Alcohol Withdrawal Seizures: Neurobiological Mechanisms, Clinical Predictors, and Evidence- Based Management.

Abstract

Background: Alcohol withdrawal (AW) seizures are acute symptomatic seizures occurring in the context of alcohol cessation in dependent individuals. Although often self-limited, seizures are associated with an increased risk of complications such as delirium tremens, prolonged hospitalization, and neurocognitive decline. This review synthesizes recent findings on the neurobiological underpinnings, clinical features, genetic risk factors, and treatment strategies for AW seizures.

Methods: We conducted a focused narrative review using PubMed and Scopus databases, covering studies published between 2000 and 2024. Key words included alcohol withdrawal seizures, pathophysiology, GABA, NMDA receptors, kindling, carbamazepine, hippocampal neurogenesis, and genetic susceptibility. Additional references were identified through manual review of citations from the key articles. Only peer-reviewed studies in English were considered. Particular emphasis was placed on high-quality clinical trials, translational animal models, and recent reviews integrating neurobiological and therapeutic insights.

Results: AW seizures arise from a neuroadaptive imbalance between inhibitory GABAergic and excitatory glutamatergic systems, which is exacerbated by abrupt alcohol cessation. Hippocampal neurogenesis and dentate gyrus dysregulation have been identified as key contributors to seizure susceptibility. Genetic polymorphisms-particularly in SLC6A3 and APOE-appear to modulate individual vulnerability. While benzodiazepines remain the first-line treatment for AW seizures, carbamazepine has demonstrated efficacy as an adjunct or alternative in high-risk cases where benzodiazepines are contraindicated or ineffective. AW seizures are predictive of further withdrawal complications and long-term cognitive deficits, highlighting the importance of early recognition and personalized management strategies.

Conclusions: AW seizures represent a critical clinical and neurobiological marker in the course of alcohol use disorders. Improved understanding of their pathophysiology and prognosis supports a stratified treatment approach incorporating both acute symptom control and long-term relapse prevention.