Reduction In Headache Days Research Articles

Retrospective Observational Study on Riboflavin Prophylaxis in Child and Adolescent Migraine

BackgroundWe evaluated the efficacy of riboflavin in pediatric migraineurs. MethodsA retrospective observational study was performed on 42 patients (aged six to 18 years) with migraine who were evaluated from January to December 2019 at Dell Children’s Medical Center in Austin, Texas. Weight-based dosing of riboflavin was recommended for migraine prevention. Descriptive statistics were used to study the population demographics. Nonparametric tests were used for inferential statistics to study the effect of riboflavin on headache frequency, intensity, and duration. ResultsPatients treated with riboflavin had a significant reduction in headache days per month (frequency) at the first follow-up visit at 2 to 4 months (T1) (11.07 ± 10.52 days) compared with the baseline T0 (21.90 ± 9.85 days); P < 0.001 in regard to the primary outcome in 42 patients (mean age, 13.38 ± 3.38). Mean headache intensity decreased from 8.85 (±6.41; T0) to 2.30 (±2.51; T1); P < 0.001 on a 0 to 10 scale. The headache duration also reduced significantly from 18.23 ± 17.07 hours (T0) to 10.18 ± 10.49 hours (T1); P = 0.001. There was a positive correlation between riboflavin efficacy and reduced use of acute medications (rs = 0.304; P = 0.05). Riboflavin was useful in reducing the frequency and intensity in two patients with new daily persistent headache. ConclusionsPatients treated with riboflavin had a reduction in headache frequency, use of acute medications, and days of school missed. Riboflavin prophylaxis also reduced migraine intensity and duration. Riboflavin is recommended as a safe, inexpensive, and effective nutraceutical in the treatment of pediatric migraine.

Effectiveness, Safety, and Health-Related Quality of Life of Chronic Migraine Patients Treated with Onabotulinum Toxin A

Objective: The present study aims to describe the efficacy and safety of onabotulinum toxin A (BonT-A) with evaluation of treatment satisfaction and impact on quality of life in chronic migraine (CM) patients in real life. Methods: This study was conducted in CM patients who were treated with BoNT-A with 12 months of follow-up. Data about outcome, adverse events, and patients’ pre- and post-treatment status including health-related quality of life data were analyzed. Health-related quality of life scores were measured at baseline and months 6 and 12 after the beginning of BoNT-A administration. Results: Of 42 enrolled patients, 30 were included in the analysis. At 12 months, all patients showed a reduction in number of headaches and analgesic use per month and none reported adverse events. After BoNT-A supplementation, health-related quality-of-life scores improved significantly. There was a direct association between health-related quality of life with reduction of headache days at the end of study. Conclusion: This study confirms that BoNT-A treatment is effective on CM and improves the functional well-being and quality of life of patients.

Identification of neural and psychophysical predictors of headache reduction after cognitive behavioral therapy in adolescents with migraine.

Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.

Iron Deposits in Periaqueductal Gray Matter Are Associated with Poor Response to OnabotulinumtoxinA in Chronic Migraine.

Previous studies have reported increased brain deposits of iron in patients with chronic migraine (CM). This study aims to determine the relation between iron deposits and outcome after treatment with OnabotulinumtoxinA (OnabotA). Demographic and clinical data were collected for this study through a prospective cohort study including 62 CM patients treated with OnabotA in the Hospital Clínico Universitario de Santiago de Compostela (Spain). Demographic and clinical variables were registered. Selected biomarkers in plasma during interictal periods (calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX3)) and neuroimaging changes (iron deposits in the red nucleus (RN), substantia nigra (SN), globus pallidus (GP), and periaqueductal gray matter (PAG), and white matter lesions (WML)) were determined. Subjects were classified in responders (≥50% reduction in headache days) or non-responders (<50%). Responders to treatment were younger (mean age difference = 12.2; 95% confidence interval (CI): 5.4–18.9, p = 0.001), showed higher serum levels of CGRP (≥50 ng/mL) and PTX3 (≥1000 pg/mL) and smaller iron deposits in the GP and PAG (mean difference = 805.0; 95% CI: 37.9–1572.1 μL, p = 0.040 and mean difference = 69.8; 95% CI: 31.0–108.6 μL, p = 0.008; respectively). Differences in PAG iron deposits remained significant after adjusting for age (mean difference = 65.7; 95% CI: 22.8–108.6 μL, p = 0.003) and were associated with poor response to OnabotA after adjustment for clinical and biochemical variables (odds ratio (OR) = 0.963; 95% CI: 0.927–0.997, p = 0.041). We conclude that larger PAG iron deposits are associated with poor response to OnabotA in CM.

Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 ± 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis.

Multidimensional assessment of the effects of erenumab in chronic migraine patients with previous unsuccessful preventive treatments: a comprehensive real-world experience

Backgrounderenumab was safe and effective in clinical trials for the prevention of migraine. However, real-life data are still lacking. Here we report the clinical experience from an Italian real-world setting using erenumab in patients with chronic migraine experiencing previous unsuccessful preventive treatments.MethodsSeventy patients with chronic migraine and failure to ≥4 migraine preventive medication classes initially received monthly erenumab 70 mg s.c. Patients without a clinically meaningful improvement, considered as a > 30% reduction in headache days per month, after ≥3 months of therapy switched to monthly erenumab 140 mg. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity and migraine-related disability and impact, and validated questionnaires to explore depression/anxiety, sleep, and quality of life (QoL). Finally, the Pain Catastrophizing Scale, Allodynia Symptom Checklist-12 and MIGraine attacks-Subjective COGnitive impairments scale (MIG-SCOG) were administered.Results70% of patients were “responders” after the third administration of erenumab 70 mg, whereas 30% switched to erenumab 140 mg; 29% (6 pts) responded after the sixth administration. The headache-day frequency was reduced from 21.1 ± 0.7 to 11.4 ± 0.9 days after the third administration (p < 0.001) and to 8.9 ± 0.7 days after the sixth administration (p < 0.001). 53% and 70% of patients, respectively, showed a reduction of ≥50% of headache days/month after the third and the sixth administrations.Also improved were headache pain severity, migraine-related disability, and impact on daily living, QoL, pain catastrophizing and allodynia (all p < 0.001), quality of sleep, symptoms of depression or anxiety (p < 0.05) but not MIG-SCOG. There were no new adverse event signals.ConclusionThese real-world data support monthly erenumab 70 or 140 mg s.c. as a safe and effective preventive treatment to reduce headache frequency and severity in chronic migraine patients experiencing previous unsuccessful preventive treatments.

Sustained response to onabotulinumtoxin A in patients with chronic migraine: real-life data

BackgroundTreatment with onabotulinumtoxin A (BT-A) is safe and effective for chronic migraine (CM). Several studies assessed possible predictors of response to treatment with BT-A, but there is little knowledge on the frequency and predictors of sustained response. The aim of this study was to evaluate sustained response to BT-A in patients with CM.Main bodyIn this prospective open-label study, 115 patients with CM and treated with BT-A were consecutively enrolled in two Italian headache centers and followed up for 15 months. Anytime responders were defined as those patients who achieved a ≥ 50% reduction in headache days during any three-month treatment cycle compared with the 3 months prior to initiation of BT-A treatment. Sustained responders were defined as those who achieved a ≥ 50% reduction in headache days within the third treatment cycle and maintained response until the end of follow-up. Non-responders were defined as those patients who never achieved a ≥ 50% reduction in headache days during the follow-up. Headache characteristics prior to BT-A treatment were assessed in order to evaluate their ability in predicting treatment response.The 115 enrolled patients (84.3% female; median age 50 years) had a median migraine duration of 30 years (interquartile range 22–38). At the end of follow-up, 66 patients (57.4%) were classified as anytime responders. Among the 51 patients who achieved a clinical response within the third month of treatment, 33 (64.7%) were sustained responders. Patients with sustained response had a lower CM duration (median 31 vs 65 months; P = 0.030) and a lower number of headache days (median 25 vs 30; P = 0.013) at baseline compared with non-responders.ConclusionsAbout two thirds of patients who gain ≥50% response to BT-A within the third cycle of treatment maintain this positive response over time. More recent onset of CM and more headache-free days at baseline are associated with sustained response. We suggest not to delay preventive treatment of CM with BT-A, in order to increase the likelihood to achieve sustained clinical response.

Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes.

We aimed to evaluate the efficacy of an enhanced mindfulness-based stress reduction (MBSR+) vs stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n = 50) with SMH (n = 48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then biweekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. Magnetic resonance imaging (MRI) outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula to DLPFC and cognitive task network, and gray matter volume of DLPFC, dorsal anterior insula, and anterior midcingulate. Secondary outcomes were headache-related disability, pain severity, response to treatment, migraine days, and MRI whole-brain analyses. Reduction in headache days from baseline to 20 weeks was greater for MBSR+ (7.8 [95% CI, 6.9-8.8] to 4.6 [95% CI, 3.7-5.6]) than for SMH (7.7 [95% CI 6.7-8.7] to 6.0 [95% CI, 4.9-7.0]) (P = 0.04). Fifty-two percent of the MBSR+ group showed a response to treatment (50% reduction in headache days) compared with 23% in the SMH group (P = 0.004). Reduction in headache-related disability was greater for MBSR+ (59.6 [95% CI, 57.9-61.3] to 54.6 [95% CI, 52.9-56.4]) than SMH (59.6 [95% CI, 57.7-61.5] to 57.5 [95% CI, 55.5-59.4]) (P = 0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. Enhanced mindfulness-based stress reduction is an effective treatment option for episodic migraine.

Real-world effectiveness of onabotulinumtoxinA treatment for the prevention of headaches in adults with chronic migraine in Australia: a retrospective study

BackgroundOnabotulinumtoxinA (BOTOX®, Allergan plc, Dublin, Ireland) is approved for the preventive treatment of headaches in adult patients with chronic migraine (CM) in Australia by the country’s reimbursement mechanism for medicines, the Pharmaceutical Benefits Scheme (PBS). To our knowledge, this study represents the first focused report evaluating real-world evidence of onabotulinumtoxinA treatment via the PBS in Australian clinics.MethodsThis study reviewed the medical records of adults with inadequately controlled CM from 7 private neurology practices in Australia who, beginning in March 2014, received PBS-subsidized onabotulinumtoxinA per product labelling for the first time. The primary effectiveness measure was the percentage of patients achieving a response defined by 50% or greater reduction in headache days from baseline after 2 treatment cycles. Additional data were recorded in the case report form when available and included demographics, clinical characteristics, headache severity and frequency, Headache Impact Test (HIT-6) score, medication use, and days missed of work or study at baseline, after 2 treatment cycles, and at last follow-up. Differences in mean changes from baseline were evaluated with a 1-tailed t-test or Pearson’s chi-squared test (p < 0.05).ResultsThe study population included 211 patients with a mean (SD) of 25.2 (5.3) monthly headache days at baseline. In the primary outcome analysis, 74% of patients achieved a response, with a mean (SD) of 10.6 (7.9) headache days after 2 treatment cycles (p < 0.001). Secondary effectiveness outcomes included mean (SD) reductions in HIT-6 score of − 11.7 (9.8) and − 11.8 (12.2) after 2 treatment cycles (p < 0.001) and final follow-up (p < 0.001), respectively, and mean (SD) decreases in days per month of acute pain medication use of − 11.5 (7.6) after 2 treatment cycles (p < 0.001) and − 12.7 (8.1) at final follow-up (p < 0.001).ConclusionThis study provides additional clinical evidence for the consistent effectiveness of onabotulinumtoxinA for the treatment of CM in Australia. This effectiveness was made evident by reductions in migraine days, severe headache days, and HIT-6 scores from baseline.

Smartphone-based migraine behavioral therapy: a single-arm study with assessment of mental health predictors

Progressive muscle relaxation (PMR) is an under-utilized Level A evidence-based treatment for migraine prevention. We studied the feasibility and acceptability of smartphone application (app)-based PMR for migraine in a neurology setting, explored whether app-based PMR might reduce headache (HA) days, and examined potential predictors of app and/or PMR use. In this single-arm pilot study, adults with ICHD3 migraine, 4+ HA days/month, a smartphone, and no prior behavioral migraine therapy in the past year were asked to complete a daily HA diary and do PMR for 20 min/day for 90 days. Outcomes were: adherence to PMR (no. and duration of audio plays) and frequency of diary use. Predictors in the models were baseline demographics, HA-specific variables, baseline PROMIS (patient-reported outcomes measurement information system) depression and anxiety scores, presence of overlapping pain conditions studied and app satisfaction scores at time of enrollment. Fifty-one patients enrolled (94% female). Mean age was 39 ± 13 years. The majority (63%) had severe migraine disability at baseline (MIDAS). PMR was played 22 ± 21 days on average. Mean/session duration was 11 ± 7 min. About half (47%) of uses were 1+ time/week and 35% of uses were 2+ times/week. There was a decline in use/week. On average, high users (PMR 2+ days/week in the first month) had 4 fewer days of reported HAs in month 2 vs. month 1, whereas low PMR users (PMR < 2 days/week in the first month) had only 2 fewer HA days in month 2. PROMIS depression score was negatively associated with the log odds of using the diary at least once (vs. no activity) in a week (OR = 0.70, 95% CI = [0.55, 0.85]) and of doing the PMR at least once in a week (OR = 0.77, 95% CI = [0.68, 0.91]). PROMIS anxiety was positively associated with using the diary at least once every week (OR = 1.33, 95% CI = [1.09, 1.73]) and with doing the PMR at least once every week (OR = 1.14 [95% CI = [1.02, 1.31]). In conclusion, about half of participants used smartphone-based PMR intervention based upon a brief, initial introduction to the app. App use was associated with reduction in HA days. Higher depression scores were negatively associated with diary and PMR use, whereas higher anxiety scores were positively associated.

Early onset of effect of onabotulinumtoxinA for chronic migraine treatment: Analysis of PREEMPT data.

The Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials demonstrated efficacy/tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis assessed time of onset of onabotulinumtoxinA after the first treatment in total and responder populations and consistency weekly through five treatment cycles. In the 24-week, double-blind, placebo-controlled phase of PREEMPT, individuals were randomized 1:1 to onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for two cycles. The primary pooled efficacy variable was change in headache days per 28 days at week 24. We assessed change in headache and migraine/probable migraine (hereafter migraine) days/week compared with baseline week 4. Baseline mean (SD) headache days/week (week 4 of baseline) for onabotulinumtoxinA (n = 688) and placebo (n = 696) were similar (4.8 [1.6] vs. 4.8 [1.6] days/week, respectively), as were migraine days/week (4.6 [1.7] vs. 4.6 [1.7] days/week). The effect of onabotulinumtoxinA on change in headache and migraine days/week was significantly greater than placebo at week 1, persisting from week 3 after the first treatment (-1.6 [2.2] vs. -1.1 [2.2] headache days/week [ p < 0.001] and -1.6 [2.2] vs. -1.1 [2.2] migraine days/week [ p < 0.001]). Headache and migraine days decreased in onabotulinumtoxinA responders beginning 1 week after treatment 1. Treatment with onabotulinumtoxinA is associated with significant reductions in headache and migraine days/week at week 1, persisting after week 3, compared with placebo. Combined with earlier reports showing onabotulinumtoxinA treatment results in a persistent and progressive reduction in headache days over 56 weeks, it is suggested peak benefit may require multiple treatments. ClinicalTrials.gov: NCT00156910 and NCT00168428.

Patient Preferences for Preventive Migraine Treatments: A Discrete‐Choice Experiment

To understand treatment preferences of people with migraine and the relative importance of improvements in efficacy and avoiding adverse events (AEs), such as cognition problems or weight gain. Current preventive migraine medicines are associated with poor adherence and tolerability. There is an unmet need for effective migraine-specific preventive treatments with fewer AEs. In a web-based discrete-choice experiment survey, respondents who self-reported having ≥6 migraine days/month were offered choices between pairs of hypothetical preventive migraine medicines. Six attributes, each with 3 levels, defined the medicines: reduction in headache days per month (10%, 25%, or 50%), frequency of limitations with physical activities (none, 1-category improvement, or 2-category improvement), cognition problems (no problems, thinking problems, or memory problems), weight gain (none, 5% body weight gain, or 10% body weight gain), how the medicine is taken (daily oral pill, once-monthly injection, or twice-monthly injection), and monthly out-of-pocket cost ($5, $60, or $175). The attributes and levels were informed by clinician input, the clinical literature, and 2 focus groups. An experimental design was used to create the pairs of hypothetical medicines for the discrete-choice experiment questions. Random-parameters logit was used to estimate the relative importance of the medicine attributes, and the results were used to predict the percentage of respondents who would select one medicine profile over another and to calculate willingness to pay for changes in attribute levels. The sample included 300 respondents; 72% indicated that migraines make physical activities difficult all or most of the time, and 81% had taken a prescription medicine to prevent migraine in the last 6months. Respondents reported having, on average, approximately 16 headache days per month. Among noncost attributes, respondents valued a change from a 10% reduction in migraine days to a 50% reduction more highly than avoiding the worst levels of AEs, but were willing to trade off efficacy for less-severe AEs. Avoiding memory problems was more important than avoiding thinking problems. Avoiding a 10% weight gain was more important than avoiding thinking and memory problems. Respondents preferred a once-monthly injection or daily pill to twice-monthly injection. Respondents, on average, were willing to pay $84 (95% confidence interval [CI], $64-$103) per month to avoid a 10% weight gain, $59 (95% CI, $42-$76) per month to avoid memory problems, $35 (95% CI, $20-$51) per month to avoid a 5% weight gain, and $32 (95% CI, $18-$46) per month to avoid thinking problems. A preventive migraine medicine with improved efficacy and AE profile and a favorable mode of administration would be valuable to migraine sufferers. Patients may be willing to trade off efficacy for better AE profiles. Clinicians should work with patients to select treatments that meet each patient's needs.

Effects of onabotulinumtoxinA treatment in patients with and without allodynia: results of the COMPEL study

BackgroundOnabotulinumtoxinA is effective in treating chronic migraine (CM), but there are limited data assessing how allodynia affects preventive treatment responses. This subanalysis of the 108-week, multicenter, open-label COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without allodynia.MethodsPatients (n = 715) were treated with onabotulinumtoxinA 155 U every 12 weeks for 9 treatment cycles. The Allodynia Symptom Checklist was used to identify patients with allodynia (scores ≥3). The primary outcome for this subanalysis was reduction in monthly headache days from baseline for weeks 105 to 108 in groups with and without allodynia. Other outcomes included assessments of moderate to severe headache days, disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire [MSQ] v2). Adverse events and their relation to treatment were recorded.ResultsOnabotulinumtoxinA was associated with a significant mean (SD) reduction in headache day frequency at week 108 relative to baseline in patients with (n = 289) and without (n = 426) allodynia (− 10.8 [7.1] and − 12.5 [7.4], respectively; both P < 0.001) that was significantly greater in patients without allodynia (P = 0.044 between-subgroup comparison). Moderate to severe headache days were significantly reduced at week 108 in patients with and without allodynia (− 9.6 [6.9] and − 10.5 [7.2]; both P < 0.001); reduction was similar between groups. MIDAS scores improved significantly at week 108 (− 53.0 [50.3] and − 37.7 [53.0]; both P < 0.001), with a significant between-group difference in favor of those with allodynia (P = 0.005). Similarly, MSQ subscale scores (Role Function Preventive, Role Function Restrictive, Emotional Function) significantly improved at week 108 for patients with and without allodynia: 20.6 (21.9) and 16.9 (20.7), 28.0 (23.3) and 24.7 (22.7), and 27.6 (26.5) and 24.9 (26.1), respectively (all P < 0.001). OnabotulinumtoxinA was well tolerated in patients with and without allodynia.ConclusionResults indicate that onabotulinumtoxinA is associated with reductions from baseline in multiple efficacy outcomes for up to 108 weeks whether or not allodynia is present. The allodynia group showed a smaller treatment response for reduction in headache days, but a similar or greater treatment response for improvement in other measures. No new safety concerns were identified.

Wearing Off Response to OnabotulinumtoxinA in Chronic Migraine: Analysis in a Series of 193 Patients.

Long-term real-life studies have supported a cumulative effect of OnabotulinumtoxinA (OnabotA) for the prophylactic treatment of chronic migraine (CM) during consecutive cycles, and individual adaptations have been described to improve clinical response. This was a cohort longitudinal retrospective study of consecutive adult patients from the Headache Unit of the Hospital Clínico Universitario de Valladolid and the Hospital Universitario de La Princesa (Madrid) on OnabotA treatment for chronic migraine from May 2012 to December 2017. All patients were followed for 24 weeks. Full-length response to OnabotA was defined as ≥50% reduction in headache days for at least 12 weeks, and wearing off response was defined as a clinical response but with duration shorter than 10 weeks. We have analyzed the incidence and clinical predictors of this wearing off response. A total of 193 patients were included, of whom 91 (47.1%) were considered full-length responders and 45 (23.3%) wearing off responders. No statistically significant clinical predictors (including demographic variables and baseline headache characteristics) of full-length response or wearing off response were detected in our study. An increase in dose during the second treatment cycle was attempted in 68.9% of the wearing off patients, achieving a longer duration of response of up to 12 weeks in 74.2%. Wearing off response to OnabotA during the first treatment cycle is not uncommon in patients with CM. Increasing the dose in subsequent cycles could improve clinical response, but further multicenter long-term studies are needed to establish predictors and solutions to this problem.

Healthcare behavior of migraine and headache patients when treatment is accompanied by the digital migraine app

Tension-type headache and migraine are the second and third most prevalent disorders of mankind worldwide, after dental caries. The widespread implementation of smartphones enables the use of specific software applications (apps) for digital treatment accompaniment. In this study, the use of the migraine app (Migräne-App) for iOS and Android was examined in the practical treatment of migraine and headache patients in an extensive population sample. An online survey was developed for the analysis of experiences as part of the treatment accompaniment and app usage. It contains questions concerning sociodemographic variables, the course of headache disorders and the previous treatment as well as the usage of the migraine app. The survey establishes compliance to the recommended treatment, the treatment plan, and treatment rules devised by the treating physician. The data collected were compared to traditional pen and paper documentation, prior to using the migraine app. A total of 1464 users participated in the standardized survey. The average age was 47.19 ± 11.37 years (87.4% female, 12.5% male). On average, users suffered from headaches for 27.28 ± 13.6 years. The majority (76.5%) were cared for by a general practitioner. Of the users 70.9% reported that they presented the aggregated data from the app to their physician on consultation, 76.4% reported that the migraine app helped them to adhere to the treatment plan designed together with their physician and the rules about headache therapy. It showed both ahighly significant reduction of headache days per months prior to usage (13.30 ± 7.45 days) in comparison to at the time of conducting the survey (10.03 ± 7.30 days) as well as ahighly significant reduction of intake of acute medication (before 7.61 ± 5.58 vs. ongoing 6.78 ± 4.72 days). The data show that the digital treatment control for therapy decisions made by the physician is highly relevant and established. Therapy compliance is improved and possible complications such as headache due to medication overuse are reduced. At the same time, asignificant improvement of headache parameters and amarked overall improvement of treatment quality, amongst other things due to more easily available information and self-help tools can be observed.

Effects of onabotulinumtoxinA treatment for chronic migraine on common comorbidities including depression and anxiety

ObjectiveTo assess the effects of onabotulinumtoxinA treatment for chronic migraine (CM) on comorbid symptoms of depression, anxiety, fatigue and poor sleep quality.MethodsThe Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open-Label (COMPEL) study...

Treatment of posttraumatic headache migraine phenotype with erenumab – An observational study

Objective To report the observed effect of erenumab in mild posttraumatic headache migraine phenotype with and without aura. Background There is no clinical algorithm of pharmacotherapy for migraine following posttraumatic headache. Most migraine preventatives that are typically used are either ineffective or not tolerated. Methods Seven patients who met the clinical criteria for migraine with or without aura following posttraumatic headache who failed or were intolerant of conventional migraine preventatives were treated with erenumab 140 mg subcutaneously. Most had no history of migraine. In those patients with a history of migraine, the posttraumatic headache migraine headaches were different than the past migraine experience. Descriptive headache intensity or disability using the Head Impact Test-6 and monthly headache days were recorded before and after treatment. All patients were debilitated on presentation and demonstrated no signs of spontaneous resolution. Results Patients responded with a 95% (SD 1.22, p &lt; .001) reduction in headache days. All Head Impact Test-6 scores went from disabling to non-disabling without adverse effects. Most required only one dose of erenumab with no migraine recurrence. Onset of efficacy often became apparent within days to four weeks. Extended follow-up six months after treatment revealed no relapses. Conclusions Erenumab is effective in the treatment of posttraumatic headache with migraine phenotype in this small cohort. Large-scale studies are urgently required for this highly prevalent, disabling, condition which has no effective established treatment.

Behavioral Therapies and Mind-Body Interventions for Posttraumatic Headache and Post-Concussive Symptoms: A Systematic Review.

There are no clear guidelines on how to treat posttraumatic headache (PTH) or post-concussive symptoms (PCS). However, behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation are Level-A evidence-based treatments for headache prevention. To understand how to develop and study further mind-body interventions (MBIs) and behavioral therapies for PTH and PCS, we developed the following question using the PICO framework: Are behavioral therapies and MBIs effective for treating PTH and PCS? We conducted a systematic search of 3 databases (Medline, PsycINFO, and EMBASE) for behavioral interventions and MBIs with the subject headings and keywords for PTH, concussion, and traumatic brain injury (TBI). Inclusion criteria were (1) randomized controlled trials, (2) the majority of the intervention had to be behavioral or mind-body therapy focused, (3) the majority of the participants (>50%) had to have had a mild TBI (not a moderate or severe TBI), (4) published in a peer-reviewed publication, and (5) meeting pre-specified primary and/or secondary outcomes. Primary outcome(s): whether there was a significant change in concussion symptom severity (yes/no) based on the symptom severity checklist/scale used, whether there was a 50% reduction in headache days and/or disability; secondary outcome(s): sleep variables, cognitive complaints, depression, and anxiety. The search identified 917 individual studies. Two independent reviewers screened citations and full-text articles independently. Nineteen articles were pulled for full article review. Seven articles met the final inclusion criteria. The systematic review was registered in Prospero (CRD42017070072). Overall, there was vast heterogeneity across the studies, making it difficult to fully assess efficacy. The heterogeneity ranged from differences in patient populations, the timing of when the interventions were initiated, the types of intervention implemented, and the measures used to assess outcomes. Seven studies were identified as meeting final inclusion criteria, resulting in a total of 1108 adult participants ranging from 18 to 80. Sixty-nine percent were male. Of the 7 studies, 3 were focused on military staff (retired and active). Time post-injury for inclusion into the studies varied from 48 hours post-injury to more than 2 years post-injury. One of the 7 studies did not include time post-TBI in the inclusion criteria. Two studies recruited patients who had visited their emergency departments, 4 of the studies recruited subjects through outpatient referrals, and 1 study recruited patients who had been in a prior traffic accident with resulting chronic PTH directly from a headache center. Group cognitive behavioral therapy (CBT) sessions and telephonic counseling or communication were common intervention methods used in the studies, with group CBT being used in 2 of the studies and telephonic counseling being used in 3. Other intervention methods used included individual CBT, cognitive training, psychoeducation, and computer-based and/or therapist-directed cognitive rehabilitation. Many of the interventions offered vastly different methods of delivery of intervention and doses of intervention. Many of the negative studies were done after an extended duration post-injury (>1-year posttraumatic brain injury [TBI]). In addition, the participants were lumped together regardless of their pre-concussion comorbidities, their mechanism of injury, their symptoms, and the duration from injury to the start of the intervention. The mass heterogeneity found between the studies led to inconclusive findings. Thus, there are various considerations for the design of the intervention for future behavioral/MBI studies for PTH and concussion that must be addressed before the leading question of this review may be effectively answered.

Guideline on the use of onabotulinumtoxinA in chronic migraine: a consensus statement from the European Headache Federation

OnabotulinumtoxinA is being increasingly used in the management of chronic migraine (CM). Treatment with onabotulinumtoxinA poses challenges compared with traditional therapy with orally administered preventatives. The European Headache Federation identified an expert group that was asked to develop the present guideline to provide recommendations for the use of onabotulinumtoxinA in CM. The expert group recommend onabotulinumtoxinA as an effective and well-tolerated treatment of CM. Patients should preferably have tried two to three other migraine prophylactics before start of onabotulinumtoxinA. Patients with medication overuse should be withdrawn from the overused medication before initiation of onabotulinumtoxinA if feasible, if not onabotulinumtoxinA can be initiated from the start or before withdrawal. OnabotulinumtoxinA should be administered according to the PREEMPT injection protocol, i.e. injecting 155 U–195 U to 31–39 sites every 12-weeks. We recommend that patients are defined as non-responders, if they have less than 30% reduction in headache days per month during treatment with onabotulinumtoxinA. However other factors such as headache intensity, disability and patient preferences should also be considered when evaluating response. Treatment should be stopped, if the patient does not respond to the first two to three treatment cycles. Response to continued treatment with onabotulinumtoxinA should be evaluated by comparing the 4 weeks before with the 4 weeks after each treatment cycle. It is recommended that treatment is stopped in patients with a reduction to less than 10 headache days per month for 3 months and that patients are re-evaluated 4–5 months after stopping onabotulinumtoxinA to make sure that the patient has not returned to CM. Questions regarding efficacy and tolerability of onabotulinumtoxinA could be answered on the basis of scientific evidence. The other recommendations were mainly based on expert opinion. Future research on the treatment of CM with onabotulinumtoxinA may further improve the management of this highly disabling disorder.

Neurophysiological correlates of clinical improvement after greater occipital nerve (GON) block in chronic migraine: relevance for chronic migraine pathophysiology

BackgroundTherapeutic management of Chronic Migraine (CM), often associated with Medication Overuse Headache (MOH), is chiefly empirical, as no biomarker predicting or correlating with clinical efficacy is available to address therapeutic choices. The present study searched for neurophysiological correlates of Greater Occipital Nerve Block (GON-B) effects in CM.MethodsWe recruited 17 CM women, of whom 12 with MOH, and 19 healthy volunteers (HV). Patients had no preventive treatment since at least 3 months. After a 30-day baseline, they received a bilateral betamethasone-lidocaine GON-B of which the therapeutic effect was assessed 1 month later. Habituation of visual evoked potentials (VEP) and intensity dependence of auditory evoked potentials (IDAP) were recorded before and 1 week after the GON-B.ResultsAt baseline, CM patients had a VEP habituation not different from HV, but a steeper IDAP value than HV (p = 0.01), suggestive of a lower serotonergic tone. GON-B significantly reduced the number of total headache days per month (− 34.9%; p = 0.003). Eight out 17CM patients reversed to episodic migraine and medication overuse resolved in 11 out of 12 patients. One week after the GON-B VEP habituation became lacking respect to baseline (p = 0.01) and to that of HV (p = 0.02) like in episodic migraine, while the IDAP slope significantly flattened (p < 0.0001). GON-B-induced reduction in headache days positively correlated with IDAP slope decrease (rho = 0.51, p = 0.03).ConclusionsGON-B may be effective in the treatment of CM, with or without MOH. The pre-treatment IDAP increase is compatible with a weak central serotonergic tone, which is strengthened after GON-B, suggesting that serotonergic mechanisms may play a role in CM and its reversion to episodic migraine. Since the degree of post-treatment IDAP decrease is correlated with clinical improvement, IDAP might be potentially useful as an early predictor of GON-B efficacy.