Preferences and perceptions of 617 migraine patients on acute and preventive migraine treatment attributes and clinical trial endpoints.

BACKGROUND: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important. DESIGN AND METHODS: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used. RESULTS: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.

Results of a Web-Based Survey on 2565 Greek Migraine Patients in 2023: Demographic Data, Imposed Burden and Satisfaction to Acute and Prophylactic Treatments in the Era of New Treatment Options.

Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients' satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were "fairly happy", 10.6% were "very happy", and 5.5% were "extremely happy"). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease.

Reporting Quality and Risk of Bias Analysis of Published RCTs Assessing Anti-CGRP Monoclonal Antibodies in Migraine Prophylaxis: A Systematic Review.

Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs. Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7-100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process. Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology.

Effects of OnabotulinumtoxinA on Allodynia and Interictal Burden of Patients with Chronic Migraine.

BACKGROUND: We primarily aimed to ascertain whether treatment with OnabotulinumtoxinA (BoNTA) might influence the extent of the interictal burden and cutaneous allodynia in patients with chronic migraine (CM). METHODS: Seventy CM patients, who received three consecutive cycles of BoNTA, were studied. The interictal burden was assessed with the Migraine Interictal Burden Scale (MIBS-4), while cutaneous allodynia was examined with the Allodynia Symptom Checklist (ASC-12) together with PI-NRS VAS to obtain hair brushing scores, and then these were compared from baseline (T0) to the last efficacy evaluation follow-up (T1). Efficacy outcomes, mostly mean headache days (MHD) and "Headache Impact Test" scores, were also assessed between T0 and T1. RESULTS: BONTA improved the interictal burden, with a decrease in MIBS-4 scoring by an average of -7 at T1, compared to baseline (p < 0.001). The percentage of patients with a moderate/severe interictal burden was substantially decreased. Likewise, BoNTA reduced the extent of cutaneous allodynia, with a significant reduction in both the ASC-12 (1 vs. 6; p < 0.001) and PI-NRS VAS (1 vs. 5; p < 0.001) to hair brushing median scores at T1, compared to baseline. Reduced MHD rates were significantly associated with a smaller interictal burden at T1. The efficacy of BoNTA, with a significant reduction in MHD and HIT-6 scores at T1 compared to T0, was re-confirmed. CONCLUSIONS: BoNTA resulted in a statistically significant reduction in the interictal burden and also improved cutaneous allodynia. The reduction in ictal burden was associated with the down-scaling of the interictal burden. Hence, BoNTA improved the full spectrum of migraine impairment by diminishing the clinical expression of central sensitization.

Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine.

Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Conclusions: Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.

Single OnabotulinumtoxinA Session Add-On to Carbamazepine or Oxcarbazepine in Treatment-Refractory Trigeminal Neuralgia: A Case Series with 24-Week Follow Up.

We sought to assess the efficacy of combining onabotulinumtoxinA (BoNTA) as add-on therapy to carbamazepine or oxcarbazepine in treatment-refractory patients with trigeminal neuralgia (TGN) who failed to respond (less than 30% response rate) to adequate monotherapy. We conducted a retrospective study on 15 patients with a definite diagnosis of TGN, according to the established criteria, and underwent BoNTA as part of their treatment plan. A single BoNTA session was administered subcutaneously, according to patients' perceived zone of pain, at different dosages ranging from 30 to 200 units (mean ± standard deviation: 87.3 ± 39.2). All patients (15/15; 100%) reported large reductions in the severity of their TGN-related neuropathic pain. The mean pain score on the VAS scale significantly decreased from 9.3 ± 1.1 to 3.7 ± 1.2 at 2 weeks after injecting BoNTA (p < 0.001) and remained stable at 4 and 24 weeks post-injection. Regarding the impact of BoNTA on patients' health-related quality of life, there were significant improvements in both the physical and mental health domains (p < 0.05) of SF-36 tool. BoNTA may be a safe and effective treatment option for patients with refractory TGN when added on to carbamazepine or oxcarbazepine. The use of a single BoNTA session for TGN treatment may be an alternative to surgical interventions and as add-on treatment to oral medications, providing patients with a minimally invasive, effective, safe and well-tolerated option.

Genetic Variability in Vitamin D Receptor and Migraine Susceptibility: A Southeastern European Case-Control Study.

Migraine is a common primary headache disorder with both environmental and genetic inputs. Cumulative evidence indicates an association between vitamin D and headache. Unravelling the precise role of vitamin D and its receptor in the pathophysiology of migraine can eventually contribute to more efficient prevention and management of this headache disorder. The aim of the study was to investigate the relation of the three most studied VDR variants, i.e., FokI (rs2228570), TaqI (rs731236) and BsmI (rs1544410), with migraine susceptibility and distinct clinical phenotypes in a Southeastern European case-control population residing in Greece. DNA was extracted from 191 unrelated patients diagnosed with migraine and 265 headache-free controls and genotyped using real-time PCR (LightSNiP assays) followed by melting curve analysis. Genotype frequency distribution analysis of the TaqI and BsmI variants showed a statistically significant difference between migraine cases and controls. In addition, subgroup analyses revealed a significant association between all three studied VDR variants, particularly with a migraine without aura subtype. Therefore, the current study provides supporting evidence for a possible association of VDR variants with migraines, particularly migraine without aura susceptibility in Southeastern Europeans residing in Greece, further reinforcing the emerging role of vitamin D and its receptor in migraines.

Effects of Fremanezumab on Psychiatric Comorbidities in Difficult-to-Treat Patients with Chronic Migraine: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry.

OBJECTIVE: this post hoc analysis aimed to evaluate the efficacy of fremanezumab in difficult-to-treat chronic migraine (CM) patients with and without psychiatric comorbidities (PCs), mainly anxiety and/or depression. METHODS: We assessed data from CM patients with and without PCs who failed at least 3 preventives and eventually received at least 3 consecutive monthly doses of fremanezumab 225 mg. Outcomes included the crude response (≥50% reduction in monthly headache days (MHDs)) rates to fremanezumab from the baseline to the last clinical follow-up. The changes in MHDs; MHDs of moderate/greater severity; monthly days with intake of abortive medication; and the proportion of patients' changing status from with PCs to decreased/without PCs were also compared. Disability and quality of life (QOL) outcomes were also assessed. RESULTS: Of 107 patients enrolled, 65 (60.7%) had baseline PCs. The percentage of patients with (n = 38/65; 58.5%) and without (n = 28/42; 66.6%) PCs that achieved a ≥50% reduction in MHDs with fremanezumab was comparable (p = 0.41), whereas MHDs were significantly reduced (difference vs. baseline) in both patients with PCs (mean -8.9 (standard error: 6.8); p < 0.001) and without PCs (-9.8 (7.5); p < 0.001). Both groups experienced significant improvements in all other efficacy, disability, and QOL outcomes at comparable rates, including in MHD reduction. A significant proportion of fremanezumab-treated patients with baseline PCs de-escalated in corresponding severities or even reverted to no PCs (28/65; 43.1%) post-fremanezumab. CONCLUSIONS: fremanezumab appears to be effective as a preventive treatment in difficult-to-treat CM patients with and without PCs while also being beneficial in reducing the severity of comorbid anxiety and/or depression.

Predictors of Response to Fremanezumab in Migraine Patients with at Least Three Previous Preventive Failures: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry.

OBJECTIVE: To define, in a real-world population of patients with high-frequency episodic (HFEM) or chronic migraine (CM), the predictive role of socio-demographic or phenotypic profiling of responders to fremanezumab. PATIENTS AND METHODS: Two-hundred and four adult fremanezumab-treated patients with either HFEM or CM, who failed to at least three preventive treatments, provided data at baseline on several individual socio-demographic and phenotypic variables. These variables were analyzed for their ability to independently predict the response (50-74% response rates) or super-response (≥ 75% response rates) to fremanezumab. Patients were followed from 3-18 months of fremanezumab exposure. RESULTS: The main finding to emerge from univariate analyses was that three baseline socio-demographic/clinical variables, i.e., age group 41-70 years (p = 0.02); female gender (p = 0.03); patients with HFEM (p = 0.001), and three clinical phenotypic variables, i.e., strict unilateral pain (p = 0.05); pain in the ophthalmic trigeminal branch (p = 0.04); and the "imploding" quality of pain (p = 0.05), were significantly related to fremanezumab response. However, in multivariate analysis, only HFEM (p = 0.02), the presence of strict unilateral (p = 0.03), and pain location in the ophthalmic trigeminal branch (p = 0.036) were independently associated with good fremanezumab response. Allodynia (p = 0.04) was the only clinical predictive variable of super-responsiveness to fremanezumab. CONCLUSIONS: A precise phenotypic profiling with identification of pain characteristics consistent with peripheral and/or central sensitization might reliably predict the responsiveness to fremanezumab in migraine prophylaxis.

A Survey of Greek Primary Care Physicians on Their Likeability in Treating Migraines and Other Common Diseases.

Background and objectives: Migraine is considered the most clinically important primary headache due to its high prevalence and significant burden. Although globally categorized as one of the leading causes of disability, it is still largely underdiagnosed and undertreated. Worldwide, migraine care is in most cases provided by primary care physicians. The aim of our study was to assess the attitudes of Greek primary care physicians toward treating migraine compared to other common neurological and general medical disorders. Methods: We surveyed 182 primary care physicians with the use of a 5-point questionnaire regarding their preference in treating ten common medical conditions, including migraine, hypertension, hyperlipidemia, upper respiratory tract infections, diabetes mellitus, lower back pain, dizziness, transient ischemic attack, diabetic peripheral neuropathy, and fibromyalgia. Results: Overall, with regards to preference to treat, migraine scored very low (3.6 ± 1.0), next to diabetic peripheral neuropathy (3.6 ± 1.0), and third from the bottom to fibromyalgia (3.25 ± 1.06). In contrast, physicians reported a much higher preference to treat hypertension (4.66 ± 0.60) and hyperlipidemia (4.6 ± 1.0). Conclusions: Our results indicate that Greek primary care physicians dislike treating migraines but also other neurological diseases. Topics for further investigation include the reasons for this dislike, any associations with poor patient satisfaction, treatment results, or both.

Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real-world data from a Greek registry.

OBJECTIVE: To prospectively assess the efficacy and safety of fremanezumab for migraine prophylaxis in patients with failure of at least three previous preventive treatments. Changes in disability as quality-of-life outcomes after fremanezumab treatment were also examined. METHODS: Two hundred and four patients with either high-frequency EM (HFEM) or chronic migraine (CM), who attained at least three consecutive monthly sessions with fremanezumab 225 mg and otherwise met the inclusion criteria, were included in the study. The crude response (at least 50% reduction in monthly headache days [MHD]) rates to fremanezumab were assessed. Scores in the following efficacy outcomes were then compared from baseline to the last efficacy evaluation follow-up: (i) MHD, (ii) monthly days with moderate/severe peak headache intensity, and (iii) monthly days with intake of abortive medication. The disability was evaluated with the Migraine Disability Assessment; the quality of life (QOL) status was assessed with the Headache Impact-6 Test, and the EQ-5D questionnaire. RESULTS: In the majority of HFEM cases (n = 81/97; 83.5%) and CM patients (n = 67/107; 62.6%), fremanezumab proved effective in reducing the MHDs by at least 50% and was associated with clinically meaningful improvement in all other efficacy variables. The migraine-related disability experienced by our patients decreased and their QOL increased. We recorded just 36 cases reporting mild adverse events, including pain, rash or pruritus (n = 26), flu-like symptoms (n = 8), and hair loss (n = 2). CONCLUSION: With our prospective results, we provide further real-world data to support the favorable benefit/risk profile of fremanezumab in the prophylaxis of both HFEM and CM.

OnabotulinumtoxinA Add-On to Monoclonal Anti-CGRP Antibodies in Treatment-Refractory Chronic Migraine.

We sought to assess the effectiveness of combining dual therapy with onabotulinumtoxinA (BTX) add-on to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (anti-CGRP MAbs) in treatment-refractory patients with chronic migraine (CM). We retrospectively reviewed the medical files of 19 treatment-refractory patients with CM who had failed to two oral migraine preventatives, at least three consecutive BTX cycles (less than 30% response rate), at least three consecutive sessions with either fremanezumab or erenumab (less than 30% response rate), and were eventually switched to dual therapy with BTX add-on to any of the already-given anti-CGRP MAbs. We then assessed from baseline to each monotherapy or dual intervention predefined efficacy follow-up the changes in the following efficacy outcomes: (i) monthly headache days (MHD), (ii) monthly days with moderate/severe peak headache intensity, and (iii) monthly days with intake of any acute headache medication. Response (50% reduction in MHD) rates, safety, and tolerability were also determined. In the majority of cases (n = 14), dual targeting proved effective and was associated with clinically meaningful improvement in all efficacy variables; 50% response rates (also disability and QOL outcomes) coupled with favorable safety/tolerability. Our results advocate in favor of the view that dual therapy is effective and should be considered in difficult-to-treat CM patients who have failed all available monotherapies.

Results of a Web-based survey of 2105 Greek migraine patients in 2020: demographics, clinical characteristics, burden and the effects of the COVID-19 pandemic on the course of migraine.

The Greek Society of Migraine and Headache Patients (GSMHP), maintaining a strong commitment to research and information, conducted its second web-based online survey named "Migraine in Greece-2020", following its first one conducted in 2018. The 2020 study included 2,105 migraine patients who were called to answer 151 questions. The purposes of the current research were to record the demographic and clinical characteristics of migraine patients in Greece, including the severity and effects of migraine on respondents' quality of life, as well as to survey the effects of the coronavirus pandemic on the course of migraine. Our population, internet-based study provides data that will hopefully contribute to better comprehend the clinical phenotype and course of migraine during the COVID-19 pandemic.

Prospective Comparison of Longer Needle Lengths to Assess the Risk of OnabotulinumtoxinA-Associated Neck Pain in Patients with Chronic Migraine.

BACKGROUND: We aimed to prospectively assess the role of needle length in improving the tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis, with a specific focus on neck pain, based on patients' body habitus and other variables. METHODS: BoNTA was administered quarterly for two consecutive cycles, using the standard 0.5-inch 27 G needle at all pre-defined PREEMPT injection sites, except the left-hand side trapezius and paraspinal muscles, which were injected using longer needles of 1-inch 23 G at first and 1-inch 27 G at second infusion. Participants were interviewed at day 14 following each session for evidence of neck pain. The predictive significance of Body Mass Index (BMI) and other variables with neck pain was also examined. RESULTS: A total of 100 consecutive CM patients were evaluated, and each patient served as her/his self-control. The incidence, duration and intensity of neck pain did not significantly differ using either 1-inch needle compared with standard 0.5-inch 27 G needle, although the incidence and characteristics of neck pain with the use of longer needles appeared slightly higher and more intense. The BMI index and other tested variables remained unrelated to neck pain. CONCLUSIONS: We were not able to identify significant differences or correlations in the incidence, characteristics and location of neck pain with the use of different needle length to inject BoNTA, although the use of the longer 1-inch needles likely increased the risk of this adverse event.

Assessing the Significance of the Circadian Time of Administration on the Effectiveness and Tolerability of OnabotulinumtoxinA for Chronic Migraine Prophylaxis.

We aimed to provide insights on the role of the circadian time of administration in influencing the efficacy and tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis. Methods: We retrospectively reviewed the medical files of BoNTA-naïve patients with CM who completed three consecutive cycles of treatment, according to the standard PREEMPT paradigm. Participants were classified to those scheduled to be treated in the morning hours from 8:00 to 12:00 (AM) or afternoon hours from 13:00 to 18:00 (PM). We then assessed and compared between groups the changes from baseline (T0­trimester before BoNTA's first administration) to the period after its third administration (T3) in the following efficacy outcomes: (i) mean number of headache days/month, (ii) mean number of days/month with peak headache intensity of >4/10, (iii) mean number of days/month with consumption of any abortive treatment. Safety−tolerability was also compared between groups. Results: A total of 50 AM and 50 PM-treated patients were evaluated. The within-group analysis in both groups showed a significant decrease in all efficacy variables between T0 and T3. However, the between-group comparisons of all BoNTA-related efficacy outcomes at T3 vs. T0 documented comparable improvements between AM vs. PM-treated patients. Safety/tolerability was also similar between groups. Conclusions: We were not able to identify significant differences between patients treated in the AM vs. PM, so as to demonstrate that the circadian time of administration should be considered before initiating BoNTA in CM patients.

Long-term adherence, safety, and efficacy of repeated onabotulinumtoxinA over five years in chronic migraine prophylaxis.

BACKGROUND: OnabotulinumtoxinA (BoNTA) demonstrated a positive benefit-risk in chronic migraine (CM) patients in PREEMPT I and II phase III trials and many subsequent real-world studies. We herein aimed at evaluating the adherence to repeated BoNTA over a period of five years, while secondary objectives included the assessment of its long-term safety/efficacy and patients' satisfaction to treatment. METHODS: We studied 56 CM patients who had successfully received consequent cycles of BoNTA over five years. Adherence was calculated as the percentage of patients actively choosing to follow with repeated BoNTA treatment, as instructed. Safety and efficacy data were collected throughout the study period. The overall patients' belief in and satisfaction by the efficacy of treatment was assessed at last follow-up, using the self-report 7-point measure patient global impression of change (PGIC). RESULTS: A total of 36 (64.3%) out of 56 patients remained adherent to BoNTA over five years. Long-term BoNTA exposure was safe and well-tolerated, without severe side-effects justifying treatment discontinuation. The mean monthly headache days and associated clinical efficacy outcomes remained consistent and quite low at last follow-up with evidence of continuous improvements in headache monthly frequency between year three and over five years of therapy. All patients who were able to maintain treatment over five years (n = 36), remained very satisfied and scored at least 5 in PGIC. CONCLUSION: Considerably high adherence, considerable satisfaction and sustained safety/efficacy were observed in patients followed up for five years, supporting a favorable benefit/risk profile for consistently delivering long-term BoNTA in CM.

Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features.

Introduction: Migraine is a complex disorder with genetic and environmental inputs. Cumulative evidence implicates oxidative stress (OS) in migraine pathophysiology while genetic variability may influence an individuals' oxidative/antioxidant capacity. Aim of the current study was to investigate the impact of eight common OS-related genetic variants [rs4880 (SOD2), rs1001179 (CAT), rs1050450 (GPX1), rs1695 (GSTP1), rs1138272 (GSTP1), rs1799983 (NOS3), rs6721961 (NFE2L2), rs660339 (UCP2)] in migraine susceptibility and clinical features in a South-eastern European Caucasian population. Methods: Genomic DNA samples from 221 unrelated migraineurs and 265 headache-free controls were genotyped for the selected genetic variants using real-time PCR (melting curve analysis). Results: Although allelic and genotypic frequency distribution analysis did not support an association between migraine susceptibility and the examined variants in the overall population, subgroup analysis indicated significant correlation between NOS3 rs1799983 and migraine susceptibility in males. Furthermore, significant associations of CAT rs1001179 and GPX1 rs1050450 with disease age-at-onset and migraine attack duration, respectively, were revealed. Lastly, variability in the CAT, GSTP1 and UCP2 genes were associated with sleep/weather changes, alcohol consumption and physical exercise, respectively, as migraine triggers. Discussion: Hence, the current findings possibly indicate an association of OS-related genetic variants with migraine susceptibility and clinical features, further supporting the involvement of OS and genetic susceptibility in migraine.

Results of a Web-Based Survey on 2105 Greek Migraine Patients-Second Part: Efficacy of Acute and Prophylactic Migraine Treatments and Corresponding Patients' Reported Satisfaction.

Background and Objectives: The Greek Society of Migraine and Headache Patients conducted, in 2020, its second online survey, titled "Migraine in Greece-2020", after publication of the first similar online survey conducted in 2018. To compare the current findings with the corresponding data obtained in 2018, we herein release the second part of results obtained from the 2020 survey on the efficacy of preventive and symptomatic anti-migraine medications and the patients' reported satisfaction with these treatments. Materials and Methods: We surveyed 2105 migraine patients from all over Greece with the use of a 151-questions specific migraine-focused questionnaire in Greek language, which was distributed through the online research software "SurveyMonkey". Results: Triptans were mostly used with efficacy for the symptomatic relief of migraine attacks. About 2 of 3 surveyed patients had received various prophylactic oral medications and the majority of them discontinued these prophylactic medications as a result of inefficacy/safety issues. BoNTA was reported to be effective only when administration was commenced by a trained neurologist/headache specialist, while our current findings are generally comparable to those obtained in our 2018 pre-COVID-19 survey and the pandemic has not imposed any significant attitudes on migraine therapies and corresponding patients' satisfaction. Conclusion: Although a market change is anticipated with the evolving widespread use of anti-CGRPs monoclonal antibodies or gepants in the symptomatic and prophylactic treatment of migraine, it is of great interest to review published results of larger longitudinal population-based studies to further ascertain the satisfaction of patients to migraine therapies.

Therapeutic Benefits of Short-Arm Human Centrifugation in Multiple Sclerosis-A New Approach.

Short-arm human centrifugation (SAHC) is proposed as a robust countermeasure to treat deconditioning and prevent progressive disability in a case of secondary progressive multiple sclerosis. Based on long-term physiological knowledge derived from space medicine and missions, artificial gravity training seems to be a promising physical rehabilitation approach toward the prevention of musculoskeletal decrement due to confinement and inactivity. So, the present study proposes a novel infrastructure based on SAHC to investigate the hypothesis that artificial gravity ameliorates the degree of disability. The patient was submitted to a 4-week training programme including three weekly sessions of 30 min of intermittent centrifugation at 1.5-2 g. During sessions, cardiovascular, muscle oxygen saturation (SmO2) and electroencephalographic (EEG) responses were monitored, whereas neurological and physical performance tests were carried out before and after the intervention. Cardiovascular parameters improved in a way reminiscent of adaptations to aerobic exercise. SmO2 decreased during sessions concomitant with increased g load, and, as training progressed, SmO2 of the suffering limb dropped, both effects suggesting increased oxygen use, similar to that seen during hard exercise. EEG showed increased slow and decreased fast brain waves, with brain reorganization/plasticity evidenced through functional connectivity alterations. Multiple-sclerosis-related disability and balance capacity also improved. Overall, this study provides novel evidence supporting SAHC as a promising therapeutic strategy in multiple sclerosis, based on mechanical loading, thereby setting the basis for future randomized controlled trials.

Open Label Prospective Experience of Supplementation with a Fixed Combination of Magnesium, Vitamin B2, Feverfew, Andrographis Paniculata and Coenzyme Q10 for Episodic Migraine Prophylaxis.

BACKGROUND: To investigate the efficacy and safety of supplementation with a fixed combination of magnesium, vitamin B2, feverfew, andrographis paniculata and coenzyme Q10 in episodic migraine (EM) prevention. METHODS: A pilot, single-arm, open-label study was conducted. After a one-month baseline period, the above-described supplementation was introduced in 113 EM Greek patients, who were prospectively followed-up for three months. The primary endpoint was the change in monthly migraine days between baseline period (BSL) and the third month of supplementation (T3). Secondary endpoints included changes in mean intensity of migraine and in days with use of acute migraine medications. Changes in scores of Migraine Disability Assessment questionnaire (MIDAS), Headache Impact Test-6 (HIT-6), Migraine Therapy Assessment questionnaire (MTAQ), Migraine-Specific Quality-of-life questionnaire (MSQ-QOL), Hospital Anxiety and Depression Scale (HADS) were also evaluated. Those with ≥50% reduction in monthly migraine days at T3, compared to BSL were considered supplementation-responders. RESULTS: The mean number of migraine days was significantly decreased between BSL and T3 (9.4 ± 3.7 vs. 6.1 ± 3.5; p < 0.001). Likewise, days with peak headache intensity of >4/10 (5.7 ± 3.4 vs. 4.9 ± 3.1; p < 0.001) as well as days using acute headache medications per month (8.9 ± 3.6 vs. 5.7 ± 3.4; p < 0.001) were significantly reduced. At T3, 64 patients (56.6%) were classified as responders. The beneficial effect of supplementation was also associated with significant changes in HIT-6, MIDAS, MTAQ and MSQ-QOL scores. There were no safety concerns. CONCLUSIONS: The supplementation we have tested appears to be an effective and well-tolerated preventive approach against EM. A randomized, placebo-controlled study is needed to confirm our results.