Abstracts

Rationale: Dravet Syndrome is an epileptic encephalopathy that is characterized by intractable epilepsy. In addition to seizures, patients typically have delays in multiple domains of development including motor, frequently manifested as an acquired crouched gait. SCN1A is expressed throughout the central and peripheral nervous system, including the axon initial segment of motor neurons. However, the pathophysiology of the gait abnormalities is unknown. Recently, Gitiaux et al published a study of EMG/NCS data of 12 children with SCN1A positive Dravet Syndrome with findings suggesting motor neuropathy/neuronopathy in this cohort, although there were multiple limitations to this study including small sample size. A large population of children with Dravet syndrome was reviewed for electromyographic findings. Methods: We performed a retrospective chart review in children with Dravet Syndrome who have had EMG/NCS studies performed for clinical purposes and have been followed in a single-institution neurology clinic between 2004 and 2018. Data collected and analyzed included gender, age at which EMG/NCS was completed, SCN1A mutation type, seizure frequency, medications at the time of EMG/NCS, neurologic exam abnormalities, and EMG/NCS results. Results: We identified 17 patients (10 male, 7 female) ages 3 to 21 years who met inclusion criteria. All had identified SCN1A mutations, most commonly missense or frameshift mutations (59% and 29%, respectively). No patients were seizure free at the time of EMG/NCS and they were taking an average of 2.8 anti-seizure medications. Gait abnormalities were documented in all patients. EMG/NCS were completed in 16 patients although limited due to cognitive abilities to comply with testing in 3 patients; the EMG portion was declined by one family. EMG/NCS abnormalities were identified in a total of 9 patients (53%) including 5 with NCS abnormalities and 8 with EMG abnormalities. Eight of these studies (89% of the abnormal studies) were suggestive of a neuropathy or polyneuropathy; 1 was felt to be abnormal due to reduced muscle activation alone. Of the 5 with NCS abnormalities, 1 had a pattern consistent with a demyelinating sensory neuropathy, 1 with a demyelinating predominantly motor neuropathy, 1 with an axonal sensory neuropathy, and 2 with mixed predominantly demyelinating sensorimotor neuropathies. EMG abnormalities were mixed and included evidence for chronic reinnervation or the presence of both ongoing denervation and chronic innervation. Conclusions: This study supports findings that peripheral nerve changes occur in patients with Dravet syndrome with gait abnormalities. The electrophysiologic changes include primary demyelinating or primary axonal changes, seen in motor nerves, sensory nerves, or in both.  Together with growing basic science knowledge in this area, it remains plausible that SCN1A expression in peripheral nerves contributes to the observed gait abnormalities in these patients. This supports the need for multifaceted care of patients with Dravet Syndrome beyond seizure management. Funding: None