The assessment of clinical, genetic and electrophysiological features in the comorbidity of juvenile myoclonic epilepsy and migraine

Epilepsy and migraine are common paroxysmal and chronic disorders. Their comorbidity might be explained by cortical spreading depression, genetic mechanisms, and channelopathies. The aim of this study is to compare the demographic characteristics, seizure, and migraine triggers, electrophysiological findings of juvenile myoclonic epilepsy (JME) with other idiopathic generalized epilepsy (IGE) subgroups and to investigate underlying genetic variants that explain the comorbidity with migraine. We assessed a total of 146 IGE patient; their clinical, electrophysiological and neuroimaging features were evaluated by a standardized epilepsy form and a detailed headache questionnaire was completed for each patient. Furthermore, Beck depression inventory (BDI), allodynia scale and Epworth sleepiness scale (ESS) were also applied. Migraine was diagnosed in 30.1% (44) of all IGE patients and 30.8% (24) of JME patients. Twenty patients (83.3%) of the JME and migraine group were women. Family history of migraine was more frequent in patients with JME and migraine (50%) (p<0.05). Epileptic seizure triggers such as mental activity, sun and light sensitivity, noise, exam days were more frequently cited in JME and migraine group compared to JME and migraine-free group, whereas stress was more frequent in JME and migraine group compared to other IGE and migraine-free group (p<0.05). Inter-ictal (p=0.002) and post-ictal headaches (p=0.001) were also significantly higher in the JME with migraine group. In the subgroup investigated by whole-exome analysis (WES); there were no overlapping or separate variants to explain all patients with migraine and IGE comorbidity. Among the rare variants, especially CPA6 and EHFC1 where associated with JME, on the other side HEATR3 and SDR9C7 were prominent variants in the comorbidity, whereas KCNK18 was likely patogenic. In conclusion, although patients with comorbidity of JME and migraine do not have a much worse course, they describe more frequent seizure triggers suggesting an increased sensitivity. New generation sequencing and deep phenotyping strategies are expected to further enhance understanding of migraine pathophysiology, frequent comorbidities, and related genetic mechanisms.