Objective: To explore the safety and efficacy of external trigeminal nerve stimulation (eTNS) in patients with drug-resistant epilepsy (DRE) using a double-blind randomized controlled trial design, and to test the suitability of treatment and control parameters in preparation for a phase III multicenter clinical trial.Methods: This is a double-blind randomized active-control trial in DRE. Fifty subjects with 2 or more partial onset seizures per month (complex partial or tonic-clonic) entered a 6-week baseline period, and then were evaluated at 6, 12, and 18 weeks during the acute treatment period. Subjects were randomized to treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters.Results: At entry, subjects were highly drug-resistant, averaging 8.7 seizures per month (treatment group) and 4.8 seizures per month (active controls). On average, subjects failed 3.35 antiepileptic drugs prior to enrollment, with an average duration of epilepsy of 21.5 years (treatment group) and 23.7 years (active control group), respectively. eTNS was well-tolerated. Side effects included anxiety (4%), headache (4%), and skin irritation (14%). The responder rate, defined as .50% reduction in seizure frequency, was 30.2% for the treatment group vs 21.1% for the active control group for the 18-week treatment period (not significant, p 5 0.31, generalized estimating equation [GEE] model). The treatment group experienced a significant within-group improvement in responder rate over the 18-week treatment period (from 17.8% at 6 weeks to 40.5% at 18 weeks, p 5 0.01, GEE). Subjects in the treatment group were more likely to respond than patients randomized to control (odds ratio 1.73, confidence interval 0.59-0.51). eTNS was associated with reductions in seizure frequency as measured by the response ratio (p 5 0.04, analysis of variance [ANOVA]), and improvements in mood on the Beck Depression Inventory (p 5 0.02, ANOVA). Conclusions:This study provides preliminary evidence that eTNS is safe and may be effective in subjects with DRE. Side effects were primarily limited to anxiety, headache, and skin irritation. These results will serve as a basis to inform and power a larger multicenter phase III clinical trial. Drug-resistant epilepsy (DRE) affects 30% of all people with epilepsy, and may lead to disability and death. [1][2][3][4] Trigeminal nerve stimulation (TNS) is a novel investigational neuromodulation therapy for patients with DRE. Classification of evidence:5 TNS can be delivered noninvasively, bilaterally, and at high frequencies, with positive effects on mood.5-7 The anatomy and biology of the trigeminal nerve support potential mechanisms by which TNS may impact epilepsy and mood disorders, and animal data demonstrate that stimulation of the trigeminal nerve and its related structures

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Summary:Purpose: To investigate the clinical characteristics and surgical outcomes in patients with unilateral hippocampal sclerosis whose scalp ictal EEG recordings localize to the opposite temporal lobe.Methods: We retrospectively reviewed the data of all adult patients who had undergone depth electrode implantation for suspected temporal lobe epilepsy (TLE) at UCLA (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000) or the Montreal Neurological Institute (1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998) to identify patients who had (a) unilateral hippocampal atrophy, and (b) surface ictal recordings in which the majority of seizures appeared to initiate in the opposite temporal lobe, with few or none that were concordant with the hippocampal atrophy.Results: Of 109 patients with suspected TLE who underwent depth electrode study at the two centers, five patients met the aforementioned criteria. Four of these five had very severe hippocampal atrophy, whereas the fifth had mild atrophy but extensive signal change on magnetic resonance imaging (MRI). Depth electrode recordings in four of the five patients yielded clear ictal onset in the mesial temporal lobe ipsilateral to the imaging abnormality (contralateral to apparent scalp ictal onset). One patient had an unusual bitemporal onset pattern, which was nonetheless suggestive of onset in the sclerotic hippocampus. No patient had intracranial ictal onset contralateral to the imaging abnormality. All patients underwent resection of the structurally abnormal temporal lobe. After follow-up of ≥2 years, four (80%) of five patients were seizure free, while the fifth showed lesser improvement (class III).Conclusions: Some patients with severe hippocampal sclerosis (sometimes called a "burned-out hippocampus") have atypical spread of ictal discharges, resulting in apparent gross discordance between imaging and scalp ictal recordings. These patients nonetheless have excellent surgical outcomes on the whole. Whether such patients may forego intracranial recordings requires further study.