G.P.74 Clinical aspects of presynaptic neuromuscular transmission defect in anti-GQ1b IgG antibody-related disorders

Abstract

Abstract Guillain–Barre syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff’s brainstem encephalitis (BBE) are immune-mediated disorders with overlapping clinical features, whereby anti-GQ1b IgG antibody is detected in variable frequencies. In vitro studies of MFS have demonstrated anti-GQ1b IgG antibody-mediated presynaptic damage at the neuromuscular junction. Previous studies have provided electrophysiological evidence of presynaptic neuromuscular transmission defect in anti-GQ1b positive MFS patients, which persisted up to 3 months from initial presentation. In this study, we compared incremental responses antibody-positive MFS and BBE (Group 1) with antibody-negative GBS and MFS variants (Group 2) using repetitive nerve stimulation (RNS) as an electrophysiological measurement of presynaptic neuromuscular transmission defect. With 20 Hz RNS, Group 1 showed significantly greater incremental responses compared to Group 2 (t-test, p = 0.0006). With 50 Hz RNS, Group 1 also showed significantly greater incremental responses compared to Group 2 (t-test, p = 0.002). Repeat studies at 6 months demonstrated return of increments to within normal limits in all three patients in Group 1. There was significant correlation of the initial increments (mean of 20 Hz and 50 Hz) and anti-GQ1b IgG antibody titer (Pearson’s correlation coefficient r = 0.76, p = 0.011). In addition to MFS, we have also shown that presynaptic dysfunction can occur in BBE. To this end, incremental responses in upper limb muscles may serve as surrogate markers for NM transmission defect in these disorders. As immunotherapy is the mainstay of treatment in these conditions, our findings of presynaptic neuromuscular transmission defect may serve as a potential parameter in selecting patients for future therapeutic trials.