International Headache Society global practice recommendations for the acute pharmacological treatment of migraine.

BACKGROUND: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications. METHODS: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group. RESULTS: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained. CONCLUSION: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited.

Specific cognitive and psychological alterations are more strongly linked to increased migraine disability than chronic migraine diagnosis.

INTRODUCTION: The efficiency of The International Classification of Headache Disorders (ICHD-3) in reflecting patients' disability has recently been questioned. This prompts consideration that clinical features beyond pain may more accurately indicate the extent of underlying brain impairment than the mere frequency of headache days. Important cognitive dysfunctions and psychological impairment have been reported in burdensome cases of migraine, and the presence of these alterations has been associated with biological changes in the nervous system. This study aimed to compare migraine-related disability within a specific patient group, classified using ICHD-3 criteria or classified based on findings from a neuropsychological evaluation using machine learning. Additionally, a complementary voxel-based morphometry (VBM) comparison was conducted to explore potential neuroanatomical differences between the resulting groups. PATIENTS AND METHODS: The study included episodic and chronic migraine patients seeking consultation at a specialized headache department. A neuropsychological evaluation protocol, encompassing validated standardized tests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) and disability (MIDAS), was administered. Results from this evaluation were input into an automated K-means clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxel-based Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts between the two distinct grouping configurations. RESULTS: The study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine. Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Cluster two exhibited significantly higher levels of depression, anxiety, and perceived stress, and performed worse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores between episodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs 62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients in cluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS (68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significant differences in grey matter volume between the two clusters were noted, particularly involving the precuneus, while differences between chronic and episodic migraine patients did not withstand correction for multiple comparisons. CONCLUSIONS: The classification of migraine patients based on neuropsychological characteristics demonstrates a more effective separation of groups in terms of disability compared to categorizing them based on the chronic or episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explain differences in treatment responses among apparently similar patients.

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature.

BACKGROUND: We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. METHODS: MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines. RESULTS: Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving n = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan. CONCLUSION: Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself.PROSPERO trial registration: CRD42022308224.

Bridging the gaps of headache care for underserved populations: Current status of the headache field in Latin America.

OBJECTIVE: To evaluate the current status of specialized headache care and research in Latin America. BACKGROUND: Latin America corresponds to about 9% of the global population. There is considerably limited access to headache services, and very few resources are allocated to headache research in this region. METHODS: The study consisted of two parts. First, in order to evaluate headache-related scientific output from Latin American countries we performed a 10-year bibliometric analysis and contrasted the results with a human developmental index-adjusted projection model. Secondly, we conducted a survey addressing different aspects of headache research, education, clinical practice, and awareness among members of the Latin American Headache Society. RESULTS: During the last 10 years 70% of Latin American countries published less than three articles regarding headache disorders. This contrasts with an average expected publication rate of 889 scientific papers. Indeed, none of the countries fulfilled their human developmental index - adjusted projected scientific output, with Brazil being the closest reaching 84.1% of what would be considered optimal according to the model. From the 86 headache-dedicated professionals that responded to the survey, most (64%) reported not having a headache specialization programme of any kind available in their countries. The biggest impediments towards conducting research observed by participants were the lack of time (39%), resources (22%), and training (21%). CONCLUSIONS: Latin American countries have a considerable gap in headache-related scientific production, and also in formal education, research, and implementation of multidisciplinary services. Access to specialized headache care is particularly limited for patients with lower economic income.

High rates of (treated) hypothyroidism among chronic migraine patients consulting a specialized headache clinic: are we missing something?

BACKGROUND: Roughly three percent of episodic migraine patients evolve into the most burdensome chronic form of this condition every year. While some of the determinants behind this transformation are well established, others are still ill defined. Hypothyroidism is a prevalent endocrinological disorder that can both produce a secondary headache or aggravate a pre-existing primary headache disorder such as migraine. OBJECTIVE: We aimed to re-assess the association between hypothyroidism and chronic migraine controlling for factors such as hormone replacement treatment status and bodyweight. METHODS: We retrospectively analyzed the medical records of episodic and chronic migraine patients who consecutively consulted our headache clinic in order to determine the prevalence of adequately treated hypothyroidism in each group. Only patients receiving a stable dose regimen were included. The body mass index and other possibly confounding covariates were also collected. RESULTS: Data from 111 migraine patients was included for analysis. Most (88.6%) of chronic migraine sufferers were overusing acute medication. Treated hypothyroidism was significantly more prevalent in chronic migraine patients (29.55%) compared to episodic migraine patients (8.96%). This association was independent of the patients' body mass index or other variables. CONCLUSION: Alterations of neuronal metabolism, deficient calcitonin release, or focal inflammation causing local hormonal deactivation might explain why hypothyroidism, in spite of levothyroxine replacement therapy, is associated with migraine chronification. Further studies evaluating these factors are warranted.

Old Habits Die Hard: Dietary Habits of Migraine Patients Challenge our Understanding of Dietary Triggers.

Introduction: Migraine is a multifactorial neurological disorder with a major metabolic facet. Dietary approaches represent a commonly implemented lifestyle modifying strategy in headache clinics, yet the precise relationship between diet and migraine is still a matter of debate. Materials and Methods: The study consisted of two parts: first, in a cross-sectional design, we compared alimentary habits of migraine subjects and a control group of healthy volunteers. For the second part, we prospectively evaluated patients' daily consumption of various potentially migraine-triggering foods over a two-month period in order to examine their possible association with the occurrence of a migraine attack. Results: Most migraine patients reported avoiding at least one potentially migraine-triggering food/drink from their diet. In spite of that, with the sole exemption of citrus fruits, there were no statistically significant differences with respect to consumption patterns between migraine patients and controls (including wine and chocolate). Consumption frequency over time was proportional to intake of potentially migraine-triggering foods the day before a migraine attack. Conclusion: Our results underline the need of performing trigger challenges in order to avoid falling into an association-causation fallacy when attempting to identify possible alimentary migraine triggers. Indeed, it is possible that intake of certain foods like chocolate before attacks is a consequence of pre-attack cravings or a simple coincidence facilitated by previously established dietary habits.

The prevalence of migraine in Argentina: A reappraisal.

BACKGROUND: Argentina has one of the largest territories in the world, which spreads over a lengthy latitudinal span. Its population is mainly composed of a mixture of South American natives and the descendants of numerous waves of European immigrants. Results from a previous study suggested that the prevalence of migraine in Argentina is the lowest in the region. Here we aimed to reassess the prevalence of migraine in Argentina applying a more sensitive and specific screening tool. METHODS: We conducted a random computer assisted telephonic interview (n= 2500) using the Migraine Screen Questionnaire to evaluate the prevalence of migraine and some of its features among Argentinian adults. RESULTS: The overall prevalence of migraine was 9.5% (14% in females and 5% in males). Estimated migraine prevalence rates ranged between 6.3% and 12% across different regions. The approximated prevalence of high frequency and chronic migraine were 1.9% and 1.5% of the total population respectively. Consumption of analgesics on 10 or more days per month was reported by 18% of migraine sufferers (≈1.7% of the population). CONCLUSIONS: The prevalence of migraine in Argentina is higher than previously reported. Prevalence rates vary extensively across the territory. Specifically evaluating the determinants of these variations might be a promising avenue of research.

Impaired short-term visual paired associative plasticity in patients with migraine between attacks.

ABSTRACT: A common experimental neurophysiological method to study synaptic plasticity is pairing activity of somatosensory afferents and motor cortical circuits, so-called paired associative stimulation (PAS). Dysfunctional inhibitory and excitatory PAS mechanisms within the sensorimotor system were described in patients with migraine without aura (MO) between attacks. We have recently observed that the same bidirectional PAS rules also apply to the visual system. Here, we have tested whether dysfunctioning associative plasticity might characterize the visual system of patients with MO. In 14 patients with MO between attacks and in 15 healthy volunteers, we performed a previously validated visual PAS (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with low-frequency transcranial magnetic stimulation pulses over the occipital cortex at 2 interstimulus intervals of -25/+25 ms around the visual-evoked potential (VEP) P1 latency. We recorded VEPs (600 sweeps) before, immediately after, and 10 min after each vPAS session. We analysed VEP N1-P1 amplitude and delayed habituation. Although vPAS-25 significantly enhanced and vPAS + 25 reduced VEP amplitude habituation in healthy volunteers, the same protocols did not significantly change VEP amplitude habituation in MO between attacks. We provide evidence for lack of habituation enhancing and habituation suppressing visual PAS mechanisms within the visual system in interictal migraine. This finding, in combination with those previously obtained studying the sensorimotor system, leads us to argue that migraine disease-related dysrhythmic thalamocortical activity prevents the occurrence of physiological bidirectional synaptic plasticity induced by vPAS.