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Background: The present study aimed to assess the burden of neck pain in adults with migraine and tension-type headache (TTH), utilizing the Neck Disability Index (NDI) and Numeric Pain Rating Scale (NPRS)., Methods: A systematic literature search was conducted on PubMed and Embase to identify observational studies assessing NDI and NPRS in populations with migraine or TTH. The screening of articles was independently performed by two investigators (HMA and ZA). Pooled mean estimates were calculated through random-effects meta-analysis. The I 2 statistic assessed between-study heterogeneity, and meta-regression further explored heterogeneity factors., Results: Thirty-three clinic-based studies met the inclusion criteria. For participants with migraine, the pooled mean NDI score was 16.2 (95% confidence interval (CI) = 13.2-19.2, I 2  = 99%). Additionally, the mean NDI was 5.5 (95% CI = 4.11-6.8, p  < 0.001) scores higher in participants with chronic compared to episodic migraine. The pooled mean NDI score for participants with TTH was 13.7 (95% CI = 4.9-22.4, I 2  = 99%). In addition, the meta-analysis revealed a mean NPRS score of 5.7 (95% CI = 5.1-6.2, I 2  = 95%) across all participants with migraine., Conclusions: This systematic review and meta-analysis shows a greater degree of neck pain-related disability in migraine compared to TTH. Nevertheless, the generalizability of these findings is constrained by methodological variations identified in the current literature., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HMA reports personal fees from Pfizer and Lundbeck, outside of the submitted work. HS reports receiving personal fees from AbbVie, Teva, Lundbeck, Novartis and Eli Lilly outside of the submitted work. MA reports receiving personal fees from AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer and Teva Pharmaceuticals outside of the submitted work. MA also serves as an associate editor of Cephalalgia, The Journal of Headache and Pain and Brain. SA has received honoraria for consulting from Allergan/AbbVie, Eli Lilly, Impel NeuroPharma, Linpharma, Lundbeck, Pfizer, Satsuma, Teva and Theranica. SA is an Associate Editor for Neurology Reviews, BMC Neurology and Frontiers in Neurology; serves on the Advisory Board for Journal of Headache and Pain; and is a member of Education Committee of the International Headache Society. The other authors declare that they have no conflicts of interest.

Background: Migraine and vestibular migraine are disorders associated with a heightened motion sensitivity that provoke symptoms of motion-induced nausea and motion sickness. VM affects ∼3% of adults in the USA and affects three-fold more women than men. Triptans (selective serotonin receptor agonists) relieve migraine pain but lack efficacy for vertigo. Murine models of photophobia and allodynia have used injections of calcitonin gene-related peptide (CGRP) or other migraine triggers, such as sodium nitroprusside (SNP), to induce migraine sensitivities in mice to touch and light. Yet, there is limited research on whether these triggers affect motion-induced nausea in mice, and whether migraine blockers can reduce these migraine symptoms. We hypothesized that systemic delivery of CGRP or SNP will increase motion sickness susceptibility and motion-induced nausea in mouse models, and that migraine blockers can block these changes induced by systemically delivered CGRP or SNP., Methods: We investigated two measures of motion sickness assessment [motion sickness index (MSI) scoring and motion-induced thermoregulation] after intraperitoneal injections of either CGRP or SNP in C57BL/6J mice. The drugs olcegepant, sumatriptan and rizatriptan were used to assess the efficacy of migraine blockers., Results: MSI measures were confounded by CGRP's effect on gastric distress. However, analysis of tail vasodilatations as a surrogate for motion-induced nausea was robust for both migraine triggers. Only olcegepant treatment rescued tail vasodilatations., Conclusions: These preclinical findings support the use of small molecule CGRP receptor antagonists for the treatment of motion-induced nausea of migraine, and show that triptan therapeutics are ineffective against motion-induced nausea of migraine. Trial Registration: Not Applicable., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines., Case Report: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur., Conclusion: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine., Competing Interests: Declaration of conflicting interestsTTa is a consultant/advisor and/or serves on an advisory board for Otsuka, Eli Lilly, Amgen, Pfizer and Teijin. TTa received speaker honoraria from Otsuka, Eli Lilly, Daiichi Sankyo, Amgen, Kowa, Kyowa Kirin, Eisai, UCB Japan, Takeda and Santen Pharmaceutical, as well as research funding from Eli Lilly and Tsumura outside the submitted work. JN received honoraria and research scholarships from Amgen and Daiichi Sankyo.

Introduction: Migraine is a common headache syndrome associated with various other comorbidities. Thyroid replacement in migraine patients with hypothyroidism improves headaches; however, thyroid hormone replacement in subclinical hypothyroidism is debatable, and its efficacy is not known., Objective and Methodology: This prospective, single-centre, quasi-randomised interventional study was conducted on patients visiting the General Medicine and Neurology outpatient department at a tertiary centre to look at the efficacy of thyroxine in subclinical hypothyroidism., Results: We assessed 87 patients for analysis; no patients were lost to follow-up. There was a decrease in all parameters evaluated (headache frequency, severity, duration, MIDAS score, MIDAS grade) at three months of follow-up in the treatment group compared to placebo group. There was a significant decrease in headache frequency and severity in the levothyroxine group compared to the placebo group at three months of follow-up. Also, the follow-up MIDAS score (mean ± SD: 6.30 ± 2.455 scores vs. 8.45 ± 5.757 scores) was significantly decreased by treatment at three months follow-up., Conclusion: Treatment of subclinical hypothyroidism effectively reduces migraine headaches, and it is logical to check thyroid function status in patients presenting with migraine headaches. However, a larger randomised controlled trial is required to prove the efficacy of levothyroxine in migraine with subclinical hypothyroidism., Competing Interests: Declaration of conflicting interestsThe authors do not have any conflict of interest to disclose in terms of research, authorship, and/or publication of this article.

Background: Epidemiological studies have reported a comorbid relationship between migraine and thyroid dysfunction., Methods: We investigated the genetic relationship between migraine and thyroid function traits using genome-wide association study (GWAS) data., Results: We found a significant genetic correlation ( r g ) with migraine for hypothyroidism ( r g  = 0.0608), secondary hypothyroidism ( r g  = 0.195), free thyroxine (fT4) ( r g  = 0.0772), and hyperthyroidism ( r g  = -0.1046), but not thyroid stimulating hormone (TSH). Pairwise GWAS analysis revealed two shared loci with TSH and 11 shared loci with fT4. Cross-trait GWAS meta-analysis of migraine identified novel genome-wide significant loci: 17 with hypothyroidism, one with hyperthyroidism, five with secondary hypothyroidism, eight with TSH, and 15 with fT4. Of the genes at these loci, six ( RERE , TGFB2 , APLF , SLC9B1 , SGTB , BTBD16 ; migraine + hypothyroidism), three ( GADD45A , PFDN1 , RSPH6A ; migraine + TSH), and three ( SSBP3 , BRD3 , TEF ; migraine + fT4) were significant in our gene-based analysis ( p Fisher's combined P-value  < 2.04 × 10 -6 ). In addition, causal analyses suggested a negative causal relationship between migraine and hyperthyroidism ( p  = 8.90 × 10 -3 ) and a positive causal relationship between migraine and secondary hypothyroidism ( p  = 1.30 × 10 -3 )., Conclusion: These findings provide strong evidence for genetic correlation and suggest complex causal relationships between migraine and thyroid traits.

Background: It has been suggested that patients with migraine have a higher risk of stroke. Despite considerable research on this topic in younger populations, a clear answer is still lacking for older individuals. We studied the association between migraine and the risk of stroke in a middle-aged and elderly population., Methods: Within the ongoing prospective population-based Rotterdam Study, the presence of migraine was assessed using a validated questionnaire in a structured interview between 2006 and 2011, which formed the baseline. The association between migraine and the risk of stroke was analyzed using Cox proportional-hazards models with adjustments for age, sex, and cardiometabolic risk factors., Results: A total of 6925 (mean age 65.7 ± 11.3 years, 57.8% females) stroke-free participants were included. At baseline, 1030 (14.9%) participants had lifetime history of migraine. During a median follow-up of 6.2 years, 195 participants developed a stroke (163 ischemic stroke). Analyzing the association between migraine and stroke, we found a hazard ratio of 1.44 with a 95% confidence interval of 0.96-2.15. The results were similar for the ischemic stroke (HR 1.50, CI: 0.97-2.32)., Conclusion: Our data suggested an association between migraine and the risk of stroke in a middle-aged and elderly population, but this was not statistically significant.

Objective: The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders., Methods: This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords "COVID 19" or "vaccine" and "headache" to assess the appropriateness of all published articles for their inclusion in the review., Results: Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced., Conclusions: The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

Objectives: To investigate previous treatment and clinical characteristics in migraine and tension-type headache patients at their first visit to a tertiary headache center., Methods: This was a cross-sectional study using data obtained from electronic questionnaires and medical charts. Migraine and tension-type headache patients were investigated at their first visit to the Danish Headache Center., Results: Out of 382 patients the main diagnoses of primary headaches were: 36% with episodic migraine, 43% with chronic migraine, 3% with episodic tension-type headache and 17% with chronic tension-type headache. The majority had attempted non-pharmacological treatment options such as physiotherapy (episodic migraine: 53%, chronic migraine: 68%, episodic tension-type headache: 50%, chronic tension-type headache: 65%) and acupuncture: (episodic migraine: 45%, chronic migraine: 62%, episodic tension-type headache: 17%, chronic tension-type headache: 51%). The majority of migraine patients had tried no more than one triptan (episodic migraine: 71%, chronic migraine: 66%). In total, 35% of episodic migraine and 19% of chronic migraine patients as well as 50% of episodic tension-type headache and 41% of chronic tension-type headache patients had never tried preventive medication. The headache under-response to treatment (HURT) questionnaire score was higher in chronic migraine (score 15) and chronic tension-type headache (score 16) patients than the episodic forms ( P  < 0.004)., Conclusions: Headache patients had attempted several non-pharmacological treatments prior to their first visit at a tertiary headache center in Denmark. The limited use of acute and preventive treatment before the first visit demonstrates a need for better treatment at the primary and secondary care level.

Background: Headache is a common presentation of postural tachycardia syndrome, yet robust prevalence data is lacking., Objectives: To undertake a systematic review and meta-analysis to estimate the prevalence of headache disorders in postural tachycardia syndrome, and to explore the potential shared pathophysiological mechanisms that underpin these conditions as well as treatment options., Methods: Three databases were searched for publications evaluating prevalence of migraine (primary outcome) and general and orthostatic headache (secondary outcomes) in patients with postural tachycardia syndrome. Two independent reviewers selected studies and extracted data. A random-effects meta-analysis calculated the pooled prevalence of migraine in postural tachycardia syndrome. A narrative literature review explored the pathophysiology and treatment options for concurrent headache disorders and postural tachycardia syndrome., Results: Twenty-three articles met inclusion criteria. Estimated pooled prevalence of migraine in postural tachycardia syndrome was 36.8% (95% CI 2.9-70.7%). Various shared pathophysiological pathways for these conditions, as well as proposed treatment strategies, were identified. Limitations : Heterogeneity of study design, populations, and methodology for identifying headache disorders and postural tachycardia syndrome limited the generalisability of results., Conclusions: Migraine is a commonly reported comorbidity in POTS, however the true prevalence cannot be determined from the current literature. Further studies are required to assess this comorbidity and investigate the underlying mechanisms, as well as identify effective treatment strategies.

Objective: This meta-analysis compared pressure pain sensitivity in trigeminal, cervical spine and remote pain-free areas between migraine patients and headache-free controls considering diagnosis (episodic versus chronic) and sex. Databases and data treatment: Electronic databases were searched for cross-sectional or prospective case-control studies comparing pressure pain thresholds between migraine and headache-free controls. Data were extracted by two reviewers. The risk of bias and methodological quality was assessed by Newcastle-Ottawa Quality Assessment Scale. Meta-analyses of trigeminal, extra-trigeminal (cervical spine) and remote pain-free areas were compared. Frequency of migraine and sex were taken into account. Mean differences (MD) and random effects were calculated., Results: Eighteen studies were included. Patients with migraine showed lower pressure pain thresholds than headache-free controls: trigeminal (MD -71.33 kPa, 95%CI -92.14 to -50.53), cervical spine (MD -68.50 kPa, 95%CI -84.67 to -52.33), and remote pain-free (MD -62.49 kPa, 95%CI -99.52 to -25.45) areas. Differences were consistently significant for episodic migraine in all locations, but only significant in the trigeminal area for chronic migraine (MD -67.36 kOPa, 95%CI -101.31 to -33.42). Overall, women had lower pressure pain thresholds than men. The methodological quality of most studies (66.7%) was good. The results showed a high heterogeneity., Conclusion: This meta-analysis found low to high quality evidence showing lower pressure pain thresholds in trigeminal, extra-trigeminal, and remote pain-free areas in migraine sufferers when compared with headache-free controls. Hypersensitivity to pressure pain locally and widespread was consistently observed in episodic migraine, but locally in chronic migraine as compared to headache-free controls. Women with migraine were more sensitive than men.Registration number: https://doi.org/10.17605/OSF.IO/YJTAK.

Background: Chiari I malformation typically presents with cough headache. However, migraine-like or tension-type-like headaches may also occur. There are limited publications on Chiari I malformation-associated headache semiologies and the effect of foramen magnum decompression on different headache types., Methods: A retrospective analysis complemented by structured phone interviews was performed on 65 patients with Chiari I malformation, treated at our hospital between 2010 and 2021. Headache semiology (according to ICHD-3), frequency, intensity, and radiological characteristics were evaluated pre- and postoperatively., Results: We included 65 patients. 38 patients were female and 27 male. Mean age was 43.9 ± 15.7 years. Headache was predominant in 41 patients (63.0%). Twenty-one patients had cough headache and 20 had atypical headache (12 migrainous, eight tension-type headache-like). Thirty-five patients with headache underwent surgery. Frequency, intensity, and analgesic use was significantly reduced in cough headache ( p  < 0.001). Atypical headaches improved less ( p  = 0.004 to 0.176). Exploratory analysis suggested that larger preoperative tonsillar descent correlated with larger postoperative headache intensity relief ( p  = 0.025)., Conclusion: Decompression was effective in Chiari I malformation-related cough headache. Atypical headache responded less well, and the causal relation with Chiari I malformation remains uncertain. For atypical headache, decompression should only be considered after failed appropriate preventive therapy and within an interdisciplinary approach involving a neurologist.

Background: The role of the NOTCH3 p.R544C variant, the predominant variant of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in multiple East Asian regions, in migraine is unknown., Methods: Migraine patients (n = 2,884) (2,279F/605M, mean age 38.8 ± 11.7 years), including 324 (11.2%) with migraine with aura, were prospectively enrolled by headache specialists according to the International Classification of Headache Disorders criteria. These patients and 3,502 population controls free of stroke, dementia, and headache were genotyped for NOTCH3 p.R544C by TaqMan genotyping assay or Axiom Genome-Wide TWB 2.0 Array. Clinical manifestations and brain magnetic resonance images were examined and compared between migraine patients with and without NOTCH3 p.R544C., Results: Thirty-two migraine patients (1.1%) and 36 controls (1.0%) harbored the p.R544C variant, and the percentages were comparable among migraine patients without and with aura, and controls (1.2%, vs. 0.6% vs. 1.0%, p = 0.625). Overall, migraine patients with and without the p.R544C variant had similar percentages of migraine with aura, headache characteristics, frequencies and disabilities. However, those with p.R544C were less likely to have pulsatile headaches (50.0% vs. 68.2%, p = 0.028), and more likely to have moderate to severe white matter hyperintensities in the external capsule (18.8% vs. 1.2%, p = 0.006) and anterior temporal lobe (12.5% vs. 0%, p = 0.008)., Conclusions: Our findings suggest that NOTCH3 p.R544C does not increase the risk of migraine with aura, or migraine as a whole, and generally does not alter clinical manifestations of migraine. The role of NOTCH3 variants, as well as potential influences from ethnicity or modifier genes, in migraine needs to be further clarified.

Background and Objectives: Increased sensitivity to light and patterns is typically associated with migraine, but has also been anecdotally reported in cluster headache, leading to diagnostic confusion. We wanted to assess whether visual sensitivity is increased ictally and interictally in cluster headache., Methods: We used the validated Leiden Visual Sensitivity Scale (L-VISS) questionnaire (range 0-36 points) to measure visual sensitivity in people with episodic or chronic cluster headache: (i) during attacks; (ii) in-between attacks; and in episodic cluster headache (iii) in-between bouts. The L-VISS scores were compared with the L-VISS scores obtained in a previous study in healthy controls and participants with migraine., Results: Mean L-VISS scores were higher for: (i) ictal vs interictal cluster headache (episodic cluster headache: 11.9 ± 8.0 vs. 5.2 ± 5.5, chronic cluster headache: 13.7 ± 8.4 vs 5.6 ± 4.8; p < 0.001); (ii) interictal cluster headache vs controls (5.3 ± 5.2 vs 3.6 ± 2.8, p < 0.001); (iii) interictal chronic cluster headache vs interictal ECH in bout (5.9 ± 0.5 vs 3.8 ± 0.5, p = 0.009), and (iv) interictal episodic cluster headache in bout vs episodic cluster headache out-of-bout (5.2 ± 5.5 vs. 3.7 ± 4.3, p < 0.001). Subjective visual hypersensitivity was reported by 110/121 (91%; 9 missing) participants with cluster headache and was mostly unilateral in 70/110 (64%) and ipsilateral to the ictal pain in 69/70 (99%) participants., Conclusion: Cluster headache is associated with increased ictal and interictal visual sensitivity. In contrast to migraine, this is mostly unilateral and ipsilateral on the side of the ictal pain.

Background: Primary headache associated with sexual activity is a rare benign headache disorder that is provoked by sexual excitement. It is a diagnosis of exclusion after the underlying secondary causes have been ruled out. The cause of this headache disorder is still unknown. Cerebral vasospasm, pericranial muscular contraction, hemodynamic and respiratory changes during sexual activity are most commonly listed as possible pathophysiological mechanisms. Several acute and prophylactic options with good clinical response have been described in the case series., Case Report: We present a case of a 30-year-old woman with primary headache associated with sexual activity and comorbid with frequent episodic migraine without aura. Both headache disorders were successfully managed with monoclonal antibody against calcitonine gene-related peptide (CGRP) receptor erenumab 70 mg., Conclusion: The efficacy of erenumab in our case presumes that CGRP might also be an important mediator in facilitating primary headache associated with sexual activity.

Background: Allodynia in adults with migraine is related to disease duration. In pediatric patients with migraine, the same proportion reported allodynia in the first six months of migraine presentation as in prolonged disease. This study examined a possible association between migraine pediatric allodynia and maternal allodynia., Methods: We interviewed children with migraine first, and then their mothers, regarding allodynia and headache symptoms. We reviewed hospital charts on pediatric medical background and headache symptoms. Mothers and children older than 11 years filled the Strengths and Difficulties Questionnaire., Results: Ninety-eight children with migraine, mean age 13.49 ± 3.1 years, and their mothers, mean age 43.5 ± 6.2 years were recruited to the study. Pediatric allodynia was associated with maternal allodynia; the latter was reported in 82.8% of children with allodynia versus 35.3% of children without allodynia (p < 0.001). Maternal migraine was reported in 44 (68.7%) of children with allodynia versus 16.3% without allodynia, p < 0.001. No difference was found in Strengths and Difficulties Questionnaire scores, between children with and without allodynia., Conclusions: Pediatric allodynia is associated with maternal migraine. Genetic and environmental factors such as maternal behavior may contribute to reduced pain threshold.

Background: Retinal migraine is defined by fully reversible monocular visual phenomena. We present two cases that were complicated by permanent monocular vision deficits., Cases: A 57-year-old man with history of retinal migraine experienced persistent monocular vision loss after one stereotypical retinal migraine, progressing to finger-count vision over 4 days. He developed paracentral acute middle maculopathy that progressed to central retinal artery occlusion. A 27-year-old man with history of retinal migraine presented with persistent right eye superotemporal scotoma after a retinal migraine. Relative afferent pupillary defect and superotemporal visual field defect were noted, consistent with ischemic optic neuropathy., Conclusion: Retinal migraine can complicate with permanent monocular visual loss, suggesting potential migrainous infarction of the retina or optic nerve. A thorough cerebrovascular evaluation must be completed, which was unrevealing in our cases. Acute and preventive migraine therapy may be considered in retinal migraine patients, to mitigate rare but potentially permanent visual loss.

Objective: There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls., Methods: Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep., Results: The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group., Conclusion: This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

Introduction: The migraine-preventive drug propranolol is efficacious in reducing pain from temporomandibular disorder, suggesting potential modifying or mediating effects of comorbid migraine., Methods: In this randomized controlled trial, myofascial temporomandibular disorder patients were treated with propranolol or placebo for 9 weeks. The primary endpoint was change in a facial pain index derived from daily symptom diaries. Linear and logistic regression models tested for a migraine × treatment-group interaction in reducing facial pain index. Counterfactual models explored changes in headache impact and heart rate as mediators of propranolol's efficacy., Results: Propranolol's efficacy in reducing facial pain index was greater among the 104 migraineurs than the 95 non-migraineurs: For example, for the binary ≥ 30% reduction in facial pain index, odds ratios were 3.3 (95% confidence limits: 1.4, 8.1) versus 1.3 (0.5, 3.2), respectively, although the interaction was statistically non-significant ( p  = 0.139). Cumulative response curves confirmed greater efficacy for migraineurs than non-migraineurs (differences in area under the curve 26% and 6%, respectively; p  = 0.081). While 9% of the treatment effect was mediated by reduced headache impact, 46% was mediated by reduced heart rate., Conclusions: Propranolol was more efficacious in reducing temporomandibular disorder pain among migraineurs than non-migraineurs, with more of the effect mediated by reduced heart rate than by reduced headache impact., Study Identification and Registration: SOPPRANO; NCT02437383; https://clinicaltrials.gov/ct2/show/NCT02437383.

Aim: Little is known about short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). We present our experience with SUNCT/SUNA patients to aid identification and management of these disorders., Methods: A retrospective review of patient records of one orofacial pain clinic was performed. Inclusion criteria was a diagnosis of SUNCT/SUNA confirmed with at least one follow-up visit., Results: Six of the 2464 new patients seen between 2015-2018 met the selection criteria (SUNCT n = 2, SUNA n = 4). Gender distribution was one male to one female and average age of diagnosis was 52 years (range 26-62). Attacks were located in the V1/V2 trigeminal distributions, and five patients reported associated intraoral pain. Pain quality was sharp, shooting, and burning with two patients reporting "numbness". Pain was moderate-severe in intensity, with daily episodes that typically lasted for seconds. Common autonomic features were lacrimation, conjunctival injection, rhinorrhea, and flushing. Frequent triggers were touching the nose or a specific intraoral area. Lamotrigine and gabapentin were commonly used as initial therapy., Conclusions: Differentiating between SUNCT/SUNA does not appear to be clinically relevant. Presenting symptoms were consistent with those published, except 5/6 patients describing intraoral pain and two patients describing paresthesia.

Background: Dopaminergic symptoms may be extremely pronounced in some migraine patients during the attack, representing a major source of disability., Objectives: We aimed to carefully characterize the clinical picture of migraine patients with dopaminergic symptoms in a large patients' population as a putative migraine endophenotype, allowing more precise disease management, treatment and outcome prediction., Methods: We screened 1148 consecutive tertiary care episodic and chronic migraine patients with face-to-face interviews collecting thorough data on lifestyle, socio-demographic factors, and clinical migraine features., Results: We identified 374 patients with migraine with dopaminergic symptoms (32.6%). The most frequent dopaminergic symptom was yawning followed by somnolence, nausea, vomiting, fatigue, mood changes and diuresis. Migraine patients with dopaminergic symptoms had longer attack duration (OR: 1.82; 95% CI: 1.41-2.36, p  < 0.0001), more frequent osmophobia (OR: 2.01; 95% CI: 1.50-2.69, p  < 0.0001), allodynia (OR: 1.43; 95% CI: 1.10-1.85, p  = 0.0071) and unilateral cranial autonomic symptoms (OR: 1.31; 95% CI: 1.01-1.68, p  = 0.045), but used less preventative treatments (OR: 0.74; 95% CI: 0.57-0.98, p  = 0.033) than patients without dopaminergic symptoms., Conclusions: Migraine patients with dopaminergic symptoms are characterized by a full-blown, more disabling migraine. Dopaminergic system modulation should be carefully considered in individuals with migraine with dopaminergic symptoms for both acute and preventative treatments in future ad hoc designed studies.

Background: Sparse evidence has detailed the clinical phenotype of migraine presenting as isolated facial pain. Objective and methods: This was a prospective audit, part of our multidisciplinary facial pain service evaluation, aiming to phenotype patients with migraine presenting as isolated facial pain who attended our service between 2013 and 2018., Results: Fifty-eight patients were diagnosed with migraine with isolated facial pain (F = 46, 79.3%; mean age: 49.0 years, ± 9.85). Sixty-six percent of patients met the criteria for episodic migraine. The pain was strictly unilateral in 79% and located over the maxillary region in 85% of patients. Associated cranial autonomic signs/symptoms were reported by 45% of our cohort. A percentage of 77% of patients was triptan responders., Conclusions: Migraine presenting as isolated facial pain is a rare but treatable condition with some distinct demographic and clinical characteristics. It is a diagnosis of exclusion that should be evaluated in specialised multidisciplinary facial pain clinics.

Objective: To assess the proportion of individuals who report dizziness and/or vertigo during the prodromal phase or headache phase of migraine., Methods: The databases of MEDLINE and EMBASE were searched for studies on dizziness and/or vertigo during the prodromal phase or headache phase of migraine. Pooled relative frequencies were estimated using a random-effects meta-analysis., Results: We identified nine articles eligible for inclusion. Of these, one study reported results for the prodromal phase, seven studies for the headache phase and one study for both the prodromal and headache phase. In the prodromal phase, 9.0% of individuals with migraine reported dizziness, while 3.3% reported vertigo. During the headache phase, relative frequency of dizziness ranged from 6.7% to 59.6%, while vertigo ranged from 6.4% to 44.7%. The meta-analysis showed a relative frequency of 35.7% for dizziness (95% CI = 13.7-61.5%, I 2  = 99%) and 33.9% for vertigo (95% CI = 26.7-41.5%, I 2  = 87%). Study quality was rated 5/9 or below for seven studies and 6/9 or above for two studies., Conclusion: We found that there is a scarcity of literature on dizziness and vertigo as prodromal- and headache-associated symptoms in individuals with migraine. Methodological variations confound comparisons of epidemiological patterns, although it appears that dizziness and vertigo are more frequent during the headache phase of migraine, compared with the prodromal phase. Future studies should ensure use of standardized definitions and rigorous methodology to enable accurate measurements of dizziness and vertigo in migraine.

Background: Ictal neck pain is a frequent symptom reported by half of migraine patients. It is unknown if neck pain is caused by peripheral or central mechanisms. Neck muscle stiffness can be investigated with ultrasound shear wave elastography., Objectives: To determine if migraine patients with ictal neck pain have stiffer neck muscles interictally compared with patients without ictal neck pain and controls., Methods: This was a cross-sectional study investigating neck muscle stiffness, pressure pain thresholds and neck pain symptoms in 100 migraine patients recruited from a tertiary headache center and 46 controls., Results: Patients with ictal neck pain had increased mean neck muscle stiffness interictally compared to both migraine patients without ictal neck pain ( p  = 0.018) and controls ( p  = 0.036). Muscle stiffness was negatively correlated with pressure pain thresholds in the neck in migraine patients with ictal neck pain (r = -0.292, p  = 0.042). There were no differences in mean pressure pain thresholds between migraine subgroups., Conclusions: Migraine patients with ictal neck pain have stiffer neck muscles interictally compared with migraine patients without ictal neck pain and controls measured with ultrasound shear wave elastography. The increased stiffness could be due to local alterations in the neck muscles. Trial registration: clinical-trials.gov, identifier: NCT03626805.

Objective: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders., Background: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation., Conclusion: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Objective: To review and discuss the literature on the role of thalamic structure and function in migraine., Discussion: The thalamus holds an important position in our understanding of allodynia, central sensitization and photophobia in migraine. Structural and functional findings suggest abnormal functional connectivity between the thalamus and various cortical regions pointing towards an altered pain processing in migraine. Pharmacological nociceptive modulation suggests that the thalamus is a potential drug target., Conclusion: A critical role for the thalamus in migraine-related allodynia and photophobia is well established. Additionally, the thalamus is most likely involved in the dysfunctional pain modulation and processing in migraine, but further research is needed to clarify the exact clinical implications of these findings.

Objective: To investigate the association between the presence of self-reported neck pain in patients with migraine and clinical features, upper cervical mobility, and neck muscle performance., Methods: A total of 142 patients with migraine were recruited and stratified by the presence (n = 99) or absence of self-reported neck pain (n = 43). The clinical examination included the Migraine Disability Assessment, the 12-item Allodynia Symptom Checklist, a flexion rotation test, and the Craniocervical Flexion Test., Results: Migraine-related disability was reported by more than 80% in both groups ( p  = 0.82). However, there was a greater prevalence and severity of cutaneous allodynia observed in the group with neck pain ( p  < 0.001). Reduced upper cervical mobility was verified in 67% of the patients with neck pain and in 41% of those without neck pain ( p  = 0.005). In addition, 67% of the patients with neck pain and 40% without neck pain were not able to maintain the third stage of the Craniocervical Flexion Test without compensation ( p  = 0.003)., Conclusions: The presence of self-reported neck pain in patients with migraine was associated with a poor clinical presentation regarding cutaneous allodynia, neck mobility, and muscle function. However, there were no differences in migraine-related disability.

Introduction: This study quantified risks of cardiovascular, cerebrovascular, and mortality events among patients with migraine receiving prophylaxis., Methods: Patients with migraine aged 18-65 years were identified from 2010 through 2015 within a United States administrative claims database. Topiramate initiators during follow-up were propensity score-matched separately to anticonvulsant, cardiovascular treatment, antidepressant, and other prophylactic treatment initiators. Incident outcomes were identified, and hazard ratios were calculated comparing outcome occurrence among topiramate initiators relative to each comparator. A case-control analysis was nested within the full migraine cohort, and odds ratios quantified the association between outcomes and use or non-use of individual prophylactic treatments (anticonvulsants, serotonin norepinephrine reuptake inhibitors, beta blockers, antihypertensives, tricyclic antidepressants, and other prophylactic treatments)., Results: The cohort included 119,243 patients with migraine. The matched topiramate initiators had a lower mortality risk versus antidepressant (hazard ratio: 0.44, 95% CI: 0.24, 0.83) and anticonvulsant initiators (hazard ratio: 0.45, 95% CI: 0.25, 0.84). In the case-control analysis, increased risks of several outcomes were observed with all prophylactic treatments relative to non-use of that treatment (odds ratios range from 1.54 to 7.90, and 95% CIs exclude 1.0) except for topiramate and calcium channel blockers., Conclusions: Although increased risks for several outcomes were observed with certain prophylactic treatments, the treatments other than topiramate likely represent markers for outcome risk factors that developed or progressed after cohort entry, rather than being a direct effect of the treatments. Factors including migraine severity, frequency, and other treatment indications should be considered in future migraine prophylactic treatment safety assessments.

Background: Cutaneous allodynia is a common clinical feature of migraine that has been associated with reduced efficacy of acute migraine treatments and an increased risk of disease progression., Objective: Identify factors associated with allodynia in a sample of adults with migraine., Methods: An online survey panel was used to identify adults with migraine who averaged at least 1 monthly headache day over the previous 3 months. Data on sociodemographics, headache frequency, headache pain intensity, migraine symptom severity, medication use, depression and anxiety, and cutaneous allodynia (via the Allodynia Symptom Checklist) were obtained. Binary logistic modeling predicted the presence of allodynia. Odds ratios and 95% confidence intervals (CI) were calculated., Results: In total, 15,133 individuals with migraine met the eligibility criteria. Mean age was 43.1 years, 73.0% were female, and 81.0% were Caucasian. Allodynia was present in 39.9%. The fully adjusted model, controlling for sociodemographics and headache features, demonstrated that allodynia was significantly associated with a higher migraine symptom severity score (odds ratio 1.17, confidence interval 1.15, 1.19) and more severe pain intensity (odds ratio 1.11, confidence interval 1.08, 1.14); probable depression and/or anxiety (odds ratio 1.83, confidence interval 1.67, 2.00); and overuse of acute medication (odds ratio 1.23, confidence interval 1.09, 1.38). A higher number of monthly headache days increased the likelihood of allodynia, but the effect was attenuated in the fully adjusted model., Conclusion: In a representative sample of US adults with migraine, there were significant associations between allodynia and headache frequency and intensity, anxiety and/or depression, symptom severity, and acute medication overuse.

Objectives: The aim was to evaluate the association of self-perceived levels of attention deficit and hyperactivity symptoms with non-migraine and migraine headaches among university students. We also evaluated their association with migraine aura., Methods: Study subjects were all participants in the internet-based Students Health Research Enterprise. Scores were built to evaluate global attention and hyperactivity symptom levels, self-perceived attention deficit levels and self-perceived hyperactivity symptom levels based on the Adult Attention Deficit and Hyperactivity Disorder Self-Report Scale (ASRS v1.1.). We used standardised questions to classify headache and group participants into "no headache," "non-migraine headache," "migraine without aura" or "migraine with aura"., Results: A total of 4816 students were included (mean age 20.3 ± 2.8 years; 75.5% women). Compared with participants without headache, we found significant associations between global ADHD scores and migraine. Students in the highest quintile of global ASRS scores had adjusted odds ratio (aOR) of 1.95 (95% CI 1.56-2.45) when compared to the lowest. This association was mainly driven by an association between self-perceived hyperactivity and migraine with aura. The aOR for migraine with aura was 2.83 (95% CI 2.23-3.61) for students in the highest quintile of hyperactivity. No significant association was found for any attention and hyperactivity symptom level measure and non-migraine headache and between self-perceived levels of attention deficit and migraine., Conclusions: Among students in higher education in France, self-perceived levels of attention deficit and hyperactivity symptoms were selectively associated with migraine. The association was strongest for the hyperactivity domain and migraine with aura.

Background and Objective: Some individuals with migraine report the presence of speech changes during their migraine attacks. The goal of this study was to compare objective features of speech during the migraine pre-attack, the migraine attack, and during the interictal period., Methods: This was a prospective, longitudinal, observational study of adults with episodic migraine and healthy non-migraine controls. Participants provided speech samples three times per day using a speech elicitation tool included within a mobile app. Six complementary speech features that capture articulation and prosody were extracted from speech samples. Participants with migraine maintained a daily headache diary using the same app. A mixed effects model and t-tests were used to investigate differences in speech features between controls, the migraine pre-attack phase, the migraine attack, and the interictal period., Results: In total, 56,767 speech samples were collected, including 43,102 from 15 individuals with migraine and 13,665 from matched healthy controls. Significant group-level differences in speech features were identified between those with migraine and healthy controls and within the migraine group during the pre-attack vs. attack vs. interictal periods (all p < .05). Most consistently, speech changes occurred in the speaking rate, articulation rate and precision, and phonatory duration. Within-subject analysis revealed that seven of 15 individuals with migraine showed significant change in at least one speech feature when comparing the migraine attack vs. interictal phase and four showed similar changes when comparing the pre-attack vs. interictal phases., Conclusions: Changes in speech occurred in almost half of the individuals during migraine attacks. Once confirmed in subsequent studies, speech changes could be considered a feature of the migraine attack.

Introduction: Osmophobia has been suggested as an additional symptom of migraine without aura, and a high prevalence of osmophobia of up to 50% has been reported in the literature. We conducted a nosographic study of osmophobia in all migraineurs and tension-type headache patients and a field testing of suggested diagnostic criteria of osmophobia, presented in the appendix of the second edition of The International Classification of Headache Disorders and suggested by Silva-Néto et al. and Wang et al ., in migraine without aura and tension-type headache patients (n = 1934)., Materials and Methods: Each patient received a validated semi-structured interview. All subjects fulfilled the diagnostic criteria of the second edition of The International Classification of Headache Disorders for migraine or tension-type headache. Statistical analyses were performed using statistical software R. The statistical R package "Caret" was used to construct a confusion matrix and retrieve sensitivity, which is defined as the suggested criteria's ability to correctly diagnose migraine without aura patients, and specificity, defined as the suggested criteria's ability to not wrongly diagnose tension-type headache patients., Results: Osmophobia was present in 33.5% of patients with migraine with aura, in 36.0% of patients with migraine without aura, and in 1.2% of patients with tension-type headache. All migraineurs with osmophobia also fulfilled the current criteria for migraine by having nausea or photophobia and phonophobia. The appendix criteria had a sensitivity of 0.96 and a specificity of 0.99 for migraine without aura, and a sensitivity of 0.65 and a specificity of 0.99 for probable migraine without aura. Both the criteria by Silva-Néto et al. and Wang et al. had a sensitivity of 0.98 and a specificity of 0.99 for migraine without aura, and a sensitivity of 0.66 and a specificity of 0.99 for probable migraine without aura., Discussion: This study demonstrates the remarkable specificity of osmophobia. The criteria by Silva-Néto et al. and Wang et al. both had a higher sensitivity than the appendix criteria for migraine without aura; all three criteria had a low sensitivity for probable migraine without aura. However, neither the appendix criteria nor the criteria by Silva-Néto et al. or Wang et al. added any extra patients that would not have been diagnosed by the current diagnostic criteria for migraine. Osmophobia is a valuable symptom that may be useful to differentiate between migraine without aura and tension-type headache in difficult clinical cases., Conclusion: Our results do not suggest that alterations of the current diagnostic criteria for migraine without aura are needed.

Objective: To assess the presence and handicap due to vestibular symptoms in three subgroups of patients with migraine and controls., Methods: Women between 18-55 years old were diagnosed by headache specialists and stratified as migraine with aura (n = 60), migraine without aura (n = 60), chronic migraine (n = 60) and controls (n = 60). Information regarding demographics, headache and vestibular symptoms were collected in this cross-sectional study. The self-perceived handicap related to vestibular symptoms was assessed through the Dizziness Handicap Inventory questionnaire., Results: A total of 85% of women with migraine with aura and chronic migraine had vestibular symptoms contrasted to 70% of the migraine without aura group ( p < 0.05), and 12% of the control group reported symptoms ( p < 0.0001). Patients with migraine exhibited greater Dizziness Handicap Inventory scores than controls ( p < 0.001); and migraine with aura and chronic migraine groups reached greater scores than migraine without aura ( p < 0.01). Presence of migraine is associated with a greater risk of vestibular symptoms (migraine without aura: 5.20, migraine with aura: 6.60, chronic migraine:6.20, p < 0.0003) and with a greater risk of moderate-to-severe handicap (migraine without aura: 20.0, migraine with aura: 40.0, chronic migraine: 40.0, p < 0.0003). The presence of aura and greater migraine frequency adds to the risk of any handicap (migraine with aura: 1.9, chronic migraine: 1.7, p < 0.04) and to the risk of moderate-to-severe handicap (migraine with aura: 2.0, chronic migraine: 2.0, p < 0.0003). Migraine aura, intensity and frequency predict 36% of the dizziness handicap., Conclusion: The prevalence of vestibular symptoms is increased in migraine during and between headache attacks, particularly in migraine with aura and chronic migraine along with an increased handicap due to those symptoms. Vestibular symptoms among subgroups of migraine should be considered when evaluating the functional impact of migraine.

Background: Allodynia is prevalent in adults with migraine and has been associated with long disease duration and severe course. Studies of the pediatric population are sparse. The aim of this study was to evaluate the rate of cephalic cutaneous allodynia in children and adolescents within the first 6 months of migraine onset and to identify associated clinical and migraine-related parameters., Methods: The electronic database of a tertiary pediatric headache clinic from 2014 to 2017 was retrospectively searched for all children and adolescents diagnosed with migraine headache within 6 months or less of symptom onset. Cephalic cutaneous allodynia was identified by validated questionnaire. Demographics, symptoms, and headache-related parameters were compared between patients with and without allodynia., Results: The cohort included 119 patients, 69 girls (58.0%) and 50 (42.0%) boys, of mean age 11.6 ± 3.6 years. Mean time since onset of migraine disease was 3.6 ± 1.8 months. Cephalic cutaneous allodynia was reported by 31.1% of patients. It was significantly associated with female gender ( p = 0.03), older age at admission ( p = 0.037), older age at onset ( p = 0.042) migraine with aura ( p = 0.002), and higher rate of awakening pain ( p = 0.017)., Conclusions: Cephalic cutaneous allodynia may occur in children and adolescents already in the first 6 months of migraine onset. Contrary to adult studies, we found no association of allodynia with migraine frequency or long disease duration. Allodynia was significantly associated with migraine with aura, female gender, and awakening pain. A genetic tendency may contribute to the appearance of allodynia in the pediatric age group.

Background: There are cases in the headache literature described as "cluster-migraine," but none of stereotyped cases of cluster headache evolving into status migrainosus. We believe this is the first documented case of "cluster-status migrainosus"., Case: A 54 year-old female hospital administrator presented with headaches with a unique periodicity and semiology that were acutely responsive to high-flow oxygen. She experienced cluster headache attacks every Thursday morning at 3-4 am, which would evolve into status migrainosus lasting through Sunday evening. These attacks were preceded by prodromal depressed mood changes and fluid retention, and later followed by postdromal euphoria and auto-diuresis. These attacks initially occurred every other week and progressed to weekly attacks for 1.5 years. These headaches did not respond to trials of propanolol, sodium valproate, topiramate, amitriptyline, gabapentin, and carbamazepine for preventive treatment or to oral sumatriptan and butalbital-acetaminophen-caffeine for acute treatment. We started her on high-flow 100% oxygen for cluster headache, which successfully aborted greater than 80% of her weekly cluster headache attacks and prevented them from evolving into status migrainosus., Conclusion: We believe this is the first case of "cluster-status migranosus" described in the medical literature. High-flow oxygen both aborted the cluster headaches and prevented the ensuing status migrainosus.

Background Few studies have examined whether migraine is associated with an increased risk of incident hypertension. Methods We performed a prospective cohort study among 29,040 women without hypertension at baseline. Women were classified as having active migraine with aura, active migraine without aura, a past history of migraine, or no history of migraine. Incident hypertension was defined as new physician diagnosis or newly self-reported systolic or diastolic blood pressure ≥140 mmHg or ≥90 mmHg respectively. Cox proportional hazards models were used to evaluate the association between migraine and incident hypertension. Results During a mean follow-up of 12.2 years, 15,176 incident hypertension cases occurred. Compared to those with no history of migraine, women who experience migraine with aura had a 9% increase in their risk of developing hypertension (95% CI: 1.02, 1.18); women who experience migraine without aura had a 21% increase in their risk of developing hypertension (95% CI: 1.14, 1.28); and women with a past history of migraine had a 15% increase in their risk of developing hypertension (95% CI: 1.07, 1.23). Conclusions Women with migraine have a higher relative risk of developing hypertension compared to women without migraine.

Aim To evaluate aerobic exercise in migraine and co-existing tension-type headache and neck pain. Methods Consecutively recruited persons with migraine and co-existing tension-type headache and neck pain were randomized into an exercise group or control group. Aerobic exercise consisted of bike/cross-trainer/brisk walking for 45 minutes, three times/week. Controls continued usual daily activities. Pain frequency, intensity, and duration; physical fitness, level of physical activity, well-being and ability to engage in daily activities were assessed at baseline, after treatment and at follow-up. Results Fifty-two persons completed the study. Significant between-group improvements for the exercise group were found for physical fitness, level of physical activity, migraine burden and the ability to engage in physical activity because of reduced impact of tension-type headache and neck pain. Within the exercise group, significant reduction was found for migraine frequency, pain intensity and duration, neck pain intensity, and burden of migraine; an increase in physical fitness and well-being. Conclusions Exercise significantly reduced the burden of migraine and the ability to engage in physical activity because of reduced impact of tension-type headache and neck pain. Exercise also reduced migraine frequency, pain intensity and duration, although this was not significant compared to controls. These results emphasize the importance of regular aerobic exercise for reduction of migraine burden.

Background The association between migraine and cognitive performance is unclear. We analyzed whether migraine is associated with cognitive performance among participants of the Brazilian Longitudinal Study of Adult Health, ELSA-Brasil. Methods Cross-sectional analysis, including participants with complete information about migraine and aura at baseline. Headache status (no headaches, non-migraine headaches, migraine without aura and migraine with aura), based on the International Headache Society classification, was used as the dependent variable in the multilinear regression models, using the category "no headache" as reference. Cognitive performance was measured with the Consortium to Establish a Registry for Alzheimer's Disease word list memory test (CERAD-WLMT), the semantic fluency test (SFT), and the Trail Making Test version B (TMTB). Z-scores for each cognitive test and a composite global score were created and analyzed as dependent variables. Multivariate models were adjusted for age, gender, education, race, coronary heart disease, heart failure, hypertension, diabetes, dyslipidemia, body mass index, smoking, alcohol use, physical activity, depression, and anxiety. In women, the models were further adjusted for hormone replacement therapy. Results We analyzed 4208 participants. Of these, 19% presented migraine without aura and 10.3% presented migraine with aura. All migraine headaches were associated with poor cognitive performance (linear coefficient β; 95% CI) at TMTB -0.083 (-0.160; -0.008) and poorer global z-score -0.077 (-0.152; -0.002). Also, migraine without aura was associated with poor cognitive performance at TMTB -0.084 (-0.160, -0.008 and global z-score -0.077 (-0.152; -0.002). Conclusion In participants of the ELSA-study, all migraine headaches and migraine without aura were significantly and independently associated with poorer cognitive performance.

Background and objectives Abdominal pain is a well-known headache-associated symptom in migraine in children, but rarely in adults. We describe a case of a female patient with typical accompanying migraine symptoms without headache but with thoracic pain. Case report The present case of a 41 year-old-woman shows recurrent attacks with thoracic pain and typical accompanying migraine symptoms but without headache. Symptoms resolved upon treatment with triptans and beta blockers. Discussion This case might be interpreted as "thoracic migraine", and extends the spectrum of migraine forms. Conclusion In patients with facial pain secondary to lung cancer, an anatomical connection between the vagal nerve, the nucleus tractus solitarii, the jugular ganglion and trigeminal system has been suggested. The present case might be an analogy to this explanation.

Introduction Cognitive symptoms have been described during migraine attacks since the Roman era; while being neglected throughout the centuries, they are relevant contributors to migraine-related disability. Objective To determine whether cognitive symptoms are included in clinical series describing migraine attack phenomenology, and which symptoms occur in each attack phase. Method Systematic review of existing data on clinical descriptions of migraine attacks, focusing on cognitive symptomatology. Data were organized and analyzed qualitatively, due to methodological differences between studies. Results Twenty-four articles were reviewed, with a total sample of 7007 patients, including 82.9% females with an average age of 39.2 years. Twenty one (75%) studies analyzed one phase of the attack (eight prodromes, five auras, one between aura and pain, three headaches and three postdromes), the remaining studied more than one phase. Cognitive complaints were the most frequent symptom of the prodromic (30%) and headache (38%) phases, while fatigue (70%) dominated the resolution phase. Not enough data is available to estimate the frequency of cognitive symptoms during the aura. Discussion Cognitive symptoms are described in all phases of the migraine attack phenomenology in published clinical series of migraine. Their characteristics appear to be different in each attack phase, although methodological limitations prevent generalization of this finding.

Objective The aim of this project was to evaluate the prevalence and pattern of musculoskeletal dysfunctions in migraine patients using a rigorous methodological approach and validating an international consensus cluster of headache assessment tests. Methods A physiotherapist, blinded towards the diagnosis, examined 138 migraine patients (frequent episodic and chronic), recruited at a specialised headache clinic, and 73 age and gender matched healthy controls following a standardised protocol. Eleven tests, previously identified in an international consensus procedure, were used to evaluate cervical and thoracic musculoskeletal dysfunctions. Results Primary analyses indicated statistically significant differences across groups for the total number of trigger points, flexion-rotation test, thoracic screening, manual joint testing of the upper cervical spine, cranio-cervical flexion test, and reproduction and resolution. Ninety three percent of the assessed patients had at least three musculoskeletal dysfunctions. Post-hoc tests showed significant differences between episodic or chronic migraine patients and healthy controls, but not between migraine groups. Conclusions A standardised set of six physical examination tests showed a high prevalence of musculoskeletal dysfunctions in migraine patients. These dysfunctions support a reciprocal interaction between the trigeminal and the cervical systems as a trait symptom in migraine.

Background The association between RLS and migraine is still debated. The aim of this study is to investigate the prevalence and grade of RLS in Chinese patients with migraine and to evaluate the relationship between RLS and migraine. Methods A multi-center case-control study of contrast-enhanced transcranial Doppler was conducted in 931 consecutive patients with migraine (240 of 931 had migraine with aura and 691 of 931 were in the migraine without aura group) and 282 were healthy adults. Clinical trial no. NCT02425696. Results The prevalence of RLS was 63.8% and 39.9% in the migraine with aura group (MA+) and migraine without aura group (MA-), respectively, significantly higher than that of the healthy group (29.4%, p < 0.001; p < 0.001). The positive rate of large RLS in the MA+ group and MA- group was 32.1% and 16.5%, respectively, significantly higher than healthy group (6.4%, p < 0.001; p < 0.001). There was no difference among groups in terms of positive rate of permanent RLS ( p = 0.704). Conclusion This multi-centre case-control study suggested that there is an association between RLS and migraine with and without aura, especially when the shunt is large.

Background Cranial autonomic parasympathetic symptoms (CAPS) appear in at least half of migraine patients theoretically as a result of the release of peptides by the trigemino-vascular system (TVS). Cranial pain pathways become sensitised by repeated episodes of TVS activation, leading to migraine chronification. Objective The objective of this article is to correlate the presence of CAPS with serum levels of vasoactive intestinal peptides (VIP) and calcitonin gene-related peptide (CGRP). Patients and methods Patients with chronic migraine (CM) were asked about the presence - during migraine attacks - of five CAPS, which were scored from 0 to 10 by using a quantitative scale. Serum VIP and CGRP levels were determined by ELISA. Results We interviewed 87 CM patients (82 females; mean age 44.7 ± 10.6 years). Seventeen had no CAPS, while 70 reported at least one CAPS. VIP levels ranged from 20.8 to 668.2 pg/ml (mean 154.5 ± 123.2). There was a significant positive correlation between scores in the CAPS scale and VIP levels (Spearman correlation coefficient = 0.227; p = 0.035). VIP levels were significantly higher in CM patients by at least one point in the scale vs those with 0 points ( p = 0.002). Analysing symptoms individually, VIP levels were numerically higher in those patients with symptoms, though they were significantly higher only in those patients with lacrimation vs those without it ( p = 0.013). There was no significant correlation between CGRP levels and the score in the CAPS scale. Conclusions Serum VIP, but not CGRP, levels seem to reflect the rate of activation of the parasympathetic arm of the TVS in migraine.

Background Autonomic dysfunction and light sensitivity are core features of the migraine attack. Growing evidence also suggests changes in these parameters between attacks. Though sensory and autonomic responses likely interact, they have not been studied together across the spectrum of disease in migraine. Methods We performed digital infrared pupillometry while collecting interictal photophobia thresholds (PPT) in 36 migraineurs (14 episodic; 12 chronic; 10 probable) and 24 age and sex-matched non-headache controls. Quantitative pupillary light reflexes (PLR) were assessed in a subset of subjects, allowing distinction of sympathetic vs parasympathetic pupillary function. A structured questionnaire was used to ascertain migraine diagnosis, headache severity, and affective symptoms. Results Photophobia thresholds were significantly lower in migraineurs than controls, and were lowest in chronic migraine, consistent with a disease-related gradient. Lower PPT correlated with smaller dark-adapted pupil size and larger end pupil size at PPT, which corresponded to a reduced diameter change. On PLR testing, measures of both parasympathetic constriction and sympathetic re-dilation were reduced in migraineurs with clinically severe migraine. Conclusions In summary, we show that severity of photophobia in migraine scales with disease severity, in association with shifts in pupillary light responses. These alterations suggest centrally mediated autonomic adaptations to chronic light sensitivity.

Background The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. Method A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Results Both cohorts ( n = 119,017 each) were followed for a mean period of 3.6 ± 1.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. Compared to the comparison cohort, patients with migraine were at an increased risk of ischemic stroke (aHR: 1.24, 95% CI: 1.12-1.38, p < 0.001). Subgroup analysis by age and sex revealed the highest risk in women aged ≤ 45 years (aHR: 3.44, 95% CI: 2.20-5.39, p < 0.001), especially among those with migraine with aura (aHR: 4.58, 95% CI: 2.45 - 8.56, p < 0.001). A trend for increased stroke risk was observed in men aged ≤ 45 years (aHR: 1.54, 95% CI: 0.96-2.48, p = 0.075). Conclusion Migraine is associated with an increased risk of ischemic stroke, especially in younger (age ≤ 45 years) women with migraine with aura. The trend toward ischemic stroke in younger men merits further exploration.

Background Migraine-tic syndrome was first reported in 2004 in a 44-year-old woman who had concomitant symptoms of both typical trigeminal neuralgia and migraine. We report here two further cases of migraine-tic syndrome and speculate on the relevance of this condition to the pathophysiology of headache. Case reports A 43-year-old woman presented with typical trigeminal neuralgia symptoms that preceded the onset of migraine headache; both headache types responded to treatment with sumatriptan. A 35-year-old woman presented with trigeminal neuralgia that consistently followed the onset of migraine headache. The former aspect responded to baclofen, but the migraine headache required treatment with amitriptyline. Discussion These two patients provide further support for the presence of an overlap syndrome of migraine-tic. We suggest that there is a common pathway for trigeminal neuralgia and migraine.

Background Migraine is a common neurological condition that often involves differences in visual processing. These sensory processing differences provide important information about the underlying causes of the condition, and for the development of treatments. Review of psychophysical literature Psychophysical experiments have shown consistent impairments in contrast sensitivity, orientation acuity, and the perception of global form and motion. They have also established that the addition of task-irrelevant visual noise has a greater effect, and that surround suppression, masking and adaptation are all stronger in migraine. Theoretical signal processing model We propose utilising an established model of visual processing, based on signal processing theory, to account for the behavioural differences seen in migraine. This has the advantage of precision and clarity, and generating clear, falsifiable predictions. Conclusion Increased effects of noise and differences in excitation and inhibition can account for the differences in migraine visual perception. Consolidating existing research and creating a unified, defined theoretical account is needed to better understand the disorder.

Background: Migraine attacks may present different features in different patients and also within the same patient. The percentage of patients reporting stereotyped attacks and those reporting attacks with different phenotypes has not been the object of specific investigations., Objective: The objective of this article is to evaluate the percentage of migraine patients reporting the same characteristics, in terms of phenotype and response to symptomatic medications on three consecutive migraine attacks., Methods: Thirty patients with migraine without aura prospectively recorded the features of three consecutive attacks in a headache diary. Characteristics recorded were: pain intensity, presence of nausea, vomiting, photophobia, phonophophia, osmophobia, allodynia, cranial autonomic symptoms (at least one), and premonitory symptoms. Patients were allowed to take frovatriptan as symptomatic medication, whose efficacy was evaluated as the two hours pain-free status., Results: None of the patients presented identical characteristics on the three studied attacks. This was still the case if we reduced the number of variables evaluated from 11 to seven of the eight core features indicated by the ICHD. Considering just six variables: unilaterality and quality of pain, presence/absence of nausea, vomiting, photophobia and phonophobia, only two patients (6%) had identical features on three consecutive attacks.With respect to the response to frovatriptan, 39% of patients had the same response, either positive (i.e. pain free after two hours) or negative (i.e. not pain free after two hours) on three consecutive attacks., Conclusion: Migraine attacks show a high variability not just among patients, but also within the same patient. Our data indicate that stereotypy of attacks is uncommon, and reinforces the underlying logic of the current operational classification system., (© International Headache Society 2015.)