{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:15:51Z","timestamp":1768569351651,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,10]]},"group-title":"Neurology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Sleep and rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe the extent of RAR perturbations in adults with epilepsy and intellectual disability (\u201cE+ID\u201d), using a cross-sectional case-control design. We examined whether RAR phenotypes correlated with epilepsy severity, deficits in adaptive function and\/or comorbid psychopathology.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Primary caregivers of E+ID adults provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers were also asked to ensure that subjects wore an Actiwatch-2 device continuously on their nondominant wrist for at least ten days. From recorded actograms, we calculated RAR amplitude, acrophase, robustness, intradaily variability (IV), interdaily stability (IS) and estimates of sleep quantity and timing. We compared these RAR metrics against those from (i) a previously published cohort of adults with epilepsy without ID (E\u2013 ID), and (ii) a cohort of age- and sex-matched intellectually able subjects measured within the Study of Latinos (SOL) Ancillary actigraphy study (SOL). Within E+ID subjects, we applied\n                    <jats:italic>k-<\/jats:italic>\n                    means analysis to divide subjects into three actigraphically distinct clusters.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    46 E+ID subjects (median age 26 [20-68], 47% female) provided a median recording duration of 11 days [range 6-27]. Surveys reflected low to\n                    <jats:italic>extremely<\/jats:italic>\n                    low levels of adaptive function (ABAS3 General Adaptive Composite score: median 50 [49-75]), and low\/subclinical levels of psychopathology (ABCL total score: median 54.5 [25-67]). Compared with E-ID (n=57) and SOL (n=156) cohorts, E+ID subjects displayed significantly lower RAR amplitude, robustness and IS, with significantly higher IV and total daily sleep. K-means clustering of E+ID subjects recognized an intermediate cluster \u201cB\u201d, with RAR values indistinguishable to E-ID. Cluster \u201cA\u201d subjects displayed pronounced hypoactivity and hypersomnia with high rates of rhythm fragmentation, while cluster \u201cC\u201d subjects featured hyper-robust and high amplitude RARs. All three clusters were similar in age, body mass index, antiseizure medication (ASM) polytherapy, ABAS3 and ABCL scores. We qualitatively describe RAR examples from all three clusters.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>We show that adults with epilepsy and intellectual disability display a wide spectrum of RAR phenotypes that do not neatly correlate with measures of adaptive function or epilepsy severity. Prospective studies are necessary to determine whether continuous actigraphic monitoring can sensitively capture changes in chronobiological health that may arise with disease progression, iatrogenesis (e.g., ASM toxicity) or acute health deteriorations (e.g., seizure exacerbation, pneumonia). Similar long-term data is necessary to recognize whether behavioral interventions targeted to \u2018normalize\u2019 RARs may promote improvements in adaptive function and therapy engagement.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.09.24313145","type":"posted-content","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:00:39Z","timestamp":1726030839000},"source":"Crossref","is-referenced-by-count":0,"title":["Rest-Activity Rhythm Phenotypes in Adults with Epilepsy and Intellectual Disability"],"prefix":"10.64898","author":[{"given":"Nandani","family":"Adhyapak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace E","family":"Cardenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A","family":"Abboud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishnav","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024091216500397000_2024.09.09.24313145v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa371"},{"key":"2024091216500397000_2024.09.09.24313145v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.80"},{"key":"2024091216500397000_2024.09.09.24313145v1.3","first-page":"458","article-title":"Transient Cognitive Impairment in Epilepsy","volume":"11","year":"2018","journal-title":"Front Mol Neurosci"},{"issue":"11","key":"2024091216500397000_2024.09.09.24313145v1.4","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1111\/epi.17060","article-title":"Features of intracranial interictal epileptiform discharges associated with memory encoding","volume":"62","year":"2021","journal-title":"Epilepsia"},{"issue":"5","key":"2024091216500397000_2024.09.09.24313145v1.5","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1684\/epd.2022.1467","article-title":"Cumulative effects of antiseizure medication on intelligence in children with focal epilepsy","volume":"24","year":"2022","journal-title":"Epileptic Disord"},{"key":"2024091216500397000_2024.09.09.24313145v1.6","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002060"},{"key":"2024091216500397000_2024.09.09.24313145v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2017.08.039"},{"issue":"18","key":"2024091216500397000_2024.09.09.24313145v1.8","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1212\/WNL.0b013e3182a9f482","article-title":"NINDS epilepsy and autism spectrum disorders workshop report","volume":"81","year":"2013","journal-title":"Neurology"},{"key":"2024091216500397000_2024.09.09.24313145v1.9","doi-asserted-by":"crossref","first-page":"108191","DOI":"10.1016\/j.yebeh.2021.108191","article-title":"The relationship between antiepileptic drug load and challenging behaviors in older adults with intellectual disability and epilepsy","volume":"122","year":"2021","journal-title":"Epilepsy Behav"},{"issue":"3","key":"2024091216500397000_2024.09.09.24313145v1.10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/ane.12943","article-title":"Behavioural changes in patients with intellectual disability treated with brivaracetam","volume":"138","year":"2018","journal-title":"Acta Neurol Scand"},{"key":"2024091216500397000_2024.09.09.24313145v1.11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02536.x"},{"key":"2024091216500397000_2024.09.09.24313145v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108324"},{"key":"2024091216500397000_2024.09.09.24313145v1.13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.seizure.2015.04.004","article-title":"Mortality in people with intellectual disabilities and epilepsy: A systematic review","volume":"29","year":"2015","journal-title":"Seizure"},{"issue":"5","key":"2024091216500397000_2024.09.09.24313145v1.14","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1007\/s00415-021-10938-3","article-title":"Epilepsy related multimorbidity, polypharmacy and risks in adults with intellectual disabilities: a national study","volume":"269","year":"2022","journal-title":"J Neurol"},{"key":"2024091216500397000_2024.09.09.24313145v1.15","doi-asserted-by":"crossref","unstructured":"Downs J , Ludwig NN , Wojnaroski M , et al. 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