HIT-6 Scores Research Articles

Cerebral Blood Flow and Other Predictors of Responsiveness to Erenumab and Fremanezumab in Migraine-A Real-Life Study.

IntroductionMonoclonal antibodies (mAbs) showed efficacy in migraine prevention. The aim of this study was to check if baseline clinical parameters and cerebral blood flow (CBF) measured by transcranial Doppler (TCD) may help predict mAbs efficacy.MethodsElectronic charts of migraineurs treated with erenumab or fremanezumab, with baseline TCD evaluations were collected, including data on migraine type, pain localization, monthly migraine days (MMD), medication overuse headache (MOH), mean blood flow velocity (Vm), and pulsatility index (PI) in cerebral arteries.ResultsA total of 123 patients were enrolled, mean age 38, 75 years, 87 with chronic migraine, 61 with MOH, 72 were good responders (GR), and reported ≥50% reduction in MMD, 43 ≥75% reduction in MMD. Baseline Vm values in MCAs were significantly lower in GR as compared with non-responders. MAbs responsiveness ≥50% was positively associated with unilateral pain localization (OR: 6.53, 95% CI: 2.01–23.93; p = 0.003) and HIT-6 score (OR: 1.14, 95% CI: 1.01–1.30; p = 0.036) whereas negatively associated with Vm in right MCA (OR: 0.96, 95% CI: 0.92–0.99; p = 0.012), and having no relatives with migraine (OR: 0.40, 95% CI: 0.16–0.95; p = 0.040).ConclusionsBaseline Vm in MCA is lower in mAbs GR as compared with non-responders which may reflect increased secretion of CGRP with further vasodilation in GR. Simple clinical features and baseline CBF in anterior circulation might help to predict the patient's responsiveness.

Effectiveness of yoga therapy for migraine treatment: A meta-analysis of randomized controlled studies

IntroductionYoga therapy may have some potential in treating migraine, and thus this meta-analysis aims to explore the efficacy of yoga therapy for patients with migraine. MethodsPubMed, EMbase, Web of science, EBSCO and Cochrane library databases have been systematically searched and we included the randomized controlled trials (RCTs) reporting the efficacy of yoga therapy for migraine patients. The outcomes included. ResultsThis meta-analysis included six RCTs. The results revealed that compared with control group for migraine, yoga therapy was associated with remarkably decreased pain intensity (SMD = -1.21; 95% CI = -2.17 to −0.25; P = 0.01), headache frequency (SMD = -1.43; 95% CI = -2.23 to −0.64; P = 0.0004), headache duration (SMD = -1.03; 95% CI = -1.85 to −0.21; P = 0.01), HIT-6 score (SMD = -2.28; 95% CI = -3.81 to −0.75; P = 0.003) and MIDAS score (SMD = -0.52; 95% CI = -0.77 to −0.27; P < 0.0001). ConclusionsYoga therapy may be effective to treat migraine patients, but it should be recommended with caution because of heterogeneity.

Real-world effectiveness of fremanezumab in migraine patients initiating treatment in the United States: results from a retrospective chart study

BackgroundThe efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice.MethodsThis retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures.ResultsThis study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were − 4.6 (36.2%) and − 4.7 (33.6%) at Month 1, − 6.7 (52.8%) and − 6.8 (48.6%) at Month 3, and − 9.2 (72.4%) and − 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from − 6.2 (21.6%) and − 8.4 (14.0%) at Month 1 to − 18.1 (63.1%) and − 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups.ConclusionsThis real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

Fremanezumab in the prevention of high-frequency episodic and chronic migraine: a 12-week, multicenter, real-life, cohort study (the FRIEND study)

BackgroundFremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8–14 days/month) or CM.MethodsThis is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9–12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥ 50%, ≥ 75% and 100% responder rates at the same time intervals.ResultsSixty-seventh number migraine patients had received ≥ 1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p < 0.05), MHDs (-9.4, p < 0.001), MAI (-5.7, p < 0.05; -11.1, p < 0.001), NRS (-3.1, p < 0.001; -2.5, p < 0.001), and MIDAS scores (-58.3, p < 0.05; -43.7; p < 0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p < 0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥ 50%, ≥ 75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR = 0.91; 95% CI 0.85–0.98, p = 0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason.ConclusionsFremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor.

Association of migraine with patent foramen ovale closure: A systematic review and meta-analysis.

BackgroundThe potential correlation between patent foramen ovale (PFO) and migraine has been previously reported, but whether PFO closure plays a role in reducing migraine burden has not reached an agreement.MethodWe searched PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Science Technology Periodical Database and China Biology Medicine Database (CBM) through September 30, 2021 to identify associations between PFO closure and outcome of migraine burden. The control groups consisted of drug treatment or sham procedure.ResultThree randomized clinical trials (RCT) and 9 case-control studies were eligible for inclusion (1754 participants), of which 7 reported nonrecurrence of migraine, 4 reported reduced migraine-frequency and migraine-days, and 5 reported HIT-6 score and 4 reported MIDAS score. The mean (SD) age of participants was 40.68 (3.81) years and 1340 (76.39%) were women. PFO closure was significantly associated with a reduced risk of migraine-recurrence by 4.47 (95% CI, 2.94–6.80; I2 = 12%), frequency of migraine by 0.35 (95% CI, 0.17–0.53; I2 = 0%) and monthly migraine days by 0.28 (95% CI, 0.10–0.46), and decreased score of HIT-6 (SMD 1.23, 95 %CI 0.52–1.95, I2 = 93%).ConclusionTranscatheter PFO closure is significantly associated with burden reduction of migraine headache.

The relevance of migraine in the clinical spectrum of mitochondrial disorders

Recent scientific evidence suggests a link between migraine and brain energy metabolism. In fact, migraine is frequently observed in mitochondrial disorders. We studied 46 patients affected by mitochondrial disorders, through a headache-focused semi-structured interview, to evaluate the prevalence of migraine among patients affected by mitochondrial disorders, the possible correlations between migraine and neuromuscular genotype or phenotype, comorbidities, lactate acid levels and brain magnetic resonance spectroscopy. We explored migraine-related disability, analgesic and prophylactic treatments. Diagnoses were achieved according to International Classification of Headache Disorders, 3rd edition. Lifetime prevalence of migraine was 61% (28/46), with high values in both sexes (68% in females, 52% in males) and higher than the values found in both the general population and previous literature. A maternal inheritance pattern was reported in 57% of cases. MIDAS and HIT6 scores revealed a mild migraine-related disability. The high prevalence of migraine across different neuromuscular phenotypes and genotypes suggests that migraine itself may be a common clinical manifestation of brain energy dysfunction. Our results provide new relevant indications in favour of migraine as the result of brain energy unbalance.

Quality of Life in Patients with Idiopathic Intracranial Hypertension and the Impact of the COVID-19 Pandemic

ABSTRACT The COVID-19 pandemic became a challenge to maintain care for patients with idiopathic intracranial hypertension (IIH). We aimed to find out how they were affected during lockdown. Thirty IIH patients admitted to hospital during the COVID-19 pandemic were studied. Their demographic and neuro-ophthalmological findings were evaluated. The World Health Organization – Five Well-Being Index (WHO-5), the EUROHIS Quality of Life (QOL) 8-item index, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), Headache Impact Test (HIT-6), and COVID-19 Fear Scale were used to assess QOL and pandemic-associated fear. Thirty age, sex, and body mass index matched volunteers constituted the control group. Apart from the COVID-19 Fear Scale and colour vision subscale of the NEI-VFQ-25, all scale scores were worse in IIH patients than in healthy control subjects. Patients with severe visual field defects had higher HIT-6 scores (p = .036). Both vision-specific and overall QOL was reduced in patients with IIH. Headache severity and disability were more prominent in patients with severe visual loss. Fear caused by the COVID pandemic was not different in IIH patients than in healthy control subjects.

Adjunctive treatment of chronic migraine using an oral dental device: overview and results of a randomized placebo-controlled crossover study

ObjectiveTo assess the nocioceptive input of habitual nocturnal jaw clenching that acts as a contributing factor in migraine pathogenesis.BackgroundHabitual nocturnal jaw clenching has been implicated as a trigger, particularly in those whose headaches are present upon waking or shortly thereafter. Nocturnal EMG studies of patients diagnosed with migraine show nearly twice the temporalis clenching EMG levels and double the bite force as matched asymptomatic controls, leading to the speculation that parafunctional clenching activity may have some role in headache pathogenesis. The NTI (Nociceptive Trigeminal Inhibition) oral device is a dental splint designed to reduce nocturnal jaw clenching intensity and is FDA approved for the prevention of medically diagnosed migraine pain based on open label studies. There are no prior placebo-controlled trials to assess the migraine prevention efficacy of the NTI splint. This is the first placebo-controlled cross-over study to assess the efficacy of the NTI splint in patients with Chronic Migraine.MethodA placebo controlled, single-blinded cross-over study was done with IRB oversight assessing the efficacy of the NTI splint compared to placebo using the change in the HIT-6 score as the outcome measure.Results68% of refractory chronic migraine sufferers using the NTI as measured by sequential HIT 6 scores had at least a one-category improvement (severe to substantial, or substantial to some, or some to none) compared to 12% when using a placebo device. 36% of subjects using the NTI device reported a two-category improvement in their HIT-6 score, compared to 0% when using placebo.ConclusionThe improvement in HIT-6 scores produced by the NTI device, suggests that patients with Chronic Migraine may have intense nocturnal jaw clenching as a contributing factor to their headache related disability. An NTI device is one method of assessing whether jaw-clenching is a contributing factor to ongoing migraine.Trial registrationCurrent Controlled Trials NCT04871581. 04/05/2021. Retrospectively registered.

Treatment satisfaction with calcitonin gene-related peptide monoclonal antibodies as a new patient-reported outcome measure: A real-life experience in migraine.

To evaluate treatment satisfaction with galcanezumab as a patient-reported outcome measure (PROM) in migraine. Patients with ≥8 headache days/month that had failed at ≥3medications were included. Demographic and medical history were collected. Patient´s satisfaction (effectiveness, safety, convenience, and global satisfaction [GS]) was assessed by the Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4©). We included 30 patients with migraine (76.7% chronic migraine). After 12weeks of galcanezumab treatment, median monthly headache days (MHDs) decreased 11.5 (IQR 14.0) and median monthly migraine days (MMDs) 9.0 (IQR 7.5); at 24weeks, the change was 15.0 (IQR 12.0) and 8.0days (IQR 6.0). HIT-6 score decreased from 68.0 (IQR 7.5) to 54.0 (IQR 9.5) at 12weeks (p<.001) and to 52.0 (IQR12.0) at 24weeks (p<.001) and MIDAS from 60.0 (IQR 62.7) to 25.5 (IQR 41.2, p=.004) and 7.0 (IQR 18.5, p<.001), respectively. TSQM-1.4© at 12weeks was higher compared to other preventive therapy in effectiveness (80.6/50.4, p<.001), convenience (83.3/66.7, p=.001), and GS (78.6/50.0, p<.001). These rates of satisfaction were similar at 24weeks of galcanezumab treatment. Reductions in HIT-6 (r=-.444, p=.014), MIDAS (r=-.423, p=.020), MMDs (r=-.515, p=.004), and MHDs (r=-.477, p=.008) were associated significantly with GS at 12weeks. This correlation was significantly associated with changes in HIT-6 and MHDs at 24weeks. The results of this study suggest that migraine patients receiving galcanezumab are significantly more satisfied compared to other preventive therapies, associating treatment GS with meaningful reductions in frequency, impact, and disability caused by migraine.

Diagnostic Delay and Its Predictors in Cluster Headache.

ObjectiveCluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH.MethodsData from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, <1 year; 2nd tertile, 1–6 years; and 3rd tertile, ≥7 years).ResultsOverall, 445 patients were evaluated. The mean duration of diagnosis delay was 5.7 ± 6.7 years, (range, 0–36 years). Regarding the age of onset, majority of young patients (age <20 years) belonged to the third tertile (60%), whereas minority of old patients (>40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42–14.48], chronic CH (aOR = 8.87, 95% CI = 2.66–29.51), and probable CH (aOR = 4.12, 95% CI = 1.48–11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95–0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93–0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay (p = 0.041).ConclusionsPatients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH.

Long-Term Effectiveness of Three Anti-CGRP Monoclonal Antibodies in Resistant Chronic Migraine Patients Based on the MIDAS score.

BackgroundCriteria, including clinical features and effective outcomes, for access and persistence of novel but costly treatments may vary between countries, thus affecting the health of patients. Monoclonal antibodies against the calcitonin gene-related peptide pathway (anti-CGRP mAbs) for migraine treatment are currently prescribed following strict criteria.ObjectiveThe aim was to assess the effectiveness and safety of three anti-CGRP mAbs (erenumab, galcanezumab, and fremanezumab) in consecutive resistant chronic migraine patients presenting at our Headache Center and the impact of criteria set by the Italian Medicines Agency to start and continue (achieving a ≥ 50% reduction in Migraine Disability Assessment [MIDAS] score) with treatment under the reimbursement program.MethodsA monocentric, prospective, cohort study was conducted, enrolling 203 severe (resistant to three or more preventive treatments) chronic migraine patients (84.7% with medication overuse) treated with erenumab (47.2%), galcanezumab (36.5%), or fremanezumab (16.3%), with up to 12 months follow-up. Patients completed a headache diary that included monthly migraine days (MMDs), number of analgesics and days with analgesic use, and patient-reported outcome questionnaires (MIDAS, Headache Impact Test 6 [HIT-6] questionnaires, and the Patient Global Impression of Change [PGIC] scale). Moreover, percentages of patients showing ≥ 50%, ≥ 75% and 100% reduction in MMDs (responder rates) were calculated at different follow-ups. A subgroup analysis was performed for patients with 12-month follow-up. Potential predictors of response were assessed at different follow-ups.ResultsIn the overall population, all three anti-CGRP mAbs were similarly effective and dropouts were 17.2%. The percentage of patients with ≥ 50% reduction in MMDs (min–max 36.4–56.8%) and in monthly analgesic consumption (51.1–75.7%) was inferior to the percentage of patients who reported a ≥ 50% reduction in MIDAS score (89.5–100%). HIT-6 score was also consistently reduced at all follow-ups. In patients with a 12-month follow-up, MIDAS and HIT-6 scores were also reduced at all follow-ups compared with baseline, with 84.4–100% of patients achieving a ≥ 50% reduction in MIDAS score, and patients with a ≥ 50% response rate ranging from 36.4 to 66.6%. No severe adverse events were recorded. Fewer migraine days at baseline were associated with ≥ 50% response rate at 1 month and fewer MMDs, years of chronic migraine, and monthly analgesic use at 6 months.ConclusionIn resistant chronic migraine patients, anti-CGRP mAbs are effective and safe. A ≥ 50% reduction in MIDAS score seems to be the most advantageous outcome measure in this setting, which allows most severe migraine patients to persist with treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-021-00893-y.

Clinical and imaging outcomes of cerebrospinal fluid-venous fistula embolization

BackgroundWe report outcomes of spontaneous intracranial hypotension (SIH) patients who underwent transvenous embolization of cerebrospinal fluid-venous fistulas (CSFVFs) confirmed on digital subtraction myelography (DSM) performed at our institution.MethodsThis is a...

Efficiency of erenumab in neurologist's real practice

To assess the effectiveness and safety of erenumab in real-life study. 33 patients with episodic and chronic migraine (30 females, mean age 39.2±9.2, 3 males, mean age - 49.3±7.6) received erenumab 70 mg for each 3 months. Patients achieved a 50% reduction in the number of days with headache, pain intensity, duration, the number of days of acute medication use, effect on daily activity (HIT-6), side effects, neuropsychological testing (Beck Depression scale, Spielberger-Khanin questionnaire, Hospital Depression and Anxiety Scale) were assessed. During the first month of therapy, a 50% decrease in headache days was observed in 48% of patients, during the second - in 53% of patients, during the third - in 51.5% of patients (p<0.001), a reduce in pain intensity, HIT-6 score, duration of migraine attack was observed (p<0.005). A decrease in situational anxiety was revealed (Spielberger-Khanin questionnaire, p=0.02), but not depression. There was a decrease in the consumption of triptans (p<0.0005) and other analgesics (p=0.0018). 1 patient noted transient constipation. The effectiveness and safety of erenumab in the outpatient practice is shown.

Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Treatment of Patients With Concussion

Investigate the efficacy of 3 anti-Calcitonin Gene-Related Peptide monoclonal antibodies (anti-CGRP mAbs), fremanezumab, galcanezumab, and erenumab, in concussion patients with post-traumatic headache (PTH) with a migraine phenotype. A study using monoclonal antibodies in mice with mild traumatic brain injury saw improvements in cutaneous allodynia.1 A study from Denmark using erenumab for PTH found patients had an 82% decrease in the number of headache days. This study also demonstrated that 44% of patients had a reduction in HIT-6 score = 5 after 9-12 weeks of treatment.2. Retrospective chart review of patients diagnosed with PTH (n = 168) evaluated HIT-6, number of reported headache days, and the number of modifiable concussion variables (headache, dizziness, attention/concentration deficit, mood and sleep disturbance) prior to initiation of anti-CGRP mAbs and after at least 3 months of treatment were recorded. Patients saw a decrease in HIT-6 score (p < 0.0001), with a mean difference of -4.26 from pre-treatment to at least 3 months after treatment. When evaluating 5 concussion symptom categories, patients experienced x¯ = 2.35 symptoms prior to anti-CGRP mAbs treatment, and x¯ = 1.67 after at least 3 months of treatment. Patients also experienced a decrease in the number of headache days per month (<0.0001) with a mean difference of -7.25 (range 0-30) headache days per month. Seven patients experienced adverse effects (1 patient had 2 different adverse effects), including injection site rash, fatigue, constipation, and dizziness. Only one patient discontinued medication due to adverse event. Anti-CGRP mAbs used to treat PTH showed improved headache severity and frequency, as well as a decreased number of overall concussion symptoms. There was a subset of patients with a more robust response. Switching anti-CGRP mAbs was beneficial in some patients.

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.

The prevalence and severity of insomnia in university students and their associations with migraine, tension-type headache, anxiety and depression disorders: a cross-sectional study

BackgroundThere is possibly an association between migraine, tension-type headache, anxiety, depression and insomnia. These conditions are prevalent among university students. Our primary objective was to verify whether students with primary headaches (migraine and tension-type headache) have a higher prevalence of insomnia. Our secondary objective was to assess whether the impact of headaches was associated with greater severity of insomnia. MethodsCross-sectional study. 440 students out of 3030 were randomly selected. A semi-structured questionnaire containing information about the characteristics of the headaches, including their frequencies in the last 3 months; the Headache Impact Test (HIT-6); the Hospital Anxiety Depression Scale; and the Insomnia Severity Index were used. Results420 students (95.5%) agreed to participate; 51.4% men; median age of 21 (19, 23); 95 (22.6%) had insomnia; 265 (63.1%), migraine; 152 (36.2%), tension-type headache; 201 (47.9%) suffered from anxiety and 108 (25.7%), from depression. The severe impact of headache (HIT-6>55 points; OR = 3.9; p = 0.003) and anxiety (OR = 3.6; p = 0.003) were associated with insomnia (logistic regression). The severity of insomnia was positively and significantly correlated with the impact (HIT-6 score), with frequency of headache, and with having anxiety (multiple linear regression). ConclusionsThe diagnoses of migraine and tension-type headache are not associated with the presence of insomnia. The severity of insomnia is associated with the impact and the frequency of the headaches.

The Effect of Hamstring Relaxation Program on Headache, Pressure Pain Threshold, and Range of Motion in Patients with Tension Headache: A Randomized Controlled Trial.

The purpose of this study was to determine if the severity of headache is reduced by decreasing hamstring tension in patients with tension headache. Thirty patients participated in this study. The participants were randomly allocated to two groups: hamstring relaxation program (HR) group (n = 15) and control group (n = 15). The participants in the HR group participated in a HR program for 25 min per day, three times per week, for a period of 4 weeks, and the control group participated in an electrotherapy for 25 min per day, three times per week, for a period of 4 weeks. Both groups participated in a self-myofacial release for 5 min per day, three times per week, for a period of 4 weeks. Headache was evaluated using the headache impact test (HIT-6) and visual analog scale (VAS). The pain pressure threshold (PPT) was evaluated using a digital pressure algometer. The range of motion (ROM) was evaluated using a goniometer and two special tests: straight leg raise test (SLRT) and popliteal angle test (PAT). The two groups showed no significant differences in terms of age, sex, height, and weight. The VAS and HIT-6 scores (p < 0.05) and neck and hamstring PPT showed significant improvements (p < 0.05). Neck flexion ROM and SLRT and PAT scores showed significant improvements (p < 0.05) in both groups, and the HR group showed significantly more improvements than the control group. This study confirmed that the HR program has positive effects on tension headache and is a good intervention for alleviating headaches in patients with tension headache.

SuPAR: A newer biomarker of systemic chronic inflammation

Migraine is a chronic neurological disorder. Inflammation has a key role in migraine pathophysiology. Urokinase plasminogen activator receptor (uPAR) directly involves in inflammatory conditions by facilitating migration of inflammatory cells to different tissues. The aim of this study was to investigate whether uPAR rs344781, common genetic polymorphism in the uPAR promoter region, might be associated with migraine without aura susceptibility in an Iranian population.We enrolled 103 newly diagnosed patients with migraine and 100 healthy controls. Peripheral blood sample was used for DNA extraction and uPAR rs344781 gene polymorphism was determined. Patients filled HIT-6 as a tool to evaluate headache severity.The genotype frequency of uPAR is significantly different between migraine patients and control subjects. Heterozygote genotype (AG) was statistically more frequent in the patients than the controls (P = 0.001; OR = 2.67, 95% CI = 1.51–4.7). Also G allele was more frequent in the patients. Total HIT-6 score was not significantly different between heterozygote and homozygote patients (55.50 ± 2.22 vs. 49.60 ± 3.68 respectively, P = 0.075).In conclusion, our study showed a significant association between uPAR rs344781 gene promoter polymorphism and migraine without aura susceptibility but not with headache severity.

Altered thalamo-cortical functional connectivity in patients with vestibular migraine: a resting-state fMRI study.

To explore the functional connectivity (FC) between the bilateral thalamus and the other brain regions in patients with vestibular migraine (VM). Resting-state fMRI and 3D-T1 data were collected from 37 patients with VM during the interictal period and 44 age-, gender-, and years of education-matched healthy controls (HC). The FC of the bilateral thalamus was analyzed using a standard seed-based whole-brain correlation method. Furthermore, the correlations between thalamus FC and clinical characteristics of patients were investigated using Pearson's partial correlation. Compared with HC, VM patients showed decreased FC between the left thalamus and the left anterior cingulate cortex (ACC), bilateral insular and right supplementary motor cortex. We also observed decreased FC between the right thalamus and the left insular and ACC in VM patients. Furthermore, patients with VM also exhibited increased FC between the left thalamus and the right precuneus and middle frontal gyrus, between the right thalamus and superior parietal lobule. FC between the right thalamus and the left insular was negatively correlated with disease duration (p = 0.019, r = - 0.399), FC between the left thalamus and the left ACC was negatively correlated with HIT-6 score (p = 0.004, r = - 0.484). VM patients showed altered FC between thalamus and brain regions involved in pain, vestibular and visual processing, which are associated with specific clinical features. Specifically, VM patients showed reduced thalamo-pain and thallamo-vestibular pathways, while exhibited enhanced thalamo-visual pathway, which provided first insight into the underlying functional brain connectivity in VM patients.

Chronic migraine in the first COVID-19 lockdown: the impact of sleep, remote working, and other life/psychological changes.

AimsThe objective of this study was to evaluate the impact of the first Italian COVID-19 lockdown on patients with chronic migraine (CM).Material and methodsThe study was based on an e-mail survey addressed to CM patients of our headache center. The survey evaluated demographic, life style, sleep, psychological, and migraine features during the COVID-19 lockdown period and the month before. The outcomes were migraine impact on daily life and variation in attack frequency, attack duration, migraine pain intensity, migraine symptomatic drugs use per week, and efficacy.ResultsNinety-two patients completed the survey. During the lockdown period, attack frequency was stable in 40,2%, increased in 33,7%, and reduced in 26,1% of patients; attack duration was stable in 55,4%, increased in 23,9%, and reduced in 20,7%. Migraine pain was stable or reduced in 65,2% and increased in 34,8%; number of symptomatic drugs per week was stable in 50%, reduced in 29,3%, and increased in 20,7%; migraine drug efficacy was stable in 73,9%, reduced in 17,4%, and increased in 8,7%. Patients had a HIT-6 score of 64,63 ± 8,81. Significant associations were found with remote working, smoke, education, discontinuation of the therapy performed within headache center, migraine familiarity, sleep, anxiety, perceived stress, concern about future, and COVID-19.ConclusionDuring the lockdown, approximately half of the patients had a clinical stability, a quarter an improvement, and another quarter a worsening. We identified different migraine-influencing elements; in particular, the remote working could represent an easy way to ameliorate migraineurs’ life.Supplementary InformationThe online version of this article contains supplementary material available (10.1007/s10072-021-05521-7).