Abstracts

Rationale: Reflex seizures, defined as seizures consistently evoked by a stimulus, are rare. They are classified into symptomatic/acquired and idiopathic/genetic subtypes. Dravet Syndrome is a severe childhood epileptic encephalopathy due to underlying mutations in a neuronal sodium channel (SCN1A), in which stimulus-provoked seizures are frequently observed, including temperature and light sensitivity. In DS, the pathophysiology of seizures has been attributed to dysfunction of the affected inhibitory interneurons. We examined a cohort of children with DS to determine the prevalence and clinical characteristics of reflex seizures. We propose that the underlying interneuronopathy accounts for the predisposition to reflex seizures which result from faulty gating of afferent stimuli. Subcortical networks are an essential component in the mediation of stimulus-sensitive seizures.Methods: 12 children with DS were retrospectively reviewed to determine the prevalence, clinical characteristics, and treatment response of stimulus-sensitive seizures. Results: 6/12 (50%) children had reflex seizures, 12/12 (100%)if hyperthermia is considered a stimulus. Of the non-hyperthermia triggered reflex seizures, the majority were photosensitive. Three children had seizures triggered by emotion (being chastised, told no , or with temper tantrums). No children had audiogenic (startle) or touch sensitive seizures. When performed during an EEG, photic stimulation triggered clinical seizures or a photoparoxysmal response in 1 and 5 children (out of 11), respectively. Parents reported being able to interrupt seizures by redirecting or distracting their child in 3 cases, though this method was not consistently successful. One child had special blue lenses which were partly useful in suppressing seizure sensitivity. All children had medically refractory epilepsy with other seizure types. Conclusions: Reflex seizures have been reported in about 40% of children with Dravet Syndrome; in our cohort they were present in 50% (excluding hyperthermia-associated seizures). Dravet Syndrome-associated mutations in the neuronal sodium channel SCN1A are mainly expressed in inhibitory interneurons which modulate afferent stimuli and help determine the degree of cortical excitability. In experimental models of reflex seizures, cortical hyperexcitability appears to be a necessary substrate, but studies have clearly demonstrated the role of subcortical networks as well. Dravet Syndrome provides a useful model for studying reflex seizures in the human brain. The observation that some reflex seizures can be provoked by emotion and interrupted by distraction/redirection suggests novel approaches to treatment of these medically-resistant seizures.