Cluster Headache, SUNCT, and SUNA.

OBJECTIVE: This article reviews the epidemiology, clinical features, differential diagnosis, pathophysiology, and management of three types of trigeminal autonomic cephalalgias: cluster headache (the most common), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). LATEST DEVELOPMENTS: The first-line treatments for trigeminal autonomic cephalalgias have not changed in recent years: cluster headache is managed with oxygen, triptans, and verapamil, and SUNCT and SUNA are managed with lamotrigine. However, new successful clinical trials of high-dose prednisone, high-dose galcanezumab, and occipital nerve stimulation provide additional options for patients with cluster headache. Furthermore, new genetic and imaging tests in patients with cluster headache hold promise for a better understanding of its pathophysiology. ESSENTIAL POINTS: The trigeminal autonomic cephalalgias are a group of diseases that appear similar to each other and other headache disorders but have important differences. Proper diagnosis is crucial for proper treatment.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Patients with chronic cluster headache may show reduced activity energy expenditure on ambulatory wrist actigraphy recordings during daytime attacks.

OBJECTIVE: To investigate the changes in activity energy expenditure (AEE) throughout daytime cluster headache (CH) attacks in patients with chronic CH and to evaluate the usefulness of actigraphy as a digital biomarker of CH attacks. BACKGROUND: CH is a primary headache disorder characterized by attacks of severe to very severe unilateral pain (orbital, supraorbital, temporal, or in any combination of these sites), with ipsilateral cranial autonomic symptoms and/or a sense of restlessness or agitation. We hypothesized increased AEE from hyperactivity during attacks measured by actigraphy. METHODS: An observational study including patients with chronic CH was conducted. During 21 days, patients wore an actigraphy device on the nondominant wrist and recorded CH attack-related data in a dedicated smartphone application. Accelerometer data were used for the calculation of AEE before and during daytime CH attacks that occurred in ambulatory settings, and without restrictions on acute and preventive headache treatment. We compared the activity and movements during the pre-ictal, ictal, and postictal phases with data from wrist-worn actigraphy with time-concordant intervals during non-headache periods. RESULTS: Four patients provided 34 attacks, of which 15 attacks met the eligibility criteria for further analysis. In contrast with the initial hypothesis of increased energy expenditure during CH attacks, a decrease in movement was observed during the pre-ictal phase (30 min before onset to onset) and during the headache phase. A significant decrease (p < .01) in the proportion of high-intensity movement during headache attacks, of which the majority were oxygen-treated, was observed. This trend was less present for low-intensity movements. CONCLUSION: The unexpected decrease in AEE during the pre-ictal and headache phase of daytime CH attacks in patients with chronic CH under acute and preventive treatment in ambulatory settings has important implications for future research on wrist actigraphy in CH.

Involvement of the ipsilateral-to-the-pain anterior-superior hypothalamic subunit in chronic cluster headache.

BACKGROUND: Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. METHODS: We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. RESULTS: Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. CONCLUSIONS: We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

Refractory primary and secondary headache disorders that dramatically responded to combined treatment of ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks and non-invasive vagus nerve stimulation: a case series.

In 1981, Devoghel achieved an 85.6% success rate in treating patients with treatment-refractory cluster headaches with alcoholization of the pterygopalatine ganglion (PPG) via the percutaneous suprazygomatic approach. Devoghel's study led to the theory that interrupting the parasympathetic pathway by blocking its transduction at the PPG could prevent or treat symptoms related to primary headache disorders (PHDs). Furthermore, non-invasive vagus nerve stimulation (nVNS) has proven to treat PHDs and has been approved by national regulatory bodies to treat, among others, cluster headaches and migraines.In this case series, nine desperate patients who presented with 11 longstanding treatment-refractory primary headache disorders and epidural blood patch-resistant postdural puncture headache (PDPH) received ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks (PPGB), and seven also received nVNS. The patients were randomly selected and were not part of a research study. They experienced dramatic, immediate, satisfactory, and apparently lasting symptom resolution (at the time of the writing of this report). The report provides the case descriptions, briefly reviews the trigeminovascular and neurogenic inflammatory theories of the pathophysiology, outlines aspects of these PPGB and nVNS interventions, and argues for adopting this treatment regime as a first-line or second-line treatment rather than desperate last-line treatment of PDPH and PHDs.

The Untold Story of Occipital Nerve Stimulation in Patients With Cluster Headache: Surgical Technique in Relation to Clinical Efficacy.

OBJECTIVES: Approximately one in every 1000 adults experiences cluster headache (CH). Although occipital nerve stimulation (ONS) appears encouraging in treatment for most patients with refractory CH, some patients do not reach adequate pain relief with ONS. A reason for failure of ONS might be anatomical variations and different surgical approaches. Therefore, an extensive literature analysis was performed, and cadaveric experimentation was combined with our clinical experience to provide a standardized proposal for ONS and obtain optimal management of patients with refractory CH. MATERIALS AND METHODS: Data from 36 articles published between 1998 and 2023 were analyzed to retrieve information on the anatomical landmarks and surgical technique of ONS. For the cadaveric experimentation (N = 1), two electrodes were inserted from the region over the foramen magnum and projected toward the lower third of the mastoid process. RESULTS: The existence of multiple approaches of ONS has been confirmed by the present analysis. Discrepancies have been found in the anatomical locations and corresponding landmarks of the greater and lesser occipital nerve. The surgical approaches differed in patient positioning, electrode placement, and imaging techniques, with an overall efficacy range of 35.7% to 90%. CONCLUSIONS: Reports on the surgical approach of ONS remain contradictory, hence emphasizing the need for standardization. Only if all implanting physicians perform the ONS surgery using a standardized protocol, can future data be combined and outcomes compared and analyzed.

A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache.

BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. 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. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). 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). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

Association of Clinical and Neuroanatomic Factors With Response to Ventral Tegmental Area DBS in Chronic Cluster Headache.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) of the ventral tegmental area (VTA) is a surgical treatment option for selected patients with refractory chronic cluster headache (CCH). We aimed to identify clinical and structural neuroimaging factors associated with response to VTA DBS in CCH. METHODS: This prospective observational cohort study examines consecutive patients with refractory CCH treated with VTA DBS by a multidisciplinary team in a single tertiary neuroscience center as part of usual care. Headache diaries and validated questionnaires were completed at baseline and regular follow-up intervals. All patients underwent T1-weighted structural MRI before surgery. We compared clinical features using multivariable logistic regression and neuroanatomic differences using voxel-based morphometry (VBM) between responders and nonresponders. RESULTS: Over a 10-year period, 43 patients (mean age 53 years, SD 11.9), including 29 male patients, with a mean duration of CCH 12 years (SD 7.4), were treated and followed up for at least 1 year (mean follow-up duration 5.6 years). Overall, there was a statistically significant improvement in median attack frequency from 140 to 56 per month (Z = -4.95, p < 0.001), attack severity from 10/10 to 8/10 (Z = -4.83, p < 0.001), and duration from 110 to 60 minutes (Z = -3.48, p < 0.001). Twenty-nine (67.4%) patients experienced ≥50% improvement in attack frequency and were therefore classed as responders. There were no serious adverse events. The most common side effects were discomfort or pain around the battery site (7 patients) and transient diplopia and/or oscillopsia (6 patients). There were no differences in demographics, headache characteristics, or comorbidities between responders and nonresponders. VBM identified increased neural density in nonresponders in several brain regions, including the orbitofrontal cortex, anterior cingulate cortex, anterior insula, and amygdala, which were statistically significant (p < 0.001). DISCUSSION: VTA DBS showed no serious adverse events, and, although there was no placebo control, was effective in approximately two-thirds of patients at long-term follow-up. This study did not reveal any reliable clinical predictors of response. However, nonresponders had increased neural density in brain regions linked to processing of pain and autonomic function, both of which are prominent in the pathophysiology of CCH.

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.

BACKGROUND: Chronic 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. METHODS: An 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. DISCUSSION: The 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 REGISTRATION: The study is registered at Clinicaltrials.gov (trial registration number NCT05023460, registration date 07-27-2023).

Use of spinal cord stimulation in treatment of intractable headache diseases.

Headache diseases remain one of the leading causes of disability in the world. With the development of neuromodulation strategies, high cervical spinal cord stimulation (hcSCS) targeting the trigeminocervical complex has been deployed to treat refractory headache diseases. In this article, we review the proposed mechanism behind hcSCS stimulation, and the various studies that have been described for the successful use of this treatment strategy in patients with chronic migraine, cluster headache, and other trigeminal autonomic cephalalgias.

Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments-a consensus article.

AIM: Treatment for cluster headache is currently based on a trial-and-error approach. The available preventive treatment is unspecific and based on few and small studies not adhering to modern standards. Therefore, the authors collaborated to discuss acute and preventive treatment in cluster headache, addressing the unmet need of safe and tolerable preventive medication from the perspectives of people with cluster headache and society, headache specialist and cardiologist. FINDINGS: The impact of cluster headache on personal life is substantial. Mean annual direct and indirect costs of cluster headache are more than 11,000 Euros per patient. For acute treatment, the main problems are treatment response, availability, costs and, for triptans, contraindications and the maximum use allowed. Intermediate treatment with steroids and greater occipital nerve blocks are effective but cannot be used continuously. Preventive treatment is sparsely studied and overall limited by relatively low efficacy and side effects. Neurostimulation is a relevant option for treatment-refractory chronic patients. From a cardiologist's perspective use of verapamil and triptans may be worrisome and regular follow-up is essential when using verapamil and lithium. CONCLUSION: We find that there is a great and unmet need to pursue novel and targeted preventive modalities to suppress the horrific pain attacks for people with cluster headache.

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

OBJECTIVES AND BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Management of cluster headache: Treatments and their mechanisms.

BACKGROUND: The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms. METHODS: Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies. RESULTS: Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus. CONCLUSIONS: The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.

Neuromodulation for the Sphenopalatine Ganglion-a Narrative Review.

PURPOSE OF REVIEW: To provide an integrated overview of the current state of knowledge of neuromodulation for the sphenopalatine ganglion (SPG) by reviewing relevant and significant literature. RECENT FINDINGS: There are several case reports and clinical trials evaluating neuromodulation for the SPG. We identified two blinded, randomized clinical trials for patients with chronic cluster headache. The randomized trials and additional studies demonstrated the long-term safety, efficacy, and cost-effectiveness of neuromodulation for the SPG. Recent studies in Europe and the USA suggest that SPG neuromodulation is a novel modality with clinical importance for treating acute cluster headaches and reducing the frequency of attacks.

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.

People with cluster headache (CH) experience headache attacks of excruciating stabbing pain, usually on one side of the head around the eye. These headache attacks typically last between 15 min and 3 h, and come in clusters (or bouts) occurring up to several times a day for a few weeks or months at a time. This greatly impacts a patient's quality of life.We surveyed doctors and their patients across the United States, the United Kingdom and Germany, looking at symptoms that occurred during CH attacks, how long the headache attacks lasted, how often the patient had them, and what medicines were being given.Our results showed that patients with CH suffered from clusters (bouts) of headache attacks several times a year. Nearly, a third of patients had a wrong diagnosis before being diagnosed with CH. Patients experienced stress, agitation, restlessness, difficulty relaxing and depression during a headache attack, especially those who had more CH attacks each day.Although many patients were taking medication, only half of patients were prescribed medicines to prevent their headache attack from starting. Side effects and the medicines not working were the most common reasons patients stopped taking medicine to prevent their headache attacks. The differences seen in medicines prescribed between countries suggest differences in guidance, or in doctors' awareness of current medication guidelines. Further studies about the need for and benefits of medicines to prevent CH attacks are needed.

European Academy of Neurology guidelines on the treatment of cluster headache.

BACKGROUND AND PURPOSE: Cluster headache is a relatively rare, disabling primary headache disorder with a major impact on patients' quality of life. This work presents evidence-based recommendations for the treatment of cluster headache derived from a systematic review of the literature and consensus among a panel of experts. METHODS: The databases PubMed (Medline), Science Citation Index, and Cochrane Library were screened for studies on the efficacy of interventions (last access July 2022). The findings in these studies were evaluated according to the recommendations of the European Academy of Neurology, and the level of evidence was established using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RECOMMENDATIONS: For the acute treatment of cluster headache attacks, there is a strong recommendation for oxygen (100%) with a flow of at least 12 L/min over 15 min and 6 mg subcutaneous sumatriptan. Prophylaxis of cluster headache attacks with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy and tolerability) is recommended. Corticosteroids are efficacious in cluster headache. To reach an effect, the use of at least 100 mg prednisone (or equivalent corticosteroid) given orally or at up to 500 mg iv per day over 5 days is recommended. Lithium, topiramate, and galcanezumab (only for episodic cluster headache) are recommended as alternative treatments. Noninvasive vagus nerve stimulation is efficacious in episodic but not chronic cluster headache. Greater occipital nerve block is recommended, but electrical stimulation of the greater occipital nerve is not recommended due to the side effect profile.

Deep Brain Stimulation for Chronic Cluster Headaches: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic cluster headache (CCH) is a severe and debilitating sub-type of trigeminal autonomic cephalalgia that can be resistant to medical management and associated with significant impairment in quality of life. Studies of deep brain stimulation (DBS) for CCH have provided promising results but have not been assessed in a comprehensive systematic review/meta-analysis. OBJECTIVE: The objective was to perform a systematic literature review and meta-analysis of patients with CCH treated with DBS to provide insight on safety and efficacy. METHODS: A systematic review and meta-analysis were performed according to PRISMA 2020 guidelines. 16 studies were included in final analysis. A random-effects model was used to meta-analyze data. RESULTS: Sixteen studies reported 108 cases for data extraction and analysis. DBS was feasible in >99% of cases and was performed either awake or asleep. Meta-analysis revealed that the mean difference in headache attack frequency and headache intensity after DBS were statistically significant (p < 0.0001). Utilization of microelectrode recording was associated with statistically significant improvement in headache intensity postoperatively (p = 0.006). The average overall follow-up period was 45.4 months and ranged from 1 to 144 months. Death occurred in <1%. The rate of major complications was 16.67%. CONCLUSIONS: DBS for CCHs is a feasible surgical technique with a reasonable safety profile that can be successfully performed either awake or asleep. In carefully selected patients, approximately 70% of patients achieve excellent control of their headaches.

Clinical Profile of Chronic Cluster Headaches in a Regional Headache Center in Japan.

Objective Little is known about the prevalence and characteristics of chronic cluster headache (CCH) in Japan. We therefore characterized the clinical profile of CCH in Japan by surveying patients with CCH who were registered at a Japanese regional headache center. We also reviewed the existing literature for the prevalence and clinical characteristics of CCH reported in various populations. Methods In this single-center retrospective study, we assessed consecutive patients with cluster headache (CH) who visited a regional tertiary headache center between February 2011 and July 2020. They were treated following the Clinical Practice Guideline for Chronic Headache 2013. We compared their demographic characteristics and clinical features according to the CCH onset pattern (primary vs. secondary). Results Of 420 patients with CH, 19 (4.2%) had CCH (9 primary and 10 secondary). The incidence of CCH in Japan is relatively low compared to that in Western countries but is comparable to that in other Asian countries. CCH showed a higher predominance of men than women. Compared to primary CCH, secondary CCH included a higher proportion of current smokers and older patients during clinic visits. Subcutaneous sumatriptan and oxygen inhalation were the most common abortive treatments, and oral prednisolone and verapamil were the most common preventive treatments. Home oxygen therapy was effective in six of seven patients. Only two patients with coexisting migraine received calcitonin gene-related peptide (CGRP)-targeted therapies. Conclusions CCH remains refractory to treatment. Improving treatment outcomes will require maximizing the use of currently available drugs and expanding the use of neuromodulation, nerve block, and CGRP-targeted therapies.