Acute Headache Research Articles

Clinical prediction scale approach derived from a retrospective study to reduce the number of urgent, low-value cranial CT scans.

Fifty percent of cranial CT scans performed achieve no benefit and entail risks. Our aim is to determine the yield of non-traumatic urgent cranial-CT and develop a pretest clinical probability scale approach. Adult patients seen in our emergency department between 2017-2021 and referred for urgent cranial-CT for non-traumatic reasons were retrospectively recruited and randomly selected.Presenting complaint (PC), demographic variables, Relevant radiological findings (RRF) on the urgent cranial-CT and Relevant clinical-radiological findings (RCRF: admission need or RRF detection on the urgent cranial-CT or cranial CT/MRI in the following three months) were recruited. We recruited 702 patients, with median age 62 [47-76] years, 363 (51.7%) females.RCRFwere observed in 404 (57.55%); of these, 352 (50.1%) required admission. RRF were detected in 190 (27.06%): 36 acute ischemic and 27 acute hemorrhagic lesions, 115 masses, 9 edema, and 27 hydrocephalus.Predictive PC for urgent cranial-CT were motor, speech, sensory deficits, sudden alteration of mental status, epileptic seizure, cognitive impairment, neurological symptoms in cancer patients, acute headache without a prior history and with meningeal signs; nausea, vomiting, or hypertensive crisis; visual deficits, and dizziness. This algorithm provided sensitivity, specificity, positive predictive value, and negative predictive value (NPV, 95%CI in brackets) of 92.1% (89-94.5%), 27.5% (22.5-33.0%), 63.3% (59.2-67.2%), and 71.9% (62.7-80.0%), to diagnose RCRF, and 97.4% (93.4-99.1%), 21.3% (17.8-25.1%), 31.5% (27.7-35.4%), and 95.6% (90.1-98.6%), to diagnose RRF.In patients not requiring admission (n = 350), the NPV for RRF was 98.8% (93.6-100%); the negative likelihood ratio 0.08 (0.01-0.57), and sensitivity remained at 97.8% (82.2-99.9%). Applying it would have avoided performing 85/350 urgent cranial-CT (24.29%). To find one RRF, we would have gone from performing 7.8 (350/45) to 5.9 (265/45) CTs, failing to diagnose 1/45 (2.2%) RRF. This proposed clinical scale could potentially decrease 24% of urgent cranial-CT.

Acute headache with a twist

This case report follows the events of a 36-year-old woman who presented to a hospital five days post-partum with an acute severe headache and vomiting. Despite a normal initial computed tomography (CT) head scan, a CT venogram was done due to neurological deterioration and revealed hydrocephalus secondary to subarachnoid haemorrhage (SAH). We discuss the role of CT imaging in the diagnosis of SAH, the risks of current guidelines for lumbar puncture (LP) and describe other important differential diagnoses for headache in the postpartum patient.

Long-term effectiveness of eptinezumab in the treatment of patients with chronic migraine and medication-overuse headache.

This post hoc analysis of the PREVAIL study explored the effectiveness of eptinezumab for up to 2 years of open-label treatment in the subgroup of patients with chronic migraine who had a confirmed diagnosis of medication-overuse headache (MOH) at screening. MOH is a disabling and costly secondary headache disorder characterized by increased headache frequency and/or severity with increased acute headache medication use. Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduces headache frequency, severity, and associated disability and improves functioning and health-related quality of life as a preventive migraine therapy; short-term benefits in patients with concurrent MOH have also been reported. Participants received up to eight quarterly intravenous infusions of eptinezumab 300 mg in the phase 3, single-arm, open-label PREVAIL study. Safety and patient-reported outcome measures (Migraine Disability Assessment [MIDAS], 6-item Headache Impact Test [HIT-6], patient-identified most bothersome symptom [PI-MBS], Patient Global Impression of Change [PGIC], and 36-item Short-Form Health Survey [SF-36]) were conducted at predefined intervals. Patients were observed up to 20 weeks after their last infusion (Week 104). A total of 49/128 (38.3%) patients enrolled in PREVAIL had an MOH diagnosis at screening. In the MOH subgroup, long-term eptinezumab treatment was associated with reductions in headache frequency (43/49 [87.8%] patients reported ≥50% reduction in MIDAS-derived headache days at ≥1 visit), severity (2.2-point reduction [on a 10-point scale]), disability (mean MIDAS total score reduction of 51.9 points), and impact (mean HIT-6 total score reduction of 9.7 points) at Week 104. Most patients described a "much improved" or "very much improved" status by Week 48 (PI-MBS, 31/46 [67.4%]) and Week 104 (PGIC, 31/36 [86.1%]). Health-related quality of life improvements in the SF-36 were also observed. Eptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH.

Diagnostic workup of acute headache and subarachnoid hemorrhage in a Norwegian population: An observational study.

Acute headache may be the primary symptom of subarachnoid hemorrhage (SAH). Recent guidelines suggest that non-contrast computed tomography (CT) is adequate to exclude aneurysmal SAH if performed within 6 h after symptom onset. However, most studies of acute headache including CT, lumbar puncture and SAH are multicenter studies from referral hospitals with highly selected patient populations. The main purpose of this study was to describe the diagnostic properties of head CT and cerebrospinal fluid (CSF) spectrophotometry for detecting SAH in an unselected primary hospital population with acute headache. A retrospective cross-sectional study conducted at a large primary hospital serving roughly 10% of the Norwegian population. Diagnostic workup from consecutive patients evaluated for acute headache in 2009-2020 were collected. All CSF-spectrophotometry reports were standardized and the same CT scanner was used during the study. A total of 3227 patients were included. Median age was 45 years and 63% were women. In total, 170 (5.3% of all acute headache patients) had SAH. Of 3071 CT-negative patients, 2852 (93%) underwent lumbar puncture. Of the CSF reports, 2796 (98%) were negative for xanthochromia. Overall, the rate for detection of aneurysmal SAH by positive xanthochromia was 9 in 2852 cases (3‰). The miss rate for the detection of an aneurysmal SAH with a CT scan within 6 h was 0 and within 12 h 1 in 2852 cases (0.3‰). In acute headache, a CT scan taken within 6 h is practically 100% sensitive for detecting any SAH.

Oxytocin Receptors on Calvarial Periosteal Innervation: Therapeutic Target for Post-Traumatic Headache?

Following a mild traumatic brain injury (mTBI), the most prevalent and profoundly debilitating occurrence is the emergence of an acute and persistent post-traumatic headache (PTH), for which there are presently no approved treatments. A crucial gap in knowledge exists regarding the consequences of an mTBI, which could serve as a foundation for the development of therapeutic approaches. The activation of trigeminal sensory nerve terminals that innervate the calvarial periosteum (CP)-a densely innervated tissue layer covering the calvarial skull-has been implicated in both migraines and PTHs. We have previously shown that trigeminal oxytocin receptors (OTRs) may provide a therapeutic target for PTHs. This study examined the expression of oxytocin receptors on trigeminal nerves innervating the periosteum and whether these receptors might serve as a therapeutic target for PTHs using a direct application of oxytocin to the periosteum in a rodent model of PTH. We used retrograde tracing and immunohistochemistry to determine if trigeminal ganglion (TG) neurons innervating the periosteum expressed OTRs and/or CGRPs. To model the impact of local inflammation that occurs following an mTBI, we applied chemical inflammatory mediators directly to the CP and assessed for changes in immediate-early gene expression as an indication of neuronal activation. We also determined whether mTBI would lead to expression changes to OTR levels. To determine whether these OTRs could be a viable therapeutic target, we assessed the impact of oxytocin injections into the CP in a mouse model of PTH-induced periorbital allodynia. The results of these experiments demonstrate the following: (1) the cell bodies of CP afferents reside in the TG and express both OTRs and CGRPs; (2) inflammatory chemical stimulation of the periosteum leads to rapid activation of TG neurons (phospho-ERK (p-ERK) expression), (3) mTBI-induced inflammation increased OTR expression compared to the sham group; and (4) administration of oxytocin into the periosteum on day 2 and day 40 blocked cutaneous allodynia for up to one hour post-administration for both acute and persistence phases in the PTH model-an effect that was preventable by the administration of an OTR antagonist. Taken together, our observations suggest that periosteal trigeminal afferents contribute to post-TBI craniofacial pain, and that periosteum tissue can be used as a potential local target for therapeutics such as oxytocin.

Evaluating patient and family preferences for acute and preventive pediatric headache treatment.

To describe acute and preventive treatment preferences among youth with migraine and their parents/guardians, and to describe the degree of youth-parent/guardian preference agreement. Headache disorders are common in youth, but little is known about patient and family preferences for headache treatments and outcomes. In this cross-sectional survey, a headache treatment preferences questionnaire was co-created with stakeholders, piloted, and distributed to consenting youth with migraine aged 9-18 years and parents/guardians at a tertiary care headache clinic in western Canada. Response data were summarized for youth and parents/guardians separately, and agreement rates within a youth-parent/guardian pair were compared to a hypothesized agreement rate of 80% for the primary questionnaire items. Seventy-two youth and n = 94 parents/guardians participated, with n = 63 in youth-parent/guardian pairs. Freedom from pain and rapid relief, and reducing pain severity and headache frequency were top acute and preventive treatment priorities, respectively. More than 90% (69/72) agreed that ≥ 50% reduction in headache frequency was a good target. For both acute and preventive interventions, swallowed pill-based options were most often selected as the preferred first-line treatment, with neuromodulation selected as the preferred second-line treatment. The level of agreement within youth-parent/guardian pairs on preferred treatment modalities was lower than hypothesized for acute (63% [40/63], 95% confidence interval [CI] = 52-75%, χ2 = 10.73, p = 0.001) but not for preventive treatment (73% [46/63], 95% CI = 62-84%, χ2 = 1.92, p = 0.166). Regarding which treatment modalities were perceived as most effective, youth-parent agreement was lower than hypothesized for both acute (48% [30/63], 95% CI = 35-60%, χ2 = 41.29, p < 0.001) and preventive treatment (46% [29/63], 95% CI = 34-58%, χ2 = 45.43, p < 0.001). Youth and family preferences aligned qualitatively, but sometimes diverged quantitatively, from typical clinical trial outcomes. The level of agreement within youth-parent/guardian pairs on treatment preferences and perceptions was low. Clinicians should consider both perspectives as they may be divergent.

Brain structural and functional abnormalities associated with acute post-traumatic headache: iron deposition and functional connectivity

BackgroundThe purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI.MethodsSixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T2* maps and resting-state functional connectivity imaging. Between group T2* differences were determined using T-tests (p < 0.005, cluster size threshold of 90 voxels). For regions with T2* differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p < 0.05 with family wise error correction for multiple comparisons).ResultsThe acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T2* values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T2* in the left posterior cingulate with SCAT symptom severity score (p = 0.05) and T2* in the left cuneus with headache frequency (p = 0.04).ConclusionsIron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T2* (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH.

Comparative Efficacy of Magnesium Sulphate and Dexamethasone/Metoclopramide in the Treatment of Acute Migraine Headaches

Background: Migraine, a neurological condition characterized by intense and debilitating headaches, poses a significant public health issue affecting millions worldwide. The complexity of migraine pathophysiology often makes its management challenging. Despite various treatment modalities, the quest for the most effective and rapid relief from acute migraine episodes remains a pertinent concern in clinical practice. Objective: This study aimed to compare the efficacy of magnesium sulfate and a combination of dexamethasone/metoclopramide in treating acute migraine headaches to identify the most effective treatment option for rapid pain relief. Methods: This randomized controlled trial was conducted at the Department of Emergency Medicine, Benazir Bhutto Hospital, Rawalpindi, over six months from November 25, 2015, to May 24, 2016. A total of 70 patients were enrolled, with 35 patients assigned to Group A and 35 to Group B. Group A received 1g of magnesium sulfate in 100ml normal saline over 15 minutes, while Group B received 8mg of dexamethasone and 10mg of metoclopramide in a similar saline solution and infusion time. Pain severity was assessed using the Numeric Rating Scale (NRS) at baseline and two hours after medication administration. Data were analyzed using SPSS Version 25, with mean ± standard deviation calculated for age and NRS scores. Frequency and percentages were computed for gender and efficacy. Efficacy between the groups was compared using Chi-square tests, and stratification was applied to control for age and gender, followed by post-stratification Chi-square testing. A p-value of ≤ 0.05 was considered statistically significant. Results: The results showed a significant difference in pain relief between the two groups. In Group A, 23 patients (65.7%) reported significant pain relief compared to 13 patients (34.3%) in Group B (p=0.017). Stratification by age revealed that in patients under 30 years, 11 patients (31.4%) in Group A experienced pain relief compared to 8 patients (22.9%) in Group B (p=0.202). For patients over 30 years, 12 patients (34.3%) in Group A reported pain relief, compared to 5 patients (14.3%) in Group B (p=0.084). Gender stratification showed that among males, 5 (14.3%) in Group A experienced pain relief compared to 9 (25.7%) in Group B (p=0.408), while among females, 18 (51.4%) in Group A reported pain relief compared to 4 (11.4%) in Group B (p=0.000). Conclusion: Magnesium sulfate was found to be a more effective and faster-acting medication compared to a combination of dexamethasone and metoclopramide for the treatment of acute migraine headaches. This finding highlights the potential of magnesium sulfate as a preferred option for rapid pain relief in clinical settings, particularly for female patients.

Can Long-Term Outcomes of Posttraumatic Headache be Predicted?

Headache is one of the most common symptoms of traumatic brain injury, and it is more common in patients with mild, rather than moderate or severe, traumatic brain injury. Posttraumatic headache can be the most persistent symptom of traumatic brain injury. In this article, we review the current understanding of posttraumatic headache, summarize the current knowledge of its pathophysiology and treatment, and review the research regarding predictors of long-term outcomes. To date, posttraumatic headache has been treated based on the semiology of the primary headache disorder that it most resembles, but the pathophysiology is likely to be different, and the long-term prognosis differs as well. No models exist to predict long-term outcomes, and few studies have highlighted risk factors for the development of acute and persistent posttraumatic headaches. Further research is needed to elucidate the pathophysiology and identify specific treatments for posttraumatic headache to be able to predict long-term outcomes. In addition, the effect of managing comorbid traumatic brain injury symptoms on posttraumatic headache management should be further studied. Posttraumatic headache can be a persistent symptom of traumatic brain injury, especially mild traumatic brain injury. It has traditionally been treated based on the semiology of the primary headache disorder it most closely resembles, but further research is needed to elucidate the pathophysiology of posttraumatic headache and determine risk factors to better predict long-term outcomes.

Headache and Vision Loss as Initial Symptoms for an Acute Invasive Rhino-orbital-cerebral Mucormycosis

Background: Acute invasive rhino-orbital-cerebral mucormycosis (ROCM) is a rare fungal infection commonly caused by Rhizopus species. It occurs in immune- compromised individuals who have acquired immune deficiency syndrome (AIDS), leukemia, uncontrolled diabetes mellitus, or organ transplant patients who are on immunosuppressive therapy. Diagnosing invasive ROCM is challenging because its clinical presentation can be nonspecific, and it is not frequently observed in ophthalmic practices. Case Report: A 66-year-old Hispanic male with poorly controlled diabetes mellitus presented with the complaint of severe headache and retrobulbar pain in the right eye. An ophthalmic examination revealed normal ocular health in both eyes. Computerized tomography scan showed mild inflammatory mucosal thickening in the sinuses. Initially, he was diagnosed and treated for giant cell arteritis. The patient’s vision deteriorated to no light perception in the right eye with persistent 10 out of 10 headache and eye pain despite various treatments. Further evaluation revealed ROCM involving the sphenoid sinus. This was confirmed by a positive smear and culture of Rhizopus species from the sinus and from the patient’s symptoms improving with antifungal treatment. Conclusion: Sphenoid sinusitis is an unusual site of involvement with ROCM. The absence of nasal drainage adds to the difficulty of diagnosis without contrast imaging. Although rare, acute invasive ROCM should always be considered in any uncontrolled diabetic or immunosuppressed patient with acute headache and vision loss.

Headache and Vision Loss as Initial Symptoms for an Acute Invasive Rhino-orbital-cerebral Mucormycosis

Background: Acute invasive rhino-orbital-cerebral mucormycosis (ROCM) is a rare fungal infection commonly caused by Rhizopus species. It occurs in immune- compromised individuals who have acquired immune deficiency syndrome (AIDS), leukemia, uncontrolled diabetes mellitus, or organ transplant patients who are on immunosuppressive therapy. Diagnosing invasive ROCM is challenging because its clinical presentation can be nonspecific, and it is not frequently observed in ophthalmic practices. Case Report: A 66-year-old Hispanic male with poorly controlled diabetes mellitus presented with the complaint of severe headache and retrobulbar pain in the right eye. An ophthalmic examination revealed normal ocular health in both eyes. Computerized tomography scan showed mild inflammatory mucosal thickening in the sinuses. Initially, he was diagnosed and treated for giant cell arteritis. The patient’s vision deteriorated to no light perception in the right eye with persistent 10 out of 10 headache and eye pain despite various treatments. Further evaluation revealed ROCM involving the sphenoid sinus. This was confirmed by a positive smear and culture of Rhizopus species from the sinus and from the patient’s symptoms improving with antifungal treatment. Conclusion: Sphenoid sinusitis is an unusual site of involvement with ROCM. The absence of nasal drainage adds to the difficulty of diagnosis without contrast imaging. Although rare, acute invasive ROCM should always be considered in any uncontrolled diabetic or immunosuppressed patient with acute headache and vision loss.

Headache and Vision Loss as Initial Symptoms for an Acute Invasive Rhino-orbital-cerebral Mucormycosis

Background: Acute invasive rhino-orbital-cerebral mucormycosis (ROCM) is a rare fungal infection commonly caused by Rhizopus species. It occurs in immune- compromised individuals who have acquired immune deficiency syndrome (AIDS), leukemia, uncontrolled diabetes mellitus, or organ transplant patients who are on immunosuppressive therapy. Diagnosing invasive ROCM is challenging because its clinical presentation can be nonspecific, and it is not frequently observed in ophthalmic practices. Case Report: A 66-year-old Hispanic male with poorly controlled diabetes mellitus presented with the complaint of severe headache and retrobulbar pain in the right eye. An ophthalmic examination revealed normal ocular health in both eyes. Computerized tomography scan showed mild inflammatory mucosal thickening in the sinuses. Initially, he was diagnosed and treated for giant cell arteritis. The patient’s vision deteriorated to no light perception in the right eye with persistent 10 out of 10 headache and eye pain despite various treatments. Further evaluation revealed ROCM involving the sphenoid sinus. This was confirmed by a positive smear and culture of Rhizopus species from the sinus and from the patient’s symptoms improving with antifungal treatment. Conclusion: Sphenoid sinusitis is an unusual site of involvement with ROCM. The absence of nasal drainage adds to the difficulty of diagnosis without contrast imaging. Although rare, acute invasive ROCM should always be considered in any uncontrolled diabetic or immunosuppressed patient with acute headache and vision loss.

Brain Iron Accumulation in Participants with Acute Post-traumatic Headache (S20.007)

Brain Iron Accumulation in Participants with Acute Post-traumatic Headache (S20.007)

Prediction of Headache Improvement Using Multimodal Machine Learning in Patients with Acute Post-traumatic Headache (P5-12.002)

Prediction of Headache Improvement Using Multimodal Machine Learning in Patients with Acute Post-traumatic Headache (P5-12.002)

Familial hemiplegic migraine in Indian children-a tertiary center experience.

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1-18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks.

Lumbar Puncture.

Lumbar puncture (LP) is a procedural skill that is required for practice in the emergency care setting, most often for diagnostic purposes. Rarely, it can also be used therapeutically, to alleviate the pain of patients presenting to the emergency department with acute headache from idiopathic intracranial hypertension. In either case, LP constitutes an invasive procedure in which the subarachnoid space is entered in order to obtain a sample of cerebrospinal fluid from one of the most vulnerable areas of the human anatomy. It is essential for the emergency clinician to carefully weigh the risks and benefits of LP, to ensure informed consent when possible, and to proceed in a manner that ensures optimal patient safety and effectiveness. This article reviews current recommendations and considerations around performing LP, in addition to the process for performing the procedure.

An Unusual Case of Headache: Joining the Dots in the Emergency Room

Headache is one of the commonest presenting complaints in the Emergency Room. In the young population with no significant history of any medical condition or trauma, it seldom raises suspicion of an ominous etiology. In this case report we present an unusual case of a young unmarried female presenting to the ED with acute onset headache and vomiting. After initiation of primary treatment, the patient was subjected to MRA and MRV of the brain which was suggestive of thrombosed mid part of Superior Sagittal Sinus, right Sigmoid and right Transverse sinus. On eliciting the SAMPLE history of the patient, the risk factor of polycystic ovarian syndrome and intake of Norethisterone for Abnormal Uterine Bleeding was known. Provisional diagnosis of Norethisterone induced Cerebral Venous Sinus Thrombosis was considered and patient was initiated on treatment with Enoxaparin (Low Molecular weight Heparin) followed by long term NOAC and lifetime avoidance of Norethisterone and other prothrombotic drugs.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI

BackgroundHeadache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury.MethodsA large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors.ResultsA total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury.ConclusionsHeadache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache.Trial registrationClinicalTrials.gov NCT02210221.

Coffee consumption and migraine: a population-based study

Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1–2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment—adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking—was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache

BackgroundBoth epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance.MethodTo explore the relationship between acute headache and acute sleep disturbance, we primarily employed nitroglycerin (NTG)-induced migraine-like headache and acute sleep deprivation (ASD) models. Initially, we conducted experiments to confirm that ASD enhances headache and that acute headache can lead to acute sleep disturbance. Subsequently, we examined the separate roles of the LC in sleep and headache. We observed the effects of drug-induced activation and inhibition and chemogenetic manipulation of LC noradrenergic neurons on ASD-induced headache facilitation and acute headache-related sleep disturbance. This approach enabled us to demonstrate the bidirectional function of LC noradrenergic neurons.ResultsOur findings indicate that ASD facilitated the development of NTG-induced migraine-like headache, while acute headache affected sleep quality. Furthermore, activating the LC reduced the headache threshold and increased sleep latency, whereas inhibiting the LC had the opposite effect. Additional investigations demonstrated that activating LC noradrenergic neurons further intensified pain facilitation from ASD, while inhibiting these neurons reduced this pain facilitation. Moreover, activating LC noradrenergic neurons exacerbated the impact of acute headache on sleep quality, while inhibiting them alleviated this influence.ConclusionThe LC serves as a significant anatomical and functional region in the interaction between acute sleep disturbance and acute headache. The involvement of LC noradrenergic neurons is pivotal in facilitating headache triggered by ASD and influencing the effects of headache on sleep quality.