The location of pain in cluster headache: Data from the International Cluster Headache Questionnaire.

OBJECTIVE: To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. BACKGROUND: Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. METHODS: The International Cluster Headache Questionnaire was an internet-based cross-sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta-analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. RESULTS: One thousand five hundred eighty-nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta-analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2-3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361-1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. CONCLUSIONS: The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex.

A brief diagnostic screen for cluster headache: Creation and initial validation of the Erwin Test for Cluster Headache.

OBJECTIVE: To use 1) newly generated data, 2) existing evidence, and 3) expert opinion to create and validate a new cluster headache screening tool. METHODS: In phase 1 of the study, we performed a prospective study of an English translation of an Italian screen on 95 participants (45 with cluster headache, 17 with other trigeminal autonomic cephalalgias, 30 with migraine, and 3 with trigeminal neuralgia). In phase 2, we performed a systematic review in PubMed of all studies until September 2019 with diagnostic screening tools for cluster headache. In phase 3, a 6-person panel of cluster headache patients, research coordinators, and headache specialists analyzed the data from the first two phases to generate a new diagnostic screening tool. Finally, in phase 4 this new screen was validated on participants at a single headache center (all diagnoses) and through research recruitment (trigeminal autonomic cephalalgias only, as recruitment was essential but was otherwise low). RESULTS: In total, this study included 319 unique participants including 109 cluster headache participants (95 total participants/45 cluster headache participants in phase 1, and 224 total participants/64 cluster headache participants in phase 4). It also found 123 articles on potential screening tools in our systematic review. In phase 1, analysis of the English translation of an Italian screen generated 7 questions with high sensitivity and specificity against migraine, trigeminal neuralgia, and other trigeminal autonomic cephalalgias, but had grammatical and other limitations as a general screening tool. In phase 2, the systematic review revealed nine studies that met inclusion criteria as diagnostic screening tools for cluster headache, including four where sensitivity and specificity were available for individual questions or small groups of questions. In phase 3, this data was reviewed by the expert panel to generate a brief (6-item), binary (yes/no), written screening test. In phase 4, a total of 224 participants completed the new 6-item screening test (81 migraine, 64 cluster headache, 21 other trigeminal autonomic cephalalgias, 35 secondary headaches, 7 neuralgias, 5 probable migraine, and 11 other headache disorders). Answers to the 6 items were combined in a decision tree algorithm and three items had a sensitivity of 84% (confidence interval or 95% confidence interval 73-92%), specificity of 89% (95% confidence interval 84-94%), positive predictive value of 76% (95% confidence interval 64-85%), and negative predictive value of 93% (95% confidence interval 88-97%) for the diagnosis of cluster headache. These three items focused on headache intensity, duration, and autonomic features. CONCLUSION: The 3-item Erwin Test for Cluster Headache is a promising diagnostic screening tool for cluster headache.

Cluster headache epidemiology including pediatric onset, sex, and ICHD criteria: Results from the International Cluster Headache Questionnaire.

OBJECTIVE: To validate the diagnoses and to investigate epidemiological data from an international, non-clinic-based, and large (n = 1604) survey of participants with cluster headache. BACKGROUND: There are several limitations in current epidemiological data in cluster headache including a lack of large non-clinic-based studies. There is also limited information on several aspects of cluster headache, such as pediatric incidence. METHODS: The International Cluster Headache Questionnaire was an internet-based survey that included questions on cluster headache demographics, criteria from the International Classification of Headache Disorders (ICHD), and medications. RESULTS: A total of 3251 subjects participated in the survey, and 1604 respondents met ICHD criteria for cluster headache. For validation, we interviewed a random sample of 5% (81/1604) of participants and confirmed the diagnosis of cluster headache in 97.5% (79/81). Pediatric onset was found in 27.5% (341/1583) of participants, and only 15.2% (52/341) of participants with pediatric onset were diagnosed before the age of 18. Men were more likely to have episodic cluster headache between ages 10 and 50, but the sex ratio was approximately equal for other ages. An overwhelming majority of respondents had at least one autonomic feature (99.0%, 1588/1604) and had restlessness (96.6%, 1550/1604), but many also had prototypical migrainous features including photophobia or phonophobia (50.1%, 804/1604), pain aggravated by physical activity (31.4%, 503/1604), or nausea and vomiting (27.5%, 441/1604). Interestingly, the first-line medications for acute treatment (oxygen) and preventive treatment (calcium channel blockers) were perceived as significantly less effective in chronic cluster headache (3.2 ± 1.1 and 2.1 ± 1.0 respectively on a 5-point ordinal scale) compared with episodic cluster headache (3.5 ± 1.0 and 2.4 ± 1.1, respectively, p < 0.001 for both comparisons). CONCLUSIONS: Cluster headache often occurs in the pediatric population, although they are typically not diagnosed until adulthood. The onset of cluster headache is the inverse of that in migraine; in migraine women are more likely to have migraine between ages 10 and 50 but the sex ratio is approximately equal otherwise. Prototypical migrainous features are not useful in differentiating cluster headache from migraine. Participant data from a large international study also suggest that chronic cluster headache is not only less responsive to newer treatments (like noninvasive vagus nerve stimulation and galcanezumab), but to traditional first-line treatments as well.

Cluster headache is one of the most intensely painful human conditions: Results from the International Cluster Headache Questionnaire.

OBJECTIVE: To determine the pain intensity of cluster headache through a large survey by comparing it to other painful disorders. Furthermore, to investigate the relationship between maximal pain, autonomic, and other clinical symptoms, as well as demographic attributes of cluster headache. BACKGROUND: The pain of cluster headache is anecdotally considered to be one of the worst pains in existence. The link between pain and autonomic features of cluster headache is understood mechanistically through the trigeminovascular reflex, though it is not clear if this is a graded response. Links between pain and other features of cluster headache are less well understood. METHODS: This Internet-based cross-sectional survey included questions on cluster headache diagnostic criteria, which were used as part of the inclusion/exclusion criteria for the study. Respondents were asked to rate a cluster headache attack on the 0-10 numerical rating scale. Additionally, they were asked if they had experienced a list of other painful conditions such as labor pain or nephrolithiasis; if so they were asked to rate that pain as well. The survey also included demographics, mood scores, and treatment responses. RESULTS: A total of 1604 cluster headache respondents were included in the analysis. Respondents rated cluster headache as significantly (p < 0.001) more intense than every other pain condition examined. Cluster headache attacks were rated as 9.7 ± 0.6 (mean ± standard deviation) on the numerical rating scale, followed by labor pain (7.2 ± 2.0), pancreatitis (7.0 ± 1.5), and nephrolithiasis (6.9 ± 1.9). The majority of cluster headache respondents rated a cluster headache attack at maximal or 10.0 pain (72.1%, 1157/1604). Respondents with maximal pain were statistically significantly more likely to have cranial autonomic features compared to respondents with less pain: conjunctival injection or lacrimation 91% (1057/1157) versus 85% (381/447), eyelid edema 77% (887/1157) versus 66% (293/447), forehead/facial sweating 60% (693/1157) versus 49% (217/447), fullness in the ear 47% (541/1157) versus 35% (155/447), and miosis/ptosis 85% (1124/1157) versus 75% (426/447) (all p values <0.001). Respondents with maximal pain also had other statistically significant findings: more frequent attacks (4.0 ± 2.0 attacks per day vs. 3.5 ± 2.0 attacks per day), higher Hopelessness Depression Symptom Questionnaire scores (24.5 ± 16.9 vs. 21.1 ± 15.2), decreased overall effectiveness from calcium channel blockers (on a 5-point Likert scale), and more likely female: 34% (389/1157) versus 24% (108/447) (all p values <0.001). Pain intensity was not associated with restlessness, headache duration, age of onset, episodic/chronic status, or the effectiveness of any acute or preventive medication other than calcium channel blockers. CONCLUSIONS: Cluster headache is an intensely painful disorder, even in the context of other disorders considered intensely painful. Maximal pain intensity is associated with more cranial autonomic features, suggesting a graded response between pain and autonomic features. Maximal pain intensity is also associated with headache frequency but not duration, suggesting a relationship between pain intensity and mechanisms controlling headache onset, but not between pain intensity and mechanisms controlling headache offset.

Effectiveness of Oxygen and Other Acute Treatments for Cluster Headache: Results From the Cluster Headache Questionnaire, an International Survey.

OBJECTIVE: To assess the effectiveness and adverse effects of acute cluster headache medications in a large international sample, including recommended treatments such as oxygen, commonly used medications such as opioids, and emerging medications such as intranasal ketamine. Particular focus is paid to a large subset of respondents 65 years of age or older. BACKGROUND: Large international surveys of cluster headache are rare, as are examinations of treatments and side effects in older cluster headache patients. This article presents data from the Cluster Headache Questionnaire, with respondents from over 50 countries and with the vast majority from the United States, the United Kingdom, and Canada. METHODS: This internet-based survey included questions on cluster headache diagnostic criteria, which were used as part of the inclusion/exclusion criteria for the study, as well as effectiveness of medications, physical and medical complications, psychological and emotional complications, mood scores, and difficulty obtaining medications. The diagnostic questions were also used to create a separate group of respondents with probable cluster headache. Limitations to the methods include the use of nonvalidated questions, the lack of a formal clinical diagnosis of cluster headache, and the grouping of some medications (eg, all triptans as opposed to sumatriptan subcutaneous alone). RESULTS: A total of 3251 subjects participated in the questionnaire, and 2193 respondents met criteria for this study (1604 cluster headache and 589 probable cluster headache). Of the respondents with cluster headache, 68.8% (1104/1604) were male and 78.0% (1245/1596) had episodic cluster headache. Over half of respondents reported complete or very effective treatment for triptans (54%, 639/1139) and oxygen (54%, 582/1082). Between 14 and 25% of respondents reported complete or very effective treatment for ergot derivatives (dihydroergotamine 25%, 42/170; cafergot/ergotamine 17%, 50/303), caffeine and energy drinks (17%, 7/41), and intranasal ketamine (14%, 5/37). Less than 10% reported complete or very effective treatment for opioids (6%, 30/541), intranasal capsaicin (5%, 7/151), and intranasal lidocaine (2%, 5/241). Adverse events were especially low for oxygen (no or minimal physical and medical complications 99%, 1077/1093; no or minimal psychological and emotional complications 97%, 1065/1093), intranasal lidocaine (no or minimal physical and medical complications 97%, 248/257; no or minimal psychological and emotional complications 98%, 251/257), intranasal ketamine (no or minimal physical and medical complications 95%, 38/40; no or minimal psychological and emotional complications 98%, 39/40), intranasal capsaicin (no or minimal physical and medical complications 91%, 145/159; no or minimal psychological and emotional complications 94%, 150/159), and caffeine and energy drinks (no or minimal physical and medical complications 89%, 39/44; no or minimal psychological and emotional complications 91%, 40/44). This is in comparison to ergotamine/cafergot (no or minimal physical and medical complications 83%, 273/327; no or minimal psychological and emotional complications 89%, 290/327), dihydroergotamine (no or minimal physical and medical complications 81%, 143/176; no or minimal psychological and emotional complications 91%, 160/176), opioids (no or minimal physical and medical complications 76%, 416/549; no or minimal psychological and emotional complications 77%, 423/549), or triptans (no or minimal physical and medical complications 73%, 883/1218; no or minimal psychological and emotional complications 85%, 1032/1218). A total of 139 of 1604 cluster headache respondents (8.7%) were age 65 and older and reported similar effectiveness and adverse events to the general population. The 589 respondents with probable cluster headache reported similar medication effectiveness to respondents with a full diagnosis of cluster headache. CONCLUSIONS: Oxygen is reported by survey respondents to be a highly effective treatment with few complications in cluster headache in a large international sample, including those 65 years or over. Triptans are also very effective with some side effects, and newer medications deserve additional study. Patients with probable cluster headache may respond similarly to acute medications as patients with a full diagnosis of cluster headache.