A study to evaluate the feasibility of an aerobic exercise program in patients with migraine

Objectives.— The aim of this study was to develop and evaluate an exercise program to improve maximum oxygen uptake (VO_{2 max}) in untrained patients with migraine without making their migraines worse.
Patients and methods.— Twenty-six patients were studied at a headache clinic in Sweden. The exercise program, based on indoor cycling, was performed 3 times per week during 12 weeks. VO_{2 max}, migraine status, side effects, and quality of life were evaluated.
Results.— VO_{2 max} increased from 32.9 mL/kg/minute to 36.2 mL/kg/minute ( P  = .044). Quality of life increased and significant improvements in migraine status (attack frequency, symptom intensity, and intake of medicine) were seen. During the 12 weeks of exercise, on one occasion one patient had a migraine attack, which started immediately after training. No other side effects were reported.
Conclusions.— The evaluated exercise program was well tolerated by the patients and improved their VO_{2 max} with no deterioration of migraine status.     

Air pollution and daily ED visits for migraine and headache in Edmonton,Canada

Background

A variety of environmental factors have been identified as possible triggers for migraine and other headache syndromes.

Objective

We analyzed associations between air pollution and emergency department (ED) visits for migraine and headache.

Methods

Analysis was based on 56 241 ED visits for migraine and 48 022 ED visits for headache to Edmonton hospitals between 1992 and 2002. A Poisson model of counts hierarchically clustered by day of week, month, and year was applied using generalized linear mixed models. Temperature and relative humidity were included as covariates.

Results

Females accounted for 78.5% of migraine visits and 56.3% of headache visits. An interquartile range (IQR) increase (6.2 μg/m³) in daily average particulate matter of median aerodynamic diameter less than 2.5 μm (PM_2.5) was associated with increases in visits of 3.3% for migraine (95% confidence interval [CI]: 0.6-6.0), lagged 2 days, and 3.4% for headache (95% CI: 0.3-6.6), lagged 0 days, among females in the cold season (October-March). PM_2.5 was also associated with cold season migraine visits among females at lag 0 and 1 day (P < .1). In the warm period (April-September), a 2.3-ppb IQR increase in sulfur dioxide was associated with a 2.5% increase in migraine visits (95% CI: 0.3-4.6) among females, whereas a 12.8-ppb IQR increment in nitrogen dioxide was associated with a 6.8% increase in headache visits (95% CI: 1.5-12.5) for males.

Conclusions

Findings provide preliminary evidence of an association between air pollution and ED visits for migraine and nonspecific headache. Findings were most consistent for particulate matter.     

Air pollution and daily emergency department visits for headache in Montreal, Canada

BACKGROUND: Many studies have indicated that weather can trigger headache. Here we propose a new methodological approach to assess the relationship between weather, ambient air pollution, and emergency department (ED) visits for this condition. OBJECTIVE: To examine the associations between ED visits for headache and selected meteorological and air pollution factors. DESIGN AND METHODS: A hierarchical clusters design was used to study 10,497 ED visits for headache (ICD-9: 784) that occurred at a Montreal hospital between 1997 and 2002. The generalized linear mixed models technique was applied to create Poisson models for the clustered counts of visits for headache. RESULTS: Statistically significant positive associations were observed between the number of ED visits for headache and the atmospheric pressure for all and for female visits for 1-day and 2-day lagged exposures. The percentage increase in daily ED female visits was 4.1% (95% CI: 2.0, 6.2), 3.4% (95% CI: 1.4, 5.6), and 2.2% (95% CI: 1.4, 5.6) for current day, 1-day and 2-day lagged exposure to SO(2), respectively, for an increase of an interquartile range (IQR) of 2.4 ppb. The percentage increase was also statistically significant for current day and 1-day lagged exposure to NO(2) and CO for all and for female visits. CONCLUSIONS: Presented findings provide support for the hypothesis that ED visits for headache are correlated to weather conditions and ambient air pollution - to atmospheric pressure and exposure to SO(2), NO(2), CO, and PM(2.5). An increase in levels of these factors is associated with an increase in the number of ED visits for headache.     

Prophylactic pharmacological treatment of chronic daily headache

Objective.—To review all the prophylactic pharmacological treatments for chronic daily headache from the past decade.
Background.—Chronic daily headache is among the most common diagnoses seen in specialized headache centers. Prior to 1988, there were no criteria for the diagnosis of chronic tension-type headache and chronic daily headache. An expanded chronic daily headache classification has been proposed.
Methods.—A MEDLINE search was performed using the following key words: chronic daily headache, intractable headache, transformed migraine, chronic tension headache, and chronic tension-type headache. We limited our review to those studies published in English in the last decade, including published abstracts and letters to the editor. Double-blind studies carried out prior to 1988 were also included.
Results.—Pharmacological treatments for chronic daily headache include antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors), anticonvulsants, muscle relaxants, 5-HT₁ agonists, ergots, 5-HT₂ antagonists, antianxiety agents, and miscellaneous drugs. Many of these reports are anecdotal, and most are open rather than double-blind studies.
Conclusions.—There is a great variety of pharmacological treatments available for chronic daily headache. Only the antidepressants have been extensively studied. Other medications may be used if these fail. Recommendations based on our experience at the Headache Unit of the Montefiore Medical Center are outlined here.     

Prevalence and impact of migraine among US Army soldiers deployed in support of Operation Iraqi Freedom

Objectives.— To assess the prevalence and impact of migraine headaches in US Army soldiers deployed in support of Operation Iraqi Freedom.
Methods.— A brigade of US Army soldiers stationed at Ft. Lewis, Washingtion was given a self-administered headache questionnaire within 10 days of return from a 1-year combat tour in Iraq. Soldiers who screened positive for migraine were surveyed again by phone 3 months after return from Iraq.
Results.— In total, 19% of soldiers screened positive for migraine and 17% for possible migraine. Soldiers with a positive migraine screen had a mean of 3.1 headache days per month, a mean headache duration of 5.2 hours, and a mean of 2.4 impaired duty days per month due to headache. Soldiers with migraine made a total of 490 sick call visits for headache over a 3-month period compared with 90 sick call visits among those with possible migraine. In all, 75% of the soldiers with migraine used over-the-counter analgesics and only 4% used triptans. Soldiers with migraine contacted 3 months after returning from Iraq had a mean of 5.3 headache days per month and 36% had a Migraine Disability Assessment Scale grade of 3 or 4.
Conclusions.— Migraine headaches are common in deployed US Army soldiers exceeding the expected prevalence. These headaches result in impaired duty performance and are a frequent cause of sick call visits. Migraine headaches tend to persist after deployment in many soldiers.     

Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs rizatriptan or acetaminophen alone for acute migraine treatment

Objective.— To evaluate the efficacy and tolerability of coadministration of rizatriptan and acetaminophen in the acute treatment of migraine.
Background.— Rizatriptan is a selective 5-HT_1B/1D agonist approved for the acute treatment of migraine. Acetaminophen has been studied for acute migraine treatment. In consideration of the prominent central and peripheral mechanisms in migraine, the use of "multi-mechanism therapy" is gaining momentum in the treatment of acute migraine attacks.
Study Design.— This was a randomized, double-blind, placebo-controlled trial conducted at 10 centers. Eligible patients with migraine according to International Headache Society criteria treated a single migraine attack of moderate or severe intensity within 4 h from pain onset. Patients were randomized into 1 of 4 groups (rizatriptan 10 mg + acetaminophen 1000 mg [RA], rizatriptan alone [R], acetaminophen alone [A], and placebo [P]). There were 3 co-primary hypotheses tested sequentially for 2-h pain relief: (1) RA would be superior to P; (2) if the first was fulfilled, RA would be superior to A; and (3) if the first 2 were fulfilled, RA would be superior to R.
Results.— Of 173 patients who treated a migraine, 123 patients (71.5%) achieved pain relief within 2 h. RA (90%) was significantly better than P (46%) and A (70%), but only numerically better than R (77%) for 2-h pain relief. No significant differences were seen between the active treatment groups in adverse events.
Conclusion.— Rizatriptan coadministered with acetaminophen achieved 2 of the 3 primary hypotheses, proving superior to both acetaminophen and placebo for 2-h pain relief, but failing to achieve superiority to rizatriptan alone. RA was as well tolerated as each of the individual agents.     

Clinical Efficacy of Frovatriptan: Placebo-Controlled Studies

Objective.—To confirm the clinical efficacy of frovatriptan 2.5 mg.
Background.—Frovatriptan is a new 5-hydroxytryptamine (5-HT)_1B/1D receptor agonist being developed for the acute treatment of migraine with or without aura. Results from preclinical and clinical pharmacology studies showed frovatriptan to be a potent 5-HT_1B receptor agonist with a long terminal elimination half-life (26 hours) and a broad therapeutic index.
Design.—Three randomized, placebo-controlled, double-blind, parallel-group trials, in a total of 2676 patients, were performed to confirm the clinical efficacy of frovatriptan 2.5 mg for the acute treatment of migraine.
Results.—In all three studies, headache response 2 hours after frovatriptan dosing was significantly greater than that seen with placebo ( P .001) with approximately a two-fold measure of effect over placebo for headache response at 2 and 4 hours postdosing. Time to headache response occurred within 1.5 hours in a substantial proportion of patients. The incidence of 24-hour headache recurrence with frovatriptan was low (10% to 25%). Frovatriptan therapy also was associated with a high degree of patient satisfaction.
Conclusions.—Frovatriptan represents a consistently effective acute treatment for migraine and accompanying symptoms.     

Evaluation of Pre- and Posttreatment Pulse Oximetry in Acute Childhood Asthma

Objectives : To evaluate the utility of pre- and posttreatment O₂ saturation (SpO₂) for prediction of admission or relapse after ED release in acute asthma exacerbations using a standardized treatment protocol.
Design : A prospective, double-blind, observational study was performed at a pediatric ED. Children with acute asthma were enrolled upon ED presentation. SpO₂ was measured prior to treatment and after disposition decision. Two experienced physicians determined disposition based on history and physical examination alone, while blinded to SpO₂. Relapse of released patients was determined by telephone follow-up.
Results : A pretreatment room-air SpO₂ of ≤91% had a sensitivity of 0.24, a specificity of 0.86, and a likelihood ratio of 1.77 to predict admission/relapse. A posttreatment room-air SpO₂ of ≤91% had a sensitivity of 0.34, a specificity of 0.98, and a likelihood ratio of 16.43 to predict admission/relapse.
Conclusions : As opposed to some previous studies, this study found pretreatment SpO₂ to be a relatively poor predictor of admission. A posttreatment SpO₂ of ≤91% occurred in a minority (32%) of patients, but increased the odds of admission 16-fold and may be used as an adjunct to objectively confirm the need for admission.     

Expanding Access to Triptans: Assessment of Clinical Outcome

Objective.— To evaluate whether access to more liberal quantities of rizatriptan improves clinical outcome in patients with episodic migraine.
Background.— Currently many pharmacy benefit programs limit the number of triptan tablets/injections per month based on perceived cost savings and the belief that too-frequent use of triptans may lead to medication overuse headache and headache chronification.
Methods.— This observer-blind, randomized, parallel-group study enrolled 197 subjects with migraine with or without aura. Subjects completed a 3-month baseline period to establish migraine frequency and then were randomly assigned to receive 9 (formulary limit [FL]) or 27 (clinical limit [CL]) tablets of 10 mg rizatriptan orally disintegrating tablet (ODT) per month for 3 months. The primary endpoint was change in the mean number of migraine days from the baseline to treatment period.
Results.— There was no statistically significant difference between the FL and CL groups in mean number of migraine days (FL-CL LS mean: −0.08 [−0.39, 0.23]; P  = .613). Subjects in the CL group treated attacks at lower headache severity. No CL subjects were reported to have developed chronic migraine despite utilization of greater than 10 rizatriptan ODT tablets per month. Rizatriptan was generally well tolerated by both groups.
Conclusion.— Providing a greater quantity of rizatriptan ODT 10 mg did not reduce the number of migraine days compared with providing 9 tablets per month for this population with episodic migraine with a frequency of 3-8 migraines per month. Regardless of quantity provided, rizatriptan was generally well tolerated.     

Clinical Significance of Brush Allodynia in Emergency Patients With Migraine

Background.— Cutaneous brush allodynia may be a practical and readily assessable marker of progression of an acute migraine attack. We determined the relative frequency of this finding in emergency department (ED) patients with acute migraine and tested the hypothesis that the presence of cutaneous brush allodynia prior to initial treatment in the ED could predict poor 2-hour and 24-hour pain intensity outcomes.
Methods.— As part of a multicenter ED-based clinical trial testing the benefit of dexamethasone vs placebo for the adjuvant parenteral treatment of acute migraine, cutaneous brush allodynia was assessed prior to treatment using an established methodology. In addition to dexamethasone or placebo, all patients received intravenous metoclopramide + diphenhydramine as primary treatment for their migraine. Pain intensity outcomes were assessed in the ED 2 hours after medication administration and again by telephone 24 hours after medication administration.
Results.— An assessment of cutaneous brush allodynia was performed in 182 migraineurs from 3 different EDs, of whom 26 (14%, 95% CI: 10-20%) had cutaneous brush allodynia. A pain-free state within 2 hours of medication administration was achieved by 46% of the allodynic patients and by 47% of the nonallodynic patients ( P  = .91). Median headache intensity over the 24 hours after ED discharge, as measured on a pain intensity scale from zero to 10, was 3 in the allodynic patients and 3 in the nonallodynic patients ( P  = .23).
Conclusions.— Cutaneous brush allodynia is an uncommon finding in the ED, occurring in fewer than 1 in 5 migraineurs. It does not seem to have prognostic relevance for the ED-based management of the acute migraine attack.     

The Event-Related Potential P300 During Headache-Free Period and Spontaneous Attack in Adult Headache Sufferers

The event-related potential P300 has been studied in 15 migraine without aura sufferers, and in 15 episodic tension-type headache sufferers, during pain-free periods and during spontaneous headache attacks. There were no variations of potential, either of P₃ latency or N₂ -P₃ amplitude, in either group during the interictal period. Similarly, there were no variations of the P300 parameters in the group of tension-type headache subjects during headache attacks; by contrast, a significant elongation of latency ( P <0.01) and an increment of N₂-P₃ wave amplitude ( P <0.002) was observed in the group of migraineurs. The authors discuss the data in accordance with the etiopathogenic theories of migraine and the hypothesis that acetylcholine and norepinephrine are the neurotransmitters able to affect the event-related potential P300, which reflects cerebral activity during sensory information processing and analysis.     

Serotonin receptor adaptation in patients with analgesic-induced headache

Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, alteration of serotonin receptor function is one possible mechanism. To assess the plasticity of 5HT₂ serotonin receptors in this condition, we investigated receptor binding by the platelet membrane in patients with analgesic-induced headache (AIH), migraine and non-headache controls. The technique involved radioligand binding with (phenyl-4-³H)spiperone and ketanserin. A greater density of receptor numbers (B_max) was found in patients with AIH and in non-headache controls (96.47±10.2 and 92.01±13.15 fmol/mg protein), as compared to migraine patients (49.52±5.14 fmol/mg protein). The value of dissociation equilibrium constant (K_D) remained unchanged (3.07±0.49, 2.24±0.24 and 2.9±0.42 nM for patients with AIH, migraine and non-headache controls, respectively). Based on these findings, we suggest that up-regulation of 5HT₂ serotonin receptors may be a possible mechanism of headache transformation in patients with AIH.     

Air pollution and ED visits for chest pain

This was a study of 157 028 emergency department (ED)-diagnosed visits for chest pain (International Classification of Diseases, Ninth Revision [ICD-9]: 786) in 6 cities in Canada. The generalized linear mixed methods technique was applied to analyze the relations between daily counts of ED visits for chest pain on the levels of ambient air pollutants after adjusting for meteorological variables. The daily counts of visits were analyzed separately for the whole period (January-December), warm (April-September), and cold (October-March). The results are presented in the form of the excess risks associated with an increase in the mean values of the pollutant concentrations. The highest increase was obtained for nitrogen dioxide (NO₂) exposure in the warm period as follows: 5.9% (95% confidence interval, 3.3-5.8) for mean value equals to 20.1 ppb. The associations of ED visits for chest pain with air pollution are very similar to the associations of ED visits related to cardiac problems.     

Lack of association of endothelial nitric oxide synthase polymorphisms and migraine

Objective.— The aim of this study was to evaluate if 2 functional endothelial nitric oxide synthase (eNOS) gene polymorphisms might be risk factors for migraine.
Background.— Nitric oxide synthase promotes the synthesis of nitric oxide (NO). NO is a potent vasodilator and mediates several processes involved in migraine pathophysiology. Only one study has suggested an association with migraine with aura.
Methods.— We performed a sex- and age-matched case-control study using 2 eNOS polymorphisms (rs1800779 and rs1799983), which are in linkage disequilibrium. Genotypes were obtained with allele-specific probes in a real-time polymerase chain reaction assay. Genotypic and allelic distributions were compared with χ² method. We also estimated the reconstructed haplotypes and calculated ORs for individual haplotypes.
Results.— A total of 337 migraine patients (188 with aura) and 341 healthy controls were recruited. We found no significant differences in the distribution of genotypes and alleles for either polymorphism among clinical subgroups. Neither rs1800779 nor rs1799983 polymorphisms increased the risk for suffering from migraine aura.
Conclusions.— As others have previously reported, we failed to demonstrate genetic association of the eNOS gene with migraine.     

Utilization, Diagnosis, Treatment and Cost of Migraine Treatment in the Emergency Department

Objective.— To determine the percentages of patients receiving migraine-specific therapy and to estimate the rate of unnecessary neuroimaging studies in the emergency department (ED).
Methods.— A retrospective study was conducted analyzing medical records and hospital charge data of ED visits for migraine during 2005 in 2 university-affiliated hospitals. Following a preliminary review of 23 randomly selected ED charts selected to determine the reliability of the coding process, 172 other charts were selected to include 1 visit per patient with a primary discharge diagnosis code of 346.0, 346.1, or 346.9. The diagnosis of migraine was confirmed using predefined criteria. Demographic information, treatment strategies, laboratory and neuroimaging tests, response to therapy, discharge planning, and charge data were evaluated.
Results.— Of 156 patients with completed visits, neuroimaging studies were performed in 36 patients (23%), and only 4 patients had no documented justification for obtaining imaging studies. Seventy-eight patients (50%) had a potential contraindication to receiving migraine-specific therapy. Nine patients (11.5% of eligible patients) received migraine-specific therapy. Most patients were treated with a combination of parenteral antiemetics, narcotics, or ketorolac.
Conclusion.— This analysis supports previous studies indicating the underutilization of migraine-specific treatment in the ED, and suggests that the ED is generally used as a "last resort" when the patient's home medication fails. Because of various contraindications, migraine-specific medications may not be a treatment option in up to 50% of patients seen in the ED. Although almost all of the neuroimaging studies were justified, the radiology charges were a major contributing factor to the overall financial burden of emergency migraine care.     

Time to Equilibration of Oxygen Saturation Using Pulse Oximetry

Objective: To determine the time it takes for O₂, saturation measured by pulse oximetry to equilibrate after a change is made in supplemental O₂, administered by nasal cannula in patients with cardiac and pulmonary disease.
Methods: A prospective, observational study of a convenience sample of 51 patients treated in a university-affiliated ED with nasal cannula O₂. Patients were placed on and/or subsequently taken off O₂ via nasal cannula set at 2 or 4L/min based on clinical indications. Oxygen saturation was measured at l-minute intervals over a 30-minute period using finger-probe pulse oximetry. Of the 51 patients in the study, 43 were monitored while O₂, treatment was initiated and 18 were monitored when it was discontinued.
Results: Most (95%) of the patients placed on O₂, attained equilibration of O₂, saturation within 3.5 minutes. Most (95%) of the patients taken off supplemental O₂, attained equilibration of O₂, saturation within 4.5 minutes.
Conclusion: The interval to equilibration of O₂, saturation in patients receiving O₂ by nasal cannula is considerably shorter than the 20–30 minutes generally suggested. Adequacy of O₂, supplementation should be assessable much sooner than was previously taught.     

Leukotriene B4 Generation by Polymorphonuclear Leukocytes: Possible Involvement in the Pathogenesis of Headache

SYNOPSIS
Leukotriene B₄ (LTB₄) levels in plasma and its generation in vitro from isolated polymorphonuclearleukocytes (PMN) were measured in migraine and cluster headache patients during and between painattacks. The LTB₄plasma levels in cluster headache patients during an attack were significantly higherthan in patients between attacks. There was a positive correlation between the time of sampling from thebeginning of attack and the LTB₄level. The LTB₄ plasma levels in migraine patients during and betweenattacks did not differ significantly from control levels. The results suggest that LTB₄appears rapidly in thecirculation at the beginning of a cluster attack and thereafter declines in amount. LTB₄release from PMNwas induced by stimulation with the calcium ionophore A23187. The release of LTB₄was significantlyhigher in migraine patients during attacks on stimulation with a submaximal dose of A23187 0.5 μM. LTB₄ release induced by A23187 in migraine patients during symptom-free intervals and cluster headachepatients did not differ from healthy controls. LTB₄ release was not affected by 5HT and NA inconcentrations up to 10^-4M. The results suggest that LTB₄is more easily generated in migraine patientsduring attacks. These studies on isolated cells provide a suitable model for the investigation of themetabolism of lipoxygenase derivates in headache patients.     

Increased cerebrovascular pCO2 reactivity in migraine with aura- a transcranial Doppler study during hyperventilation

Cerebrovascular reactivity during hypocapnia was tested in 20 migraineurs (8 with aura, 12 without aura) and 30 sex- and age-matched healthy subjects, and during nitroglycerin-induced headache in 12 healthy subjects. Before and during hyperventilation, mean blood-flow velocity (V_mean) in the middle cerebral artery was measured with transcranial Doppler. In each subject a pCO₂ reactivity index (RI) was calculated as DV_mean/baseline V_mean)/ DpCO₂. Interictally, patients with migraine with aura showed higher RI ( p < 0.05 ANOVA and multiple range test) than controls, whereas migraineurs without aura did not differ from healthy subjects. Ictal and interictal RIs were similar in 9 patients suffering from migraine without aura. No side-to-side differences were detected in RI. During nitroglycerin-induced headache, the RIs were no different from those recorded during migraine attacks and in non-nitroglycerin-provoked healthy controls (p > 0.05, ANOVA and multiple range test). The exaggerated response in migraine with aura might predispose for the characteristic changes in rCBF seen during attacks.     

Pharmacology of the Selective 5-HT1B/1D Agonist Frovatriptan

Objective.—To determine the pharmacological profile of frovatriptan.
Background.—Frovatriptan is a new 5-HT_1B/1D agonist developed for the treatment of migraine.
Methods.—Pharmacological studies were performed using in vitro and in vivo techniques.
Results.—Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT_1B and 5-HT_1D receptors, and moderate affinity for 5-HT_1A, 5-HT_1F, and 5-HT₇ receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT_1B and 5-HT_1D receptors, and as a moderately potent full agonist at 5-HT₇ receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow.
Conclusion.—The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects.     

Cluster Headache: The Peripheral Chemosensitivity as Indicated by the Single-Breath CO2 Test

SYNOPSIS
A single-breath CO₂ test was carried out in cluster headache patients both during bout and remission, and in matchedhealthy individuals (n = 10 for each group) to assess peripheral chemosensitivity. The test subjects inhaled one tidal breath of13% CO₂ in air. The response was expressed as the maximal increase in inspiratory minute ventilation (V_I) within 20 secondsfrom the exposure to CO₂, divided by the increase in end-tidal PCO₂ (P_ETCO₂) (the difference in PCO₂ between the testbreath and the preceding control breaths): DV_I/DP_ETCO₂.
Under the initial resting condition, cluster headache patients within the bout showed a slight hyperventilation in that therewas a significantly reduced P_ETCO₂ (P < 0.05, Student's paired t-test), and during remission, higher V_I, and a lower P_ETCO₂ (P < 0.05, Wilcoxon signed rank test), in comparison with the controls. There was no statistically significantdifference as regards the peripheral chemosensitivity between cluster headache and control groups. These results indicatethat cluster headache patients have an intact and properly-functioning carotid body.