Giant SEPs and SEP-recovery function in Unverricht–Lundborg disease

Abstract: Objective: To evaluate the relationship between sensory hyperexcitability as revealed by giant SEPs and the SEP recovery function (SEP-R) in a series of patient with progressive myoclonic epilepsy of Unverricht–Lundborg type, identified as epilepsy, progressive myoclonic 1A (EPM1A), MIM #254800. Methods: We evaluated SEPs by applying median nerve stimuli and SEP-R using paired stimuli at inter-stimulus intervals (ISIs) of between 20 and 600ms in 25 patients and 20 controls. The SEPs were considered “giant” if the N20P25 and P25N33 amplitudes exceeded normal mean values by +3SD. Results: During the paired-stimulus protocol, the SEPs elicited by the second stimulus (S2) were detectable at all ISIs but consistently suppressed in the 13 patients with giant SEPs reflecting a significantly delayed SEP-R. Maximal suppression roughly corresponded to the plateau of a broad middle latency (>100ms) wave pertaining to the S1 response. Conclusions: The cortical processing dysfunction generating giant SEPs in EPM1A patients consistently combines with a long-lasting suppression of hyperexcitability that leads to a delayed giant SEP-R without obstructing the response to incoming stimuli. Significance: The delayed SEP-R is not due to true inhibition but the suppression of aberrant hyper-synchronisation sustaining giant SEPs. A broad middle latency SEP component adds a significantly suppressive effect. This suggests that cortico-subcortical circuitries contribute to both the gigantism and the delayed SEP-R. [Copyright &y& Elsevier]