Alcohol-Related and Non-Alcohol-Related Wernicke Encephalopathy: A Systematic Review and Meta-Analysis of Epidemiology and Clinical Features.

Abstract

Introduction To characterize the epidemiology, risk factors, and clinical presentation of Wernicke encephalopathy (WE), and analyze differences between cases with and without excessive alcohol consumption. Methods A systematic search was conducted in PubMed, Scopus, and Web of Science up to April 1st, 2025. The included studies provided data on prevalence, risk factors, clinical and radiological findings, mortality, and prognosis in patients with WE. Pooled proportions and weighted means were calculated using random-effect models with Freeman-Tukey transformation. Heterogeneity was assessed using the I² statistic. Subgroup comparisons were performed based on the presence or absence of excessive alcohol consumption. Results A total of 12 studies comprising 5,510 patients were analyzed. Overall, 65.4% (95% CI: 56.0-74.2) were male, with a weighted mean age of 60.7 years. Among cases related to excessive alcohol consumption, 78.7% were male (mean age 55.2); in cases not related to such consumption, 52.6% were male (mean age 63.5). The classic triad was present in 32.7% of cases (95% CI: 19.2-47.7). Among patients evaluated by magnetic resonance imaging, typical lesions were identified in 82.0%, and atypical lesions in 44.8%. Overall mortality was 5.1% (95% CI: 2.3-8.8%) and higher in non-alcohol-related cases (8.8%). Alcohol consumption was the main risk factor (90.7%); among non-alcohol-related cases, the most frequent clinical settings were malnutrition (30.2%), infections (25.1%), and psychiatric disorders (15.4%). Conclusions WE is a multifactorial syndrome that extends beyond alcohol misuse, with wide clinical and pathophysiological variability. These findings underscore the importance of early recognition and prompt thiamine replacement, particularly in non-alcohol-related cases.