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Published on: June 23, 2023
Alcohol use disorder and epileptogenesis in primary malignant brain tumors: temporal associations in a nationwide EHR
Kevin Hoffman1, Malay Shah1, James Madsen1
1School of Medicine, Baylor College of Medicine, Houston, TX, United States.
Purpose:
Low-grade primary malignant brain tumors (PMBTs) frequently cause seizures and epilepsy, which worsen patient morbidity and quality of life. Alcohol use disorder (AUD) is a known risk factor for seizures in the general population, but its role in PMBT-associated seizures remains poorly understood.
Methods:
We conducted a retrospective cohort study using the Cosmos EHR database (2015-2025), identifying 244,955 adult patients with low-grade PMBTs. Seizure/epilepsy and AUD diagnoses were defined via ICD-10 codes. Associations were assessed using chi-square tests and pooled Mantel-Haenszel (adjusting for age, sex, and race). Cumulative incidence of new AUD and seizure/epilepsy diagnoses was analyzed in six-month intervals across a 102-month follow-up period.
Results:
Low-grade PMBT patients with AUD were nearly twice as likely to have seizures/epilepsy compared to those without AUD exposure (OR = 1.90, 95 % CI 1.83-1.97, p < 0.001). After adjusting for demographics, AUD remained significantly associated with seizure risk (OR = 1.37, 95 % CI 1.24-1.51, p < 0.001). This association was strongest among younger patients. Cumulative incidence comparison indicated that AUD preceded seizure onset more than the reverse (p < 0.001). Tumor sub-type analysis demonstrated heterogeneity in seizure/epilepsy prevalence in glioma and non-glioma tumors.
Conclusions:
AUD is potentially associated with increased seizure risk in PMBT patients, with a stronger effect in younger individuals. These findings suggest that alcohol-related hyperexcitability may compound tumor-associated epileptogenesis, highlighting AUD as a potentially modifiable risk factor. Prospective studies are warranted to confirm these relationships and to evaluate interventions targeting alcohol use for seizure mitigation.
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