Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd Edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.

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The misdiagnosis of headache disorders is a serious issue, and AI-based headache model diagnoses with external validation are scarce. We previously developed an artificial intelligence (AI)-based headache diagnosis model using a database of 4000 patients’ questionnaires in a headache-specializing clinic and herein performed external validation prospectively. The validation cohort of 59 headache patients was prospectively collected from August 2023 to February 2024 at our or collaborating multicenter institutions. The ground truth was specialists’ diagnoses based on the initial questionnaire and at least a one-month headache diary after the initial consultation. The diagnostic performance of the AI model was evaluated. The mean age was 42.55 ± 12.74 years, and 51/59 (86.67%) of the patients were female. No missing values were reported. Of the 59 patients, 56 (89.83%) had migraines or medication-overuse headaches, and 3 (5.08%) had tension-type headaches. No one had trigeminal autonomic cephalalgias or other headaches. The models’ overall accuracy and kappa for the ground truth were 94.92% and 0.65 (95%CI 0.21–1.00), respectively. The sensitivity, specificity, precision, and F values for migraines were 98.21%, 66.67%, 98.21%, and 98.21%, respectively. There was disagreement between the AI diagnosis and the ground truth by headache specialists in two patients. This is the first external validation of the AI headache diagnosis model. Further data collection and external validation are required to strengthen and improve its performance in real-world settings.

Nitric oxide (NO) is involved in the pathogenesis of cerebral ischemic injury. Here, we investigated the effects of aging on NO production during cerebral ischemia-reperfusion (IR). Male Wister rats (WRs) were assigned to 12-month-old (older; n = 5) and 3-month-old (younger; n = 7) groups. Similarly, male spontaneous hypertensive rats (SHRs) were allocated to 12-month-old (older; n = 6) and 3-month-old (younger; n = 8) groups. After anesthesia, their NO production was monitored using in vivo microdialysis probes inserted into the left striatum and hippocampus. Forebrain cerebral IR injuries were produced via ligation of the bilateral common carotid arteries, followed by reperfusion. The change in the NO₃⁻ of the older rats in the SHR groups in the striatum was less compared to that of the younger rats before ischemia, during ischemia, and after reperfusion (p < 0.05). In the hippocampus, the change in the NO₃⁻ of the older rats in the SHR groups was lower compared to that of the younger rats after reperfusion (p < 0.05). There were no significant differences between the two WR groups. Our findings suggested that aging in SHRs affected NO production, especially in the striatum, before and during cerebral ischemia, and after reperfusion. Hypertension and aging may be important factors impacting NO production in brain IR injury.