{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:06:44Z","timestamp":1790503604357,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS115868"],"award-info":[{"award-number":["R01NS115868"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Epileptic encephalopathy with spike\u2010wave activation in sleep (EE\u2010SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non\u2010rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high\u2010dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE\u2010SWAS: (1) spikes and spindles would be anti\u2010correlated, (2) high\u2010dose diazepam would increase spindles and decrease spikes, and (3) spindle response would be greater in those with cognitive improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Consecutive EE\u2010SWAS patients treated with high\u2010dose diazepam that met the criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre\u2010 and post\u2010treatment NREM sleep. Spikes were quantified using a validated automated spike detector. The cognitive response was determined from a chart review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Spindle rate was anti\u2010correlated with the spike rate in the channel with the maximal spike rate (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) and averaged across all channels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high\u2010dose diazepam treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20092e\u20105, all tests). Spindle rate, duration, and percentage (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spindle rate but not changes in spike rate distinguished between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These findings confirm thalamocortical disruption in EE\u2010SWAS, identify a mechanism through which benzodiazepines may support cognitive recovery, and introduce sleep spindles as a promising mechanistic biomarker to detect treatment response in severe epileptic encephalopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51840","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T12:59:04Z","timestamp":1687784344000},"page":"1513-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy"],"prefix":"10.1002","volume":"10","author":[{"given":"John R.","family":"McLaren","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston 02114 Massachusetts USA"},{"name":"Harvard Medical School Boston 02115 Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yancheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston 02114 Massachusetts USA"},{"name":"Harvard Medical School Boston 02115 Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-2546","authenticated-orcid":false,"given":"Hunki","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston 02114 Massachusetts USA"},{"name":"Harvard Medical School Boston 02115 Massachusetts 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