bluuebunny/crossref_metadata_2025 huggingface dataset:
Amitriptyline and Dexamethasone Combined Treatment in Drug-Induced Headache
Authors: Bonuccelli U , Nuti A , Lucetti C , Pavese N , Dell'Agnello G , Muratorio A
Published: March 2003

Frequent or regular intake of antimigraine drugs, including analgesics, constitutes a common cause of chronic daily headache. Discontinuation. of symptomatic medication can produce an increase in head pain accompanied by withdrawal symptoms. We report the favourable outcome of treating a group of outpatients with the combination of amitriptyline, dexamethasone and sumatriptan. Dexamethasone (4 mg/day) was given intramuscularlv for 2 weeks, amitriptyline orally at night (50 mg/day) for at least 6 months, and sumatriptan subcutaneously to treat acute headache attacks. Eighteen out of 20 patients abstained from drug abuse. Eleven of these 18 patients showed a marked reduction in headache frequency (at least 75% in relation to the basal value), and were considered “very good responders”. The other seven patients experienced at least 50%, reduction in headache frequency compared to baseline. This preliminary report suggests that drug-induced headache can be treated effectively in outpatients using dexamethasone, amitriptyline and sumatriptan in combination with significant benefit in everyday life conditions.
Exteroceptive Suppression of Temporal Muscle Activity is Normal in Chronic Tension-Type Headache and Not Related To Actual Headache State
Authors: Bendtsen L , Jensen R , Brennum J , Arerndt-Nielser L , Olesen J
Published: March 2003

The aim of the present study was to compare the late exteroceptive suppression period (ES2) of temporalis muscle activity between patients with chronic tension-type headache and healthy controls, and to investigate the influence, if any, of actual headache on ES2. ES2 was recorded in 55 patients and in 55 controls with a previously evaluated methodology and analysed by a blinded observer. The first 20 patients were randomly studied on 2 additional days, 1 day with and 1 day without headache. The duration of ES2 did not differ between patients and controls and did not differ on days with headache compared with days without headache. ES2 duration was not related to the frequency of headache, headache intensity, age, pericranial muscle tenderness or electrical pain threshold. Our results strongly indicate that ES2 is normal in chronic tension-type headache and therefore may not be related to the pathophysiology of this disorder.
Recurrent Paroxysmal Headache Associated with Facial Ecchymosis
Authors: Comabella M , Titus F , Huguet P
Published: March 2003

The case of a 58-year-old man with chronic paroxysmal headache and facial ecchymosis is described. The headache was pulsating, of short duration without nausea or vomiting, and occasionally associated with flashing lights. Ecchymoses were mainly located in the middle forehead region and their appearance was associated with a reduction in intensity of the headache. Blood coagulation tests were within normal limits, and a skin biopsy of the ecchymotic lesior ruled out an underlying vasculitis. These attacks were difficult to include in any particular type of headache, although some aspects were similar to migraine headache. The possible mechanism of hemorrhages it discussed.
Magnesium in the Prophylaxis of Migraine—a Double-Blind, Placebo-Controlled Study
Authors: Pfaffenrath V , Wessely P , Meyer C , Isler HR , Evers S , Grotemeyer KH , Taneri Z , Soyka D , G”bel H , Fischer M
Published: March 2003

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18–64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 1 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.
Long-Term Outcome of Patients with Headache and Drug Abuse after Inpatient Withdrawal
Authors: Schnider P , Aull S , Baumgartner C , Marterer A , Wöber C , Zeiler K , Wessely P
Published: March 2003

Thirty-eight patients with “chronic daily” headache and ergotamine and/or analgesics abuse according to the criteria proposed by the international Headache Society were re-investigated 5 years after inpatient drug withdrawal. At the end of the observation period, 19 patients (50.0%) had their headaches on only 8 days per month or less, 18 patients (47.4%) were free of symptoms or had only mild headaches. A close correlation was found between the frequency of headache and the duration of drug abuse, as well as between the intensity of headache and the number of tablets taken per month. Frequency and intensity of headache had changed within the first 2 years after withdrawal, but remained stable afterwards. Fifteen patients (39.5%) reported on recurrent drug abuse. Patients with migraine showed a tendency towards a better prognosis compared to patients with tension-type headache or with combined migraine and tension-type headache. The results of this study highlight the long-term efficacy of inpatient drug withdrawal in patients with headache and ergotamine and/or analgesics abuse.
Chronic Post-Traumatic Headaches Classified and Compared with Natural Headaches
Authors: Haas DC
Published: March 2003

This study sought to determine whether chronic post-traumatic headaches are different from or identical to the naturally occurring headaches. The chronic post-traumatic headaches of 48 patients were classified, as if they were natural headaches, by the diagnostic criteria of the International Headache Society. Thirty-six patients' headaches (75%) were chronic tension-type headache, 10 (21%) were migraine without aura, and 2 (4%) were unclassifiable. The characteristics and accompaniments of the headaches within each diagnostic group were then compared to those in a control group with natural headaches of the same type. No notable differences between the post-traumatic and control groups were found. Hence, chronic post-traumatic headaches have no special features, but are symptomatically identical to either chronic tension-type headache or migraine without aura (in this series of patients). This identity suggests that post-traumatic headaches are generated by the same processes causing the natural headaches, not by intracranial derangement from head blows or jolts.
Melatonin Versus Placebo in the Prophylaxis of Cluster Headache
Authors: Leone M , D'Amico D , Moschiano F , Fraschini F , Bussone G
Published: March 2003

A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg ( n=10) or placebo ( n=10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p<0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p<0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who cannot tolerate other drugs.
An Epidemiologic Study of Headache Among Children and Adolescents of Southern Brazil
Authors: Barea LM , Tannhauser M , Rotta NT
Published: March 2003

To study the epidemiology of pediatric headache, we conducted a cross-sectional study of a randomized and proportional sample of 538 male and female students, 10 to 18 years old. They were in the 5th to 8th grade of the schools of Porto Alegre, RS Brazil. The headache disorders were classified on the basis of clinical interview as well as a physical and neurological examination using the operational diagnostic criteria of the International Headache Society (IHS The following headache prevalences were found: lifetime, 93.2%; last year, 82.9%; last week, 31.4%; last 24 h, 8.9%. Last week and last 24 h headache complaints were twice as prevalent in the female group. During the last year the prevalence of headache disorders was 72.8% for tension-type and 9.9% for migraine headache and was not associated with age distribution. Only the last year and last week prevalences of tension-type headache were significantly higher in the female group. The last year prevalence of headache disorder-proved to be positively associated with sex and age variables. The prevalence of headache disorders was found to be extremely high in this population group, requiring more attention on the part of investigators as a public health problem.
Chest Symptoms after Sumatriptan
Authors: Visser WH , Jaspers NMWH , de Vriend MD Ferrari RHM
Published: March 2003

Objectives: To assess, in clinical practice, the (i) incidence, (ii) within-patient consistency, and (iii) clinical spectrum of chest symptoms (chest symptoms) after subcutaneous (sc) and oral sumatriptan, and (iv) to identify risk factors for chest symptoms. Design: Two-year retrospective survey with mailed self-administered questionnaire. Setting: Neurolgy outpatient clinic of university hospital. Subjects: Migraine patients with or without aura ( n=869). Main outcome measures: incidence, within-patient consistency and characteristics of chest symptoms; demographic and clinical characteristics of patients. Results: There were 735 (85%) respondents. Sumatriptan was used by 453 patients, during 25 months (median), for 28 000 attacks (median: 33 attacks/patient). Of sumatriptan users, 41 % (sc) and 24% (oral) had chest symptoms in all attacks, 39% (sc) and 58% (oral) in none, and the remaining in some attacks. Because of chest symptoms, 10% discontinued sumatriptan. Chest symptoms mostly consisted of heavy arms and chest pressure, started within 5 (sc) to 30 (oral) min, and lasted 30 (sc) to 60 (oral) min. Compared with patients without chest symptoms, patients with chest symptoms more often were females and younger, and went to rest immediately after sumatriptan administration (all p<0.001); they also tended to have lower body mass indices, more severe attacks and less efficacy of sumatriptan (all 0.001 p<0.05). Patients with chest symptoms had no higher incidence of cardiovascular symptoms or risk factors. Conclusions: Chest symptoms are frequent, within-patients consistent, but rarely important, adverse events of (notably sc) sumatriptan. The risk of chest symptoms is patient-dependent and not related, even opposite, to cardiovascular disease. This contradicts the hypothesis that chest symptoms after sumatriptan are caused by cardiac ischemia. Patient acceptance of chest symptoms is improved by pre-advising of the risk and nature of chest symptoms.
Agraphia as the Only Symptom of Migraine Aura
Authors: Evers S , Homann B , Vollmer J
Published: March 2003

A 37-year-old female migrain patient is described, who suffered from episodes with pure lexical agraphia as the only symptom of migraine aura. The MRI showed multiple subcortical white matter lesions. Central inflammatory and demyelinating disorders were excluded. This case suggests that, during a migraine aura, even very circumscribed brain areas involved in complex neuropsychological processing can be affected.
The Comorbid Association of Migraine with Osteoarthritis and Hypertension
Authors: Peroutka SJ , Price SC , Jones KW
Published: March 2003

Migraine is known to have a major genetic component and has been associated with a wide variety of comorbid disorders including arthritis and heart disease. Since migraine and some of its comorbid disorders involve inflammation, complement C3, a protein involved in acute inflammation, was selected for analysis as a candidate gene in an ongoing study of the genetic basis of migraine. Polymorphism frequencies for complement C3F (0.19) and C3S (0.81) in a sample of 137 unrelated migraineurs were found to be consistent with a control group as well as previous population studies, indicating that this common polymorphism has no association with migraine susceptibility. However, C3F positive individuals with migraine were found to have an increased incidence of osteoarthritis (Chi square = 10.06; p < 0.0008) and hypertension (Chi square = 5.18; p < 0.01). Therefore, the data in the present study indicate that certain migraine comorbidities that have been reported in the literature may result from Berkson's bias as opposed to a shared pathophysiological variation in the C3 gene.
Treatment of Migraine Attacks with A Long-Acting Somatostatin Analogue (Octreotide, SMS 201-995)
Authors: Kapicioglu S , Gökce E , Kapicioglu Z , Ovali E
Published: March 2003

Long-acting somatostatin analogue (SMS 201-995) inhibits serotonin, bradykinin, prostaglandins, substance P, and vasoactive intestinal peptide, which may be involved in migraine. We therefore decided to test the efficacy of SMS 201-995 in relieving the pain of acute migraine attacks. Headache relief was defined as a reduction in severity from grade 3 or 2 (severe or moderate) to 1 or 0 (mild or none). Patients experiencing migraine attacks were evaluated clinically. A double-blind parallel group trial was performed in which patients randomly received either a subcutaneous injection of placebo (saline) or SMS 201-995 (100 μg). SMS 201-995 was significantly more effective than placebo in reducing headache grade at 2 h (1.5 0.6 vs 2.2 0.7; p < 0.01), 4 h (1.6 ± 0.6 vs 2.1 ± 0.8; p < 0.05) and 6 h (0.8 ± 0.9 vs 2.1 ± 0.8; p < 0.001) after the initiation of treatment. By 6 h, apparent headache relief (reduction in severity from grade 3 or 2 to 1 or 0) was experienced in 76.5% of SMS 201-995 treated patients and 25% of the placebo-treated group. Headache relief was significantly better in patients taking SMS 201-995 ( p < 0.02). Furthermore, none of the patients became pain-free (headache grade 0) on placebo, while significantly more patients (47%) were pain-free on SMS 201-995 at 6 h ( p < 0.01). Headache improvement started significantly earlier in those patients treated with SMS 201-995 than with placebo. SMS 201-995 significantly improves the pain of migraine attacks, 2 h after the beginning of treatment. Additionally, we observed no side effects of SMS 201-995. We therefore conclude that a single dose of 100 μg given subcutaneously is an effective and well-tolerated agent for the treatment of migraine attacks.
Home-Based Behavioral Treatments for chronic Benign Headache
Authors: Haddock C Keith , Rowan AB , Andrasik F , Wilson PG , Talcott G Wayne , Stein RJ
Published: March 2003

Controlled clinical trials have consistently demonstrated that behavioral treatments for chronic benign headache produce clinically beneficial outcomes both post-treatment and at follow-up. Given these results there is interest in cost-reduction and redesign of these treatments to improve their accessibility. One promising approach in this regard is home-based headache treatment. These treatments seek to provide the same amount of treatment as clinic-based treatments; however, some of the material typically presented to the patient by a clinician is presented through home-study materials (e.g., manuals, audiotapes). To date, the published literature contains 20 controlled clinical trials which have examined the outcomes produced by home-based treatments. This article presents the first comprehensive meta-analysis of these clinical outcome studies. Results of the quantitative analyses suggest that home-based treatments produce comparable, or with certain outcome measures, superior results to clinic-based treatments. Moreover, cost-effectiveness scores of home-based treatments were found to be more than five times larger than those of clinic-based therapies. Methodological analyses are also presented along with suggestions for future research.
Oral and Subcutaneous Sumatriptan in the Acute Treatment of Migraine
Authors: Carpay HA , Matthijsse P , Steinbuch M , Mulde PGH
Published: March 2003

In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sum triptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41% improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.
Convergence of Occipital Nerve and Superior Sagittal Sinus input in the Cervical Spinal Cord of the Cat
Authors: Angus-Leppan H , Lambert GA , Michalicek J
Published: March 2003

Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches.
Migraine Therapy
Authors: Cohen ML , Johnson KW , Schenck KW , Phebus LA
Published: March 2003

Canine and rabbit vascular contractile responses to serotonergic agonists have been used to predict antimigraine efficacy for several antimigraine agents, including sumatriptan. The purpose of the present study was to establish the assumed predictive value of contractile responses in canine and rabbit saphenous veins to contractile efficacy for a series of agonists in human cerebral and coronary arteries and to understand better the receptors mediating such responses. The canine and rabbit saphenous veins contracted similarly (both qualitatively and quantitatively) to series of structurally diverse serotonergic agonists, suggesting that the receptors mediating serotonin-induced contractility in these tissues were similar. In addition, the contractile potency (estimated as EC50 values) for these structurally diverse serotonergic agonists in either the rabbit or canine saphenous vein significantly correlated with contractile potency for these agonists in human cerebral arteries. Thus, to the extent that contractile responsiveness of human cerebral arteries may predict antimigraine agents, contractile responses of the rabbit and/or canine saphenous vein may be useful surrogates for antimigraine efficacy. In addition, the contractile potency for this series of serotonergic agonists in the rabbit or canine saphenous vein significantly correlated with contractile potency of these agonists in human coronary arteries. These data suggest that the use of the saphenous vein to identify potent vasoconstrictors will also reveal agents capable of contracting human coronary arteries, a liability for using this approach to evaluate promising antimigraine therapies.
Erythrocyte and Plasma Levels of Glutamate and Aspartate in Children Affected by Migraine
Authors: D'Eufemia P , Finocchiaro R , Lendvai D , Celli M , Viozzi L , Troiani P , Turri E , Giardini O
Published: March 2003

In this study we determined plasma and erythrocyte amino acids in children affected by migraine, in order to evaluate glutamate and aspartate metabolism in the pathogenesis of this disorder. Fifteen children with migraine with aura (mean ageSD=10.31.56), 19 children with migraine without aura (mean ageSD=10.41.48) and 16 healthy normal controls (mean ageSD 10.61.53) were investigated. In both migraine groups there were significantly lower plasma glutamate and aspartate levels and significantly higher erythrocyte/plasma concentration (E/P) ratios of these amino acids with respect to the controls. Erythrocyte aspartate concentrations were significantly elevated in migraine children compared to the controls, while erythrocyte glutamate concentrations showed no significant differences between groups. Similar results were observed in both migraine groups. These results seem to suggest the presence of a higher activity of the erythrocytes' glutamate/aspartate transport system that could reflect a similar alteration at the neuronal/glial cell level in the CNS. Our study suggests an imbalance of the excitatory amino acid turnover in the pathogenesis of migraine in children.
The M-Chlorophenylpiperazine Test in Cluster Headache
Authors: Leone M , Attanasio A , Croci D , Libro G , Grazzi L , D'Amico D , Nespolo A , Bussone G
Published: March 2003

The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at 30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima: delta maximum = maximum response-baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol ( p<0.02) and increased PRL ( p<0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels ( p<0.05) and reduced basal PRL plasma levels ( p=0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology.
Olfaction in Migraine
Authors: Snyder RD , Drummond PD
Published: March 2003

Olfactory thresholds for acetone and vanillin and the unpleasantness rating of concentrated acetone were measured in 20 migraine sufferers and 21 controls. The olfactory threshold for vanillin was lower in migraine sufferers than in controls. In addition, patients who reported that odours frequently seemed stronger during attacks of migraine were able to detect acetone, at a lower concentration than most other patients. No differences were found between migraine sufferers and controls for ratings of the unpleasantness of concentrated acetone. These findings suggest that hyperacuity to odours persists between episodes of migraine. Sensitivity to odours could contribute to the migraine predisposition.
Post-Lumbar Puncture Headache
Authors: Vilming ST , Kloster R
Published: March 2003

The aim of the present prospective study was to describe clinical features of post-lumbar puncture headache (PPH), and to test the validity of the diagnostic criteria of the International Headache Society (IHS). Eighty-eight of the 239 included patients (36.8%) experienced PPH. Females were affected more frequently than males (45.2% vs 21.4%; p<0.001) First onset of PPH occurred within the first day in 40 patients (53%), within 2 days in 89%, and never after the fourth day. When PPH occurred for the first time on the day the lumbar puncture was performed, it was usually experienced much later in the day (median 14.00 h) than it first occurred on the second day (median 09.30 h) or later. The median duration of PPH was 6 days (range 1–29 days). Patients with headache performed a “Rising Manoeuvre” twice daily as long as the headache period lasted, and recorded pair and time variables. The severity of PPH was negatively correlated to the time till the headache started or worsened upon rising (T1 and the time from the headache started to increase till it reached its maximum (T2) but was not significantly correlated to the time to restitution upon lying down (T3). The results are in good accordance with the leakage theory. T1 varied from immediate onset to 265 min (median 20 sec). T2 (median 30 sec, range 0–60 min) and T3 (median 20 sec, range 0–15 min) varied considerably as well. During the course of PPH, 45% of the patients occasionally reported non-postural headache or no headache when the Rising Manoeuvre was performed. It is suggested that PPH should be diagnosed in any patient who experiences postural headache at least once within 4 days of lumbar puncture.
Ineffectiveness of Neurokinin-1 Antagonist in Acute Migraine
Authors: Goldstein DJ , Wang O , Saper JR , Stoltz R , Silberstein SD , Mathew NT
Published: March 2003

Lanepitant is a high-affinity selective neurokinin-1 receptor (NK-1) and is effective in the dural inflammation model of acute migraine. Lanepitant 30, 80, and 240 mg given orally was evaluated in a double-blind, placebo-controlled crossover study to determine its effect in reducing migraine pain and severity of associated symptoms. Outpatients treated four migraine headaches of moderate or severe pain intensity with study drug according to a randomization schedule. They recorded their pain intensity and severity of migraine-associated symptoms at 30, 60, 90, and 120 min. Although 53 patients were randomly allocated to a treatment sequence, only 40 patients, completed all treatments. There was no statistically significant difference in improvement in migraine pain at any time for any of the treatments. Additionally, there was no change in severity of migraine associated symptoms associated with lanepitant therapy. No adverse events could be attributed to lanepitant Lanepitant was ineffective orally in treating acute migraine in this trial. This may be due to poor bioavailability during a migraine attack. Alternatively, the neurogenic inflammation hypothesis may not apply to migraine.
Serotonin Metabolism in Chronic Tension-Type Headache
Authors: Bendtsen L , Jensen R , Hindberg I , Gammeltoft S , Olesen J
Published: March 2003

Serotonergic neurons play a major role in the regulation of pain and may therefore also be involved in the pathophysiology of tension-type headache. Platelets are important in the regulation of the free serotonin level in plasma and may be a model of serotonergic neurons. The aim of the present study was to investigate the peripheral serotonin (5HT) metabolism in patients with chronic tension-type headache. The 5HT levels in platelets and in plasma, the beta-thromboglobulin (ß-TG) levels in plasma, and the urinary excretion of 5-hydroxyindoleacetic acid (5HIAA) were measured in 40 patients with chronic tension-type headache and in 40 healthy controls. The platelet uptake index was calculated as the ratio between platelet 5HT and plasma 5HT levels. There were, no significant differences in platelet 5HT, plasma 5HT ß-TG, or 5HIAA between patients and controls. The platelet uptake index was significantly lower in patients 243 (136-367) than in controls 352 (202-508), p=0.03. Our results indicate that the peripheral 5HT metabolism is largely normal in patients with chronic tension-type headache.
Altered Allelic Distributions of the Serotonin Transporter Gene in Migraine Without Aura and Migraine with Aura
Authors: Ogilvie AD , Russell MB , Dhall P , Battersby S , Ulrich V , Smith CA Dale , Goodwin GM , Harmar AJ , Olesen J
Published: March 2003

Allelic variation of the human serotonin transporter gene (HSERT), a highly plausible candidate gene for susceptibility to migraine, was investigated in 266 individuals with migraine, including 173 having migraine without aura (MO), 94 having migraine with aura (MA), 18 with co-occurrence of MO and MA, plus 133 unaffected controls. The distribution of a polymorphism with different forms of a variable tandem number repeat (VNTR) in intron 2 were compared. The MO group had an over-representation of genotypes with two twelve repeat alleles (STin2.12) and a reduction of genotypes containing one ten repeat (STin2.10) compared to controls. The MA group showed a similar pattern, but also a trend towards an increase in genotypes containing the nine repeat allele of the VNTR (STin2.9). Genotypes containing this allele were found in 6.4% of the MA group compared to 2.3% of controls. The group with co-occurrence of MO and MA had a significantly different pattern of overall allele frequency distribution from controls, reflecting a reduction in genotypes containing the STin2.10 allele and a shift both to STin2.9 carriers and to STin2.12 homozygosity. These results support the view that susceptibility to MO and MA has a genetic component, that these disorders are distinct, and that genetic susceptibility may in some cases be associated with a locus at or near the serotonin transporter gene.
Cognitive Processing in Migraine: A Failure To Find Facilitation in Patients with Aura
Authors: Palmer JE , Chronicle EP
Published: March 2003

Recent interest in cognitive processing in migraine has been based on the assumption that cortical hyperexcitability in migraine with aura may manifest itself in the form of response time advantages in migraine as compared to controls. The study reported here attempted to replicate and extend the findings of Wray and colleagues (Brain 1995;118:25–35). Using identical cognitive tasks, three experiments failed to find differences between migraine with aura patients and controls: furthermore, an additional group of patients without aura were also statistically indistinguishable from controls with respect to response times. Error rates were consistently high across experiments, indicating that subjects were responding at or near chance levels. These findings cast doubt on the utility of straightforward cognitive psychological methods for the study of cortical hyperexcitability in migraine. Some theoretical difficulties concerning the interpretation of response times in the context of migraine pathophysiology are discussed.
Cerebral Dura Mater and Cephalalgia: Relationships Between Mast Cells and Catecholaminergic Nerve Fibers in the Rat
Authors: Artico M , De Santis S , Cavallotti C
Published: March 2003

The aim of the present study was to examine whether mast cells have the same variations as the related catecholaminergic nerve fibers. Chemical sympathectomy or surgical removal of right superior cervical ganglion induced a rapid decrease of fluorescence in both nerve fibers and mast cells, as confirmed by quantitative analysis (nerve fibers 19±1.1 vs 1.3±0.6; mast cell 10.8±1.9 vs 2.1±0.3). The results of quantitative analysis after nerve fiber stimulation (electrical), however, showed an increase of the fluorescence in both the nerve fibers and the mast cells (nerve fibers 43.4 ±2.4; mast cells 18.6 ±1.6). Moreover, we found that the basal zone is more innervated (regarding catecholaminergic nerve fibers) than the apical one, and that the fluorescence level decreases passing from the vasal zone to the perivasal and intervasal zones. Further studies are needed in order to clarify the role of fluorescent nerve fibers and mast cells of cerebral dura mater in cephalalgia.
Age-Related Cerebrovascular Disease Alters the Symptomatic Course of Migraine
Authors: Meyer JS , Terayama Y , Konno S , Margishvili GM , Akiyama H , Rauch RA , Mortel KF , Wills PM
Published: March 2003

Migraine headaches usually decrease in frequency and severity and often cease during advancing age. Occasionally, migraineurs report late-life migrainous accompaniments, i.e., auras without headache, particularly when typical migraine attacks terminate or diminish following major or minor strokes, at which time the auras may become atypical. Clinical observations such as these suggest that degenerative cerebrovascular changes accompanying aging may modify the course of migraine headaches particularly those with aura. To test this hypothesis, we quantitated age-related changes in cerebral vasodilator capacitance by measuring local cerebral blood flow utilizing xenon contrast computed tomography (CT) scanning before and after oral administration of the pharmacological cerebral vasodilator, acetazolamide (Diamox®). Measurements were compared among 27 normal volunteers without headache (aged 24–94 years; mean age 61.1 ± 17.6) and 37 carefully categorized groups of migraine patients (aged 27–83 years; mean age 59.4 ±12.4). The normals comprised Group A. Migraineurs were divided into two subgroups: Group B consisted of 27 migraineurs with and without aura who continued to suffer from incapacitating and frequent headaches and Group C consisted of 10 migraineurs who no longer suffered from severe and frequent headaches, two of whom still complained of atypical auras of the “late-life migrainous accompaniments” type. Cerebral vasodilator capacitance significantly declined with advancing age among normals and the two groups of migraineurs, confirming the development of age-related cerebrovascular diseases. Global CBF increases after Diamox® in Group B (with persistent and severe migraine), were significantly greater compared with normals without headache, and with Group C consisting of migraineurs whose headaches had decreased, subsided, or become replaced by late-life migrainous accompaniments (Group C). Results establish that cerebrovasodilator capacitance declines with advancing age, probably due to progressive cerebral atherosclerosis, since these declines were accentuated by risk factors for stroke, particularly TIAs or documented lacunar infarcts by CT. Progressive impairments of cerebral vasodilator capacitance among migraineurs were associated with: (i) reductions in frequency and severity of migrainous cephalalgia and (ii) appearance of late-life migrainous accompaniments.
Orbital Pain as an Isolated Sign of Internal Carotid Artery Dissection, A Diagnostic Pitfall
Authors: Guillon B , Biousse V , Massiou H , Bousser M-G
Published: March 2003

Head pain is one of the main presenting symptoms of internal carotid artery (ICA) dissection, us association with ischemic and/or local signs such as Homer's syndrome, lower cranial nerve pal tinnitus. In rare cases, head pain remains isolated and mimics other conditions. We report a patie suffered isolated prolonged orbital pain as the only sign of intrapetrous ICA dissection. Early recog such unusual facial pain may be crucial in decreasing the risk of secondary cerebral or retinal ische
Cerebral Blood Flow Changes in Pseudomigraine with Pleocytosis Analyzed by Single Photon Emission Computed Tomography. A Spreading Depression Mechanism?
Authors: Fuentes B , Diez Tejedor E , Pascual J , Coya J , Quirce R
Published: March 2003

Pseudomigraine with pleocytosis is a benign and autolimited syndrome. The etiology has been related to viral infection, but its pathophysiology is not yet well identified. To investigate this point, and to see if there were changes in cerebral blood flow (as in migraine), we performed single photon emission computed tomography (SPECT) studies in four patients who fulfilled the diagnostic criteria for this syndrome. This was done during the acute phase and we repeated SPECT after resolution of the syndrome in two of them. We found a reduction in brain blood flow on the side of origin of the neurological deficits during the acute phase. This normalized after recovery of the syndrome. The finding suggests that the neurological deficits in this syndrome could be produced by a spreading depression-like mechanism similar to that proposed for migraine with aura.
Cluster Headache and Lifestyle: Remarks on A Population of 374 Male Patients
Authors: Manzoni GC
Published: March 2003

To investigate the relation between cluster headache (CH) and lifestyle, some lifestyle factors were considered in a population of 374 CH male patients consecutively referred to the same headache center, including 306 with episodic CH, 22 with chronic CH unremitting from onset, 20 with chronic CH evolved from episodic, and 26 with CH periodicity undetermined. CH patients had jobs involving greater responsibilities and were more frequently self-employed than controls. In addition, their past medical histories often reported head injury, either with loss of consciousness (13.4%) or without loss of consciousness (23.5% of cases). As regards nonessential consumption habits, both cigarette-smoking and coffee and alcohol intake were more frequently reported in CH patients than in the general population, with a higher prevalence in chronic CH as opposed to episodic CH sufferers. In particular, smokers accounted for 78.9% of episodic CH patients and 87.8% of chronic CH patients—12.9% of episodic CH patients and 19.6% of chronic CH patients smoked over 30 cigarettes a day. Alcohol abuse was reported in 16.2% of episodic and 26.8% of chronic CH patients, while coffee abuse was reported in 6.9% of episodic and in 36.6% of chronic CH patients. Rather than pointing to a single lifestyle factor directly implicated in CH onset, my review suggests a common trend among CH patients to overindulge in certain living habits.
A Double-Blind, Randomized, Crossover Assessment of Blood Pressure Following Administration of Avitriptan, Sumatriptan, Or Placebo To Patients with Mild To Moderate Hypertension
Authors: Jhee SS , Salazar DE , Ford NF , Fulmor IE , Sramek JJ , Cutler NR
Published: March 2003

We examined the effects of avitriptan, a 5-hydroxytiyptamine 1-like (5HT1) receptor agonist for the treatment of migraine, in patients with medicated, controlled, mild to moderate hypertension relative to placebo and sumatriptan. The study was randomized, double-blinded, placebo-controlled, and 4-way crossover in design. Twenty patients (12M, 8F) participated. As required by protocol, all were stable on medications for mild to moderate hypertension, with a supine diastolic blood pressure of < 95 mmHg. Qualified subjects were randomized to receive oral administration of either 75 or 150 mg of avitriptan, 100 mg sumatriptan or placebo during the four treatment visits. Supine blood pressure and pulse rates were recorded up to 24 h after drug administration. Avitriptan 150 mg significantly increased peak diastolic and systolic blood pressure, and mean arterial pressure compared to placebo and sumatriptan 100 mg ( p < 0.05). Only those hypertensive patients receiving medication for hypertension should receive anti-migraine medications, such as avitriptan, which are 5HT1-like receptor agonists.
Dynamic Changes of Cognitive Habituation and Serotonin Metabolism During the Migraine Interval
Authors: Evers S , Quibeldey F , Grotemeyer K-H , Suhr B , Husstedt I-W
Published: March 2003

Migraine patients show a specific cognitive processing with a loss of habituation in the interval and a normal habituation in the attack as measured by event-related potentials (ERPs). It is unknown whether the loss of habituation changes during the migraine interval or is a stable state. Serotonin (5HT) metabolism is involved in the pathophysiology of migraine and also in the generation of ERPs. We enrolled 14 patients with regular migraine attacks in order to measure visually evoked ERPs repetitively during the migraine interval and in the migraine attack. Cognitive habituation was evaluated by analysis of P3 latency. Platelet serotonin content and free serotonin plasma level were measured at the same time points. The loss of habituation increased continuously during the migraine interval and abruptly normalized in the migraine attack ( p < 0.05, time series analysis). The platelet 5HT content decreased significantly in the migraine attack ( p < 0.03) and was at its maximum in the middle of the interval. The P3 latency was significantly increased in the attack ( p < 0.01) and was significantly inversely correlated with the platelet 5HT content ( r= -0.44, p < 0.001). Free 5HT plasma levels did not show any significant change. Our findings suggest that loss of cognitive habituation continuously increases during the migraine interval until its normalization in the migraine attack. This phenomenon cannot be attributed to serotonergic transmission. In patients with regular changes of cognitive habituation before the migraine attack, it might be possible to predict the attack by analysing ERPs.
Migraine Prescription Density and Recommendations. Results of the pcaom Study
Authors: Krobot KJ , Steinberg HW , Pfaffenrath V
Published: March 2003

We estimate the extent to which recommendations on the prevention and treatment of migraine issued by professional medical bodies are implemented in medical practice in Germany. Computerized data (MediPlus, IMS Health) were analyzed in 4,636 male and 16,573 female migraineurs from 383 primary care practices 1994 through 1996 (Primary Care of Migraine, PCAOM study). A total of 90,540 drug prescriptions with a documented diagnosis of migraine were issued in 45,669 person-years (1.492 prescriptions [DM 40.99] per person-year to men, 2.109 prescriptions [DM 62.01] per person-year to women). Approximately three of every four prescriptions were incompatible with the recommendations of the German Migraine and Headache Society (DMKG), amounting to extrapolated costs of DM 49 million per year borne by the German statutory health insurance fund for combination migraine preparations. The density of non-DMKG therapies for diagnosed migraine followed a sigmoid curve with increasing patient age, while DMKG-compliant therapies described a bell-shaped curve. Referrals to neurological care specialists were not associated with subsequent primary care focus on recommended therapies. We conclude that medication prescribed for migraine is largely not according to long-standing recommendations by medical societies in Germany.
Cluster Headache-Like Pain in Multiple Sclerosis
Authors: Leandri M , Craccu G , Gottlieb A
Published: March 2003

We describe a case with simultaneous occurrence of cluster headache-like pain and multiple sclerosis. Both neuroimaging and neurophysiology (trigeminal evoked potentials) revealed a demyelination plaque in the pons, at the trigeminal root entry zone, on the side of pain. Although that type of lesion is usually associated with trigeminal neuralgia pain, we hypothesize that in this case it may be linked with the concomitant cluster headache, possibly by activation of trigemino-vascular mechanisms.
Clinical Characteristics of Migraine in A Population-Based Twin Sample: Similarities and Differences Between Migraine with and Without Aura
Authors: Kallela M , Wessman M , Färkkilä M , Palotie A , Koskenvuo M , Honkasalo M-L , Kaprio J
Published: March 2003

Objective: To look into clinical differences between migraine with and without aura in a population-based sample of migraineurs.

Background: Migraine presents in two major forms, migraine with and migraine without aura. With the exception of the aura phase, the clinical characteristics of these entities are very similar. Despite this, however, the recent epidemiological data underline differences between migraine with and without aura. We tried to examine whether other features besides the aura differ between these two major forms of migraine.

Methods: We studied 321 twins suffering from migraine with aura and 166 twins with migraine without aura from the population-based Finnish Twin Cohort. Migraine was diagnosed according to the criteria of the International Headache Society (MS). Analysis was based on the combination of a mailed questionnaire and a telephone interview by a neurologist. Special attention was paid to differences between migraine with and without aura.

Results: Some qualities of headaches differed between IHS defined migraine with and without aura. Unilateral headache (Chi-squared p=0.039) and photophobia (Chi-squared p=0.010) were more typical for migraine with aura, while nausea was more typical for migraine without aura (Chi-squared p=0.002). Duration of headache in migraine without aura was also longer man in migraine with aura (Mann-Whitney U-test 0.007).

Conclusions: There are clinical differences between IHS defined migraine with and without aura; even the headache phase between the two entities differs. It is worthwhile distinguishing between them when looking for the elusive genes for these more common forms of migraine.
Intracellular Mg++ Concentration and Electromyographical Ischemic Test in Juvenile Headache
Authors: Mazzotta G , Sarchielli P , Alberti A , Gallai V
Published: March 2003

One-hundred-and-twenty-eight young headache outpatients underwent an electromyographical (EMG) ischemic test and determination of Mg+ + levels in red and mononuclear blood cells. In migraine patients, with and without aura (MwA and MwoA), Mg+ + concentration in the erythrocytes and in mononuclear cells was significantly reduced compared to tension-type headache (TTH) patients and healthy controls ( p <0.0001). The EMG ischemic test was positive in 71% of migraineurs, but only in 9.5% of TTH patients. Low intra-erythrocyte and mononuclear cell levels were evident in 84.3% and 81.2% of migraine patients, respectively; those whose ischemic tests were positive had intra-erythrocyte and mononuclear cell levels of Mg+ + below the norm, respectively. However, reduced levels of Mg+ + in erythrocytes were found in only two patients with TTH, and in mononuclear cells in one patient with TTH. These data provide further confirmation of the role of Mg+ + in determining the status of neuromuscular hyperexcitability in about two-thirds of migraine patients, including childhood and adolescence. They also support the validity of carrying out EMG ischemic testing for distinguishing this condition, which can be corrected with adequate oral Mg+ + supplementation and with a possible positive impact on headache.