Treatment Of Cluster Headache Research Articles

Pre-cluster symptoms in a Taiwanese cohort of cluster headache: symptom profiles and clinical predictions

BackgroundPre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy.MethodsWe prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients’ headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil.ResultsA total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7–9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3–4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4–5.1], p = 0.003).ConclusionPCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications.

ANODYNE study: A double-blind randomized trial of greater occipital nerve block of methylprednisolone and lignocaine versus placebo as a transitional preventive treatment for episodic cluster headache.

There is inadequate evidence of the efficacy of greater occipital nerve block (GONB) for the preventive treatment of cluster headaches. We assessed the efficacy and tolerability of GONB injections as a transitional preventive treatment for episodic cluster headaches (ECH). This randomized, double-blind, placebo-controlled, parallel-group trial conducted at GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India, included ECH patients diagnosed by ICHD-3 criteria, aged 18-65, with one or more attacks per 24 h for seven days before randomization (baseline). ECH patients were either not on preventive medications or on stable doses for at least three months. ECH patients were randomized to receive active GONB (2 ml methylprednisolone (80 mg) and 2 ml lignocaine (2%)) and placebo (4 ml saline injections). Before giving GONB, lignocaine jelly was applied topically to mask the effect of numbness following the GONB. The primary efficacy endpoint was the mean change in weekly attack frequency from baseline to Week 4. Efficacy analyses were performed in a modified intention-to-treat population that included all patients who received at least one injection of GONB and had a follow-up for one week following GONB. The safety analysis included treatment-emergent adverse effects (TEAE) in all patients who received at least one dose of investigational product. The trial was registered with the Clinical Trials Registry of India (CTRI/2021/21/038397). Forty ECH patients were randomized between December 2021 and January 2023. Thirty-nine patients (19 in the active and 20 in the placebo groups) were available for efficacy analysis. The change in weekly attack frequency from baseline to Week 4 was -11.1 (95% CI: -8.5 to -4.4) for the active group compared to -7.7 (95% CI: -11.8 to -9.8) for placebo (mean difference -3.4 (95% CI: -5.2 to -1.7, p < 0.001). We noted TEAE in 18 (90%) of 20 patients who received the active drug and in 18 (90%) of 20 patients who received a placebo (p = 0.38). The common TEAE were local site bleeding and pain, which were mild and transient. No serious adverse events were reported. This study found that GONB with methylprednisolone and lignocaine significantly reduced the weekly attack frequency from baseline to Week 1 through Week 4 in ECH patients compared to a placebo. GONB was well tolerated.

ID: 316629 In-Silico Methodology to Produce Innovative Designs for a Cranial Nerve Stimulator to Treat Cluster Headache

ID: 316629 In-Silico Methodology to Produce Innovative Designs for a Cranial Nerve Stimulator to Treat Cluster Headache

Quality by Design Approach to Nasal Mucoadhesive Microspheres: Enhanced Sumatriptan Succinate Delivery through Formulation and Characterization.

The primary therapeutic indications for sumatriptan succinate (STS) include the treatment of migraine and cluster headaches. To enhance mucoadhesion, sodium carboxymethyl cellulose (SCMC) and hydroxyl propyl methyl cellulose (HPMC K15M) were used in this study to develop nasal mucoadhesive microspheres of STS. A central composite design, facilitated by Design Expert software, was employed to assess the impact of polymer concentrations on mucoadhesion, involving nine different formulations. The study’s findings indicated that the microspheres were uniformly sized and spherical and that the polymers were compatible with STS. The optimal formulation, consisting of 220.711 mg of SCMC and 150 mg of HPMC K15M, demonstrated the highest level of mucoadhesion. This combination effectively regulated the discharge of STS from the mucoadhesive microspheres and significantly improved their mucoadhesive properties. These results suggest that the strategic use of SCMC and HPMC K15M can enhance the performance of nasal mucoadhesive microspheres, ensuring a controlled release of STS and improved adhesion to mucosal surfaces. This has the potential to optimize the therapeutic efficacy of STS in treating migraine and cluster headaches.

Acute and preventive medical treatment of cluster headache in Taiwan: A narrative review.

Cluster headache (CH) is a debilitating neurological disorder characterized by severe, unilateral pain and ipsilateral autonomic symptoms. Chronic CH is exceedingly rare in Taiwan, constituting approximately 1% of all CH cases. This narrative review provides an up-to-date overview of the acute and preventive treatment strategies for CH in Taiwan, focusing on currently available pharmacological options in the country. The treatment approach for CH in Taiwan involves a stepwise strategy. High-flow oxygen and triptan nasal sprays are the mainstays of acute treatment, providing rapid relief and good tolerability. Transitional treatments, such as oral steroids and suboccipital steroid injections, serve as a crucial bridge between acute and long-term preventive therapies, offering temporary relief while minimizing side effects through a carefully limited duration. For preventive treatment, verapamil is the first-line option, with lithium and topiramate being the second-line alternatives. Among the CGRP monoclonal antibodies, galcanezumab has demonstrated efficacy in the prevention of episodic CH. Preventive treatments are personalized to individual patients, starting with low doses and close monitoring for adverse effects. Neuromodulatory therapies, such as non-invasive vagus nerve stimulation, show promise for chronic and refractory CH but have limited availability in Taiwan. In conclusion, despite the availability of various acute and preventive treatment options, unmet needs in the management of CH in Taiwan remain. In particular, increased awareness and education among healthcare professionals to improve the diagnosis and management of CH in Taiwan should be implemented.

Effectiveness of greater occipital nerve blockade in chronic cluster headache.

Greater occipital nerve (GON) blockade injections can be used to prevent episodic and chronic cluster headaches. In recent studies, prophylactic treatment has been used in addition to the GON blockade. In this study, we aimed to elucidate the effect of GON blockade on the attack frequency, pain intensity, and duration in patients diagnosed with chronic cluster headaches. The demographic characteristics of 30 patients who received GON blockade along with acute attack treatment, short- and long-term prophylactic treatment for cluster headache, and 24 patients who received only acute attack treatment, short- and long-term prophylactic treatment, before blockade treatment, in the 1st week and 1st month after blockade were investigated. Attack frequency, attack duration, and visual analog scale (VAS) variables were compared. We evaluated the VAS score, daily attack frequency, and duration of pain attacks after repeated GON blockade and found a statistically significant difference in the VAS score, daily attack frequency, duration of pain attacks, average values of the treatment, and time interaction of pain intensity in the group in which GON blockade was applied in the 1st week and 1st month compared to the pre-treatment period (p<0.01), (p<0.01), (p=0.044). Regarding the outcomes of this research, GON blockade provided significant improvement in pain frequency, attack duration, and VAS score in the period from attack treatment to the start of long-term prophylaxis treatment and one month after treatment, without the need to switch to different prophylaxis treatments. Therefore, GON blockade may be a preferable and reliable treatment option.

Sphenopalatine Ganglion Block ‘Miracle Block’- A Review Article

The sphenopalatine ganglion has maximum number of neurons in the calvarium that are not situated within the brain. In the sympathetic, parasympathetic and sensory nervous system it’s the largest and most superior ganglion. SPG block in conjunction with topical anaesthetic and radiofrequency ablation is currently advised for the treatment of trigeminal neuralgia, cluster headaches, migraines, and persistent idiopathic facial discomfort. The block of SPG is also known as “the miracle block”. The sphenopalatine ganglion block is a simple and safe procedure which can be used for eliminating acute or chronic pain and reduces the episodic recurrence of the pain.

Ketamine as Treatment for Cluster Headache: A Systematic Review of Literature and a Case Series.

Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients' experience of treatment success and quality of life. The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged.

Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies

Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.Graphical

Use of Prescribed and Non-Prescribed Treatments for Cluster Headache in a Swedish Cohort.

Cluster headache (CH) is a debilitating condition, but current therapies leave CH patients in pain. The extent of this problem in Sweden is unknown. An anonymized questionnaire was sent to 479 Swedish CH patients to investigate patterns and perceived effects of treatments. Three hundred fourteen answers were analyzed. The population was representative regarding age of onset and sex. Less than half (46%) were satisfied with their abortive treatments, 19% terminated functioning abortive treatments due to side effects. Additionally, 17% of chronic CH patients had not tried the first-line preventive drug verapamil. A small subset had tried illicit substances to treat their CH (0-8% depending on substance). Notably, psilocybin was reported effective as an abortive treatment by 100% (n = 8), and with some level of effect as a preventive treatment by 92% (n = 12). For verapamil, some level of preventive effect was reported among 68% (n = 85). Our descriptive data illustrate that many Swedish CH patients are undertreated, lack functional therapies, and experience side effects. Further studies are warranted to search for new treatment strategies as well as a revision of current treatment guidelines with the aim of reducing patient disease burden to the greatest extent possible.

Oxygen as an abortive therapy in cluster headache: a narrative review and clinical practice aspects.

Cluster headache (International Classification of Headache Disorders third edition, ICHD-3 3.1) is a primary headache disorder affecting around 0.12% of individuals. It is characterized by severe headache attacks causing significant negative impact on the lives of patients. While administration of 100% oxygen is considered to be the first-choice acute treatment, undertreatment also exists. Reasons for undertreatment may entail problems with the correct prescription of oxygen, reimbursement issues or the practical implementation of home oxygen therapy. The aim of this manuscript is to review the scientific evidence on oxygen therapy for cluster headache and provide a practical guidance for both physicians and patients to optimize its use in an acute setting. The current evidence of the administration of 100% oxygen as a safe and effective treatment for cluster headache is strong. Based on several clinical trials and surveys, the recommended flow rates range between 12 and 15L/min via a non-rebreathing mask, for at least fifteen minutes. The frequency of cluster headache attacks and thus the need for acute treatment can be very high. Fortunately, the Belgian social security system provides a full and lifetime reimbursement of oxygen therapy for cluster headache if the diagnosis and the need for this therapy has been certified by a neurologist, neurosurgeon or neuropsychiatrist.

Cluster headache: an update on clinical features, epidemiology, pathophysiology, diagnosis, and treatment.

Cluster headache (CH) is one of the worst primary headaches that remain underdiagnosed and inappropriately treated. There are recent advances in the understanding of this disease and available treatments. This paper aims to review CH's recent clinical and pathophysiological findings, diagnosis, and treatment. We performed a narrative literature review on the socio-demographics, clinical presentations, pathophysiological findings, and diagnosis and treatment of CH. CH affects 0.1% of the population with an incidence of 2.07-9.8/100,00 person-years-habitants, a mean prevalence of 53/100,000 inhabitants (3-150/100,000 inhabitants). The male-to-female ratio remains inconclusive, as the ratio of 4.3:1 has recently been modified to 1.3-2.6, possibly due to previous misdiagnosis in women. Episodic presentation is the most frequent (80%). It is a polygenetic and multifactorial entity that involves dysfunction of the trigeminovascular system, the trigeminal autonomic reflex, and the hypothalamic networks. An MRI of the brain is mandatory to exclude secondary etiologies. There are effective and safe pharmacological treatments oxygen, sphenopalatine, and great occipital nerve block, with the heterogeneity of clinical trial designs for patients with CH divided into acute, transitional, or bridge treatment (prednisone) and preventive interventions. In conclusion, CH remains underdiagnosed, mainly due to a lack of awareness within the medical community, frequently causing a long delay in reaching a final diagnosis. Recent advances in understanding the principal risk factors and underlying pathophysiology exist. There are new therapeutic possibilities that are effective for CH. Indeed, a better understanding of this challenging pathology will continue to be a subject of research, study, and discoveries in its diagnostic and therapeutic approach.

Effects of non-invasive vagus nerve stimulation on clinical symptoms and molecular biomarkers in Parkinson's disease.

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson's disease (PD) patients. In a subgroup of patients, we measured selected neurotrophins, inflammatory markers and markers of oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomized to either active nVNS or sham nVNS. After baseline assessments, patients were instructed to deliver six 2 min stimulations (12 min/day) of the active nVNS/sham nVNS device for 1 month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with active nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly (p < 0.05) after active nVNS treatment. Here we present the first evidence of the efficacy and safety of nVNS in the treatment of gait in PD patients, and propose that nVNS can be used as an adjunctive therapy in the management of PD patients, especially those suffering from FOG. Clinical trial registration: identifier ISRCTN14797144.

Neuromodulation Techniques for Headache Management.

This narrative review aims to summarize evidence regarding the current utilization and future applications of neuromodulation in patients with headaches, with special attention paid to migraine and chronic cluster headache. A search was conducted in PubMed in August of 2023 to survey the current literature on neuromodulation for the treatment of headache. In total, the search yielded 1989 results, which were further filtered to include only systematic reviews published between 2022 to 2023 to capture the most up-to-date and comprehensive research on this topic. The citation lists of these articles were reviewed to find additional research on neuromodulation and supplement the results presented in this paper with primary literature. Research on the use of neuromodulation for the treatment of headache has predominantly focused on four neuromodulation techniques: peripheral nerve stimulation (PNS), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and spinal cord stimulation (SCS). Outcome measures reported in this article include impact on migraine and headache frequency and/or pain intensity, adverse effects of the neuromodulation technique, and associated costs, when available. We found that neuromodulation has developed utility as an alternative treatment for both chronic cluster headaches and migraines, with a reduction in frequency and intensity of headache most elucidated from the articles mentioned in this review.

Efficacy of Oxygen Treatment Using Home Oxygen Concentrators for the Treatment of Cluster Headaches: A Randomized, Crossover, Multicenter Study.

Oxygen treatment is the first-line acute treatment for cluster headaches (CHs), but this can be impeded by insurance coverage and oxygen-tank maintenance. Oxygen concentrators filter nitrogen from ambient air to produce oxygen-rich gas, and can therefore be an alternative to conventional oxygen therapy using a tank. We investigated the effectiveness and safety of using two home oxygen concentrators and compared them with using oral zolmitriptan for the acute treatment of CHs. Forty patients with episodic CHs in an active cluster period were enrolled in this randomized, crossover, multicenter study. Two attacks during the cluster period were treated using oxygen delivered by connecting two home oxygen concentrators, whereas the other two attacks were treated using oral zolmitriptan (5 mg) in a random sequence. The primary endpoint was substantial pain reduction (0 or 1 on a five-point rating scale from 0 to 4 points) at 15 min after treatment. In total, 125 attacks among 32 patients were randomized and treated (63 attacks using oxygen and 62 using zolmitriptan) according to the study protocol. More attacks treated using oxygen reached the primary endpoint than did those treated using zolmitriptan (31.7% [20/63] vs. 12.9% [8/62], p=0.013). After 30 min, 57.1% of the patients who received oxygen and 38.7% who received zolmitriptan reported pain relief (p=0.082). All patients treated using oxygen reported an improvement in pain, and 61.3% preferred oxygen while only 9.7% preferred zolmitriptan. No adverse events occurred during the oxygen treatment. Oxygen treatment administered using two home oxygen concentrators resulted in better pain relief than oral zolmitriptan in patients with episodic CHs. Our results suggest that home oxygen concentrators are capable of efficiently supplying oxygen in a similar manner to using an oxygen tank.

Recent Clinical Research on Acupuncture Therapy for Cluster Headache

Objectives: This study presents evidence by analyzing the research trends in acupuncture treatment for cluster headache in the last 10 years.Methods: Randomized controlled trials (RCTs) about acupuncture for cluster headache were searched from the China National Knowledge Infrastructure, PubMed, Cochrane Library, Oriental Medicine Advanced Searching Integrated System, ScienceON, Korean Studies Information Service System, and Research Information Sharing Service. The search terms were the combinations of “cluster headache”, “acupuncture”, and “needle therapy”, and the articles were restricted to those published between 2013 and 2023. Only RCTs were selected. The risk of bias (RoB) was assessed according to the revised Cochrane RoB2 criteria.Results: Six RCTs were selected and analyzed in this review. All selected studies were conducted in China. All RCTs comprised 628 participants. Manual acupuncture was used in all studies. Acupuncture targeting the sphenopalatine ganglion was performed in two papers published after 2020. ST8, Ex-HIN3, and GB14 were the most frequently used acupoints in acupuncture treatment. The most commonly used indicators for evaluation were headache attack frequency, clinical efficacy, and the visual analog scale. In each study, adding acupuncture treatment to conventional therapy had significant effects in relieving the symptoms of cluster headaches.Conclusion: The results suggest that acupuncture is an effective treatment for cluster headache. To ensure objective evidence for the effectiveness of acupuncture treatment in cluster headache, it is important to continue large-scale case reports and RCTs.

The HortONS study. Treatment of chronic cluster headache with transcutaneous electrical nerve stimulation and occipital nerve stimulation: study protocol for a prospective, investigator-initiated, double-blinded, randomized, placebo-controlled trial

BackgroundChronic cluster headache (CCH) is a debilitating primary headache disorder. Occipital nerve stimulation (ONS) has shown the potential to reduce attack frequency, but the occipital paresthesia evoked by conventional (tonic) stimulation challenges a blinded comparison of active stimulation and placebo. Burst ONS offers paresthesia-free stimulation, enabling a blinded, placebo-controlled study.Identification of a feasible preoperative test would help select the best candidates for implantation.This study aims to explore ONS as a preventive treatment for CCH, comparing burst stimulation to tonic stimulation and placebo, and possibly identifying a potential preoperative predictor.MethodsAn investigator-initiated, double-blinded, randomized, placebo-controlled trial is conducted, including 40 patients with CCH. Eligible patients complete a trial with the following elements: I) four weeks of baseline observation, II) 12 weeks of transcutaneous electrical nerve stimulation (TENS) of the occipital nerves, III) implantation of a full ONS system followed by 2 week grace period, IV) 12 weeks of blinded trial with 1:1 randomization to either placebo (deactivated ONS system) or burst (paresthesia-free) stimulation, and V) 12 weeks of tonic stimulation.The primary outcomes are the reduction in headache attack frequency with TENS and ONS and treatment safety. Secondary outcomes are treatment efficacy of burst versus tonic ONS, the feasibility of TENS as a predictor for ONS outcome, reduction in headache pain intensity (numeric rating scale), reduction in background headache, the patient’s impression of change (PGIC), health-related quality of life (EuroQoL-5D), self-reported sleep quality, and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS).Data on headache attack characteristics are registered weekly. Data on patient-reported outcomes are assessed after each trial phase.DiscussionThe study design allows a comparison between burst ONS and placebo in refractory CCH and enables a comparison of the efficacy of burst and tonic ONS. It will provide information about the effect of burst ONS and explore whether the addition of this stimulation paradigm may improve stimulation protocols.TENS is evaluated as a feasible preoperative screening tool for ONS outcomes by comparing the effect of attack prevention of TENS and tonic ONS.Trial registrationThe study is registered at Clinicaltrials.gov (trial registration number NCT05023460, registration date 07–27-2023).

Effects of Non-Invasive Neuromodulation of the Vagus Nerve for the Management of Cluster Headache: A Systematic Review.

Cluster headache (CH) is a type of headache that has a global prevalence of 0.5-3/1000 people, provokes severe, strictly unilateral pain through the first branch of the trigeminal nerve, and is associated with observable autonomous responses. CH provokes intense pain and decreases quality of life. In this study, we aimed to carry out a systematic review of the effectiveness of non-invasive neuromodulation of the vagus nerve in patients with cluster headaches, which was registered on PROSPERO No. CRD42021265126. Six databases were used from their date of inception to February 2023 to obtain studies with the group intervention of non-invasive neuromodulation of the vagus nerve for cluster headache, with outcomes based on pain attacks, duration, and disabilities. Data on the subjects, group intervention, main outcomes, and results were collected by two authors. The search provided 1003 articles, with three clinical trials being eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 points (mean: 7.3, SD: 0.8) out of a maximum of 10 points. The post-treatment results showed some positive effects using n-VNS as a treatment for cluster headache, more specifically regarding cervical neuromodulation of the vagus nerve. The systematic review found moderate-to-high-quality evidence supporting that n-VNS and cervical n-VNS may have some positive effects at the end of the treatment being effective to relieve the frequency and intensity of cluster headaches. The poor quantity of studies available and the lack of homogeneity in the study protocols did not allow the pooling of data for a meta-analysis.

Clinical characteristics and treatment patterns of patients with episodic cluster headache: results from the United States, United Kingdom and Germany

Objective To describe clinical characteristics and regional treatment patterns of episodic cluster headache (CH). Methods A point-in-time survey of physicians and their patients with CH was conducted in the United States, United Kingdom and Germany in 2017. Results Overall, 1012 patients with episodic CH were analyzed. Demographic and clinical findings were generally consistent across regions. Most patients were men (66.6%) and the mean age was 40.9 years. The greatest proportion of patients (38.3%) had ≤1 attack per day. The mean number of attacks per day (APD) was 2.4 and mean number of cluster periods per year was 2.6; the mean cluster period duration was 30.8 days. Most patients (69.3%) did not report a specific or predicable time when cluster periods occurred. Acute treatment was prescribed for 47.6% of patients, 10.3% of patients received preventive treatment, and 37.9% of patients received combined acute and preventive treatment; 4.2% of patients were not receiving treatment. Frequently prescribed acute treatments were sumatriptan, oxygen, and zolmitriptan; oxygen use varied considerably across countries and was prescribed least often in the United States. Frequently prescribed preventive treatments were verapamil, topiramate, and lithium. Lack of efficacy and tolerability were the most common reasons for discontinuing preventive treatment. Conclusions We observed high use of acute treatments, but only half of patients used preventive treatments despite experiencing several cluster periods per year with multiple cluster APD. Further studies about the need for and benefits of preventive treatment for episodic CH are warranted.

Treatment of chronic cluster headache with burst and tonic occipital nerve stimulation: A case series.

Chronic cluster headache (CCH) is a rare but severely debilitating primary headache condition. A growing amount of evidence suggests that occipital nerve stimulation (ONS) can offer effective treatment in patients with severe CCH for whom conventional medical therapy does not have a sufficient effect. The paresthesia evoked by conventional (tonic) stimulation can be bothersome and may thus limit therapy. Burst ONS produces paresthesia-free stimulation, but the amount of evidence on the efficacy of burst ONS as a treatment for intractable CCH is scarce. In this case series, we report 15 patients with CCH treated with ONS at Aarhus University Hospital, Denmark, from 2013 to 2020. Nine of these received burst stimulation either as primary treatment or as a supplement to tonic stimulation. The results were assessed in terms of the frequency of headache attacks per week and their intensity on the Numeric Rating Scale, as well as the Patient Global Impression of Change (PGIC) with ONS treatment. At a median (range) follow-up of 38 (16-96) months, 12 of the 15 patients (80%) reported a reduction in attack frequency of ≥50% (a reduction from a median of 35 to 1 attack/week, p < 0.001). Seven of these patients were treated with burst ONS. A significant reduction was also seen in maximum pain intensity. Overall, 10 patients stated a clinically important improvement in their headache condition following ONS treatment, rated on the PGIC scale. A total of 16 adverse events (nine of which were in the same patient) were registered. Occipital nerve stimulation significantly reduced the number of weekly headache attacks and their intensity. Burst ONS seems to function well alone or as a supplement to conventional tonic ONS as a preventive treatment for CCH; however, larger prospective studies are needed to determine whether the effect can be confirmed and whether the efficacy of the two stimulation paradigms is even.