Cluster Headache Research Articles

Results of sphenopalatine ganglion pulsed radio- frequency treatment in patients suffering from episodic cluster headache

Background & Objective: The aim of this study was to investigate the short- to medium-term effects of pulsed radiofrequency (PRF) of the sphenopalatine ganglion on episodic cluster headache. Methods: This is a retrospective observational study, 26 patients who underwent PRF of the sphenopalatine ganglion were retrospectively evaluated. The Visual Analogue Scale (VAS) score, number of headache attacks per week, autonomic symptoms and medication use were recorded at 1, 3 and 6 months after the procedure. Results: The mean VAS scores were significantly lower at the 1-, 3-, and 6-month evaluations compared with pre-procedure values (P < 0.001). At the 6th month after the procedure, the proportion of subjects who completely stopped using medications was 26.9%, and the proportion with a decrease in autonomic symptoms was 61.5%. No complications were encountered as a result of the procedure. Conclusion: The application of PRF to the sphenopalatine ganglion is an effective and safe treatment option for episodic cluster headache in the short to medium term.

Testing the Decision Support Tool for Responsible Pain Management for Headache and Facial Pain Diagnosis with Opioid-Risk-Stratified Treatment

In primary and urgent care, headache and facial pain are common and challenging to diagnose and manage, especially with using opioids appropriately. We therefore developed the Decision Support Tool for Responsible Pain Management (DS-RPM) to assist healthcare providers in diagnosis (including multiple simultaneous diagnoses), workup (including triage), and opioid-risk-informed treatment. A primary goal was to supply sufficient explanations of DS-RPM’s functions allowing critique. We describe the process of iteratively designing DS-RPM adding clinical content and testing/defect discovery. We tested DS-RPM remotely with 21 clinician-participants using three vignettes—cluster headache, migraine, and temporal arteritis—after first training to use DS-RPM with a trigeminal-neuralgia vignette. Their evaluation was both quantitative (usability/acceptability) and qualitative using semi-structured interviews. The quantitative evaluation used 12 Likert-type questions on a 1–5 scale, where 5 represented the highest rating. The mean ratings ranged from 4.48 to 4.95 (SDs ranging 0.22–1.03). Participants initially found structured data entry intimidating but adapted and appreciated its comprehensiveness and speed of data capture. They perceived DS-RPM as useful for teaching and clinical practice, making several enhancement suggestions. The DS-RPM was designed, created, and tested to facilitate best practice in management of patients with headaches and facial pain. Testing the DS-RPM with vignettes showed strong functionality and high usability/acceptability ratings from healthcare providers. Risk stratifying for opioid use disorder to develop a treatment plan for headache and facial pain is possible using vignettes. During testing, we considered the need to adapt usability/acceptability evaluation tools for clinical decision support, and future directions.

Clinical characteristics, medication use, and impact of primary headache on daily activities: an observational study using linked online survey and medical claims data in Japan

BackgroundLimited epidemiological data are available for headache disorders in Japan, and no recent studies have reported the impact of several primary headache disorders in Japan. This study aimed to report the up-to-date epidemiological data and impact of primary headaches on daily activities as well as the use of medical care, clinical features, and pain severity/activity impairment using nationwide data in Japan.MethodsWe used anonymized online survey data coupled with medical claims data, from individuals aged 19–74 years old, that were provided by DeSC Healthcare Inc. The outcomes included the prevalence of migraine, tension-type headache, cluster headache, and other headache types stratified by age and sex, use of medical care, clinical features, medication use, and severity of pain/activity impairment. All outcomes were examined separately for each headache type. This is the second paper reported concurrently with this research.ResultsThe study population comprised 691/1,441/21/5,208 individuals with migraine/tension-type headache/cluster headache/other headache types, respectively. The prevalence of migraine and tension-type headache was higher in women than in men but was similar for cluster headache (male vs. female, 1.7% vs. 7.4%, 5.3% vs. 10.8%, and 0.1% vs. 0.1%, respectively). The percentage of individuals with migraine, tension-type headache, cluster headache who had not seen a doctor was 81.0%, 92.0%, 57.1%, respectively. The common headache triggers were fatigue in migraine and tension-type headache, and weather-related phenomena and turning of the seasons in migraine. Common activities refrained from or reduced by headaches were “operating a computer or smartphone”, “drinking alcohol”, and “going to crowded places” in all three headache types and housework-related activities in women. Among individuals taking medicines, 16.8%, 15.8%, 47.6% with migraine, tension-type headache, and cluster headache reported moderate to severe pain, respectively, and 12.6%, 7.7%, 19.0% reported moderate to severe disability, respectively.ConclusionsThis study found various triggers of headache attacks, and daily activities refrained from or reduced by headaches. Additionally, this study suggested that the disease burden in people possibly experiencing tension-type headaches, many of whom had not seen a doctor. The study findings are of clinical value for the diagnosis and treatment of primary headaches.

Cluster Headache: Literature Review with Reference to Sex Differences

Cluster headache is a pain syndrome characterised by severe, unilateral and predominantly orbital pain which lasts 15 - 180 minutes. It is accompanied by a range of ipsilateral autonomic symptoms, such as lacrimation, rhinorrhoea and myosis. Cluster headaches can be episodic with periods of remission or chronic. Even though it is a relatively rare condition, the excruciating pain causes significant disruption of patients’ daily life. The pathophysiology behind cluster headaches is complex and despite making significant progress, the pathogenetic cascade of events hasn’t been entirely elucidated yet. However, research into this subject has discovered brain structures, peripheral pathways and neuropeptides which have key roles in pathogenesis. The basis of diagnosing cluster headaches is a detailed patient history and the exclusion of other primary headaches and potential secondary causes. Sex differences in clinical presentation need to be taken into consideration in order to avoid misdiagnosis. Treatment options are divided into three categories: acute, transitional and prophylactic treatment. Although there are a lot of treatment modalities available, further research is necessary in order to find new therapeutic targets and more effective prophylaxis, especially for chronic cluster headache.

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.

Hypnic Headache - What do we know in 2022?

Hypnic Headache, also known as "alarm clock headache", is a rare primary headache disorder. It is characterized by frequently recurring headache attacks, which only develop during sleep, especially nighttime sleep. This article gives a narrative review on the current knowledge about Hypnic Headache with a focus on secondary Hypnic Headache. Based on literature research, using Pubmed and Google Scholar, latest case reports, studies, and systematic reviews about Hypnic Headache were analyzed and summarized focusing on therapeutic options and causes of secondary Hypnic Headache. Hypnic Headache mainly occurs in elderly patients. However, younger patients and children may also suffer from Hypnic Headache. Many different causes of secondary Hypnic Headache are described in the literature and ought to be ruled out before diagnosing primary Hypnic Headache. The pathophysiology of primary Hypnic Headache remains unclear, but a dysfunction of the hypothalamus seems to play a key role.

Cranial Autonomic Symptoms and Neck Pain in Differential Diagnosis of Migraine

Cranial autonomic symptoms and neck pain have been reported to be highly prevalent in migraine, although they are rarely considered in clinical evaluation. The aim of this review is to focus on the prevalence, pathophysiology, and clinical characteristics of these two symptoms, and their importance in the differential diagnosis between migraines and other headaches. The most common cranial autonomic symptoms are aural fullness, lacrimation, facial/forehead sweating, and conjunctival injection. Migraineurs experiencing cranial autonomic symptoms are more likely to have more severe, frequent, and longer attacks, as well as higher rates of photophobia, phonophobia, osmophobia, and allodynia. Cranial autonomic symptoms occur due to the activation of the trigeminal autonomic reflex, and the differential diagnosis with cluster headaches can be challenging. Neck pain can be part of the migraine prodromal symptoms or act as a trigger for a migraine attack. The prevalence of neck pain correlates with headache frequency and is associated with treatment resistance and greater disability. The convergence between upper cervical and trigeminal nociception via the trigeminal nucleus caudalis is the likely mechanism for neck pain in migraine. The recognition of cranial autonomic symptoms and neck pain as potential migraine features is important because they often contribute to the misdiagnosis of cervicogenic problems, tension-type headache, cluster headache, and rhinosinusitis in migraine patients, delaying appropriate attack and disease management.

Intra- and interindividual attack frequency variability of chronic cluster headache

The lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration. We analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency. Weekly median (14.4 [8.2-24.0]) and instantaneous (14.2 [8.0-24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2-140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period. Weekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those with <3 daily attacks. An optimal balance between 90% accuracy and feasibility is achieved at a baseline period of seven weeks.The ICON trial is registered in ClinicalTrials.gov under number NCT01151631.

The Perplexing Mental Health Comorbidity of Alice in Wonderland Syndrome (AIWS): A Case Study

The Alice in Wonderland Syndrome (AIWS) is an unusual and uncommon condition that falls under the umbrella of neurology and psychiatry. It is characterized by the presence of complex perceptual and visual discord. Additionally, there are visual hallucinations that are multi-dimensional. This syndrome was first described by John Todd in the 1950s, and it was loosely based on the book Alice in Wonderland. A man in his 30s arrived at his doctor’s appointment with a chief complaint of a pounding cluster headache that lasted over a full day. In addition, he mentioned that there was an aura preceding his headaches. The pain was so intense, it was debilitating him from routine activities. Before the headaches, he explained that he would sense bizarre physical and visual behaviors. During these episodes, he explained that things around him appeared distorted and of various sizes. Things in his room appeared to be more distant than they really were and larger in size (macropsia and micropsia). He described the fingers on his right hand to be much smaller compared to his left hand (micropsia). Objects around him were deformed and distorted (metamorphopsia). His symptoms lasted 45 minutes. He did not suffer from any previous headaches or hallucinations. He was a healthy man with a clean bill of health as per his medical records. Upon examination, the attending physician described the patient as alert, oriented to time and place, and under no obvious distress. All labs performed returned normal including a 10-panel drug test. These were tested to see if he was under the influence of any narcotic, stimulant, or other substances. The physician prescribed 500 mg of valproic acid to take daily. Three months later during his follow-up, he mentioned his symptoms had subsided but were still present. His dose was again increased to 1000 mg/day, eventually stopping all further symptoms from surfacing. He has not had another episode in three months. The Alice in Wonderland Syndrome is known to be associated with headaches with preceding auras. It is common in the pediatric and adult populations. In this paper, I introduce a case of a patient who displays migraines with preceding auras, indicative of AIWS.

Are psychedelics the answer to chronic pain: A review of current literature.

We aim to provide an evidence-based overview of the use of psychedelics in chronic pain, specifically LSD and psilocybin. Chronic pain is a common and complex problem, with an unknown etiology. Psychedelics like lysergic acid diethylamide (LSD) and psilocybin, may play a role in the management of chronic pain. Through activation of the serotonin-2A (5-HT2A) receptor, several neurophysiological responses result in the disruption of functional connections in brain regions associated with chronic pain. Healthy reconnections can be made through neuroplastic effects, resulting in sustained pain relief. However, this process is not fully understood, and evidence of efficacy is limited and of low quality. In cancer and palliative related pain, the analgesic potential of psychedelics was established decades ago, and the current literature shows promising results on efficacy and safety in patients with cancer-related psychological distress. In other areas, patients suffering from severe headache disorders like migraine and cluster headache who have self-medicated with psychedelics report both acute and prophylactic efficacy of LSD and psilocybin. Randomized control trials are now being conducted to study the effects in cluster headache Furthermore, psychedelics have a generally favorable safety profile especially when compared to other analgesics like opioids. In addition, psychedelics do not have the addictive potential of opioids. Given the current epidemic use of opioids, and that patients are in desperate need of an alternative treatment, it is important that further research is conducted on the efficacy of psychedelics in chronic pain conditions.

Parasympathetic control of gastrointestinal motility and cross-branch actions of parasympathetic neuromodulation.

Parasympathetic control of gastrointestinal motility and cross-branch actions of parasympathetic neuromodulation.

Biomarkers of Migraine and Cluster Headache: Differences and Similarities.

This study was undertaken to identify magnetic resonance imaging (MRI) biomarkers that differentiate migraine from cluster headache patients and imaging features that are shared. Clinical, functional, and structural MRI data were obtained from 20 migraineurs, 20 cluster headache patients, and 15 healthy controls. Support vector machine algorithms and a stepwise removal process were used to discriminate headache patients from controls, and subgroups of patients. Regional between-group differences and association between imaging features and patients' clinical characteristics were also investigated. The accuracy for classifying headache patients from controls was 80%. The classification accuracy for discrimination between migraine and controls was 89%, and for cluster headache and controls it was 98%. For distinguishing cluster headache from migraine patients, the MRI classifier yielded an accuracy of 78%, whereas MRI-clinical combined classification model achieved an accuracy of 99%. Bilateral hypothalamic and periaqueductal gray (PAG) functional networks were the most important MRI features in classifying migraine and cluster headache patients from controls. The left thalamic network was the most discriminative MRI feature in classifying migraine from cluster headache patients. Compared to migraine, cluster headache patients showed decreased functional interaction between the left thalamus and cortical areas mediating interoception and sensory integration. The presence of restlessness was the most important clinical feature in discriminating the two groups of patients. Functional biomarkers, including the hypothalamic and PAG networks, are shared by migraine and cluster headache patients. The thalamocortical pathway may be the neural substrate that differentiates migraine from cluster headache attacks with their distinct clinical features. ANN NEUROL 2023;93:729-742.

Sphenopalatine ganglion volumetry in episodic cluster headache: from symptom laterality to cranial autonomic symptoms

BackgroundSphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles.MethodsWe prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0–5) were recorded to analyze their association with SPG volume.ResultsThe inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84–0.90, p < 0.001). The mean [SD] SPG volume was larger in CH patients than in non-headache controls (35.89 [12.94] vs. 26.13 [8.62] μL, p < 0.001). In CH patients, the SPG volume was larger on the pain side than on the non-pain side (38.87 [14.71] vs. 32.91 [12.70] μL, p < 0.001). The number of CASs was positively moderately correlated with the pain-side SPG volume (Pearson r = 0.320, p = 0.004) but not the non-pain side SPG volume (Pearson r = 0.207, p = 0.066).ConclusionsThis proof-of-concept study successfully measured the SPG volume and demonstrated its associations with symptomatology in patients with episodic CH. The direct measurement of SPG provide insights into studies on peripheral mechanism of CH.

Infodemiology of cluster headache seasonality: A proof of concept by a Google Trends analysis.

Cluster headache is commonly reported to follow an annual pattern with a peak in the spring and a second peak in autumn. Patients with headache frequently use search engines, such as Google, to look for terms related to their disease, creating trend data that can be analyzed with Google Trends. Indeed, Google Trends has been used for surveillance studies and can provide indirect estimates of the burden of diseases and symptoms. The present cross-sectional study investigated the seasonality of searches for "cluster headache" in the northern and southern hemispheres using 10 years of Google Trends data. The term "cluster headache" or its translation in the 10 most spoken languages in the world was searched on Google Trends to obtain relative search volumes (from 0 to 100), in order to compare variations in searches across periods. Twenty-eight countries were selected according to the following criteria: (1) a relative search volume of >40 for the term for cluster headache; and (2) a population of at least 5 million inhabitants. For statistical purposes, countries were grouped in relation to hemisphere (northern or southern). Relative search volumes were extracted from January 2012 to January 2022 and analyzed according to two subgroups based on meteorological seasons (summer and winter vs. spring and autumn). A seasonal trend for in searches for cluster headache was found worldwide exhibiting higher relative search volumes in spring and autumn compared with summer and winter (17 [0, 39] vs. 13 [0, 37]; p= 0.016). Higher search volumes for the term during the meteorological seasons of spring and autumn clearly reflect a circannual pattern of cluster headache occurrence, representing new evidence for its seasonality.

Transition of cluster headache phenotype: An interview-based study

Background Cluster headache exists diagnostically in a chronic and episodic variant between which patients can convert. We aimed to describe how many patients change phenotype, elucidate possible factors associated with this transition and identify differences in clinical features between primary and secondary phenotypes.Methods 540 well-defined cluster headache patients according to current ICHD-criteria completed a cross-sectional semi-structured interview.Results Total transition-incidence for the cohort was 20.7%. Conversion from chronic to episodic was reported by 6.3% and transition from episodic to chronic by 14.4% with attack side shift as a possible predictor (p = 0.007). Compared to primary chronic patients, secondary chronic patients had more frequent (60 vs 34 per month, p = 0.0487), but shorter (60 vs 90 minutes, p = 0.041) attacks. Secondary episodic patients experienced shorter remission periods than primary episodic patients (6 vs 11 months, p = 0.010). Treatment response was poor in all groups and only one third had effective prevention.Conclusion Cluster headache is a fluctuating disorder with a fifth of our cohort having experienced at least one phenotype change during course of disease. Apart from attack side shifts, no predictors for transition were identified. Severity differed between primary and secondary subtypes. Overall, there is an urgent need for better understanding of cluster headache.

Wildfire smoke exposure and emergency department visits for headache: A case-crossover analysis in California, 2006-2020.

To evaluate the association of short-term exposure to overall fine particulate matter of <2.5 μm (PM2.5 ) and wildfire-specific PM2.5 with emergency department (ED) visits for headache. Studies have reported associations between PM2.5 exposure and headache risk. As climate change drives longer and more intense wildfire seasons, wildfire PM2.5 may contribute to more frequent headaches. Our study included adult Californian members (aged ≥18 years) of a large de-identified commercial and Medicare Advantage claims database from 2006 to 2020. We identified ED visits for primary headache disorders (subtypes: tension-type headache, migraine headache, cluster headache, and "other" primary headache). Claims included member age, sex, and residential zip code. We linked daily overall and wildfire-specific PM2.5 to residential zip code and conducted a time-stratified case-crossover analysis considering 7-day average PM2.5 concentrations, first for primary headache disorders combined, and then by headache subtype. Among 9898 unique individuals we identified 13,623 ED encounters for primary headache disorders. Migraine was the most frequently diagnosed headache (N=5534/13,623 [47.6%]) followed by "other" primary headache (N=6489/13,623 [40.6%]). For all primary headache ED diagnoses, we observed an association of 7-day average wildfire PM2.5 (odds ratio [OR] 1.17, 95% confidence interval [CI] 0.95-1.44 per 10 μg/m3 increase) and by subtype we observed increased odds of ED visits associated with 7-day average wildfire PM2.5 for tension-type headache (OR 1.42, 95% CI 0.91-2.22), "other" primary headache (OR 1.40, 95% CI 0.96-2.05), and cluster headache (OR 1.29, 95% CI 0.71-2.35), although these findings were not statistically significant under traditional null hypothesis testing. Overall PM2.5 was associated with tension-type headache (OR 1.29, 95% CI 1.03-1.62), but not migraine, cluster, or "other" primary headaches. Although imprecise, these results suggest short-term wildfire PM2.5 exposure may be associated with ED visits for headache. Patients, healthcare providers, and systems may need to respond to increased headache-related healthcare needs in the wake of wildfires and on poor air quality days.

Migraines, occipital neuralgia, and cluster headaches What are the treatments when nothing else works?

Migraines, occipital neuralgia, and cluster headaches What are the treatments when nothing else works?

Comorbidity or combination – more evidence for cluster-migraine?

While migraine and cluster headache share some clinical features and therapies, they differ considerably in the frequency and duration of the headache, as well as the inter-attack, or inter-bout, pathophysiology. Neither is fully understood, with their shared pathways being of interest. Five patients for whom it was difficult to distinguish migraine from cluster headache are presented. They had aspects of their phenotypes, which could be attributed to both disorders. Each patient was thoroughly examined, excluding secondary causes of headache, and had been treated with a number of medicines. A correct diagnosis is key to the appropriate treatment approach. Especially, if treatment is not successful for the suspected headache type, and enlargement of the diagnostic and therapeutic range, respectively, should be evaluated. Whether in such settings there is shared or different pathophysiology can only be speculated upon.

Efficacy of Leksell gamma knife radiosurgery of the sphenopalatine ganglion in cluster headache

Efficacy of Leksell gamma knife radiosurgery of the sphenopalatine ganglion in cluster headache

The role of BDNF in the clinical course of primary headaches

Objective: Brain-derived neurotrophic factor (BDNF) is associated with the pathophysiology of primary headaches. The present study aimed to investigate interictal and ictal BDNF levels and its association with clinical parameters in patients with primary headaches. Methods: Three groups of headache patients enrolled in this study: patients with episodic migraine with and without aura, cluster headaches, and tension-type headaches according to the current criteria of the International Headache Society. In migraine patients and cluster headache patients, venous blood samples were collected twice: outside and during attacks. In patients with tension-type headaches and healthy controls, one single blood sample was taken. The research comprised 120 patients (males and females) suffering from primary headaches. The control group consisted of 30 healthy volunteers. Results: This is the first study to show that there is no gender difference BDNF levels in Uzbek patients with primary headaches. Migraine and cluster headache patients revealed significantly higher BDNF serum levels during headache attacks compared with attack-free periods ( p &lt; 0.02). Conclusion: This reinforces the view that BDNF may be implicated in the pathophysiology of primary headaches.