Cortical excitability changes associated with fixation-off sensitivity: a case report

"Fixation-off sensitivity" (FOS) is an ideal human model for studying the features of epileptic discharges. Physiologically, FOS is expected to correspond to enhanced excitability of widespread cortical structures. To test this hypothesis, we measured by transcranial magnetic stimulation (TMS), the excitability level of the primary motor area in a 22-year-old woman with eyelid myoclonias and absences, who presented with generalized FOS. We also explored her visual system by pattern-reversal and flash-visual evoked potentials (VEPs). Both outside and within FOS, the cortical silent period was dramatically short, indicating defective γ-aminobutyric acid (GABA)(B) inhibition as a persistent background factor. The same was true for the short-interval intracortical inhibition, a TMS marker of cortical GABA(A) inhibition. The FOS state corresponded then to a pathologic enhancement of intracortical facilitation, a TMS marker of Glu/Asp transmission. During FOS, the flash VEP exhibited a hugely enhanced afterdischarge, expressing a pathologic overactivity of secondary visual areas. Within the limits of a single-case study, we thus provide electrophysiologic evidence supporting a grossly imbalanced cortical excitability, in both the frontal and posterior areas, as an important correlate of the present FOS subtype.