{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T15:40:52Z","timestamp":1776786052447,"version":"3.51.2"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Episodic ataxias (EA) comprise a heterogeneous group of genetic conditions with spells of gait difficulty and imbalance, for which the main causes are EA1 (\n                      <jats:italic>KCNA1<\/jats:italic>\n                      gene) and EA2 (\n                      <jats:italic>CACNA1A<\/jats:italic>\n                      gene). While EA1 may respond to some antiepileptics and EA2 responds to acetazolamide, no guideline exists to inform decision-making in settings where genetic testing is unavailable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We sought to determine distinguishing clinical features between EA1 and EA2 and propose an algorithm based on our findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Systematized literature review to identify individuals with confirmed pathogenic variants in\n                      <jats:italic>KCNA1<\/jats:italic>\n                      and\n                      <jats:italic>CACNA1A,<\/jats:italic>\n                      followed by statistical analysis to compose a management algorithm. Subsequently, the algorithm was tested in cases described within the last three years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Attack duration with a cut-off of &amp;lt; 10\u202fmin had high sensitivity (75.3%) and specificity (94.0%) for EA1. Additional features with high specificity included symptoms during the attacks (e.g., headaches in EA2, 95.7%) and symptoms between attacks (e.g., myokymia in EA1 99.6%; nystagmus in EA2, 98.8%). Kinesigenic triggers were more frequently reported in EA1 (68.4% vs. 5.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). EA1 subjects also had more frequent attacks (Daily 37.9% vs. 15.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) and had a lower age of onset (7y, IQR [4\u201310] vs. 10y, IQR [5\u201315],\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.003). Testing our algorithm in a case cohort yielded a sensitivity of 87.5% in identifying EA2 cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EA1 and EA2 patients represent clinically different populations. We propose a management algorithm based on features with highest diagnostic accuracy, which may inform decision-making in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1735246","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:47:00Z","timestamp":1776782820000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic approach to episodic ataxia types 1 and 2: a proposed algorithm for limited resource-settings"],"prefix":"10.3389","volume":"17","author":[{"given":"Claudio M.","family":"de Gusmao","sequence":"first","affiliation":[{"name":"Department of Neurology, Mass General Brigham Hospital","place":["Boston, MA, United States"]},{"name":"Department of Neurology, Universidade de S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas H. M. R.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa, Hospital Sirio-Liban\u00eas","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan W.","family":"Mink","sequence":"additional","affiliation":[{"name":"Independent Researcher, Pittsford","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex R.","family":"Paciorkowski","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Rochester Medical Center","place":["Rochester, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Pringsheim","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Calgary","place":["Calgary, AB, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Assis","family":"Della Ripa","sequence":"additional","affiliation":[{"name":"Mendelics Genomic Analysis","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina Silva","family":"Rauffus","sequence":"additional","affiliation":[{"name":"Mendelics Genomic Analysis","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Carolina","family":"Coan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Universidade Estadual de Campinas","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Silveira-Moriyama","sequence":"additional","affiliation":[{"name":"Department of Neurology, Universidade Estadual de Campinas","place":["S\u00e3o Paulo, Brazil"]},{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology","place":["London, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ng1094-136","article-title":"Episodic ataxia\/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1","volume":"8","author":"Browne","year":"1994","journal-title":"Nat Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0092-8674(00)81373-2","article-title":"Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4","volume":"87","author":"Ophoff","year":"1996","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1086\/302909","article-title":"Coding and noncoding variation of the human Calcium-Channel \u03b24-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic 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