Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis

BackgroundInitial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine.MethodsThis is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders).ResultsOne hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3–56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0–26.0) to 13.0 days (IQR: 5.75–24.0) (P = 0.002, r = − 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75–22.0) to 9.0 (IQR: 4.0–15.25) (P = 0.002, r = − 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64–69) at baseline to 62 at month 3 (IQR: 56–65) (P < 0.001, r = − 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity.ConclusionsThis open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.     

Shift from high-frequency to low-frequency episodic migraine in patients treated with Galcanezumab: results from two global randomized clinical trials

BackgroundPatients with episodic migraine (EM) with a higher-frequency of migraine headache days (HFEM: 8–14 migraine headache days/month) have a greater disease burden and a higher risk of progressing to chronic migraine (CM) with associated acute treatment overuse versus those with low-frequency EM (LFEM: 4–7 migraine headache days/month). In this post hoc analysis, we assessed the proportions of patients who shifted from HFEM to LFEM and to very low-frequency EM (VLFEM: 0–3 migraine headache days/month) status following treatment with galcanezumab versus placebo.MethodsEVOLVE-1 and EVOLVE-2 were double-blind, Phase 3 studies in patients with EM. Patients (18–65 years) were randomized (2:1:1) to subcutaneous monthly injections of placebo, galcanezumab 120 mg (240 mg loading dose) or 240 mg, for up to 6 months. Data were pooled and endpoints were change from baseline in number of migraine headache days/month and patients who shifted from HFEM to LFEM or VLFEM status. Impact of change in HFEM status on migraine headache days/month, quality of life and disability was also assessed.ResultsA total of 66% (1176/1773) patients from EVOLVE studies had HFEM status at baseline and were included in this analysis; placebo: 592, galcanezumab 120 mg: 294 and galcanezumab 240 mg: 290. At each month, both doses of galcanezumab resulted in a higher proportion of patients who shifted to 0–7 monthly headache days/month (VLFEM or LFEM status). Patients who shifted from HFEM at baseline to VLFEM status at Month 3, a relatively larger proportion of patients on galcanezumab 120 mg versus placebo remained at VLFEM status at Months 4–6; Months 4–5 for galcanezumab 240 mg versus placebo. Among the galcanezumab-treated patients who did-not-shift or shifted to LFEM or VLFEM status for ≥3 consecutive months until the end of the study, patients who shifted from HFEM to VLFEM status experienced the largest reduction in migraine headache days/month and the largest clinically meaningful improvements in daily functioning (MSQ-RFR) and disability (MIDAS).ConclusionsIn patients with HFEM, treatment with galcanezumab (120 mg and 240 mg) significantly reduced migraine headache days/month, maintained remission status at subsequent months until the end of the study, and improved patients’ quality of life versus placebo.Trial registrationClinicalTrials.gov Identifier: EVOLVE-1, {"type":"clinical-trial","attrs":{"text":"NCT02614183","term_id":"NCT02614183"}}NCT02614183; EVOLVE-2, {"type":"clinical-trial","attrs":{"text":"NCT02614196","term_id":"NCT02614196"}}NCT02614196.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01222-w.     

Medication-overuse headache: an update

Background

Headache disorders are common worldwide, causing pain and disability. India appears to have a very high prevalence of migraine, and of other headache disorders in line with global averages. Our objective was to estimate the burdens attributable to these disorders in order to inform health policy.

Methods

In a door-to-door survey, biologically unrelated adults (18–65 years) were randomly sampled from urban and rural areas of Bangalore and interviewed by trained researchers. The validated structured questionnaire enquired into several aspects of burden.

Results

Of 2,329 participants (non-participation rate 7.4 %), 1,488 (63.9 %; 621 male, 867 female) reported headache in the preceding year. Symptom burden was high. Migraine (1-year prevalence 25.2 %) occurred on average on 28 days/year but, in 38.0 % of cases (ie, 9.6 % of adults), on ≥3 days/month (≥10 % of days). All causes of headache on ≥15 days/month (prevalence 3.0 %) occurred on a mean of 245 days/year. Both these and migraine were rated severe in intensity.

Participants with headache lost 4.3 % of productive time; those with migraine lost 5.8 % (equating to 1.5 % from the adult population). Lost paid worktime accounted for 40 % of this, probably detracting directly from GDP.

We estimated population-level disability attributable to migraine using the disability weight from GBD2010 for the ictal state (0.433). Mean disability per person with migraine was 1.8 %, reducing the functional capacity of the entire adult population by 0.46 %.

Fewer than one quarter of participants with headache had engaged with health-care services for headache in the last year. Actual expenditure on headache care was greatest among those with headache on ≥15 days/month (especially probable medication-overuse headache), but otherwise not high. Expressed willingness to pay for effective treatment for headache was higher, signalling dissatisfaction with current treatments.

Conclusions

In Karnataka State, southern India, prevalent headache disorders, especially migraine, give rise to commensurately heavy burdens. Limited access to health care fails to alleviate these. Structured headache services, with their basis in primary care, are the most efficient, effective, affordable and equitable solution. They could be implemented within the health-care infrastructure of India and are likely to be cost-saving. This solution requires political will, itself dependent on awareness.

     

Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study

This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.     

Migraine,Tension-Type Headache,and Attention-Deficit/Hyperactivity Disorder in Childhood: A Population-Based Study

Abstract

Objectives: Primary headache syndromes (eg, migraine and tension-type headache [TTH]) and attention-deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause impairment in social and academic functioning. We tested if ADHD or its symptoms are associated with specific headache syndromes or with headache frequency. Study design: Cross-sectional epidemiological study with direct interviews to parents and teachers using validated and standardized questionnaires. Setting: Populational study. Participants: Children aged 5 to 11 years (n = 1856). Outcome measures: Prevalence of ADHD as a function of headache status in crude and adjusted analyses. Results: The prevalence of migraine was 3.76%. Infrequent episodic TTH occurred in 2.3% of the sample, and frequent episodic TTH occurred in 1.6%. The prevalence of ADHD was 6.1%. The prevalence of ADHD was not significantly different by headache category. For hyperactivity-impulsivity symptoms, the prevalence was 8.1% in children without headache, 23.7% in children with migraine (relative risk [RR], 2.6; 95% confidence interval [CI], 1.6–4.2), and 18.4% in children with probable migraine (RR, 2.1; 95% CI, 1.4–3.2). For inattention, no significant differences were seen. In multivariate analyses, ADHD or inattention symptoms were not predicted by headache subtypes or headache frequency. Hyperactivity-impulsivity symptoms were significantly associated with any headache (P < 0.01), TTH (P < 0.01), or migraine (P < 0.001). Conclusion: Migraine and TTH are not comorbid to ADHD overall, but are comorbid to hyperactive-impulsive behavior. Providers and educators should be aware of the association.     

Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

BackgroundMonoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.MethodsThis observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO).ResultsWe enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01).ConclusionMigraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.     

Air pollution and daily ED visits for migraine and headache in Edmonton,Canada

Background

A variety of environmental factors have been identified as possible triggers for migraine and other headache syndromes.

Objective

We analyzed associations between air pollution and emergency department (ED) visits for migraine and headache.

Methods

Analysis was based on 56 241 ED visits for migraine and 48 022 ED visits for headache to Edmonton hospitals between 1992 and 2002. A Poisson model of counts hierarchically clustered by day of week, month, and year was applied using generalized linear mixed models. Temperature and relative humidity were included as covariates.

Results

Females accounted for 78.5% of migraine visits and 56.3% of headache visits. An interquartile range (IQR) increase (6.2 μg/m³) in daily average particulate matter of median aerodynamic diameter less than 2.5 μm (PM_2.5) was associated with increases in visits of 3.3% for migraine (95% confidence interval [CI]: 0.6-6.0), lagged 2 days, and 3.4% for headache (95% CI: 0.3-6.6), lagged 0 days, among females in the cold season (October-March). PM_2.5 was also associated with cold season migraine visits among females at lag 0 and 1 day (P < .1). In the warm period (April-September), a 2.3-ppb IQR increase in sulfur dioxide was associated with a 2.5% increase in migraine visits (95% CI: 0.3-4.6) among females, whereas a 12.8-ppb IQR increment in nitrogen dioxide was associated with a 6.8% increase in headache visits (95% CI: 1.5-12.5) for males.

Conclusions

Findings provide preliminary evidence of an association between air pollution and ED visits for migraine and nonspecific headache. Findings were most consistent for particulate matter.     

Providing Care for Patients with Chronic Migraine: Diagnosis,Treatment, and Management

Chronic migraine, a subtype of migraine defined as ≥ 15 headache days per month for ≥ 3 months, in which ≥ 8 days per month meet criteria for migraine with or without aura or respond to migraine‐specific treatment, is a disabling, underdiagnosed, and undertreated disorder associated with significant disability, poor health‐related quality of life, and high economic burden. The keys to caring for chronic migraine patients include: (1) making a proper diagnosis; (2) identifying and eliminating exacerbating factors; (3) assessing for medication overuse (patients with chronic headache often overuse acute medications); and (4) continued management. Communication between patient and physician about treatment goals is important. The patient management guidelines presented in this article should help physicians improve treatment success and proactively address common comorbidities among their patients with chronic migraine.     

Remote electrical neuromodulation for migraine prevention: A double-blind,randomized, placebo-controlled clinical trial

Objective

To assess the clinical efficacy of remote electrical neuromodulation (REN), used every other day, for the prevention of migraine.

Background

Preventive treatment is key to managing migraine, but it is often underutilized. REN, a non-pharmacological acute treatment for migraine, was evaluated as a method of migraine prevention in patients with episodic and chronic migraine.

Methods

We conducted a prospective, randomized, double-blind, placebo-controlled, multi-center trial, with 1:1 ratio. The study consisted of a 4-week baseline observation phase, and an 8-week double-blind intervention phase in which participants used either REN or a placebo stimulation every other day. Throughout the study, participants reported their symptoms daily, via an electronic diary.

Results

Two hundred forty-eight participants were randomized (128 active, 120 placebo), of which 179 qualified for the modified intention-to-treat (mITT) analysis (95 active; 84 placebo). REN was superior to placebo in the primary endpoint, change in mean number of migraine days per month from baseline, with mean reduction of 4.0 ± SD of 4.0 days (1.3 ± 4.0 in placebo, therapeutic gain = 2.7 [confidence interval −3.9 to −1.5], p < 0.001). The significance was maintained when analyzing the episodic (−3.2 ± 3.4 vs. −1.0 ± 3.6, p = 0.003) and chronic (−4.7 ± 4.4 vs. −1.6 ± 4.4, p = 0.001) migraine subgroups separately. REN was also superior to placebo in reduction of moderate/severe headache days (3.8 ± 3.9 vs. 2.2 ± 3.6, p = 0.005), reduction of headache days of all severities (4.5 ± 4.1 vs. 1.8 ± 4.6, p < 0.001), percentage of patients achieving 50% reduction in moderate/severe headache days (51.6% [49/95] vs. 35.7% [30/84], p = 0.033), and reduction in days of acute medication intake (3.5 ± 4.1 vs. 1.4 ± 4.3, p = 0.001). Similar results were obtained in the ITT analysis. No serious device-related adverse events were reported in any group.

Conclusion

Applied every other day, REN is effective and safe for the prevention of migraine.     

Smartphone based music intervention in the treatment of episodic migraine headaches – A pilot trial

ObjectivesMigraine headaches are a prevalent and burdening disorder for the public worldwide. Both traditional preventive drugs and behavioral-based interventions have been used as treatment in the prevention of migraine attacks. However, benefits of alternative interventions in patients with primary headache disorders have not yet been fully explored.The present investigation sought to examine the impact of a patient controlled music intervention (MUSIC CARE) on episodic migraine headache.DesignA sample of 20 episodic migraine patients (17 females, mean age of 42 years) was included in the pilot trial. Patients completed a pre-treatment assessment on headache severity, associated psychopathological distress (anxiety and depression) and functional impairment, and provided reports on their medication intake. During the 3-months intervention period, patients required 1–2 music sessions (based on the “U” sequence) per day with a minimum of 15 per month.ResultsFollowing the intervention, patients reported a significant reduction in the frequency of migraine attacks (M_Diff = −2.8, p = .01). Ten patients reported a 50% reduction in the frequency of migraine attacks. Additionally, there was a significant reduction in medication intake (M_Diff = −2.85, p = .02), the duration of migraine attacks (M_Diff = −5.45, p = .002), anxiety (M_Diff = −1.65 (2.88), p = .02) and depression (M_Diff = −2.45 (3.5), p = .002).ConclusionThese data provide evidence that music intervention may significantly prevent migraine attacks. Moreover, this method is easily accessible and administered. Future well-controlled clinical trials are necessary to further explore the efficiency of the intervention.     

Self-reported cocaine use is not associated with elevations in high-sensitivity troponin I

Objective: High-sensitivity troponin (hsTn) assays detect 10 times lower concentrations of cardiac troponin than conventional assays. We examined the effects of self-reported cocaine use to determine whether those with acute cocaine use being evaluated for ACS are more likely to have elevated hsTnI than those nonusers being evaluated for ACS.

Methods: We conducted a sub-analysis of a prospective cohort of ED patients evaluated for acute coronary syndrome. Recent cocaine use was determined by structured patient interviews. High-sensitivity troponin (Abbott) and conventional troponin I (Abbott, cTnI) were measured on samples drawn at presentation. Urine toxicology screen for cocaine metabolite was obtained at the discretion of treating clinicians.

Results: Of 1862 patients enrolled, 444 reported prior cocaine use and 99 reported cocaine use within the preceding month. Median hsTn in patients with last cocaine use within 24?h, 2–7 days, 1 week–1 month, >1 month, and no prior cocaine use were: 9 (IQR: 3–17) ng/L, 6 (IQR: 3–24.3) ng/L, 6 (IQR: 3–89.5) ng/L, 3 (IQR: 3–18.5) ng/L and 3 (IQR: 3–17) ng/L, respectively. Urine toxicology assays (UTox) for cocaine were performed in 640 (34.4%) patients. The median hsTn for those who were UTox+, UTox???and those without a UTox were: 9?ng/L (IQR: 3–48.5), 9?ng/L (IQR: 3–40) and 3?ng/L (IQR: 3–12), respectively. There were no differences in the prevalence of new troponin elevations (hsTn >99th percentile but cTnI <99th percentile) in those with recent cocaine use compared to those without recent cocaine use.

Conclusions: In this first investigation of hsTn in patients with self-reported recent cocaine use, we have determined that hsTn does not lead to an increase in the prevalence of troponin elevation in cocaine users.     

Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months

BackgroundIn daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort.MethodsThis is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment.ResultsOf 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: − 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054–0.975]; p = 0.049).ConclusionsIn real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01328-1.     

11th European Headache Federation Congress jointly with 31st Congress of the Italian Society for the Study of Headaches

Background

Mainly based on evidence of success in adults, various medications are commonly used to prevent pediatric migraines. Topiramate has been approved for migraine prevention in children as young as 12 years of age. In this meta-analysis, we aimed to assess the currently published data pertaining to the efficacy of topiramate for migraine prevention in patients less than 18 years of age.

Methods

We searched PubMed/Medline, Embase and the Cochrane Library (from inception to April 2017) for randomized controlled trials (RCTs) published in English. Two independent investigators performed data extraction and quality evaluation using the Cochrane Collaboration’s tool. The data extracted were analyzed by Review Manager 5.3 software.

Results

A total of four RCTs matching the inclusion criteria were included, with an aggregate of 465 patients. Of these patients, 329 were included in the topiramate group, and 136 were included in the placebo group. This meta-analysis revealed that compared with placebo, topiramate failed to decrease the number of patients experiencing a ≥ 50% relative reduction in headache frequency (n = 465, RR = 1.26, 95% CI = [0.94,1.67], Z = 1.55, P = 0.12) or the number of headache days (n = 465, MD = −0.77, 95% CI = [−2.31,0.76], Z = 0.99, P = 0.32) but did reduce PedMIDAS scores (n = 205, MD = −9.02, 95% CI = [−17.34, −0.70], Z = 2.13, P = 0.03). Higher rates of side effects and adverse events in the topiramate group than in the placebo group were observed in the included trials.

Conclusions

Topiramate may not achieve a more effective clinical trial endpoint than placebo in the prevention of migraines in patients less than 18 years of age, and topiramate may lead to more side effects or adverse events in the included patients.

     

Chronic migraine classification: current knowledge and future perspectives

In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days).     

Classification and clinical features of headache patients: an outpatient clinic study from China

This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.     

Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter,double-blind,randomized, placebo-controlled,parallel group study

Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.     

Transcranial Magnetic Stimulation for Migraine: A Safety Review

(Headache 2010;50:1153‐1163) Objective.— To review potential and theoretical safety concerns of transcranial magnetic stimulation (TMS), as obtained from studies of single‐pulse (sTMS) and repetitive TMS (rTMS) and to discuss safety concerns associated with sTMS in the context of its use as a migraine treatment. Methods.— The published literature was reviewed to identify adverse events that have been reported during the use of TMS; to assess its potential effects on brain tissue, the cardiovascular system, hormone levels, cognition and psychomotor tests, and hearing; to identify the risk of seizures associated with TMS; and to identify safety issues associated with its use in patients with attached or implanted electronic equipment or during pregnancy. Results.— Two decades of clinical experience with sTMS have shown it to be a low risk technique with promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults. Tens of thousands of subjects have undergone TMS for diagnostic, investigative, and therapeutic intervention trial purposes with minimal adverse events or side effects. No discernable evidence exists to suggest that sTMS causes harm to humans. No changes in neurophysiological function have been reported with sTMS use. Conclusions.— The safety of sTMS in clinical practice, including as an acute migraine headache treatment, is supported by biological, empirical, and clinical trial evidence. Single‐pulse TMS may offer a safe nonpharmacologic, nonbehavioral therapeutic approach to the currently prescribed drugs for patients who suffer from migraine.     

Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States

BackgroundFremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation.MethodsData were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation.ResultsOverall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P < 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P < 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232).ConclusionsSignificant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting.     

Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures

BackgroundGalcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives.MethodsPatients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed.ResultsGalcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo − 0.2; galcanezumab − 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1–3 (all p < 0.05) and at weeks 1–4 of month 1 compared to placebo (all p < 0.01).ConclusionGalcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments.Trial registrationClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03559257","term_id":"NCT03559257"}}NCT03559257. Registered 18 June 2018.