Altered cortical excitability in tuberous sclerosis and the effect of mTOR inhibitors: An intracranial electrical stimulation study.
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OBJECTIVE: We used electrical stimulation mapping (ESM) of functional responses, after-discharges (ADs), and unwanted electrical stimulation-induced seizures (EIS) to explore differences in cortical excitability in tuberous sclerosis complex (TSC) patients on mTOR inhibitors, TSC patients not on mTOR inhibitors, and drug-resistant epilepsy (DRE) of unknown etiology. METHODS: In 20 patients with TSC and 10 patients with DRE of unknown etiology, incidence and current thresholds of physiologic (language and motor) and pathologic (ADs, EIS) responses were analyzed using mixed effects models against disease phenotype (TSC vs unknown) and use of mTOR inhibitors. RESULTS: Patients with TSC showed a higher incidence and required a lower threshold current to elicit motor responses and ADs compared to those with DRE of unknown etiology. In TSC patients, mTOR inhibitors increased the threshold for motor responses and ADs, and decreased the incidence of face motor responses, language responses, and ADs. CONCLUSIONS: TSC patients exhibit higher physiologic and pathologic cortical excitability evidenced by a higher incidence and lower current thresholds of ESM responses, which appears to be mitigated by mTOR inhibitors. SIGNIFICANCE: To our knowledge, this is the first study providing direct intracranial evidence for altered cortical excitability in TSC and the corrective effect of mTOR inhibitors.