Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience

BackgroundMigraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption.MethodsPatients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13–16 of the drug holiday; 4) in weeks 9–12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period.ResultsThis study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 ± 6.3 at the end of the drug holiday to 7.8 ± 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 ± 6.3 MMD vs. 7.5 ± 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life.ConclusionsReinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.     

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

BackgroundTo compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls.MethodsWe performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression.ResultsThe questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression.Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p <  0.001; cluster headache 5.62 ± 0.99, p <  0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p <  0.001; cluster headache: − 5.25 ± 0.56, p <  0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001).ConclusionMen with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.     

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.     

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.     

Impact of the COVID-19 pandemic on ophthalmologic outpatient care: experience from an Italian Tertiary Medical Center

PurposeTo evaluate the impact the COVID-19-related national lockdown has had on Ophthalmologic Outpatient Care in an Italian Tertiary Medical Centre.MethodsWe reviewed all the performances that were carried out as outpatient services at our department between 1 January 2020 and 30 November 2020. We compared data among four different periods: from 1 January 2020 to 17 March 2020 (“Pre-Lockdown”); from 18 March 2020 to 17 May 2020 (Lockdown); from 18 May 2020 to 2 November 2020 (Post-Lockdown) and from 3 November 2020 to 30 November 2020 (Regional Lockdown).ResultsThe overall number of performed routine outpatient visits per day (ROVs) was 11,871 (Mean ± SD = 35.76 ± 17.81), whereas booked appointments (BAs) were 21272 (Mean ± SD = 63.86 ± 9.27), meaning a decline in the number of ROVs by 44.01%. (Mean ± SD = 28.10 ± 12.11, p<.001). Post-Lockdown and Regional Lockdown clinical activities, dropped respectively by 31 and 25.14% (38.87 ± 3.88 vs. 56.34 ± 11.06, p<.001 and 6.04 ± 4.51 vs. 56.34 ± 11.06 p<.001). The number of BAs per day decreased during the pandemic, going from a mean of 77.81 ± 2.57 booked appointments per day before the lockdown, to a mean of 53.14 ± 4.94, 61.80 ± 4.62 and 72.07 ± 1.09 appointments per day respectively during the lockdown, the post-lockdown and the regional lockdown periods.ConclusionsDuring the various lockdown periods, at our institution the volume of outpatient ophthalmological visits drastically dropped. This testifies the dramatic impact the COVID-19 pandemic has had on the supply of ophthalmic care.     

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation

BackgroundCalcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre.MethodsThis was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up.ResultsOne hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p < 0.0001) and severe (15 to 5, 67% reduction, p < 0.0001) headache days. 39.8% of patients achieved at least a 30% reduction in total headache days; 61.8% of patients achieved at least a 50% reduction in severe headache days. Meeting either of these thresholds was considered a positive response, 68% of patients achieved this. Presence of daily headache pattern was negatively associated with response, (56% response vs. 90% without daily headache, p = 0.0003). There was no association between age, gender, presence of medication overuse or number of previously tried prophylactic treatments and response to erenumab. 43% of patients reported at least one adverse effect, most commonly constipation (26%); treatment was discontinued in 3 patients due to adverse effects.ConclusionsErenumab was an effective treatment for chronic migraine in this treatment resistant population over 3 months of follow up. Presence of daily headache predicted poorer response but there was still a significant positive response rate in this group.     

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention

BackgroundErenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results.MethodsPatients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response.ResultsWe included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A—BoNT/A—had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%).ConclusionsIn real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.     

Impact of the COVID-19 pandemic on migraine in Japan: a multicentre cross-sectional study

ObjectivesTo assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan.MethodsWe conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic.ResultsFinally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic.ConclusionsIn this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01263-1.     

Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials

BackgroundIn patients with migraine, overuse of acute medication, including migraine-specific medication (MSM) such as triptans and ergots, can lead to adverse health outcomes, including development of medication overuse headache. Here, we examined the effect of erenumab on reducing acute medication use, in particular MSM, in patients with episodic migraine (EM) and chronic migraine (CM).MethodsThe current post-hoc analyses were based on data from the double-blind treatment phase (DBTP) of two erenumab studies, a pivotal EM (N = 955) and a pivotal CM (N = 667) trial, and their respective extensions. Patients were administered subcutaneous placebo or erenumab (70 or 140 mg) once monthly. Daily acute headache medication use (including MSM and non-MSM) was recorded using an electronic diary during a 4-week pretreatment baseline period until the end of the treatment period. Outcome measures included change in monthly acute headache medication days (HMD) in acute headache medication users at baseline, and changes in monthly MSM days (MSMD) in MSM users at baseline and non-MSMD in non-MSM users at baseline.ResultsIn total, 60 and 78 % of patients (all acute headache medication users) with EM and CM used MSM at baseline, respectively. For acute headache medication users, the change in mean monthly acute HMD over Months 4, 5 and 6 compared with the pre-DBTP was 1.5, 2.5, and 3.0 for placebo, erenumab 70 mg and 140 mg, respectively for the EM study. The respective change in monthly MSMD in MSM users was 0.5, 2.1 and 2.8, and in monthly non-MSMD in non-MSM users was 2.3, 2.6, and 2.7. In the acute headache medication users at baseline, the change in monthly acute HMD at Month 3 compared with pre-DBTP was 3.4, 5.5, and 6.5 for placebo, erenumab 70 mg and 140 mg, respectively for the CM study. The respective change in monthly MSMD in MSM users was 2.1, 4.5, and 5.4, and in monthly non-MSMD in non-MSM users was 5.9, 6.4, and 6.6. Reductions in MSMD versus placebo were sustained in the extension periods of both studies. Erenumab was also associated with a higher proportion of MSM users achieving ≥ 50 %, ≥ 75 and 100 % reduction from baseline in monthly MSMD versus placebo in both EM and CM.ConclusionsIn both EM and CM, treatment with erenumab is associated with a significant and sustained reduction in the use of acute headache medication, in particular MSM.Trial registrations{"type":"clinical-trial","attrs":{"text":"NCT02456740","term_id":"NCT02456740"}}NCT02456740; {"type":"clinical-trial","attrs":{"text":"NCT02066415","term_id":"NCT02066415"}}NCT02066415; {"type":"clinical-trial","attrs":{"text":"NCT02174861","term_id":"NCT02174861"}}NCT02174861.     

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.     

Comparative study of magnesium,sodium valproate,and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial

ObjectiveThis study aimed to assess the efficacy of concurrent magnesium-sodium valproate therapy and compare it with either magnesium or sodium valproate alone in migraine prophylaxis.Materials and methodsThis randomized single-center double-blind parallel-group controlled clinical trial study was conducted on migraine patients within the age range of 18–65 years. The subjects with at least four monthly attacks were randomly assigned to group A (n = 82) sodium valproate, group B (n = 70) magnesium with sodium valproate, and group C (n = 70) magnesium. The patients passed a one-month baseline without prophylactic therapy and then received a 3-month treatment. The characteristics of migraine, including frequency, severity, duration of the attacks, and the number of painkillers taken per month, were monthly recorded in each visit. The Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) scores were recorded at the baseline and after 3 months of treatment in each group. Within- and between-group analyses were performed in this study.ResultsThe obtained results revealed a significant reduction in all migraine characteristics in all groups compared to those reported for the baseline (P <  0.001). Intragroup data analysis indicated that there was no statistically significant difference in headache frequency between groups A and B in the third month (P = 0.525); nevertheless, three other parameters showed a significant reduction in group B, compared to those reported for group A in the third month (P <  0.05). On the other hand, group C could not effectively reduce measured parameters in the patients, compared to groups A and B after 3 months (P <  0.001). Furthermore, the MIDAS and HIT-6 scores significantly diminished in groups A, B, and C compared to those reported at the baseline (P <  0.001), and these changes were more significant in groups A and B than in group C (P <  0.001).ConclusionThe obtained results of this study revealed that magnesium could enhance the antimigraine properties of sodium valproate in combination therapy and reduce the required valproate dose for migraine prophylaxis.     

Cranial autonomic symptoms: prevalence,phenotype and laterality in migraine and two potentially new symptoms

BackgroundWhilst cranial autonomic symptoms (CAS) are typically associated with trigeminal autonomic cephalalgias (TAC’s), they have also been reported in migraine. Identification and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management.MethodsMigraineurs seen in a tertiary headache service between 2014 and 2018 (n = 340): cohort one, and a separate cohort of headache patients seen between 2014-May 2021 reporting voice change, or throat swelling, or both, as CAS were selected (n = 64): cohort two. We performed a service evaluation of our records regarding age, sex, diagnosis, headache and CAS frequency and laterality as acquired from the first consultation, during which a detailed headache history is taken by a headache trained physician.ResultsCohort 1: Mean age 43 (range 14–94, SD 15). The most common diagnosis was chronic migraine (78%). Median monthly headache frequency was 26 days (IQR 15–75). At least one CAS was reported in 74%, with a median of two (IQR 0–3). The most common were nasal congestion (32%), lacrimation (31%) and aural fullness (25%). Most patients reported their most common headache as unilateral (80%) and with it strictly unilateral CAS (64%). There was a positive association between headache and CAS laterality (χ²₁ = 20.7, P < 0.001), with a positive correlation between baseline headache frequency and number of CAS reported (r = 0.11, P = 0.047). Cohort two: mean age 49 (range 23–83, SD 14). Diagnoses were chronic migraine (50%), chronic cluster headache (11%), undifferentiated continuous lateralised headache (9%), SUNCT/SUNA (8%), hemicrania continua (8%), episodic migraine (8%), episodic cluster headache (3%) and trigeminal neuropathies (3%). Most (89%) described trigeminal distribution pain; 25% involving all three divisions. Throat swelling was reported by 54, voice change by 17, and both by 7. The most common CAS reported were lacrimation (n = 47), facial swelling (n = 45) and rhinorrhoea (n = 37). There was significant agreement between the co-reporting of throat swelling (χ²₁ = 7.59, P = 0.013) and voice change (χ²₁ = 6.49, P = 0.02) with aural fullness.ConclusionsCAS are common in migraine, are associated with increasing headache frequency and tend to lateralise with headache. Voice change and throat swelling should be recognized as possible parasympathetically-mediated CAS. They may be co-associated and associated with aural fullness, suggesting a broadly somatotopic endophenotype.     

Interictal osmophobia is associated with longer migraine disease duration

BackgroundSensitization to sensory stimuli is an essential feature of migraine attacks. The relationship between the clinical course of migraine and increased sensitivity to olfactory stimuli has been little studied so far.MethodsWe analyzed the frequency and quality of osmophobia depending on the phase of migraine in patients with episodic and chronic migraine treated in an tertiary headache center with regard to gender, age, medical history and migraine disability assessment score (MIDAS). Standardized diagnostic questions were used for the assessment of osmophobia.ResultsIn our cross-sectional investigation (n = 113), 38.1% of the patients showed an increased preictal hypersensitivity to odors, whereas 61.9% described ictal and 31.9% interictal hypersensitivity to odors, odor-triggered migraine was described in 30.1%. Median migraine disease duration has been statistically significantly longer in patients who suffered from interictal hypersensitivity to odors (28.5 years vs. 20 years; p = 0.012). There was a significant correlation between interictal hypersensitivity and higher age (54.50 vs. 45; p = 0.015). Patients with higher migraine disability in MIDAS experienced more frequently preictal and interictal olfactory sensitization and odor triggered migraine attacks.ConclusionsIn patients with longer migraine disease duration and higher migraine-related impairment, osmophobia was more frequently observed. These results might support the hypothesis of increasing sensitization with increasing burden of migraine.     

Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case–control study

BackgroundThe burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group.MethodsTwo groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale.ResultsThe Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04–2.45, P-value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064–2.596, P-value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645, P-value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145–6.195, P-value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975, P-value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108, P-value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739, P-value = 0.003), and headache (OR = 3.148, 95%CI = 1.616–6.136, P-value =  ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (P-value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3–7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2–5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1–6).ConclusionThe study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.     

Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension

ObjectiveHeadache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.MethodsIIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m² were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.ResultsSixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m². The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).ConclusionsWe demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures.Trial registrationThis work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT02124486","term_id":"NCT02124486"}}NCT02124486.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01321-8.     

Avoid or seek light – a randomized crossover fMRI study investigating opposing treatment strategies for photophobia in migraine

BackgroundPhotophobia, the aberrantly increased sensitivity to light, is a common symptom in migraine patients and light discomfort is frequently found as a trigger for migraine attacks. In behavioral studies, planned exposure to light was found to reduce headache in migraine patients with photophobia, potentially by increasing habituation to this migraine trigger. Here, we aimed to elucidate neurophysiological mechanisms of light exposure versus light deprivation in migraine patients using functional magnetic resonance imaging (fMRI).MethodsTen migraine patients (9 female, age = 28.70 ± 8.18 years) and 11 healthy controls (9 female, age = 23.73 ± 2.24 years) spent one hour on 7 consecutive days exposed to flashing light (Flash) or darkness (Dark) using a crossover design with a wash-out period of 3 months. Study participants kept a diary including items on interictal and ictal photophobia, presence and severity of headache 7 days before, during and 7 days after the interventions. One week before and one day after both interventions, fMRI using flickering light in a block design was applied. Functional activation was analyzed at whole-brain level and habituation of the visual cortex (V1) was modeled with the initial amplitude estimate and the corrected habituation slope.ResultsMean interictal photophobia decreased after both interventions, but differences relative to the baseline did not survive correction for multiple comparisons. At baseline, flickering light induced activation in V1 was higher in the patients compared to the controls, but activation normalized after the Flash and the Dark interventions. V1 habituation indices correlated with headache frequency, headache severity and ictal photophobia. In the Flash condition, the individual change of headache frequency relative to the baseline corresponded almost perfectly to the change of the habituation slope compared to the baseline.ConclusionsOn average, light exposure did not lead to symptom relief, potentially due to the short duration of the intervention and the high variability of the patients’ responses to the intervention. However, the strong relationship between visual cortex habituation and headache symptoms and its modulation by light exposure might shed light on the neurophysiological basis of exposure treatment effects.Trial registration{"type":"clinical-trial","attrs":{"text":"NCT05369910","term_id":"NCT05369910"}}NCT05369910 (05/06/2022, retrospectively registered).     

Selective denervation of the corrugator supercilii muscle for the treatment of idiopatic trigeminal neuralgia purely paroxysmal distributed in the supraorbital and suprathrochlear dermatomes

IntroductionIdiopatic trigeminal neuralgia purely paroxysmal (ITNp) distributed in the supraorbital and suprathrochlear dermatomes (SSd), refractory to conventional treatments have been linked to the hyperactivity of the corrugator supercilii muscle (CSM). In these patients, the inactivation of the CSM via botulinum toxin type A (BTA) injections has been proven to be safe and effective in reducing migraine burden. The main limitation of BTA is the need of repetitive injections and relative high costs. Based on the study of the motor innervation of the CSM, we describe here an alternative approach to improve these type of migraines, based on a minimally invasive denervation of the CSM.Materials and methodsMotor innervation and feasibility of selective CSM denervation was first studied on fresh frozen cadavers. Once the technique was safely established, 15 patients were enrolled. To be considered eligible, patients had to meet the following criteria: positive response to BTA treatment, migraine disability assessment score > 24, > 15 migraine days/month, no occipital/temporal trigger points and plausible reasons to discontinue BTA treatment. Pre- and post- operative migraine headache index (MHI) were compared, and complications were classified following the Clavien-Dindo classification (CDC).ResultsFifteen patients (9 females and 6 males) underwent the described surgical procedure. The mean age was 41 ± 10 years. Migraine headache episodes decreased from 24 ± 4 day/month to 2 ± 2 (p < 0.001) The MHI decreased from 208 ± 35 to 10 ± 11 (p < 0.001). One patient (7%) had a grade I complication according to the CDC. No patient needed a second operative procedure.ConclusionsOur findings suggest that the selective CSM denervation represents a safe and minimally invasive approach to improve ITNp distributed in the SSd associated with CSM hyperactivation.Trial registrationThe data collection was conducted as a retrospective quality assessment study and all procedures were performed in accordance with the ethical standards of the national research committee and the 1964 Helsinki Declaration and its later amendments.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01218-6.     

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

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