Gender Differences in 3-Month Outcomes of Erenumab Treatment—Study on Efficacy and Safety of Treatment With Erenumab in Men

Objective: We reported gender-specific data on the efficacy and safety of erenumab, a monoclonal antibody antagonizing the calcitonin gene-related peptide (CGRP) receptor.Methods: Our pooled patient-level analysis of real-world data included patients treated with erenumab and followed up for 12 weeks. We considered the following outcomes at weeks 9–12 of treatment compared with baseline: 0–29%, 30–49%, 50–75%, and ≥75% responder rates, according to the decrease in monthly headache days (MHDs), rate of treatment stopping, change in MHDs, monthly migraine days (MMDs), monthly days of acute medication and triptan use, and Headache Impact Test-6 (HIT-6) score from baseline to weeks 9–12. Outcomes were compared between men and women by the chi-squared test or t-test, as appropriate. An analysis of covariance (ANCOVA) was performed to identify factors influencing the efficacy outcomes.Results: We included 1,410 patients from 16 centers, of which 256 (18.2%) were men. Men were older than women and had a lower number of MHDs at baseline. At weeks 9–12, compared with baseline, 46 (18.0%) men had a ≥75% response, 75 (29.3%) had a 50–74% response, 35 (13.7%) had a 30–49% response, and 86 (33.6%) had a 0–29% response, while 14 (5.5%) stopped the treatment. The corresponding numbers for women were 220 (19.1%), 314 (27.2%), 139 (12.0%), 402 (34.8%), and 79 (6.8%). No gender difference was found in any of the outcomes. The ANCOVA showed that gender did not influence the efficacy of outcomes.Conclusion: We found that erenumab is equally safe and effective in men compared with women after 12 weeks.

Correlation between depression level and headache severity: A study among medical students during the COVID-19 pandemic

Headache is the most prevailing disorder and the third leading cause of disability worldwide. The prevalence of primary headaches has been reported to increase by 2-4 times in patients with psychiatric comorbidities, including depression. This study sought to assess the correlation between depression level and headache severity among medical students. To the best of our knowledge, this is the first study to evaluate the correlation between depression level and headache severity in Indonesia. A cross-sectional study was conducted among students of Airlangga University in 2021. To evaluate the level of depression and the severity of headache, Depression Anxiety Stress Scales (DASS-42) and Headache Impact Test 6 (HIT-6) were used, respectively. A set of validated questionnaires were used to assess students’ demographic characteristics. A total of 82 medical students were included in this study and most of them were female (86.6%). The third-semester students represented the highest proportion (45.2%) of subjects. The mean age and body mass index (BMI) were 19.88 ± 1.03 and 22.55±4.44, respectively. The average DASS-42 score was 10.98±11.47 which indicated a mild depression level. The average HIT-6 score was 45.74±6.130 which revealed a mild impact. The data of Spearman correlation suggested that headache severity was significantly correlated with depression level (r=0.396, p<0.001). This study provides insights on the importance of stress management and depression prevention to decrease the risk of headache, and vice versa.

Deterioration of headache impact and health-related quality of life in migraine patients after cessation of preventive treatment with CGRP(−receptor) antibodies

Background Migraine preventive treatment with CGRP(−receptor) monoclonal antibodies (mAbs) has a positive effect on patients’ health-related quality of life (HRQoL). The German treatment guidelines recommend discontinuing successful treatment with CGRP(−receptor) mAbs after 6–12 months. We aimed to evaluate headache-specific and generic HRQoL for three months after discontinuation of CGRP(−receptor) mAb treatment. Methods We conducted a prospective, longitudinal cohort study, including patients with migraine after 8–12 months of therapy with a CGRP(−R) mAb and before a planned discontinuation attempt. HRQoL was assessed at the time of the last mAbs injection (V1), eight weeks later (V2), and sixteen weeks later (V3). For headache-specific HRQoL, we used the Headache Impact Test-6 (HIT-6). Generic HRQoL was determined with the EuroQol-5-Dimension-5-Level (ED-5D-5L) form, and the Short-Form 12 (SF-12), which comprises a Physical Component Summary (PCS-12) and a Mental Component Summary (MCS-12). Questionnaires’ total scores were compared across the three observation points using nonparametric procedures. Results The study cohort consisted of n = 61 patients (n = 29 treated with the CGRP-receptor mAb erenumab and n = 32 with the CGRP mAbs galcanezumab or fremanezumab). The HIT-6 sum score was 59.69 ± 6.90 at V1 and increased by 3.69 ± 6.21 at V3 (p < 0.001), indicating a greater headache impact on patients’ lives. The mean total EQ-D5-L5 score declined from 0.85 ± 0.17 at V1 by − 0.07 ± 0.18 at V3 (p = 0.013). Both Mental and Physical Component Scores of the SF-12 worsened significantly during treatment discontinuation: The PCS-12 total score decreased by − 4.04 ± 7.90 from V1 to V3 (p = 0.013) and the MCS-12 score by − 2.73 ± 9.04 (p = 0.003). Changes in all questionnaires’ scores but the MCS-12 were already significant in the first month of the drug holiday (V2). Conclusions Our results show a significant decline in headache impact and generic HRQoL of migraine patients after treatment discontinuation of a CGRP(−R) mAb. The observed deterioration is above the established minimally clinically important differences for each of the questionnaires and can therefore be considered clinically meaningful. Monitoring HRQoL during a discontinuation attempt could facilitate the decision whether or not to resume preventive treatment with CGRP(−R) mAbs.

Abnormalities in Resting-State EEG Microstates are a Vulnerability Marker of Migraine

Background: Resting-state EEG microstates are thought to reflect brief activations of several interacting components of resting-state brain networks. Surprisingly, we still know little about the role of these microstates in migraine. In the present study, we attempted to address this issue by examining EEG microstates in patients with migraine without aura (MwoA) during the interictal period and comparing them with those of a group of healthy controls (HC). Methods: Resting-state EEG was recorded in 61 MwoA patients (50 females) and 66 HC (50 females). Microstate parameters were compared between the two groups. We computed four widely identified canonical microstate classes A-D.Results: Microstate classes B and D displayed higher time coverage and occurrence in the MwoA patient group than in the HC group, while microstate class C exhibited significantly lower time coverage and occurence in the MwoA patient group. Meanwhile, the mean duration of microstate class C was significantly shorter in the MwoA patient group than in the HC group. Moreover, among the MwoA patient group, the duration of microstate class C correlated negatively with clinical measures of headache‐related disability as assessed by the six-item Headache Impact Test (HIT-6). Finally, microstate syntax analysis showed significant differences in transition probabilities between the two groups, primarily involving microstate classes B, C and D. Conclusions: By exploring EEG microstate characteristics at baseline we were able to explore the neurobiological mechanisms underlying altered cortical excitability and aberrant sensory, affective and cognitive processing, thus deepening our understanding of migraine pathophysiology.

A Case Report on a Patient Treated with Combined Korean Medicine for Chronic Headache with Digestive Symptoms

Objectives: The purpose of this study was to examine the effect of combined Korean medical treatment on chronic headache with digestive symptoms.Methods: We collected data from October to December 2020 and evaluated the efficacy of combined Korean medical treatment using the Korean Headache Impact Test-g (KHIT-6), European Quality of Life Five Dimensions (EQ5D) Scale, and Numerical Rating Scale (NRS) at admission, after two weeks of hospitalization, and on discharge.Results: At the end of treatment, the patient had increased EQ5D and reduced KHIT-6 and NRS scores.Conclusions: After the combined Korean medical treatment, the patient showed improvement, suggesting the efficacy of treatment.

Clinical correlates of hypothalamic functional changes in migraine patients

Objective To elucidate the hypothalamic involvement in episodic migraine and investigate the association between hypothalamic resting state functional connectivity changes and migraine patients’ clinical characteristics and disease progression over the years. Methods Ninety-one patients with episodic migraine and 73 controls underwent interictal resting state functional magnetic resonance imaging. Twenty-three patients and controls were re-examined after a median of 4.5 years. Hypothalamic resting state functional connectivity changes were investigated using a seed-based correlation approach. Results At baseline, a decreased functional interaction between the hypothalamus and the parahippocampus, cerebellum, temporal, lingual and orbitofrontal gyrus was found in migraine patients versus controls. Increased resting state functional connectivity between the hypothalamus and bilateral orbitofrontal gyrus was demonstrated in migraine patients at follow-up versus baseline. Migraine patients also experienced decreased right hypothalamic resting state functional connectivity with ipsilateral lingual gyrus. A higher migraine attack frequency was associated with decreased hypothalamic-lingual gyrus resting state functional connectivity at baseline, while greater headache impact at follow-up correlated with decreased hypothalamic-orbitofrontal gyrus resting state functional connectivity at baseline. At follow-up, a lower frequency of migraine attacks was associated with higher hypothalamic-orbitofrontal gyrus resting state functional connectivity. Conclusions During the interictal phase, the hypothalamus modulates the activity of pain and visual processing areas in episodic migraine patients. The hypothalamic-cortical interplay changes dynamically over time according to patients’ clinical features.

Effects of Korean Medicine Treatment focusing on Acupotomy of headache: A Case Report of Four Patients

Background: The aim of this study was to report the effect of acupotomy for patients with headache. Methods: Four patients with headache were treated with acupotomy. The improvement of symptoms was evaluated by numeric rating scale(NRS), Headache impact test-6(HIT-6) and headache attack frequency. Results: The numeric rating scale score and headache attack frequency decreased throughout the treatment period. No side effects were observed during treatment. Conclusion: Acupotomy had shown a positive clinical effect in the treatment of a headache in this case series. Further studies are required for its application on various headache.

Role of acetazolamide in treatment of patients with menstrual migraine

Objective: According to the ICHD-3 criteria, menstrual migraine (MM) is divided into two groups: pure menstrual migraine (PMM) and menstrually-related migraine (MRM). The present study aimed to evaluate and compare the severity of headache using a visual analog scale (VAS) and the effect on quality of life using the Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS) tests before and after 3 months of treatment in using short-term prophylaxis with acetazolamide. Methods: Patients who presented to the headache outpatient clinic of the neurology department with a diagnosis of MM were retrospectively reviewed. Acetazolamide was given at a dosage of 500 mg daily for 5 days starting two days before the predicted onset of the menstrual cycle as a short-term prophylactic treatment. VAS, MIDAS, and HIT assessments were performed before and after treatment. Results: A total of 26 patients with PMM and 26 patients with MRM were identified. After acetazolamide treatment, statistically significant improvement was found in MIDAS, VAS and HIT scores in both groups of patients. The post-treatment MIDAS score was significantly lower in the MRM group, but there was no significant difference in post-treatment VAS and HIT scores between the groups. Conclusion: Using acetazolamide for short-term prophylaxis in patients with MM leads to decreased severity and frequency of headache and improvement in quality of life. The study is the first in the literature to use acetazolamide for short-term prophylaxis in patients diagnosed with MM.

Association between sleep and awake bruxism in patients with migraine

IntroductionWhen migraine undergoes transformation from episodic to chronic form it becomes more disabling due to the refractoriness in treatment and the emergence of comorbidities, with the establishment of a bidirectional relationship between sleep bruxism and chronic migraine. This study aimed to assess whether sleep and awake bruxism are more prevalent in chronic migraine when compared to episodic migraine and also to establish possible clinical correlations with the process of chronification.Methods210 patients were allocated to the study, 97 with episodic migraine and 113 with chronic migraine, who underwent face-to-face interviews with the completion of the scales: specific questionnaire for the diagnosis of sleep and awake bruxism, PHQ-9 (depression), GAD-7 (anxiety), Epworth Scale (daytime sleepiness), MIDAS (migraine incapacity) and HIT-6 (impact of headache). ResultsThe prevalence of sleep and awake bruxism was similar in patients with episodic versus chronic migraine (p = 0.300 and p = 0.238). The correlation of patients with concomitant awake and sleep bruxism and with high scores on the migraine incapacity (MIDAS) and headache impact (HIT-6) scales was higher among patients with chronic migraine than in patients with episodic migraine. (p <0.001 and p <0.001). ConclusionSleep and awake bruxism alone are not more prevalent in chronic migraine when compared to episodic migraine, although bruxism causes greater impact and disability on individuals with chronic migraine.