16th European Headache Congress

Chair

Prof.

Prof. Dr.

Long-term effectiveness and safety of occipital nerve stimulation in medically intractable chronic cluster headache: a prospective follow-up study of the randomised controlled ICON trial.

Cluster headache 

Headache, thalamus and other brain nuclei

Abstract text (incl. figure legends and references) Question: We have shown in the ICON study that occipital nerve stimulation (ONS) is safe and effective in medically intractable chronic cluster headache (MICCH). This prospective follow-up evaluates the long-term effectiveness and safety. Methods: Every six months, participants completed questionnaires on the attack-frequency, adverse events, subjective improvement and willingness to recommend this treatment to other patients. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. Results: Of the n=119 eligible participants, n=88 (74%) provided informed consent and were followed ≥2 years unless the device was prematurely removed. There were n=73 (83%) active participants after 2 years, n=60 (68%) after 3 years, n=32 (36%) after 5 years and n=3 (3%) after 8.5 years. Mean follow-up was 4.2 ± 2.2 years for a total of 370 person-years. Of the 49/88 (56%) ≥50% responders at the end of the ICON study, 35/49 (71%) retained this response and 15/39 (38%) of the non-responders became a ≥50% responder for at least half the follow-up period. The pooled geometric mean [95% CI] weekly attack frequency remained considerably lower after one (4,2; 2,8 - 6,3), two (5,1; 3,5 - 7,6) and five years (4,1; 3,0 - 5,5) compared to baseline (16,2; 14,4 - 18,3). Most participants (69/88; 78%) reported a subjective improvement from baseline at the last follow-up and 70/88 (81%) would recommend this treatment to other patients. Additional surgery was required in 112/122 (92%) hardware related events in 44/88 participants (50%), corresponding to a hardware-related additional surgery rate of 0.35 person-year-1 [0.28 – 0.41]. No predictive factors for effectiveness at 2 years after the ICON study, i.e. 3 years after ONS implantation were observed. Conclusions: ONS is a safe, well-tolerated and long-term effective treatment for MICCH.

ePoster

Efficacy and safety of Galcanezumab as chronic cluster headache preventive treatment in real world conditions

CGRP inhibitors in the clinic

Abstract text (incl. figure legends and references) Question: Calcitonin gene-related peptide(CGRP) has shown to play a pivotal role in cluster headache(CH) pathophysiology. A clinical trial with Galcanezumab has been carried out in chronic cluster headache(CCH) that did not achieve significant reduction of headache attacks. However, its off-label use in patients with CCH refractory to other therapies could be considered.We aim to asses the efficacy and security of Galcanezumab as preventive treatment in a CCH population in a real-life setting. Methods: Observational prospective study. CCH patients who received at least 1 administration of 240mg monthly subcutaneous Galcanezumab. Data were obtained from clinical interviews, headache diaries, dissability scales and PGIC score. Results: 21 patients, 76.2% males, mean age of 47.8 years with 12.2 years of CH. 6.3±1.9 previous preventive therapies, incluiding onabotulinumtoxinA in 90.5%. Furthermore, occipital neuroestimulation in 38.1%, occipital radiofrequency in 9.5% and GON section in 4.8%. The average number of attacks per month was 76.6±61.1 with 8.9±1.5 intensity (NRS) at baseline. After one month of treatment number of attacks reduced to 34.7±25.3 with 8.1±17 intensity; 10(47.6%) patients achieved a reduction of at least 50% in monthly headache attacks, of which 4(19%) achieved a 75% reduction. Triptans abusers reduced from 61.9% to 33.3%. Of the 15 patients of whom we have 3 months follow-up, 7(46.6%) reduced their monthly attacks by 50% and 4(26.6%) 75%, with an average of attacks/month of 35.9±28.1 and an intensity of 7.5±2.3. Triptans abusers were 26.6%. 47.6% considered the improvement as a real difference in their lives (PGIC≥5) after 1 dose of Galcanezumab and 60% after 3 doses. 52% experienced adverse events, mostly mild, most common constipation(19%) leading to discontinuation in 1 patient. Conclusions: Despite how refractory our CCH cohort is, Galcanezumab was effective in nearly 50% patients. This supports individual off-label treatment attempts.

Intra- and inter-individual attack frequency variability of chronic cluster headache

Data science in research and digital medicine

Abstract text (incl. figure legends and references) Question: Little is known regarding the AF variability of CCH, hampering power and sample size calculations, and consensus on the most optimal duration of pre-trial baseline observation periods. Methods: We used detailed data from the 12-week baseline period of the randomized controlled occipital nerve stimulation ICON trial in patients with medically intractable CCH. Participants were post hoc divided into four mean daily AF groups: &lt;2; &gt;2-3; &gt;3-4; &gt;4. We analyzed the following four variables for the total and four AF groups: (i) weekly vs. instantaneous recording of the AF; (ii) intra-individual AF variability by using (a) the mean absolute deviation from the mean and (b) the coefficient of variation; (iii) seasonal variability of the AF ; (iv) the smallest number of weeks to obtain a reliable estimate of the baseline AF over the entire 12-week period. Results: Weekly median (14.4 [8.2 – 24.0]) and instantaneous (14.2 [8.0 – 24.5]) AF recordings were similar (p=0.20; Bland-Altman plot). The median weekly AF over all 12 weeks was 15.3 (range 4.2-140). Absolute AF variation was lower in the lowest AF group in comparison to the other AF groups (p&lt;0.001). Relative AF variability decreased with increasing AF (p=0.010). During spring AF was higher compared to the other seasons (p=0.001). We tabulated the weekly AF estimation accuracies compared to, and the associated deviations from the 12-week gold standard for different lengths of the observation period. Conclusion: Weekly retrospective recording of the AF is as good as instantaneous recording and more convenient. Participants with ≥3 daily attacks show less AF variability than those with &lt;3 daily attacks. Mean AF is highest in spring. The data suggest that an optimal balance between feasibility and an accuracy of 90% with a deviation of no more than 20% is achieved at an observation period of 7 weeks.

Galcanezumab for refractory chronic cluster headache in clinical practice

Abstract text (incl. figure legends and references) QUESTION: To evaluate the efficacy and safety of galcanezumab for refractory chronic cluster headache (RCCH) patients in clinical practice. RCCH patients usually fail to most of preventive treatments started on them. There&quot;s a need for new drugs to improve their bad quality of life. METHODS: We prescribed galcanezumab 360 mg alternating with 240 mg per month in RCCH patients willing to participate in this exploratory study. All of them received at least a 6 month treatment period. They had tested all kind of preventive treatments, including botulinumtoxinA injections. No previous treatment was stopped, galcanezumab was started as add-on therapy. We analyse mean cluster headache attacks (CHA) per week reduction after treatment. Adverse events were also collected. Informed consent was obtained. RESULTS: 7 patients (6 men / 1 woman) 23-59 years (mean 44,43) were included in the registry, all of them at least &gt; 2 years of RCCH (mean 12,57 years (4-24). Most of them were smokers, just one with alcohol consumption. 3 of them continued with botulinumtoxinA injections each 3 months due to partial response. Mean CHA of 24,14 per week before treatment. 9,29 CHA per week after treatment; this means a reduction of 54,2 % in CHA per week (3,7 – 95 %). In most patients a significant reduction in intensity was found. 3 of them were high responders (reduction more than 75 %) and 3 no responders (25 % or less). No significant adverse events were found, the most usual: local dermal reactions in sites of punction (erythema, swallowing, pruritus) CONCLUSIONS: High doses of galcanezumab can be an option for RCCH patients. The treatment is safe and ameliorates at least half of patients in which we prescribed it. In this very difficult to treat population any benefit is welcome, so the use of galcanezumab should be tested in RCCH patients.

A Systematic Review and Meta-Analysis on the Preventive Treatment of Refractory Chronic Cluster Headache

Neuromodulation and nerve blocks

Abstract text (incl. figure legends and references) QUESTION- Which is the best preventive treatment strategy for Refractory Chronic Cluster Headache (rCCH) based on current scientific evidence? METHODS- The review and meta-analysis were performed following PRISMA guidelines. The protocol was registered in PROSPERO (ID CRD42021290983). The search was performed on September 2021 on databases Pubmed, Embase and Cochrane. Studies of preventive strategies for rCCH defined by the European Headache Federation criteria were selected. For risk of bias assessment, the Cochrane Handbook Risk Of Bias tool was used for randomized clinical trials (RCT) and ROBINS-E was used for observational studies (OS). RESULTS- 43 articles met the inclusion criteria. The largest number of articles studied occipital nerve stimulation (ONS) accounting for 1 ECA and 11 OS for a total of 436 patients, followed by deep brain stimulation (DBS): 1 RCT and 8 OS; 118 patients. All ONS studies reported a significant reduction in attack frequency and the 50% responder rate ranged from 29.4% to 80.0%. Meta-analysis of ONS studies revealed a pooled 50% responder rate of 57.3% (95%CI 0.48-0.67, p&lt;0.001). DBS studies reported a 50% responder rate of 50-100%, with a pooled result of 71.6% (95%CI 0.45-0.978, p&lt;0.001). Reported adverse events (AE) were more serious in DBS studies. The remaining 24 articles (anti-CGRP pathway drugs, ketamine-magnesium infusions, serial occipital nerve blocks, clomiphene, onabotulinum toxin A, ketogenic diet, sphenopalatine ganglion radiofrequency or stimulation, vagus nerve stimulation, percutaneous bioelectric current stimulation, upper cervical cord stimulation and vidian neurectomy) present weaker results or have poorer quality of evidence. CONCLUSIONS- Considering the quality of the published studies, their results and the profile of AE, ONS could be the first therapeutic strategy for patients with rCCH based on the current evidence.

Side-shift of cluster headache attacks after Greater Occipital Nerve-injection.

Abstract text (incl. figure legends and references) Objectives: Attacks of cluster headache (CH) are usually side-locked in most, but not all patients. In a few patients, the side may alternate between or, rarely, within cluster episodes. Methods: We observed 7 cases in whom the side of CH attacks shifted immediately or shortly after unilateral injection of the greater occipital nerve (GON) with steroids. Side-shift was defined as a temporary or persistent displacement of CH attacks to the contralateral side of the regular headache attack previous to the GON-injection. Results: In five patients with previously side-locked CH attacks and in two patients with previously side-alternating CH attacks, a side-shift occurred immediately (N=6) or shortly (N=1) after GON-injection. Conclusion: Unilateral GON-injections might cause a side-shift of CH attacks, illustrating the complex role of the GON in CH pathophysiology.

Retrospective Validation of a New Tool for the Identification of Suspected Cluster Headache

Multidisciplinary clinical assessments

Abstract text (incl. figure legends and references) Question: Cluster headache is a disorder often referred to as &quot;suicide headache&quot; and is associated with significantly disabling attacks[Newman et al 2015]. Although it is as prevalent as neurological conditions such as multiple sclerosis[Wei et al.2018, Leray et al. 2016] these patients often go over 5 years before diagnosis[Rosen et al. 2012]. This study aims to determine whether a screening tool can be retrospectively validated to reliably identify patients with a high likelihood of having cluster headache to prioritize rapid consultation with a headache specialist. Methods: A screening clinical questionnaire was developed utilizing criteria specific to cluster and to best differentiate it from other headache disorders. The tool was then retrospectively applied to all patients seen at a tertiary care specialty headache clinic between January 2021 and December 2021. Eligibility criteria include adult patients (&gt;18 years), any reason for referral, any referring headache diagnosis and an initial consultation note including all data required to complete the scoring tool. A total score was calculated for each patient and the area under the receiver operating curve (ROC) used to identify the score with the highest sensitivity and specificity for a diagnosis of cluster headache. Results: A total of 415 patients were ultimately included in the study, of which there were 25 cluster headache patients. identified with an average screening score of 12.28. In comparison, the 255 migraine patients included had an average score of 1.45 on the screening tool. A ROC analysis indicated that a cutoff score of 8 had a 100% sensitivity and 85-87% specificity for a diagnosis of cluster headache. Conclusions: Our study was able to develop and retrospectively validate a cluster headache screening tool that can reliably differentiate cluster headache from other disorders. Figure 1. Cluster headache screening toolTable 1. Average score by headache disorderTable 2. Coordinates of the ROC.

Cluster Headache – The Worst Possible Pain on YouTube

Abstract text (incl. figure legends and references) Background: In clinical practice, patients with cluster headache often ask questions or mention information that they have seen or heard on the Internet. Since YouTube (www.youtube.com) is the second most visited Web site worldwide and offers a plethora of video content, we found it timely to ascertain the quality of information on cluster headache that is freely available on YouTube. Methods: We conducted an inquiry on YouTube on January 24, 2022, with the search term &quot;cluster headache&quot;. Eligible YouTube videos included those with ≥10.000 views and content related to cluster headache. We assessed the quality and reliability of the videos with the Global Quality Scale and DISCERN, respectively. Results: The search strategy identified 644 videos of which 134 were eligible for inclusion. The sources of the included videos were categorized as &quot;Healthcare Professional/Institution&quot; (n=45), &quot;Personal Experience&quot; (n=52), and &quot;Other&quot; (n=37). According to the Global Quality Scale, 70 (52%) were low quality, 34 (25%) were of moderate quality and 30 (22%) were of high quality. According to DISCERN, 104 (78%) were of low reliability, 28 (21%) were of moderate reliability and 2 (1%) were of high reliability. Conclusion: The quality and reliability of cluster headache-related information on YouTube has room for improvement, even the content provided by healthcare providers. These findings should incentivize stakeholders, e.g., governmental services, professional societies, healthcare providers, to provide accessible and better information on cluster headache.

A retrospective evaluation of use of gammaCore at The Walton Centre NHS Trust

Abstract text (incl. figure legends and references) Introduction GammaCore is a non-invasive vagus nerve stimulator (nVNS) which modifies pain pathways and has been approved by NICE for management of cluster headaches. For use in other headache disorders, in the UK, an IGFR form needs to be completed. Cluster headache (CH) is a trigeminal autonomic cephalalgia characterised by severe, strictly unilateral headache attacks accompanied by ipsilateral autonomic symptoms and restlessness associated with suicide. Objective To assess the effectiveness of gammaCore in management of headache disorders Methods Retrospective review of 100 patients who are currently using gammaCore was undertaken Results Out of 100 patients (F:M 62:38), with an average age of 48, 52 had CH, 39 hemicrania continua (HCC), 3 SUNCT, 4 NDPH and 2 CM. On Average 6 previous preventatives were tried including Verapamil, Botox and CGRP MABs. Duration of treatment was 1.5 years on average, with one patient on treatment for over 6 years. Headache diaries was available in 57 patients at start of treatment and 36 at 3 months, 20 at 6 months and 16 at 1 year. At 3 months, there was 6 days reduction in severe days and 7 day increase in clear days for the entire group. Patients with CH continued to show 8 days reduction in severe days at 1 year. Please see attached table. Conclusion In our experience, GammaCore is effective in management of a variety of headache disorders, particularly CH. The flaws in our study are limited headache diary data, due to a number of factors including lack of compliance and storage of the information, and lack of data on tolerability.

Galcanezumab vs Placebo in Cluster Headache Prevention and Treatment: A Systematic Review

Abstract text (incl. figure legends and references) Question: Cluster headache (CH) causes excruciating unilateral temporal or periorbital pain with ipsilateral autonomic symptoms. Classified as primary headache, it is characterized by daily headaches that persist for weeks to months with direct impact on quality life. Treatment with galcanezumab (GZB) is an upcoming option for preventive treatment of CH. What is the impact of this new therapy in preventing and reducing the frequency of CH? Methods: A total of 122 articles were identified in databases: Pubmed, Embase and Cochrane), by two independent researchers. Three randomized controlled trials were included in this systematic review using a PRISMA protocol. The outcome of interest was change in weekly frequency of CH attacks and mean reduction in attack frequency compared with baseline. Results: A total of 449 patients were randomized into 2 groups, the intervention group received the standard dose of 300mg of GZB versus the placebo control group. The studies primarily evaluated the reduction of CH and the mean &gt;= 50% reduction in attack frequency compared with baseline. Goadsby et al. obtained a mean percentage reduction in the weekly frequency of CH attacks in the first 3 weeks of 52% in the intervention group and 27% in the placebo group. Kudrow et al. reported the observed reduction by approximately 43% in the intervention group over the same period. Both studies showed compatible efficacy reducing attacks &gt;= 50% (71% (p=0.046) and 78.3%, respectively). However, Dodick et al. showed no statistically significant effect of GZB in both outcomes: the reduction in weekly attack frequency (p=0.334) and mean reduction in attacks 32.6% (p=0.170). Conclusions: The effects of GZB in reducing the number of seizures, especially in the first few weeks of treatment, are encouraging, although further studies are required to establish the efficacy of GZB in long-term use for CH prevention and treatment.

Coexistence of migraine and cluster headache - is it more than just a coincidence?

Migraine

Abstract text (incl. figure legends and references) Introduction: Cluster headache (CH) and migraine are recurrent painful primary hedaches. They are typically presented with different clinical appearance, but they show some common features, such as unilateral pain, triggers, pathophysiological mechanisms and response to therapy (triptans and monoclonal antibodies against the calcitonine-related peptide receptors). In the general population, the prevalence of CH and migraine is estimated to 0,1% and 12% respectively. Their coexistence is not common, though ranging from 0-65%1. Some data are showing that in 92% of migraine begins first and persists in only 20% of patients after CH began2. Case report: A 30-year-old woman presented with typical CH lasting for 3 weeks. Headache was present every day, twice a day - one during a day and once during at night. If untreated duration was 3 h. Rizatriptan coud release her from pain, while ibuprofen and paracetamol were not helpful. She already had a headache with similar characteristics at the age of 17. Her migraine attacks with complex aura started at the age of 13. Attacks were quite infrequent, till age of 28, after she gave birth, and the attacks became much more frequent. In her medical history there were no other diseases and she was not taking any medication. Conclusion: The aim of the present report was to draw attention to coexistence of CH and migraine since it can go unrecognised in clinical practice. Better education of health-care providers and spreading awarness of possibile coexistence of more primary headaches could provide better life quality for our patients. Only population-based studies can confirm or disprove an association between migraine and CH by determing whether they occur together more commonly then expected by chance. Reference list: 1. Ewans W. et al,Migraine and CH:Coexistence,Laterality and Gender,2004,44;186-188. 2. Solomon S. et al., The time relationship of migrane and CH when occuring in the same patient, Headache, 1986;26:500-502.

Clinical neurophysiology of hemiplegic cluster headache - case report

Abstract text (incl. figure legends and references) Introduction Cluster headache (CH) is trigeminal autonomic headache presented by the recurrence of unilateral short duration (15-180min) pain attacks with coexisting same-side cranial autonomic symptoms. The atypical form of cluster headache associated with transient hemi-motor, sensory or even visual and aphasic symptoms analogically to migraine is called hemiplegic cluster headache (HCH). This rare form of trigeminal autonomic cephalalgia is not recognised by the International Classification of Headache Disorders (ICHD). Since the first published case series in 2002, only a few cases have been presented so far. Case presentation We presented a case of a 50-year-old male that fulfilled the ICHD criteria for episodic CH who experienced atypical attacks characterized by concomitant acute onset of hemi-sensory and hemi-motor symptoms. Using extensive diagnostic panel we excluded the secondary cause of the headache. Exploring the localisation of motor and sensory pathways affectation we used the sensory and motor evoked potentials method. Conclusion Neurophysiological parameters show that during the cluster period there is a transient affectation of sensory and motor pathways in the projections of the brain stem and medulla oblongata. This points to potential differences in the mechanism of neural pathway involvement among HCH and different types of primary headaches with coexisting motor and sensory symptomatology.

Poster session 2

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