Abstracts

Rationale: Reflex seizures are provoked by a specific stimulus and have been divided into pure reflex epilepsies and reflex seizures also associated with spontaneous seizures. The latter group typically has symptomatic epilepsy. The mechanism of reflex seizures has been reported to be dependent on cortical hyperexcitability. However, there is evidence from animal studies that stimulus provokable seizures arise from the brainstem and occur because of insufficient cortical inhibition. Detailed clinical and neurophysiological features of 11 children with reflex seizures are presented, providing evidence to support the hypothesis that reflex seizures arise in the brainstem and result from insufficient cortical inhibition. Methods: 11 children with stimulus-sensitive seizures were studied in detail. V-EEG monitoring results were included in the analysis. Review of the literature on animal models of reflex seizures with an emphasis on available information as to seizure mechanism was considered in interpreting the data. Results: See Table 1. Conclusions: 11 children with acquired startle or other reflex seizures are presented. Reflex seizures likely result from a lack of cortical modulation on subcortical pathways involving the reticulo-thalamic circuitry. Infantile spasms, other age-dependent epileptic encephalopathies, and neonatal seizures are thought to involve the brainstem, with some of the seizures termed "brainstem release phenomena". Startle seizures typically involve patients with early life extensive cerebral damage. The generalized nature of startle seizures despite a variety of cortical substrates suggests a brainstem origin and propogation via subcortical networks to the cortex or spinal cord. The startle reflex is a motor response originating in the lower brainstem. Startle seizures may require the proprioceptive input of the startle via the lemniscal pathway to the sensorimotor cortex. Although Chauvel et al.(1992) demonstrated a cortical origin (motor and premotor cortex) in 20 patients with stimulus-provoked seizures, it seems more likely that cortical activation follows the activation of subcortical networks and that there is a lack of inhibition or "gating" of the stimulus. Subcortical networks have been proposed to explain seizures in hydranencephalic patients. Animal models of stimulus-sensitive seizures have demonstrated a mesencephalic origin; in some models there is no (cortical) EEG correlate, particularly if the origin of the seizures is lower brainstem. Interestingly, in our most severely affected patients there was no EEG correlate seen as well. Patient #1 is of great interest in that he had a global deficiency of neurotransmitters on analysis of CSF. In one animal model (the genetically epilepsy prone rat--GEPR), serotonin system abnormalities have been described in the superior collicus and treatment with an SSRI ameliorated the seizures. With additional study of these patients, who are typically refractory to conventional AED therapy, there may be novel treatment approaches based on increased understanding of the neurochemistry of subcortical, brainstem systems.