16th European Headache Congress

Chair

Professor

Prof.

Whole exome sequencing of hemiplegic migraine patients shows an increased burden of missense variants in CACNA1H and CACNA1I genes

Abstract text (incl. figure legends and references) Background: Hemiplegic migraine (HM) is a migraine subtype with aura characterized by attacks associated with motor weakness. Given that causal mutations in the voltage-gated calcium channel a1A subunit gene CACNA1A have been found in a subset of HM patients, we investigated whether there is an increased burden in HM of missense variants in other CACNA1x genes. Methods: Whole exome sequencing data of a clinically-referred Australian cohort of unrelated HM patients (n = 187), along with public data from Genome Aggregation Database (gnomAD v2.1.1) as controls, was used for a comprehensive analysis of missense variants in CACNA1x genes that included burden testing with the TRAPD package. Replication was performed in a Dutch clinical HM cohort (n = 32). Results: Individual variant analysis of the Australian cohort revealed variants in multiple CACNA1x genes. Using TRAPD, we found a significant burden of missense variants in CACNA1H (p = 8.84 x 10-79) and CACNA1I (p = 3.00 x 10-169) in the Australian cohort that replicated in Dutch patients (CACNA1H, p = 0.012 and CACNA1I, p = 0.044), although CACNA1I did not remain significant after correction for multiple testing. The burden effect was slightly higher for CACNA1I (OR = 1.43, 95% CI:1.28 - 1.58) than for CACNA1H (OR = 1.83, 95% CI:1.54 - 2.12). Conclusion: Our data suggest that HM, in the absence of a single causal mutation in CACNA1A, ATP1A2, or SCN1A, is a complex trait, in which, at least to certain extent, increased burden of missense variants in CACNA1H and CACNA1I increases the risk of disease.

Genetics genomics | RNA

Migraine

Abstract lecture

Arterial responses to infusion of glucagon-like peptide-1 in humans: A randomized trial study

Abstract text (incl. figure legends and references) Objective: Glucagon-like-peptide-1 (GLP-1) is an incretin hormone implicated in several metabolic and neurological disorders. GLP-1 induces vasodilation and increases blood flow in the peripheral circulation. Whether GLP-1 alters cerebral hemodynamics in humans is yet to be elucidated. Methods: In a crossover, double-blind, placebo-controlled, and randomized design, 21 healthy volunteers were assigned to receive intravenous GLP-1 infusion (2.5 pmol/kg/min) or placebo over 20 min on two different days separated by at least one week. We used a noninvasive, well-validated transcranial doppler (TCD) and ultrasound dermascan to reveal the effect of GLP-1 on intra- and extracerebral arteries. The mean blood flow velocity in the middle cerebral artery (VMCA), the diameter of the superficial temporal artery (STA) and radial artery (RA), and facial skin blood flow were measured. In addition, we documented headache and its associated symptoms during and after infusion. Results: Twenty participants were included in the final analysis. We found no difference in the VMCA (P = 0.227), diameter of the STA (P = 0.096), the RA (P = 0.221), or facial blood flow (P = 0.814) after GLP-1 compared to placebo. There were no differences in HR, SAT, EtCO2, or RF (P &gt; 0.05) on the GLP-1 day compared to the placebo day. We found no differences in the incidence of headache after GLP-1 (n = 10) compared to placebo (n = 7) (P = 0.250). Conclusion: GLP-1 infusion did not affect cerebral hemodynamics or induce headache in humans. Further preclinical studies with validated methods are required to determine if intra – and extracerebral vasculature express GLP-1Rs in humans.

Neuropeptides, channels in headache

Prevalence of substance use in a Dutch migraine population

Abstract text (incl. figure legends and references) Objective: Tobacco, alcohol, and illicit substance use result in substantial morbidity and mortality. Moreover, there is controversy concerning their ability to increase susceptibility to migraine attacks. The current study sought to examine the prevalence of substance use in a large migraine cohort. Prevalence was compared to the general population. Methods: Data on substance use were collected by survey in a large migraine cohort1 and from the annual health survey for substances in the general Dutch population (Statistics Netherlands 2016/2017). Associations for substance consumption were standardized for sex, age and educational level and analyzed using chi-square. Results: From the Leiden Headache Center, a standardization a total of 4993 patients with migraine were included. Differences were found between migraine and the general population for illicit drug use (OR 0.53, 95%CI 0.45-0.63, p&lt;0.01), current smoking (OR 0.52, 95%CI 0.47-0.57, p&lt;0.01), life-time smoking (OR 0.52, 95%CI 0.48-0.55, p&lt;0.01) and current alcohol consumption (OR 0.44, 95%CI 0.40 – 0.47, p&lt;0.01). Prevalences for the use of illicit drugs, current smoking, life-time smoking and current alcohol consumption are shown in figure 1. Conclusion: Individuals with migraine are less likely to smoke, drink alcohol or use illicit drugs compared to the general population. Migraine patients might avoid alcohol due to presumed trigger effects.2 Differences in smoking prevalence might be due to an increased awareness of an elevated cardiovascular risk among migraine patients. References 1 Oosterhout et al Cephalalgia. 2011 Oct;31(13):1359-67 2 Onderwater et al Eur J Neurol. 2019;26:588-95 Figure 1. Substance use for Dutch General population and migraine patients after standardization adjusting for age, sex and education.

Epidemiology

Prof. Dr.

A novel approach to identify and classify visual migraine aura: a European multicenter study on 257 patients

Abstract text (incl. figure legends and references) Question: is it feasible to create standardized images representing visual disturbances (VD) of migraine aura (MA)? Objectives: To test the representativeness of a standardized MA iconography (SMAI) constituted of 25 elementary visual disturbances (EVDs) in a large population of patients suffering from visual MA. Methods: We prepared descriptions (EVD-texts) and graphical representations on a common background image (EVD-images) of 25 EVDs, that were used to create a web-based survey (WBS). Patients&gt;18years-old, suffering from visual MA and seen consecutively at one of 4 European Headache Centres (Lugano, Switzerland; Copenhagen, Denmark; Trondheim, Norway; Rome, Italy], were invited to participate. They fulfilled the WBS (via computer or mobile devices) where they were asked to choose which among EVDs they had experienced during their MAs and/or to provide a text description of any other EVDs experienced but not included in the WBS. Primary endpoint was the proportion of EVDs experienced by participants which were recognized in the set of 25 EVD-images. The study was approved by competent Ethics committees. Results: 257 patients with visual MA completed the study: 209 were female (81.3), mean age was 36.7. Patients experienced overall 1741 different VD. Of those, 73% could be recognized as variable combinations of the 25 EVDs in the SMAI. Description of EVSs experienced by pts in their lives are reported in the table. Conclusion: The majority of VD experienced by patients during their MA were recognized as composed of one or more EVDs in our SMAI. When validated, this this tool will allow a precise VA phenotyping with useful clinical and research applications.

How frequent is visual aura without headache caused by an underlying cause (structural or embolic)?

Abstract text (incl. figure legends and references) Question: How frequent is visual aura without headache (VAWOH) caused by an underlying cause? Methods: Since 2014 subjects with VAWOH were registered in the HagaTeachingHospital registry which now holds 156 consecutive patients seen at the outpatient headache clinic during the timespan of eight years. Subjects underwent standard brain imaging (mainly MRI and in some cases CT) and the first 100 received Transcranial Doppler with emboli detection in medial cerebral artery (TCD-ED). All investigations were performed interictally. Results: Mean age of 156 subjects in the VAWOH-registry was 59 (range 20-91 years), 107 (70%) were female. Brain imaging showed related lesions in 8 (5%) of 150 subjects. Three were scored as causal: one had an occipital dysembryoplastic neuroepithelial tumor with monthly occuring side-locked aura symptoms for more than 10 years. One subject had an occipital located metastasis of breast carcinoma. One subject had an arterio-venous malformation (AVM) located in the occipital cortex. In four subjects the diagnosis of acute migrainous infarction was made, one of these was caused by de novo trombotic thrombocytopenic purpura. In one subject an older occipital infarction was found. In these 5 ischemic subjects no active emboli were found. TCD-ED was performed in the first 100 VAWOH subjects. This was technically not possible in 16/100 (16%) due to thick skullbone. Four subjects (5%) showed one or more embolic signals suggesting microemboli during the 30-minute bilateral ACM registration. Two of these emboli positive subjects had recently underwent mitral valve operation or repair respectively. One patient recently underwent ablation for atrial fibrillation with atrialseptal wall puncture. Conclusions: In 7 (4.6%) of 150 evaluated subjects with VAWOH an underlying cause (structural or embolic) was found.

Neuroimigang in headache disorders

Do novel European Headache Federation criteria identify differences in migraine burden? Baseline data of an international real-life study on resistant and refractory migraine (REFINE).

Abstract text (incl. figure legends and references) Question. We evaluated if EHF criteria for resistant (RES) and refractory (REF) migraine identify patients with more severe migraine burden. Methods. We performed an observational, multi center, international study to compare baseline characteristics, comorbidities, and PROMs of non-resistant and non-refractory (NRNR) migraine, RES and REF individuals in the REFINE study. Results. We included 175 individuals with NRNR migraine, 133 (39.7%) with RES and 27 (8.0%) with REF. Individuals with RES and REF migraine as compared to those with NRNR reported higher monthly migraine days (median=8, IQR=5-14 vs. median=13, IQR=10-17 and median=15, IQR=10-20; p≤0.001), months of chronification (median=24, IQR=12-72 vs. median=40, IQR=12-108 and median=60, IQR=18-96; p=0.044), monthly days of symptomatic drugs assumption (median=8, IQR=5-15 vs. median=12, IQR=9-20 and median=15, IQR=10-20; p≤0.001), medication overuse (19.4% vs. 45.9% and 40.7%; p≤0.001). They also had more comorbidities such as depression (18.3% vs. 31.1% and 44.4%; p=0.002) and anxiety (13.7% vs. 21.1% and 37%; p=0.009). In these groups, PROMs also revealed a higher presence of anxiety (p≤0.001) and depression (p≤0.001) symptoms and poorer sleep quality (p=0.006). Regarding specific perceptions about migraine, RES and REF individuals reported higher impact of migraine on daily life (p≤0.001) and work, household work, and social life (p≤0.001), along with a lower perception of the effectiveness of their ongoing treatment for migraine (p≤0.001), when compared to NRNR subjects (Table 1). Conclusion. RES and REF migraine is associated with relevant migraine burden considering migraine features, comorbidities and scores at several scales; the severe burdensome condition of RES and REF is confirmed by the median number of monthly migraine days and PROMs.

Guidelines in headache

OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a Real-Life European Multicenter Study

Abstract text (incl. figure legends and references) QUESTION The prevalence of migraine decreases after the fifth decade of life. However, when persisting in old age, migraine may be highly disabling, and some patients can still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OBT-A as preventative therapy in elderly CM patients. METHODS: This is a post-hoc analysis of real-life prospectively collected data at 16 European headache centers on patients treated with OBT-A for CM over the first three treatment cycles. Patients aged ≥65 years were defined as OLD, and those &lt;65-year-old, nonOLD. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to each treatment cycle (i.e., Cy1-3) in OLD compared with nonOLD participants. The secondary endpoints were the frequency of responder rate (RR) ≥50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs) from baseline to Cy-3. RESULTS In a cohort of 2831 CM patients, 235 were OLD (8.3%, range 65-91 yrs, 69.6 SD 4.7; 73.2% females) with a migraine history of 47.2 yrs (SD 13.5), of which 15.2 (SD 13.9) with a chronic frequency. After Cy-3, 32.3% of OLD participants discontinued the treatment. We observed a progressive decrease in MHDs from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p&lt;.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p&lt;.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p =.001) and in DAMs from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p&lt;.00001), from Cy-1 to Cy-2 (10.9 SD 8.6, p=.012), and from Cy-2 to Cy-3 (9.6 SD 7.4, p =.049). The percentage of OLD patients with RR ≥50% increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The changes in MHDs and the frequency of RR ≥50% or conversion to EM did not differ in OLD compared with nonOLD patients along with the three cycles. CONCLUSION In a population of elderly CM patients, OnabotulinumtoxinA provided a significant benefit in the first three cycles of treatment, as good as in non-old patients.

Headache in the elderly

Abstract lecture (online)

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients

Abstract text (incl. figure legends and references) Objective: There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors. Methods: The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about pre-attack and pre-episode symptoms. Results: Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005). Conclusions: PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.

Cluster headache 

Persistent headache after first-ever ischemic stroke: clinical characteristics and factors associated with their development

Abstract text (incl. figure legends and references) Background It is poorly described how often headache attributed to stroke continues for more than 3 months, i.e. fulfills the criteria for persistent headache attributed to ischemic stroke. Our aims were: 1) to determine the incidence of these headaches; 2) to describe characteristics and acute treatment; 3) to evaluate risk factors. Methods The study population consisted of 550 patients (mean age 63.1, 54% males) with first-ever ischemic stroke, among them 529 patients were followed up at least three months after stroke. Standardized semi-structured interview forms were used to evaluate these headaches during professional face-to-face interviews at stroke onset and telephone interviews at 3 months. Results At three months, 61 patients (30 women and 31 men, the mean age 60.0) of 529 (11.5%) follow-up patients had a headache after stroke: 34 had a new type of headache, 21 had a headache with altered characteristics and 6 patients had a headache without any changes. Therefore 55 (10.4%) patients had a persistent headache attributed to ischemic stroke. Their clinical features included: less severity of accompanying symptoms, slow decreasing frequency and development of medication overuse headache in one-third of the patients. The following factors were associated with these headaches: lack of sleep (29.1%, p=0.009; ОR 2.3; 95% CI 1.2-4.3), infarct in cerebellum (18.2%, p=0.003; OR 3.0; 95% CI 1.4-6.6), stroke of undetermined etiology (50.9%, p=0.003; ОR 2.3; 95% CI 1.3-4.1), less than 8 points by NIHSS score (90.9%, p=0.007; OR 3.4; 95% CI 1.4-8.6) and low prevalence of large-artery atherosclerosis (12.7%, p=0.006; OR 0.3; 95% CI 0.2-0.80). Conclusion Persistent headache attributed to ischemic stroke is not rare and frequently leads to medication overuse. The problem is often neglected because of other serious consequences of stroke but it actually has considerable impact on quality of life. It should be a focus of interest in the follow-up of stroke patients.

SciSe 15
Abstracts clinical

Termin

Chair

Programm

SciSe 15Abstracts clinical

Termin

Chair

Programm

SciSe 15
Abstracts clinical