Cluster Headache Research Articles

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

BackgroundDespite 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.MethodsWe 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.ResultsPatients 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.ConclusionsWe 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.

Comorbidity of migraine and fibromyalgia in patients with cluster headache: psychological burden and healthcare resource utilization. A cross-sectional study

The aim was to describe the comorbidity and impact of fibromyalgia and/or migraine on patients with cluster headache. Comorbid diseases can exacerbate the physical and psychological burden experienced by patients. The comorbidities of cluster headache have been scarcely investigated, with the exception of migraine, which is well-known to coexist with cluster headache. In contrast, the comorbidity of migraine and fibromyalgia has been well investigated and firmly established. An internet survey was uploaded to the webpage of a cluster headache patient association. The survey collected sociodemographic and clinical data, and patients completed questionnaires that assessed depression, sleep quality, health-related quality of life, and health care resource utilization (HCRU) over the preceding six months. Differences in total depression, sleep quality, and health-related quality of life scores among the groups were analyzed with the Kruskal-Wallis test, and differences in HCRU were analyzed with the chi-square test. Ninety-one patients with cluster headache participated in the survey; 39 (42.9%) experienced only cluster headache, 15 (16.5%) experienced cluster headache and migraine, 10 (11%) experienced cluster headache and fibromyalgia, and 27 (29.7%) experienced cluster headache with comorbid fibromyalgia and migraine. Moderate depression scores and positive suicidal ideation were found across all subgroups. Sleep quality and health-related quality of life were consistently poor across the different subgroups, with the cluster headache with comorbid fibromyalgia and migraine subgroup showing significantly lower scores. Heavy use of health care resources was observed across all subgroups, with no notable differences among them. The comorbidity of cluster headache with fibromyalgia and/or migraine does not seem to be infrequent. This comorbidity substantially increases the psychosocial burden experienced by patients and decreases their overall quality of life.

Prevalence, Risk Factors, and Management of Cluster headache; A systematic Review

Cluster headache (CH) is intricately linked to diverse risk factors, spanning hereditary, environmental, and lifestyle elements. This systematic study, guided by PRISMA guidelines, delves into the prevalence, risk factors, and management of CH. Examining English-language articles from 2010 to 2023 via PubMed/Medline, Scopus, and Embase, our findings reveal a significant association between cluster headaches and factors including family history, smoking, alcohol consumption, male predominance, and head trauma. Notably, a reevaluation of sex discrimination in familial cases is warranted, given the observed female predominance in familial history and CH association studies. Reviewing 739 studies, 7 met inclusion criteria, predominantly utilizing surveys and national database analyses (n=7). Improving our grasp of diagnosis and treatment holds promise for future evaluation and management. Our conclusion underscores global variability in CH prevalence, urging more rigorous population-based surveys. The substantial and persistent burdens associated with CH, from suicidality to economic stress, underscore the need for comprehensive research and intervention. CH transcends the label of a mere \"trigeminal autonomic headache,\" showcasing a diverse spectrum of attack and bout characteristics across countries and ethnicities. Despite the global efficacy of current diagnostic criteria, CH emerges as a dynamic illness, demonstrating progression or regression over time. This underscores the necessity for further research in comprehending its trajectory.

Calcitonin Gene-Related Peptide Monoclonal Antibodies for Cluster Headache

Cluster headache is a disabling neurologic disorder that is characterized by daily, attacks of very severe, strictly unilateral pain occurring over a period of weeks or months. Recently, calcitonin gene-related peptide and its receptor complex have garnered attention as promising targets for treating primary headache disorders: particularly migraine and cluster headache. Calcitonin gene-related peptide is found in the trigeminal sensory innervation of major cerebral vessels thought to carry nociceptive information during a headache. Increased levels of calcitonin gene-related peptide have been seen in the ipsilateral jugular venous outflow during an attack phase, and indeed, calcitonin gene-related peptide itself can trigger an attack if administered to a patient in bout, suggesting its distinct role in the generation of attacks. Various monoclonal antibodies targeting calcitonin gene-related peptide and its receptor are emerging as a new frontier in migraine with potential further therapeutic use in cluster headache. This review summarizes the current therapeutic approaches of cluster headache before sharing the potential future role of calcitonin gene-related peptide and its relevance in cluster headache pathology and as targets for future treatment.

Timing of cluster headache preventives in episodic cluster headache: Protocol for an observational prospective cohort pilot study

Purpose: In cluster headache, patients often describe a ramp up period with initially milder headache and then build up to a persistent and severe pattern. It is possible that within the early ramp up, patients may be more treatment responsive. We propose to study if response to therapy for prevention of cluster headache is dependent on timing from onset of cluster cycle. Methods: We will conduct a prospective observational cohort study, where we examine the relationship between timing of start of preventive medication and likelihood of response to treatment. We will look at individuals exposed within 10 days of onset of cluster cycle, versus those exposed after 10 days, to preventive medication. Results: We plan to enroll patients into the study and present data on completion. Conclusion: We aim to study the relationship between cluster headache onset and response to therapy. We propose that there is some data to suggest that earlier in cycle cluster headache may be more easily prevented, and we aim to study this relationship systematically. This is an important question that can influence treatment decisions in clinical practice, as well as clinical trial design.

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.

An Analysis of the Determinants of the Health-Related Quality of Life in Asian Patients With Cluster Headaches During Cluster Periods Using the Time Trade-Off Method.

Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

Cluster headache: understandings of current knowledge and directions for whole process management.

Cluster headache (CH) is a common primary headache that severely impacts patients' quality of life, characterized by recurrent, severe, unilateral headaches often centered around the eyes, temples, or forehead. Distinguishing CH from other headache disorders is challenging, and its pathogenesis remains unclear. Notably, patients with CH often experience high levels of depression and suicidal tendencies, necessitating increased clinical attention. This comprehensive assessment combines various reports and the latest scientific literature to evaluate the current state of CH research. It covers epidemiology, population characteristics, predisposing factors, and treatment strategies. Additionally, we provide strategic insights into the holistic management of CH, which involves continuous, individualized care throughout the prevention, treatment, and rehabilitation stages. Recent advances in the field have revealed new insights into the pathophysiology of CH. While these findings are still evolving, they offer a more detailed understanding of the neurobiological mechanisms underlying this disorder. This growing body of knowledge, alongside ongoing research efforts, promises to lead to the development of more targeted and effective treatments in the future.

Прекластерные симптомы и особенности патофизиологических механизмов пучковой (кластерной) головной боли

The prevalence of cluster headaches is about 0.4–1% in the general population and is more common than epilepsy and parkinsonism. This work examines several pathophysiologically significant ways for the disease development: the trigeminovascular pathway, the trigeminal-autonomic reflex with the release of several neuropeptides, and the involvement of the hypothalamus and its suprachiasmatic nucleus as the main circadian pacemaker in cluster headaches. The authors present data on the clinical manifestations of the attack and pre-cluster symptoms that occur in some patients several days before the onset of cluster headache. An average of 6 years may pass from the disease onset to the diagnosis and prescription of effective therapy. Awareness of pre-cluster symptoms allows for the preventive treatment of a cluster headache attack to reduce the duration and intensity of clinical manifestations and, as a result, reduce the negative impact of the disease on various aspects of the patient’s life. The heterogeneity of clinical manifestations of cluster headaches, and consequently, the difficulties in making a timely diagnosis, as well as the clinically significant role of concomitant diseases on the disease course and the treatment effectiveness, require further study of this problem and the application of the results obtained in clinical practice.

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.

Review of craniofacial pain syndromes involving the greater occipital nerve: relevant anatomy, clinical findings, and interventional management.

Craniofacial pain syndromes exhibit a high prevalence in the general population, with a subset of patients developing chronic pain that significantly impacts their quality of life and results in substantial disabilities. Anatomical and functional assessments of the greater occipital nerve (GON) have unveiled its implication in numerous craniofacial pain syndromes, notably through the trigeminal-cervical convergence complex. The pathophysiological involvement of the greater occipital nerve in craniofacial pain syndromes, coupled with its accessibility, designates it as the primary target for various interventional procedures in managing craniofacial pain syndromes. This educational review aims to describe multiple craniofacial pain syndromes, elucidate the role of GON in their pathophysiology, detail the relevant anatomy of the greater occipital nerve (including specific intervention sites), highlight the role of imaging in diagnosing craniofacial pain syndromes, and discuss various interventional procedures such as nerve infiltration, ablation, neuromodulation techniques, and surgeries. Imaging is essential in managing these patients, whether for diagnostic or therapeutic purposes. The utilization of image guidance has demonstrated an enhancement in reproducibility, as well as technical and clinical outcomes of interventional procedures. Studies have shown that interventional management of craniofacial pain is effective in treating occipital neuralgia, cervicogenic headaches, cluster headaches, trigeminal neuralgia, and chronic migraines, with a reported efficacy of 60-90% over a duration of 1-9months. Repeated infiltrations, neuromodulation, or ablation may prove effective in selected cases. Therefore, reassessment of treatment response and efficacy during follow-up is imperative to guide further management and explore alternative treatment options. Optimal utilization of imaging, interventional techniques, and a multidisciplinary team, including radiologists, will ensure maximum benefit for these patients.

Analysis of Pharmaceutical Therapies for Primary Headache

Primary headaches, secondary headaches, neuropathies and facial pains, and other headaches are the four types of headache disorders, in which primary headache disorder includes migraine, cluster headache, tension-type headache, and new daily persistent headache. Pathologies of migraine and cluster headaches are still unclear but possible explanations are proved to be related to trigeminal neurons, calcitonin gene-related peptide (CGRP) release, and neuroinflammation. This research listed these possible explanations and summarized the basic factors of migraine and cluster headache attacks. Based on the pathologies, various choices of therapies were introduced. This research mentioned typical pharmaceutical therapies for headaches, including nonsteroidal anti-inflammatory drugs, paracetamol, 5-HT1 receptor agonists involving triptan and dihydroergotamine mesylate, opioids, caffeine, and botulinum toxin. Furthermore, new medications in recent studies, including CGRP antagonists and caffeine were noticed as well. Related reliable mechanisms and side effects of all these drugs were highlighted in this review. Realizing the pros and cons of current treating medications is significant for better understanding on mechanism of headaches and designing more effective drugs in order to offer better promise on treating therapies.

Pediatric Cluster Headache Case Series: Symptomatic Cases and the Migraine Relationship.

Current criteria help differentiate cluster headache from migraine. However, children may have overlapping features making it difficult to distinguish the 2 conditions, which may delay diagnosis. Differentiating cluster headache from migraine is important regarding treatment as well as diagnostic workup of secondary headache etiologies. Cases at a single pediatric children's hospital from 2015 to 2023 diagnosed with cluster headache before the age of 18 years were reviewed. Twenty-five cases were identified of which 22 cases met criteria for either chronic, episodic, or probable cluster headache. Three cases were diagnosed with cluster headache by their provider, but documentation was insufficient to meet criteria for cluster headache. There were 16 females and 9 males between ages 6 and 17 years. Five cases were identified as symptomatic, 2 cases as chronic, 7 cases as episodic, and 13 cases as probable cluster headache. Symptomatic etiologies include Graves disease, optic neuritis, prolactinoma, hypothalamic pilocytic astrocytoma with carotid stenosis, and congenital right eye blindness. Migrainous features were common, including 76% with nausea, 36% with vomiting, 68% with photophobia, and 56% with phonophobia. Patients with cluster headache also had an independent diagnosis of migraine in 64%. Children with cluster headache have a high frequency of migrainous symptoms and co-occurrent diagnosis of migraine. A careful history may differentiate cluster headache from migraine and treated accordingly. Children with cluster headache features should undergo screening for secondary causes with appropriate imaging and other studies. Except for prolactinoma, the symptomatic associations noted in this case series have not been reported before.

Baseline demographics and disease characteristics of patients with episodic or chronic cluster headache: data from two phase 3 randomized clinical trials in Europe and North America.

Two phase 3 galcanezumab trials were conducted in Europe and North America to analyze the reduction of weekly cluster headache (CH) attack frequency in populations with episodic and chronic CH. The current study aims to illustrate prospectively recorded baseline clinical data from these trials and to identify possible predictors of response. Patients (aged 18-65 years) met The International Classification of Headache Disorders 3rd edition-beta criteria for CH. Attacks were evaluated using an electronic headache diary for 7-day (episodic) or 14-day (chronic) eligibility assessments before patients were randomized 1:1 to monthly subcutaneous galcanezumab 300 mg or placebo. Data were collected from 106 patients with episodic and 237 with chronic CH. Overall, the mean age [standard deviation] was 45.4 [11.0] years; patients were predominantly White (84.5%), male (75.8%), and European (77.6%). Patients with episodic CH reported 17.5 [10.0] attacks/week; patients with chronic CH reported 18.8 [10.2] attacks/week. The average pain severity score (range 0-4) was 2.5 [0.7] for episodic CH and 2.7 [0.7] for chronic CH. Higher attack frequency was a possible predictor of response to galcanezumab; potential negative predictors of response were greater attack severity and duration. This large dataset of patients with CH provides reliable systematically and prospectively collected information on disease characteristics. The analysis in episodic CH underscores potential predictors of response worth considering for future CH trial design. ClinicalTrials.gov, identifiers: NCT02397473 and NCT02438826.

Ominous Causes of Headache.

While primary headaches like migraines or cluster headaches are prevalent and often debilitating, it's the secondary headaches-those resulting from underlying pathologies-that can be particularly ominous. This article delves into the sinister causes of headaches, underscoring the importance of a meticulous clinical approach, especially when presented with red flags. Headaches, one of the most common complaints in clinical practice, span a spectrum from benign tension-type episodes to harbingers of life-threatening conditions. For the seasoned physician, differentiating between these extremes is paramount. Headache etiologies covered in this article will include subarachnoid hemorrhage (SAH), cervical artery dissection, cerebral venous thrombosis, meningitis, obstructive hydrocephalus, and brain tumor.

Examining the Impact of Puberty on Primary Headache Disorders in Female Schoolchildren: A Cross-Sectional Study.

Introduction and aim Headaches are one of the most prevalent childhood disorders. Primary and secondary headaches are the two types of headaches affecting kids and teenagers. The three most typical primary headache forms are tension-type headaches (TTH), migraine, and cluster headaches. This study sought to determine the relationship between puberty and types of headaches. Methods This cross-sectional study was conducted from May 18 to July 31, among female schoolchildren aged between eight and 15 years in the Eastern Province of Saudi Arabia. Respondents were recruited through face-to-face interviews. A self-administered questionnaire was utilized, mainly consisting of demographic data and questions related to diagnosing and managing the impact of puberty in girls on the prevalence of primary headache disorder. Results In total, 481 female schoolchildren were interviewed, mostly between 13 and 15 years old (65.9%). Last year prevalence of headaches was 65.5%, with a significant difference among those who lived in Dhahran (p=0.001) and those with a family history of headaches (p<0.001). The most common type of headache was frequent TTH (16.4%) and chronic TTH (16%). Chronic TTH (p<0.001), frequent TTH (p<0.001), and migraine without aura (p=0.005) were significantly more common among the older age groups. Conclusion There was a high prevalence of headaches among female schoolchildren, with frequent TTH and chronicTTH being the most common. Furthermore, increasing age was associated with an increasing risk for chronic TTH, frequent TTH, and migraine headaches without aura. More epidemiological studies are necessary to determine the underlying causes of headaches among schoolchildren.

Gender differences of BDNF during the clinical course of cluster headache

Gender differences of BDNF during the clinical course of cluster headache

Self-medication with Novel Psychoactive Substances (NPS): a Systematic Review

AbstractCurrently, novel psychoactive substance (NPS) use presents a challenging issue for authorities. To effectively tackle the use of NPS, a deeper understanding of the motivations of those who use NPS is required. Evidence suggests that a subset of NPS users declare their use as ‘self-medicating’; however, there is a paucity of research in this area. The aim of this review is to provide an overview and synthesis of the research concerning self-medication with novel psychoactive substances (NPS). Seven databases (EMBASE, MEDLINE, APA PsychInfo, Global Health, PubMed, Scopus, and Google Scholar) were searched using a search strategy compromising 600 + NPS terms, yielding 3563 articles, 24 of which met the search criteria. Two independent reviewers screened the articles and appraised the quality of the included studies. The results were synthesised using a narrative synthesis approach. We identified 22 NPS being used for self-medication. We found that (1) self-medication with NPS occurs mainly for anxiety, depression, and ADHD; (2) links between cluster headaches, the use of psychedelic NPS, and anxiety and novel benzodiazepines were evident; (3) novel benzodiazepine use by young individuals represents particular concern. There is a need for greater knowledge within healthcare professions concerning self-medication practices with NPS. Primary qualitative research is needed to address the underlying motivations behind this phenomenon.

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

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. 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. 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. ONS is a safe, well-tolerated and long-term effective treatment for MICCH. The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

The objective assessment of sleep in cluster headache: State of the art and future directions.

Several lines of evidence suggest that cluster headache is related to chronobiology and sleep. Nevertheless, the nature of such a relationship is unclear. In this view, the objective evaluation of sleep in cluster headache has strong theoretical and clinical relevance. Here, we provide an in-depth narrative review of the literature on objective sleep assessment in cluster headache. We found that only a small number of studies (N = 12) focused on this topic. The key research aims were directed to assess: (a) the relationship between cluster headache and sleep breathing disorders; (b) the temporal relationship between sleep stages/events and cluster headache attacks; (c) sleep macrostructure in patients with cluster headache. No studies considered sleep microstructure. The reviewed studies are heterogeneous, conducted by a few research groups, and often characterised by relevant methodological flaws. Results are substantially inconclusive considering the main hypothesis. We outline several methodological points that should be considered for future research, and suggest that evaluating sleep microstructure, local sleep electrophysiology and actigraphic measures may strongly increase knowledge on the relationship between sleep and cluster headache.