Clinical characteristics of epilepsy patients with comorbid headache: experience from a tertiary epilepsy center
Authors: Zhang Shujiang , Lv Zhiyu , Li Jinmei , Zhou Dong 
Published: January 2025

Background
Headache is one of the most common comorbidities in epilepsy, with affected patients experiencing various types of headaches. This study aimed to investigate differences in comorbid headache types across epilepsy origins, comparing pain levels among epilepsy patients with multiple headache types, and exploring associations between headache characteristics and epilepsy prognosis.
Methods
We retrospectively analyzed consecutive adult epilepsy patients with comorbid headache, collecting comprehensive sociodemographic, epilepsy-related, and headache-related data, as well as data on headache-attributed lost time and quality of life. The overall prevalence of headache comorbidity in epilepsy was determined, and we compared clinical characteristics, quality of life, and headache-attributed lost time across different epilepsy origins. Based on the temporal relationship between headache and seizures, comorbid headaches were classified into inter-ictal headache (Inter-IH), ictal headache, pre-ictal headache (Pre-IH), and post-ictal headache (Post-IH) for subgroup analysis to explore differences in clinical characteristics by headache type. We conducted multiple logistic regression and receiver operating characteristic (ROC) analyses to calculate the area under the curve (AUC), assessing correlations between headache characteristics and epilepsy prognosis and the predictive accuracy for drug-refractory epilepsy (DRE).
Results
A total of 539 epilepsy patients with comorbid headache were included, comprising 233 with Inter-IH (43.22%), 38 with Pre-IH (7.05%), and 423 with Post-IH (78.48%); no patients had ictal headache. Among those with Inter-IH, 58 (10.76%) met the diagnostic criteria for migraine, and 87 (16.14%) met the criteria for tension-type headache. In our cohort, 7 patients (1.30%) experienced both Inter-IH and Pre-IH, 112 (22.08%) had both Inter-IH and Post-IH, 7 (1.30%) experienced Inter-IH, Pre-IH, and Post-IH, and 18 (3.34%) had both Pre-IH and Post-IH. The study included 382 patients with focal epilepsy (70.87%), 40 with generalized epilepsy (7.42%), and 117 with epilepsy of unknown origin (21.71%), with temporal lobe epilepsy being the most common focal type, representing 46.07% of cases. Patients with focal epilepsy reported lower quality of life than those with epilepsy of unknown origin (QOLIE-10, p < 0.05) and had a lower proportion of bilateral Post-IH than those with epilepsy of unknown origin (p < 0.05). The proportion of patients with level 1 Headache-Attributed Lost Time-90 Days (HALT-90) was higher in generalized epilepsy than in focal (87.50% vs. 66.23%, p < 0.05) and unknown origin (87.50% vs. 64.96%, p < 0.05). Comorbid migraine and HALT-90 were associated with DRE (p < 0.05), although predictive accuracy was low (AUC = 0.539; AUC = 0.566, respectively).
Conclusion
The most common type of epilepsy with comorbid headache was focal origin, with patients experiencing poorer quality of life than those with epilepsy of unknown origin. Clinical characteristics of comorbid headaches did not vary significantly by epilepsy origin, but patients with generalized epilepsy and comorbid headache had the least time lost. Post-IH was the most common type of comorbid headache. While comorbid migraine and HALT-90 were associated with DRE, the predictive accuracy for DRE was insufficient.