The pivotal role of the supplementary motor area in startle epilepsy as demonstrated by SEEG epileptogenicity maps

Abstract

SUMMARYStartle seizures belong to reflex epilepsy syndromes. They usually occur in patients with mental deficiency and showing widely extended cortical lesions, often involving the sensorimotor area. Here we report three cases who did not fulfill these criteria, and in whom stereotactic electroencephalography (SEEG) recordings demonstrated the prominent involvement of the supplementary motor area (SMA). Visual analysis was complemented by time-frequency analysis of SEEG signals using a neuroimaging approach (Epileptogenicity Maps), which showed at seizure onset a significant increase of high frequency oscillations (HFOs, 60-100 Hz) over the premotor and prefrontal areas. Critically, in all cases, the SMA showed ictal HFOs at seizure onset and was included in the surgical resection. All patients became seizure-free after surgery, and histopathological examinations showed no specific lesion. These cases suggest the prominent but not exclusive role of SMA in startle seizures, and highlight the fact that surgery can be considered even in the absence of any magnetic resonance imaging (MRI) lesion.

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis

“…The most common surprising stimuli are a sudden touch or a sudden noise, and these cases are, therefore, sometimes misinterpreted as audiogenic or somatosensory-induced. In MRI-negative cases, foci could be localized to the prefrontal [42] and supplementary motor areas [43]. If a similarly provoked startle response is not followed by an epileptic seizure, the diagnosis is hyperekplexia, a genetically determined condition often mistaken for epilepsy or anxiety neurosis [44].…”

Do reflex seizures and spontaneous seizures form a continuum? – Triggering factors and possible common mechanisms

“…Startle-induced seizures can occur cryptogenic or as a reflex in patients with metabolic disturbances or large lesions, possibly due to involvement of the cingulate gyrus and supplementary motor area (SMA) [47,66,99]. A recent case study gives notice of a possible genetic factor, as dysregulation of excitatory synapses after microdeletion of the IL1RAPL1 gene has been associated with startle epilepsy [100].…”

Vagus nerve stimulation therapy is effective and safe for startle-induced seizures

“…The supplementary sensorimotor area (SMA) is nowadays considered the ictal symptomatogenic onset zone in startle-induced seizures [4]. Nevertheless, functional studies with MEG, ictal SPECT and PET support the hypothesis of a large network associated with SISs [6,7].…”

“…Effective therapeutic nonpharmacological options have yet to be established. Surgery has been proposed in a few cases, but most cases report difficulties in defining an unequivocal seizureonset zone, specially in nonlesional cases [4]. A case report with nonlesional MRI has suggested that callosotomy can also be effective in the treatment of SISs [5].…”