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Once considered a self\u2010limited electroencephalographic (EEG) phenomenon, D\/EE\u2010SWAS is now recognized as a disorder of brain network dysfunction in which persistent epileptiform discharges during non\u2010rapid eye movement sleep disrupt synaptic plasticity, sleep\u2010dependent memory consolidation, and neurodevelopmental trajectories. This review synthesizes recent advances in clinical phenotyping, genetics, neurophysiology, and therapeutics. Etiologically, D\/EE\u2010SWAS is highly heterogeneous, with pathogenic variants identified in nearly half of affected individuals, including copy number variants and single\u2010gene disorders involving ion channels, synaptic proteins, and transcriptional regulators.\n                    <jats:italic>GRIN2A<\/jats:italic>\n                    is the most frequently implicated gene, although marked intrafamilial and interfamilial variability underscores the role of modifying genetic and network\u2010level factors. Structural lesions\u2014particularly those affecting thalamocortical circuits\u2014represent another major disease substrate and are critical for treatment stratification. At the mechanistic level, abnormal thalamocortical oscillations, impaired sleep architecture, and disruption of slow\u2010wave and spindle activity provide a pathophysiological framework linking EEG abnormalities to cognitive and behavioral deterioration. Neuroimaging and EEG\u2013functional magnetic resonance imaging studies support a model of widespread network inhibition and disconnection extending beyond the primary epileptogenic zone. Therapeutically, corticosteroids currently represent the most effective first\u2010line treatment, demonstrating superior cognitive outcomes compared with benzodiazepines, although relapse after tapering is common, and optimal dosing strategies remain undefined. Precision medicine approaches, including N\u2010methyl\u2010D\u2010aspartate receptor\u2010targeted therapies for\n                    <jats:italic>GRIN<\/jats:italic>\n                    variants and channel\u2010specific treatments such as primidone for\n                    <jats:italic>TRPM3<\/jats:italic>\n                    gain of function, offer promising avenues toward disease modification. Epilepsy surgery should be considered early in children with unilateral structural etiologies, where it can provide substantial neurodevelopmental benefit. Future priorities include standardized outcome measures, integration of sleep\u2010based biomarkers, refinement of steroid protocols, and international collaborative trials to improve long\u2010term neurodevelopmental outcomes in this vulnerable population.\n                  <\/jats:p>","DOI":"10.1002\/epi.70271","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:30:05Z","timestamp":1777383005000},"page":"3835-3851","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Developmental and\/or epileptic encephalopathy with spike\u2010and\u2010wave activation in sleep: Pathophysiological insights and treatment options"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-0287","authenticated-orcid":false,"given":"Nicola","family":"Specchio","sequence":"first","affiliation":[{"name":"Neurology, Epilepsy, and Movement Disorders Unit, Bambino Ges\u00f9 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