical modeling of the excitability data, using the Bostock model of the human motor axon to simulate axonal excitability measurements (QTRACP with MEMFIT). Results Nerve excitability studies showed greater supernormality in recovery cycle and greater changes in excitability with polarizing currents in threshold electrotonus. Mathematical modeling indicated that the results could best be explained by an increase in the Barrett-Barrett conductance across the myelin sheath. Discussion The abnormalities are remarkably similar to those previously reported in episodic ataxia Type 2 (Tomlinson et al. Brain 2016;139:380–91) and attributed to nodal malformation. Conclusion This study showed that patients with anti-GAD antibody exhibit abnormalities in their motor axons attributable to an increase in Barrett-Barrett conductance. This in turn suggests that anti-GAD antibody causes Schwann cell dysfunction via changes in the GABAergic system of peripheral nerve. Significance The results of this study raise the possibility that anti-GAD antibody causes some clinical symptoms by affecting glial GABAergic systems.