Exacerbation Of Headache Research Articles

Understanding Experiences of Headache-Sufferers Attending Emergency Departments Through Photovoice.

Our aim was to explore the experiences of individuals receiving emergency department (ED) care for acute headaches. Patients with headache exacerbations commonly present to EDs. This study explored the experiences of adult patients during the exacerbation period, specifically using photovoice. Recruited from two urban EDs in Alberta, Canada, participants with primary headaches took photographs over 3-4 weeks and subsequently completed a 60-90 minute, one-on-one, in-person photo-elicitation interview. Interviews were audio recorded, transcribed and thematically analyzed alongside photographs. Eight participants (six women) completed the study. The average age was 42 years (standard deviation: 16). Five themes emerged: (1) the struggle for legitimacy in light of the invisibility of their condition; (2) the importance of hope, hopelessness and fear in the day-to-day life of participants; (3) the importance of agency and becoming "your own advocate"; (4) the struggle to be and be seen as themselves despite the encroachment of their headaches; and (5) the realities of "good" and "bad" care in the ED. Participants highlighted examples of good care, specifically when they felt seen and believed. Additionally, some expressed the acute care space itself being a beacon of hope in the midst of their crisis. Others felt dismissed because providers "know it's not life or death." This study highlighted the substantial emotional impact that primary headaches have on the lives of participants, particularly during times of exacerbation and while seeking acute care. This provides insight for acute care settings and practitioners on how to effectively engage with this population.

Pharmacological Dissociation in Hemicrania Continua With Persistent Visual Aura Evolved From Episodic Migraine: A Case Report.

To report a case of hemicrania continua (HC) and persistent visual aura without infarction in a patient with previous episodic migraine with visual aura, whose persistent aura symptoms improved only after treatment with divalproex sodium. Once regarded as highly specific for migraine, visual aura has been associated with trigeminal autonomic cephalalgias, including HC. In previous descriptions of HC and episodes of typical visual aura, the aura occurred exclusively with severe headache exacerbations and, like the pain, resolved with indomethacin. Case report and literature review. A 54-year-old man with a history of episodic migraine with visual aura reported a gradual onset of HC with persistent visual aura of 15 months duration. General medical and neurological examinations were normal, including imaging studies. HC's headache responded to indomethacin, while the visual aura was recalcitrant, only improving with oral divalproex sodium treatment. As our patient experienced HC, which evolved from episodic migraine, we hypothesize that migraine and HC may share a common pathophysiology. However, the persistence of the visual aura, despite the abolition of pain and autonomic features with a therapeutic dose of indomethacin, and the subsequent successful treatment of the aura with divalproex sodium, suggest that aura and HC headache arise from distinct and dissociable mechanisms.

A case report of reversible cerebral vasoconstriction syndrome with thunderclap headache significantly exacerbated in the supine position and alleviated in the standing position

BackgroundReversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden onset thunderclap headache and multiple segmental reversible cerebral vasoconstrictions that improve within 3 months. The postpartum period is a well-known precipitating factor for the onset of RCVS. Cerebral venous thrombosis (CVT) causes thunderclap headaches in the postpartum period. While headache in CVT is sometimes exacerbated in the supine position, the severity of the headache in RCVS is usually independent of body position. In this study, we report a case of RCVS with thunderclap headache exacerbated in the supine position, and headache attacks that resolved quickly in the standing position during the postpartum period.Case presentationA 33-year-old woman presented with a sudden increase in blood pressure and thunderclap headache on the fifth postpartum day (day 1: the first sick day). The headache was severe and pulsatile, with onset in the supine position in bed, and peaked at approximately 10 s. It was accompanied by nausea and chills but there were no scintillating scotomas or ophthalmic symptoms. The headache resolved in the standing or sitting position but was exacerbated and became unbearable within a few seconds when the patient was in the supine position. Therefore, she was unable to lie supine at night. Computed tomography angiography (CTA) of the head on day 2 and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) on day 3 showed no abnormalities. However, considering the possibility of RCVS, verapamil was initiated on day 3. The headache resolved the following day. MRA of the head on day 10 revealed diffuse and segmental stenoses in the bilateral middle and posterior cerebral arteries and basilar artery. Therefore, the patient was diagnosed with RCVS. The headache gradually resolved and disappeared completely on day 42. Cerebral vasoconstriction was also improved on MRA on day 43.ConclusionsThis postpartum RCVS case was notable for the exacerbation of headaches in the supine position. For the diagnosis of thunderclap headache in the postpartum period, RCVS should be considered in addition to CVT when the patient presents with a headache that is exacerbated in the supine position.

Assessing the Prevalence of Ectopic Cerebellar Tonsils and Accompanying Symptoms in Individuals with Various Headaches.

Chiari malformation exhibits well-defined clinical signs, symptoms, and incidence rates in clinical studies. However, cerebellar tonsil ectopia presents with ambiguous symptoms and undetermined incidence rates in numerous studies. Our objective was to determine the incidence of cerebellar tonsil ectopia in individuals with headaches and identify additional clinical symptoms. This aims to improve diagnosis accuracy for clinicians and neurologists, leading to more effective treatment approaches. A cross-sectional study conducted in 2022 included 2305 participants aged 4-78 years presenting with headache. Chiari malformation was diagnosed using magnetic resonance imaging (MRI) scans, with a definition of cerebellar tonsil herniation extending beyond 5mm into the cervical canal. The prevalence of Chiari malformation was 3.4%, with no significant gender difference (p = 0.72). There was a significant correlation between Chiari malformation and headache exacerbation due to the Valsalva maneuver (p < 0.001) and the presence of vertigo (p < 0.001). No significant association was found between Chiari malformation and accompanying symptoms such as nausea (p = 0.43), photophobia (p = 0.2), phonophobia (p = 0.52), and speech disorders (p = 0.45). These findings suggest a notable prevalence of Chiari malformation among headache patients and its association with specific headache characteristics, such as acute and occipital headaches, exacerbation by the Valsalva maneuver, and the co-occurrence of vertigo. These results underscore the need to consider Chiari malformation in the differential diagnosis of patients presenting with these specific headache features.

COVID-19 Pandemisi Sırasında Sağlık Çalışanlarında Maskeyle İlişkili Baş Ağrısı: Somali'den Çalışma

Aim: After the outbreak of Coronavirus Disease 2019 (COVID-19), new headaches have been reported to develop or worsen among healthcare workers who regularly wear personal protective equipments. In this study, we investigated the possible relationship between de-novo (new-onset) headache features associated with the mask used and pre-existing and exacerbated headaches. It is the first study on this subject on behalf of Somalia. Methods: This is a cross-sectional study conducted at the Mogadishu COVID-19 pandemic hospital, Somalia, with volunteer healthcare workers. Data were collected through a questionnaire. Participants were asked 15 questions in the survey and Pearson-chi-square test was used as statistics. Results: This study was conducted with 200 healthcare workers working in the hospital, 114 (57%) were male, 86 (43%) were female, and the mean age was 28. Participants 90 (45%) used surgical masks, 32 (16%) filtered masks (N95), 78 (39%) both; majority of 109 (54.5%) wore masks for more than 6 hours a day. Pre-existing headache was reported by78(39%) of the subjects. 55(70%) of those with pre-existing headache reported aggravation of their headache. Statistically significant relationship was found between duration of mask use and aggravation of pre-existing headache. De-novo headache characteristics were throbbing 21(20%), pressing 31(29%), unilateral 19(18%), and 35(33%) bilateral. A statistically significant relationship was also found between the duration of use of face mask and the development of de-novo headache, regardless of mask type. Conclusion: As per our study, prolonged use of face masks during COVID-19 pandemics was associated with de-novo headaches and exacerbation of pre-existing headache. This situation, which has caused complaints as healthcare professionals and some patients continue to wear masks, will continue to be investigated.

Activation of the microglial P2X7R/NLRP3 inflammasome mediates central sensitization in a mouse model of medication overuse headache.

Excessive use of headache treatments often leads to the development, progression and exacerbation of primary headache, which is defined as medication overuse headache (MOH). A significant pathophysiological mechanism of MOH is central sensitization. Recent evidence suggests that central sensitization in chronic headache is a result of inflammatory responses mediated by microglial activation in the trigeminal nucleus caudalis (TNC). However, it is unknown whether microglial activation has an impact on the central sensitization of MOH. Accordingly, the goal of this research was to determine how microglial activation and the P2X7R/NLRP3 inflammasome signaling pathway in the TNC contribute to the pathogenesis of MOH. Repeated intraperitoneal injection of sumatriptan (SUMA) was used to establish a mouse model of MOH. Basal mechanical hyperalgesia was evaluated using von Frey filaments. As central sensitization biomarkers, the c-Fos and CGRP expression levels were measured by immunofluorescence analysis. We estimated the expression of microglial biomarkers (Iba1 and iNOS) within the TNC by qRT-PCR, western blotting and immunofluorescence analysis. To elucidate the effect of microglial activation and the P2X7/NLRP3 signaling pathway on central sensitization in MOH, we evaluated whether the microglia-specific inhibitor minocycline, the P2X7R-specific antagonist BBG and the NLRP3-specific inhibitor MCC950 altered SUMA-caused mechanical hyperalgesia. Furthermore, we examined c-Fos and CGRP expression within the TNC following individual injections of these inhibitors. Repeated SUMA injection induced basal mechanical hyperalgesia, increased c-Fos and CGRP levels, and activated microglia within the TNC. Inhibiting microglial activation with minocycline prevented the emergence of mechanical hyperalgesia and cut down c-Fos and CGRP expression. Immunofluorescence colocalization analysis revealed that P2X7R was predominantly co-localized with microglia. The levels of P2X7R and the NLRP3 inflammasome were elevated by repeated SUMA injection, and blocking P2X7R and NLRP3 inhibited mechanical hyperalgesia and cut down c-Fos and CGRP expression within the TNC. Based on the current findings, inhibiting microglial activation could reduce central sensitization caused by chronic SUMA treatment via the P2X7R/NLRP3 signaling pathway. The clinical management of MOH may benefit from a novel strategy that inhibits microglial activation.

Headache associated with COVID-19 vaccination: how to classify?

In the setting of acute COVID-19 infection, headache occurs in 10-60% of patients and may last for days and, in asmaller proportion of patients, weeks (about 10%). However, it is less recognized that headache may also occur after vaccination with ashort latency and may persist for alonger period in astill unclear number of patients. Retrospective description of headache and course in acase series of32 outpatients with headache that changed or recurred after COVID-19 vaccination. The majority of patients experienced an exacerbation of migraine headache; rare headache syndromes such as intracranial hypertension or thunderclap headache occurred in 2patients. Headache manifested in more than 50% of patients within the first 48 h after vaccination. Over 50% of patients who received atriptan improved. The pathophysiological relationship between vaccination and persistent headache is not yet clearly understood. The short latency, partial efficacy of cortisone, and initial findings showing an increase of various inflammatory markers during the course of headache in COVID infection suggest apossible involvement of the innate immune system and here the inflammasome. Furthermore, the response to triptan in aproportion of patients also indicates activation of the trigeminovascular system.

The Relationship Between Food Allergens and Migraine Among Patients With Migraine Referring to Shahid Mohammadi Neurology Clinic

Background: Although diet-induced migraines affect many people, the triggering foodstuffs are not fully identified yet. Detecting migraine-triggering foods and susceptible individuals assist in effective headache management. The aim of this study was to determine the relationship between eating allergens and developing or exacerbating migraine. Methods: This was a descriptive-analytical cross-sectional study with 230 migraine patients referring to the neurology clinic of Shahid Mohammadi hospital in Bandar Abbas. They were selected through purposive sampling. After obtaining informed consent from the patients, the required data were collected and then underwent analysis. Results: Overall, 52.4% and 47.6% of participants were females and males, respectively. Their mean age was 40.57±14.04. Based on the results, 61.9% of participants were married, and 60.3% of them had a family history of migraine. The average number of headaches per month and the duration of each headache were 3.16-4.19 times and 3.76-4.41 hours, respectively. Based on the findings, sausages (55.6%), carbonated beverages (0.54%), peanuts (0.46%), beef (44.4%), and canned food, coffee, and eggs (41.3%) are the most common foodstuffs that cause or exacerbate migraines. On the other hand, chicken (15.9%), strawberry, rice, and wheat (17.5%) had the least impact on the onset and exacerbation of migraine headaches. Conclusion: According to the results, identifying food allergens and eliminating them from patients’ diets can be effective in the prognosis of migraine and individuals’ quality of life.

Migraine and infertility, merging concepts in women's reproductive health: A narrative review.

The objective is to examine issues around treating infertility in patients with migraine. Women outnumber men in migraine diagnosis with a 3:1 ratio; the disease is commonly expressed in women of child-bearing age and is influenced by changes in circulating hormones. Infertility is also common, and the use of treatment options, such as assisted reproductive technology, have expanded exponentially in recent years. We summarized the literature around the effect of infertility treatments on headache in the general population and migraine population. We also discuss sociobehavioral, economic, and biological factors affecting fertility in patients with migraine, describe infertility protocols, and propose areas of focus for future research. We searched PubMed for the combined key terms in vitro fertilization or assisted reproductive technology AND migraine, or headache. The search included all dates and specified English-language results only. Migraine may negatively influence family planning and fertility. Patients face obstacles stemming from the impact of migraine on social relationships and the interference of preventive medications on pregnancy. Migraine may also be associated with an increased prevalence of endocrine disorders which in turn affect fertility. Moreover, infertility treatments are associated with mild headache as a side effect. In addition, we found only one retrospective study demonstrating an increase in headache frequency during in vitro fertilization in the migraine population. We determined that there is little research focused specifically on migraine headache exacerbation and other migraine-associated health outcomes with infertility treatment. This topic merits further interdisciplinary exploration.

Migraine and light: A narrative review.

In this narrative review, we summarize clinical and experimental data on the effect of light in migraine and discuss future prospects. Effective nonpharmacological treatment of hypersensitivity to light in migraine is an unmet clinical need. Current management strategies primarily consist of seeking a dark room and avoiding light exposure. Advances in the past 2 decades have improved our understanding of the underlying pathophysiology of how migraine is influenced by light. This may provide promising avenues for novel approaches in clinical management. We searched MEDLINE for articles published from database inception up to September 1, 2021. We used the search term "migraine" with the search terms "light," "photophobia," "treatment," "trigger," "circadian rhythm," "environment," and/or "pathophysiology." Light is commonly reported as a trigger factor of migraine attacks, however, early manifestation of photophobia and false attribution is likely the actual cause based on data deriving from retrospective, prospective, and experimental studies. The most common photophobia symptoms in migraine are exacerbation of headache by light and abnormal sensitivity to light with the underlying neural pathways likely being dependent on ongoing activity in the trigeminovascular system. Clinical studies and experimental models have identified mediators of photophobia and uncovered narrow wavebands of the light spectrum that may reduce pain intensity during a migraine attack. Consequently, novel devices have undergone exploratory clinical trials with promising results. False attribution is likely the reason why light is commonly reported as a trigger factor of migraine attacks, and a prospective confirmation is required to prevent unnecessary avoidance. The observation that individuals with migraine are not equally photophobic to all wavebands of the light spectrum opens the potential for innovative pain management strategies. In this context, using human-centric lighting (also called integrative lighting) to mimic the natural daylight cycle and avoid harmful wavebands through modern technology may prove beneficial. Future research should identify direct and indirect consequences of light and other environmental factors in migraine to fill out knowledge gaps and enable evidence-based care strategies within institutions, work environments, and other settings.

COVID-19-related headache and sinonasal inflammation: A longitudinal study analysing the role of acute rhinosinusitis and ICHD-3 classification difficulties in SARS-CoV-2 infection.

BackgroundThe genesis of headache in coronavirus disease 2019 (COVID-19) is currently unclear and the multitude of disease symptoms often further hinders locating the source of pain. Interestingly, many subjects with COVID-19 have symptoms of acute rhinosinusitis. The relation between nasal symptoms and headache in SARS-CoV-2 infection remains unknown.MethodsThis bi-center longitudinal study evaluated symptoms in consecutive COVID-19 patients in the participating practices. The first assessment was performed during the initial consultation after infection confirmation. That was followed up by a second consultation after a median 9 days.Results130 patients were included in the study (80 women, 50 men; mean age 46.9 years). Headache was highly prevalent at the first visit (72%) and significantly associated with acute rhinosinusitis symptoms. The odds ratio for headache in subjects with rhinosinusitis was 3.5. Headache could be attributed to systemic viral infection in 96% and to acute rhinosinusitis in 51% of cases according to 3rd edition of the International Classification of Headache Disorders. Criterium C.3 (exacerbation of headache by pressure applied over paranasal sinuses) and C.4 (ipsilaterality of headache and sinusitis) had low sensitivity in headache attributed to acute rhinosinusitis.ConclusionsNasal inflammation is associated with headache in COVID-19, although the pain mechanism lies probably in a systemic reaction to the virus. 3rd edition of the International Classification of Headache Disorders criteria for headache attributed to acute rhinosinusitis need adjusting to the current understanding of acute sinonasal infection.

COVID-19 in a Hemorrhagic Neurovascular Disease, Cerebral Cavernous Malformation

COVID-19 in a Hemorrhagic Neurovascular Disease, Cerebral Cavernous Malformation

Air pollution, methane super-emitters, and oil and gas wells in Northern California: the relationship with migraine headache prevalence and exacerbation

BackgroundMigraine–an episodic disorder characterized by severe headache that can lead to disability–affects over 1 billion people worldwide. Prior studies have found that short-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone increases risk of migraine-related emergency department (ED) visits. Our objective was to characterize the association between long-term exposure to sources of harmful emissions and common air pollutants with both migraine headache and, among patients with migraine, headache severity.MethodsFrom the Sutter Health electronic health record database, we identified 89,575 prevalent migraine cases between 2014 and 2018 using a migraine probability algorithm (MPA) score and 270,564 frequency-matched controls. Sutter Health delivers care to 3.5 million patients annually in Northern California. Exposures included 2015 annual average block group-level PM2.5 and NO2 concentrations, inverse-distance weighted (IDW) methane emissions from 60 super-emitters located within 10 km of participant residence between 2016 and 2018, and IDW active oil and gas wells in 2015 within 10 km of each participant. We used logistic and negative binomial mixed models to evaluate the association between environmental exposures and (1) migraine case status; and (2) migraine severity (i.e., MPA score > 100, triptan prescriptions, neurology visits, urgent care migraine visits, and ED migraine visits per person-year). Models controlled for age, sex, race/ethnicity, Medicaid use, primary care visits, and block group-level population density and poverty.ResultsIn adjusted analyses, for each 5 ppb increase in NO2, we observed 2% increased odds of migraine case status (95% CI: 1.00, 1.05) and for each 100,000 kg/hour increase in IDW methane emissions, the odds of case status also increased (OR = 1.04, 95% CI: 1.00, 1.08). We found no association between PM2.5 or oil and gas wells and migraine case status. PM2.5 was linearly associated with neurology visits, migraine-specific urgent care visits, and MPA score > 100, but not triptans or ED visits. NO2 was associated with migraine-specific urgent care and ED visits, but not other severity measures. We observed limited or null associations between continuous measures of methane emissions and proximity to oil and gas wells and migraine severity.ConclusionsOur findings illustrate the potential role of long-term exposure to multiple ambient air pollutants for prevalent migraine and migraine severity.

Air pollution, methane super-emitters, and oil and gas wells in Northern California: the relationship with migraine headache prevalence and exacerbation (1194)

Air pollution, methane super-emitters, and oil and gas wells in Northern California: the relationship with migraine headache prevalence and exacerbation (1194)

Headache in Susac’s Syndrome

Provide an overview of the current diagnosis, pathophysiology, and treatment of Susac's syndrome (SuS), with special emphasis on summarizing what is currently known about headache as a symptom of disease activity. The most recent literature in SuS has focused on furthering the understanding of the underlying pathology and efficacy of treatments for SuS. The importance of early recognition to facilitate timely treatment and avoid long-term disability has been highlighted. Headache, the most common symptom experienced by patients with SuS, can occur up to 6 months in advance of other symptoms, and exacerbations of headache can herald increased disease activity. Susac's syndrome (SuS) is a rare disorder classically characterized by triad of encephalopathy, branch retinal artery occlusion (BRAO), and sensory neuronal hearing loss (SNHL). The full triad is uncommon at initial presentation, which can confound efforts to make timely diagnosis and treatment decisions. Headache is the most common symptom in SuS, is often an early feature, and can help separate SuS from other diagnoses in the differential. However, the features and management of the headache associated with SuS have not been systematically defined in the literature.

New therapeutic agents marketed in 2020: Part 1

New therapeutic agents marketed in 2020: Part 1

Three dimensional reconstruction imaging of temporomandibular joint synovial chondromatosis

AbstractAimWe have completed the first documented three dimensional (3D) reconstruction of temporomandibular joint synovial chondromatosis from computed tomography and discuss the application of this technique in diagnosis and treatment of this condition with particular relevance to its surgical management.We describe our case of a 52‐year‐old woman who was admitted to the medical assessment unit with an acute exacerbation of headaches; diagnostic head imaging revealed left TMJ calcification most suggestive of synovial osteochondromatosis.Methods and materialsMaterialise Mimics inPrint 3.0 is an advanced tool that allows for the import of medical image data from either CT or magnetic resonance imaging (MRI) as DICOM files. The data is analysed by the user and then an image is segmented in an accessible environment resulting in an accurate 3D anatomical model that can be 3D printed or visualised in either augmented reality or virtual reality (AR/VR).ResultsWe demonstrate our novel 3D reconstruction of this florid appearance of TMJ SC from an incidental finding on CT.ConclusionThis is an unusual presentation of a rare condition; despite the florid appearance on imaging, the patient’s function was entirely normal. TMJ SC is a benign condition but can require surgical management. We present our novel 3D imaging technique for diagnosis and to aid surgical management.

The Effectiveness of Compassion-focused Therapy for Improving Emotional Control and Reducing the Severity of Pain in Migraine Patients

Objective: Because of the unwanted effects of the patient’s migraine headaches and the role of excitement and stress in the development and exacerbation of headaches, migraine headaches are psychosomatic disorders that affect the patients’ psychological lives. The present study aimed to investigate the effectiveness of Compassion-Focused Therapy (CFT) for improving emotional control and reducing the severity of pain in patients with migraines. Methods: A total of 30 patients with migraines referred to Isfahan Al-Zahra Hospital, Isfahan City, Iran, were selected and randomly divided into experimental and control groups. The research instruments included the Emotion Control Questionnaire (ECQ), von Korff’s questionnaire for grading the severity of chronic pain, and the Migraine Disability Assessment (MIDAS) questionnaire. The experimental group received eight 90-min sessions of CFT, and both groups took the post-test after finishing the training sessions. Analysis of the data involved both descriptive and inferential statistics, including mean, standard deviation, Multivariate Analysis of Covariance (MANCOVA), and Analysis of Covariance (ANCOVA). Results: The results showed that the training based on CFT had a significant effect on improving emotional control and its subscales (F=21.81; P&lt;0.01), as well as reducing pain severity in the patients (F=17.21; P&lt;0.01). Conclusion: Therefore, in treating migraine patients, CFT can be a useful supplementary approach along with medications.

Cortical pain modulatory functional enhancement after rTMS associated with durable headache improvement in mTBI patients

Background: Repetitive transcranial magnetic stimulation (rTMS) is able to alleviate mild traumatic brain injury-related headache (mTBI-HA). This functional magnetic resonance imaging (fMRI) study assessed the supraspinal correlates associated with the lasting analgesic effect of rTMS at the left dorsolateral prefrontal cortex (LDLPFC). Methods: Patients with mTBI-HA were randomized to receive either real or sham rTMS and subjected to pre- and post-treatment resting state and evoked heat pain fMRI consisting of 20 cycles of baseline temperature at 32°C for 30 seconds and 46°C for 10 seconds. Real rTMS consisted of 2000 pulses delivered at 10hz, 80% resting motor threshold at the LDLPFC. A follow-up fMRI was then performed one week after the treatment and headache clinical outcomes were assessed for one month. Results: 14 and 12 patients received real and sham treatments, respectively. The REAL group demonstrated significant (P<0.01) decreases in average daily headache intensity, debilitating headache exacerbation frequency and composite scores, and prevalence of persistent headache at one week following treatment. At one month, the REAL group demonstrated a significant decrease in daily headache intensity (P<0.01), a strong trend toward decreased debilitating headache frequency (P=0.057), and a trend toward decreased prevalence of persistent headaches (P=0.106). Correlated fMRI studies in the REAL group showed increase in evoked heat pain activity and resting functional connectivity at the LPFC after rTMS. This significant analgesic effect and correlated fMRI findings were not found in the sham group. Conclusions: This study correlates the durable analgesic effect of rTMS in alleviating mTBI-HA with enhanced supraspinal functional connectivity in the left prefrontal cortex, which is a brain area known to be involved in “top-down” pain inhibition along the descending midbrain-thalamic-cingulate pathway. Conflicts of Interests: None to report. Funding: This work was supported by VA Rehabilitation and Research Development SPIRE Awards (21RX001359, 21RX002366) and Department of Defense Congressionally Directed Medical Research Program Grant (W81XWH-16-1-0754).

Hypersensitivity to Calcitonin Gene-Related Peptide in Post-Traumatic Headache.

To demonstrate that calcitonin gene-related peptide (CGRP) induces headache exacerbation with migraine-like features in patients with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). A randomized, double-blind, placebo-controlled, two-way crossover study was conducted. Analyses were intention-to-treat. Eligible patients were aged 18 to 65 years and had a history of persistent PTH after mild TBI for at least 12 months. Patients were randomized to receive an intravenous infusion of 1.5μg/min of CGRP or placebo (isotonic saline) over 20 minutes on two separate experimental days. A 12-hour observational period was used to evaluate the following outcomes: (1) difference in incidence of headache exacerbation with migraine-like features and (2) difference in area under the curve for headache intensity scores. Thirty patients (mean age = 37 years, 25 women [83%]) were randomized and completed the study. During the 12-hour observational period, 21 of 30 patients (70%) developed headache exacerbation with migraine-like features after CGRP, compared with 6 patients (20%) after placebo (p < 0.001). The baseline-corrected area under the curve for headache intensity scores was significantly larger after CGRP, compared with placebo (p < 0.001). Patients with persistent PTH are hypersensitive to CGRP, which underscores its pathophysiological importance. Furthermore, CGRP-targeted therapies might provide a novel mechanism-based treatment option for patients with persistent PTH. ANN NEUROL 2020;88:1220-1228.