ObjectivesInvasive vagal nerve stimulation (iVNS) is an established treatment option for drug-resistant focal seizures and has been assumed to diminish frequent co-incidental daily headache/migraine. However, long-term effects on cognitive/affective head pain perception, headache intensity/frequency are lacking. We therefore investigated potential iVNS-induced effects in patients with drug-resistant focal seizure and daily headache/migraine. Materials and MethodsA clinical database was used to select 325 patients with drug-resistant epilepsy treated by either iVNS plus best medical treatment (BMT) or BMT alone, compared to a healthy control group (HC). We assessed headache intensity (VAS), headache frequency, affective/cognitive pain perception (PASS; FSVA), migraine disability scores (MIDAS), sleep architecture (PSQI), depressive symptoms (BDI), and body weight (BMI). ResultsNineteen patients with daily headache/migraine composed the clinical groups (10 iVNS and 9 BMT; iVNS mean age 49 years, range 36-61 years; BMT mean age 45 years, range 23-63 years; equally distributed gender). Cervical iVNS was applied from 5-13 years (mean 8 years) with following stimulation patterns: 1.3 mA (0.5-2 mA), 20 Hz, 250 sec, 30 sec on/1.9 min off (0.5-5 min). The iVNS group had significantly lower VAS scores (iVNS 5.4; BMT 7.8; p=0.03) and PASS cognitive/anxiety subscores (iVNS 21; BMT 16; p=0.02) compared to BMT and HC. Global PASS (p=0.07), FSVA, PSQI, BDI, and BMI scores did not differ significantly between groups. ConclusionsiVNS appears to have positive modulatory long-term effects on headache and affective/cognitive head pain perception in patients with drug-resistant focal epilepsy, thus deserving further attention.