Efficacy and safety of galcanezumab as chronic cluster headache preventive treatment under real world conditions: Observational prospective study.

BACKGROUND: Calcitonin gene-related peptide has shown to play a central role in cluster headache (CH) pathophysiology. A clinical trial with galcanezumab was carried out in chronic cluster headache (CCH) but did not meet its primay endpoint. However, its off-label use in patients with CCH refractory to other therapies could be considered. We aimed to asses the efficacy and safety of galcanezumab as CCH preventive treatment in a real-life setting. METHODS: An observational study was conducted. Patients with CCH who received at least one dose of 240 mg of galcanezumab. RESULTS: Twenty-one patients who tried a mean of 6.3 ± 1.9 preventive therapies, including onabotulinumtoxinA in 90.5%. At baseline, the median of frequency was 60 (37.5-105) monthly attacks with 10 (8.3-10) points in pain intensity (Numerical Rating Scale). After one month, the frequency decreased to 31 (10.5-45) (p = 0.003) with 8.5 (8-9.5) intensity (p = 0.007); 10 (47.6%) patients were 50% responders of whom four (19%) were 75% responders. Of the 15 patients with 3 months of follow-up, seven (46.6%) reduced their frequency by 50% and four (26.6%) by 75%, with 40 (10-60) monthly attacks (p = 0.07) and pain intensity of 8 (5-10) (p = 0.026). Some 52% patients experienced adverse events, mostly mild. CONCLUSIONS: In our cohort of refractory CCH, galcanezumab was effective in almost 50% of patients. This finding supports individual off-label treatment attempts.

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

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Feasibility, Utility, and Interrater Reliability of the Cluster Headache Severity Scale, Cluster Headache Quality of Life, Cluster Headache Index, and 6-Item Headache Impact Test in Pediatric Cluster Headache.

Introduction: Cluster headache is rare in children and only a few clinical studies have systematically evaluated cluster headache in children. Methods: This study was conducted between August 2019 and December 2021 with the primary aim to evaluate the feasibility and utility of the Cluster Headache Severity Scale in determining the severity of cluster headache in patients aged less than 18 years and monitoring response to prescribed treatment. Secondary objectives were to evaluate the feasibility and utility of Cluster Headache Quality of Life, Cluster Headache Index, and 6-item Headache Impact Test in pediatric cluster headache patients to assess the quality of life, severity, and impact of cluster headache. Results: A total of 32 children (age of onset 11.9 ± 2.3 years, age of diagnosis 13.7 ± 2.4 years, 68% boys) were enrolled. Although 30 cases had their headache episodes occurring during nighttime, only 16 children had a Children's Sleep Habits Questionnaire (CSHQ) score >41 at baseline. All children responded to prednisolone as bridging therapy and 23 of 32 showed adequate pain relief after sumatriptan nasal spray for an acute attack. The average time taken for completion of Cluster Headache Index, Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 scores were 5.2 ± 0.7, 5.1 ± 0.8, 27.4 ± 3.5, and 6.2 ± 0.8 minutes, respectively. The interrater reliability was good for Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 (Cronbach α 0.93, 0.81, and 0.89, respectively). There was a strong positive correlation between the Cluster Headache Severity Scale score with Headache Impact Test-6 score and Cluster Headache Quality of Life score (correlation coefficient r = 0.90 and 0.98). Conclusion: Majority of pediatric cluster headache patients are likely to respond to prednisolone and sumatriptan. Cluster Headache Severity Scale, Cluster Headache Quality of Life, and Headache Impact Test-6 can be used for pediatric cluster headache patients for treatment monitoring.

Essential oils and cluster headache: insights from two cases.

Essential oils with proconvulsive properties are known to cause seizures and may worsen migraine. Here, we report two cases of cluster headache temporally related to the use of toothpastes containing essential oils of camphor and eucalyptus.

Comprehensive clinical phenotyping of nitroglycerin infusion induced cluster headache attacks.

BACKGROUND: Nitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way. METHODS: A single-blind, placebo-controlled, cross-over study using weight-calculated intravenous nitroglycerin administration at 0.5 µg/kg/min over 20 minutes to study cluster headache attacks, including accompanying non-headache symptoms and cranial autonomic symptoms. RESULTS: Thirty-three subjects with cluster headache were included in the study; 24 completed all three study visits. Nitroglycerin-induced attacks developed in 26 out of 33 subjects (79%) receiving unblinded nitroglycerin infusion, and in 19 out of 25 subjects (76%) receiving single-blinded nitroglycerin infusion, compared with one out of 24 subjects (4%) receiving single-blinded placebo infusion. Episodic cluster headache subjects had a shorter latency period to a nitroglycerin-induced attack compared to the chronic cluster headache (CCH) subjects (U = 15, z = -2.399, p = 0.016). Sixteen of nineteen episodic cluster headache (mean, 84%; 95% confidence interval, 66-100%) and 11 of 14 chronic cluster headache subjects developed a nitroglycerin-induced attack (79%, 54-100%) following the unblinded nitroglycerin infusion. Following the single-blinded nitroglycerin infusion, eight out of 13 episodic cluster headache (62%, 31-92%) and 11 out of 12 chronic cluster headache (92%, 73-100%) subjects developed nitroglycerin-induced attacks. Nitroglycerin induced non-headache symptoms in the majority of subjects receiving it: 91% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visits, compared with 33% in the single-blinded placebo visit. Cranial autonomic symptoms were induced by nitroglycerin infusion, 94% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visit, compared with 17% in the single-blinded placebo visit. CONCLUSION: Intravenous weight-adjusted nitroglycerin administration in both episodic cluster headache in bout and chronic cluster headache is effective and reliable in inducing cluster headache attacks, cranial autonomic symptoms and non-headache symptoms.

S100B and NSE in Cluster Headache - Evidence for Glial Cell Activation?

OBJECTIVE: Neuronal-specific enolase (NSE) and protein S100B have gained considerable interest as the markers of CNS injury, glial cell activation, and/or blood-brain barrier (BBB) disruption. No studies have investigated NSE and S100B in cluster headache (CH), but these biomarkers could contribute to the understanding of CH. METHODS: Patients with episodic CH in bout (eCHa), in remission (eCHr), and chronic CH (cCH) were included in this randomized, double-blind, placebo-controlled, 2-way cross-over provocation study carried out at the Danish Headache Center. The primary endpoints included (1) differences of NSE and S100B in between groups (eCHa, eCHr, and cCH) at baseline; (2) differences over time in plasma concentrations of NSE and S100B between patient developing an attack and those who did not; (3) differences in plasma concentrations over time of NSE and S100B between active day and placebo day. Baseline findings were compared to the historical data on migraine patients and healthy controls and presented with means ± SD. RESULTS: Nine eCHa, 9 eCHr, and 13 cCH patients completed the study and blood samples from 11 CGRP-induced CH attacks were obtained. There were no differences in NSE levels between CH groups at baseline, but CH patients in active disease phase had higher levels compared with 32 migraine patients (9.1 ± 2.2 µg/L vs 6.0 ± 2.2 µg/L, P < .0001) and 6 healthy controls (9.1 ± 2.2 µg/L vs 7.3 ± 2.0 µg/L, P = .007). CGRP-infusion caused no NSE changes and, but a slight, non-significant, increase in NSE was seen in patients who reported a CGRP-induced CH attack (2.39 µg/L, 95% Cl [-0.26, 3.85], P = .061). At baseline S100B levels in eCHa patients were higher compared to cCH patients (0.06 ± 0.02 µg/L vs 0.04 ± 0.02 µg/L, P = .018). Infusion of CGRP and CGRP-induced attacks did not change S100B levels. Apart from induced CH-attacks no other adverse events were noted. CONCLUSIONS: At baseline eCHa patients had higher S100B plasma levels than cCH patients and there was a slight, however not significant, NSE increase in response to CGRP-induced CH attack. Our findings suggest a possible role of an ictal activation of glial cells in CH pathophysiology, but further studies are warranted.

Effect of Infusion of Calcitonin Gene-Related Peptide on Cluster Headache Attacks: A Randomized Clinical Trial.

Importance: Signaling molecule calcitonin gene-related peptide (CGRP) induces migraine attacks and anti-CGRP medications abort and prevent migraine attacks. Whether CGRP provokes cluster headache attacks is unknown. Objective: To determine whether CGRP induces cluster headache attacks in episodic cluster headache in active phase, episodic cluster headache in remission phase, and chronic cluster headache. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled, 2-way crossover study set at the Danish Headache Center, Rigshospitalet Glostrup, in Denmark. Analyses were intent to treat. Inclusion took place from December 2015 to April 2017. Inclusion criteria were diagnosis of episodic/chronic cluster headache, patients aged 18 to 65 years, and safe contraception in women. Exclusion criteria were a history of other primary headache (except episodic tension-type headache <5 days/mo), individuals who were pregnant or nursing; cardiovascular, cerebrovascular, or psychiatric disease; and drug misuse. Interventions: Thirty-seven patients with cluster headaches received intravenous infusion of 1.5 µg/min of CGRP or placebo over 20 minutes on 2 study days. Main Outcomes and Measures: Difference in incidence of cluster headache-like attacks, difference in area under the curve (AUC) for headache intensity scores (0 to 90 minutes), and difference in time to peak headache between CGRP and placebo in the 3 groups. Results: Of 91 patients assessed for eligibility, 32 patients (35.2%) were included in the analysis. The mean (SD) age was 36 (10.7) years (range, 19-60 years), and the mean weight was 78 kg (range, 53-100 kg). Twenty-seven men (84.4%) completed the study. Calcitonin gene-related peptide induced cluster headache attacks in 8 of 9 patients in the active phase (mean, 89%; 95% CI, 63-100) compared with 1 of 9 in the placebo group (mean, 11%; 95% CI, 0-37) (P = .05). In the remission phase, no patients with episodic cluster headaches reported attacks after CGRP or placebo. Calcitonin gene-related peptide-induced attacks occurred in 7 of 14 patients with chronic cluster headaches (mean, 50%; 95% CI, 20-80) compared with none after placebo (P = .02). In patients with episodic active phase, the mean AUC from 0 to 90 minutes for CGRP was 1.903 (95% CI, 0.842-2.965), and the mean AUC from 0 to 90 minutes for the placebo group was 0.343 (95% CI, 0-0.867) (P = .04). In patients with chronic cluster headache, the mean AUC from 0 to 90 minutes for CGRP was 1.214 (95% CI, 0.395-2.033), and the mean AUC from 0 to 90 minutes for the placebo group was 0.036 (95% CI, 0-0.114) (P = .01). In the remission phase, the mean AUC from 0 to 90 minutes for CGRP was 0.187 (95% CI, 0-0.571), and the mean AUC from 0 to 90 minutes for placebo was 0.019 (95% CI, 0-0.062) (P > .99). Conclusions and Relevance: Calcitonin gene-related peptide provokes cluster headache attacks in active-phase episodic cluster headache and chronic cluster headache but not in remission-phase episodic cluster headache. These results suggest anti-CGRP drugs may be effective in cluster headache management. Trial Registration: ClinicalTrials.gov (NCT02466334).

Linking Cigarette Smoking/Tobacco Exposure and Cluster Headache: A Pathogenesis Theory.

INTRODUCTION: To propose a hypothesis theory to establish a linkage between cigarette smoking and cluster headache pathogenesis. BACKGROUND: Cluster headache is a primary headache syndrome grouped under the trigeminal autonomic cephalalgias. What distinguishes cluster headache from all other primary headache conditions is its inherent connection to cigarette smoking. It is undeniable that tobacco exposure is in some manner related to cluster headache. The connection to tobacco exposure for cluster headache is so strong that even if an individual sufferer never smoked, then that individual typically had significant secondary smoke exposure as a child from parental smoking behavior and in many instances both scenarios exist. The manner by which cigarette smoking is connected to cluster headache pathogenesis is unknown at present. If this could be determined this may contribute to advancing our understanding of cluster headache pathophysiology. METHODS/RESULTS: Hypothesis statement. CONCLUSION: The hypothesis theory will include several principles: (1) the need of double lifetime tobacco exposure, (2) that cadmium is possibly the primary agent in cigarette smoke that leads to hypothalamic-pituitary-gonadal axis toxicity promoting cluster headache, (3) that the estrogenization of the brain and its specific sexually dimorphic nuclei is necessary to develop cluster headache with tobacco exposure, and (4) that the chronic effects of smoking and its toxic metabolites including cadmium and nicotine on the cortex are contributing to the morphometric and orexin alterations that have been previously attributed to the primary headache disorder itself.

Cluster Headache Clinical Phenotypes: Tobacco Nonexposed (Never Smoker and No Parental Secondary Smoke Exposure as a Child) versus Tobacco-Exposed: Results from the United States Cluster Headache Survey.

OBJECTIVE: To present results from the United States Cluster Headache Survey comparing the clinical presentation of tobacco nonexposed and tobacco-exposed cluster headache patients. BACKGROUND: Cluster headache is uniquely tied to a personal history of tobacco usage/cigarette smoking and, if the individual cluster headache sufferer did not smoke, it has been shown that their parent(s) typically did and that individual had significant secondary smoke exposure as a child. The true nontobacco exposed (no personal or secondary exposure) cluster headache sufferer has never been fully studied. METHODS: The United States Cluster Headache Survey consisted of 187 multiple choice questions related to cluster headache including: patient demographics, clinical headache characteristics, family history, triggers, smoking history (personal and secondary), and headache-related disability. The survey was placed on a website from October through December 2008. RESULTS: One thousand one hundred thirty-four individuals completed the survey. One hundred thirty-three subjects or 12% of the surveyed population had no personal smoking/tobacco use history and no secondary smoke exposure as an infant/child, thus a nontobacco exposed population. In the nonexposed population, there were 87 males and 46 females with a gender ratio of 1.9:1. Episodic cluster headache occurred in 80% of nonexposed subjects. One thousand and one survey responders or 88% were tobacco-exposed (729 males and 272 females) with a gender ratio of 2.7:1. Eighty-three percent had a personal smoking history, while only 17% just had parents who smoked with secondary smoke exposure. Eighty-five percent of smokers had double exposure with a personal smoking history and secondary exposure as a child. SIGNIFICANT HIGHLIGHTS FROM THE SURVEY: Nonexposed cluster headache subjects are significantly more likely to develop cluster headache at ages 40 years and younger, while the exposed sufferers are significantly more likely to develop cluster headache at 40 years of age and older. Nonexposed patients have a statistically significant higher frequency of a migraine family history. The exposed population is statistically significantly more likely to have a history of head trauma 19% vs the nonexposed population 10% (P = .02). Tobacco exposed are significantly more likely to transition from episodic to chronic cluster headache (23% vs 14%, P = .02). Cranial autonomic symptoms as well as agitation are more common in tobacco exposed. Nonexposed are less likely to have specific cluster headache triggers. Exposed are significantly more likely to be triggered by alcohol. Tobacco exposed are significantly heavier caffeine users than nonexposed. Nonexposed are significantly more likely to have cluster headache cycles that vary throughout the year than exposed (52% vs 40%, P = .02). Exposed are much more likely to develop cluster headache from 12 am to 6 am than non exposed. Exposed experience significantly more frequent attacks per day and longer duration cycles than nonexposed. A significantly larger percent of the exposed population (57%) has suicidal ideations with their syndrome than nonexposed (43%) (P = .003). In regard to disability, both subtypes are disabled by their headaches, but exposed have more work related disability and lost home-days from headache. Both subgroups have a poor overall response to preventive and abortive medication outside of inhaled oxygen and injectable sumatriptan. CONCLUSION: Cluster headache sufferers who were never exposed to tobacco (personal or secondary as a child) appear to present uniquely compared to the tobacco exposed subgroup. The tobacco exposed clinical phenotype appears to have a more severe syndrome based on attack frequency, cycle duration, and headache related disability. Tobacco exposure is associated with cluster headache chronification. The nonexposed subtype appears to have an earlier age of onset, higher rate of familial migraine, and less circadian periodicity and daytime entrainment, suggesting a possible different underlying pathology than in the tobacco exposed sub-form.

Tobacco, Nicotine, and Headache.

BACKGROUND: Migraineurs variably attribute the cause of their headache to tobacco exposure, whereas tobacco is often stated to cause headache-related disability worldwide. Given tobacco's physiological and emotional addictiveness and migraine's substantial economic impact, improved functionality can be difficult for those with migraine exposed to tobacco products. Environmental tobacco exposure in indoor spaces and workplaces is associated with exacerbation of headache. Avoidance of headache triggers is included in most comprehensive migraine treatment programs, yet tobacco awareness, avoidance, or coping is rarely emphasized as part of that regimen. OBJECTIVE: The aims of this study were to examine the various types of tobacco products to which headache sufferers are exposed and the known basic mechanisms by which tobacco (nicotine) exposure promotes headache pain, and to review the extensive literature on tobacco related to headache with a detailed descriptive narrative providing the basis for conclusions regarding association of noncluster headache-related tobacco exposure. Tobacco-related recommendations are offered. METHODS: MEDLINE, EMBASE, and Google Scholar databases were searched without yearly restriction through the date of submission (May 2015), using the MeSH terms "tobacco," "tobacco products," "smoking," "tobacco use," "headache," and "headache disorders." The selection of articles was not limited to English studies or to humans. Articles were excluded when "headache" and "tobacco" were not both mentioned with data provided. Case series were included. Bibliographies of all articles were screened for additional relevant articles. RESULTS: Although migraineurs worldwide report tobacco smoke among triggers, it is rarely among the highest in frequency, and biases abound with predominantly noncontrolled retrospective data. Prospective population-based diary data are extremely limited, and no controlled trials exist to confirm a cause and effect for headache of any type. Although some studies are nonsupportive and even conflicting, headache, pain, and tobacco exposure currently remain associated. CONCLUSION: Conflicting data support the validity of patient-reported environmental tobacco exposure as a headache trigger. Prospective controlled studies are needed, but unlikely to be performed, to determine the extent that tobacco influences the headache process, in addition to other under-recognized factors. Meanwhile, because of numerous other negative health effects, decreased tobacco exposure should be recommended to headache patients of all ages in hopes of decreasing disability and improving functionality.

Role of Methadone in Induction and/or Exacerbation of Cluster Headache in Patients Treated for Opioid Addiction.

Methadone is a potent opioid agonist widely used in opioid maintenance therapy. In some countries, methadone is available for pain treatment. We report the cases of two patients with history of substance abuse (mainly heroin), who presented with cluster headache possibly related to high-dose methadone. One possible explanation for the severe pain described in these cases is hyperalgesia induced by high doses of methadone.

Intolerancia a la histamina como causa de síntomas digestivos crónicos en pacientes pediátricos / Histamine intolerance as a cause of chronic digestive complaints in pediatric patients

Introducción: la intolerancia a la histamina (IH) es una patología poco descrita en gastroenterología y que puede tener una sintomatología digestiva predominante. Los objetivos de este estudio son describir los casos diagnosticados en una consulta de gastroenterología pediátrica. Material y métodos: estudio observacional y retrospectivo analizando los pacientes diagnosticados de IH desde septiembre de 2010 a diciembre de 2011 en la consulta de gastroenterología pediátrica de un hospital terciario. Se consideraron con diagnóstico de IH al presentar 2 o más síntomas digestivos característicos, determinación de diaminooxidasa disminuida y/o respuesta a la dieta baja en histamina con pruebas de alergia IgE-mediada a alimentos negativos. Resultados: se han diagnosticado 16 pacientes. Hubo un predominio de niños (11/5) frente a las niñas. La edad media al inicio de los síntomas fue de 4 años (6 meses vs. 13 años y 6 meses) y la edad media al diagnóstico fue de 6 años y 6 meses (17 meses vs. 13 años y 11 meses). Los síntomas predominantes fueron dolor abdominal difuso (16/16), diarrea intermitente (10/16), cefalea (5/16) y vómitos intermitentes (4/16). Conclusiones: la intolerancia a la histamina es una patología poco conocida pero con una incidencia que puede ser relevante. Los síntomas predominantes son dolor abdominal difuso, diarrea, cefalea y vómitos de aparición crónica e intermitente. El diagnóstico se realiza por sospecha clínica, determinación de diaminooxidasa plasmática y respuesta a dieta baja en histamina. Con el tratamiento de dieta baja en histamina presentan una mejoría inmediata (AU)

Introduction: histamine intolerance (HI) is a poorly described disease in gastroenterology that may present with predominant digestive complaints. The goals of this study include a report of two cases diagnosed in a pediatric gastroenterology clinic. Material and methods: observational, retrospective study of patients diagnosed with HI from September 2010 to December 2011 at the pediatric gastroenterology clinic of a tertiary hospital. They were deemed to have a diagnosis of HI in the presence of 2 or more characteristic digestive complaints, decreased diamino oxidase (DAO) levels and/or response to a low histamine diet with negative IgE-mediated food allergy tests. Results: sixteen patients were diagnosed. Males predominated versus females (11/5). Mean age at symptom onset was 4 years (6 months vs. 13 years and 6 months) and mean age at diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months), with an interval of 2 years and 1 month between symptom onset and diagnosis (5 months vs. 4 years). Predominant symptoms included diffuse abdominal pain (16/16), intermittent diarrhea (10/16), headache (5/16), intermittent vomiting (4/16), and skin rash (2/16). The diagnosis was established by measuring plasma diamino oxidase levels, which were below 10 kU/L (normal > 10 kU/L) in 14 cases, and symptom clearance on initiating a low histamine diet. In two patients DAO levels were above 10 kU/L but responded to diet. Treatment was based on a diet low in histamine-contaning food, and antihistamines H1 y H2 had to be added for two cases. Conclusions: histamine intolerance is a little known disease with a potentially relevant incidence. Predominant complaints include diffuse abdominal pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is based on clinical suspicion, plasma DAO measurement, and response to a low histamine diet. Management with the latter provides immediate improvement (AU)

Headaches related to psychoactive substance use.

AIM: To investigate a possible association between headache and psychoactive substance use. METHODS: 1055 psychoactive substance abusers were consecutively admitted. All patients filled out a detailed headache questionnaire and 1015 patients were included. RESULTS: Twenty seven percent of patients reported having headache. Eighteen percent of patients reported having headache attributed to a substance or its withdrawal and 1.4% had unclassified headache. The most commonly used substances were cannabis (80.5%), alcohol (74.6%), methylamphetamine (18.7%), benzodiazepine (10.4%), volatile solvent (5.8%), cocaine (4.4%), heroin (2.1%), opioids (0.5%), and other substances (1.7%). Fifteen patients reported that onset of headache occurred prior to onset of substance use, while 94.5% had headaches occurred after substance abuse. A higher incidence of headache was found in the benzodiazepine, methylamphetamine, cocaine, heroin, volatile solvent abusers. Seventy-eight percent of headache patients have never sought help from a physician despite the severity and frequency of headache. CONCLUSIONS: In our study, the prevalence of headache among all psychoactive substance abusers was 26.9%. Although this is one-group study without any comparison with non-addict population and associational data must be interpreted with caution, the results of this study indicate a possible relationship may exist between headache and substance use since 94.5% of substance users described headaches after the onset of substance use. The younger start and the longer duration of cannabis use caused the higher incidence of headache, but this correlation was not observed in other substance use. Migraine was far more prevalent in the abusers than in previously reported community populations.

Recurrence of cluster headache with pramipexole.

Cluster headache (CH) is among the most painful headache disorders. There is still no unifying pathophysiological hypothesis to explain the trigeminal distribution, the circadian periodicity and the autonomic symptoms of the syndrome. We report the case of a patient with worsening of CH following administration of pramipexole for a restless legs syndrome (RLS). This observation supports the hypothesis that the dopaminergic system may play a role in the genesis or trigger of CH.

Cluster headache is associated with the alcohol dehydrogenase 4 (ADH4) gene.

BACKGROUND/OBJECTIVES: Alcohol is a well-known trigger factor for cluster headache attacks during the active phases of the disease. The alcohol dehydrogenase (ADH) pathway, which converts alcohol to the toxic substance acetaldehyde, is responsible for most of the alcohol breakdown in the liver. Humans have 7 ADH genes, tightly clustered on chromosome 4q21-q25, that encode different ADH isoforms. The ADH4 gene encodes the class II ADH4 pi subunit, which contributes, in addition to alcohol, to the metabolization of a wide variety of substrates, including retinol, other aliphatic alcohols, hydroxysteroids, and biogenic amines. The purpose of this study was to investigate the association of genetic variants within the ADH4 gene with cluster headache susceptibility and phenotype. METHODS: A total of 110 consecutive unrelated cluster headache patients and 203 age- and sex-matched healthy controls of Caucasian origin were involved in the study. Patients and controls were genotyped for 2 bi-allelic single nucleotide polymorphisms (SNPs) of the ADH4 gene: SNP1 - rs1800759 and SNP2 - rs1126671. Allele, genotype, and haplotype frequencies of the examined polymorphisms were compared between cases and controls. RESULTS: Genotype frequencies of the rs1126671 polymorphism resulted significantly different between cluster headache patients and controls (chi(2) = 10.269, P = .006). The carriage of the AA genotype, in comparison with remaining genotypes, was associated with a significantly increased disease risk (OR = 2.33, 95% CI: 1.25-4.37). Haplotype analysis confirmed the association between the ADH4 gene and the disease. No association between different clinical characteristics of cluster headache and the examined polymorphisms was found. CONCLUSION: Our data suggest that cluster headache is associated with the ADH4 gene or a linked locus. Additional studies are warranted to elucidate the role of this gene in the etiopathogenesis of the disease.

Cluster headache as the result of secondhand cigarette smoke exposure during childhood.

Unique to cluster headache (CH) compared with all other primary headache conditions is its association with a personal history of cigarette smoking. Studies have indicated that greater than 80% of CH patients have a prolonged history of tobacco usage prior to CH onset. How tobacco exposure can lead to CH has not yet been elucidated. As secondhand smoke exposure during childhood has been linked to multiple medical illnesses could CH also be the result of childhood exposure to tobacco smoke? The United States Cluster Headache survey is the largest survey ever done of CH sufferers living in the United States. The survey addressed various clinical, epidemiologic, and economic issues related to CH. Several survey questions dealt with the issue of personal and parental smoking history. Results from the survey suggest that CH can result from secondhand cigarette smoke exposure during childhood as greater than 60% of non-smoking CH patients had parents who smoked. Strengthening the probable association between secondhand smoke exposure and the development of CH is the fact that double the number of survey responders developed CH at or before 20 years of age if during their childhood they lived with a parent who smoked cigarettes.