Cerebral arteriopathy and its role in persistent post-COVID headache and brain fog: a quantitative study

Abstract Background Headache and brain fog are common after COVID-19 infection, and inflammation and vasculopathy might be the potential underlying mechanisms. This study aimed to delineate the extent and impact of cerebrovascular involvement in patients with persistent long-COVID syndrome in a large Asian cohort. Methods We prospectively collected data from patients with persistent (≥ 3 months) post-COVID headache or brain fog, and controls were free from neurological symptoms within 3 months after COVID-19 resolution. The anterior and posterior Focal Cerebral Arteriopathy Severity Score (FCASS) was used to assess the severity of arteriopathy and was modified to account for bilateral involvement (total score: anterior: 0–40; posterior: 0–52). Symptom severity was assessed using monthly headache days, Migraine Disability Assessment (MIDAS), and brain fog severity scale (0–10). Results A total of 108 patients (M: F = 27:81) were divided into four groups based on symptoms categories. The presence of more symptom categories was associated with higher anterior-FCASS (combined 6.6 [2.1] vs. headache 3.6 [1.6] vs. brain-fog 4.7 [1.7] vs. control 0.8 [0.6], p < 0.001 by one-way ANOVA) and a posterior-FCASS (combined 5.5 [2.2] vs. headache 4.2 [1.6] vs. brain-fog 4.4 [2.3] vs. control 0.8 [0.8], p < 0.001 by one-way ANOVA). Pure brain- fog was more likely have predominance of anterior circulation involvement than pure headache (80.8% vs. 48.0%, p = 0.020), but the severity of brain fog was correlated with only the posterior-FCASS (Pearson’s r = 0.338, p = 0.009) rather than the anterior-FCASS (Pearson’s r = 0.173, p = 0.195). Conclusions Anterior circulation arteriopathy and hypoperfusion may underlie persistent post-COVID brain fog. However, post-COVID headaches may not depend solely on changes in intracranial vessels.