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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.
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Trastornos Migrañosos , Trastornos Migrañosos/tratamiento farmacológico , Humanos , Analgésicos/uso terapéutico , Sociedades Médicas/normasRESUMEN
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.
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Personas con Discapacidad , Trastornos de Cefalalgia , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/diagnóstico por imagen , Cefalea , Trastornos de Cefalalgia/diagnóstico , Recolección de DatosRESUMEN
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.
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Trastornos Migrañosos , Adulto , Humanos , Metaanálisis en Red , Método Doble Ciego , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/diagnóstico , Resultado del TratamientoRESUMEN
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.
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Bibliometría , Cefalea , Brasil , Cefalea/epidemiología , Cefalea/terapia , Humanos , América Latina/epidemiologíaRESUMEN
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.
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Hipotiroidismo , Trastornos Migrañosos , Cefalea , Humanos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/epidemiología , Derivación y Consulta , Estudios RetrospectivosRESUMEN
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.
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Cefaleas Secundarias/epidemiología , Trastornos Migrañosos/epidemiología , Adulto , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Argentina/epidemiología , Femenino , Cefaleas Secundarias/diagnóstico , Cefaleas Secundarias/tratamiento farmacológico , Humanos , Masculino , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/tratamiento farmacológico , Uso Excesivo de Medicamentos Recetados , Prevalencia , Encuestas y CuestionariosRESUMEN
PURPOSE: The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the frequency of attacks. METHODS: We analysed the relation between brain glucose (18F-fluorodeoxyglucose) uptake and age in healthy volunteers (n = 20) and episodic migraine patients (n = 19). In the latter, we additionally compared the correlation between 18F-fluorodeoxyglucose uptake and disease duration and monthly migraine days. RESULTS: In contrast to controls, in migraine patients advancing age was positively correlated to increased metabolism in the brainstem (especially the posterior pons), hippocampus, fusiform gyrus and parahippocampus. Conversely, no significant correlations between cerebral metabolism and disease duration or migraine days were observed. CONCLUSIONS: Findings of this cross-sectional study show that episodic migraine patients exhibit specific metabolic brain modifications while ageing. As such, age is correlated with metabolic changes in key regions of the brain previously associated with migraine's pathophysiology to a better extent than disease duration or the number of monthly migraine days. More than the repeated headache attacks, the continuous interaction with the environment seemingly models the brain of migraine sufferers in an adaptive manner. A positive control (e.g. chronic pain) is missing in this study and therefore findings cannot be proven to be migraine-specific.
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Envejecimiento/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Trastornos Migrañosos/diagnóstico por imagen , Trastornos Migrañosos/metabolismo , Adulto , Envejecimiento/patología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/tendencias , Adulto JovenRESUMEN
BACKGROUND: The purpose of this review is to provide a comprehensive overview of the findings of clinical electrophysiology studies aimed to investigate changes in information processing of migraine with aura patients. MAIN BODY: Abnormalities in alpha rhythm power and symmetry, the presence of slowing, and increased information flow in a wide range of frequency bands often characterize the spontaneous EEG activity of MA. Higher grand-average cortical response amplitudes, an increased interhemispheric response asymmetry, and lack of amplitude habituation were less consistently demonstrated in response to any kind of sensory stimulation in MA patients. Studies with single-pulse and repetitive transcranial magnetic stimulation (TMS) have reported abnormal cortical responsivity manifesting as greater motor evoked potential (MEP) amplitude, lower threshold for phosphenes production, and paradoxical effects in response to both depressing or enhancing repetitive TMS methodologies. Studies of the trigeminal system in MA are sparse and the few available showed lack of blink reflex habituation and abnormal findings on SFEMG reflecting subclinical, probably inherited, dysfunctions of neuromuscular transmission. The limited studies that were able to investigate patients during the aura revealed suppression of evoked potentials, desynchronization in extrastriate areas and in the temporal lobe, and large variations in direct current potentials with magnetoelectroencephalography. Contrary to what has been observed in the most common forms of migraine, patients with familial hemiplegic migraine show greater habituation in response to visual and trigeminal stimuli, as well as a higher motor threshold and a lower MEP amplitude than healthy subjects. CONCLUSION: Since most of the electrophysiological abnormalities mentioned above were more frequently present and had a greater amplitude in migraine with aura than in migraine without aura, neurophysiological techniques have been shown to be of great help in the search for the pathophysiological basis of migraine aura.
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Electroencefalografía/métodos , Potenciales Evocados Motores/fisiología , Migraña con Aura/diagnóstico , Migraña con Aura/fisiopatología , Adulto , Parpadeo/fisiología , Femenino , Humanos , Masculino , Transmisión Sináptica/fisiología , Estimulación Magnética Transcraneal/métodosRESUMEN
Background Migraine is a complex multifactorial disease that arises from the interaction between a genetic predisposition and an enabling environment. Habituation is considered as a fundamental adaptive behaviour of the nervous system that is often impaired in migraine populations. Given that migraineurs are hypersensitive to light, and that light deprivation is able to induce functional changes in the visual cortex recognizable through visual evoked potentials habituation testing, we hypothesized that regional sunlight irradiance levels could influence the results of visual evoked potentials habituation studies performed in different locations worldwide. Methods We searched the literature for visual evoked potentials habituation studies comparing healthy volunteers and episodic migraine patients and correlated their results with levels of local solar radiation. Results After reviewing the literature, 26 studies involving 1291 participants matched our inclusion criteria. Deficient visual evoked potentials habituation in episodic migraine patients was reported in 19 studies. Mean yearly sunlight irradiance was significantly higher in locations of studies reporting deficient habituation. Correlation analyses suggested that visual evoked potentials habituation decreases with increasing sunlight irradiance in migraine without aura patients. Conclusion Results from this hypothesis generating analysis suggest that variations in sunlight irradiance may induce adaptive modifications in visual processing systems that could be reflected in visual evoked potentials habituation, and thus partially account for the difference in results between studies performed in geographically distant centers. Other causal factors such as genetic differences could also play a role, and therefore well-designed prospective trials are warranted.
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Potenciales Evocados Visuales/fisiología , Habituación Psicofisiológica/fisiología , Trastornos Migrañosos/epidemiología , Luz Solar , HumanosRESUMEN
Background Identifying specific subsets of patients within the clinical spectrum of migraine could help in personalizing migraine treatment. Profiling patients by combining clinical characteristics and neurophysiological biomarkers is largely unexplored. We studied the association between migraine attack triggers and habituation of visual evoked potentials. Methods We personally interviewed 25 patients about their migraine triggers following a structured list, and measured the N1-P1 habituation slope over six blocks of 100 averaged pattern-reversal VEP afterwards. Results The mean number of triggers per patient was 4.52 ± 1.42. Habituation slopes differed significantly between subjects who reported stress as a migraine trigger (deficient VEP habituation) and subjects who did not (preserved VEP habituation). For the remaining categories, the mean amplitude slope was always positive, indicating deficient habituation, and was not significantly different between subgroups. Conclusions Migraine patients not reporting perceived stress as a trigger for their attacks might constitute a distinct clinic-physiological subset within the migraine spectrum.
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Potenciales Evocados Visuales/fisiología , Habituación Psicofisiológica/fisiología , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/fisiopatología , Adulto , Ayuno/fisiología , Femenino , Humanos , Masculino , Trastornos Migrañosos/etiología , Factores Desencadenantes , Privación de Sueño/complicaciones , Privación de Sueño/diagnóstico , Privación de Sueño/fisiopatología , Estrés Psicológico/complicaciones , Estrés Psicológico/diagnóstico , Estrés Psicológico/fisiopatología , Corteza Visual/fisiología , Tiempo (Meteorología) , Adulto JovenRESUMEN
BACKGROUND: Percutaneous occipital nerve stimulation (ONS) is effective in refractory chronic cluster headache (rCCH) patients. Responders to ONS differ from non-responders by greater glucose metabolism in subgenual anterior cingulate cortex (sgACC). We reasoned that transcranial direct current stimulation (tDCS), a non-invasive approach, might be able to activate this area and thus improve rCCH patients. Our objective was to explore in a pilot trial the therapeutic potential of tDCS (anode at Fz, cathode over C7) and its possible effects on pain perception, frontal executive functions and mood in rCCH patients. METHODS: Thirty-one patients were asked to apply daily 20-min sessions of 2 mA tDCS for 4 or 8 weeks after a 1-month baseline. CH attacks were monitored with paper diaries. The primary outcome measure was change in weekly attacks between baseline and the last week of tDCS. Twenty-three patients were available for a modified ITT analysis, 21 for per-protocol analysis. We also explored treatment-related changes in thermal pain thresholds and nociceptive blink reflexes (nBR), frontal lobe function and mood scales. RESULTS: In the per-protocol analysis there was a mean 35% decrease of attack frequency (p = 0.0001) with 41% of patients having a ≥ 50% decrease. Attack duration and intensity were also significantly reduced. After 8 weeks (n = 10), the 50% responder rate was 45%, but at follow-up 2 weeks after tDCS (n = 16) mean attack frequency had returned to baseline levels. The treatment effect was significant in patients with high baseline thermal pain thresholds in the forehead (n = 12), but not in those with low thresholds (n = 9). The Frontal Assessment Battery score increased after tDCS (p = 0.01), while there was no change in depression scores or nBR. CONCLUSION: tDCS with a Fz-C7 montage may have a preventive effect in rCCH patients, especially those with low pain sensitivity, suggesting that a sham-controlled trial in cluster headache is worthwhile. Whether the therapeutic effect is due to activation of the sgACC that can in theory be reached by the electrical field, or of other prefrontal cortical areas remains to be determined.
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Cefalalgia Histamínica/fisiopatología , Cefalalgia Histamínica/terapia , Giro del Cíngulo/fisiología , Dimensión del Dolor/métodos , Prueba de Estudio Conceptual , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Mapeo Encefálico/métodos , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción del Dolor/fisiologíaRESUMEN
BACKGROUND: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers. METHODS: Twenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups. RESULTS: The mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann's areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers. CONCLUSION: This study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology. This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata.
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Potenciales Evocados Visuales/fisiología , Glucosa/metabolismo , Trastornos Migrañosos/fisiopatología , Neuronas/fisiología , Tomografía de Emisión de Positrones , Corteza Visual/fisiopatología , Adulto , Área Bajo la Curva , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Masculino , Trastornos Migrañosos/diagnóstico por imagen , Examen Neurológico , Radiofármacos/administración & dosificación , Descanso , Corteza Visual/diagnóstico por imagenRESUMEN
Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. The burden of disease on individuals and societies is significant due to high costs and comorbidities. In the Third Edition of the International Classification of Headache Disorders, medication-overuse headache is recognized as a separate secondary entity next to mostly primary headache disorders, although many clinicians see the disease as a sole complication of primary headache disorders. In this review, we explore the historical background of medication-overuse headache, its epidemiology, phenomenology, pathophysiology and treatment options. The review explores relevant unanswered questions and summarizes the current debates in medication-overuse headache.
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Cefaleas Secundarias/epidemiología , Cefaleas Secundarias/diagnóstico , Cefaleas Secundarias/terapia , Humanos , PrevalenciaRESUMEN
Background Lack of habituation of visual evoked potentials (VEP) is a common finding in migraine patients between attacks. Previous studies have suggested an electrophysiological familial aggregation pattern associated with migraine. The aim of this study was to evaluate the influence of a positive familial history of migraine on VEP amplitude and habituation. Methods We recorded six blocks of 100 VEP during continuous pattern-reversal stimulation in 30 patients with migraine between attacks (MO) and in 30 healthy volunteers, of whom 15 had a first-degree relative suffering from migraine (HVm) and 15 had not (HV). Results Both MO and HVm had a significant deficit of VEP habituation and similarly reduced N1-P1 first block amplitudes, compared to HV (habituation slope: MO = 0.033, HVm = 0.021, HV = -0.025, HV vs. MO p = 0.002, HV vs. HVm p = 0.036; mean N1-P1 amplitude in the first block: MO = 9.08 µV, HVm = 9.29 µV, HV = 12.19 µV. HV vs. MO p = 0.041, HV vs. HVm p = 0.076). The first block N1-P1 amplitude was negatively correlated with the habituation slope for both MO (ρ = -.44, p = 0.015) and HVm (ρ = -.56, p = 0.031) while no significant correlation was found in HV (ρ = .17, p = 0.53). There were no differences in VEP latencies between the groups. Conclusions Our study suggests that lack of habituation of visual evoked potentials is probably a genetically determined endophenotypic trait that is associated with both migraine and migraine susceptibility. We hypothesize that genetic diversity of populations could account for some of the discrepancies between electrophysiological studies performed in migraine and for interindividual variations among the subgroups.
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Potenciales Evocados Visuales/fisiología , Habituación Psicofisiológica/fisiología , Trastornos Migrañosos/fisiopatología , Adulto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Trastornos Migrañosos/genética , Adulto JovenRESUMEN
PURPOSE OF REVIEW: In migraine, the brain is 'hyperresponsive', which refers to a deficit of habituation to repeated sensory stimuli between attacks. This deficit normalizes in peri-ictal and ictal phases. A decreased cortical preactivation of thalamo-cortical origin and an impaired intracortical inhibition are probably involved in its pathophysiology. RECENT FINDINGS: The reality of a habituation deficit of visual evoked potentials, a neurophysiological 'hallmark' of interictal migraine, has been questioned. Blinding may be an issue, but some genetic, environmental, or behavioural differences could also exist between populations. A habituation deficit is found interictally in other sensory modalities, and strongly depends on the time of the recordings within the migraine cycle. An impaired thalamocortical drive is demonstrated in interictal phase, and normalizes in ictal phase as well as in chronic migraine, where a strength enhancement of primary cortical activation is observed. An interictal dysexcitability, of subcortical or primary cortical origin, is suggested by magnetic stimulation. These phenomena could occur in varying degrees depending on patients and on the migraine cycle, and account for the heterogeneity of electrophysiological results. SUMMARY: Finding a reliable electrophysiological biomarker for such a multifaceted and cycling disease as migraine is still a challenge. A better standardization of protocols would be worthwhile.
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Encéfalo/fisiopatología , Potenciales Evocados Visuales/fisiología , Habituación Psicofisiológica/fisiología , Trastornos Migrañosos/fisiopatología , Electrofisiología , HumanosRESUMEN
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.
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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.
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Habituación Psicofisiológica , Trastornos Migrañosos , Potenciales Evocados Visuales , Humanos , Plasticidad Neuronal , Estimulación Luminosa , Estimulación Magnética TranscranealRESUMEN
Introduction: Most preventive migraine treatments modify the brain's excitation/inhibition balance and/or serotonin metabolism, which likely accounts for their unfavorable adverse effect profile. Novel biological therapies blocking CGRP transmission are effective and better tolerated, but they are expensive and may not influence brain dysfunctions upstream in the pathophysiological cascade of migraine, including premonitory and aura symptoms. Biochemical and clinical studies suggest that there may be another complimentary treatment strategy, the one that targets the underestimated metabolic facet of migraine pathophysiology.Areas covered: After a brief description of the metabolic abnormalities found in migraine patients, we will review and discuss published data on metabolic treatments of migraine. There is evidence that riboflavin and co-enzyme Q10 are effective for the prevention of migraine and quasi devoid of adverse effects. Response rates are close to those of topiramate, propranolol, and CGRP/CGRPrec mAbs. The evidence is weaker for thioctic acid. Dietary and pharmacological strategies inducing ketosis are novel promising approaches for which preliminary trials with favorable outcomes have been published.Expert opinion: Metabolic treatments of migraine constitute an effective, well-tolerated, inexpensive, and evidence-supported therapeutic option for migraine prophylaxis, and may be considered as first treatment line in many patients, including in children and adolescents.
Asunto(s)
Dieta Cetogénica , Trastornos Migrañosos , Riboflavina/farmacología , Ubiquinona/análogos & derivados , Vitaminas/farmacología , Humanos , Trastornos Migrañosos/dietoterapia , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/prevención & control , Ubiquinona/farmacologíaRESUMEN
Migraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 interictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analyzed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days. Compared to healthy controls, interictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days. Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. PERSPECTIVE: This study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signaling that differ with the presence of headache.