Abstract
BACKGROUND: Alice in Wonderland syndrome (AIWS) is a neuropsychiatric disorder characterized by sensory perception distortions, including altered body image perception and distortions of shape, size, motion, color, and speed. Migraine and infectious diseases are among the most common etiologies of AIWS. However, it has not been studied in individuals with persistent headache after COVID-19. METHODS: This cross-sectional study included a subset of individuals with AIWS symptoms derived from a survey conducted in Latin America to identify adults with persistent headache after COVID-19. For data analysis, AIWS individuals were characterized by sex and analyzed using univariable tests. Subsequently, the entire study cohort was stratified into two groups: the AIWS group and the non-AIWS group. Binomial logistic regression using the backward stepwise selection method was performed to identify the factors associated with AIWS after COVID-19. RESULTS: Out of 421 participants with persistent headache after COVID-19, 106 (25.2%) reported at least one AIWS symptom. The AIWS group was significantly younger (median age 36 vs. 39 years, p = 0.011) and had a higher proportion of pre-existing migraine (40.6% vs. 29.5%, p = 0.035) compared to the non-AIWS group. The most common post-COVID-19 AIWS symptoms were time distortion (32.1%), derealization/depersonalization (24.5%), and hyperchromatopsia (20.8%). Logistic regression analysis revealed that experiencing any AIWS symptom during acute COVID-19 was the strongest predictor for post-acute AIWS (OR = 9.937, 95% CI = 5.603-17.62, p <0.001). Other significant predictors included phonophobia (OR = 2.322, 95% CI = 1.288-4.185, p = 0.005) and depressive symptoms (OR = 1.937, 95% CI = 1.099-3.413, p = 0.022) during acute COVID-19. CONCLUSION: In this cohort, AIWS was a notable feature in adults with persistent headache after COVID-19, particularly in younger individuals with a history of migraine. Experiencing AIWS symptoms during acute infection increased the odds of post-acute AIWS symptoms nearly tenfold, suggesting SARS-CoV-2 may be a potent trigger. Clinicians should be aware of this association and screen for perceptual disturbances in patients with post-COVID-19 neurological sequelae.