{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:36:35Z","timestamp":1768566995381,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,15]]},"group-title":"Genetic and Genomic Medicine","reference-count":39,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>\n                    Since the initial description of\n                    <jats:italic>CACNA1A-<\/jats:italic>\n                    related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially life-threatening events frequently seen in individuals with developmental and epileptic encephalopathies. However, the overall longitudinal course throughout childhood remains unknown.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We analyzed HM and seizure history in individuals with\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    -related HM, delineating frequency and severity of events in monthly increments through a standardized approach. Combining these data with medication prescription information, we assessed the response of HM to different agents.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Our cohort involved 15 individuals between 3 and 29 years (163 patient years) and included 11 unique and two recurrent variants (p.R1349Q and p.V1393M; both\n                    <jats:italic>n=<\/jats:italic>\n                    2). The age of first confirmed HM ranged from 14 months to 13 years (average 3 years). 25% of all HM events were severe (lasting &gt;3 days) and 73% of individuals had at least 1 severe occurrence. Spacing of HM events ranged from 1 month to 14 years and changes in HM severity over time of showed increases or decreases of &gt;2 severity levels in 12\/122 events. Eight individuals had epilepsy, but severity of epilepsy did not correlate with frequency and severity of HM events. While levetiracetam (\n                    <jats:italic>n=<\/jats:italic>\n                    6) and acetazolamide (\n                    <jats:italic>n=<\/jats:italic>\n                    5) were the most frequently used medications, they did not show efficacy in HM prevention or HM severity reduction. However, verapamil (\n                    <jats:italic>n=<\/jats:italic>\n                    3) showed efficacy in preventing HM episodes (OR 2.68, CI 1.39-5.67).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The longitudinal course of\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    -related HM lacks recognizable patterns for timing and severity of HM events or correlation with seizure patterns. Our data underscores the unpredictability of\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    -related HM, highlighting the need for close surveillance for reoccurring HM events even in individuals with symptom-free periods.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>\n                        24% of hemiplegic migraines (HM) in\n                        <jats:italic>CACNA1A-<\/jats:italic>\n                        related disorders are severe, involving cerebral edema and greater than 4 days to recover\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Timing and severity of HM are unpredictable, with large changes in severity between events, and age of onset ranging from 1-13 years<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Epilepsy occurred in 53% of individuals, with neither the timing nor severity of seizures correlated with HM<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2024.06.14.24308953","type":"posted-content","created":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T15:25:12Z","timestamp":1718465112000},"source":"Crossref","is-referenced-by-count":1,"title":["A Longitudinal Exploration of\n                  <i>CACNA1A<\/i>\n                  -related Hemiplegic Migraine in Children"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-3097","authenticated-orcid":false,"given":"Donna","family":"Schaare","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-9890","authenticated-orcid":false,"given":"Laina","family":"Lusk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4254-4267","authenticated-orcid":false,"given":"Alexis","family":"Karlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2718-296X","authenticated-orcid":false,"given":"Michael C.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-4939","authenticated-orcid":false,"given":"Jan","family":"Magielski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-7404","authenticated-orcid":false,"given":"Sara M.","family":"Sarasua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendra","family":"Allison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Boccuto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-0558","authenticated-orcid":false,"given":"Ingo","family":"Helbig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"4","key":"2024062006300847000_2024.06.14.24308953v1.1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/mgg3.24","article-title":"Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies","volume":"1","year":"2013","journal-title":"Mol Genet Genomic Med"},{"key":"2024062006300847000_2024.06.14.24308953v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.04.027"},{"key":"2024062006300847000_2024.06.14.24308953v1.3","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3215189\/v1"},{"key":"2024062006300847000_2024.06.14.24308953v1.4","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.577544"},{"key":"2024062006300847000_2024.06.14.24308953v1.5","unstructured":"Gobel H. 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