Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures

ObjectiveTo evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video-electroencephalography (EEG) monitoring. MethodsMedical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ. ResultsIn total, 75 epilepsy patients (mean age 3414.7years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12h after in-MDZ, the number of seizures was significantly lower (p=0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37h; IQR 4.87, range 0.03-21.87; p=0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually after 12h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41-15.45; p=0.009). SignificanceIctal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12h period and of generalized tonic-clonic seizures for 24h following in-MDZ.