16th European Headache Congress

Prof. Dr.

Chair

Prof.

Professor

Recording pre-ictal migraine changes in cortical responsivity using EEG in a patient's home environment

Abstract text (incl. figure legends and references) Brain excitability appears a critical biosignature of migraine leading up to attacks that can help to monitor a participant's susceptibility to develop an attack. We have shown – in our clinical EEG laboratory – that differences in cortical responsivity (as measure of brain excitability) in relation to the initiation of a migraine attack can be identified using longitudinal measurements of electroencephalographic (EEG)1 responses to flashing light, using the 'Chirp' paradigm2 (fig. 1c). For the current study we have moved out of the lab to the patient's home environment. We will record EEG changes toward the (pre-)ictal phase of individual attacks using visual evoked potential EEG (VEP-EEG) (fig. 1a). Participants fill out our validated headache E-Diary, providing daily information about headache, medication use and menstrual bleeding.3,4 Recordings will start six days prior to an expected (menstrual) migraine attack. In the majority of cases 3-7 days of daily sessions (~30 min each) will be performed, but if needed recordings will be extended until an attack occurs. VEP-EEGs will be measured using a mobile EEG-system and flashing lights presented by LED goggles (fig. 1b).1 The flash light sequences consist of a short pulse-train over a broad frequency range of 10-40 Hz ('chirp' stimulation).2 We have successfully set up a home-based neuromonitoring system that will help us understand brain excitability changes in a patient's home environment by capturing daily fluctuations as possible early warning signs of upcoming migraine attacks. We have set up a neuromonitoring system to perform home-based VEP-EEG measurements in a large group of migraine patients. For the future, picking up early changes in EEG signals in relation to attacks may form the basis for guiding early interventions and monitoring treatment effects. Perenboom et al. 2020 Cephalalgia Gantenbein et al. 2014 Cephalalgia van Casteren et al. 2021 Cephalalgia van Casteren et al. 2021 Neurology

Headache, thalamus and other brain nuclei

Migraine

ePoster

Vestibular signs in experimentally induced migraine attacks: a post-hoc, exploratory analysis

Abstract text (incl. figure legends and references) Question: Vestibular migraine (VM) as defined in ICHD-3 represents one of the most common vestibular syndromes, although its pathophysiology is not fully understood. The acute phase of VM is characterized by transitory oculo-vestibular signs (OVSs) that usually disappear outside of the VM attack. The difficulty to study spontaneous migraine attacks led to inconsistent results, and we believe that the adoption of human migraine models can help overcome this issue. Methods: In this post-hoc analysis, we investigated the incidence of OVSs during experimentally induced migraine attacks in 24 episodic migraine patients without VM and 19 healthy controls exposed to sublingual nitroglycerin (NTG 0.9 mg). A comprehensive oculo-vestibular examination was performed at baseline, at migraine-like onset and before hospital discharge (180 minutes after NTG). Results: Sixteen out of the 24 migraine patients developed a migraine-like attack (66.7%). Three of them (12.5%) developed OVSs during the migraine-like attack. In line with previous literature, we described a combination of central (down-beating nystagmus) and peripheral (bilateral deficit of vestibulo-ocular reflex) vestibular signs. Noteworthy, no patients with a negative induction test developed OVSs. No OVSs were detected in healthy subjects at any timepoints. Noteworthy, no subjects complained of vestibular symptoms throughout the study procedures. Conclusions: Human migraine models may indeed be appropriate tools to evaluate the vestibular dysfunction in migraine and in VM under well-controlled experimental conditions. The present findings represent a starting point to design future ad-hoc and well-powered studies to deepen our knowledge on this topic.

NMDA, AMPA, Kainate Receptors in Medication Overuse Headache – Focus on Correlations of the Therapy with the HPA-Axis and Pineal Gland Activities

Abstract text (incl. figure legends and references) BACKGROUND Observation examined effects of dextromethorphan, a manageable N-methyl-D-aspartate receptor antagonist involved with AMPA and kainate receptors trafficking, for medication overuse headache (MOH) and correlations of its effect with variables of patients. In 2006 we wrongly indicated the drug ineffectiveness. It was due to treatment shortness. The drug was shown needing a longer time for sensory remapping. METHOD Participants 576 MOH. Presented data regard 378 (34.6+7.9SD 284 females) divided in 2 matched groups. Procedure: dextromethorphan 1.5 mg/kg/PO vs amitriptyline 1 mg/kg day/PO, 2 months treatment-period. Baseline evaluation of: Adrenocorticotropic hormone (ACTH), cortisol, L-citrulline co-product in nitric oxide synthesis, microbiome, methylation, patterns, pineal gland volume (MRI), melatonin, psychometric tests. RESULTS Dextromethorphan Therapeutic and Side Effects Drop-out n= 1 Effect decrease pain severity (87%), hrs./pain (72%) p&gt;0.0001 vs amitriptyline (42%, 39% respectively) Less than 35% benefit Post-traumatic stress disorder n= 9 females,2 males Opioids abusers n=25 females Absolute Refractoriness n=2 females surgically treated pyneocitoma Side effects Drowsiness n=135 first week Dextromethorphan: Therapeutic Effect Correlations Positive Cortisol abnormal pattern and high values p&lt; 0.02 or low values p &lt;0.01 ACTH abnormal pattern and value p&gt;0.02 L-citrulline high p&gt;0.009 Sleep rhythm alteration p&lt;0.009 Depression Hamilton D p&gt;0.01 Anxiety Hamilton A p&lt;0.05 Microbiome disturbances p&lt;0.001 Melatonin abnormalities p&lt;0.02 Pineal dimensions RMN p&lt;0.05 No/Poor Methylation patterns NS Social stress test TSST p&lt;0.6 CONCLUSION Hypothalamic-pituitary-adrenal axis function and pineal gland may play role in MOH mechanism and in dextromethorphan effectiveness

Medication overuse headache

Reversible cerebral vasoconstriction syndrome and polymorphisms of thrombophilia genes.

Abstract text (incl. figure legends and references) Background and aims: (RCVS)characterized by the acute intense headache, focal and/or universal cerebral symptoms, epileptic paroxysms,accompanied by reversible segmental multifocal cerebral vasospasm, which disappears in three months.Aim of our study was to identify gene polymorphisms predisposing to hereditarv thrombophilia in REVS patients Methods: 24 patients (age 38+11 years) with RCVS were examined: 19 women (79.1%) aged 38.0+11.4 years,5 men (20.8%) aged 38.2+11.3 years. There didn't find significant gender difference in age. Investigation included routine clinica and neurological examination,neurolayme research methods (brain MRI on 1.5T or 3T, MR arterio-graphy) and molecular genetic study of polymorphisms predisposing to thrombophilia: G20210A of prothrombin gene,C677T methylenetetrahydrofolate reductase gene, 675 4G/5G gene of endothelial plasminogen activator inhibitor (PA1-1, SERPINE1), 455 G/A gene of the beta-polypeptide chain of fioninogen Results: Polymorphism G20210A in the prothrombin gene was not detected in the examined patients. Heterozygous carriage in the methylenetetrahydrofolate reductase gene was observed in 10 patients - in nine women and one man (43.5%), homozygous-in two women (8.3%). Polymorphism of the endothelial plasminogen activator inhibitor gene was detected in 16 patients (12 women and four men) in the heterozygous state (66.7%) and in three - in the homozygous state (12.5%). Polymorphism 455 G/A was detected in heterozygous state in six patients (25%): five women and one man and in homozygous state in four patients 16.7%- two women and two men Conclusion: The role of the revealed changes in the development of the complicated course of CVS requires further study.

Genetics genomics | RNA

Secondary headaches

Painful trigeminal neuropathy. A series of 30 cases.

Abstract text (incl. figure legends and references) QUESTION Painful Trigeminal Neuropathy (PTN) is an entity which affects the trigeminal nerve axonally and has not yet been well studied. We present our series of the last five years. METHODS Observational, descriptive and retrospective study from a database consisting of patients with trigeminal pain followed up in a tertiary hospital for the last five years. We include patients with PTN (ICHD3 criteria: code 13.1.2). We analyzed epidemiological, etiological, clinical and therapeutic variables. RESULTS We found 30 patients with PTN (4%) out of 262 patients with trigeminal pain (classic TN: 33%, secondary: 15%, idiopathic: 40%). Women: 67%, mean age of debut: 61.1y [21-92] with an evolution of 3.6y and mean follow-up of 18 months. Symptoms: right side 48%, left side 31%, bilateral 21%. Affected branches: V1 31%, V2 17%, V3 7%, V1+V2 21%, V2+V3 14%, V1+V2+V3 10%. Burchiel type 2: 94%, Burchiel type 1+2: 7%. Causes: post-herpetic 28%, post-surgery 24%, post-traumatic 10%, oral infection 3%, idiopathic 34%. Need for therapy: 90%. Most frequently used drug at start: PGB 38%, GBP 35%, others 27%. Average number of therapies: 2. Monotherapy efficacy: 73%; Polytherapy: 27%. Most effective drug: GBP 30.7% (mean dose: 1212mg/d); CBZ/OXC/ESLI 23%; PGB 19%; AMT 19%; transdermal lidocaine 15%; Duloxetine 8%, LCS 8%, anaesthetic blockade of affected branch 8%. Most frequent associations: post-herpetic + V1: 100%. Response to transdermal lidocaine in herpetic causes: 50%. Bilateral involvement + idiopathic cause: 100%. CONCLUSIONS PTN is an infrequent entity in trigeminal pain (4%) and it is clinically and etiologically heterogeneous. Bilateral affection is associated with an idiopathic cause, and herpetic causes always affect V1. The most effective drug was gabapentin and 50% of post-herpetic cases showed a good response to transdermal lidocaine.

Posttraumatic headache disorders

Trigeminal neuralgia

Pressure Pain Threshold over Neural Structures in Patients with Acute Whiplash Associated Disorders with and without Headache: A Case-Control Study

Abstract text (incl. figure legends and references) Objective: To evaluate whether there are differences in pressure pain thresholds (PPT) over neural structures in the cranio-cervical region and upper limbs between patients who present with headache and those who do not shortly after a whiplash injury Methods: A case-control study was conducted from September 2020 to February 2021 in a Traumatology Clinic in Madrid, Spain. PPT (N/cm2) were evaluated with an algometer twice over the median, ulnar, radial, supra-orbitaire and greater occipital nerves bilaterally. The evaluator was blinded to the group allocation. Results: Among 49 consecutive patients who were assessed, 41 eligible patients were included in this study, 22 and 19 with and without headache, respectively. Baseline differences between groups were found in relation to sex; there were more women in the group with headache (73.7% vs 50% in the non-headache group). No baseline differences were found in age, height, weight and days from the accident to the evaluation. When compared to the non-headache group, significantly lower PPT (mean ± SD; p-value) were found in the headache group for left (20,92±7,4; p=0,031) and right (20.90±8,5; p=0,028) radial nerves, right ulnar nerve (16.64±5,52; p=0,016) left (8.47±2,62; p=0,008) and right (8.79±3,15; p=0,008) supra-orbitaire nerves and left (8.79±3,10; p&lt;0,001) and right (8.64±2,83; p&lt;o,001) greater occipital nerves. Conclusion: People who present with headache soon after a whiplash injury show lower PPT over neural structures when compared to those patients who did not develop headache. These findings suggest the presence of greater sensitization in those who develop headache following a whiplash trauma.

Post-traumatic headache, a narrative review and a report of the latest therapeutic and management guideline (EHF abstract)

Abstract text (incl. figure legends and references) Post traumatic headache (PTH) is referred to any newly developed or worsened previously existing headache, occurring within 7 days after trauma or regaining consciousness post-trauma. Headaches resolving within 3 months after onset are called acute and persisting beyond 3 months are called persistent. A prevalence of 33-92% has been reported for PTH. Considering the significant increase in the amount of traumatic injuries, PTH as the most prevalent sequel of trauma is also believed to rapidly increase. Interestingly, there is no dose-response relationship between the injury and headache severity. PTH mostly resembles migraine, tension type, and cervicogenic headaches as well as trigeminal autonomic cephalalgias. PTH has a benign course with complete symptom resolution. It usually resolves within 3-6 months after its onset, though it might persist for one year or even longer. In a minority of patients headache have a prolong course and sometimes resistant to different treatment modalities. Risk factors for PTH include age, sex, headache at emergency department at first admission, psychological disorders and medications, substance abuse, history of pre-injury headaches, history of physical or sexual abuse, low educational achievements, medication overuse and associated factors including dizziness, fatigue, decreased concentration, psychomotor slowing, memory problems, insomnia, anxiety, personality changes are addressed for PTH. Pathophysiology of PTH is mainly related to inflammatory markers increasing in CNS after trauma and increased permeability of blood brain barrier to immune agents and pathogens. Work up includes comprehensive patient evaluation and tests to rule out serious conditions. Medication usually begins with analgesics and NSAIDs with management of comorbidities and psychological support. If the pain didn&quot;t get resolved, further pharmacologic medication will be prescribed according to the therapeutic management of the nearest headache phenotype.

Guidelines in headache

Differences on the Flexion-Rotation Test in Patients ith Acute Whiplash Associated Disorders with and without Headache: A Case-Control Study

Abstract text (incl. figure legends and references) Objective: To assess if subjects who develop headache shortly after a whiplash injury show less range of motion on the flexion-rotation test (FRT) than those who do not develop headache Methods: A case-control study was conducted on patients between 18-65 years old diagnosed with whiplash associated disorders (WAD) grade II according to the Quebec Task Force. Patients were excluded if they had previous headache prior to the whiplash injury, were evaluated more than 30 days after the whiplash injury and/or who had a serious disease or congenital condition. Range of motion (º) on the FRT was evaluated bilaterally in consecutively recruited patients. The evaluator was blinded to the headache status. Results: 41 patients were included in this study, 22 and 19 with and without headache, respectively. Baseline differences between groups were found only in relation to sex; there were more women in the group with headache (73.7% vs 50% in the non-headache group). Statistical analysis revealed that range of motion (º) on the FRT was significantly reduced in patients with headache on both the left (mean±SD: 28,98±7,76 vs 35,29±4,92; p=0,002) and right side (29,73±7,7 vs 36,84±4,05; p&lt;0,001) when compared to the non-headache group. Conclusion: A decreased range of motion was observed on the FRT in patients who have developed headache shortly after a whiplash injury when compared to those patients who did not develop headache. These findings suggest that the upper cervical structures may be involved in the presence of headache in patients with acute WAD.

Poster session 9

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