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We define severe acute motor exacerbations (SAME) as acute\/subacute motor symptoms that persist for hours\u2010to\u2010days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing\/dysphagia). Phenomenology includes dystonia, choreoathetosis, combined movement disorders, weakness, and hemiplegic attacks. SAME can develop in diverse diseases and can be preceded by triggers or catabolic states. Recent descriptions of SAME in complex neurodevelopmental and epileptic encephalopathies have broadened appreciation of this presentation beyond inborn errors of metabolism. A high degree of clinical suspicion is required to identify appropriately targeted investigations and management. We conducted a comprehensive literature analysis of etiologies. Reported triggers are described and classified as per pathophysiological mechanism. A video of six cases displaying multiple SAME with diverse outcomes is provided. We identified 50 different conditions that manifest SAME, some associated with developmental regression. Etiologies include disorders of metabolism: energy substrate, amino acids, complex molecules, vitamins\/cofactors, minerals, and neurotransmitters\/synaptic vesicle cycling. Non\u2010metabolic neurodegenerative and genetic disorders that present with movement disorders and epilepsy can additionally manifest SAME. A limited number of triggers are grouped here, together with an approach to investigations and general management strategies. Several neurogenetic and neurometabolic disorders manifest SAME. Identifying triggers can help in certain cases narrow the differential diagnosis and guide the expeditious application of targeted therapies to minimize adverse developmental and neurological consequences. This process may inform pathogenesis and eventually improve our understanding of the mechanisms that lead to the development of SAME. \u00a9 2024 International Parkinson and Movement Disorder Society.<\/jats:p>","DOI":"10.1002\/mds.29905","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T06:32:38Z","timestamp":1723185158000},"page":"1446-1467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Severe Acute Motor Exacerbations (\n                    <scp>SAME<\/scp>\n                    ) across Metabolic, Developmental and Genetic Disorders"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-7488","authenticated-orcid":false,"given":"Blas","family":"Couto","sequence":"first","affiliation":[{"name":"Edmond J. 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