Search

Purpose of Review This study explores legal aspects of migraine in the workplace. While the high prevalence of migraine is well-documented, its effects on the livelihoods of those living with the disease are less understood. Because migraine symptoms are often invisible, discussions concerning migraine in the workplace can be challenging. What are the rights of persons with migraine in the workplace? Time off may provide a brief respite, but it is not a long-term solution. Claiming disability for migraine has challenges, including barriers to doing so and required paperwork. How can persons with migraine remain employed and productive? How can persons with migraine receive accommodation from their employer or take time off to treat their condition? Recent Findings Many employers offer comprehensive benefit packages that allow for sick days, time off, mental health days, and accommodations that may give persons with migraine temporary reprieve. However, it may not be sufficient, particularly for those with chronic migraine. Further, not all employers offer comprehensive benefits. Employees with migraine may need to seek protection under the law. Our research closely examines the primary legal avenues that persons with migraine may pursue while living and working with migraine. In exploring the legal aspects of migraine, we couple our exploration with relevant case law. Summary Through this lens, we conclude that migraine is becoming less stigmatized and more legitimized in the eyes of the court. It is the belief of the authors that at least some of the change in the attitude towards migraine is the result of strong patient advocacy and significant advances in research over the past several years.

Background and ObjectivesThis study sought to describe migrainous headache frequency and severity and to examine the relationship between trauma, discrimination, and migraine-associated disability in a sample of sexual and/or gender minority (SGM) adults.MethodsWe performed a cross-sectional study of SGM people in The Population Research in Identity and Disparities for Equality Study from August to October 2018. The primary exposure was any trauma or discrimination, regardless of attribution. The primary outcome was moderate-severe migraine disability, as defined by a Migraine Disability Assessment (MIDAS) Questionnaire score of ≥11. We performed descriptive analysis comparing respondents with any migrainous headache with those without. Multivariable logistic regression examined the association between trauma/discrimination and migraine disability, controlling first for sociodemographic and clinical factors and then for psychiatric comorbidities.ResultsOf the 3,325 total respondents, 1,126 (33.9%) screened positive for migrainous headache by ID-Migraine criteria. Most people with migraine self-reported moderate (n = 768, 68.2%) or severe (n = 253, 22.5%) intensity. The median MIDAS score was 11 (interquartile range 5–25). Most respondents with migraine (n = 1,055, 93.7%) reported a history of trauma or discrimination. In unadjusted analysis, exposure to both trauma and discrimination was associated with higher odds of moderate-severe disability (OR 1.76, 95% CI 1.34–2.32). After adjustment for self-reported psychiatric comorbidities of anxiety, depression, and posttraumatic stress disorder, this association lost statistical significance.DiscussionMigrainous headache is common among our sample of SGM adults, and prior experiences with trauma and discrimination are associated with increased migraine disability. Our findings suggest that psychiatric comorbidities play a significant role in this relationship, identifying a potentially modifiable risk factor for disability in SGM people with migraine.

BackgroundMonoclonal antibodies to calcitonin gene-related peptide or its receptor have clinical trial evidence in adults with headache, but data are lacking in adolescents. The objective of this study was to describe the safety and efficacy of calcitonin gene-related peptide monoclonal antibody treatment in adolescents with chronic headache disorders.MethodsWe performed a retrospective multisite cohort study of patients less than 18years of age who received a calcitonin gene-related peptide monoclonal antibody for headache prevention. Demographics, baseline headache characteristics, efficacy, and side effect data were collected.ResultsThe study population comprised 112 adolescents who received at least one dose of a calcitonin gene-related peptide monoclonal antibody. Mean (S.D.; range) age at first dose was 15.9years (1.4; 10.3 to 17.8). Ninety-four patients (83.9%) had chronic migraine, 12 (10.7%) had new daily persistent headache, and six (5.4%) had persistent post-traumatic headache. At baseline, the mean (S.D.) number of headache days per month was 26.9 (6.1) (n=109) and headache was continuous in 75 of 111 (67.6%). At first follow-up visit there was a significant reduction in headache frequency compared with baseline (-2.0days; 95% confidence interval,-0.8 to-3.2). Significant benefit was perceived by 29.5% of patients at first follow-up visit (n=33/112) and 30.1% (n=22/73) at second follow-up visit. A significant functional improvement was perceived by 31% of patients (n=31/94) at the first follow-up visit and 22.4% (n=15/67) at the second follow-up visit. The most common side effects were injection site reactions in 17.0% (n=19) and constipation in 8.0% (n=9). Five patients (4.5%) discontinued because of side effects.ConclusionsSide effects with calcitonin gene-related peptide monoclonal antibody treatment in adolescents were similar to those reported in adult trials. Calcitonin gene-related peptide monoclonal antibody treatment appears to benefit a proportion of adolescents with chronic refractory headache disorders.

ObjectiveTo determine whether high school start time is associated with headache frequency in adolescents with migraine.BackgroundAdolescence is marked by a physiologic delayed circadian phase, characterized by later bedtimes and wake times. The American Academy of Pediatrics (AAP) recommends that high schools start no earlier than 8:30a.m., but most high schools in the United States start earlier. The study hypothesis was that adolescents with migraine whose high schools start at 8:30a.m. or later (late group) would have lower headache frequency than those whose schools start earlier than 8:30a.m. (early group).MethodsThis was a cross-sectional Internet survey study of US high schoolers with migraine recruited online through social media. Comparisons were made between the late group and the early group. The primary outcome measure was self-reported headache days/month.ResultsIn total, 1012 respondents constituted the analytic set: n=503 in the late group versus n=509 in the early group. Mean (SD) self-reported headache days/month was 4.8 (4.6) versus 7.7 (6.1) in the late and early groups, respectively (p&nbsp

The pathophysiology of migraine remains to be elucidated. We have recently shown that interictal migraineurs exhibit reduced fractional anisotropy (FA) in the root entry zone of the trigeminal nerve when compared to controls, but it is not known if this altered nerve anatomy is associated with changes within the brainstem or higher cortical brain regions. Diffusion tensor imaging of the brain was used to calculate regional measures of structure, including mean diffusivity (MD), axial diffusivity (AX) and radial diffusivity (RD) in addition to voxel-based morphometry of T1-weighted anatomical images. Linear relationships between trigeminal nerve anatomy (FA) and MD throughout the brainstem and/or higher cortical regions were determined in both controls (n = 31, brainstem; n = 38, wholebrain) and interictal migraineurs (n = 32, brainstem; n = 38, wholebrain). Additionally, within the same brain areas, relationships of AX and RD with nerve FA were determined. We found that in both interictal migraine and control participants, decreasing trigeminal nerve FA was associated with significantly increased MD in brainstem regions including the spinal trigeminal nucleus and midbrain periaqueductal gray matter (PAG), and in higher brain regions such as the hypothalamus, insula, posterior cingulate, primary somatosensory and primary visual (V1) cortices. Whereas, both control and migraineur groups individually displayed significant inverse correlations between nerve FA and MD, in migraineurs this pattern was disrupted in the areas of the PAG and V1, with only the control group displaying a significant linear relationship (PAG controls r = –0.58, p = 0.003; migraineurs r = –0.25, p = 0.17 and V1 controls r = −0.52, p = 0.002; migraineurs r = –0.10, p = 0.55). Contrastingly, we found no gray matter volume changes in brainstem or wholebrain areas. These data show that overall, trigeminal nerve anatomy is significantly related to regional brain structure in both controls and migraineurs. Importantly, the PAG showed a disruption of this relationship in migraineurs suggesting that the anatomy and possibly the function of the PAG is uniquely altered in episodic migraine, which may contribute to altered orofacial pain processing in migraine.

Introduction Gender medicine is a new medical approach aimed at the study of the differences between women and men in terms of prevention, diagnosis, and the outcome of all diseases. Migraines are among these. They represent the most common neurological illness; they are most prevalent in adults between 20 and 50 years of age and are three to four times more frequent in woman than in men. Affecting people in working age, migraines are a problem that strongly impacts the psychophysical health and productivity of workers, regardless of the specific job task they have. Methods A narrative review was performed, searching for the most relevant articles describing gender differences in people suffering from migraines, and particularly in workers. Results Migraine global prevalence is 20.7% in women and 9.7% in men whereas prevalence in Italy is 32.9% for women and only 13.0% for men. This difference is partly explained by hormonal differences, as well as by differences in brain structure, genetic polymorphisms and neuronal pathways. Sex differences may also play a role in the progression from episodic to chronic migraine. In workers, migraines are mostly associated with strenuous physical work in men, whilst migraines triggered by night shifts, lack of sleep, or irregular sleep patterns are more common in women. Conclusions To this day, the reasons of sex/gender disparity for migraine are still obscure. However, migraines, chronic migraine in particular, have a negative impact on the lives of all individuals affected by this disease, but particularly in women in which family cares and working activity are often superimposed. Migraine prevention strategies should be planned in workers through the occupational health physician.

Background The precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli. Methods Functional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity. Results Despite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons. Conclusions These data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.

BackgroundBenign paroxysmal torticollis (BPT) is characterized by attacks of head tilt associated with vomiting, irritability, and/or ataxia in early childhood. BPT is associated with migraine but risk factors are unknown. Impact on quality of life is also unknown.MethodsParents/caregivers of children with ongoing or resolved BPT participated in telephone interviews (n = 73). Those with ongoing BPT completed the Infant Toddler Quality of Life questionnaire (ITQoL).ResultsMedian age of children at the time of interview was 2.9 years (range 0.25-23). BPT was ongoing in 52% (n = 38). Nineteen percent (n = 14) developed migraine (median age 9.25 years, range 2.5-23) and 63% (n = 46) developed another episodic syndrome associated with migraine. Proportion of patients who developed migraine was higher among those with certain migrainous symptoms during BPT attacks vs. those without: phonophobia (58 vs. 21%, p = 0.02), photophobia and phonophobia (55 vs. 23%, p = 0.05), and photophobia, phonophobia, and motion sensitivity (60 vs. 22%, p = 0.02). ITQoL results showed significant impact of BPT on quality of life.ConclusionsChildren with BPT may develop migraine or other episodic syndromes associated with migraine. Presence of migrainous features during BPT episodes may increase likelihood of developing migraine. Though characterized as "benign," BPT can significantly impact children and families.ImpactBenign paroxysmal torticollis (BPT) is a rare condition of early childhood characterized by episodes of head tilt associated with vomiting, irritability, ataxia, pallor, and/or malaise. This cohort study describes the phenotypic spectrum of BPT, variable treatment, natural history and association with migraine, and impact on development and quality of life. Children with BPT may go on to develop migraine or episodic syndromes that may be associated with migraine; presence of migrainous features during attacks may increase odds of developing migraine. BPT can have significant impact on quality of life, demonstrated by findings from the Infant Toddler Quality of Life questionnaire.

Author(s): Goshtasbi, Khodayar; Abouzari, Mehdi; Risbud, Adwight; Mostaghni, Navid; Muhonen, Ethan G; Martin, Elaine; Djalilian, Hamid R | Abstract: ObjectivesTo investigate whether migraine is independently associated with tinnitus and subjective hearing loss (HL) in a large national database.MethodsThe de-identified 1999 to 2004 National Health and Nutrition Examination Survey database was retrospectively queried for subjects aged 18 to 65. HL and tinnitus were subjectively reported by subjects.ResultsA total of 12,962 subjects (52.9% female) with a mean age of 38.1 ± 14.6 years were included. This consisted of 2,657 (20.5%), 2,344 (18.1%), and 2,582 (19.9%) subjects who had migraine, subjective-HL, and tinnitus, respectively. In patients with tinnitus or subjective-HL, migraine was reported in 35.6% and 24.5%, respectively. Migraineurs were more likely to have subjective-HL (25.0% vs. 16.6%, p l 0.001) and tinnitus (34.6% vs. 16.9%, p l 0.001) compared to the nonmigraineurs. This corresponded to migraine having an odds ratio of 1.5 (95% confidence interval [CI] 1.3-1.7, p l 0.001) and 2.2 (95% CI 2.0-2.4, p l 0.001) for subjective-HL and tinnitus, respectively. After adjusting for confounders, subjective-HL (odds ratio [OR] = 1.2, 95% CI 1.1-1.4, p = 0.003), tinnitus (OR = 2.1, 95% CI 1.9-2.3, p l 0.001), and neck pain (OR = 4.0, 95% CI 3.6-4.5, p l 0.001) were more common in migraineurs. Among migraineurs, a higher proportion of those with tinnitus also had subjective-HL compared to those without tinnitus (40.0% vs. 15.3%, p l 0.001), and a higher proportion of those with subjective-HL also had tinnitus compared to those without HL (58.1% vs. 27.3%, p l 0.001).ConclusionsThis study suggests an independent association between migraine with subjective-HL and tinnitus. Otologic migraine, which is the effects of migraine on the ear, may be partly responsible for the link between HL, tinnitus, neck pain, and migraine.

Author(s): Risbud, Adwight; Muhonen, Ethan G; Tsutsumi, Kotaro; Martin, Elaine C; Abouzari, Mehdi; Djalilian, Hamid R | Abstract: ObjectiveTo compare the presence of migraine features between patients with isolated aural fullness (AF) who meet the diagnostic criteria for migraine headache and those who do not, and to propose diagnostic criteria for migraine-related AF based on our results.MethodsWe performed a retrospective study of patients presenting to a tertiary-care neurotology clinic between 2014 and 2020 with migraine-related AF. This was defined as isolated, prolonged aural fullness concurrent with migraine features once other etiologies were ruled out via examination, audiometry, and imaging. Migraine features were compared between patients meeting the diagnostic criteria for migraine headache and those not meeting the criteria.ResultsSeventy-seven patients with migraine-related AF were included. The mean age was 56 ± 15 years and 55 (71%) patients were female. Eleven (14%) patients fulfilled the criteria for migraine headache (migraine group). Of the 66 patients who did not meet the criteria (nonmigraine group), 17 (26%) met 4/5 criteria, and 32 (48%) met 3/5 criteria, for a total of 49 (74%) patients. The migraine and nonmigraine groups were only different in 5 of 20 features, including family history of migraine (p = 0.007), sound sensitivity (p l 0.001), mental fogginess (p = 0.008), visual motion sensitivity (p = 0.008), and light sensitivity (p l 0.001).ConclusionThere are minimal differences in the overall prevalence of migraine features between patients with migraine-related AF who meet and do not meet the diagnostic criteria for migraine. Our findings suggest that the criteria may be too stringent and exclude many patients from potentially benefitting from treatment with migraine prophylaxis.

Introduction: Sensitisation of the nervous system in a patient with migraine is supposed to be associated with calcitonin gene-related peptide (CGRP) activity. Therefore, the vascular response to human αCGRP (hαCGRP) could be a surrogate marker for the sensitization. We hypothesize that vascular response to hαCGRP is augmented in a patient with migraine. Methods: Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in the middle cerebral artery (vm MCA). Simultaneously, end-tidal CO2 (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. The reconstruction of the signals was made for basal conditions, during and after CGRP infusion which were compared using statistics. Results: In both groups, we found significant decrease between measurement points of vm MCA and Et-CO2 during and after hαCGRP infusion. MAP did not show significant trends during the infusion, but it was significantly increased after the infusion in migraine patients only. Responses to hαCGRP, defined as differences between two measurement points, were significantly higher for vm MCA and Et-CO2 in patients with migraine. A significant difference between groups was found in MAP response. Significant relationships were found between migraine and vm MCA, Et-CO2, and MAP. Conclusion: In patients with migraine, vm MCA responses to hαCGRP are significantly higher and are associated with CGRP-induced headache which indicates that patients with migraine are more prone to sensitization.

Highlights • Individual migraineurs’ brainstem function alters through the migraine cycle. • Functional changes occurred in the 24-hour period immediately prior to a migraine. • Greater resting activity variability was found in the SpV, pons and PAG. • Increased infra-slow oscillations and regional homogeneity in the SpV and pons., Although the mechanisms responsible for migraine initiation remain unknown, recent evidence shows that brain function is different immediately preceding a migraine. This is consistent with the idea that altered brain function, particularly in brainstem sites, may either trigger a migraine or facilitate a peripheral trigger that activates the brain, resulting in pain. The aim of this longitudinal study is therefore to expand on the above findings, and to determine if brainstem function oscillates over a migraine cycle in individual subjects. We performed resting state functional magnetic resonance imaging in three migraineurs and five controls each weekday for four weeks. We found that although resting activity variability was similar in controls and interictal migraineurs, brainstem variability increased dramatically during the 24-hour period preceding a migraine. This increase occurred in brainstem areas in which orofacial afferents terminate: the spinal trigeminal nucleus and dorsal pons. These increases were characterized by increased power at infra-slow frequencies, principally between 0.03 and 0.06 Hz. Furthermore, these power increases were associated with increased regional homogeneity, a measure of local signal coherence. The results show within-individual alterations in brain activity immediately preceding migraine onset and support the hypothesis that altered regional brainstem function before a migraine attack is involved in underlying migraine neurobiology.

OBJECTIVES To identify migraine features present in a cohort of patients with recurrent benign paroxysmal positional vertigo (BPPV). METHODS Patients presenting with recurrent BPPV were surveyed. Recurrent BPPV was defined as three episodes or greater in 6 months before presentation, with resolution of symptoms after Epley maneuver. Current or past migraine headache (MH) diagnosis was made according to the International Headache Society guidelines. RESULTS Fifty-eight patients with recurrent BPPV with a mean age of 53.8 ± 17.4 years were included. Half (29 patients) fulfilled criteria for MH and half (29 patients) did not meet the criteria for MH (non-MH). No statistically significant difference was found in a majority of migraine-related symptoms between the MH and non-MH cohorts with recurrent BPPV. History of migraine medication usage (p = 0.008), presence of a weekly headache (p = 0.01), and duration of dizziness after positional vertigo (p = 0.01) were the only variables that were different on multivariate analysis between the MH and non-MH cohorts. CONCLUSIONS Half of recurrent BPPV patients suffer from migraine headaches. The other half presented with migraine-related symptoms, but do not meet criteria for MH. The high comorbidity of MH in our recurrent BPPV cohort as well as the absence of a statistically significant difference in a majority of migraine-related features among patients who did and did not fulfill criteria for MH may suggest that recurrent BPPV has a relationship with migraine. Recurrent BPPV may potentially be a manifestation of migraine in the inner ear, which we term otologic migraine including cochlear, vestibular, or cochleovestibular symptoms.

Background We performed a post hoc, subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled study of erenumab for prevention of episodic migraine (STRIVE) to determine the efficacy and safety of erenumab in women with self-reported menstrual migraine. Methods Patients received placebo, erenumab 70 mg, or erenumab 140 mg subcutaneously once monthly during the 6-month double-blind treatment phase of STRIVE. Women who reported history of menstrual migraine and who were ≤ 50 years old were included in the analysis. Endpoints were change from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD; among patients who took acute migraine-specific medications at baseline), proportion of patients achieving ≥ 50% reduction from baseline in MMD, and incidence of adverse events. Results Among 814 women enrolled in STRIVE, 232 (28.5%) reported a history of menstrual migraine and were ≤ 50 years old. Of the 232 patients, 214 (92%) had a baseline MMD > 5, suggesting a high proportion of women with attacks outside of the 5-day perimenstrual window (2 days before and 3 days after the start of menstruation). Information on “migraine days” includes (and does not discriminate between) perimenstrual and intermenstrual migraine attacks. Between-group differences from placebo over months 4–6 for erenumab 70 mg and 140 mg were − 1.8 (P = 0.001) and − 2.1 (P P = 0.002) and − 2.4 (P P = 0.024) and 2.8 (P = 0.002) times greater for erenumab 70 mg and 140 mg, respectively, than for placebo. Erenumab had an overall safety profile comparable to placebo. Conclusion Data from this subgroup analysis of women with menstrual migraine are consistent with data from the overall STRIVE episodic migraine population, supporting the efficacy and safety of erenumab in women who experience menstrual migraine. Trial registration: ClinicalTrials.gov, NCT02456740. Registered 28 May 2015.

Background There is histological evidence of microstructural changes in the zygomaticotemporal branch of the trigeminal nerve in migraineurs. This raises the possibility that altered trigeminal nerve properties contribute to migraine pathophysiology. Whilst it is not possible to explore the anatomy of small trigeminal nerve branches it is possible to explore the anatomy of the trigeminal root entry zone using magnetic resonance imaging in humans. The aim of this investigation is to assess the microstructure of the trigeminal nerve in vivo to determine if nerve alterations occur in individuals with episodic migraine. Methods In 39 migraineurs and 39 matched controls, T1-weighted anatomical images were used to calculate the volume (mm3) and maximal cross-sectional area of the trigeminal nerve root entry zone; diffusion tensor images were used to calculate fractional anisotropy, mean diffusion, axial diffusion and radial diffusion. Results There were significant differences between the left and right nerve of controls and migraineurs with respect to volume and not cross-sectional area. Migraineurs displayed reduced axial diffusion in the right nerve compared to the left nerve, and reduced fractional anisotropy in the left nerve compared to left controls. Furthermore, although there were no differences in mean diffusion or radial diffusion, regional analysis of the nerve revealed significantly greater radial diffusion in the middle and rostral portion of the left trigeminal nerve in migraineurs compared with controls. Conclusions Migraine pathophysiology is associated with microstructural abnormalities within the trigeminal nerve that are consistent with histological evidence of altered myelin and/or organization. These peripheral nerve changes may provide further insight into migraine pathophysiology and enable a greater understanding for targeted treatments of pain alleviation.

Objectives: To evaluate the efficacy of a multi-modal migraine prophylaxis therapy for patients with hyperacusis. Methods: In a prospective cohort, patients with hyperacusis were treated with a multi-modal step-wise migraine prophylactic regimen (nortriptyline, verapamil, topiramate, or a combination thereof) as well as lifestyle and dietary modifications. Pre- and post-treatment average loudness discomfort level (LDL), hyperacusis discomfort level measured by a visual analogue scale (VAS), and scores on the modified Khalfa questionnaire for severity of hyperacusis were compared. Results: Twenty-two of the 25 patients (88%) reported subjective resolution of their symptoms following treatment. Post-treatment audiograms showed significant improvement in average LDL from 81.3 ± 3.2 dB to 86.4 ± 2.6 dB ( P < .001), indicating increased sound tolerability. The VAS discomfort level also showed significant improvement from a pre-treatment average of 7.7 ± 1.1 to 3.7 ± 1.6 post-treatment ( P < .001). There was also significant improvement in the average total score on modified Khalfa questionnaire (32.2 ± 3.6 vs 22.0 ± 5.7, P < .001). Conclusions: The majority of patients with hyperacusis demonstrated symptomatic improvement from migraine prophylaxis therapy, as indicated by self-reported and audiometric measures. Our findings indicate that, for some patients, hyperacusis may share a pathophysiologic basis with migraine disorder and may be successfully managed with multimodal migraine prophylaxis therapy.

Author(s): Abouzari, Mehdi; Goshtasbi, Khodayar; Chua, Janice T; Tan, Donald; Sarna, Brooke; Saber, Tina; Lin, Harrison W; Djalilian, Hamid R | Abstract: Objectives/hypothesisTo examine the hearing outcomes of patients with sudden sensorineural hearing loss (SSNHL) treated with oral and intratympanic (IT) steroid only or a combination of steroid and migraine treatment. Our hypothesis was that adjuvant migraine medications may improve outcomes in SSNHL.MethodsA retrospective chart review at a tertiary otology center was conducted to identify patients with SSNHL who received oral steroid and IT dexamethasone injection(s) with or without migraine medications (a combination of nortriptyline and topiramate).ResultsA total of 47 patients received oral steroid and IT dexamethasone injection(s) only, and 46 patients received oral steroid and IT dexamethasone injection(s) as well as migraine lifestyle changes plus a combination of nortriptyline and topiramate. There were no significant differences in demographics and baseline audiometric data between the two groups. Both groups demonstrated improvements in pure tone average (PTA) and hearing thresholds at 250 Hz and 8000 Hz posttreatment. However, compared to steroid-only group, the adjuvant migraine medications group had significantly greater improvements in hearing thresholds at the lower frequencies (250 Hz, 500 Hz, 1000 Hz). Patients in the latter cohort also had greater improvement in PTA (P = .01) and received fewer IT injections (P = .04) PTA improvement of ≥ 10 dB was observed in 36 patients (78%) in the adjuvant migraine medications group and 22 patients (46%) in the control group (P l .001).ConclusionIn multimodal treatment of SSNHL, supplementing oral and IT steroid with migraine medications may result in greater improvements in lower frequency hearing thresholds and PTA. Furthermore, adjuvant migraine treatment can lead to decrease in number of IT injections, thus reducing procedure-related risks and complications.Level of evidence3 Laryngoscope, 131:E283-E288, 2021.

Between 2016 and 2017, several U.S. Diplomats in Havana, Cuba, experienced perplexing vestibular and neurological symptoms attributed to an unknown source. They presented with significant vestibular and headache symptoms similar to individuals who experience vestibular migraine (VM). As such, we hypothesize that VM may be a possible explanation for the Havana cohort's presenting symptoms. To evaluate this hypothesis, we compared symptoms reported by the affected individuals in Havana, Cuba, to symptoms reported by corresponding patients from a tertiary academic neurotology clinic with a chief complaint of vertigo or disequilibrium, who met the International Classification of Headache Disorders criteria for VM. The prevalence of the Havana subjects experiencing various symptomatic domains was compared with the VM cohort, leading to 26 unique domains and statistical comparisons between the cohorts. Of the 26 domains compared between the two cohorts, 18 were not significantly different. This included the two most important components of meeting criteria for VM, namely the co-existence of headache and vestibular symptoms. On regression analysis, the only feature which kept its significant difference between the two cohorts was acute intense head pressure (P=0.007). The domains with similar occurrence ratios included dizziness, headache, light sensitivity, hearing reduction, and tinnitus. In other words, multiple headache and vestibular symptoms, consistent with VM criteria, were similar between the two cohorts. The considerable similarities across various domains between VM patients and Havana subjects could be due to migraine as a possible common etiology for both groups. We propose VM as a potential etiology for the symptomatology in the U.S. diplomats in Cuba.

Premise Migraine is a complex neurologic disorder that leads to significant disability, yet remains poorly understood. Problem One potential triggering mechanism in migraine with aura is cortical spreading depression, which can activate the trigeminal nociceptive system both peripherally and centrally in animal models. A primary neuropeptide of the trigeminal system is calcitonin gene-related peptide, which is a potent vasodilatory peptide and is currently a major therapeutic target for migraine treatment. Despite the importance of both cortical spreading depression and calcitonin gene-related peptide in migraine, the relationship between these two players has been relatively unexplored. However, recent data suggest several potential vascular and neural connections between calcitonin gene-related peptide and cortical spreading depression. Conclusion This review will outline calcitonin gene-related peptide-cortical spreading depression connections and propose a model in which cortical spreading depression and calcitonin gene-related peptide act at the intersection of the vasculature and cortical neurons, and thus contribute to migraine pathophysiology.

BackgroundCerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat’s brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients Pcp and Pbc, respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients and , respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in and . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of Pcp, and to a much lesser extent by perturbations of . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of Pbc and than variations of Pcp and within 30 minutes of the onset of the perturbations. However, Pcp is the most sensitive model parameter, followed by Pbc and , in controlling brain tissue and subarachnoid CSF sodium levels within 2 hours of the perturbation onset.

Trabajo fin de máster. Defendido en octubre de 2020. Introducción: el dolor de cabeza es un trastorno con un importante impacto socioeconómico debido a la elevada prevalencia afectando al 78,6% de la población, siendo los dolores de cabeza primarios los cuadros clínicos más habituales. Técnicas de terapia manual como la manipulación espinal son utilizadas por diferentes profesionales de la salud para el tratamiento del dolor de cabeza por sus importantes efectos biomecánicos y, sobre todo, neurofisiológicos. Objetivo: esta revisión de revisiones pretende recopilar y sintetizar toda la evidencia existente a cerca de los efectos de la manipulación espinal en personas con cefaleas primarias. Métodos: se realizaron búsquedas en seis bases de datos Pubmed, Web of Science, Scopus, CINAHL, Academy Search y PEDro desde su inicio hasta enero de 2020. El análisis crítico de las revisiones sistemáticas incluidas se llevó a cabo a través de la herramienta AMSTAR II y se evalúo la confianza general de los resultados a partir de los dominios críticos de dicha herramienta. Resultados: se sintetizó y se estudió los resultados de seis revisiones sistemáticas que estudiaron los efectos que se producen tras la realización de una manipulación espinal en personas con migrañas, cefalea tensional y cefalea cervicogénica. El nivel de confianza fue considerado como críticamente bajo en todas las revisiones sistemáticas incluidas. Conclusión: debido a la alta heterogeneidad de los resultados y a la escasa rigurosidad de los diseños de estudio los resultados sobre el efecto de la manipulación espinal en personas con cefaleas primarias son no concluyentes. Abstract:Introduction: headache is a disorder with a significant socioeconomic impact due to the high prevalence that affects 78.6% of the population, being the primary headache the most frequent clinical picture. Manual therapy techniques such as spinal manipulation are used by different healthcare professionals for the treatment of headaches due to their important biomechanical and, above all, neurophysiological effects. Objective: This review of reviews aims to collect and synthesize all the existing evidence on the effects of spinal manipulation in people with primary headaches. Methods: Six databases were searched Pubmed, Web of Science, Scopus, CINAHL, Academy Search and PEDro from inception to January 2020. A critical analysis of the systematic reviews included was performed using the AMSTAR II tool and the overall confidence of the results was assessed. of the critical domains of said tool. Results: the results of six systematic reviews that studied the effects that occur after performing spinal manipulation in people with migraines, tension headaches and cervicogenic headaches were synthesized and studied. The level of confidence was judged critically low in all included systematic reviews. Conclusion: due to the high heterogeneity of the results and the low rigor of the study designs, the results on the effect of spinal manipulation in people with primary headaches are not conclusive. Ordenador con navegador de Internet ; Adobe Acrobat Reader 37 p. (Según el contador de la aplicación)

In this observational study, using the Global Burden of Disease and Risk Factors Study, we aimed to (i) report the magnitude of health loss due to non-communicable neurological disorders in the USA in 2017 by sex, age, years and States and (ii) to identify non-communicable neurological disorders attributable environmental, metabolic and behavioural risk factors. We provide estimates of the burden of non-communicable neurological disorders by reporting disability-adjusted life-years and their trends from 1990 to 2017 by age and sex in the USA. The non-communicable neurological disorders include migraines, tension-type headaches, multiple sclerosis, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, motor neuron diseases and other neurological disorders. In 2017, the global burdens of non-communicable neurological disorders were 1444.41 per 100 000, compared to the USA burden of 1574.0. Migraine was the leading age-standardized disability-adjusted life-years 704.7 per 100 000, with Alzheimer’s disease and other dementias (41.8.7), and epilepsy (123.8) taking the second and third places, respectively. Between 1990 and 2017, the age-standardized disability-adjusted life-years rates for aggregate non-communicable neurological disorders relative to all cause increased by 3.42%. More specifically, this value for motor neuron diseases, Parkinson’s disease and multiple sclerosis increase by 20.9%, 4.0%, 2.47%, 3.0% and 1.65%, respectively. In 2017, the age-standardized disability-adjusted life-years rates for the aggregate non-communicable neurological disorders was significantly higher in females than the males (1843.5 versus 1297.3 per 100 000), respectively. The age-standardized disability-adjusted life-years rates for migraine were the largest in both females (968.8) and males were (432.5) compared to other individual non-communicable neurological disorders. In the same year, the leading non-communicable neurological disorders age-standardized disability-adjusted life-years rates among children ≤9 was epilepsy (216.4 per 100 000). Among the adults aged 35–60 years, it was migraine (5792.0 per 100 000), and among the aged 65 and above was Alzheimer’s disease and other dementias (78 800.1 per 100 000). High body mass index, smoking, high fasting plasma glaucous and alcohol use were the attributable age-standardized disability-adjusted life-years risks for aggregate and individual non-communicable neurological disorders. Despite efforts to decrease the burden of non-communicable neurological disorders in the USA, they continue to burden the health of the population. Children are most vulnerable to epilepsy-related health burden, adolescents and young adults to migraine, and elderly to Alzheimer’s disease and other dementias and epilepsy. In all, the most vulnerable populations to non-communicable neurological disorders are females, young adults and the elderly., Non-communicable neurological disorders in the USA continue to burden the health of the population. Children are most vulnerable to epilepsy, adolescents and young adults to migraine, and elderly to Alzheimer’s disease and other dementias, and epilepsy. In all, the most vulnerable populations are females, young adults and the elderly., Graphical Abstract Graphical Abstract

In 1944, three decades before the start of the artisanal bread movement, H. E. Jacob published Six Thousand Years of Bread: Its Holy and Unholy History capturing bread’s cultural, political, religious, and technological impacts over time. In the introduction of the 2007 edition of the text, prominent American baker Peter Reinhart wrote that bread is “inextricably woven into our cultural and personal histories.” Reinhart notes that while bread does have its own story, “it is also the medium through which so many other stories are told: stories of escape from bondage; of historical and political battles ...; of the intermingling of the supernatural and mystical into the natural world” (vi). In the same way, Artisan: On Bread and a Meaningful Life, a collection of three nonfiction essays, utilizes aspects of the bread baking processing (kneading, shaping and communion) to explore and tell the author’s personal story with work, the body and the scared. Bouncing between the science and technique of bread and personal experiences related to these broader themes, this work sought to answer the question, what can bread tell us about what makes a balanced and meaningful life?

OBJECTIVE: We aimed to assess the association between migraine headache and incident dementia. BACKGROUND: Migraine is a risk factor for white matter hyperintensities and ischemic stroke, which are both associated with increased risk of dementia. However, it is unknown whether migraine is independently associated with dementia. METHODS: History of migraine was ascertained via questionnaire. Adjudicated cases of dementia were identified using cognitive tests, neuropsychological exams, and clinician review of suspected cases. Incident dementia was identified using adjudicated cases, follow-up calls, and surveillance of hospital and death codes. We assessed hazards of incident dementia by migraine status. Sex differences were also examined and stratified results were presented. RESULTS: Analysis included 12,495 White and African American participants ages 51–70 with a median follow-up time of 21 years. Prevalence of dementia was 18.5% (1821/9955) among those with no migraine history, 15.8% (196/1243) among those with severe non-migraine heading, and 16.7% (233/1397) among migraineurs. There was no association between migraine and incident dementia [hazard ratio: 1.04 (0.91, 1.20)]. There was also no statistically significant interaction between sex and migraine status on risk of dementia. CONCLUSION: Despite evidence of brain abnormalities in migraineurs, there was no association between migraine and incident dementia in this prospective cohort.

Takotsubo Cardiomyopathy (TCM) is an increasing recognized form of acute reversible left ventricular systolic dysfunction not related to obstructive coronary disease. The exact physiology of this disorder is not yet known, however multiple agents have been hypothesized to have a link to this condition. Most commonly, TCM has been hypothesized as being triggered by a catecholamine surge after an inciting event. New evidence now suggests certain medications as a link to the disease. We describe a unique case of TCM in a woman after taking Treximet (naproxen and sumatriptan) as abortive therapy for a migraine.

The use of advanced imaging in routine diagnostic practice appears to provide only limited value in patients with migraine who have not experienced recent changes in headache characteristics or symptoms. However, advanced imaging may have potential for studying the biological manifestations and pathophysiology of migraine headaches. Migraine with aura appears to have characteristic spatiotemporal changes in structural anatomy, function, hemodynamics, metabolism, and biochemistry, whereas migraine without aura produces more subtle and complex changes. Large, controlled, multicenter imaging-based observational trials are needed to confirm the anecdotal evidence in the literature and test the scientific hypotheses thought to underscore migraine pathophysiology.

BackgroundThe commercial formulation of sumatriptan nasal spray is an effective option for migraine patients requiring or preferring a non-oral route of drug administration, but its utility is limited by poor absorption and tolerability issues. DFN-02, a new formulation of sumatriptan 10mg nasal spray, is co-formulated with a permeation enhancer that gives it pharmacokinetics comparable to subcutaneous sumatriptan. As reported previously, DFN-02 was significantly better than placebo on multiple efficacy endpoints at 2h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.ObjectiveThe objective of this study was to assess the efficacy of acute treatment of migraine with DFN-02, including its effect on migraine-related functional disability and patient satisfaction with treatment.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-02 in adults with episodic migraine. Functional disability and subject satisfaction with treatment were prespecified endpoints, assessed in real-time by subjects, using an electronic diary.ResultsIn total, 107 subjects were randomized. DFN-02 was significantly superior to placebo for the reduction in functional disability score from predose level at 2h after treatment (-1.2 vs. -0.6, p

In this case series, we set out to describe the clinical entity of isolated, prolonged aural fullness (AF) and its relationship with migraine. Patients with isolated, persistent AF for 6 months or more were included with all possible etiologies ruled out. Migraine dietary and lifestyle changes and medical migraine prophylactic therapy were prescribed to all. Eleven patients were included (mean age, 52 years). Six (54%) patients fulfilled International Headache Society criteria for migraine with or without aura. Changes in perceived sensation of AF using the visual analog scale and quality of life questionnaires resulted in a statically significant improvement ( P < .001, 95% confidence interval [CI], 4.7 to 6.72, and P < .001, 95% CI, -5.3 to -2.7, respectively). As such, an improvement of isolated, prolonged AF with migraine lifestyle changes and prophylactic treatment may suggest an etiological association between migraine and prolonged aural fullness.

The incidence of brain pathologies has increased during last decades. Better diagnosis (autism spectrum disorders) and longer life expectancy (Parkinson’s disease, Alzheimer’s disease) partly explain this increase, while emerging data suggest pollutant exposures as a possible but still underestimated cause of major brain disorders. Taking into account that the brain parenchyma is rich in gap junctions and that most pollutants inhibit their function; brain disorders might be the consequence of gap-junctional alterations due to long-term exposures to pollutants. In this article, this hypothesis is addressed through three complementary aspects: (1) the gap-junctional organization and connexin expression in brain parenchyma and their function; (2) the effect of major pollutants (pesticides, bisphenol A, phthalates, heavy metals, airborne particles, etc.) on gap-junctional and connexin functions; (3) a description of the major brain disorders categorized as neurodevelopmental (autism spectrum disorders, attention deficit hyperactivity disorders, epilepsy), neurobehavioral (migraines, major depressive disorders), neurodegenerative (Parkinson’s and Alzheimer’s diseases) and cancers (glioma), in which both connexin dysfunction and pollutant involvement have been described. Based on these different aspects, the possible involvement of pollutant-inhibited gap junctions in brain disorders is discussed for prenatal and postnatal exposures.

Objectives Increasing evidence demonstrates effectiveness of Mindfulness-Based Stress Reduction (MBSR) for pain-related and functional disorders. In order to conduct successful and efficient trials of MBSR, evidence regarding the relative performance of strategies to improve recruitment, retention, and adherence is required, but few studies have examined these issues specifically. Design In preparation for a fully powered trial, we conducted a 2-arm, parallel comparison randomized controlled feasibility trial of MBSR vs. usual-care for 60 patients with migraine headache. Setting Two large U.S. health systems in Northern California. Intervention MBSR is an 8-week classroom-based intervention that combines mindfulness meditation and yoga, with didactic presentations about stress psychology and group process/experiential education. Participants received the intervention at their choice of one of several existing, vetted community-based classes. Main outcome measures Successful recruitment was defined a priori as 18 participants within any 9-week period or 60 participants enrolled within a 36-week period. We considered participants adherent to the intervention if they attended at least 5 of the 8 weekly classes and the day-long retreat. Results We successfully enrolled 18 participants within a 7-week period, however, we did not attain our second goal of recruiting 60 participants within a 36-week period. Sixty-eight percent of our participants were adherent to the intervention. Conclusions We found that close monitoring of recruitment activities, flexibility in protocol modifications, and integration within the delivery system were crucial factors for successful participant recruitment, retention, and adherence in mindfulness research.

The neural mechanisms responsible for the initiation and expression of migraines remain unknown. Although there is growing evidence of changes in brainstem anatomy and function between attacks, very little is known about brainstem function and structure in the period immediately prior to a migraine. The aim of this investigation is to use brainstem-specific analyses of diffusion weighted images to determine whether the brainstem pain processing regions display altered structure in individuals with migraine across the migraine cycle, and in particular immediately prior to a migraine. Diffusion tensor images (29 controls, 36 migraineurs) were used to assess brainstem anatomy in migraineurs compared with controls. We found that during the interictal phase, migraineurs displayed greater mean diffusivity (MD) in the region of the spinal trigeminal nucleus (SpV), dorsomedial pons (dmPons)/dorsolateral pons (dlPons), and midbrain periaqueductal gray matter (PAG)/cuneiform nucleus (CNF). Remarkably, the MD returned to controls levels during the 24-h period immediately prior to a migraine, only to increase again within the three following days. Additionally, fractional anisotropy (FA) was significantly elevated in the region of the medial lemniscus/ventral trigeminal thalamic tract in migraineurs compared with controls over the entire migraine cycle. These data show that regional brainstem anatomy changes over the migraine cycle, with specific anatomical changes occurring in the 24-h period prior to onset. These changes may contribute to the activation of the ascending trigeminal pathway by either an increase in basal traffic or by sensitizing the trigeminal nuclei to external triggers, with activation ultimately resulting in perception of head pain during a migraine attack.

There are currently 13 indications approved by the U.S. Food and Drug Administration for use of hyperbaric oxygen therapy. The European Consensus Conference on Hyperbaric Medicine has 28 indications approved for its use. However, neither includes the use of hyperbaric oxygen therapy for neurological conditions such as migraines with aura. Recent research has made the attempt to fully understand the use of hyperbaric therapy in treatment of neurological conditions, but results have so far been inconclusive. We report a 23-year-old female with an 11-year history of migraines with aura who has received inadequate pharmacological treatment for her migraines since she began having them. Migraines have led her to significant loss of function. The patient underwent treatment at 1.5 absolute atmospheres in a hyperbaric chamber Monday through Friday for 1 hour each day for a total of 40 sessions but reported missing a few sessions over the 8-week period. No more than 1 session during a given week was missed and the patient received no other treatments for her migraines throughout this time period. By her 24th treatment, the patient had only experienced a single migraine with aura but without debilitating pain. The patient stated she had never had a migraine with such little intensity prior to initiation of hyperbaric treatment and did not have to take any days off from work or school. Follow-up at the end of her 40-day treatment period revealed a highly-satisfied patient who had only experienced the single episode of a mild migraine during the entire course of treatment. Thus, we believe that further research needs to be done to realize the full potential of hyperbaric oxygen therapy in the treatment of neurological conditions as this case highlights the potential for using hyperbaric oxygen therapy as prophylaxis against attacks in patients with treatment resistant migraines with aura.

Introduction: Over 70% of traumatic brain injuries (TBI) are classified as mild (mTBI), which present heterogeneously. Associations between pre-injury comorbidities and outcomes are not well-understood, and understanding their status as risk factors may improve mTBI management and prognostication. Methods: mTBI subjects (GCS 13-15) from TRACK-TBI Pilot completing 3- and 6-month functional [Glasgow Outcome Scale-Extended (GOSE)] and post-concussive outcomes [Acute Concussion Evaluation (ACE) physical/cognitive/sleep/emotional subdomains] were extracted. Pre-injury comorbidities >10% incidence were included in regressions for functional disability (GOSE ≤ 6) and post-concussive symptoms by subdomain. Odds ratios (OR) and mean differences (B) were reported. Significance was assessed at p < 0.0083 (Bonferroni correction). Results: In 260 subjects sustaining blunt mTBI, mean age was 44.0-years and 70.4% were male. Baseline comorbidities >10% incidence included psychiatric-30.0%, cardiac (hypertension)-23.8%, cardiac (structural/valvular/ischemic)-20.4%, gastrointestinal-15.8%, pulmonary-15.0%, and headache/migraine-11.5%. At 3- and 6-months separately, 30.8% had GOSE ≤ 6. At 3-months, psychiatric (GOSE ≤ 6: OR = 2.75, 95% CI [1.44-5.27]; ACE-physical: B = 1.06 [0.38-1.73]; ACE-cognitive: B = 0.72 [0.26-1.17]; ACE-sleep: B = 0.46 [0.17-0.75]; ACE-emotional: B = 0.64 [0.25-1.03]), headache/migraine (GOSE ≤ 6: OR = 4.10 [1.67-10.07]; ACE-sleep: B = 0.57 [0.15-1.00]; ACE-emotional: B = 0.92 [0.35-1.49]), and gastrointestinal history (ACE-physical: B = 1.25 [0.41-2.10]) were multivariable predictors of worse outcomes. At 6-months, psychiatric (GOSE ≤ 6: OR = 2.57 [1.38-4.77]; ACE-physical: B = 1.38 [0.68-2.09]; ACE-cognitive: B = 0.74 [0.28-1.20]; ACE-sleep: B = 0.51 [0.20-0.83]; ACE-emotional: B = 0.93 [0.53-1.33]), and headache/migraine history (ACE-physical: B = 1.81 [0.79-2.84]) predicted worse outcomes. Conclusions: Pre-injury psychiatric and pre-injury headache/migraine symptoms are risk factors for worse functional and post-concussive outcomes at 3- and 6-months post-mTBI. mTBI patients presenting to acute care should be evaluated for psychiatric and headache/migraine history, with lower thresholds for providing TBI education/resources, surveillance, and follow-up/referrals. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01565551.

OBJECTIVE::To evaluate the change in quality of life (QOL) of patients with Meniere's disease (MD) after treatment with migraine prophylaxis therapy. METHODS::Patients with definite MD were given the Meniere's Disease Outcomes Questionnaire-Retrospective (MDOQ-R) after migraine prophylactic therapy to assess QOL. Changes in physical, emotional, and social parameters affected by MD were calculated, along with a global pre- and posttreatment QOL scores. RESULTS::The MDOQ-R was given to 27 consecutive patients with definite MD. Patients who had at least an 18-month follow-up were included, resulting in 25 questionnaires. The mean change in QOL score was 25 ± 16 (range, -3 to 55), P = .02. Quality of life was improved in 23 (92%) of the respondents in every metric measured, unchanged in 1 (4%), and poorer in 1 (4%) of patients after migraine prophylaxis treatment. CONCLUSIONS::Majority of MD patients who had all failed diuretic therapy responded positively to medications used for migraine prophylaxis, as indicated by a significant improvement in QOL. This study may further suggest a correlation between the pathophysiologic basis of disease in MD and vestibular migraine. Patients with MD may be successfully managed with medications intended to treat migraine.

The neural mechanism responsible for migraine remains unclear. While an external trigger has been proposed to initiate a migraine, it has also been proposed that changes in brainstem function are critical for migraine headache initiation and maintenance. Although the idea of altered brainstem function has some indirect support, no study has directly measured brainstem pain modulation circuitry function in migraineurs particularly immediately before a migraine. In male and female humans, we performed fMRI in 31 controls and 31 migraineurs at various times in their migraine cycle. We measured brainstem function during noxious orofacial stimulation and assessed resting-state functional connectivity. First, we found that, in individual migraineurs, pain sensitivity increased over the interictal period but then dramatically decreased immediately before a migraine. Second, despite overall similar pain intensity ratings between groups, in the period immediately before a migraine, compared with controls and other migraine phases, migraineurs displayed greater activation in the spinal trigeminal nucleus during noxious orofacial stimulation and reduced functional connectivity of this region with the rostral ventromedial medulla. Additionally, during the interictal phase, migraineurs displayed reduced activation of the midbrain periaqueductal gray matter and enhanced periaqueductal gray connectivity with the rostral ventromedial medulla. These data support the hypothesis that brainstem sensitivity fluctuates throughout the migraine cycle. However, in contrast to the prevailing hypothesis, our data suggest that, immediately before a migraine attack, endogenous analgesic mechanisms are enhanced and incoming noxious inputs are less likely to reach higher brain centers.SIGNIFICANCE STATEMENTIt has been hypothesized that alterations in brainstem function are critical for the generation of migraine. In particular, modulation of orofacial pain pathways by brainstem circuits alters the propensity of external triggers or ongoing spontaneous activity to evoke a migraine attack. We sought to obtain empirical evidence to support this theory. Contrary to our hypothesis, we found that pain sensitivity decreased immediately before a migraine, and this was coupled with increased sensitivity of the spinal trigeminal nucleus to noxious stimuli. We also found that resting connectivity within endogenous pain modulation circuitry alters across the migraine cycle. These changes may reflect enhanced and diminished neural tone states proposed to be critical for the generation of a migraine and underlie cyclic fluctuations in migraine brainstem sensitivity.

Summary The treatment of epilepsy is not limited to the achievement of a seizure‐free state. It must also incorporate the management of common psychiatric and neurologic comorbidities, affecting on average between 30 and 50% of patients with epilepsy, which have a significant impact on their lives at various levels, including quality of life and the prognosis of the seizure disorder. Mood and anxiety disorders are the most frequent psychiatric comorbidities, whereas stroke and migraine are among the more common neurologic comorbidities, migraine among the younger patients and stroke among the older patients. Not only do these psychiatric and neurologic comorbidities each have a bidirectional relation with epilepsy, but primary mood disorders have a bidirectional relation with these 2 neurologic disorders. Furthermore, depression and migraine have been each associated with a more severe epilepsy course, whereas depression has been associated with a more severe course of stroke and migraines. The purpose of this article is to review the clinical implications of the complex relations among epilepsy and these 3 comorbid disorders, and to identify any clinical and/or experimental evidence that may suggest that having more than one of these comorbid disorders may increase the risk of and course of epilepsy.

This study was completed to better understand and treat couples wherein one partner suffers from chronic migraines. I interviewed eight couples about their experiences in dealing with migraines as a patient, as a partner, and together. The interviews were transcribed and analyzed by a team of seven researchers. We developed a theory that can be used to understand how patients and their partners adapt to chronic migraines. The theory was grounded in the experiences of the patients and partners who were interviewed. We found that patients and partners alike dealt with burdens and costs associated with chronic migraines. Coping, healthcare, couple experience, and identity were found to be the means through which patients and partners adapted to their burdens. These concepts are broken down and discussed in greater detail. A model is provided that can be used to create a visual representation of how well a couple deals with migraines. Suggestions for couples who are dealing with chronic migraines, and for medical providers and therapists who work with couples affected by chronic migraines, are provided.

BackgroundIn a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed.ResultsA total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P = 0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90min postdose (P ≤ 0.0195). DFN-11 was significantly superior to placebo for pain relief at 60min, 90min, and 2h postdose (P ≤ 0.0179). At 2h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P = 0.0056) and phonophobia (P = 0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%).ConclusionsThis study met its primary endpoint, pain freedom at 2h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015).

BackgroundDFN-11, a 3mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks.MethodsThis was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity.ResultsOverall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings.ConclusionDFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine.Trial registrationClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.

The neural mechanism responsible for migraine remains unclear. While the role of an external trigger in migraine initiation remains vigorously debated, it is generally assumed that migraineurs display altered brain function between attacks. This idea stems from relatively few brain imaging studies with even fewer studies exploring changes in the 24h period immediately prior to a migraine attack. Using functional magnetic resonance imaging, we measured infra-slow oscillatory activity, regional homogeneity, and connectivity strengths of resting activity in migraineurs directly before (n = 8), after (n = 11), and between migraine attacks (n = 26) and in healthy control subjects (n = 78). Comparisons between controls and each migraine group and between migraine groups were made for each of these measures. Directly prior to a migraine, increased infra-slow oscillatory activity occurred in brainstem and hypothalamic regions that also display altered activity during a migraine itself, that is, the spinal trigeminal nucleus, dorsal pons, and hypothalamus. Furthermore, these midbrain and hypothalamic sites displayed increased connectivity strengths and regional homogeneity directly prior to a migraine. Remarkably, these resting oscillatory and connectivity changes did not occur directly after or between migraine attacks and were significantly different to control subjects. These data provide evidence of altered brainstem and hypothalamic function in the period immediately before a migraine and raise the prospect that such changes contribute to the expression of a migraine attack.

The discovery that intravenous (IV) infusions of the neuropeptide PACAP-38 (pituitary adenylyl cyclase activating peptide-38) induced delayed migraine-like headaches in a large majority of migraine patients has resulted in considerable excitement in headache research. In addition to suggesting potential therapeutic targets for migraine, the finding provides an opportunity to better understand the pathological events from early events (aura) to the headache itself. Although PACAP-38 and the closely related peptide VIP (vasoactive intestinal peptide) are well-known as vasoactive molecules, the dilation of cranial blood vessels per se is no longer felt to underlie migraine headaches. Thus, more recent research has focused on other possible PACAP-mediated mechanisms, and has raised some important questions. For example, (1) are endogenous sources of PACAP (or VIP) involved in the triggering and/or propagation of migraine headaches?; (2) which receptor subtypes are involved in migraine pathophysiology?; (3) can we identify specific anatomical circuit(s) where PACAP signaling is involved in the features of migraine? The purpose of this review is to discuss the possibility, and supportive evidence, that PACAP acts to induce migraine-like symptoms not only by directly modulating nociceptive neural circuits, but also by indirectly regulating the production of inflammatory mediators. We focus here primarily on postulated extra-dural sites because potential mechanisms of PACAP action in the dura are discussed in detail elsewhere (see X, this edition).

This article reviews the evidence for an association between infant colic and migraine. Infant colic, or excessive crying in an otherwise healthy and well-fed infant, affects approximately 5%-19% of infants. Multiple case-control studies, a cross-sectional study, and a prospective cohort study have all found an association between infant colic and migraine. Although infant colic is often assumed to have a gastrointestinal cause, several treatment trials aimed at gastrointestinal etiologies have been negative. Teaching parents how to respond best to inconsolable crying may be helpful and important for preventing shaken baby syndrome. Given accumulating evidence for a connection between infant colic and pediatric migraine, future studies should examine migraine-oriented treatments for infant colic. Infant colic should be moved into the main body of International Classification of Headache Disorders (ICHD-III beta) as one of the "Episodic syndromes that may be associated with migraine."

BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6months to treat episodic migraine acutely.

SummaryObjective Low-cost evidence-based tools are needed to facilitate the early identification of patients with possible psychogenic nonepileptic seizures (PNES). Prior to accurate diagnosis, patients with PNES do not receive interventions that address the cause of their seizures and therefore incur high medical costs and disability due to an uncontrolled seizure disorder. Both seizures and comorbidities may contribute to this high cost. Methods Based on data from 1,365 adult patients with video-electroencephalography–confirmed diagnoses from a single center, we used logistic and Poisson regression to compare the total number of comorbidities, number of medications, and presence of specific comorbidities in five mutually exclusive groups of diagnoses: epileptic seizures (ES) only, PNES only, mixed PNES and ES, physiologic nonepileptic seizurelike events, and inconclusive monitoring. To determine the diagnostic utility of comorbid diagnoses and medication history to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and age, trained using a retrospective database and validated using a prospective database. Results Our model differentiated PNES only from ES only with a prospective accuracy of 78% (95% confidence interval =72–84%) and area under the curve of 79%. With a few exceptions, the number of comorbidities and medications was more predictive than a specific comorbidity. Comorbidities associated with PNES were asthma, chronic pain, and migraines (p < 0.01). Comorbidities associated with ES were diabetes mellitus and nonmetastatic neoplasm (p < 0.01). The population-level analysis suggested that patients with mixed PNES and ES may be a population distinct from patients with either condition alone. Significance An accurate patient-reported medical history and medication history can be useful when screening for possible PNES. Our prospectively validated and objective score may assist in the interpretation of the medication and medical history in the context of the seizure description and history.

Author(s): Chang, Melinda Y; Phasukkijwatana, Nopasak; Garrity, Sean; Pineles, Stacy L; Rahimi, Mansour; Sarraf, David; Johnston, Mollie; Charles, Andrew; Arnold, Anthony C | Abstract: PurposeMigraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC).MethodsWe recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images.ResultsOn macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups.ConclusionsMigraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

Objective:To determine outcomes among patients with migraine in the emergency department (ED) who receive IV hydromorphone vs IV prochlorperazine + diphenhydramine.Methods:This study was conducted in 2 EDs in New York City. Patients who met international criteria for migraine were eligible for participation if they had not used an opioid within the previous month. Clinicians, participants, investigators, and research personnel were blinded to treatment. Patients were randomized in blocks of 4. Participants received hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg. Diphenhydramine was administered to prevent akathisia, a common side effect of IV prochlorperazine. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining that level for 48 hours without the requirement of rescue medication. A planned interim analysis was conducted once 48-hour data were available for 120 patients.Results:The trial was halted by the data monitoring committee after 127 patients had been enrolled. The primary outcome was achieved in the prochlorperazine arm by 37 of 62 (60%) participants and in the hydromorphone arm by 20 of 64 (31%) participants (difference 28%, 95% confidence interval 12–45, number needed to treat 4, 95% confidence interval 2–9).Conclusions:IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the ED and should not be used as first-line therapy.ClinicalTrials.gov identifier:NCT02389829.Classification of evidence:This study provides Class I evidence that for patients in the ED with migraine, IV prochlorperazine + diphenhydramine is superior to IV hydromorphone.

Background Primary headache disorders are among the most common neurological complaints worldwide, and are significant causes of disability. Data are limited on the prevalence of primary headaches among individuals aged 60 years and older in China. The purpose of our study was to investigate the prevalence and characteristics of primary headaches among people aged 60 years and older in a rural area of northern China. Methods A door-to-door survey was conducted in Ji County of Tianjin Province. A total of 5248 residents aged 60 years and older were visited from 2014 to 2015, unannounced, and basic sociodemographic and headache diagnostic information was collected via a questionnaire. Primary headache was classified tension-type headaches, migraines, chronic headache, and unclassified headache. Results The 1-year prevalence for primary headaches in Ji county is 10.30 %. The 1-year prevalence of tension-type headaches, migraines, chronic headache, and unclassified headache is 2.02 %, 0.85 %, 3.79 %, and 3.63 %. The 1-year prevalence of primary headache was higher in women than in men. The 1-year prevalence of primary headache was decreased with increasing age. The 1-year prevalence of tension-type headaches and chronic headache were decreased with higher education. Headache in the elderly was mild to moderate and not serious. Conclusions In a population older than 60 years of age in rural, northern China, we found the 1-year prevalence of primary headache was 10.30 %, of tension-type headaches was 2.02 %, of migraines was 0.85 %, of chronic headache was 3.79 %, and of unclassified headache was 3.63 %. The prevalence of all of these was much lower than those observed in previous studies examining prevalence rates in the general population. The results of our study also indicated that women are more likely to have primary headache than men. We also found that chronic headache was frequent among the elderly. Participants with higher education levels were more predisposed than healthy participants to tension-type headaches. We also found that respondents who did not participate in social activities had a decreased predisposition for primary headache in general, as well as for unclassified headache. Lastly, we found that participants who had heart disease were more likely than healthy participants to experience primary headache, tension-type headache, chronic headache, and unclassified headache.

ObjectivesIn evaluating the historical context of the first description of Menière's disease, its association with migraine headaches is compelling. We have outlined the events and observations of Prosper Menière, which led him to establish a link between migraine headaches and his eponymous disease.Study designProsper Menière's original French writings were translated by our group and used to recount his observations and thoughts. Miles Atkinson's English translations were used as a reference. Additional otological texts of the era were also reviewed as it relates to Menière's disease.MethodsProsper Menière wrote a series of four articles 1 year before his death. In one of these articles, he makes references to migraine headaches on several occasions. These original writings were analyzed, and the physical findings he described were interpreted based on their relation to migraine headaches.ResultsThe passages in his published articles provide historical insight into Menière's observations. His writings describe in detail symptoms of migraine headaches uniquely evident in his patient population. Through his observations, he recognized that in addition to exhibiting symptoms of tinnitus, hearing loss and vertigo his patients also suffered from migraine headaches.ConclusionsAlthough his colleagues discounted Menière's theory concerning migraine headaches, he continued to make deductive inferences and publish his findings, leading to the association of migraine headaches and Menière's disease. Today, this association continues to be debated, adding to Prosper Menière's legacy.

BackgroundCluster headache (CH) is considered the most excruciating primary headache syndrome; although much less prevalent than migraine, it is not rare as it affects more than 1/1000 people. While its clinical presentation is considered stereotypic, atypical features are often encountered. Internationally, cluster headache is often misdiagnosed, undertreated and mistreated.MethodsWe prospectively studied 302 CH patients, all examined by the same headache specialist. The aim of our study was to describe the demographic and clinical characteristics of CH patients in Greece and draw attention to under-management, under-treatment and mis-treatment often encountered in clinical practice; our purpose is to improve recognition and successful treatment of cluster patients by Greek neurologists and other physicians.ResultsIn the present cohort, clinical characteristics of CH are similar to those described in other populations. Beyond the standard clinical characteristics, features like side shifts (12.6%), location of maximal pain intensity outside the first trigeminal branch division (10.2%), lack of autonomic features (7%), presence of associated features of migraine and aggravation by physical activity (10%) were encountered. Four out of five patients had consulted a physician prior to diagnosis. The median number of physicians seen prior to diagnosis was 3 and the median time to diagnosis was 5years, though it improved for patients with recent onset. Chronic cluster headache, side shifts, pain location in the face or the back of the head and aggravation by physical activity were found, among others, to be statistically significantly related to delayed diagnosis or more physicians seen prior to diagnosis. Even properly diagnosed patients were often undertreated or mistreated.ConclusionsCluster headache, in a large cohort of Greek patients, has the same phenotypic characteristics as described internationally. Uncommon clinical features do exist and physicians should be aware of those, since they may eventuate in diagnostic problems. Most CH patients in Greece remain misdiagnosed or undiagnosed for rather lengthy periods of time, but time to diagnosis has improved recently. Even after diagnosis, treatment received was suboptimal.