{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:19:20Z","timestamp":1756991960353,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rescue benzodiazepine medication can be used to treat seizure clusters, which are intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. The NeuroPace RNS\u00ae System is a device that detects abnormal electrographic activity through intracranial electrodes and administers electrical stimulation to control seizures. Reductions in electrographic activity over days to weeks have been associated with the longer\u2010term efficacy of daily antiseizure medications (ASMs). In this pilot study, electrographic activity over hours to days was examined to assess the impact of a single dose of a proven rescue therapy (diazepam nasal spray) with a rapid onset of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult volunteers (&gt;18\u2009years old) with clinically indicated RNS (stable settings and ASM usage) received a weight\u2010based dose of diazepam nasal spray in the absence of a clinical seizure. Descriptive statistics for a number of detections and a sum of durations of detections at 10\u2010min, hourly, and 24\u2010h intervals during the 7\u2010day (predose) baseline period were calculated. Post\u2010dose detections at each time interval were compared with the respective baseline\u2010detection intervals using a 1 SD threshold. The number of long episodes that occurred after dosing also were compared with the baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five participants were enrolled, and four completed the study; the excluded participant had recurrent seizures during the study. There were no consistent changes (difference\u2009&gt;1 SD) in detections between post\u2010dose and mean baseline values. Although variability was high (1 SD was often near or exceeded the mean), three participants showed possible trends for reductions in one or more electrographic variables following treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>RNS\u2010assessed electrographic detections and durations were not shown to be sensitive measures of short\u2010term effects associated with a single dose of rescue medication in this small group of participants. The variability of detections may have masked a measurable drug effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Rescue drugs are used to treat seizure clusters. Responsive neurostimulation (RNS) devices detect and record epilepsy brain waves and then send a pulse to help stop seizures. This pilot study looked at whether one dose of a rescue treatment changes brain activity detected by RNS. There was a very wide range of detections, which made it difficult to see if or how the drug changed brain activity. New studies should look at other types of brain activity, multiple doses, and larger patient groups.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12890","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T10:35:01Z","timestamp":1703241301000},"page":"380-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intracerebral electrographic activity following a single dose of diazepam nasal spray: A pilot study"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0862-5975","authenticated-orcid":false,"given":"Michael D.","family":"Privitera","sequence":"first","affiliation":[{"name":"Department of Neurology University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2700-0762","authenticated-orcid":false,"given":"Lucy C.","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-0722","authenticated-orcid":false,"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"},{"name":"John A. Burns School of Medicine University of Hawaii  Honolulu Hawaii USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-0606","authenticated-orcid":false,"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"volume-title":"VALTOCO\u00ae (diazepam nasal spray). Full prescribing information","year":"2023","author":"Neurelis, Inc","key":"e_1_2_14_2_1"},{"volume-title":"Nayzilam\u00ae (midazolam nasal spray). Full Prescribing Information","year":"2023","author":"UCB, Inc","key":"e_1_2_14_3_1"},{"volume-title":"LLC. Diastat\u00ae C\u2010IV (diazepam rectal gel). Full Prescribing Information","year":"2023","author":"Bausch Health US","key":"e_1_2_14_4_1"},{"issue":"1","key":"e_1_2_14_5_1","first-page":"S6","article-title":"Recognizing seizure clusters in the community: the path to uniformity and individualization in nomenclature and definition","volume":"63","author":"Haut SR","year":"2022","journal-title":"Epilepsia"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.04.022"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.15159"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16300"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806253382602"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.5.1274"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17041"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17385"},{"key":"e_1_2_14_13_1","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1111\/epi.17363","article-title":"Future opportunities for research in rescue treatments","volume":"63","author":"Wheless JW","year":"2022","journal-title":"Epilepsia"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17434440.2021.1994388"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16412"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2018.04.003"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.2689"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.11.1595"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170612"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100000342"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00464-1"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12890","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:49:04Z","timestamp":1707288544000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,4]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/epi4.12890"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12890","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"type":"print","value":"2470-9239"},{"type":"electronic","value":"2470-9239"}],"subject":[],"published":{"date-parts":[[2024,1,4]]},"assertion":[{"value":"2023-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}