{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:24:46Z","timestamp":1768505086436,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,24]]},"group-title":"Neuroscience","reference-count":57,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non-rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high-dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE-SWAS: 1) spikes and spindles would be anticorrelated, 2) high-dose 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-SWAS patients treated with high-dose diazepam that met criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre- and post-treatment NREM sleep. Spikes were quantified using a validated automated spike detector. Cognitive response was determined from chart review.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Spindle rate was anticorrelated with spike rate in the channel with the maximal spike rate (\n                    <jats:italic>p<\/jats:italic>\n                    =0.002) and averaged across all channels (\n                    <jats:italic>p<\/jats:italic>\n                    =0.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high-dose diazepam treatment (\n                    <jats:italic>p\u2264<\/jats:italic>\n                    2e-5, all tests). Spindle rate, duration, and percentage (\n                    <jats:italic>p<\/jats:italic>\n                    \u22640.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spike rate did not distinguish 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-SWAS, 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":"10.1101\/2023.04.22.537937","type":"posted-content","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T20:30:17Z","timestamp":1682368217000},"source":"Crossref","is-referenced-by-count":0,"title":["Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy"],"prefix":"10.64898","author":[{"given":"John 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