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Cognition and Cognitive Impairment in Migraine. Gil-Gouveia Raquel,Martins Isabel Pavão Current pain and headache reports BACKGROUND:Migraine is a complex neurological disorder that affects a significant percentage of the human species, from all geographic areas and cultures. Cognitive symptoms and dysfunctions are interim and disabling components of this disorder and may be related to the brain processes underlying the pathophysiology. Yet they are often undervalued by clinicians. In this review, we present the different types of cognitive dysfunctions associated with migraine and the mechanisms that are potentially causing them. FINDINGS:While reversible attack-related cognitive dysfunction seems extremely consistent and likely related to functional cortical and subcortical brain changes occurring during attacks, interictal cognitive dysfunction is less consistent and might become more relevant as attack frequency and disease complexity increase. Migraine traits do not seem a predisposition to long-term cognitive decline. Cognitive dysfunction is a frequent manifestation of migraine attacks and may be specific to this disorder; it is important to understand if it could be useful in migraine diagnosis. Attack-related cognitive dysfunction is clinically relevant and contributes to disability, so it should be perceived as a therapeutic target. While there is no evidence to support that migraine increases the risk of long-term or persistent cognitive dysfunction, the fact that it occurs during the attacks and may persist in subjects with frequent or complicated attacks should prompt the understanding of the mechanisms related to its pathophysiology for it may also clarify the processes underlying migraine. 10.1007/s11916-019-0824-7
Early Age of Migraine Onset is Independently Related to Cognitive Decline and Symptoms of Depression Affect Quality of Life. Bao Jiajia,Ma Mengmeng,Dong Shuju,Gao Lijie,Li Changling,Cui Chaohua,Chen Ning,Zhang Yang,He Li Current neurovascular research BACKGROUND:People with migraine experience cognitive decline more often than healthy controls, resulting in a significant functional impact. Early identifying influencing factors that contribute to cognitive decline in migraineurs is crucial for timely intervention. Although migraine may onset early in childhood and early onset migraine is related to significant disability, there is no research investigating the association between the age of migraine onset and migraineurs' cognitive decline. Therefore we aim to explore possible factors that correlate to the cognitive function of migraineurs, especially focus on age of migraine onset. METHODS:531 patients with migraine were included. Data on demographics and headache-related characteristics were collected and evaluated using face-to-face interviews and questionnaires. We used the Montreal Cognitive Assessment scale to assess cognitive function. In addition, we analyzed independent correlations between cognitive decline and the age of migraine onset in patients with migraine. And all patients completed the Headache Impact Test-6 to evaluate their quality of life. RESULTS:Migraineurs with cognitive decline showed significant differences from those without in age (OR=1.26, P<0.0001), years of education (OR=0.89, P=0.0182), the intensity of headache (OR=1.03, P=0.0217), age of onset (OR=0.92, P<0.0001) and anxiety scores (OR=1.09, P=0.0235). Furthermore, there was no interaction in the age of onset between subgroups. Multivariate linear regression analyses of HIT-6 scores showed that the intensity of headache (β=0.18, P<0.0001) and depression scores (β=0.26, P=0.0009) had independent effects on decreased quality of life. CONCLUSION:Our findings suggest that younger age of migraine onset is independently related to migraineurs' cognitive decline, and migraine accompanying anxiety symptoms significantly related to decreased quality of life in migraineurs. 10.2174/1567202617666200207130659
Cognitive dysfunction and migraine. Vuralli Doga,Ayata Cenk,Bolay Hayrunnisa The journal of headache and pain Cognitive dysfunction has recently gained attention as a significant problem among migraine sufferers. All of the clinical studies show poor cognitive performance during migraine attacks, though, the interictal data are conflicting. Migraineurs show impaired cognitive function interictally in most of the clinic-based studies. Population-based studies did not reveal a difference in cognitive functions between migraineurs and controls. The specific cognitive domains involved are information processing speed, basic attention, executive functions, verbal and non-verbal memory and verbal skills. Neurophysiological, imaging and pharmacological studies support clinical symptoms of cognitive impairment in migraine. Longitudinal studies do not suggest progressive cognitive decline over time in migraine patients. Preventive medications and comorbid disorders such as depression and anxiety can impact cognitive function, but cannot fully explain the cognitive impairment in migraine. In contrast to migraine, tension type or cluster headache are not associated with cognitive impairment, at least during headache-free periods. 10.1186/s10194-018-0933-4
Cognitive Behavioral Therapy for Migraine Headache: A Systematic Review and Meta-Analysis. Bae Ji-Yong,Sung Hyun-Kyung,Kwon Na-Yoen,Go Ho-Yeon,Kim Tae-Jeong,Shin Seon-Mi,Lee Sangkwan Medicina (Kaunas, Lithuania) : Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. : Seven electronic databases were searched from the date of inception to December 2020. Randomized controlled studies (RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on Visual Analog Scale (VAS), the frequency of drug use, Migraine Disability Assessment (MIDAS), and Headache Impact Test (HIT-6) index. The two authors independently conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. : Among the 373 studies, 11 RCTs were included in this systematic review. Seven out of the 11 RCTs were conducted in the USA, and four were conducted in the UK, Germany, Iran, and Italy, respectively. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache strength was significantly reduced. Two of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. : CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis and headache intensity subgroup analysis, with few adverse events. Additional RCTs with CBT for migraine headaches are needed for a more accurate analysis. 10.3390/medicina58010044
Predictors of Improvement in Pediatric Chronic Migraine: Results from the Cognitive-Behavioral Therapy and Amitriptyline Trial. Journal of clinical psychology in medical settings Explore predictors of improvement in headache days and migraine-related disability through a secondary analysis of the cognitive-behavioral therapy plus amitriptyline trial in children and adolescents (Clinical Trials Registration Number: NCT00389038). Participants were 135 youth aged 10-17 years old diagnosed with chronic migraine. Predictor variables included group assignment (treatment or control), baseline scores from depression and quality of life measures, and demographic variables. Criterion variables included headache days and migraine-related disability. Higher baseline depression scores were indicative of more days with headache post-treatment regardless of group assignment. Family income at the higher-end of the low-income range was significantly associated with less migraine-related disability regardless of group assignment (Household Income: HINC-01 in The United States Census Bureau. Bureau, U, 2020). Results from this secondary analysis identify depression symptoms and family income as predictors that can impact headache frequency and migraine-related disability. Self-reported symptoms of depression and family income are important factors to consider as part of the biopsychosocial model of care. 10.1007/s10880-021-09782-4
Alterations in Brain Function After Cognitive Behavioral Therapy for Migraine in Children and Adolescents. Nahman-Averbuch Hadas,Schneider Victor J,Chamberlin Leigh Ann,Kroon Van Diest Ashley M,Peugh James L,Lee Gregory R,Radhakrishnan Rupa,Hershey Andrew D,King Christopher D,Coghill Robert C,Powers Scott W Headache OBJECTIVES:This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine. BACKGROUND:Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. METHODS:Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. RESULTS:Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P < .001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed. CONCLUSIONS:Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients. 10.1111/head.13814
Interictal Cognitive Deficits in Migraine Sufferers: A Meta-Analysis. Neuropsychology review While a significant proportion of the population suffer from migraine, the existing research literature does not provide a clear indication as to whether migraineurs experience objective cognitive deficits outside of acute migraine attacks. This meta-analysis was conducted to investigate which cognitive domains if any were affected by migraine, by synthesising the existing research quantitatively. The meta-analysis was prospectively registered with the PROSPERO International prospective register of systematic reviews (registration no.: CRD42019134138). A search of the electronic databases PubMed, Ovid MEDLINE, and PsycINFO was conducted for journal articles published between January 1980 and January 2020. Seventeen studies met the inclusion criteria, allowing for the calculation of pooled effect sizes between migraineurs (with and without aura) and healthy controls in the several cognitive domains. During the interictal period, migraineurs demonstrated a moderate, negative effect on complex attention immediate and delayed memory, spatial cognition, and executive functioning. This effect was not attributable to migraine history, attack frequency, or participant age. However, the lack of performance validity testing, and limited data on mood symptomatology and migraine medication use in the included studies may be confounds potentially overestimating the magnitude of effect. Comparison with a clinical control group, which may have accounted for some these extraneous variables, was unable to be conducted. Recommendations for comprehensive future neuropsychological research are provided. 10.1007/s11065-021-09516-1
Association between migraine and cognitive impairment. The journal of headache and pain BACKGROUND:Previous studies revealed inconsistent results regarding association between migraine and cognitive impairment. In addition, previous studies found inconsistent results regarding the association between migraine and risk of dementia. Thus, the study aimed to make a meta-analysis exploring comparison result in different types of cognitive function between migraine patients and non-migraine subjects. In addition, meta-analysis was made to explore the association between migraine and risk of dementia. METHODS:Articles published before June 2022 were searched in the following databases: PubMed, Web of Science, SCOPUS, EMBASE, EBSCO, PROQUEST, ScienceDirect and Cochrane Database of Systematic Reviews. Results were computed using STATA 12.0 software. RESULTS:Meta-analysis showed lower general cognitive function and language function in migraine group, compared to no migraine group (general cognitive function: standard mean difference (SMD) = - 0.40, 95% CI = - 0.66 to - 0.15; language: SMD = - 0.14, 95% confidence interval (CI) = - 0.27 to - 0.00), whereas the study showed no significant difference in visuospatial function, attention, executive function and memory between migraine group and no migraine group (visuospatial function: SMD = - 0.23, 95% CI = - 0.53 to 0.08; attention: SMD = - 0.01, 95% CI = - 0.10 to 0.08; executive function: SMD = - 0.05, 95% CI = - 0.16 to 0.05; memory: SMD = - 0.14, 95% CI = - 0.30 to 0.03). In addition, the meta-analysis showed a significant association between migraine and risk of dementia (odds ratio (OR)/relative risk (RR) = 1.30, 95% CI = 1.11 to 1.52). CONCLUSIONS:In conclusion, the meta-analysis demonstrated lower general cognitive function and language function in migraine. In addition, migraine is associated with an increased risk of all-cause dementia, VaD and AD. These results suggest a significant association between migraine and cognitive impairment. Because of the association between migraine and cognitive impairment, neurological physician should be vigilant and effectively intervene in migraineurs with high risk factors of cognitive impairment to prevent the development of cognitive impairment. 10.1186/s10194-022-01462-4
Vestibular Migraine: Cognitive Dysfunction, Mobility, Falls. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology OBJECTIVE:Recent evidence has shown that vestibular migraine is strongly associated with cognitive difficulties. However, limited data exist on real-world effects of that dysfunction. The objective of this study is to understand the epidemiology of cognitive dysfunction with vestibular migraine and associated sequelae using National Health Interview Survey data. STUDY DESIGN:Randomized, population-based survey study of US adults. SETTING:We generated a case definition approximating probable vestibular migraine based on Bárány Society criteria and validated that definition in a tertiary care vestibular clinic. PATIENTS:Adult respondents to the 2016 NHIS, which queries a representative sample of the civilian, noninstitutionalized US population. INTERVENTION:Diagnostic. MAIN OUTCOME MEASURES:We evaluated incidence of self-reported cognitive dysfunction with vestibular migraine and whether individuals were more likely to have impaired mobility, falls, and work absenteeism than those without either condition. RESULTS:Among individuals with vestibular migraine, 40% reported "some" and 12% reported "a lot" of difficulty thinking versus 13% and 2% of those without vestibular migraine, respectively. Vestibular migraine sufferers were more likely to have difficulty thinking or remembering compared with respondents without dizziness (odds ratio, 7.43; 95% confidence interval, 6.06-9.10; p < 0.001) when controlled for age, sex, education, stroke, smoking, heart disease, and diabetes. Individuals with both vestibular migraine and cognitive dysfunction had fivefold increased odds of falls and 10-fold increased odds of mobility issues compared with those without either condition. Furthermore, individuals with both vestibular migraine and cognitive dysfunction missed 12.8 more days of work compared to those without either condition. CONCLUSION:Our findings indicate vestibular migraine is not only associated with cognitive dysfunction, but they are together associated with mobility issues, fall risk, and work absenteeism. 10.1097/MAO.0000000000003700
[Cognitive and emotional disorders in patients with migraine and signs of leukoencephalopathy]. Pozhidaev K A,Parfenov V A Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova OBJECTIVE:To identify cognitive and emotional disorders and their correlation with neuroimaging parameters in patients with chronic migraine. MATERIAL AND METHODS:We examined 50 patients (8 men and 42 women, mean age 41.9±11.9 years) with migraine, including 31 with chronic migraine, and signs of leukoencephalopathy according to magnetic resonance imaging (MRI). A control group comprised 40 healthy individuals (13 men and 27 women) aged 20 to 64 years (mean 42.6±12.0 years). A number of tests for neuropsychological examination and assessment of the emotional state, including a 12-word test, literal and categorical associations, Benton Test, the Montreal cognitive scale (MOCA), the Hospital Depression Scale, the Beck Depression Scale, the Center for Epidemiological Research scale, the Hospital Anxiety Scale and the Spielberger-Khanin scale, were administered at baseline and after 3 and 6 month of preventive therapy. RESULTS:Patients with migraine had lower scores (=0.004) on MOCA, memorization of 12 words (=0.0003), test for literal (=0.001) and categorical associations (=0.0002) compared with the control group. No significant correlations were found between the volume of white matter lesions according to MRI and the severity of cognitive impairment. An inverse correlation of average strength was noted (correlation coefficient R=-0.41) between the number of days with headache per month and the MOCA score (<0.05). In patients with migraine, signs of depression were found on the Hospital Depression Scale (=0.04), Beck Depression Scale (=0.003), the Center for Epidemiological Research scale (=0.0001), and increased anxiety on the Hospital Anxiety Scale (=0.0001) and the Spielberger-Khanin scale (=0.0001). A significant relationship was found between the degree of depression and the MOCA score (=0.007). The frequency of headaches decreased from 19.4±2.9 to 12.6±4.4 days per month (<0.05). CONCLUSION:There were a significant decrease of emotional disorders and improvement of cognitive functions compared with baseline scores during the 6 month therapy. Preventive treatment of migraine and concomitant emotional disorders seems to be the most effective way to improve cognitive functions. 10.17116/jnevro20211210317
A Systems Neuroscience Approach to Migraine. Neuron Migraine is an extremely common but poorly understood nervous system disorder. We conceptualize migraine as a disorder of sensory network gain and plasticity, and we propose that this framing makes it amenable to the tools of current systems neuroscience. 10.1016/j.neuron.2018.01.029
The Long-term Effect of Acupuncture for Migraine Prophylaxis: A Randomized Clinical Trial. Zhao Ling,Chen Jiao,Li Ying,Sun Xin,Chang Xiaorong,Zheng Hui,Gong Biao,Huang Yinlan,Yang Mingxiao,Wu Xi,Li Xuezhi,Liang Fanrong JAMA internal medicine Importance:The long-term prophylactic effects of acupuncture for migraine are uncertain. Objective:To investigate the long-term effects of true acupuncture compared with sham acupuncture and being placed in a waiting-list control group for migraine prophylaxis. Design, Setting, and Participants:This was a 24-week randomized clinical trial (4 weeks of treatment followed by 20 weeks of follow-up). Participants were randomly assigned to true acupuncture, sham acupuncture, or a waiting-list control group. The trial was conducted from October 2012 to September 2014 in outpatient settings at 3 clinical sites in China. A total of 249 participants 18 to 65 years old with migraine without aura based on the criteria of the International Headache Society, with migraine occurring 2 to 8 times per month. Interventions:Participants in the true acupuncture and sham acupuncture groups received treatment 5 days per week for 4 weeks for a total of 20 sessions. Participants in the waiting-list group did not receive acupuncture but were informed that 20 sessions of acupuncture would be provided free of charge at the end of the trial. Main Outcomes and Measures:Participants used diaries to record migraine attacks. The primary outcome was the change in the frequency of migraine attacks from baseline to week 16. Secondary outcome measures included the migraine days, average headache severity, and medication intake every 4 weeks within 24 weeks. Results:A total of 249 participants 18 to 65 years old were enrolled, and 245 were included in the intention-to-treat analyses. One hundred eighty-nine (77.1%) were women. Baseline characteristics were comparable across the 3 groups. The mean (SD) change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization (P < .001); the mean (SD) frequency of attacks decreased in the true acupuncture group by 3.2 (2.1), in the sham acupuncture group by 2.1 (2.5), and the waiting-list group by 1.4 (2.5); a greater reduction was observed in the true acupuncture than in the sham acupuncture group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = .002) and in the true acupuncture vs waiting-list group (difference of 1.8 attacks; 95% CI, 1.1-2.5; P < .001). Sham acupuncture was not statistically different from the waiting-list group (difference of 0.7 attacks; 95% CI, -0.1 to 1.4; P = .07). Conclusions and Relevance:Among patients with migraine without aura, true acupuncture may be associated with long-term reduction in migraine recurrence compared with sham acupuncture or assigned to a waiting list. Trial Registration:clinicaltrials.gov Identifier: NCT01687660. 10.1001/jamainternmed.2016.9378
Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiological reviews Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology. 10.1152/physrev.00034.2015
Effects of transcranial direct current stimulation on visuospatial attention in air traffic controllers. Experimental brain research Visuospatial attention is a cognitive skill essential to the performance of air traffic control activities. We evaluated the effect of an anodic session of transcranial low-intensity direct current stimulation (tDCS) right parietal associated with cognitive training of visuospatial attention of 21 air traffic controllers. Within-subject designs were used, with all volunteers undergoing two tDCS sessions; an experimental (2 mA anodic) and control (sham) performed concomitantly with the cognitive training (2-Back). Visuospatial performance was measured using the Attention Network Test for Interactions and Vigilance pre- and post-intervention. The results indicate that after an active parietal tDCS session, the ATCOs showed faster responses, but not more accurate, for visuospatial attention in its aspects of orientation and reorientation. This result was significant when comparing baseline and post-tests in the active tDCS group. Comparing the post-tests between the tDCS active and sham groups, it is possible to infer a trend of improvement in the results based on faster and more accurate responses, which suggests a possible refinement of the ATCO's attentional orientation. However, this population may eventually have reached a plateau in the performance of this skill. From the analysis of the results we arrive at the following hypotheses: (I) the increase in cortical excitability mediated by anodic tDCS frequently recorded may not be accompanied by improvements in behavioural measures; (II) the interaction between anodic tDCS with another event of increased excitability-execution of a cognitive task, may have hindered the occurrence of neuroplasticity; (III) the air traffic control activity may be associated with a high level of attention, which may have contributed to a ceiling effect for the development of this skill; (IV) online assessments may be more relevant to identify acute effects; (V) repeated sessions may be more efficient to find cumulative effects; (VI) the analysis of interactions between attentional networks can contribute to the study of visuospatial attention; (VII) tDCS protocols aimed at ATCO need to consider the specifics of this audience, such as circadian rhythm and sleep and fatigue conditions. 10.1007/s00221-022-06431-6
Functional MRI of migraine. Schwedt Todd J,Chiang Chia-Chun,Chong Catherine D,Dodick David W The Lancet. Neurology Migraine is a disabling neurological condition manifesting with attacks of headache, hypersensitivities to visual, auditory, olfactory and somatosensory stimuli, nausea, and vomiting. Exposure to sensory stimuli, such as odours, visual stimuli, and sounds, commonly triggers migraine attacks, and hypersensitivities to sensory stimuli are prominent during migraine attacks, but can persist with less magnitude between attacks. Functional MRI (fMRI) has been used to investigate the mechanisms that lead to migraine sensory hypersensitivities by measuring brain responses to visual, olfactory, and painful cutaneous stimulation, and functional connectivity analyses have investigated the functional organisation of specific brain regions and networks responsible for sensory processing. These studies have consistently shown atypical brain responses to sensory stimuli, absence of the normal habituating response between attacks, and atypical functional connectivity of sensory processing regions. Identification of the mechanisms that lead to migraine sensory hypersensitivities and that trigger migraine attacks in response to sensory stimuli might help to better understand neural dysfunction in migraine and provide new targets for migraine prevention, and could provide fMRI biomarkers that indicate early responses to preventive therapy. 10.1016/S1474-4422(14)70193-0
Neurochemical changes in the medial wall of the brain in chronic migraine. Niddam David M,Lai Kuan-Lin,Tsai Shang-Yueh,Lin Yi-Ru,Chen Wei-Ta,Fuh Jong-Ling,Wang Shuu-Jiun Brain : a journal of neurology Migraine chronification is associated with a dysfunctional thalamocortical pathway. The present study addressed whether abnormal concentrations of neurochemicals exist in key brain regions of this pathway in chronic migraine. Magnetic resonance spectroscopic imaging of the bilateral medial walls of the brain was used to measure choline, creatine, glutamate and glutamine, myo-inositol, and N-acetyl-aspartate in chronic migraine patients and in matched groups of episodic migraine patients and healthy controls. A region of interest analysis was conducted to examine whether N-acetyl-aspartate, a marker of neuronal integrity, was reduced in the thalamus, occipital cortex and anterior cingulate cortex in chronic migraine. Interregional N-acetyl-aspartate correlations among these regions of interest were also examined. Additionally, statistical mapping was performed for all the metabolites throughout the medial walls. Chronic migraine was associated with N-acetyl-aspartate reductions in the bilateral thalami and in the right anterior cingulate. The N-acetyl-aspartate reduction in the right thalamus correlated with disease duration. Compared with healthy controls, patients with chronic migraine had altered interregional N-acetyl-aspartate correlations between the right thalamus-anterior cingulate and thalamus-occipital cortex, and between the left and right anterior cingulate. N-acetyl-aspartate concentrations and interregional correlations in patients with episodic migraine were between those of healthy controls and chronic migraine patients. The unconstrained analyses revealed a reduction of myo-inositol in the left anterior and posterior cingulate in both patient groups as well as a negative association with depression scores for the anterior cingulate in the combined patient group. In addition, migraine patients with headache on the scan day (irrespective of diagnosis) had reduced N-acetyl-aspartate and total creatine concentrations in the right dorsal anterior cingulate. Reduced N-acetyl-aspartate metabolism and altered interregional N-acetyl-aspartate correlations lend support to the role of thalamocortical dysfunction in migraine chronification. It remains to be established if the pattern of changes within the N-acetyl-aspartate network is specific to chronic migraine or can be found in other chronic pain conditions. 10.1093/brain/awx331
Meningeal contribution to migraine pain: a magnetic resonance angiography study. Khan Sabrina,Amin Faisal Mohammad,Christensen Casper Emil,Ghanizada Hashmat,Younis Samaira,Olinger Anne Christine Rye,de Koning Patrick J H,Larsson Henrik B W,Ashina Messoud Brain : a journal of neurology The origin of migraine pain is unknown but possibly implicates the dura mater, which is pain sensitive in proximity to the meningeal arteries. Therefore, subtle changes in vessel calibre on the head pain side could reflect activation of dural perivascular nociceptors that leads to migraine headache. To test this hypothesis, we measured circumference changes of cranial arteries in patients with cilostazol-induced unilateral migraine without aura using 3 T high resolution magnetic resonance angiography. The middle meningeal artery was of key interest, as it is the main supply of the dura mater. We also measured the superficial temporal and external carotid arteries as additional extracranial segments, and the middle cerebral, the cerebral and cavernous parts of the internal carotid (ICAcerebral and ICAcavernous), and the basilar arteries as intracranial arterial segments. Magnetic resonance angiography scans were performed at baseline, migraine onset, after sumatriptan, and ≥27 h after migraine onset. Thirty patients underwent magnetic resonance angiography scans, of which 26 patients developed unilateral attacks of migraine without aura and were included in the final analysis. Eleven patients treated their migraine with sumatriptan while the remaining 15 patients did not treat their attacks with analgesics or triptans. At migraine onset, only the middle meningeal artery exhibited greater circumference increase on the pain side (0.24 ± 0.37 mm) compared to the non-pain side (0.06 ± 0.38 mm) (P = 0.002). None of the remaining arteries revealed any pain-side specific changes in circumference (P > 0.05), but exhibited bilateral dilation. Sumatriptan constricted all extracerebral arteries (P < 0.05). In the late phase of migraine, we found sustained bilateral dilation of the middle meningeal artery. In conclusion, onset of migraine is associated with increase in middle meningeal artery circumference specific to the head pain side. Our findings suggest that vasodilation of the middle meningeal artery may be a surrogate marker for activation of dural perivascular nociceptors, indicating a meningeal site of migraine headache.10.1093/brain/awy300_video1awy300media15983750185001. 10.1093/brain/awy300
Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Vetvik Kjersti Grøtta,MacGregor E Anne The Lancet. Neurology Migraine is two to three times more prevalent in women than men, and women report a longer attack duration, increased risk of headache recurrence, greater disability, and a longer period of time required to recover. Conditions recognised to be comorbid with migraine include asthma, anxiety, depression, and other chronic pain conditions, and these comorbidities add to the amount of disability in both sexes. Migraine-specifically migraine with aura-has been identified as a risk factor for vascular disorders, particularly in women, but because of the scarcity of data, the comparative risk in men has yet to be established. There is evidence implicating the role of female sex hormones as a major factor in determining migraine risk and characteristics, which accounts for sex differences, but there is also evidence to support underlying genetic variance. Although migraine is often recognised in women, it is underdiagnosed in men, resulting in suboptimal management and less participation of men in clinical trials. 10.1016/S1474-4422(16)30293-9
Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. Neurology BACKGROUND:Through the Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies, headache has emerged as a major global public health concern. We aimed to use data from the GBD 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache and to present the methods and results in an accessible way for clinicians and researchers of headache disorders. METHODS:Data were derived from population-based cross-sectional surveys on migraine and tension-type headache. Prevalence for each sex and 5-year age group interval (ie, age 5 years to ≥95 years) at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Disease burden measured in YLDs was calculated from prevalence and average time spent with headache multiplied by disability weights (a measure of the relative severity of the disabling consequence of a disease). The burden stemming from medication overuse headache, which was included in earlier iterations of GBD as a separate cause, was subsumed as a sequela of either migraine or tension-type headache. Because no deaths were assigned to headaches as the underlying cause, YLDs equate to disability-adjusted life-years (DALYs). We also analysed results on the basis of the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility. FINDINGS:Almost three billion individuals were estimated to have a migraine or tension-type headache in 2016: 1·89 billion (95% uncertainty interval [UI] 1·71-2·10) with tension-type headache and 1·04 billion (95% UI 1·00-1·09) with migraine. However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45·1 million (95% UI 29·0-62·8) and tension-type headache only 7·2 million (95% UI 4·6-10·5) YLDs globally in 2016. The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20·3 million (95% UI 12·9-28·5) and tension-type headache 2·9 million (95% UI 1·8-4·2) YLDs in 2016, which was 11·2% of all YLDs in this age group and sex. Age-standardised DALYs for each headache type showed a small increase as SDI increased. INTERPRETATION:Although current estimates are based on limited data, our study shows that headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. Future iterations of this study, based on sources from additional countries and with less methodological heterogeneity, should help to provide stronger evidence of the need for action. FUNDING:Bill & Melinda Gates Foundation. 10.1016/S1474-4422(18)30322-3
Parietal but not temporoparietal alpha-tACS modulates endogenous visuospatial attention. Cortex; a journal devoted to the study of the nervous system and behavior Visuospatial attention can either be voluntarily directed (endogenous/top-down attention) or automatically triggered (exogenous/bottom-up attention). Recent research showed that dorsal parietal transcranial alternating current stimulation (tACS) at alpha frequency modulates the spatial attentional bias in an endogenous but not in an exogenous visuospatial attention task. Yet, the reason for this task-specificity remains unexplored. Here, we tested whether this dissociation relates to the proposed differential role of the dorsal attention network (DAN) and ventral attention network (VAN) in endogenous and exogenous attention processes respectively. To that aim, we targeted the left and right dorsal parietal node of the DAN, as well as the left and right ventral temporoparietal node of the VAN using tACS at the individual alpha frequency. Every participant completed all four stimulation conditions and a sham condition in five separate sessions. During tACS, we assessed the behavioral visuospatial attention bias via an endogenous and exogenous visuospatial attention task. Additionally, we measured offline alpha power immediately before and after tACS using electroencephalography (EEG). The behavioral data revealed an effect of tACS on the endogenous but not exogenous attention bias, with a greater leftward bias during (sham-corrected) left than right hemispheric stimulation. In line with our hypothesis, this effect was brain area-specific, i.e., present for dorsal parietal but not ventral temporoparietal tACS. However, contrary to our expectations, there was no effect of ventral temporoparietal tACS on the exogenous visuospatial attention bias. Hence, no double dissociation between the two targeted attention networks. There was no effect of either tACS condition on offline alpha power. Our behavioral data reveal that dorsal parietal but not ventral temporoparietal alpha oscillations steer endogenous visuospatial attention. This brain-area specific tACS effect matches the previously proposed dissociation between the DAN and VAN and, by showing that the spatial attention bias effect does not generalize to any lateral posterior tACS montage, renders lateral cutaneous and retinal effects for the spatial attention bias in the dorsal parietal condition unlikely. Yet the absence of tACS effects on the exogenous attention task suggests that ventral temporoparietal alpha oscillations are not functionally relevant for exogenous visuospatial attention. We discuss the potential implications of this finding in the context of an emerging theory on the role of the ventral temporoparietal node. 10.1016/j.cortex.2022.01.021
Three Dimensions of Association Link Migraine Symptoms and Functional Connectivity. The Journal of neuroscience : the official journal of the Society for Neuroscience Migraine is a heterogeneous disorder with variable symptoms and responsiveness to therapy. Because of previous analytic shortcomings, variance in migraine symptoms has been inconsistently related to brain function. In the current analysis, we used data from two sites ( = 143, male and female humans), and performed canonical correlation analysis, relating resting-state functional connectivity (RSFC) with a broad range of migraine symptoms, ranging from headache characteristics to sleep abnormalities. This identified three dimensions of covariance between symptoms and RSFC. The first dimension related to headache intensity, headache frequency, pain catastrophizing, affect, sleep disturbances, and somatic abnormalities, and was associated with frontoparietal and dorsal attention network connectivity, both of which are major cognitive networks. Additionally, RSFC scores from this dimension, both the baseline value and the change from baseline to postintervention, were associated with responsiveness to mind-body therapy. The second dimension was related to an inverse association between pain and anxiety, and to default mode network connectivity. The final dimension was related to pain catastrophizing, and salience, sensorimotor, and default mode network connectivity. In addition to performing canonical correlation analysis, we evaluated the current clustering of migraine patients into episodic and chronic subtypes, and found no evidence to support this clustering. However, when using RSFC scores from the three significant dimensions, we identified a novel clustering of migraine patients into four biotypes with unique functional connectivity patterns. These findings provide new insight into individual variability in migraine, and could serve as the foundation for novel therapies that take advantage of migraine heterogeneity. Using a large multisite dataset of migraine patients, we identified three dimensions of multivariate association between symptoms and functional connectivity. This analysis revealed neural networks that relate to all measured symptoms, but also to specific symptom ensembles, such as patient propensity to catastrophize painful events. Using these three dimensions, we found four biotypes of migraine informed by clinical and neural variation together. Such findings pave the way for precision medicine therapy for migraine. 10.1523/JNEUROSCI.1796-21.2022
Ambient NO exposure induces migraine in rats: Evidence, mechanisms and interventions. The Science of the total environment Migraine is a complex neurological disorder with a high disability rate. Although the precipitating factors of migraine remain unclear, previous studies suggest that when there is excess nitrogen dioxide (NO) pollution in the atmosphere, the medical demand due to migraine attacks increases sharply. However, the main role of NO as a trigger for migraine is not yet well understood. The purpose of this study was to explore the relationship between NO exposure and the occurrence of migraine as well as the possible underlying mechanisms. We first investigated whether repeated short-term NO exposure could induce behavioural and biological migraine phenotypes in rats. Next, capsazepine (CZP) was used to block transient receptor potential cation channel subfamily V member 1 (TRPV1) in vivo, and CZP and vitamin E (VE) were used to verify the role of reactive oxygen species (ROS)-TRPV1 signalling in NO-induced migraine in primary trigeminal neurones in vitro. We demonstrated that short-term repeated NO exposure can significantly induce migraine in rats, and its key molecular mechanism may be related to ROS burst and its downstream TRPV1 channel activation. The findings of this study will enhance the understanding of the neurotoxic mechanism of NO, provide new clues for identifying the aetiology of migraine, and lay a new experimental basis for implementing migraine-related preventive and therapeutic control measures. 10.1016/j.scitotenv.2022.157102
Effects on pain and cognition of transcranial direct current stimulation over the dorsolateral prefrontal cortex in women with chronic migraine. Neurophysiologie clinique = Clinical neurophysiology We compared the effects of one versus two daily sessions of anodal transcranial direct current stimulation (a-tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) for 10 days in a cohort of 30 women (mean age 28.0±6.92) with chronic migraine (CM, disease duration: 37.8±48.41 month). Participants were randomly allocated to three groups: a-tDCS 1-s Group received one daily a-tDCS session; a-tDCS 2-s Group received two daily a-tDCS sessions; Group SHAM received one daily session with a simulated (placebo) current. All participants were assessed before, after and one month after treatment, using the Migraine Disability Assessment, Montreal Cognitive Assessment, d2 Test of Attention, Trail Making Test (part B), Sequence of Letters and Numbers of the Wechsler Adult Intelligence Scale - III, and Nine Hole Peg Test. We found no difference between groups in the cognitive measures and motor dexterity. However, after treatment, a significant decrease in migraine-related disability was found for the a-tDCS 1-s Group. For all variables, no cumulative effects were observed in a-tDCS 2-s compared to the a-tDCS 1-s Group. The study findings provide preliminary results for future clinical trials designed to compare different intervals between tDCS sessions in CM. 10.1016/j.neucli.2022.07.005
Effectiveness of yoga therapy for migraine treatment: A meta-analysis of randomized controlled studies. The American journal of emergency medicine INTRODUCTION:Yoga therapy may have some potential in treating migraine, and thus this meta-analysis aims to explore the efficacy of yoga therapy for patients with migraine. METHODS:PubMed, EMbase, Web of science, EBSCO and Cochrane library databases have been systematically searched and we included the randomized controlled trials (RCTs) reporting the efficacy of yoga therapy for migraine patients. The outcomes included. RESULTS:This meta-analysis included six RCTs. The results revealed that compared with control group for migraine, yoga therapy was associated with remarkably decreased pain intensity (SMD = -1.21; 95% CI = -2.17 to -0.25; P = 0.01), headache frequency (SMD = -1.43; 95% CI = -2.23 to -0.64; P = 0.0004), headache duration (SMD = -1.03; 95% CI = -1.85 to -0.21; P = 0.01), HIT-6 score (SMD = -2.28; 95% CI = -3.81 to -0.75; P = 0.003) and MIDAS score (SMD = -0.52; 95% CI = -0.77 to -0.27; P < 0.0001). CONCLUSIONS:Yoga therapy may be effective to treat migraine patients, but it should be recommended with caution because of heterogeneity. 10.1016/j.ajem.2022.04.050
Feasibility and effect of mindfulness approach by web for chronic migraine and high-frequency episodic migraine without aura at in adolescents during and after COVID emergency: preliminary findings. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology BACKGROUND:Migraine disorders are common among adolescents: however, the efficacy of medical prophylaxis is limited in this population. This study reports preliminary findings on the feasibility and effect of a mindfulness-based intervention delivered via web for adolescents with chronic migraine (CM) and high-frequency episodic migraine (HFEM) without aura. METHODS:Patients with CM or HFEM received six session of a mindfulness-based treatment and were followed-up for 6 months as part of a larger study. Repeated measure analyses were carried out to test the effect of this behavioral intervention. RESULTS:A total of 12 patients were included in this analysis. A significant improvement was observed up to 6 months for headache frequency, symptoms of depression, and catastrophizing, and up to 3 months for patients' disability. No change was detected for patients' anxiety level. CONCLUSIONS:The results of our study provides initial support to the hypothesis that patients' education and mindfulness-based programs can be very useful in populations of adolescents with CM or HFEM. 10.1007/s10072-022-06225-2
Experimental animal models of migraine. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology Animal models of migraine have been widely used during the last decades to provide clues for understanding mechanisms underlying pathophysiology of migraine attacks and for developing specific therapeutic agents. They can be grouped into two main types: vascular and neurovascular. Trigemino-vascular system (TVS) is the most relevant efferent component and the mediators of its activity have been thoroughly studied along with some of the receptors involved to characterize anatomical and functional aspects of the system and to test efficacy and mechanisms of therapeutic agents. Neurovascular models are numerous. Plasma protein extravasation (PPE) model consists of measuring the amount of proteins leaking from vessels when TVS is either electrically or chemically stimulated and evaluating its blockade by systemically administered therapeutic agents of which specific receptors have also been identified. Activation of trigeminal nucleus caudalis (TNC) through meningeal stimulation of the superior sagittal sinus served to better understand the mechanisms of central nociceptive pathway. The cortical spreading depression (CSD) model has been used to activate the TVS through application of potassium chloride and evaluate Fos expression in the trigeminal nucleus caudalis (TNC). Finally, neurochemical, cerebrovascular, and nociceptive response to systemic or central administration of nitric oxide (NO) donors served to study central nociceptive pathway and autonomic response interaction. Transgenic mouse expressing human migraine mutations has been genetically engineered to provide an understanding of familial hemiplegic migraine (FHM). Animal models of migraine also served to better understand the role of hormones, genes, and environmental factors on migraine pathophysiology. 10.1007/s10072-022-06281-8
Headache-related circuits and high frequencies evaluated by EEG, MRI, PET as potential biomarkers to differentiate chronic and episodic migraine: Evidence from a systematic review. The journal of headache and pain BACKGROUND:The diagnosis of migraine is mainly clinical and self-reported, which makes additional examinations unnecessary in most cases. Migraine can be subtyped into chronic (CM) and episodic (EM). Despite the very high prevalence of migraine, there are no evidence-based guidelines for differentiating between these subtypes other than the number of days of migraine headache per month. Thus, we consider it timely to perform a systematic review to search for physiological evidence from functional activity (as opposed to anatomical structure) for the differentiation between CM and EM, as well as potential functional biomarkers. For this purpose, Web of Science (WoS), Scopus, and PubMed databases were screened. FINDINGS:Among the 24 studies included in this review, most of them (22) reported statistically significant differences between the groups of CM and EM. This finding is consistent regardless of brain activity acquisition modality, ictal stage, and recording condition for a wide variety of analyses. That speaks for a supramodal and domain-general differences between CM and EM that goes beyond a differentiation based on the days of migraine per month. Together, the reviewed studies demonstrates that electro- and magneto-physiological brain activity (M/EEG), as well as neurovascular and metabolic recordings from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), show characteristic patterns that allow to differentiate between CM and EM groups. CONCLUSIONS:Although a clear brain activity-based biomarker has not yet been identified to distinguish these subtypes of migraine, research is approaching headache specialists to a migraine diagnosis based not only on symptoms and signs reported by patients. Future studies based on M/EEG should pay special attention to the brain activity in medium and fast frequency bands, mainly the beta band. On the other hand, fMRI and PET studies should focus on neural circuits and regions related to pain and emotional processing. 10.1186/s10194-022-01465-1
ERP evidence of heightened attentional response to visual stimuli in migraine headache disorders. Experimental brain research New findings from migraine studies have indicated that this common headache disorder is associated with anomalies in attentional processing. In tandem with the previous explorations, this study will provide evidence to show that visual attention is impacted by migraine headache disorders. 43 individuals were initially recruited in the migraine group and 33 people with non-migraine headache disorders were in the control group. The event-related potentials (ERP) of the participants were calculated using data from a visual oddball paradigm task. By analyzing the N200 and P300 ERP components, migraineurs, as compared to controls, had an exaggerated oddball response showing increased amplitude in N200 and P300 difference scores for the oddball vs. standard, while the latencies of the two components remained the same in the migraine and control groups. We then looked at two classifications of migraine with and without aura compared to non-migraine controls. One-Way ANOVA analysis of the two migraine groups and the non-migraine control group showed that the different level of N200 and P300 amplitude mean scores was greater between migraineurs without aura and the control group while these components' latency remained the same relatively in the three groups. Our results give more neurophysiological support that people with migraine headaches have altered processing of visual attention. 10.1007/s00221-022-06408-5
Long-Term Prophylactic Transcranial Direct Current Stimulation Ameliorates Allodynia and Improves Clinical Outcomes in Individuals With Migraine. Neuromodulation : journal of the International Neuromodulation Society OBJECTIVES:Migraine is a common and substantially debilitating disorder that may associate with allodynia, a marker of central sensitization in the pain circuits. Several unmet needs, like limited adherence to drugs due to adverse events and cost-effectivity, still occur in the prophylactic treatment of migraine. Transcranial direct current stimulation (tDCS) has recently been indicated to be beneficial in individuals with migraine with and without allodynia. However, to our knowledge, there are no studies evaluating the efficacy of six-month tDCS in migraine. MATERIALS AND METHODS:This study was a randomized double-blind parallel-group sham-controlled five-month extension study after a one-month lead-in trial of tDCS in individuals with migraine. A total of 23 individuals with migraine with allodynia who completed the lead-in trial were recruited after their consent and were administered three consecutive sessions of 2-mA anodal 20-minute tDCS over the left primary motor cortex every month for an additional five months. Pain-related outcomes were determined using monthly headache diaries. Allodynia, depression, anxiety, and disability because of migraine also were assessed throughout the study. RESULTS:Improvements in allodynia levels, attack frequency, number of rescue medications, and attack duration were higher, and mostly gradual during the trial, in the active group. Migraine Disability Scale grades also were lower in the active group, whereas no between-group differences were found in depression and anxiety scores. Higher responder rates of migraine attack frequency (56.8% vs 25%), number of headache days (56% vs 16.7%), and migraine attack duration (90.9% vs 8.3%) were observed after six-month tDCS in the active group than in the sham group. CONCLUSIONS:Long-term extended tDCS is shown to be a safe, efficacious, and plausible modality for prophylactic treatment in individuals with migraine with allodynia. SIGNIFICANCE:Long-term extended tDCS can alleviate allodynia, which is an indicator of drug resistance and chronicity, and meet the goals of prophylactic treatment in individuals with migraine with allodynia. 10.1016/j.neurom.2022.06.007
Insular functional connectivity in migraine with aura. The journal of headache and pain INTRODUCTION:Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA. METHODS:Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis. RESULTS:Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO. DISCUSSION:The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA. CONCLUSION:The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA. TRIAL REGISTRATION:NCT02708797. 10.1186/s10194-022-01473-1
Migraine classification by machine learning with functional near-infrared spectroscopy during the mental arithmetic task. Scientific reports Migraine is a common and complex neurovascular disorder. Clinically, the diagnosis of migraine mainly relies on scales, but the degree of pain is too subjective to be a reliable indicator. It is even more difficult to diagnose the medication-overuse headache, which can only be evaluated by whether the symptom is improved after the medication adjustment. Therefore, an objective migraine classification system to assist doctors in making a more accurate diagnosis is needed. In this research, 13 healthy subjects (HC), 9 chronic migraine subjects (CM), and 12 medication-overuse headache subjects (MOH) were measured by functional near-infrared spectroscopy (fNIRS) to observe the change of the hemoglobin in the prefrontal cortex (PFC) during the mental arithmetic task (MAT). Our model shows the sensitivity and specificity of CM are 100% and 75%, and that of MOH is 75% and 100%.The results of the classification of the three groups prove that fNIRS combines with machine learning is feasible for the migraine classification. 10.1038/s41598-022-17619-9
Behavioral and psychological factors in individuals with migraine without psychiatric comorbidities. The journal of headache and pain BACKGROUND:It is well known that the course of migraine is influenced by comorbidities and that individual psychological characteristics may impact on the disease. Proper identification of psychological factors that are relevant to migraine is important to improve non-pharmacological management. This study aimed at investigating the relationship between psychological factors and migraine in subjects free of psychiatric comorbidities. METHODS:A sample of women with episodic (EM) and chronic migraine (CM) without history of psychiatric comorbidities were included in this cross-sectional study. The study also included female healthy controls (HC) without migraine or other primary headaches. We evaluated sleep, anxiety, depression, intolerance of uncertainty, decision making style and tendence to pain catastrophizing by validated self-report questionnaires or scales. Comparisons among groups were performed using ANOVA and Bonferroni post-hoc tests. Statistical significance was set at p < 0.05. RESULTS:A total of 65 women with EM (mean age ± SD, 43.9 ± 7.2), 65 women with CM (47.7 ± 8.5), and 65 HC (43.5 ± 9.0) were evaluated. In sleep domains, CM patients reported poorer overall sleep quality, more severe sleep disturbances, greater sleep medication use, higher daytime dysfunction, and more severe insomnia symptoms than HC. EM group showed better sleep quality, lower sleep disturbances and sleep medication use than CM. On the other hand, the analysis highlighted more severe daytime dysfunction and insomnia symptoms in EM patients compared to HC. In anxiety and mood domains, CM showed greater trait anxiety and a higher level of general anxiety sensitivity than HC. Specifically, CM participants were more afraid of somatic and cognitive anxiety symptoms than HC. No difference in depression severity emerged. Finally, CM reported a higher pain catastrophizing tendency, more severe feeling of helplessness, and more substantial ruminative thinking than EM and HC, whilst EM participants reported higher scores in the three above-mentioned dimensions than HC. The three groups showed similar decision-making styles, intolerance of uncertainty, and strategies for coping with uncertainty. CONCLUSIONS:Even in individuals without psychiatric comorbidities, specific behavioral and psychological factors are associated with migraine, especially in its chronic form. Proper identification of those factors is important to improve management of migraine through non-pharmacological strategies. 10.1186/s10194-022-01485-x
Acupuncture Based on Regulating Autonomic Nerves for the Prevention of Migraine without Aura: A Prospective, Double-Dummy, Randomized Controlled Clinical Trial [Letter]. Journal of pain research 10.2147/JPR.S385406
Sleep and Migraine: Assessment and Treatment of Comorbid Sleep Disorders. Rains Jeanetta C Headache The relationship of sleep and migraine is unequivocal and familiarity with the nature and magnitude of these associations may inform clinical practice. Recent prospective, longitudinal, and time-series analysis has begun to unravel the magnitude and temporal patterns of sleep and migraine. Prospective evidence has shown that sleep variables can trigger acute migraine, precede and predict new onset headache by several years, and indeed, sleep disturbance and snoring are risk factors for chronification. The presence of a sleep disorder is associated with more frequent and severe migraine and portends a poorer headache prognosis. Interestingly, the disorders linked to migraine are quite varied, including insomnia, snoring and obstructive sleep apnea, restless legs, circadian rhythm disorders, narcolepsy, and others. Insomnia is by far the most common sleep disorder in headache patients. In fact, the majority of patients with chronic migraine presenting for treatment have insomnia. Despite a rapidly expanding literature, very few controlled treatment studies have been published to guide clinical practice. This paper focuses on clinical assessment and treatment of sleep disorders. An algorithm is presented for sleep disorders management in the migraine patient, which highlights major sleep disorders and psychiatric comorbidity. Diagnostic procedures are recommended that are conducive to clinical practice. Suggested tools include the sleep history, screening mnemonics, prediction equation, and sleep diary. New developments in treatment have produced abbreviated and cost-effective therapies for insomnia and obstructive sleep apnea that may reach a larger population. Revisions in the diagnostic manuals for sleep and headache disorders enhance recognition of sleep-related headache. Recommendations include behavioral sleep regulation, shown in recent controlled trials to decrease migraine frequency, management for sleep apnea headache, cognitive behavioral therapy (CBT) for insomnia abbreviated for the physician practice setting, sleep-related headache trigger, and others. There is no empirical evidence that sleep evaluation should delay or supersede usual headache care. Rather, sleep management is complimentary to standard headache practice. 10.1111/head.13357
Migraine: disease characterisation, biomarkers, and precision medicine. Ashina Messoud,Terwindt Gisela M,Al-Karagholi Mohammad Al-Mahdi,de Boer Irene,Lee Mi Ji,Hay Debbie L,Schulte Laura H,Hadjikhani Nouchine,Sinclair Alexandra J,Ashina Håkan,Schwedt Todd J,Goadsby Peter J Lancet (London, England) Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisation and identify novel drug targets. In this Series paper, we present the progress that has been made in the search for biomarkers of migraine within genetics, provocation modelling, biochemistry, and neuroimaging research. Additionally, we outline challenges and future directions for each biomarker modality. We also discuss the advances made in combining and integrating data from multiple biomarker modalities. These efforts contribute to developing precision medicine that can be applied to future patients with migraine. 10.1016/S0140-6736(20)32162-0
Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study. Dai Wei,Qiu Enchao,Chen Yun,Xing Xinbo,Xi Wei,Zhang Meichen,Li Ke,Tian Lixia,Dong Zhao,Yu Shengyuan The journal of headache and pain BACKGROUND:Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC). METHODS:RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. RESULTS:Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients. CONCLUSIONS:The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH. 10.1186/s10194-021-01318-3
Genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. Khan Johra,Asoom Lubna Ibrahim Al,Sunni Ahmad Al,Rafique Nazish,Latif Rabia,Saif Seham Al,Almandil Noor B,Almohazey Dana,AbdulAzeez Sayed,Borgio J Francis Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Migraine is a neurological ailment that is characterized by severe throbbing unilateral headache and associated with nausea, photophobia, phonophobia and vomiting. A full and clear mechanism of the pathogenesis of migraine, though studied extensively, has not been established yet. The current available information indicates an intracranial network activation that culminates in the sensitization of the trigemino-vascular system, release of inflammatory markers, and initiation of meningeal-like inflammatory reaction that is sensed as headache. Genetic factors might play a significant role in deciding an individual's susceptibility to migraine. Twin studies have revealed that a single gene polymorphism can lead to migraine in individuals with a monogenic migraine disorder. In this review, we describe recent advancements in the genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. We also discuss the potential roles of genetic and abnormal factors, including some of the metabolic triggering factors that result in migraine attacks. This review will help to accumulate current knowledge about migraine and understanding of its pathophysiology, and provides up-to-date prevention strategies. 10.1016/j.biopha.2021.111557
Migraine and Sleep in Children: A Bidirectional Relationship. Pavkovic Ivan M,Kothare Sanjeev V Pediatric neurology Migraine and sleep disorders in children exhibit a bidirectional relationship. This relationship is based on shared pathophysiology. Migraine involves activation of the trigeminal vascular system. Nociceptive neurons that innervate the dura release various vasoactive peptides. Calcitonin gene-related peptide is the most active of these peptides. Neural pathways that are involved in sleep generation are divided into those responsible for circadian rhythm, wake promotion, non-rapid eye movement, and rapid eye movement sleep activation. Sleep state switches are a critical component of these systems. The cerebral structures, networks, and neurochemical systems that are involved in migraine align closely with those responsible for the regulation of sleep. Neurochemical systems that are involved with both the pathogenesis of migraine and regulation of sleep include adenosine, melatonin, orexin, and calcitonin gene-related peptide. Sleep disorders represent the most common comorbidity with migraine in childhood. The prevalence of parasomnias, obstructive sleep apnea, and sleep-related movement disorders is significantly greater in children migraineurs. Infantile colic is a precursor of childhood migraine. Treatment of comorbid sleep disorders is important for the appropriate management of children with migraine. Sleep-based behavioral interventions can be of substantial benefit. These interventions are particularly important in children due to limited evidence for effective migraine pharmacotherapy. 10.1016/j.pediatrneurol.2019.12.013
Sleep Disorders and Migraine: Review of Literature and Potential Pathophysiology Mechanisms. Vgontzas Angeliki,Pavlović Jelena M Headache Migraine shares a complex and poorly understood relationship with sleep. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Are the associations between migraine and sleep simply the result of various bidirectional relationships? A growing body of evidence suggests there may be a common underlying etiology as well. Our objective was to review studies of sleep and migraine from the last 2 decades utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. We specifically focus on insomnia, obstructive sleep apnea, parasomnias, sleep related movement disorders, and REM sleep related disorders and their relationship to migraine. Parts of brainstem-cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway. Recent discoveries on anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new CNS waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems. 10.1111/head.13358
Migraine and Sleep-An Unexplained Association? Waliszewska-Prosół Marta,Nowakowska-Kotas Marta,Chojdak-Łukasiewicz Justyna,Budrewicz Sławomir International journal of molecular sciences Migraine and sleep disorders are common chronic diseases in the general population, with significant negative social and economic impacts. The association between both of these phenomena has been observed by clinicians for years and is confirmed by many epidemiological studies. Despite this, the nature of this relationship is still not fully understood. In recent years, there has been rapid progress in understanding the common anatomical structures of and pathogenetic mechanism between sleep and migraine. Based on a literature review, the authors present the current view on this topic as well as ongoing research in this field, with reference to the key points of the biochemical and neurophysiological processes responsible for both these disorders. In the future, a better understanding of these mechanisms will significantly expand the range of treatment options. 10.3390/ijms22115539
The prevalence and severity of insomnia in university students and their associations with migraine, tension-type headache, anxiety and depression disorders: a cross-sectional study. Sleep medicine BACKGROUND:There is possibly an association between migraine, tension-type headache, anxiety, depression and insomnia. These conditions are prevalent among university students. Our primary objective was to verify whether students with primary headaches (migraine and tension-type headache) have a higher prevalence of insomnia. Our secondary objective was to assess whether the impact of headaches was associated with greater severity of insomnia. METHODS:Cross-sectional study. 440 students out of 3030 were randomly selected. A semi-structured questionnaire containing information about the characteristics of the headaches, including their frequencies in the last 3 months; the Headache Impact Test (HIT-6); the Hospital Anxiety Depression Scale; and the Insomnia Severity Index were used. RESULTS:420 students (95.5%) agreed to participate; 51.4% men; median age of 21 (19, 23); 95 (22.6%) had insomnia; 265 (63.1%), migraine; 152 (36.2%), tension-type headache; 201 (47.9%) suffered from anxiety and 108 (25.7%), from depression. The severe impact of headache (HIT-6>55 points; OR = 3.9; p = 0.003) and anxiety (OR = 3.6; p = 0.003) were associated with insomnia (logistic regression). The severity of insomnia was positively and significantly correlated with the impact (HIT-6 score), with frequency of headache, and with having anxiety (multiple linear regression). CONCLUSIONS:The diagnoses of migraine and tension-type headache are not associated with the presence of insomnia. The severity of insomnia is associated with the impact and the frequency of the headaches. 10.1016/j.sleep.2021.10.029
Migraine and sleep disorders: a systematic review. The journal of headache and pain Migraine and sleep disorders are common and often burdensome chronic conditions with a high prevalence in the general population, and with considerable socio-economic impact and costs.The existence of a relationship between migraine and sleep disorders has been recognized from centuries by clinicians and epidemiological studies. Nevertheless, the exact nature of this association, the underlying mechanisms and interactions are complex and not completely understood. Recent biochemical and functional imaging studies identified central nervous system structures and neurotransmitters involved in the pathophysiology of migraine and also important for the regulation of normal sleep architecture, suggesting a possible causative role, in the pathogenesis of both disorders, of a dysregulation in these common nervous system pathways.This systematic review summarizes the existing data on migraine and sleep disorders with the aim to evaluate the existence of a causal relationship and to assess the presence of influencing factors. The identification of specific sleep disorders associated with migraine should induce clinicians to systematically assess their presence in migraine patients and to adopt combined treatment strategies. 10.1186/s10194-020-01192-5
What is the link between migraine and psychiatric disorders? From epidemiology to therapeutics. Radat F Revue neurologique The association between migraine and psychiatric disorders is well documented through numerous population-based studies. The results of these studies are coherent and show an increased risk of suffering from depression, bipolar disorders, numerous anxiety disorders, especially post-traumatic stress disorder. This raises the question of stress as a precipitating factor for migraine illness. Psychiatric comorbidity is even more frequent in chronic migraine than in episodic migraine patients. Many prospective studies have shown that psychiatric comorbidity could be considered as a risk factor for migraine chronicization. Psychiatric comorbidity is also responsible for an increase of the frequency of anti-migraine drug intake, a worsening of quality of life and a worsening of functional impairment. It is also responsible for an increase in the direct and indirect costs of migraine. The reason why psychiatric comorbidity is so high in migraineurs is not unambiguous. Multiple causal relationships and common etiological factors are linked. Recently, genome-wide association studies gave leads to a genetic common heritability between major depressive disorder and migraine. For clinicians, an important topic remains how to treat migraineurs with psychiatric comorbidity. These patients suffer frequently from severe migraine or refractory migraine. Antidepressant and anti-convulsive drugs can be useful, as well as psychological therapies. But moreover, it is of utmost importance to propose an integrated multidisciplinary approach to these difficult patients. 10.1016/j.neurol.2021.07.007
A link between gastrointestinal disorders and migraine: Insights into the gut-brain connection. Aurora Sheena K,Shrewsbury Stephen B,Ray Sutapa,Hindiyeh Nada,Nguyen Linda Headache BACKGROUND:Migraine is a complex, multifaceted, and disabling headache disease that is often complicated by gastrointestinal (GI) conditions, such as gastroparesis, functional dyspepsia, and cyclic vomiting syndrome (CVS). Functional dyspepsia and CVS are part of a spectrum of disorders newly classified as disorders of gut-brain interaction (DGBI). Gastroparesis and functional dyspepsia are both associated with delayed gastric emptying, while nausea and vomiting are prominent in CVS, which are also symptoms that commonly occur with migraine attacks. Furthermore, these gastric disorders are comorbidities frequently reported by patients with migraine. While very few studies assessing GI disorders in patients with migraine have been performed, they do demonstrate a physiological link between these conditions. OBJECTIVE:To summarize the available studies supporting a link between GI comorbidities and migraine, including historical and current scientific evidence, as well as provide evidence that symptoms of GI disorders are also observed outside of migraine attacks during the interictal period. Additionally, the importance of route of administration and formulation of migraine therapies for patients with GI symptoms will be discussed. METHODS:A literature search of PubMed for articles relating to the relationship between the gut and the brain with no restriction on the publication year was performed. Studies providing scientific support for associations of gastroparesis, functional dyspepsia, and CVS with migraine and the impact these associations may have on migraine treatment were the primary focus. This is a narrative review of identified studies. RESULTS:Although the association between migraine and GI disorders has received very little attention in the literature, the existing evidence suggests that they may share a common etiology. In particular, the relationship between migraine, gastric motility, and vomiting has important clinical implications in the treatment of migraine, as delayed gastric emptying and vomiting may affect oral dosing compliance, and thus, the absorption and efficacy of oral migraine treatments. CONCLUSIONS:There is evidence of a link between migraine and GI comorbidities, including those under the DGBI classification. Many patients do not find adequate relief with oral migraine therapies, which further necessitates increased recognition of GI disorders in patients with migraine by the headache community. 10.1111/head.14099
Clinical characteristics of sleep disorders in patients with vestibular migraine. Wu Jun,Liu Chunling,Yu Haitao,Li Hui,Jia Yanlu,Zhang Defu,Chen Lili,Li Xiaonan Sleep & breathing = Schlaf & Atmung PURPOSE:To study and analyze the sleep quality and sleep structure of patients with vestibular migraine (VM). METHODS:In this cross-sectional case-control study, the Pittsburgh Sleep Quality Index (PSQI) questionnaire and polysomnography (PSG) were used to compare the clinical characteristics of sleep disorders in 49 patients with VM, 52 patients with migraine, and 54 controls. RESULTS:The VM, migraine, and control groups did not significantly differ in terms of age or sex. Compared with the migraine and control groups, the VM group had a higher incidence of poor sleep quality (χ = 36.618, p < 0.01) and greater severity of poor sleep quality (p < 0.01). Furthermore, the VM group showed reduced sleep efficiency (p < 0.01) and reduced proportions of REM and slow wave (N3) sleep (p ≤ 0.01). Conversely, sleep latency (p = 0.01) and REM latency (p = 0.04) were prolonged, and proportions of light sleep phases (N1, p < 0.05, and N2, p < 0.01) and the micro-arousal index (p = 0.03) were increased. The migraine group had significantly higher apnea hypopnea (AHI) and periodic leg movement (PLMI) indices than the VM group. CONCLUSION:We report an effect of VM on sleep structure and an association with migraine. Similar to migraine, VM affects the sleep regulation centers and causes structural sleep disorders. 10.1007/s11325-019-01994-1
Visual snow syndrome, the spectrum of perceptual disorders, and migraine as a common risk factor: A narrative review. Headache OBJECTIVE:The aim of this narrative review is to explore the relationship between visual snow syndrome (VSS), migraine, and a group of other perceptual disorders. BACKGROUND:VSS is characterized by visual snow and additional visual and nonvisual disturbances. The clinical picture suggests a hypersensitivity to internal and external stimuli. Imaging and electrophysiological findings indicate a hyperexcitability of the primary and secondary visual areas of the brain possibly due to an impairment of inhibitory feedback mechanisms. Migraine is the most frequent comorbidity. Epidemiological and clinical studies indicate that other perceptual disorders, such as tinnitus, fibromyalgia, and dizziness, are associated with VSS. Clinical overlaps and parallels in pathophysiology might exist in relation to migraine. METHODS:We performed a PubMed and Google Scholar search with the following terms: visual snow syndrome, entoptic phenomenon, fibromyalgia, tinnitus, migraine, dizziness, persistent postural-perceptual dizziness (PPPD), comorbidities, symptoms, pathophysiology, thalamus, thalamocortical dysrhythmia, and salience network. RESULTS:VSS, fibromyalgia, tinnitus, and PPPD share evidence of a central disturbance in the processing of different stimuli (visual, somatosensory/pain, acoustic, and vestibular) that might lead to hypersensitivity. Imaging and electrophysiological findings hint toward network disorders involving the sensory networks and other large-scale networks involved in the management of attention and emotional processing. There are clinical and epidemiological overlaps between these disorders. Similarly, migraine exhibits a multisensory hypersensitivity even in the interictal state with fluctuation during the migraine cycle. All the described perceptual disorders are associated with migraine suggesting that having migraine, that is, a disorder of sensory processing, is a common link. CONCLUSION:VSS, PPPD, fibromyalgia, and chronic tinnitus might lie on a spectrum of perceptual disorders with similar pathophysiological mechanisms and the common risk factor migraine. Understanding the underlying network disturbances might give insights into how to improve these currently very difficult to treat conditions. 10.1111/head.14213
[Osmophobia and vestibular migraine] Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) Aim:Vestibular migraine is one of the most common vestibular disorders, which includes headache, photophobia, phonopobia and visual auras. Others as osmophobia are common but usually subregistered, and potentially would be involved in the vestibular migraine episodes. The aim of this study was to perform a search about the frequency and clinical interaction between vestibular migraine and osmophobia. Data search:A literature review search was conducted on PubMed, EBSCO, Scielo, Google Scholar and Bvsalud of published studies between 2011 and 2021 using the MeSH terms ‘vertigo and olfaction disorders’, ‘dizziness and olfaction disorders’, ‘migraine disorders and olfaction disorders’. Study selection:12 articles were found, where patients with diagnosis of vestibular migraine according to Barany Society, reported clinical symptoms and the prevalence of each symptom related was documented. Only two studies, presented relevant information about osmophobia and vestibular migraine Data extraction and results:From 277 individuals diagnosed with vestibular migraine in two observational studies, only 5%-12%, reported osmophobia. To date only one case report describe in extension the relationship between vestibular migraine and osmophobia. Conclusions:This symptom would be underdiagnosed and subregistered in individuals with vestibular migraine. Further studies are needed to determine this association. 10.31053/1853.0605.v79.n1.33699