title: Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Medical 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.
  
  
  RESULTS
  In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). 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 2.17 min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h 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 (5.83 h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h; 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 12 h (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).
  
  
  CONCLUSIONS
  Ictal 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 12 h period and of generalized tonic-clonic seizures for 24 h following in-MDZ.
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.|Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Kay
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.|Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Reif
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Belke
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.|Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.affiliation: Central Pharmacy, University Hospitals Giessen and Marburg, Marburg, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Fründ
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Knake
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.|Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Rosenow
authors.affiliation: Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.|Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: Adam
authors.identifier: http://orcid.org/0000-0001-6288-9915
authors.initials: A
authors.lastname: Strzelczyk
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004569:Electroencephalography; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D008875:Middle Aged; D008991:Monitoring, Physiologic; D012008:Recurrence; D012640:Seizures / Q000188:drug therapy* / Q000601:surgery; D014741:Video Recording; D055815:Young Adult
chemical_list: D018757:GABA Modulators; D008874:Midazolam
keywords: Benzodiazepine; Emergency; Epilepsy; Intranasal; Midazolam; Seizure control