bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Predictive Factors in the Prognosis of Migraine with Aura
Authors: Cologno D , Torelli P , Manzoni GC
Published: March 2003

In order to identify possible predictive factors in the prognosis of migraine with aura (MA), we conducted a review at 10 to 20 years from referral on a sample of 77 MA patients (51F, 26M) consecutively seen for the first time at the University of Parma Headache Center. Based on the date of the last MA attack reported by these patients, we divided them into two study groups: a group of 22 patients “with remission of the disease,” i.e. attack-free for at least 2 years at the end of the follow-up study; and a group of 55 patients “without remission of the disease,” i.e. still having attacks in the last 2 years of the follow-up study. A comparative analysis of the MA clinical features observed in the two groups at the time of the patients' first visit to our Center enabled us to identify a number of favorable prognostic indicators, namely: a family history of parents with MA, the absence of other associated forms of primary headache, and the absence of both natural and artificial light stimulation as trigger factors.
Genetic and Environmental Influences on Recurrent Headaches in Eight to Nine-Year-Old Twins
Authors: Svensson DA , Larsson B , Bille B , Lichtenstein P
Published: March 2003

The major objective of the present study was to estimate genetic and environmental influences on recurrent headaches in prepubescent twins. A nationwide cohort of 8 to 9-year-old Swedish twins ( n = 1,480) was screened for nonsymptomatic and recurrent headaches through a questionnaire mailed to their parents (75% response frequency). Among positives, 79% of headaches were classified as migraine or tension-type headache in close accordance with the International Headache Society criteria. The prevalences of migraine and nonmigrainous headaches were 2.4% and 11.3%, respectively, and without significant differences between the sexes or zygosity types. Inheritance on liability to recurrent headaches was estimated to 70% (a2 = 0.70, 95% CI = 0.54 − 0.82) for boys and girls but the genetic effect was found to be uncorrelated between the sexes. We conclude that genetic and individual specific effects are important for recurrent headaches of migrainous and nonmigrainous types in prepubescent children, and that different genetic etiologies might exist for boys and girls.
Comparison of the Efficacy of Zolmitriptan and Sumatriptan: Issues in Migraine Trial Design
Authors: Geraud G , Olesen J , Pfaffenrath V , Tfelt-Hansen P , Zupping R , Diener H-C , Sweet R
Published: March 2003

In this international, multicentre, double-blind, placebo-controlled, single attack study, ‘triptan naive’ migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P = 0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.
Effects of the Anti-Migraine Drug Sumatriptan on Muscle Energy Metabolism: Relationship to Side-Effects
Authors: Boska MD , Welch KMA , Schultz L , Nelson J
Published: March 2003

Sumatriptan succinate (Imitrex) is a 5-HT(5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5–20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.
Cluster of MMPI Personality Profiles in Chronic Tension-Type Headache and Predictable Response to Fluoxetine
Authors: Aguirre J , Gallardo R , Pareja Juan A , Pérez-Miranda M
Published: March 2003

A study was made of the personality profiles of a sample of 51 patients with chronic tension-type headache (CTH) employing the Minnesota Multiphasic Personality Inventory (MMPI). Two clusters were obtained by applying multivariate classification techniques: cluster 1 (with elevations on scales Hy, D and Hs only) and cluster 2 (exhibiting elevations on most scales except Pd, Mf and Si). Fifty subjects without chronic pain or known psychiatric disorders, and extracted from the same social setting as the patients, completed the MMPI as a control group. Fluoxetine treatment was started in the CTH group, with follow-up over a 1-year period. Chi-squared analysis correlating the clusters obtained to different pain-related variables and epidemiological parameters revealed a significant association to sex only. There were no differences in therapeutic response between the two clusters. However, the patients belonging to the less perturbed cluster who exhibited profiles analogous to those of the control population showed significant improvement with respect to the global sample and their own cluster.
Post-Menopausal Hormone Replacement Therapy and Stroke Risk
Authors: Kittner S J , Bousser M-G
Published: March 2003

This paper will review available data bearing on the relationship of post-menopausal hormone replacement therapy to the risk of first or recurrent ischaemic stroke. Although experimental data from both human and animal studies will be briefly mentioned, the bulk of evidence is from observational epidemiological studies. As such, the limitations of observational studies, particularly as applied to the health effects of post-menopausal hormone replacement therapy, will be emphasized. We conclude that there is no compelling consistent evidence that post-menopausal hormone replacement therapy either decreases or increases stroke risk. There are, however, reasons to be concerned that this therapy may contribute to stroke risk.
Evaluation of a Novel Solubilized Formulation of Ibuprofen in the Treatment of Migraine Headache: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study
Authors: Kellstein DE , Lipton RB , Geetha R , Koronkiewicz K , Evans FT , Stewart WF , Wilkes K , Furey SA , Subramanian T , Cooper SA
Published: March 2003

A total of 729 migraine sufferers with moderate to severe baseline pain evaluated a single 200, 400 or 600 mg dose of a new liquigel formulation of ibuprofen over 8 h. Ibuprofen liquigels were significantly superior to placebo for cumulative headache response (pain reduced to mild or none) from 0.5 (600 mg) or 1 h (200 and 400 mg) to 8 h. At 2 h, respective headache response rates for ibuprofen 200, 400 and 600 mg and placebo were 64%, 72%, 72% and 50%. All three doses were also significantly superior to placebo for 2-h pain-free (25%, 28%, 29% and 13%, respectively) and for proportions with mild or no limitation of activity (2-8 h). Ibuprofen liquigels were generally superior to placebo for reducing photophobia, phonophobia, or nausea (1-4 h) and for global evaluation. All doses were well tolerated. These data demonstrate that ibuprofen liquigels relieve the pain, ancillary symptoms, and limitation of activity, of migraine.
Headache Characteristics During the Development of Tolerance to Nitrates: Pathophysiological Implications
Authors: Christiansen I , Iversen HK , Olesen J
Published: March 2003

Recent studies suggest that nitric oxide (NO) plays an important role in nitrate‐induced headache and in spontaneous migraine attacks. Organic nitrates act as prodrugs for NO and headache is a predominant adverse effect of nitrates but often disappears during continuous treatment. Insight into tolerance to headache could lead to insight into vascular headache mechanisms in general. The specific aim of the present study was therefore to characterize the headache and accompanying symptoms during continuous nitrate administration until a state of tolerance to headache had developed. 5‐isosorbide‐mononitrate (5‐ISMN) 30 mg three times daily was administered orally for 7 days in 11 healthy subjects in a double‐blind, randomized placebo controlled cross‐over design. Wash‐out between periods was 14 days or more. Haemodynamic data from the present study were compared to the observed changes of headache over time. Headache during 5‐ISMN was longer lasting and more severe compared to placebo ( P < 0.004). In 10 subjects the headache fulfilled the pain sub‐criteria for migraine and in five subjects all diagnostic criteria for migraine without aura were fulfilled. Conversely, 20 min of intravenous infusion of glyceryl trinitrate caused a milder headache and no migraine. The present results therefore suggest that NO may elicit a migraine attack in many healthy subjects if a high enough dose is given for several hours. A close temporal association between the disappearance of headache and the attenuation of the 5‐ISMN induced dilatation of the superficial temporal artery was observed. In contrast, tolerance in the middle cerebral artery already appeared after 24 h, which was earlier than the development of tolerance to headache. If vasodilatation is the cause of headache the results point to extracerebral arteries. However, cytotoxic and pain modulating central nervous system effects of NO, the time courses of which are unknown, may also play a role, involving both intra‐ and extracranial arteries.
Tolerability and Efficacy of Naratriptan Tablets in the Acute Treatment of Migraine Attacks for 1 Year
Authors: Heywood J , Bomhof MAM , Pradalier A , Thaventhiran L , Winter P , Hassani H , of on behalf , Group the Naratriptan Long‐term Study
Published: March 2003

Objective and design: This open‐label study was conducted to evaluate the tolerability and efficacy of the 5HT1 agonist naratriptan with repeated use in the acute treatment of migraine attacks for 1 year. Four hundred and seventeen (417) migraine patients treated 15 301 migraine attacks over the course of the study. Results: The results show that 84% of attacks treated with a single 2.5 mg dose of naratriptan were not associated with the occurrence of an adverse event. The percentage of attacks associated with an adverse event did not increase with number of doses used to treat a given attack (1 vs. 2) or duration of use (0–6 months vs. > 6–12 months). The only adverse events experienced in > 2% of attacks throughout the 1‐year study were nausea (3% of attacks), hyposalivation (2% of attacks), and drowsiness/sleepiness (2% of attacks). Headache relief 4 h post‐dose was reported in a median 70% of moderate or severe attacks and a median 86% of mild attacks treated with naratriptan tablets 2.5 mg. The percentages of patients reporting headache relief did not diminish as a function of increased duration of treatment (0–6 months vs. > 6–12 months) or frequency of use (for > 36 vs. < 36 attacks). The mean number of tablets taken per attack was 1.2. A second naratriptan 2.5 mg tablet was taken for headache recurrence in a mean 16% (median 8%) of attacks. Conclusion: The results of this study demonstrate that naratriptan tablets 2.5 mg taken for acute migraine attacks over a 1‐year period are well‐tolerated and effective.
Induction of Nitrate Tolerance is not a Useful Treatment in Cluster Headache
Authors: Christiansen I , Iversen HK , Olesen J
Published: March 2003

The aims of the present study were to investigate whether induction of nitrate tolerance is a useful treatment in cluster headache and to correlate any changes in attack frequency of cluster headache and nitrate‐induced headache to the vascular adaptation during continuous nitrate administration. The results were compared to results obtained from studies of nitrate tolerance in healthy subjects. Materials and methods: 5‐isosorbide‐mononitrate (5‐ISMN) 30 mg was administered orally three times daily for 4 weeks in nine sufferers of chronic cluster headache in a double‐blind, randomized placebo‐controlled cross‐over design. Blood velocity in the middle cerebral artery was measured with transcranial Doppler and the diameters of the temporal and radial arteries were measured with high frequency ultrasound . The haemodynamic data were compared to changes in the frequency of cluster headache attacks and interval headaches over time . Results: Tolerance was complete within 24 h in the middle cerebral arteries and after 7 days in the symptomatic temporal artery, while tolerance of the radial artery was not observed within this period. The time profiles of tolerance were almost identical to the time profiles observed in healthy subjects. A close temporal association between the disappearance of nitrate‐induced headache and tolerance of the temporal artery was observed but tolerance had no effect on cluster headache attack frequency. Conclusions: Induction of tolerance to nitrates cannot be used to treat cluster headache. If pain is related to arterial dilatation the results point to extracerebral rather than cerebral arteries as the site of nociception. However, other peripheral and central pain‐modulating effects of nitric oxide, the time courses of which are unknown, should also be taken into consideration.
Comparison of Rizatriptan 10 Mg vs. Zolmitriptan 2.5 Mg in the Acute Treatment of Migraine
Authors: Pascual J , Vega P , Diener H–C , Allen C , Vrijens F , Patel K ,   Group the Rizatriptan–zolmitriptan Study
Published: March 2003

The efficacy and tolerability of rizatriptan (MAXALT™) and zolmitriptan (ZOMIG™) were compared in a randomized, double–blind, double–dummy, stratified (on prior use of rizatriptan and/or zolmitriptan), placebo–controlled, single attack study in 766 patients. Rizatriptan tended to provide freedom from pain sooner than zolmitriptan (hazard ratio 1.26, P = 0.075), acting within 60 min following dosing. More patients were pain free at 2 h on rizatriptan than on zolmitriptan (43.2% vs. 35.6%, P = 0.041), while headache relief at 2 h was similar (70.5% vs. 66.8%). At 2 h, fewer patients on rizatriptan had symptoms of photophobia (35.6% vs. 43.5%, P = 0.029) and nausea (25.2% vs. 32.5%, P = 0.046), and more patients on rizatriptan had normal function (45.4% vs. 37.0%, P = 0.025) than zolmitriptan. Headache recurred in 28% of patients taking rizatriptan, 29% taking zolmitriptan and 26% taking placebo. Both active treatments were effective compared to placebo and were well tolerated. The most common side–effects with rizatriptan were asthenia/fatigue, somnolence and dizziness, while the most common side–effects with zolmitriptan were asthenia/fatigue and dizziness.
Recurrent Short-Lasting Headache Associated With Paroxysmal Hypertension: A Clonidine-Responsive Syndrome
Authors: Dodick DW
Published: March 2003

The clinical syndrome of hypertension, headache, palpitation, diaphoresis, flushing, and emotional lability is classically associated with pheochromocytoma. Two patients are presented with this constellation of symptoms in whom investigations for pheochromocytoma were unrevealing. Headache was the presenting and most prominent complaint, with daily episodes of short-lasting, intermittent, and paroxysmal attacks. Each paroxysm of headache was associated with a dramatic increase in systolic and diastolic blood pressure. After failure to control the labile fluctuations in blood pressure and headache with several classes of anti-hypertensive medications used in combination, a prompt and persistent response occurred after the administration of clonidine. The pathophysiology of this syndrome and the mechanism of clonidine action are reviewed in the context of a possible failure of the baroreceptor reflex.
Migraine Prevalence in Adolescents Aged 13–15: A Student Population‐Based Study in Taiwan
Authors: Lu S‐R , Fuh J‐L , Juang K‐D , Wang S‐J
Published: March 2003

To estimate the lifetime migraine prevalence in school adolescents aged 13–15 in Taiwan, we conducted a self‐administered questionnaire survey in four sampled public junior high schools. Migraine was diagnosed according to the diagnostic criteria of the International Headache Society. A total of 4064 students (1983 boys, 2081 girls) completed the questionnaire (response rate 91.6%). The lifetime prevalence of migraine was 6.8%. It was significantly higher in girls than boys (7.8% vs. 5.7%) and increased with age in both sexes. Students with migraine were more likely to be absent from school because of their headaches than those with non‐migraine headaches (30% vs. 14%, odds ratio (OR) 2.7). They were also more likely to use painkillers for their headaches than their non‐migraine headache peers (72% vs. 40%, OR 4.0). These results suggest that migraine is a common disorder of adolescents in Taiwan and its impact on the quality of life can not be ignored.
Determinants of Patient Satisfaction With Migraine Therapy
Authors: Davies GM , Santanello N , Lipton R
Published: March 2003

Determinants of patient satisfaction with migraine treatment are not well understood. The objective of this study was to evaluate which treatment outcomes influence patient satisfaction with treatment. Analyses were performed on data from 1506 migraineurs from two clinical trials of rizatriptan for treatment of migraine. Satisfaction with treatment was assessed 2 h after initial treatment and prior to use of rescue therapy. Over 90% of patients who were pain-free at 2 h were at least somewhat satisfied with treatment compared with < 10% of patients with moderate or severe pain. Only 60–70% of patients with mild pain at 2 h experienced some level of satisfaction with treatment. For patients with mild pain at 2 h, results showed subjects who reported severe pain at baseline, absence of associated symptoms at 2 h and pain relief within the first 90 min had at least a 76% probability of being at least somewhat satisfied. This probability decreased with the presence of associated symptoms, slower pain relief and moderate baseline pain intensity. Fast, complete pain relief is one important factor in determining short-term patient satisfaction with treatment.
Natural History of Migraine in Childhood
Authors: Hernandez-Latorre MA , Roig M
Published: March 2003

Epidemiological studies have shown that 3–7% of the paediatric population suffer from migraine. Despite this high prevalence little has been published about the natural history of migraine or of its prognosis. The objectives of this study were: (i) to outline the natural history of migraine in childhood; and (ii) to identify early predictors of an unfavourable clinical evolution. A prospective, longitudinal, 10-year follow-up study was conducted of the clinical evolution of 181 paediatric patients with migraine. Data analysis was performed by statistical significance and logistic regression tests. In our study 24.3% of children with migraine had their onset before age 6 years and another 57% between 6 and 10 years of age. A positive family history of migraine was recorded in 77.5%. Eighty-eight percent of patients followed a favourable clinical course. The remaining 12% of patients had to be placed on prophylactic treatment owing to the increasing of their headache. Of all parameters investigated, the age of onset was the only statistically significant predictor of an unfavourable clinical evolution. We conclude: (i) most patients with migraine headache starting in childhood do not require prophylactic treatment; (ii) the earlier the disease begins the more likely is an unfavourable clinical course; (iii) genetic factors play an important role in the phenotypic expression of the disease; (iv) our study suggests the existence, at least, of two different populations among childhood migraine patients.
Cluster Headache
Authors: Dodick DW , Rozen TD , Goadsby PJ , Silberstein SD
Published: March 2003

Cluster headache is a stereotypic, primary headache disorder that is marked by repeated short-lasting attacks of severe, unilateral head pain and associated autonomic symptoms. Cluster headache is probably due to an abnormality in the circadian hypothalamic generator with subsequent trigeminovascular activation. We have reviewed the clinical manifestations, pathophysiology, gender differences, and treatment options in cluster headache.
Primary and Secondary Chronic Cluster Headache: Two Separate Entities?
Authors: Torelli P , Cologno D , Cademartiri C , Manzoni GC
Published: March 2003

The International Headache Society (IHS) classification divides chronic cluster headache (CH) into two subtypes: chronic CH unremitting from onset (CCHU) and chronic CH evolved from episodic (CCHE). The purpose of our study was to point out any similarities and differences between the two chronic CH subtypes and to determine whether or not they can be considered as two separate clinical entities. We reviewed data about 31 CCHE patients and 38 CCHU patients referred to the Parma Headache Centre between 1975 and 1999. Clinically, CCHE patients exhibited statistically significant differences from CCHU patients, i.e. earlier CH onset and duration of attacks varying more frequently between 120 and 180 min. From the point of view of lifestyle, heavy alcohol and coffee drinkers prevailed among CCHU patients, while CCHE patients were more frequently heavy smokers. Based on clinical features, it seems reasonable to suppose that chronic CH may occur as two distinct entities.
Possible Mechanisms of Glyceryl-Trinitrate-Induced Immediate Headache in Patients With Chronic Tension-Type Headache
Authors: Ashina M , Bendtsen L , Jensen R , Sakai F , Olesen J
Published: March 2003

Nitric oxide (NO) plays an important role in the pathophysiology of primary headaches including chronic tension-type headache (CTTH). Thus, a NO synthase inhibitor reduces headache and muscle hardness while the NO donor glyceryl trinitrate (GTN) causes more headache in patients than in healthy controls. Sensitization of myofascial pain pathways is important in CTTH, and the aim of the present study was to investigate if such mechanisms may also explain GTN-induced immediate headache in patients with CTTH. In a randomized, double-blind, crossover study 16 patients with CTTH and 16 healthy subjects received intravenous infusion of GTN (0.5 μg/kg per min for 20 min) or placebo on two headache-free days separated by at least 1 week. Muscle hardness, myofascial tenderness, mechanical and heat pain thresholds were measured at baseline and at 60 min and 120 min after start of infusion. In patients, GTN infusion resulted in a biphasic response with immediate headache and more pronounced delayed headache. A similar but less pronounced response was seen in controls. There was no difference between GTN and placebo regarding muscle hardness, myofascial tenderness or pressure and heat pain thresholds in either patients or controls ( P > 0.05). The unchanged sensitivity of pericranial myofascial pain pathways indicates that peripheral and central sensitization is not involved in the mechanisms of GTN-induced immediate headache.
Sumatriptan: Economic Evidence for Its Use in the Treatment of Migraine, the Canadian Comparative Economic Analysis
Authors: Caro G , Getsios D , Caro JJ , Raggio G , Burrows M , Black L
Published: March 2003

The objective of this study was to evaluate economic and health effects of sumatriptan relative to customary therapy in Canada. The relationship between treatment and functionality was established based on analysis of existing data from a multinational study. A Monte Carlo model was developed to simulate 1 year for each of customary therapy and six sumatriptan formulations. Costs are expressed in 1998 Canadian dollars. Sumatriptan is expected to reduce the time spent with migraine symptoms and resulting time lost. Under customary therapy, the annual cost of lost time is estimated at £908 ($1973). With sumatriptan, these costs ranged from £406 ($882) with subcutaneous sumatriptan to £577 ($1254) with nasal sumatriptan 10 mg, saving £331–502 ($719–1091) in the annual cost of time lost. All these benefits are expected to be obtained at an additional drug cost ranging from £869 ($1889) for subcutaneous sumatriptan to £278 ($605) for sumatriptan suppository. The cost of sumatriptan treatment is significantly offset by a substantial reduction of costs associated with time lost due to migraine symptoms.
Benign Raeder's Syndrome is Probably a Manifestation of Carotid Artery Disease
Authors: Solomon S , Lustig JP
Published: March 2003

Raeder first described Horner's syndrome with ipsilateral head pain due to paratrigeminal organic disease, but most subsequent reports of this syndrome were idiopathic. Our recent case prompted a review of past reports of idiopathic Raeder's syndrome. Because in recent years the features of Raeder's syndrome have been recognized as common manifestations of carotid artery dissection, we divided the cases into those with and those without carotid imaging studies. The classifications and differential diagnoses are discussed. Sixteen cases with carotid imaging studies were not very different from the 28 cases without such studies. Most studies were performed several weeks after onset of symptoms and carotid dissection could not be definitely excluded in any case. In most cases of idiopathic Raeder's syndrome, carotid artery dissection was not considered and in no case was that condition definitively excluded. People with Raeder's syndrome not associated with a paratrigeminal organic lesion probably have a disease of the carotid artery. Because of the different criteria and classifications of Raeder's syndrome it is best to relegate this eponym to history.
Neuropeptide Localization in the ‘Migraine Generator’ Region of the Human Brainstem
Authors: Tajti J , Uddman R , Edvinsson L
Published: March 2003

Evidence from animals and humans suggests that brainstem nuclei such as the raphe nuclei, the locus coeruleus (LC) and the periaqueductal grey matter (PAG), are involved in the pathophysiology of migraine. In order to understand possible neurotransmitters involved we have, by means of indirect immunocytochemistry, analysed these regions for the occurrence and distribution of calcitonin gene-related peptide (CGRP), substance P (SP), pituitary adenylate-cyclase activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP). CGRP-immunoreactive (-ir) cell bodies, but no fibres, were found to occur in high numbers, constituting 80% of all nerve cell bodies in the LC. A smaller number of these nerve cell bodies (40%) in the LC proved to be PACAP-ir. The LC neurones also stored the vesicular monoamine transporter (VMAT)- and the C-terminal flanking peptide of neuropeptide Y (C-PON)-ir, illustrating their adrenergic nature. Double immunostaining revealed that all VMAT-and C-PON-containing neurones, in addition, stored CGRP. Immunoreactive cell bodies were not seen in the nucleus raphe magnus (NRM) or PAG. Numerous SP-ir nerve fibres were observed in the NRM, the LC and the PAG. Few PACAP-ir nerve fibres were detected in the PAG and few VIP-ir nerve fibres were seen in the NRM and the PAG.
α1-Adrenoceptor Subtypes Mediating Vasoconstriction in the Carotid Circulation of Anaesthetized Pigs: Possible Avenues for Antimigraine Drug Development
Authors: Willems EW , Heiligers JPC , De Vries P , Kapoor K , Tom B , Villalón CM , Saxena PR
Published: March 2003

It has recently been shown that the α-adrenoceptors mediating vasoconstriction of porcine carotid arteriovenous anastomoses resemble both α1- and α2-adrenoceptors, but no attempt was made to identify the specific subtypes (α1A, α1B and α1D) involved. Therefore, the present study was designed to elucidate the specific subtype(s) of α1-adrenoceptors involved in the above response, using the α1-adrenoceptor agonist phenylephrine and α1-adrenoceptor antagonists 5-methylurapidil (α1A), L-765 314 (α1B) and BMY 7378 (α1D). Ten-minute intracarotid infusions of phenylephrine (1, 3 and 10 μgkg−1.min−1) induced a dose-dependent decrease in total carotid and arteriovenous anastomotic conductance, accompanied by a small tachycardia. These carotid vascular effects were abolished by L-765 314 (1000 μgkg−1; i.v.), while these responses were only attenuated by 5-methylurapidil (1000 μgkg−1; i.v.), and BMY 7378 (1000 μgkg−1; i.v.). Furthermore, intravenous bolus injections of phenylephrine (3 and 10 μgkg−1) produced a dose-dependent vasopressor response, which was only affected by 1000 μgkg−1 of 5-methylurapidil, while the other antagonists were ineffective. These results, coupled to the binding affinities of the above antagonists at the different α1-adrenoceptors, suggest that both α1A- and α1B-adrenoceptors mediate constriction of carotid arteriovenous anastomoses in anaesthetized pigs. In view of the less ubiquitous nature of α1B- compared to α1A-adrenoceptors, the development of potent and selective α1B-adrenoceptor agonists may prove to be important for the treatment of migraine.
Evidence for Activation of the Coagulation System in Migraine with Aura
Authors: Hering-Hanit R , Friedman Z , Schlesinger I , Ellis M
Published: March 2003

Migraine with aura has been shown to be an independent risk factor for stroke. Although the precise mechanism of migraine-related stroke is not known, risk factors for hypercoagulability have been found in migraineurs. Prothrombin factor 1.2 (F1.2) is a cleavage product of prothrombin. Elevated plasma F1.2 has been shown to be a sensitive and a specific marker of ongoing thrombin generation, and thus may serve as an indicator of hypercoagulability. In this study we determined plasma F1.2 levels in 35 patients with migraine (22 with aura and 13 without aura) and in 24 healthy age- and sex-matched volunteers. Elevated F1.2 levels were found in 11 of 22 (50%) patients with migraine with aura (1.25–3.5 nmol/l). None of the patients with migraine without aura nor any of the healthy volunteers had elevated plasma F1.2 levels (normal < 1.1 nmol/l). We conclude that prothrombin F1.2 levels are elevated in a significant number of patients with migraine with aura but not in patients with migraine without aura. This finding suggests that there is activation of the clotting system in certain patients with migraine with aura.
Application of the International Headache Society Classification Criteria in 652 Cluster Headache Patients
Authors: Torelli P , Cologno D , Cademartiri C , Manzoni GC
Published: March 2003

We applied the International Headache Society (IHS) classification coding parameters to a study population of 652 cluster headache (CH) patients, in order to determine how many patients did not fulfil the diagnostic criteria for group 3.1 and to find out any diagnostic elements that could be changed in the upcoming revision of the classification to make it more relevant to current clinical practice. Ninety-nine patients were found to have cluster-like disorder (3.3), including 74 (74.7%) who did not fulfil the diagnostic criteria for CH, because either pain was not associated with any of the accompanying autonomic phenomena listed in the classification or it was not located orbitally, supraorbitally and/or temporally. A review of our total sample showed that 72.0% of patients reported frontal and occipital pain location; in 61.8%, 33.4% and 39.1% of cases, attacks were also accompanied by restlessness/agitation, nausea and photophobia, respectively. In a coding system that took into account the diagnostic elements that we considered in our study, group 3.1 of the existing IHS classification would actually include 51 of the 99 patients currently coded as 3.3.
Migraine and Function of the Immune System: A Meta-Analysis of Clinical Literature Published Between 1966 and 1999
Authors: Kemper RHA , Meijler WJ , Korf J , Ter Horst GJ
Published: March 2003

Mechanisms underlying migraine precipitation are largely unknown. A role of the immune system in migraine precipitation is a matter of debate because of the association of atopic disorders and migraine. Recently, it was demonstrated that migraineurs benefit from eradication of a Helicobacter pylori infection, which substantiates a possible role for (sub-clinical) infections in precipitation of migraine. Since 1966, about 45 clinical investigations have reported on alterations of immune function in migraine patients, which we present in this review. Changes of serum levels of complement and immunoglobulins, histamine, cytokines and immune cells were found in some of these studies but in most cases not corroborated by others. Migraineurs suffering from comorbid atopic disorders show elevated plasma IgE levels but not patients without a type I hypersensitivity. Histamine plasma levels are chronically elevated in migraineurs, and interictally decreased lymphocyte phagocytotic function and increased plasma tumor necrosis factor alpha (TNFα) levels were found, and may be related to increased infection susceptibility. The cause of this increased susceptibility is unclear but most likely is a result of chronic stress, a well-known suppressor of the immune system. Stress relief enhances immune activity and triggers a burst of circulating vasoactive compounds that function as mediators of inflammation and potential precipitators of a migraine attack in vulnerable subjects. In conclusion, in the clinical literature of the past decades, there is no clear-cut evidence of an immune dysfunction in migraineurs, but we cannot totally exclude the possibility of an altered immune function in migraineurs. Discrepancies in the literature most likely are caused by the divergent patterns of sample collection relative to the time of the attack. We propose stringent definition of sample collection times for future studies of immune function in migraine patients.
One-Year Prevalence of Migraine in Sweden: A Population-Based Study in Adults
Authors: Dahlöf C , Linde M
Published: March 2003

A randomly selected sample of 1668 individuals (782 women and 886 men) aged 18–74 years was interviewed by telephone using a standardized questionnaire including the International Headache Society (IHS) criteria for migraine. The survey was performed by SIFO, the national public opinion poll agency. The results obtained demonstrate that 21% of the Swedish population had suffered from severe headaches during the past year. A majority of these headache sufferers (61%) fulfilled the IHS-criteria for migraine. The 1-year prevalence of migraine in Sweden was found to be 13.2 ± 1.9% (16.7% among women and 9.5% among men). The prevalence of migraine in this Swedish population did not differ between the northern, middle and southern part of Sweden, or between urban and rural areas or different income groups. Only about half (49%) of the migraineurs had been diagnosed by a physician. Among the individuals who fulfilled the IHS criteria for migraine the mean attack-frequency was 1.3 per month and the mean attack-duration was 19 h. If the duration of the attack was disregarded as a strict criterion for migraine (attacks < 4 h and > 72 h were included), the prevalence increased to 17.0 ± 1.9% without affecting the sex distribution. With this amendment, 92% of those who considered their headaches to be migraine or migraine-like in fact fulfilled the alternative criteria for migraine. However, only 76% of those who believed that they had migraine or migraine-like headaches fulfilled the strict IHS criteria for migraine. An extension of the time window from 4 to 72 h may be reasonable both from a pragmatic and from a rational clinical point of view.
Physical Impairments in Cervicogenic Headache: Traumatic Vs. Nontraumatic Onset
Authors: Dumas J-P , Arsenault AB , Boudreau G , Magnoux E , Lepage Y , Bellavance A , Loisel P
Published: March 2003

In order to quantify the physical impairments associated with different types of headache, 77 subjects belonging to four different groups (postmotor vehicle accident cervicogenic headache subjects, cervicogenic headache subjects nontraumatic, migraine patients and control subjects) were evaluated using the following variables: posture, cervical range of motion, strength of the neck flexors and extensors, endurance of the short neck flexors, manual segmental mobility, proprioception of the neck, and pain (McGill Pain Questionnaire and the skin roll test). The results of this study showed that postmotor vehicle accident cervicogenic patients have significantly limited active cervical range of motion (in flexion/extension and rotations), present decreased strength and endurance of neck flexors and decreased strength of the extensor muscles. Our results suggest that there are enough differences between the postmotor vehicle accident and nontraumatic cervicogenic headache subjects to warrant caution when analysing the data of these two subgroups together, as several studies have done in the past. The onset of headache is therefore an important variable that should be controlled for when attempting to characterize the physical impairments associated with cervicogenic headache.
Trigeminal Nociception-Induced Cerebral Fos Expression in the Conscious Rat
Authors: Ter Horst GJ , Meijler WJ , Korf J , Kemper RHA
Published: March 2003

Little is known about trigeminal nociception-induced cerebral activity and involvement of cerebral structures in pathogenesis of trigeminovascular headaches such as migraine. Neuroimaging has demonstrated cortical, hypothalamic and brainstem activation during the attack and after abolition with sumatriptan. This has led to the conclusion that the dorsal raphe and locus coeruleus may initiate events that generate migraneous headache. Using a conscious rat model of trigeminal nociception and cerebral Fos expression as histochemical markers of neuronal activity, we characterized the pattern of brain activity after noxious trigeminal stimulation with capsaicin (250 and 1000 nm). A significantly increased Fos immunoreactivity was found in the trigeminal nucleus caudalis (layers I and II), the area postrema, the nucleus of the solitary tract, the parvicellular reticular nucleus, the locus coeruleus, the parabrachial nucleus and the raphe nuclei. In addition, the ventrolateral periaqueductal grey, the intralaminar thalamic and various hypothalamic areas, showed an enhanced Fos expression after the intracisternal administration of capsaicin. Other responding areas were the amygdala, the upper lip and forelimb regions of the primary somatosensory cortex, and the insula. Many of these areas participate in (anti)-nociception, although we cannot exclude the possibility that in conscious animals the pain-associated physiological and behavioural responses that are an intrinsic and necessary part of coping with pain have generated the increased Fos expression. Trigeminal stimulation-induced locus coeruleus, dorsal raphe and hypothalamic activation are opposed to a suggested pathogenic role of these nuclei in migraine and cluster headache, respectively.
Posture-Related Headaches and Pachymeningeal Enhancement in CSF Leaks from Craniotomy Site
Authors: Mokri B
Published: March 2003

Cerebrospinal fluid (CSF) leak is recognized to cause headaches that typically but not invariably have orthostatic features (present in upright posture, relieved by recumbency). Head magnetic resonance imaging (MRI) typically shows diffuse pachymeningeal enhancement. A 24-year-old woman, after resection of a right temporoparietal glioma, developed CSF leak from the craniotomy site, resulting in subgaleal fluid collection and associated with diffuse pachymeningeal gadolinium enhancement as well as posture-related headaches. The headaches, however, were present in a recumbent position and relieved after several minutes of being in an upright position. It is postulated that CSF leak took place when the patient was recumbent and ceased when she was upright, a position in which there is decrease in intracranial pressure. After cessation of the leak, along with disappearance of subgaleal collection of CSF, both the headaches and the pachymeningeal enhancement resolved.
Splitting of the Body Image as Somesthetic Aura Symptom in Migraine
Authors: Podoll K , Robinson D
Published: March 2003

Splitting of the body image was illustrated as a somesthetic aura symptom in three of the 562 entries to the national Migraine Art competitions, confirming previous descriptions of this rare phenomenon in the migraine literature. In this type of self-experienced paroxysmal body schema disturbance, the own body is perceived as being split, usually in the mid-line, into two halves that may be displaced or separated from each other. Splitting of the body image most frequently applies to the migraine sufferer's head. The said phenomenon, the pathomechanisms of which are obscure, must not be confused with the visual illusion of illusory splitting.
Treatment of Cluster Headache with Topiramate: Effects and Side-Effects in Five Patients
Authors: Förderreuther S , Mayer M , Straube A
Published: March 2003

We report on clinical experience with topiramate in the prophylactic treatment of three patients with chronic and two patients with episodic, otherwise therapy-resistant, cluster headache. Patients were treated with daily doses of 75-200 mg topiramate. Topiramate was effective in three patients but proved ineffective and also caused intolerable side-effects in two patients. Topiramate may have prophylactic properties for treating cluster headache at lower doses than needed in epilepsy therapy, but its clinical value is limited due to central nervous system side-effects.
Cns Effects of Sumatriptan and Rizatriptan in Healthy Female Volunteers
Authors: van der Post J , Schram MT , Schoemaker RC , Pieters MSM , Fuseau E , Pereira A , Baggen S , Cohen AF , van Gerven JMA
Published: March 2003

This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9)°/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8)°/sec). Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). Temazepam caused larger, similar effects. In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation.
Muscle Tenderness in Pericranial and Neck-Shoulder Region in Children with Headache. A Controlled Study
Authors: Anttila P , Metsähonkala L , Mikkelsson M , Aromaa M , Kautiainen H , Salminen J , Viander S , Jäppilä E , Sillanpää M
Published: March 2003

Increased pericranial muscle tenderness is connected with tension-type headache in adults. In children, the importance of muscle tenderness in the pericranial or neck-shoulder region in the pathogenesis of different types of headache is unknown. The present study evaluated muscle tenderness in the pericranial and neck-shoulder region in children with migraine, those with tension-type headache and those without headache. An unselected population-based questionnaire study concerning headache was carried out in 1135 Finnish schoolchildren aged 12 years. Of them, 183 children were randomly selected for a face-to-face interview and a clinical examination. Muscle tenderness was recorded by manual palpation and dolorimeter. Children with migraine had increased overall tenderness, recorded by manual palpation, compared with those without headache. They also self-reported tenderness in the neck-shoulder region during daily activities more often than the children of the other groups. Muscle tenderness was not associated with paediatric tension-type headache. The mean pressure pain thresholds did not differ among the three groups. However, a negative correlation between the total tenderness score and the dolorimeter score was found in each group. In conclusion, children with migraine had increased muscle tenderness at palpation of the pericranial and neck-shoulder muscles and they also reported pain symptoms in the neck-shoulder region most frequently. Instead, increased pericranial and neck-shoulder muscle tenderness was not associated with tension-type headache in children.
Increase in Meningeal Blood Flow by Nitric Oxide - Interaction with Calcitonin Gene-Related Peptide Receptor and Prostaglandin Synthesis Inhibition
Authors: Strecker T , Dux M , Messlinger K
Published: March 2003

This study addresses possible interactions of the vasodilators nitric oxide (NO), calcitonin gene-related peptide (CGRP) and prostaglandins, which may be implicated in the generation of vascular headaches. Local application of the NO donator diethylamine-NONOate (NONOate) to the exposed dura mater encephali of the rat caused dose-dependent increases in meningeal blood flow recorded by laser Doppler flowmetry. Pre-application of the CGRP receptor antagonist CGRP8-37 significantly attenuated the evoked blood flow increases, while the cyclooxygenase inhibitors acetylsalicylic acid and metamizol were only marginally effective. Stimulation of rat dura mater with NONOate in vitro caused increases in CGRP release. NADPH- diaphorase activity indicating NO production was restricted to the endothelium of dural arterial vessels. We conclude that increases in meningeal blood flow caused by NO depend partly on the release and vasodilatory action of CGRP from dural afferents, while prostaglandins are not significantly involved.