Cephalalgia最新文献

Background: In this study, we aimed to evaluate the differing global access to acute and preventive medications for migraine and tension-type headache.

Methods: A custom-built questionnaire created by members of the International Headache Society Juniors Group was sent to International Headache Society members worldwide, including a list of acute and preventive treatments for migraine and tension-type headache. This list was based on evidence-based medicine guidelines. For each treatment, participants were asked about availability, type of reimbursement and variability of access within their country.

Results: Eighty-four members completed the questionnaire providing data for 84 countries. The majority were neurologists (88%) and worked at an academic/university hospital (62%). Of participants, 36% were located in high-income economy countries and 13% were located in low-income economies. Common preventive treatments such as propranolol and topiramate were available in most countries (respectively in 99% and 92% of responding countries). Sumatriptan was available in most countries (95%), whereas other triptan availability was lower. Novel migraine treatments such as rimegepant and erenumab were only available in 14% and 46% of the assessed countries, respectively.

Conclusions: Availability of headache medications, ranging from simple analgesics to novel therapies migraine-specific drugs, varied greatly across the world. Actions are needed to improve effective drug availability in many countries to ensure an adequate management of people living with headache.

Background: To evaluate the benefit-risk assessment of atogepant and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population.

Methods: The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab.

Results: In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1-6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (-1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo.

Conclusions: Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses.

Background: There are currently no intraoperative neurophysiological tools to assess the effectiveness of trigeminal nerve decompression during microvascular decompression surgery for drug-resistant trigeminal neuralgia. In microvascular decompression surgery for hemifacial spasm, an abnormal electromyographic activation of facial muscles after stimulation of the offending vessel was identified and named 'Z-L response'.

Methods: We adapted a neurophysiological protocol to elicit a Z-L response during microvascular decompression surgery for trigeminal neuralgia and applied it to a prospective series of 18 surgical patients.

Results: Patients had suffered from trigeminal neuralgia for a median 9-year timeframe, and median preoperative Barrow Neurological Institute pain score was 4.5. Through monopolar stimulation, using rising amplitudes starting from 0.1 mA, we confirmed intraoperatively the true culprit vessel before decompression. In 4/18 cases, multiple offending vessels were identified (22 conflicts overall). After decompression, a significant increase in activation threshold (p < 0.0001) confirmed the effectiveness of the maneuver; in 10 cases, Z-L response was abolished. Using this technique, we obtained excellent or good outcome (Barrow Neurological Institute 1-3) in all patients, with a significant reduction in postoperative Barrow Neurological Institute score as compared with preoperative one (median Barrow Neurological Institute 1; p = 0.0002).

Conclusion: we provide the first evidence on the applicability and clinical usefulness of Z-L response during microvascular decompression surgery for trigeminal neuralgia.

Background: Migraine with aura (MWA) is a risk factor for stroke, but the mechanisms underlying this association remain unclear. Our aim was to assess the association between MWA and cerebral small-vessel disease (CSVD) ischemic stroke after adjustment for vascular risk factors in a population of young patients hospitalized for a first-ever ischemic stroke.

Methods: Patients aged 18-54 years consecutively hospitalized for a first-ever acute ischemic stroke at the neurovascular unit of our university hospital between January 2017 and July 2021 were included in this retrospective cohort study. CSVD lesions were assessed and classified according to ASCOD (Atherosclerosis, Small-Vessel Disease, Cardiac pathology, Others causes, Dissection) classification criteria.

Results: In total, 646 patients were included (median (SD) age, 44.03 (9.01) years; 61.8% male) including 115 patients with MWA and 110 patients with migraine without aura (MWoA). Grade S1, potentially causal, CSVD lesions were significantly less frequent in patients with MWA (odds ratio (OR) = 0.35, 95% cofdence interval (CI)  =  0.13-0.95, p = 0.048) compared to non-migraine patients in univariate analysis. Logistic regression adjusting for vascular risk factors showed no significant association of CSVD of any grade (S1, S2 or S3 vs. S0) with migraine: OR = 0.78, 95% CI = 0.48-1.28, p = 0.34; MWoA: OR = 0.81, 95% CI = 0.42-1.47, p = 0.51; and MWA: OR = 0.84, 95% CI = 0.43-1.56, p = 0.60, as well as no association of grade S1 CSVD lesions with migraine: OR = 0.91, 95% CI = 0.40-1.92, p = 0.81; MWoA: OR = 1.11, 95% CI = 0.42-2.64, p = 0.81; and MWA: OR = 0.72, 95% CI = 0.20-1.98, p = 0.56.

Conclusions: In a retrospective study including almost 650 young adults hospitalized for a first ischemic stroke, MWA was not associated with CSVD cause of stroke after adjustment for vascular risk factors.

Background: Migraine has a strong genetic foundation, including both monogenic and polygenic types. The former are rare, with most migraine considered polygenic, supported by genome-wide association studies (GWAS) identifying numerous genetic variants linked with migraine risk. Surprisingly, some of the most common mutations are associated with transient receptor potential melastatin 8 (TRPM8), a non-selective cation channel that is the primary sensor of cold temperatures in cutaneous primary afferents of the somatosensory system. However, it is unlikely that the temperature sensitivity of TRPM8 is relevant in migraine-related tissues, such as the meninges, suggesting other activation mechanisms underly its role in migraine pathogenesis. Thus, to define the basis of the channel's involvement, we reasoned that cellular processes that increase cold sensitivity in the skin, such as the neurotrophic factor artemin, via its receptor glial cell-line derived neurotrophic factor family receptor alpha-3 (GFRα3), also mediate TRPM8-associated migraine-like pain in the meninges.

Methods: To investigate the role of artemin and GFRα3 in preclinical rodent migraine models, we infused nitroglycerin acutely and chronically, and measured changes in periorbital and hind paw mechanical sensitivity in male and female mice lacking GFRα3, after neutralization of free artemin with specific monoclonal antibodies, or by systemic treatment with a TRPM8-specific antagonist. Further, in mice lacking GFRα3 we tested the effects of supradural infusions of a mix of inflammatory mediators, as well as tested if dura stimulation with artemin or a TRPM8-specific agonist induce migraine-related pain in mice.

Results: We find that mechanical allodynia induced by systemic nitroglycerin, or supradural infusion of inflammatory mediators, involves GFRα3. In addition, neutralization of circulating artemin reduces the nitroglycerin phenotype, demonstrating the importance of this neurotrophic pathway in headaches. Further, we show TRPM8 expression in the meninges, and that direct supradural infusion of either a TRPM8-specific agonist or artemin itself produces mechanical allodynia, with the latter dependent on TRPM8 and ameliorated by concurrent treatment with sumatriptan.

Conclusions: These results indicate that neuroinflammatory events in the meninges can produce migraine-like pain in mice via artemin and GFRα3, likely acting upstream of TRPM8, providing a novel pathway that may contribute to headaches or migraine pathogenesis.

Background: Migraine with aura (MwA) is a debilitating disorder characterized by paroxysmal attacks of pain preceded or accompanied by reversible neurological symptoms. While the pathophysiology remains unclear, trigeminovascular system activation and cortical spreading depression have been implicated. This study aims to comprehensively investigate and characterize the diverse clinical features and manifestations of aura, as well as the types of acute medications self-administered for aura management.

Methods: A multicenter, cross-sectional study was conducted using data from the Italian Headache Registry (RICe). Aura characteristics, frequency, duration and associated migraine premonitory symptoms were collected. Acute medication use and timing (headache or aura phase) were assessed.

Results: The study included 272 patients with a diagnosis of MwA. Most patients (99.3%) experienced typical aura symptoms, with visual aura (96.3%) being the most prevalent, followed by sensory (33.0%) and speech and/or language aura (25.6%). Brainstem aura (8.5%) and motor aura (1.8%) were less common. Notably, 13.0% of patients reported aura relapses within 24 hours. Triptans (39.7%), non-steroidal anti-inflammatory drugs (47.8%) and nutraceuticals (59.9%) were commonly used for acute aura management.

Conclusions: This study reports several different aura manifestations, highlighting atypical features, aura relapse rates and treatment approaches for aura. These findings could contribute to a deeper understanding of aura and its management in clinical settings.

Background: Migraine patients unresponsive to calcitonin gene-related peptide (CGRP)(-receptor, -R) monoclonal antibodies (mAbs) may benefit from switching between CGRP(-R) mAbs. However, some patients do not tolerate or respond to any subcutaneous mAbs. This study evaluates the efficacy of the intravenous CGRP mAb eptinezumab in these therapy-refractory patients.

Methods: In this retrospective cohort study, patients with migraine who previously failed erenumab and at least one CGRP mAb (fremanezumab and/or galcanezumab) received eptinezumab 100 mg, followed by a second dose of 100 mg or 300 mg after 12 weeks. Monthly headache days, monthly migraine days, acute medication days, and migraine pain intensity were recorded from standardized headache diaries during the four weeks before the first infusion (baseline), and during weeks 9-12 and 21-24 of treatment. Patient-reported outcomes were analyzed at baseline, weeks 12, and 24.

Results: From January 2023 to February 2024, 41 patients received eptinezumab 100 mg. Of these, 38 (93%) received a second infusion after 12 weeks, with 29 (71%) increasing the dose to 300 mg. The percentage of patients with a ≥30% reduction rate in monthly migraine days was 23.1% at week 12 and 29.7% at week 24. Monthly migraine days decreased from 16.3 ± 8.0 at baseline to 15.4 ± 8.1 days during weeks 9-12 and 14.4 ± 8.0 days during weeks 21-24 (p = 0.07). During weeks 21-24, 38.5% reported a clinically meaningful reduction in HIT-6 scores and 52.4% in MIDAS scores. No adverse events were reported.

Conclusions: Eptinezumab may be an effective and well-tolerated option for some treatment-refractory migraine patients unresponsive to subcutaneous CGRP-(R) mAbs.