Background: Attack-related cognitive symptoms in migraine are frequent yet scarcely characterized and undervalued as contributors of disability. Conflicting evidence arose about an increased risk of cognitive decline in older migraine patients. Objectives: (1) to study the occurrence of cognitive symptoms in migraine attacks; (2) to evaluate objective evidence of cognitive dysfunction in migraine attacks and its neuronal correlates and (3) to study the effect of persisting migraine in cognitive function or cognitive decline in older adults. Methods: Occurrence of attack-related cognitive symptoms was detailed by systematic literature review and a cross-sectional clinical-based systematic survey; their relevance to disability was studied prospectively using headache diaries. An instrument (Mig-SCog) was developed, validated and tested to identify and quantify attack-related subjective cognitive symptoms. Cognitive function during attacks was evaluated by a systematic literature review and a clinical-based prospective two-period randomized cross-over study using an extensive neuropsychological battery. A briefer battery was tested in repeated applications in interictal patients and controls. Brain perfusion during attacks was studied with arterial spin labeling magnetic resonance imaging (ASL-MRI) and cortical response to a working memory task with blood-oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI). A prospective controlled cross-sectional population-based study of neuropsychological performance of older adults with persisting migraine and non-migraine headache was followed by a 5 years re-evaluation of the same sample, to screen for cognitive decline. Results: Cognitive symptoms were the most frequent non-migraine defining symptoms reported in the prodromic(37%) and headache(38%) phases of migraine attacks in a systematic review of 28 series, with a total sample of 8392 patients. Cognitive symptoms are also present in the postdromic or resolution phase, although fatigue (71%) is reported more often. Of 165 patients prospectively surveyed, 87% reported an average of 2.5 attack-related symptoms, over two-thirds executive (attention, processing efficiency and speed). Cognitive symptoms were ranked prospectively by 34 migraine patients recording 229 attacks, being second only to pain in terms of intensity and attack-related disability. An instrument to quantify migraine attack-related symptoms was constructed from a set of 43 candidate items, using factor analysis. The reduced 9 item Mig-SCog is fast to apply covering executive functions and language, having good internal consistency (Cronbachs’ alpha 0.82) and reliability (Cohen’s kappa 0.55) and high correlation with external validity measures such as the 43-candidate item list (rho=0.69) and the Cognitive Failures Questionnaires(rho=0.61). The Mig-SCog presents negligible recall bias (no difference in scores obtained during an attack or while headache free) and Migraine patients score it higher for migraine higher for migraine (7.9±4.6) than for non-headache pain (2.3±2.9, p<0.0006) or pain free (1.6±2.4, p<0.0006). Comparing Mig-SCog scores in migraine and tension-type headache patients, those were higher for migraine in all scale items (p<0.0001) except those related to naming (8 and 9). The AUC of Mig-SCog score for the diagnosis of Migraine was 0.835 (95% CI of 0.763-0.906, p< 0.0001) reinforcing specificity for migraine. Ten studies of neuropsychological evaluation during migraine attacks are available in the literature, only half had data allowing comparison of cognitive performance within and outside attacks (encompassing 163 migraine patients). All these were able to demonstrate some type of impairment (most often executive) although some bias could not be excluded from their study design. In our sample of 24 patients which completed an extensive neuropsychological evaluation in these two conditions (attack and headache-free) controlling for the majority of relevant bias (in particular the practice effect), performance was worse during the attack in the majority of cognitive tests, in particular in word reading speed (p=0.013), verbal learning (p=0.01), short term verbal recall with (p=0.01) and without (p=0.013) semantic cueing and delayed recall with (p=0.003) and without (p=0.05) semantic cues. Another sample of 24 interictal migraine patients and 24 matched controls performed equally in a shorter battery focused on executive functions that was applied twice with a short interval (average 45 days) to test the practice effect of repeated evaluations that was demonstrated in all tests, being significant in Stroop Interference test (p=0.002, multiplicity corrected); a meaningful score change was determined for each raw test scores. We were unable to find any relevant brain perfusion nor brain activation differences evoked by a working memory task during a spontaneous migraine without aura attack of an average intensity of 6.8 on a 0-10 VAS scale and an average duration of 16 hours in a sample of 13 women, compared to being headache-free. Persistent migraine or headache after the age of 50 related to worse performance in some neuropsychological tests (attention and processing speed in migraine patients, n=61; sematic memory and memory retrieval in non-migraine headache, n=50) in a population sample of 478 individuals tested extensively. After 5 years, 275 (57.5%) of the same sample were screened for cognitive decline, that occurred in 14.9% of the sample. Neither migraine nor non-migraine headache influenced the odds of decline. Discussion: Attack-related cognitive symptoms are very frequent, mostly executive and contribute to disability, supporting that they should be addressed as endpoint in clinical trials of acute migraine treatments and included in disability assessments. An efficient way to assess attack-related subjective cognitive symptoms in clinical practice or research is now available – the Mig-SCog. Although migraine-related reversible cognitive dysfunction was demonstrated during attacks, no advances on potential brain mechanisms underlying these findings were made. Interest is focused to obtain more functional data, with studies of evoked activation paradigms, functional connectivity and combined imaging and neurophysiological studies. Although persisting headache in older adults seems to influence executive performance, these changes are most likely adaptive and do not seem to influence the process of brain degeneration and associated cognitive decline.

The posterior hypothalamus is responsible for the defensive-aggressive response, it is implicated in the sleep/ arousal cycling and it also receives convergent multimodal sensorial input, participating in the brains' pain network. The posterior hypothalamic area may act as the trigger of Cluster Headache attacks, as it is found to be activated in brain image studies specifically in this trigemino-autonomic cephalalgias but not in other primary headaches, such as migraine. Deep brain stimulation of the posterior hypothalamic area is an effective experimental treatment in intractable Cluster Headache patients. Cluster Headache attacks are characterized by a striking clockwise regularity, excruciating unilateral trigeminal pain and concomitant ipsilateral cranial autonomic symptoms. We aimed to develop an animal model to document the effect of PH electric stimulation on the systemic and cranial autonomic system and on the peripheral cranial pain system (the trigeminal ganglion) and to evaluate the effect of nitroglycerin in this model. Using stereotaxic co-ordinates we accessed the PH area and the gasserian ganglion in male adult Wistar rats. The PH was stimulated and activity was obtained in the gasserian ganglion at baseline and after glyceryl trinitrate. Pupil size and tearing were monitored. Firing frequency and post-trigger histograms were analysed and paired-samples T test was used to compare means before and after interventions. Mean differences in firing rates of ganglion cells between experimental conditions were significant when comparing PH stimulation with baseline (t 2.353, p 0.040), PH stimulation after nitroglycerin administration with baseline (t 2.517, p 0.030) and PH stimulation after nitroglycerin with isolated PH stimulation (t 3.017, p 0.013). Stimulation of the PH produced a long latency response of 50 to 150ms. No changes were documented in pupil size and tearing.We found an evident and consistent effect of increased trigeminal ganglion neuronal firing after electric stimulation of the PH of the rat that was potentiated by nitroglycerine without activation of the trigeminal-parasympathetic system.Although with limitations, our results demonstrate a polysynaptic circuitry connecting the PH to the trigeminal peripheral system that is facilitated by nitroglycerin, supporting the hypothesis that the PH has a role in modulating cranial pain. CH attacks are cannot be simply explained by its activation.

Objetivo: Determinar a prevalência de migrânea episódica e crônica e o impacto dessa enfermidade nos indicadores de produtividade. Método: Estudo descritivo transversal. Local: Empresa de serviços de Brasília (Distrito Federal, Brasil). Material: Um total de 831 funcionários foram analisados. Medidas: Após a triagem inicial, 48 funcionários foram identificados com migrânea e responderam as versões brasileiras de questionários, como Avaliação de Incapacidade de Migrânea (MIDAS), Produtividade no Trabalho e Diminuição da Atividade (WPAIMigrânea), Inventário de Depressão de Beck (BDI), Inventário de Ansiedade de Beck (BAI) Análise: Foi realizada uma análise descritiva dos casos selecionados. Os dados também foram avaliados por meio do teste de independência do qui-quadrado de Pearson. Resultados: A maioria dos trabalhadores avaliados era do sexo feminino (73%) e 83% tinham menos de 50 anos. No estudo, observou-se uma prevalência de migrânea de 5,9% (48 funcionários), o que acometeu principalmente as mulheres entre 36 e 40 anos. Os sintomas (dor de cabeça) começaram, em média, a partir dos 18 anos. Trinta pacientes (63%) relataram dor recorrente em meses consecutivos e 53% relataram dor em todos os meses do ano. Em média, a cefaleia esteve presente pelo menos um dia em 9 meses consecutivos. Depressão tem uma forte correlação com migrânea crônica (p 0,024). O impacto da migrânea na produtividade dos trabalhadores foi medido por dois instrumentos (MIDAS e WPAIMIGRAINE). O custo mensal do absenteísmo por migrânea varia de R$ 220,00 a R$ 476,00. Por outro lado, o impacto da migrânea no presenteísmo varia de R$ 476,00 a R$ 600,00. Conclusão: No estudo, observou-se uma prevalência de migrânea de 5,9% com impacto relevante na saúde e no bem-estar. O impacto econômico da migrânea é notável e demonstra a importância dessa condição, que possui um quadro diagnóstico simples e diversos tratamentos disponíveis.

Migraines are a type of sickness that is difficult to diagnose, whose symptoms affect the quality of life and the daily tasks of the affected person, resulting in momentary disability. Its pathophysiology is still imprecise, but the most accepted hypothesis is the neurological one explained by the dysfunction of the excitability of the cortical neurons - occurrence of a wave of occipital-frontal depolarization followed by a period of suppression of neuronal activity. The main treatment used is still pharmacological, but it can trigger a series of side effects that are difficult to tolerate, in addition to being unspecific. In this context, non-pharmacological therapies such as transcranial direct current stimulation (TDCS) and mindfulness have gained prominence for their low cost, safety and effectiveness. In view of the beneficial effects of combined mindfulness therapy and ETCC in disorders of the central nervous system, combined with the theoretical gap in clinical trials that investigate the use of these treatments in patients with migraines, we have chosen to divide this work into two chapters. The first chapter was dedicated to the scoping review of clinical trials aiming to compare the specific clinical results of ETCC of the main cortical targets used in migraines (primary motor - M1, primary visual - V1 and dorsolateral prefrontal - CPFDL). The analysis of the selected articles shows supremacy of the CPFDL stimulation points with regard to the decrease in pain intensity and V1 in terms of reducing the frequency of crises in this condition. The second chapter concerns the written article based on the randomized clinical trial (RCT) that we conducted associating ETCC with mindfulness in volunteers diagnosed with chronic migraine.. The objectives of this RCT were to assess whether such techniques were safe and effective when used together in patients with chronic migraines, to compare the degree of disability and the impact of headaches on activities in daily living, as well as the levels of mindfulness of the participants before and after the entire intervention was performed, in patients subdivided into groups of active ETCC and ETCC sham, both associated with mindfulness. After treatment, the active ETCC group combinated with the mindfulness showed better results in all outcomes. The sham group also combinated with the mindfulness showed improvements, but with smaller effect sizes compared to the active group. There was a significant difference in the analysis of interactions only in the case of post-treatment equivalent to the headache impact on the performance of daily activities, highlighting the active current group.

Migraine is a pathology whose symptoms directly affect the individual's personal and work life, jeopardizing the daily chores and social relationships momentarily. Considered difficult to diagnose, its pathophysiology is still imprecise, however, despite the several hypotheses to explain the genesis of the referred disease, the most accepted one considers that migraine consists of a dysfunction in the excitability of cortical neurons, which, in turn, promotes a wave of occipital-frontal depolarization, followed by a period of suppression of neuronal activity. Parallel to the studies that seek to explain the pathophysiological aspects of chronic migraine, another current of research presses to observe and understand how the neuronal activity of these patients is characterized, in order to support the construction of future therapeutic proposals. For this purpose, in the construction of this dissertation, the theoretical framework of the variables to be analyzed in the study (electroencephalographic records of alpha asymmetry, head movement patterns and emotional states) was initially carried out, laid down in the first chapter of the work, and then an observational cross-sectional study of brain and postural correlates was performed in patients with migraine who participated in a stress reduction program based on mindfulness. The objective was to evaluate the relationship between the clinical perception of pain in patients with migraine, as well as to establish possible neurophysiological signatures related to the pathological process, through electroencephalographic and head movement findings. Significant correlations were found between alpha wave power in the right and left frontal hemispheres, head movement and self- reports of the severity of migraine symptoms and the state of mindfulness in the participants. These preliminary results indicate that the frontal alpha power and head movements could function as biomarkers of migraine and mindfulness.

The symptomatic picture of chronic migraine is quite broad with debilitating consequences and cognitive dysfunctions that impact the quality of life of the individual. In this context, transcranial Direct Current Stimulation (tDCS) may be an adjunct to drug treatment, requiring a better standardization and definition of its application protocols. Objective: To analyze if the clinical and cognitive effects of tDCS, observed in patients with chronic migraine, vary according to the number and interval between sessions. Method: This study consisted of a triple-blind, randomized, placebo-controlled trial. The sample consisted of women aged between 20 and 45 years with diagnosis of chronic migraine. A sociodemographic, clinical questionnaire and the following outcomes were used: Headache Impact Test (HIT-6), Cumulative Illness Rating Scale (CIRS), Beck Depression Inventory (BDI), Trait-State Anxiety Inventory (IDATE), Montreal Cognitive Assessment, Wechsler Adult Intelligence Scale (WAIS-III), Hayling's Test, Letter Comparison and Pattern Comparison, Nine Hole Peg Test, D2 Test, Visual Attention Test, Trail Making Test Part B . The subjects enrolled in the study were randomly assigned to 3 groups: Group A: received a single session of tDCS for 15 minutes (protocol 1); Group B: received two 15-minutes sessions with an interval of 20 minutes between them (protocol 2); Group C: received sham current for 15 minutes. The anodic electrode was allocated over the left dorsolateral prefrontal cortex region (DLPFC) and the reference electrode in the contralateral supraorbital region. The current had intensity of 2mA and was applied during 10 consecutive days, excluding the weekends. Results: We observed that anodic tDCS reduced the inability of migraine, stress level and cognitive decline. We also found an improvement in working memory and attention, executive functions, motor processing speed, and selective attention. However, the effects of tDCS on group B were not superior to group A and more adverse effects were reported. Conclusion: tDCS is a safe and effective adjuvant technique in patients with chronic migraine, but further studies are needed to standardize the protocol that is most appropriate for this population.

Objective: To investigate the forms of treatment of migraine symptoms. Methods: This is a qualitative bibliographic review, which used the keywords "migraine" and "treatment" in Portuguese and English. It obtained articles from the Up to Date, Pubmed, Scielo and Medline databases between 2010 and 2020. Results: Migraine is characterized by the presence or absence of aura in addition to the appearance of throbbing pain of unilateral location in most cases with presence of nausea, photophobia and phonophobia. It, popularly known as migraine, is present in 15 to 25% of the population, being the second most common form of headache, behind only tension headache. There are many risk factors and mechanisms for the development of migraine. As well as, its possible classifications that are based on clinical diagnosis, based on them, the specific therapeutic approach is based on lifestyle changes, complementary therapies and pharmacotherapy. Conclusion: The treatment of migraine if applied at the right time prevents disease progression and ensures a better quality of life for patients.

Vestibular migraine corresponds to one of the most frequent diagnoses in otoneurology. It is considered the most common cause of balance disorders. Its diagnosis is based on recurrent vestibular symptoms, history of migraine and association of migraine symptoms with vestibular symptoms over a period ranging from 5 minutes to 72 hours. The drug treatment of vestibular migraine aims to control the patient's symptoms in the acute phase, as well as in the prophylaxis of eventual crises. The present work is an integrative literature review, whose objective is to identify and describe the drug treatment of vestibular migraine, in order to control the patient's symptoms in the acute phase and in the prophylaxis of possible crises. The search was carried out in the electronic databases SCIELO, PUBMED and LILACS, including works published between 2016 and 2021, in Portuguese and English. The selection of studies, data extraction and validation were carried out independently by two authors, obtaining a sample of 14 articles. All research data were analyzed in Microsoft Excel and later the results were transformed into tables for a better interpretation of the information collected. It was found, through the analysis of the 14 articles, that 7 (50%) studies used treatment with antidepressants, beta-blockers and anticonvulsants concomitantly; 9 (64%) used propranolol with symptom improvement; 2 (14%) used botulinum toxin and only 1 (7%) used gentamicin injection. Thus, it was possible to systematically structure the drugs most used in prophylaxis and in the vestibular migraine crisis, laying the basis for a more adequate choice of the drug.

Chronic migraine (CM) has a wide range of symptoms, with debilitating consequences for those individuals refractory to the conventional treatments. In this context, Transcranial Direct Current Stimulation (tDCS) is a promising technique, although there is still no consensus on the most appropriate protocol, which may vary in relation to the number and interval between the application sessions. The present work consists of a protocol to assess the clinical and cognitive effects of ETCC on CM in the form of a double-blind, randomized and placebo-controlled clinical trial. The sample will consist of women aged between 20 and 45 years with a diagnosis of CM. A sociodemographic questionnaire and instruments for assessing cognitive functions, affective aspects, and clinical evaluation of migraine will be applied. Participants will be randomly distributed among 3 groups: Group 1: will receive a daily tDCS session for 15 minutes; Group 2: will receive two daily tDCS sessions of 15 minutes, with an interval of 20 minutes between them; Group 3: will receive simulated stimulation (sham) for 15 minutes. The anode electrode will be placed on the left dorsolateral prefrontal cortex and the reference electrode on the contralateral supraorbital region. In the Groups 1 and 2 the current will have an intensity of 2mA and will be applied for 10 consecutive days. We expect that tDCS will be effective in reducing symptoms in CM, with a decreased in pain and stress, and an improvement in the cognitive performance. This study will help to define a more appropriate neuromodulation protocol, contributing to the clinical decision making in CM.

Objective: To critically appraise, compare and summarize the quality of the measurement properties of all Patient-Reported Outcome Measures translated and validated for the Brazilian population that assess the impact of migraine. Background The evaluation of measurement properties of Patient-Reported Outcome Measures is needed for professionals and researchers to select instruments that ensure quality of results. Thus, reliable instruments are important to provide information on the impact of migraine. Methods: The search was conducted in MEDLINE/Pubmed, Web of Science, LILACS, and Embase databases. We included studies evaluating measurement properties of PROMs that assessed the impact of migraine and were validated for Brazil. Methodological quality, risk of bias, and quality of evidence were assessed following the Consensus-based Standards for Selecting Health Measurement Instruments for systematic reviews of Patient-Reported Outcome Measures Results: A total of 112 studies identified, and four were included. Three instruments were analyzed: Headache Impact Test, which presented a serious risk of bias with moderate quality of evidence; Pediatric Migraine Disability Assessment, which presented an extremely serious risk of bias and very low quality of evidence; and the Headache Disability Inventory¸ which presented a very serious risk of bias and low quality of evidence. Conclusion: The three instruments evaluated had important limitations regarding quality of evidence. The Headache Impact Test was the most recommended instrument because it presented a moderate quality of evidence.