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The aim of this review is to characterize headache as a vaccine adverse event (VAE) in clinical trials.Of the recent phase III vaccine RCTs (non-COVID-19), 53 studies reported on headache (13 infectious agents). The median rate (interquartile range) of headache was 15.6% (IQR: 9.6-37.6%). Of these, 24.5% of the RCTs reported headache greater in the vaccine group compared to the placebo/control group. In the herpes zoster vaccination trials, headache was more common in all active groups: median rate 33.9% (IQR: 29.7-40.5%) as compared to placebo: median rate 17.7% (IQR: 15.4-23.8%). Influenza and HPV vaccination trials were the 2nd and 3rd most common to have headache as a VAE. Of the 6 widely distributed COVID-19 vaccinations, median rate of post-vaccination headache was 39% (IQR: 28-50%). Headache is a common VAE in vaccine trials. Standardized grading methods, predictors of persistence, and treatment regimens are warranted.

There are notable health disparities and inequities in individuals with traumatic brain injury (TBI) and concussion by race, ethnicity, gender, socioeconomic status, and geography. This review will evaluate these disparities and inequities and assess the social determinants of health that drive outcomes for post-traumatic headache. Interventions for achieving this are also discussed.Significant disparities and inequities exist in TBI and concussion among people of different races, socioeconomic status, and geographic locations. Migraine is a common symptom post-concussion, for which disparities and social determinants of health are also discussed. Overall, multi-level interventions to reduce these disparities and inequities are reviewed for post-traumatic headache but require further investigation. Interventions are needed to reduce disparities and inequities including public health initiatives, improvements in clinical care, diversity/inclusion training, and research efforts. As literature expands, we can form guidance to identify solutions for eliminating disparities in care of diverse populations.

Introduction: Cluster headache [CH] is a severely disabling trigeminal autonomic cephalalgia [TAC]. Approximately 1 in 1,000 adults are affected by CH. Calcitonin gene-related peptide [CGRP] is an ...

Background Alopecia is associated with erenumab post-marketing, but no cases have been described. Methods We describe two patients that reported temporary hair loss and review the FDA Adverse Event Reporting System (FAERS). Results The first patient experienced alopecia within three months of starting erenumab, which did not improve with ongoing use or transition to fremanezumab. The second patient reported alopecia within two weeks of starting erenumab, which continued after transition to galcanezumab; months later, there was also recurrent hair loss within one month of starting fremanzeumab. According to FAERS (last accessed 18 August 2022), alopecia was reported most with erenumab (1158), followed by galcanezumab (554), fremanezumab (175), eptinezumab (23), rimegepant (26), ubrogepant (4), and atogepant (3). Conclusion Most events were reported in women and non-serious. The potential mechanism of alopecia with drugs targeting calcitonin gene-related peptide or its receptor possibly includes disruptions in the microvascular circulation and other homeostatic mechanisms.

This is an update of headache attributed to systemic disease and current therapeutic strategies. Clinical scenarios are discussed.The diagnosis of headache attributed to metabolic or systemic disorder appears in the Appendix of International Classification of Headache Disorders, Third Edition, and requires further evaluation and validation. However, recent studies characterizing headache appear in the literature. Specific treatment includes addressing underlying systemic disorders, managing concurrent primary headache, and treating comorbidities that may exacerbate headache. Evidence for specific treatment trials for headache as a symptom is lacking, including headaches post-COVID19 infection. Calcitonin gene-related peptide receptor antagonists and 5-HTHeadache is commonly encountered as a manifestation or complication of systemic disease. Further research is needed to validate headache associated with systemic disorders and to determine optimal treatment strategies.

Background Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. Methods The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. Findings We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. Interpretation Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. Funding U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411 .

Recent racial inequities as illustrated by the health disparities in COVID-19 infections and deaths, the recent killings of Black men and women by law enforcement, and the widening socioeconomic inequality and have brought systemic racism into a national conversation. These unprecedented times may have deleterious consequences, increasing stress, and trauma for many members of the neurology workforce. The Equity, Diversity, Inclusion and Anti-Racism Committee within our Department of Neurology provides infrastructure and guidance to foster a culture of belonging and addresses the well-being of faculty, staff, and trainees. Here, we present the creation and implementation of our Equity, Diversity, Inclusion, and Anti-Racism (EDIA) Pledge, which was central to our committee's response to these unprecedented times. We outline the process of developing this unique EDIA Pledge and provide a roadmap for approaching these important topics through a Continuing Medical Education Neurology Grand Rounds aimed at fostering a diverse, inclusive, equitable, and antiracist work environment. Through the lived experiences of 4 faculty members, we identify the impact of bias and microaggressions and encourage allyship and personal development for cultural intelligence. We hope that these efforts will inspire neurology departments and other academic institutions across the globe to make a similar pledge.

ObjectiveTo review contemporary issues of health care disparities in headache medicine with regard to race/ethnicity, socioeconomic status (SES), and geography and propose solutions for addressing these disparities.MethodsAn Internet and PubMed search was performed and literature was reviewed for key concepts underpinning disparities in headache medicine. Content was refined to areas most salient to our goal of informing the provision of equitable care in headache treatment through discussions with a group of 16 experts from a range of headache subspecialties.ResultsTaken together, a multitude of factors, including racism, SES, insurance status, and geographical disparities, contribute to the inequities that exist within the health care system when treating headache disorders. Interventions such as improving public education, advocacy, optimizing telemedicine, engaging in community outreach to educate primary care providers, training providers in cultural sensitivity and competence and implicit bias, addressing health literacy, and developing recruitment strategies to increase representation of underserved groups within headache research are proposed as solutions to ameliorate disparities.ConclusionNeurologists have a responsibility to provide and deliver equitable care to all. It is important that disparities in the management of headache disorders are identified and addressed.

In their article “Nonpainful remote electrical stimulation alleviates episodic migraine pain,” Dr. Yarnitsky et al.1 investigated the use of nonpainful electrical stimulation of the skin of the arm in reducing migraine attacks. Therapeutic electrical stimulation has been widely used for pain treatment. It is believed to be effective when applying the stimulation next to the painful location. For example, the Food and Drug Administration has approved the first device for migraine prevention using electrical stimulation to the area above the eyes. A number of other neurostimulators are under investigation for migraine.2 The idea is to activate parts of the brain with connections to the spine. Triggering pain systems that are remote from the site of migraine pain can relieve pain. In this case, the authors used nonpainful stimulation as a trigger for relief. The idea was to create a conditioned response. This means that giving electrical stimulation at low intensity to a different part of the body will send signals to the brain that then stop or reduce the migraine attack. The authors thought it would be easier to apply electrical stimulation to the lower arm than the head (figure).

Objective To describe a patient with migraine with aura (MWA) who was found to have a reversible lesion of the corpus callosum. Background Reversible lesions of the splenium of the corpus callosum are well-described clinical-radiographic phenomena, which have been associated with a wide array of disease states, including epilepsy, demyelinating disease, infection, and metabolic derangements. There have been few case reports in the literature to date of these lesions associated with migraine headache. Design/methods A case report. Results A 41 year-old female with a history of migraine with visual aura presented with headache associated with left-sided sensorimotor deficits. Routine laboratory tests were within normal limits. An electroencephlogram was also normal. Magnetic resonance imaging (MRI) of the brain with and without contrast revealed areas of restricted diffusion in the splenium and the genu of the corpus callosum. The patient's symptoms resolved after 2 days. A follow-up MRI 2 days after the onset of symptoms revealed resolution of the callosal lesions. The patient was diagnosed clinically with migraine with prolonged aura. Conclusion MWA may be associated with reversible lesions of the corpus callosum.

ObjectiveAsylum seekers experience a high burden of physical and psychological trauma, yet there is a scarcity of literature regarding the epidemiology and sequelae of head injury (HI) in asylum seekers. We examined HI prevalence and association with neuropsychiatric comorbidities in asylum seekers.MethodsA retrospective cross-sectional study was performed through review of 139 medical affidavits from an affidavit database. Affidavits written from 2010 to 2018 were included. Demographic and case-related data were collected and classified based on the presence of HI. For neuropsychiatric sequelae, the primary study outcome was headache and the secondary outcomes were depression, posttraumatic stress disorder, and anxiety. Multivariable logistic regression was performed to examine the association between HI and neuropsychiatric sequelae, adjusted for demographic and clinical characteristics.ResultsA total of 139 medical affidavits of asylum seekers were included. The mean age was 27.4 ± 12.1 years, 56.8% were female, and 38.8% were ConclusionsWe observed a high prevalence of HI in asylum seekers. Comprehensive screening for HI and neuropsychiatric comorbidities is encouraged when evaluating asylum seekers.

Headaches are one of the most common symptoms associated with traumatic brain injury (TBI). According the International Classification of Headache Disorders 3rd edition (ICHD-3), posttraumatic headache (PTH) may be acute if there is new onset headache or worsening primary headache for less than 3 months. Persistent posttraumatic headache (PPTH) occurs when headache is present for 3 months or more. Risk factors include the female gender, younger age, a history of recurrent head and neck injuries, medication overuse, and litigation. The exact cause of PTH is unknown; however, there are a number of pathological mechanisms in mild TBI (mTBI) that may contribute to functional and structural changes associated with the generation of head pain. This chapter reviews the recent advances in the understanding of PTH, including the epidemiology, basic science, diagnostic evaluations, treatment, and management of mTBI, as well as future research considerations. Special populations of patients with headaches associated with mTBI will be discussed.

Chronic migraine is a debilitating primary headache disorder associated with high personal, familial, and social impact. The diagnosis is made when there are at least 15 headache days monthly including 8 migraine days per month for at least 3 months. The prevalence is 1.4–2.2% in the population. Among individuals diagnosed with chronic migraine, there may be significant variability in headache days with a potential to remit, remain unchanged, or progress to even greater disability. Most chronic migraine progresses from episodic migraine, with several identified risk factors for chronic migraine and migraine progression. The exact mechanism of chronic migraine is unknown but is associated with an increased cortical excitability, central sensitization, alternations in nociceptive signaling, as well as physiological, structural, and functional brain changes. There is evidence for both nonpharmacological and pharmacological treatment options to restore function. The best currently established pharmacologic evidence for the treatment of chronic migraine is onabotulinumtoxinA and topiramate. Behavioral treatments may improve headache symptoms and comorbidities. Emerging data shows potential benefit for neurostimulation, and large well-designed studies are needed. Multicenter randomized placebo-controlled studies of monoclonal antibodies to the calcitonin gene-related peptide, or its receptor, have demonstrated efficacy, tolerability, and safety. Biomarkers are needed to guide prognosis, treatment response, and clinical trials. The concept and management of refractory chronic migraine is discussed, and clinically meaningful endpoints are reviewed.

The goal of this review is to explore the literature reports of acute confusional migraine (ACM) including patient characteristics, migraine symptomatology, and proposed diagnostic criteria. A literature review was conducted using PubMed, Scopus and Web of Science using the terms “confusional migraine” and “confusional state in migraine”. All the relevant articles from 1970 to 2016 were included. A total of 120 patients were found in the literature. Most of the cases were seen in the pediatric population with a slight male predominance. Personal or family history of migraine was common. Most patients had a headache prior to the confusional state. In addition to confusion and agitation, some developed visual (32.5%) and/or sensory symptoms (19%) and/or speech problems (39%) either prior to or during the confusional state. Data on treatment outcomes is lacking. Patients with most common forms of migraine report attention and cognitive disturbances but awareness remains intact as opposed to patients with ACM. ACM is a distinct entity and should be included as part of the appendix of International Classification of Headache Disoders-3 beta version (ICHD-3β) criteria. Prospective studies are needed to further study this disorder and its association with other migraine forms.

OBJECTIVE To review the challenges and potential solutions in treatment options for quality migraine care in adult patients who are under or uninsured. BACKGROUND The Affordable Care Act has improved access to health care for many; however, those who are underserved continue to face treatment disparities and have inadequate access to appropriate migraine management. METHODS This manuscript is the second of a 2-part narrative review which was performed after a series of discussions within the Underserved Populations in Headache Medicine Special Interest Section meetings of the American Headache Society. Literature was reviewed for key concepts underpinning conceptual boundaries and a broad overview of the subject matter. Published guidelines, state-specific Medicaid websites, headache quality measurement sets, literature review, and expert opinion were used to tailor suggested treatment options and therapeutic strategies. In this second part of our narrative review, we explored migraine care strategies and considerations for underserved and vulnerable adult populations with migraine. RESULTS Although common, migraine remains untreated, particularly among those of low socioeconomic status. Low socioeconomic status may play an important role in the disease progression, prescription of hazardous medications such as opioids, outcomes, and quality of life of patients with migraine and other headache disorders. There are some evidence-based and guideline supported treatment options available at low cost that include prescription medications and supplements, though approved devices are costly. Resources available online and simple nonpharmacological strategies may be particularly useful in the underserved migraine population. CONCLUSIONS We identified and discussed migraine treatment barriers that affect underserved populations in the US and summarized practical, cost-effective strategies to surmount them. However, more research is needed to identify the best cost-effective measures for migraine management in underserved and vulnerable patients who are uninsured or underinsured.

Objective To review the scope of the problem facing individuals with migraine who are under- or uninsured. In this first of a 2-part narrative review, we will explore migraine epidemiology and the challenges that face this vulnerable population. Background Implementation of the Affordable Care Act has improved access to health care for many individuals who were previously uninsured, but there are many, particularly those of certain demographics, who are at high risk for worse outcomes. Methods A narrative review was performed after a series of discussions within the Underserved Populations in Headache Medicine Special Interest Section meetings of the American Headache Society. Literature was reviewed for key concepts underpinning conceptual boundaries and a broad overview of the subject matter. Published guidelines, state-specific Medicaid websites, headache quality measurement set, literature review, and expert opinion were used to tailor suggested treatment options and therapeutic strategies. Results Migraine is common, yet remains underdiagnosed and associated with worse outcomes among those of under-represented backgrounds and those who are underinsured or uninsured. Low socioeconomics may play an important role in the disease progression, characteristics, outcome, and quality of life of patients with migraine and other headache disorders. Other barriers to optimal care include time constraints, lack of access to specialty providers, transportation, and financial limitations. Conclusion There are many barriers and challenges that affect people with migraine who are underinsured or uninsured, particularly those of under-represented racial backgrounds and of lower socioeconomic status.

Introduction People with migraine often report being osmophobic, both during and between acute migraine attacks. It is not clear, however, whether such reports are associated with changes in olfaction such as hyperosmia, as measured by psychophysical testing. In this case-control study we quantitatively assessed olfactory identification ability, which correlates with threshold tests of olfactory acuity, in patients with migraine at baseline (no headache), during migraine episodes, and after a treated attack and compared the test scores to those of matched control subjects. Methods Fifty episodic migraine subjects and 50 and sex- and age-matched controls without headache were tested. All completed the University of Pennsylvania Smell Identification Test (UPSIT), a standardized and well-validated olfactory test. Results At baseline, the UPSIT scores did not differ significantly between the migraine and control study groups (median paired score difference: −1, p = 0.18). During migraine attacks, a minority of migraine subjects (eight of 42) developed microsmia (i.e. lower test scores by at least four points), suggesting that, as compared to their matched controls, olfactory acuity was somewhat impaired during migraine attacks ( p = 0.02). This difference was less pronounced and not statistically significant after a successfully treated attack ( p = 0.15). Discussion People with episodic migraine were found to have similar olfactory function as age- and sex-matched controls, but a minority exhibit microsmia or hyposmia during acute attacks. The cause of this dysfunction is unknown, but could relate to autonomic symptoms, limbic system activation, or disorders of higher order sensory processing.

Our aim was identify brain areas involved in the premonitory phase of migraine using functional neuroimaging. To this end, we performed positron emission tomography scans with H2(15)O to measure cerebral blood flow as a marker of neuronal activity. We conducted positron emission tomography scans at baseline, in the premonitory phase without pain and during migraine headache in eight patients. We used glyceryl trinitrate (nitroglycerin) to trigger premonitory symptoms and migraine headache in patients with episodic migraine without aura who habitually experienced premonitory symptoms during spontaneous attacks. The main outcome was comparing the first premonitory scans in all patients to baseline scans in all patients. We found activations in the posterolateral hypothalamus, midbrain tegmental area, periaqueductal grey, dorsal pons and various cortical areas including occipital, temporal and prefrontal cortex. Brain activations, in particular of the hypothalamus, seen in the premonitory phase of glyceryl trinitrate-triggered migraine attacks can explain many of the premonitory symptoms and may provide some insight into why migraine is commonly activated by a change in homeostasis.

Objective The objective of this report is to compare computed tomography (CT) and magnetic resonance (MR) myelography with radioisotope cisternography (RC) for detection of spinal cerebrospinal (CSF) leaks. Methods We retrospectively reviewed 12 spontaneous intracranial hypotension (SIH) patients; CT and RC were performed simultaneously. Three patients had MR myelography. Results CT and/or MR myelography identified CSF leaks in four of 12 patients. RC detected spinal leaks in all three patients confirmed by CT myelography; RC identified the CSF leak location in two of three cases, and these were due to osteophytic spicules and/or discs. RC showed only enlarged perineural activity. Only intrathecal gadolinium MR myelography clearly identified a slow leak from a perineural cyst. In eight remaining cases, the leak site was unknown; however, two of these showed indirect signs of CSF leak on RC. CSF slow leaks from perineural cysts were the most common presumed etiology; and the cysts were best visualized on myelography. Conclusion RC is comparable to CT myelography but has spatial limitations and should be limited to atypical cases.

Tension-type headache (TTH) is the most prevalent primary headache disorder. An important factor in the long-term prognosis of TTH is the overuse of acute medications used to treat headache. There are many reasons why patients with TTH overuse acute medications, including biobehavioral influences, dependency, and a lack of patient education. Chronic daily headache occurs in 4.1% of the general population, and chronic tension-type headache and medication overuse headache (MOH) occur in approximately 2.2% and 1.5%, respectively. A proper diagnosis is essential for the treatment of these patients. Treatment should include pathological considerations concerning TTH and MOH, which include peripheral and central mechanisms. Because TTH with MOH carries the worst prognosis, more clinical studies focusing on the complex interaction and treatments of TTH and MOH are needed.

Objective: To examine the association between migraine and stroke/vascular outcomes in a racially/ethnically diverse, older cohort. Methods: Participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were assessed for migraine symptoms using a self-report questionnaire based on criteria from the International Classification of Headache Disorders, second edition . We estimated the association between migraine and combined vascular events including stroke and stroke only over a mean follow-up of 11 years, using Cox models adjusted for sociodemographic and vascular risk factors. Results: Of 1,292 participants (mean age 68 ± 9 years) with migraine data followed prospectively for vascular events, 262 patients (20%) had migraine and 75 (6%) had migraine with aura. No association was found between migraine (with or without aura) and risk of either stroke or combined cardiovascular events. There was an interaction between migraine and current smoking ( p = 0.02 in relation to stroke and p = 0.03 for combined vascular events), such that those with migraine and smoking were at an increased risk. The hazard ratio of stroke for migraine among current smokers was 3.17 (95% confidence interval [CI] 1.13–8.85) and among current nonsmokers was 0.77 (95% CI 0.44–1.35). In relation to combined vascular events, the hazard ratio for migraine vs no migraine among current smokers was 1.83 (95% CI 0.89–3.75) and among current nonsmokers was 0.63 (95% CI 0.43–0.94). Conclusion: In our racially/ethnically diverse population-based cohort, migraine was associated with an increased risk of stroke among active smokers but not among nonsmokers.

This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7-88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.

In this issue of Cephalalgia, Lucas et al. report on the natural history of headache following mild traumatic brain injury (TBI) in a civilian patient population. This interesting study adds to the growing body of knowledge related to the prognosis and characteristics of post-traumatic headache (PTH). It is also one of only a few studies on head-injured patients that classified headaches using standardized diagnostic criteria over multiple time points, so it is of particular interest. Study subjects consisted of 212 patients (76% male, mean age 44) at one level 1 trauma center. Subjects were enrolled within one week of sustaining a mild TBI (concussion), most often due to a motor vehicle accident (58%) or fall (24%). Interviews were initially conducted face to face and then by telephone up to one year after the injury. Subjects with ‘‘new or worse’’ headaches compared to before the injury were considered to have PTH. Headaches were classified as migraine, probable migraine, tension-type, and cervicogenic. Previous studies by this team (1,2) were based on a cohort of Veterans Administration (VA) rehabilitation patients with a wider range of head injury severity although used similar headache classification methodology. The primary findings of the present study were that a) between 54% and 69% of subjects reported new/ worse headaches at each interview although a smaller number (41%) reported this consistently at all interviews; b) of those reporting headache, the predominant subtype at three months was tension-type (37%) followed by probable migraine (25%) and migraine (24%); and c) peak incidence of new/worse headache was at the baseline (< 1 week post-injury) and first follow-up (three months post-injury) interviews. Several questions naturally flow from this and other recent studies. 1) What is the expected incidence of PTH and to what extent can we attribute this to the injury per se? In the present study, new-onset headache in general and migraine-like headache in particular were clearly more likely in these patients with head injuries than would be seen in an ageand gender-equivalent nonclinical population. For example, the one-year incidence of International Classification of Headache Disorders (ICHD) migraine in men in the general population has been reported to be less than 1 per 100 person years (3) although the incidence of subjectively worsened headache is unknown. What would be the expected incidence of ICHD migraine in a comparable ‘‘at-risk’’ population such as (for the present study) a predominantly male inpatient population with recent injuries of comparable severity not involving the head? It is possible, even likely, that an injured control group without head injuries would have a higher than expected incidence of headache for a variety of plausible reasons. The reality is that it is difficult to find truly ‘‘comparably injured’’ control groups without head injuries and then there is the added issue of generalizability and overmatching even when available. The few (to our knowledge) prospective studies of TBI patients

Despite the growing awareness of mild traumatic brain injury in military and civilian populations, understanding of the acute and chronic effects of concussion on central nervous system structure and function is limited. Even less is understood about the underpinnings of the cardinal postconcussive symptom, post-traumatic headache (PTH). Here, we review recent advances in PTH, with special emphasis on the migraine-like phenotype, the most disabling form. Considerations for future research in PTH are discussed, including diagnostic classification, and applications with advanced neuroimaging techniques, biomarkers, and treatments.

Objective: To investigate the association between migraine and hypertension in the Northern Manhattan Study (NOMAS), a multiethnic community-based sample. Design: Cross-sectional cohort study. Participants:1338 NOMAS participants (mean age 68.1±9.6 years, 37% male, 15% non-Hispanic White, 19% non-Hispanic Black, 67% Hispanic). Setting: Northern Manhattan community. Intervention: Participants were assessed for migraine symptoms using a self-report questionnaire based on criteria from the International Classification of Headache Disorders. Hypertension was defined as blood pressure ≥140/90 mm Hg, the patient’s self-reported hypertension, or use of anti-hypertensive medications. Duration (≤9 years vs >9 years) and control (BPResults: The majority of participants (80%) had no migraine, 6% had migraine with aura, and 15% had migraine without aura. Hypertension was present in 76% of the study population (7% had controlled hypertension ≤9 years duration, 5% controlled hypertension >9 years duration, 41% uncontrolled hypertension ≤9 years duration, 23% uncontrolled hypertension >9 years duration). Hypertension was associated with migraine (OR: 1.76, 95% CI: 1.21-2.54), both with and without aura. This association was particularly apparent for those with uncontrolled and long duration hypertension. Conclusion: Hypertension, particularly uncontrolled and of long duration, is associated with migraine, both with and without aura, in a predominantly Hispanic community-based cohort. Ethn Dis. 2016;26(3):323-330; doi:10.18865/ed.26.3.323

Tension type headache (TTH) is a primary headache disorder considered common in children and adolescents. It remains debatable whether TTH and migraine are separate biological entities. This review summarizes the most recent literature of TTH with regards to children and adolescents. Further studies of TTH are needed to develop a biologically based classification system that may be facilitated through understanding changes in the developing brain during childhood and adolescence.

X-linked adreno-leukodystrophy and its adult variant, adrenomyeloneuropathy, are caused by mutations in ABCD1 that encodes a peroxisomal membrane protein of unknown physiological significance. In spite of identical mutations, they can have markedly divergent neurological and neuropathologic characteristics. Adreno-leukodystrophy classically presents in normal boys with mild neuropsychiatric features, which progress to frank neurological signs, the vegetative state and death in approximately three years. Adrenomyeloneuropathy typically affects young men with spastic paraparesis and sensory ataxia that can progress over decades. The neuropathologic correlate for adreno-leukodystrophy is severe inflammatory demyelination of posterior cerebral white matter, while a chronic distal axonopathy of spinal cord and peripheral nerve occurs in adrenomyeloneuropathy. Consequently, both modifier genes and environmental factors have been implicated in their pathogeneses. We report five cases of adreno-leukodystrophy whose onsets were initiated by moderate to severe head trauma, two of whom were conversions from adrenomyeloneuropathy. Their clinical courses were rapidly incapacitating, short (i.e., weeks to a few years) and fatal due to marked cerebral inflammatory demyelination. These cases, in concert with several previous reports, indicate that head trauma is one environmental factor that can have a profoundly deleterious effect on those genetically at risk for, or with milder clinical phenotypes of, this disease. Avoidance of potential head trauma and a rapid response to episodes of moderate to severe head trauma in this patient population seem prudent.

Opinion statementThe conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT(1B/1D) receptor agonists. The ergots, consisting of ergotamine and dihydroergotamine (DHE), are the oldest specific antimigraine drugs available and are considered relatively safe and effective. Ergotamine has been used less extensively because of its adverse effects; DHE is better tolerated. The triptan era, beginning in the 1990s, was a period of considerable change, although these medicines retained vasoconstrictor actions. New methods of delivering older drugs include orally inhaled DHE and the transdermal formulation of sumatriptan, both currently under study. Novel medicines being developed are targeted at neural sites of action. Serotonin 5-HT(1F) receptor agonists have proven effective in phase II studies and have no vascular actions. Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. Other targets under investigation include glutamate (AMPA/kainate), TRPV1, prostanoid EP4, and nitric oxide synthase. With new neural targets and the potential for therapeutic advances, the next era of antimigraine medications is near.