Secondary Headache Disorders Research Articles

Regulatory T cells require peripheral CCL2-CCR2 signaling to facilitate the resolution of medication overuse headache-related behavioral sensitization

BackgroundMedication overuse headache (MOH) is the most common secondary headache disorder, resulting from chronic and excessive use of medication to treat headaches, for example, sumatriptan. In a recent study, we have shown that the peripheral C-C motif ligand 2 (CCL2), C-C motif chemokine receptor 2 (CCR2) and calcitonin-gene-related peptide (CGRP) signaling pathways interact with each other and play critical roles in the development of chronic migraine-related behavioral and cellular sensitization. In the present study, we investigated whether CCL2-CCR2 and CGRP signaling pathways play a role in the development of sumatriptan overuse-induced sensitization, and whether they are involved in its resolution by the low-dose interleukin-2 (LD-IL-2) treatment.MethodsMice received daily sumatriptan administration for 12 days. MOH-related behavioral sensitization was assessed by measuring changes of periorbital mechanical thresholds for 3 weeks. CCL2-CCR2 and CGRP signaling pathways were inhibited by targeted gene deletion or with an anti-CCL2 antibody. Ca2+-imaging was used to examine whether repetitive sumatriptan treatment enhances CGRP and pituitary adenylate cyclase–activating polypeptide (PACAP) signaling in trigeminal ganglion (TG) neurons. LD-IL-2 treatment was initiated after the establishment of sumatriptan-induced sensitization. Immunohistochemistry and flow cytometry analyses were used to examine whether CCL2-CCR2 signaling controls regulatory T (Treg) cell proliferation and/or trafficking.ResultsCCL2, CCR2 and CGRPα global KO mice exhibited robust sumatriptan-induced behavioral sensitization comparable to wild-type controls. Antibody neutralization of peripheral CCL2 did not affect sumatriptan-induced behaviors either. Repeated sumatriptan administration did not enhance the strength of CGRP or PACAP signaling in TG neurons. Nevertheless, LD-IL-2 treatment, which facilitated the resolution of sumatriptan-induced sensitization in wild-type and CGRPα KO mice, was completely ineffective in mice with compromised CCL2-CCR2 signaling. In CCL2 KO mice, we observed normal LD-IL-2-induced Treg expansion in peripheral blood, but the increase of Treg cells in dura and TG tissues was significantly reduced in LD-IL-2-treated CCL2 KO mice relative to wild-type controls.ConclusionsThese results indicate that the endogenous CCL2-CCR2 and CGRP signaling pathways are not involved in sumatriptan-induced behavioral sensitization, suggesting that distinct molecular mechanisms underlie chronic migraine and MOH. On the other hand, peripheral CCL2-CCR2 signaling is required for LD-IL-2 to reverse chronic headache-related sensitization.Graphical abstract

IIH, SIH and headache: Diagnosis and treatment update

Idiopathic intracranial hypertension (IIH) and spontaneous intracranial hypotension (SIH) are two major secondary headache disorders resulting from abnormal intracranial pressure (ICP). This short communication outlines the pathophysiology, diagnostic criteria, and management strategies for IIH and SIH. IIH predominantly affects obese women of childbearing age and presents with daily headaches, visual disturbances, and papilledema. It is characterized by elevated cerebrospinal fluid (CSF) pressure, with diagnosis supported by imaging and lumbar puncture. Treatment includes weight reduction, medications, and surgical interventions in refractory cases. SIH, conversely, is caused by spontaneous spinal CSF leaks and presents with acute orthostatic headaches. Diagnosis is supported by neuroimaging and lumbar puncture, revealing low CSF pressure. Treatment includes supported care, (targeted) epidural blood patch, with surgical repair considered in refractory cases. Advances in imaging and treatment have significantly improved outcomes for both conditions.

Comparison of ketorolac intravenous versus acetaminophen intravenous in treating headache following head trauma: a semi-experimental study

BackgroundPost-traumatic headache is a disabling secondary headache disorder often attributed to traumatic brain injury and affects millions of individuals worldwide. Few studies have been done on the treatment needs of these patients in emergency departments. The purpose was to compare the effectiveness of ketorolac intravenous versus acetaminophen intravenous in reducing headaches in patients following head trauma.MethodsThis was a semi-experimental study in which the participants were assigned two groups. In the acetaminophen intravenous group, 1 g acetaminophen and in the ketorolac intravenous group, 60 mg of this drug was injected. Statistical analysis was done with IBM SPSS statistical software version 21, and a P-value less than 0.05 was considered statistically significant.ResultsAmong samples after 6 h from the injection, the pain score in the ketorolac intravenous group was less than the acetaminophen intravenous group (P = 0.006). Also, the pain reduction rate in the ketorolac intravenous group was more than the acetaminophen intravenous group from before the injection until 2 h after it (P = 0.01) and before injection until 6 h after it (P = 0.001). The frequency of drowsiness in 2 and 6 h after drug administration in the ketorolac intravenous group was lower than the acetaminophen intravenous group, which is significant in 2 h after drug administration (P = 0.038). The verbal analog scale score comparison for two groups 2 h before medicine administration with pain control score (P = 0.03) and 6 h with pethidine use control (P = 0.003) is significant.ConclusionsAccording to this study, ketorolac’s intravenous effect on pain control is better than that of acetaminophen intravenous. With more samples, we can express the survey results more decisively in the future.

Non-Migraine Head Pain and Botulinum Toxin.

Botulinum toxin A (BT-A), a potential neurotoxin produced by the bacterium Clostridium botulinum, is known for its ability to prevent the release of acetylcholine at the neuromuscular synapse, leading to temporary muscle paralysis. BT-A is used for a wide range of therapeutic applications. Several studies have shown mechanisms beyond the inhibition of acetylcholine release for pain control. BT-A inhibits the release of neurotransmitters associated with pain and inflammation, such as glutamate, CGRP, and substance P. Additionally, it would be effective in nerve entrapment leading to neuronal hypersensitivity, which is known as a new pathogenesis of painful conditions. BT-A has been applied to the treatment of a wide variety of neurological disorders. Since 2010, BT-A application has been approved and widely used as a chronic migraine prophylaxis. Moreover, due to its effects on pain through sensory modulation, it may also be effective for other headaches. Several studies using BT-A, at different doses and administration sites for headaches, have shown beneficial effects on frequency and severity. In this review, we provide an overview of using BT-A to treat primary and secondary headache disorders.

Prevalence and Awareness of Medication Overuse Headache among Undergraduate Students at the University of Belgrade.

Medication overuse headache (MOH) is a prevalent and potentially preventable secondary headache disorder linked to the excessive use of medications intended for primary headache management, particularly migraine. The aim of our study was to assess the prevalence of MOH among undergraduate students and explore their awareness. This observational cross-sectional study included 401 active undergraduate students from the University of Belgrade. Data were collected through an anonymous online questionnaire which was distributed among student groups and via social media. The questionnaire specially designed for this study was developed in accordance with established guidelines for headache epidemiological research. Among the surveyed students, 10 of them (2.5%) met the criteria for the diagnosis of MOH. Awareness of MOH was noted in 149 (37.2%) students, with higher awareness among medical students and those aged 22-25 years. Despite this awareness, there was no significant difference in MOH occurrence between those aware and unaware of the condition (aware 2.7% vs. unaware 2.4%, p = 1.000). Additionally, significant gaps in education and communication about MOH were evident. Participants were recruited through convenience sampling from a single university at one time point. The questionnaire was not specifically validated in the student population, and the data relied on self-reporting. Our study highlighted a notable prevalence of MOH among undergraduate students, with a substantial portion exhibiting awareness of its risks. Despite this awareness, our findings suggest ongoing gaps in education and communication regarding MOH, emphasizing the need for targeted interventions.

"Code Headache": Development of a protocol for optimizing headache management in the emergency room.

Patients presenting at the emergency room (ER) with headache often encounter a hostile atmosphere and experience delays in diagnosis and treatment. The aim of this study was to design a protocol for the ER with the goal of optimizing the care of patients with urgent headache to facilitate diagnosis and expedite treatment. A narrative literature review was conducted via a MEDLINE search in October 2021. The "Code Headache" protocol was then developed considering the available characteristics and resources of the ER at a tertiary care center within the Spanish National Public Health system. The Code Headache protocol comprises three assessments: two scales and one checklist. The assessments identify known red flags and stratify patients based on suspected primary/secondary headaches and the need for pain treatment. Initial assessments, performed by the triage nurse, aim to first exclude potentially high morbidity and mortality etiologies (HEAD1 scale) and then expedite appropriate pain management (HEAD2 scale) based on scoring criteria. HEAD1 evaluates vital signs and symptoms of secondary serious headache disorders that can most benefit from earlier identification and treatment, while HEAD2 assesses symptoms indicative of status migrainosus, pain intensity, and vital signs. Subsequently, ER physicians employ a third assessment that reviews red flags for secondary headaches (grouped under the acronym 'PEACE') to guide the selection of complementary tests and aid diagnosis. The Code Headache protocol is a much needed tool to facilitate quick clinical assessment and improve patient care in the ER. Further validation through comparison with standard clinical practice is warranted.

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.

Neurofilament light chain is elevated in patients with newly diagnosed idiopathic intracranial hypertension: A prospective study.

Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aβ-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension. Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure. We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aβ-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aβ-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001). cNfL, pNfL and total-tau/Aβ-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity.

New Daily Persistent Headache.

This article describes the clinical features, etiology, differential diagnosis, management, and prognosis of new daily persistent headache. New daily persistent headache has attracted renewed attention as it may arise in the setting of a COVID-19 infection. Spontaneous intracranial hypotension, particularly from CSF-venous fistulas, remains an important secondary headache disorder to consider before diagnosing new daily persistent headache. Symptomatic treatment for new daily persistent headache may include acute and preventive therapies used for migraine and tension-type headache, such as triptans, oral preventive agents, onabotulinumtoxinA, and agents that target calcitonin gene-related peptide. New daily persistent headache is a daily headache syndrome that starts acutely and can only be diagnosed after 3 months have elapsed and other secondary and primary headache diagnoses have been excluded. The clinical manifestations largely resemble either chronic migraine or chronic tension-type headache. The underlying cause is unknown, but it is plausible that multiple etiologies exist and that it is not a single disease entity. The prognosis is variable but often poor, and the treatment approach is largely extrapolated from the management of chronic migraine and chronic tension-type headache.

Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study

Introduction: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. Methods: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. Results: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04–3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03–1.24), less than high school (OR, 1.08; 95%, 1.01–1.15), without depression (OR, 1.06; 95%, 1.01–1.12), and without anxiety (OR, 1.06; 95%, 1.01–1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. Conclusion: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Post cerebral venous thrombosis headache – Prevalence, mechanisms and risk factors

IntroductionHeadache after cerebral venous thrombosis (post-CVT headache [PCH]) is a common complaint during follow-up. Risk factors and their pathophysiology are not well known. We studied PCH prevalence in CVT patients, its pathophysiology, and possible risk factors. Materials and MethodsWe performed a retrospective observational study of patients admitted to a tertiary hospital between 2006 and 2019 with CVT and at least one follow-up appointment. We diagnosed PCH when patients reported headaches during the follow-up visit. Recanalization was retrospectively assessed by two neuroradiologists using the first available follow-up MRI/ MRV, and the PRIORITy-CVT study classification. ResultsOf 131 patients, sixty (60/131, 45.8 %) reported PCH at the 3-month follow-up. Of these PCH, 9 had previous migraine (9/60, 5.0 %) and 13 previous tension-type headaches (13/60, 21.6 %), before CVT. Forty-four (44/60, 73.3 %) PCH patients had de novo headache: 21 (21/60, 35.0 %) de novo tension-type headaches; 6 (6/60, 10.0 %) de novo migraine; 6 [(6/60, 10.0 %) secondary headache disorders: 3 due to dural arteriovenous fistula, 2 due to intracranial hypertension, and 1 recurrent CVT], and 11 other headache types. Most patients had at least partial recanalization, with no difference in PCH frequency amongst recanalization subgroups (p = 0.598). Premorbid depression (p = 0.009, OR 7.9, 95 % CI 1.6–31.4) increased the odds ratio of PCH, while superior sagittal sinus thrombosis (p = 0.005, OR 0.15, 95 % CI 0.03–0.56) decreased it. DiscussionOur study shows that PCH is a common finding after CVT and elucidates potential risk factors. PCH is common in patients with previous or de novo primary headache. In PCH patients without previous headache, secondary causes of headache, namely related to CVT complications, should be excluded. PCH is also increased in patients with premorbid depression. There was no statistically significant difference in PCH amongst the PRIORITy-CVT recanalization subgroups, but most patients had at least partial recanalization.

Treatment Options for Posttraumatic Headache: A Current Review of the Literature.

We evaluate evidence-based treatments for posttraumatic headache (PTH), a secondary headache disorder resulting from traumatic brain injury (TBI), comprising nearly 4% of all symptomatic headache disorders. Utilizing recent publications, we aim to inform clinicians of current treatment methods. There is limited research on PTH treatment. A randomized controlled trial (RCT) of metoclopramide with diphenhydramine for acute PTH found that the treatment group (N = 81) experienced more significant pain improvement than placebo by 1.4 points. For persistent PTH, an open-label study of erenumab (N = 89) found that 28% of participants reported ≥ 50% reduction in moderate-to-severe headache days, but an RCT of fremanezumab showed a non-significant reduction in moderate-to-severe headache days. A randomized crossover study of 40 patients with persistent PTH found that onabotulinum toxin-A decreased cumulative number of headaches/week by 43.3% in the treatment group and increased by 35.1% among placebos. In a study of military veterans with severe posttraumatic stress disorder and persistent/delayed onset PTH (N = 193), patients who received Cognitive Behavioral Therapy reported significant improvements in headache-related disability compared to usual care (aggregate mean HIT-6, -3.4). A transcranial magnetic stimulation (N = 24) study found that 58% of participants with mild TBI-related headache experienced a 50% reduction in headache frequency. New studies indicate promise in improving clinically important outcomes of PTH. However, more research is necessary to determine the optimal treatment and whether combining pharmacologic and nonpharmacologic treatment versus a single modality is more effective.

Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study

BackgroundFor some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH.MethodsSUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18−75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1−12 was the primary efficacy endpoint.ResultsPatients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1−12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints.ConclusionAll endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment.Trial registrationClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

The state of the art in treating patients with a dual diagnosis of chronic migraine and medication-overuse headache

Migraine is a common, highly prevalent genetic neurological disorder. Its most burdensome form is the chronic migraine, which is clinically defined by the presence of headache on ≥15 days/month for longer than three months, with eight or more typical migraine days. Medication-overuse headache (MOH) is a secondary headache disorder associated with the overuse of symptomatic headache medications on ≥10 days/month for longer than 3 months. Chronic migraine and medication-overuse headache often coexist and most chronic migraineurs have medication overuse headache. Despite that, general practitioners and health professionals do not know about MOH. This review aims at presenting insights, recent knowledge, and guidance regarding the approach and treatments for patients with a dual diagnosis of chronic migraine and medication-overuse headache.

Secondary headaches in pregnancy and the puerperium.

Headache during pregnancy can be due to primary causes such as migraine but can also be a presenting symptom of secondary causes including life threatening conditions. This is a minireview of secondary causes of headache during pregnancy and the puerperium. Unique alterations in physiological and vascular functions as well as in the coagulation pathway which occur during pregnancy increase the risk of most of these secondary conditions which include preeclampsia, eclampsia, hemorrhagic stroke, cerebral venous, sinus thrombosis, reversible cerebral vascular syndrome, and posterior reversible encephalopathy. Marked increase in progesterone level in pregnancy is also associated with the growth of tumors such as meningiomas, as 70% of these tumors are positive for progesterone receptors and increase in size can lead to headache along with other neurological symptoms. Hemodynamic changes can lead to the growth of meningiomas as well. Although hormone producing pituitary tumors are usually not conducing to pregnancy, women with known pituitary tumors who do get pregnant may become symptomatic during pregnancy and develop secondary headache. Another rare cause of secondary headache during pregnancy is pituitary apoplexy. Although its occurrence is uncommon, it needs to be properly recognized and treated to avoid endocrine and visual complications. Other rare entities with increased incidence during the puerperium such postdural puncture headache will be also discussed. In summary, new onset headache during pregnancy deserves special attention because in the absence of proper recognition and treatment, secondary headache disorders can endanger the life of the mother and the fetus.

Reliability of a telephone interview for the classification of headache disorders.

The study aimed to test the reliability of a semi-structured telephone interview for the classification of headache disorders according to the ICHD-3. Questionnaire-based screening tools are often optimized for single primary headache diagnoses [e.g., migraine (MIG) and tension headache (TTH)] and therefore insufficiently represent the diagnostic precision of the ICHD-3, which limits epidemiological research of rare headache disorders. Brief semi-structured telephone interviews could be an effective alternative to improve classification. A patient population representative of different primary and secondary headache disorders (n = 60) was recruited from the outpatient clinic (HSA) of a tertiary care headache center. These patients completed an established population-based questionnaire for the classification of MIG, TTH, or trigeminal autonomic cephalalgia (TAC). In addition, they received a semi-structured telephone interview call from three blinded headache specialists individually. The agreement of diagnoses made either using the questionnaires or interviews with the HSA diagnoses was evaluated. Of the 59 patients (n = 1 dropout), 24% had a second-order and 5% had a third-order headache disorder. The main diagnoses were as follows: frequent primary headaches with 61% MIG, 10% TAC, 9% TTH, and 5% rare primary and 16% secondary headaches. Second-order diagnosis was chronic migraine throughout, and third-order diagnoses were medication overuse headache and TTH. Agreement between main headaches from the HSA was significantly better for the telephone interview than for the questionnaire (questionnaire: κ = 0.330; interview: κ = 0.822; p < 0.001). Second-order diagnoses were not adequately captured by questionnaires, while there was a trend for good agreement with the telephone interview (κ = 0.433; p = 0.074). Headache frequency and psychiatric comorbidities were independent predictors of HSA and telephone interview agreement. Male sex, headache frequency, severity, and depressive disorders were independently predictive for agreement between the questionnaire and HSA. The telephone interview showed high sensitivity (≥71%) and specificity (≥92%) for all primary headache disorders, whereas the questionnaire was below 50% in either sensitivity or specificity. The semi-structured telephone interview appears to be a more reliable tool for accurate diagnosis of headache disorders than self-report questionnaires. This offers the potential to improve epidemiological headache research and care even in underserved areas.

Evaluating Headache and Facial Pain in a Headache Diagnostic Laboratory: Experiences from the Danish Headache Center.

Diagnostic tests are not routinely used for the diagnosis of primary headaches. It is possible that laboratory tests could be developed and implemented at tertiary headache centers to be an integrated part of the diagnosis and management of headache patients, and laboratory tests that can be used on-site at headache centers could help in evaluating patients with secondary headache disorders. In this narrative review, we present some of the studies that have been made so far at the Headache Diagnostic Laboratory at the Danish Headache Center that aim to investigate and phenotype primary headaches and investigate secondary headaches as well as improve management. Semi-structured interviews and deep phenotyping, quantitative sensory testing, and provocation studies have been shown to be valuable in categorizing primary and secondary headache subtypes, possible pathophysiology, and defining needs for further research. In patients suspected of increased intracranial pressure, transorbital ultrasound with measurement of the optic sheath diameter may be useful in monitoring patients. The management of headache patients needs to be critically evaluated to optimize treatment continuously. A Headache Diagnostic Laboratory is very useful and should be an integrated part of headache care and management at tertiary headache centers.

Two-year, real-world erenumab persistence and quality of life data in 82 pooled patients with abrupt onset, unremitting, treatment refractory headache and a migraine phenotype: New daily persistent headache or persistent post-traumatic headache in the majority of cases.

Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments. This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases. Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were "longstanding chronic" and refractory with a median of eight (IQR 4-12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3-11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3-12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6-12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab. Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6-25 months due to lack of efficacy and/or patient reported side effects (n = 33 and n = 17, respectively) or a combination of both, pregnancy planning (n = 2), and lost to follow up (n = 1). Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11-30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months.

Medication overuse headache

Medication overuse headache (MOH) is a secondary headache disorder attributed to overuse of acute headache medications by a person with an underlying headache disorder, usually migraine or tension-type headache. MOH is common among individuals with 15 or more headache days per month. Although MOH is associated with substantial disability and reductions in quality of life, this condition is often under-recognized. As MOH is both preventable and treatable, it warrants greater attention and awareness. The diagnosis of MOH is based on the history and an unremarkable neurological examination, and is made according to the diagnostic criteria of the International Classification of Headache Disorders third edition (ICHD-3). Pathophysiological mechanisms of MOH include altered descending pain modulation, central sensitization and biobehavioural factors. Treatment of MOH includes the use of headache preventive therapies, but essential to success is eliminating the cause, by reducing the frequency of use of acute headache medication, and perhaps withdrawing the overused medication altogether. Appropriate treatment is usually highly effective, leading to reduced headache burden and acute medication consumption.

Treating Vestibular Migraine When Pregnant and Postpartum: Progress, Challenges and Innovations.

Vestibular migraine is a leading cause of vertigo in pregnancy and, although not a distinct migraine subtype, is an episodic syndrome associated with migraine. Vestibular migraine is associated with diverse symptoms such as vertigo, aura, allodynia, osmophobia, nausea, vomiting and tinnitus, many of which may be exacerbated by, masked or even dismissed in pregnancy. Vestibular migraine is likely an underdiagnosed and undertreated condition in pregnancy. The aetiology of vestibular migraine remains incompletely understood, although various theories have been proposed, including genetic predisposition, neurochemical dysregulation and pro-inflammatory mechanisms, all of which are derived from the pathophysiology of classical migraine. Physiologic changes to the endocrine, haematologic and vascular systems in pregnancy may affect pathophysiological processes in vestibular migraine, and can alter the course of symptoms experienced in pregnancy. These changes also predispose to secondary headache disorders, which may have similar presentations. There has been considerable progress in therapeutic advances in vestibular migraine prophylaxis and treatment outside of pregnancy. There is currently no significant evidence base for acute treatment or prophylaxis for pregnant patients, with treatment recommendations extrapolated from studies on classical migraine, and offered on a benefit versus risk basis. Challenges commonly encountered include difficulty establishing a diagnosis, in addition to recognising and treating neuropsychiatric and gestational co-morbidities. Anxiety, depression, hypertensive disorders and cardiovascular disease are closely associated with migraine, and important contributors to morbidity and mortality during pregnancy. Identifying and treating vestibular migraine during pregnancy offers a unique opportunity to impact future patient health through screening and early treatment of associated co-morbidities. There have been innovations in classical migraine therapy that may confer benefit in vestibular migraine in pregnancy, with emphasis on lifestyle modification, effective prophylaxis, abortive therapies, cognitive behaviour therapy and management of vestibular migraine-related comorbidities.