bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Familial Hemiplegic Migraine a Hereditary form of Basilar Migraine?
Authors: Haan J , Terwindt GM , Ophoff RA , Bos PLJM , Frants RR , Ferrari MD
Published: March 2003

We studied aura symptoms in 83 patients from 6 unrelated families suffering from familial hemiplegic migraine. Fifty-five of the patients reported symptoms that allowed us to categorize them as basilar migraine (BM) patients, in accordance with the International Headache Society (IHS) criteria. In a control group of 33 patients suffering from migraine with aura and 33 patients suffering from migraine without aura, 9 patients complained of vertigo, and only one patient of diplopia during one of her attacks. None of these control patients fulfilled the IHS criteria for BM We suggest that familial hemiplegic migraine and BM may share certain pathophysiologic mechanisms, which may consist of a (genetically determined) disturbance of basilar artery blood flow.
Effects of Increasing the Intracranial Blood Volume in Cluster Headache Patients and Controls
Authors: Hannerz J , Jogestrand T
Published: March 2003

Eleven patients with episodic cluster headache in period, five patients out of period and six controls were studied concerning the effects of an increase of the intracranial blood volume by tilting. Common carotid artery (CCA) blood flow was similar in all three groups at baseline and during tilting. CCA diameters were similar at baseline and increased during tilting in all three groups, indicating that tilting caused an increase in the extra- and intracranial blood volume. Unilateral pain or sympathetic dysfunction did not appear during tilting in the patients out of period or in the controls. In four of eight studied patients with cluster headache in period, unilateral miosis and ptosis appeared during tilting. Two of these four patients developed intense unilateral pain, while the other two did not report any pain. Four other patients developed slight unilateral pain but no sympathetic dysfunction during tilting.
Sympathetic-Parasympathetic Activation During Spontaneous Attacks of Cluster Headache: Evaluation by Spectral Analysis of Heart-Rate Fluctuations
Authors: Marinis M De , Strano S , Granata M , Urani C , Lino S , Calcagnini G , Virgilio V Di , Calcagnini G
Published: March 2003

Twenty-four hour ECG Holter and blood-pressure monitorings were performed in eight patients suffering from cluster headache. Spectral analysis of heart-rate fluctuation was used to assess the autonomic balance under basal conditions, after head-up tilt, and during a spontaneous attack. Normal autonomic balance was found at rest and during sympathetic activation obtained with head-up tilt in the interparoxysmal period. Before the onset of headache, an increase in the low-frequency (LF) component of the power spectrum was apparent in all patients. This sign of sympathetic activation was followed by an increase in the high-frequency (HF) component that developed about 2000 beats after the onset of headache and rapidly overcame the LF component until the end of pain. Significant differences were found when comparing the spectral parameters [total spectral values (TP), power of the LF and HF components and LF/HF ratio] obtained before, during and after headache. During the attack, blood pressure increased and heart rate decreased in all subjects. There appears to be a primary activation of both sympathetic and parasympathetic functions in cluster headache attacks. The sympathetic component seems to be involved mostly in the development of the attack, whereas the parasympathetic activation seems to occur, following the onset of the attack, independently of the pain.
Side Effects of Ergotamine
Authors: Meyler WJ
Published: March 2003

Ergotamine has been used for many years in the treatment of migraine, although there is little formal clinical evidence that it is significantly more efficacious than placebo. A number of side effects associated with ergotamine have been reported in the literature, including myocardial infarction, ischaemia of limb extremities, and fibrotic changes. Long-term use has led to reported cases of ergotamine-induced headache, vascular reactivity, and subclinical ergotism. When the safety profile of this drug is considered, coupled with its debatable efficacy from a clinical review previously published, the resulting poor risk: benefit ratio brings into question the continued use of ergotamine as a migraine treatment and calls for better controlled trials of its efficacy, or lack of, in the acute treatment of migraine.
Mig Access: A Population-Based, Nationwide, Comparative Survey of Access to Care in Migraine in France
Authors: Michel P , Pariente P , Duru G , Dreyfuss J-P , Chabriat H , Henr P
Published: March 2003

A national control-matched survey was conducted in France to evaluate the access of migraineurs to health care. A validated IHS criteria-based diagnostic procedure for screening was conducted in adults drawn from a sample of 6,000 house holds. A group of 650 subjects fulfilling the IHS criteria for migraine were matched by sex, age and activity status with a group of non-headache, non-migraine controls. Response rates were 87% and 82% for the migraineurs and the controls, respectively. The comparability of the groups was demonstrated by the absence of statistical differences between either respondents versus non-respondents or migraineurs versus controls for sex, age and occupation. The 3-month prevalence of migraine was estimated at 13% (95% CI: 12–14). The health care consumption of migraineurs was not higher than that of the controls. Migraineurs rarely consult for headaches and seem to content themselves with their routine analgesic treatment. They believe, however, that improvement in their condition is possible and discuss this with their physicians. This ambivalent attitude mainly reflects a fatalistic outlet which may constitute the major obstacle of an improved management of migraine.
Headache as an Occupational Illness in the Treatise “De Morbis Artificum Diatriba” of Bernardino Ramazzini∗
Authors: Zanchin G , Rossi P , Maggioni F , Isler H
Published: March 2003

The treatise “De morbis artificum diatriba” (Modena, 1700) is considered to be the first text to specifically deal with occupational illnesses. It was also the last for over 150 years. Written by Bernardino Ramazzini (Carpi, 1633-Padua, 1714), a professor at the University of Padua from 1700 to 1714, the book highlights the importance given at the time to headache as an occupational symptom. Among the 69 professions described, accounting for the majority of the occupations of the period, 12 were found to lead to headache as an important symptom caused by work. Ramazzini appears to have paid more attention to this than we do today. Ramazzini's work opens up a wide view on social conditions in the 18th century, as his sensitivity for occupational hazards was exceptional. His remarks on headache are typical of his way of collecting first-hand experience of working conditions, and they underline the importance of occupational hazards in the assessment of headache, today just as in 1710.
IHS Criteria and Gender: A Study on Migraine and Tension-Type Headache in Children and Adolescents
Authors: Wöber-Bingöl C , Wöber C , Wagner-Ennsgraber C , Zebenholzer K , Vesely C , Geldner J , Karwautz A
Published: March 2003

The aim of this study was to investigate whether the IHS criteria for migraine and tension-type headache depend on gender. Among 409 children and adolescents with recurrent idiopathic headache seen at a university outpatient clinic, girls had significantly more often migraine with aura. Also, there was a trend towards a higher frequency of tension-type headache in girls. In migraine, aggravation of headache by physical activity and occurrence of aura symptoms were more common in females, whereas vomiting and phonophobia occurred more often in males. In tension-type headache, females more often reported mild intensity of headache. All other criteria were similar in both sexes. Age influenced the expression of some of the accompanying symptoms in the various types of migraine, but had only minimal influence on other diagnostic criteria of migraine and tension-type headache in females as well as in males. Our study suggests that the frequency of migraine (except that of migraine with aura) is similar among girls and boys, that tension-type headache may occur more often in girls, and that gender has some influence on the IHS criteria for migraine, but almost no influence on those of tension-type headache.
Sumatriptan: Vasoactive Effect on Human Dural Vessels, Demonstrated by Subselective Angiography
Authors: Henkes H , May A , Kühne D , Berg-Dammer E , Diener HC
Published: March 2003

Sumatriptan, a selective 5-hydroaytryptamine (5HT1D)-receptor agonist, has recently been introduced in the pharmacotherapy of acute migraine attacks. The potential vasoactive effect of sumatriptan on human dural vessels in vivo, however, is still a matter of controversy. We investigated the effects of sumatriptan on dural vessels after subcutaneous or intra-arterial injection. During interventional angiography, the middle meningeal artery (MMA) of nine patients was catheterized with a microcatheter using the transfemoral route. Three MMA were entirely normal, two supplied a dural arteriovenous fistula (AVF) and four were transdural feeders to a brain arteriovenous malformation (AVM). Sumatriptan was injected either into the subcutaneous tissue of the right shoulder (6 mg, two patients) or into the catheterized MMA (2 mg, six patients). The substance caused a marked vasoconstriction of the three normal MMA, visible angiographically and confirmed by intravascular Doppler ultrasonography. Vasoconstriction was still present in the last angiogram obtained 15 min post-injection. Slightly hypertrophied feeders to dural AVF and to brain AVM showed some vasoconstriction in one and four patients, respectively. In two patients with markedly hypertrophied dural feeders to a dural AVF and to a brain AVM, respectively, rapid shunting probably prevented obvious vasoactive effects of sumatriptan. The data obtained by angiography and intravascular Doppler ultrasonography provide strong evidence that sumatriptan has a vasoconstrictive effect on normal as well as hypertrophied dural vessels.
Migraine Without Aura and Migraine with Aura Are Distinct Clinical Entities: A Study of Four Hundred and Eighty-Four Male and Female Migraineurs From the General Population
Authors: Russell MB , Rasmussen BK , Fenger K , Olesen J
Published: March 2003

The clinical characteristics of migraine without aura (MO) and migraine with aura (MA) were compared in 484 migraineurs from the general population. We used the criteria of the International Headache Society. The lifetime prevalence of MO was 14.7% with a M:F ratio of 1:2.2; that of MA was 7.9% with a M:F ratio of 1:1.5. The female preponderance was significant in both MO and MA. The female preponderance was present in all age groups in MA, but was first apparent after menarche in MO, suggesting that female hormones are an initiating factor in MO, but not likely so in MA. The age at onset of MO followed a normal distribution, whereas the age at onset of MA was bimodally distributed, which could be explained by a composition of two normal distributions. The estimated separation between the two groups of MA was at age 26 years among the females and age 31 years among the males. The observed number of persons with co-occurrence of MO and MA was not significantly different from the expected number. The specificity and importance of premonitory symptoms are questioned, but prospective studies are needed. Bright light was a precipitating factor in MA, but not in MO. Menstruation was a precipitating factor in MO, but not likely in MA. Both MO and MA improved during pregnancy. The clinical differences indicate that MO and MA are distinct entities.
Variations in the Platelet Arginine/Nitric Oxide Pathway during the Ovarian Cycle in Females Affected by Menstrual Migraine
Authors: Sarchielli P , Tognoloni M , Russo S , Vulcano MR , Feleppa M , Malà M , Sartori M , Gallai V
Published: March 2003

Previous studies have reported the existence of an arginine/nitric oxide (NO) pathway and the involvement of a Ca2+, NADPH-dependent nitric oxide synthase enzyme (NOS) in the generation of NO in human platelets. In the present research, we determined the rate of production of NO and cGMP in the cytosol of platelets stimulated by collagen in 20 females with menstrual migraine (MM), (age range 2440 years), assessed in the follicular and luteal phases, interictally and ictally in the latter period. The same patients were also assessed at mid-cycle. At the same time, the variations in the collagen response of platelets were evaluated. Moreover, these parameters were determined in the same periods in 20 age-matched control females and in 20 females affected by non-menstrually related migraine (nMM). The collagen-stimulated production of NO in the cytosol of the platelet cytosol was significantly higher in migraine patients with MM than in the control subjects. In MM patients, the increase was greater in the luteal phase of the cycle than during the follicular phase ( p<0.005). A rise in NO production in platelets was also present, although to a lesser extent, in females affected by nMM compared to the healthy females, but this rise was most evident at ovulation ( p<0.001). A slight but significant increase was also observed at mid-cycle in control women, but this increase did not reach the values determined in the migraine groups ( p<0.02). NO production in platelets stimulated by collagen was significantly increased during attacks with respect to the interictal period in both patient groups. Similar variations were observed in the production of cGMP in MM and nMM patients. The increase in NO production was accompanied by a decrease in platelet aggregation in the migraine groups compared with the control group; this decrease was most evident at mid-cycle in nMM patients and in the luteal phase in MM patients. These data suggest an activation of the L-arginine/ NO pathway in MM and nMM patients which could explain the modifications in the platelet response to collagen evidenced in migraine-free periods and during attacks. The activation of this pathway is more accentuated in the luteal phase in MM patients, and this could be the cause of the increased susceptibility to migraine attacks in premenstrual and menstrual periods in these patients.
A Within-Patient Comparison of Subcutaneous and Oral Sumatriptan in the Acute Treatment of Migraine in General Practice
Authors: Gruffydd-Jones K , Hood CA , Price DB
Published: March 2003

This study compared, for the first time in the United Kingdom, the efficacy and safety of oral 100 mg and subcutaneous 6 mg sumatriptan within a patient for the acute treatment of migraine. The patient's preference for the two formulations of sumatriptan were also recorded. The study was a multicentre, randomized, open, crossover design with an optional open parallel group extension. Individual attacks were treated with one formulation only. Over 10% of patients who treated attack 1 in both treatment periods of the crossover phase reported headache relief with each formulation at 4 h. Only 3% of patients failed to respond to at least one of the formulations at this time point. At the end of the crossover phase patient preference for the injection more than doubled from the pretreatment level in those patients who were previously naive to sumatriptan. During the optional phase of the study, 38% of patients chose to treat some attacks with oral and some with subcutaneous sumatriptan. The main reason for choosing injection was speed of relief, whilst convenience was the major reason for the use of the tablet.
Ketoprofen and Carotico-Cavernous Fistula
Authors: Burton EA , Jamieson DG
Published: March 2003

Whilst treating a patient with traumatic direct carotico-cavernous fistula, pain relief was difficult to achieve. Adequate doses of ibuprofen and codeine were ineffective, but single doses of ketoprofen alleviated pain in a reproducible manner. Although similar in analgesic efficacy to codeine, and a potent inhibitor of cyclooxygenase like ibuprofen, ketoprofen has other actions which may account for the differential response seen. This observation may help elucidate the nature of local mediators involved in the pathogenesis of vascular headache pain.
Clinical Studies of Valproate for Migraine Prophylaxis
Authors: Rothrock JF
Published: March 2003

Within the last decade our understanding of the pathophysiologic mechanisms which generate migraine has expanded considerably. Accompanying these advances in basic science, new agents designed to treat migraine acutely have exhibited unprecedented pharmacologic selectivity and clinical efficacy. While these abortive agents clearly can provide many migraine patients with a degree of headache control they previously have not enjoyed, such treatment typically will not provide lasting benefit to individuals whose headaches are more pervasive and may require stabilization through effective prophylactic therapy. Unfortunately, our arsenal of agents for migraine prophylaxis has not grown as rapidly as that of the abortive medications, and for the most part clinicians and patients are left to rely upon a small handful of “traditional” drugs for that purpose. One notable exception to this is divalproex sodium; the safety and efficacy of this new agent for migraine prevention have been documented consistently in a series of recent clinical trials.
Lamotrigine versus Placebo in the Prophylaxis of Migraine with and Without aura
Authors: Steiner TJ , Findley LJ , Yuen AWC
Published: March 2003

Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine ( n=37) or placebo ( n=40) for up to 3 months. Initially lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.
Nitric Oxide Synthase Inhibition in the Histamine Headache Model
Authors: Schmetter L , Wolzt M , Graselli U , Findl O , Strenn K , Simak S , Kastner J , Eichler H-G , Singer EA
Published: March 2003

Histamine has been widely used experimentally to induce headache in healthy subjects and migraine in migraineurs. There is evidence that the vascular effects of histamine are at least partially mediated by nitric oxide (NO). Hence we hypothesized that subjective symptoms and hemodynamic effects of histamine could be reduced by systemic NO-synthase inhibition. We therefore studied the effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO-synthase, or placebo on headache, flush and discomfort scores during histamine infusion. Additionally, blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA blunted the effect of histamine in the ophthalmic artery and the ocular circulation, NO-synthase inhibition did not mitigate subjective symptoms. Histamine did not affect mean blood flow velocities in the middle cerebral artery. Hence, we conclude that NO-synthase inhibition reduces the histamine-induced vascular effects in the ocular circulation, but is not sufficient to attenuate or abort the subjective symptoms provoked by histamine infusion.
Haemodynamic Correlates of Early and Delayed Responses to Sublingual Administration of Isosorbide Dinitrate in Migraine Patients
Authors: Bellantonio P , Micieli G , Buzzi MG , Marcheselli S , Castellano AE , Rossi F , Nappi G
Published: March 2003

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.
Influence of Caffeine and Caffeine Withdrawal on Headache and Cerebral Blood Flow Velocities
Authors: Couturier EGM , Laman DM , van Duijn MAJ , van Duijn H
Published: March 2003

Caffeine consumption may cause headache, particularly migraine. Its withdrawal also produces headaches and may be related to weekend migraine attacks. Transcranial Doppler sonography (TCD) has shown changes in cerebral blood flow velocities, (BFV) during and between attacks of migraine. In order to examine whether headache and changes in BFV could develop from controlled caffeine alterations, 20 healthy volunteers, without a headache history, underwent clinical evaluation, TCD and serum caffeine measurements on four occasions, comparing conditions of regular caffeine intake, caffeine withdrawal and “re-caffeination”. After 24 h of complete caffeine abstinence, 10 suffered from moderate to severe headaches with complete recovery within 1 h after caffeine intake. The BFVs in both middle cerebral, both posterior cerebral and basilar arteries were higher following the withdrawal period, reaching statistical significance in the left middle cerebral, basilar and both posterior cerebral arteries. BFVs decreased significantly within half an hour after caffeine intake in all subjects, and were similar to baseline values after 2 h. Our results emphasize the relationship between caffeine withdrawal, the development of headache and alterations in cerebral blood flow velocities. Also, these findings indicate that accurate interpretation of TCD measurements should account for the influence of caffeine on BFVs.
Symptoms and Diseases and Smoking Habits in Female Episodic Cluster Headache and Migraine Patients
Authors: Hannerz J
Published: March 2003

Twenty-seven episodic female cluster headache patients were compared to 27 age-matched female migraine patients with regard to occurrence of symptoms and diseases other than headache, and also with regard to tobacco consumption. Some symptoms and diseases were found to occur significantly or almost significantly more often in the cluster headache patients than in the migraine patients: Chronic fatigue ( p < 0.01), vertigo ( p < 0.05), arthralgia ( p < 0.05), back pain ( p = 0.05), spontaneous ecchymoses ( p = 0.05) and constipation and/or periodic diarrhea ( p = 0.09). There were significantly fewer persons who had never smoked in the cluster headache group than in the migraine group ( p < 0.01). The extent of smoking was significantly greater in the cluster headache group than in the migraine group, both as to the number of cigarettes smoked per day ( p < 0.001) and as to smoking years ( p < 0.001)
Phantom Eye
Authors: Nicolodi M , Frezzott R , Diadori A , Nuti A , Sicuteri F
Published: March 2003

We prospectively evaluated the frequency, time-course and predisposing factors of phantom eye syndrome in 53 patients who underwent surgical eye amputation to cure ocular cancer. Before surgery, patients were classified as Group 1 (n=25) if they had no history of headache or Group II (n=28) if they were headache sufferers. Three clinical patterns were distinguished: phantom pain, non-painful phantom phenomena and photopsias. Their symptoms developed 7 days to 6 months after surgery, with peak incidence after 6 months (photopsia 43%; phantom pain 28%; non-painful phantom phenomena 62%). Phantom eye syndrome was more common in headache sufferers than in non-headache subjects. Headache sufferers were more prone to phantom pain, but more so to non-painful phenomena and photopsias. These findings are in accord with our previous results indicating that prima y headache sufferers are prone to phantom tooth pain.
Nocturnal Plasma Melatonin Profile and Melatonin Kinetics During Infusion in Status Migrainosus
Authors: Claustrat B , Brun J , Geoffriau M , Zaidan R , Mallo C , Chazot G
Published: March 2003

The plasma melatonin profile was significantly disturbed (phase-shift of the maximum melatonin level) in four out of six female sufferers from status migrainosus, compared with nine healthy controls. The number of secretion peaks was similar in both groups. A nocturnal 20 μg melatonin infusion (from 21.00 to 01.00 h) evoked plasma melatonin levels slightly higher than a physiological secretion peak. During infusion, the episodes of secretion were reinforced and the endogenous plasma profile was phase-advanced in two patients displaying a phase-delay. These data suggest impaired pineal function in migraine. In the absence of side effects of melatonin infusion, the relief of certain migraine symptoms described by our patients might support a controlled trial of melatonin in migraine.
Safety, Tolerability, and Pharmacokinetics of Sumatriptan in Healthy Subjects Following Ascending Single Intranasal Doses and Multiple Intranasal Doses
Authors: Moore KHP , Hussey EK , Shaw S , Fuseau E , Duquesnoy C , Pakes GE
Published: March 2003

The delivery of sumatriptan doses intranasally could add greater flexibility in the treatment of migraine than is possible with the currently available subcutaneous and oral sumatriptan preparations. Two independent double-blind, randomized, placebo-controlled clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of intranasally administered sumatriptan following ascending single doses (three different dose levels) and multiple doses. In the four-way crossover, ascending-dose study, 20 healthy female subjects were randomized to receive on separate occasions single intranasal spray doses of 5, 10, or 20 mg sumatriptan (as the hemisulphate salt) or placebo into one nostril. Adverse events were mild and consisted mainly of bitter taste at the back of the throat and events typical of sumatriptan administered by other routes (headache, lightheadedness and tingling). Area under the plasma sumatriptan concentration versus time curve (AUC) and peak plasma concentration (Cmax) increased with the dose. Dose proportionality was demonstrated between 5 and 10 mg but not across the dose range 5–20 mg. Time to maximum plasma concentration (tmax) was variable due to multiple peaking. The elimination half-life (t1/2), approximately 2 h, was unaffected by the magnitude of dose. In the two-period, multiple-dose, crossover study, 12 healthy adult male and female subjects were randomized to receive either sumatriptan hemisulphate 20 mg or placebo, administered intranasally as a spray three times a day for 4 days, The two dosing periods were separated by 3 to 14 days. Multiple doses of sumatriptan were well tolerated, with no serious adverse events occurring or withdrawals due to adverse events. All patients reported a mild to moderate drug-related disturbance of taste. Nasal examinations remained normal, and olfactory function was unaffected. The AUC over the first 8 h following dosing (AUC8) and fraction of the dose excreted in the urine (fe; 6.2% vs 3.6%) were similar on Days 1 and 4. Day 4 values were significantly higher (p0.05) for Cmax (16.9 ng/ml vs 13.1 ng/ml), renal clearance (Clr; 19.0 l/h vs 14.2 l/h), and t1/2 (2.18 h vs 1.93 h), and shorter for tmax (0.88 h vs 1.75 h). Some accumulation (22%) occurred over the 4 days of dosing. Serum concentrations of the pharmacologically inactive indole acetic acid metabolite of sumatriptan were fourfold to fivefold higher than corresponding sumatriptan concentrations. Overall, these studies show the sumatriptan intranasal spray formulation is well tolerated, allows rapid absorption of sumatriptan, and results in only a clinically insignificant degree of sumatriptan accumulation upon repeated dosing.
Oxidative Stress and Platelet Responsiveness in Migraine
Authors: Tozzi-Ciancarelli MG , De Matteis G , Di Massimo C , Marini C , Ciancarelli I , Carolei A
Published: March 2003

The aim of this study is to investigate whether oxidative stress may represent a pivotal determinant of the altered functional features of platelets in migraineurs during the headache-free period. Twenty-three patients with migraine with aura, free of attack, and 23 healthy volunteers were enrolled for the study. The involvement of an oxidative condition appears confirmed by the statistically significant increase (p<0.001) of plasma levels of thiobarbiturie acid-reactive substances which may be considered a marker for oxidative stress and themselves strong pro-oxidants. Such oxidative status seems to induce in platelets of migraineurs increased membrane rigidity ( p<0.001), reduced cytosolic calcium in the resting condition and after thrombin stimulation ( p<0.001), and decreased aggregatory responses to ADP and collagen. These findings indicate that the “in vitro” anomalous platelet behavior in migraineurs, observed in headache-free periods, may be considered as the transient expression of the exhausted platelets to “in vivo” stimulation and probably related to an increased vulnerability to oxidative stress.
Responsiveness of Non-IHS Migraine and Tension-Type Headache to Sumatriptan
Authors: Cady RK , Gutterman D , Saiers JA , Beach ME
Published: March 2003

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT1 receptors that spans a range of clinical presentations.
Double-Blind Randomized Placebo-Controlled Study of Homoeopathic Prophylaxis of Migraine
Authors: Whitmarsh TE , Coleston-Shields DM , Steiner TJ
Published: March 2003

Homoeopathic remedies for migrane are widely available over the counter, statutorily offered by the national health service in the UK, and apparently popular with patients. Do they work? Sixty-three outpatients with migraine with or without aura b IHS criteria entered a 4-month randomized placebo-controlled, double-blind, parallel-groups trial of individualized homoeopathic prophylaxis, the first month being baseline with all patients on placebo. Three patients (4.8%) dropped out, leaving 30 in each treatment group. There were chance differences in attack frequency and severity between the groups at baseline (attacks were more frequent but less severe in the placebo group). Both groups improved on therapy but neither to a great extent on the primary outcome measure of attack frequency (verum: —19%; placebo: -16%). Reduction was mostly in mild attacks on placebo, more in moderate and severe attacks on homoeopathy. Few adverse events were reported. Overall, there was no significant benefit over placebo of homoeopathic treatment. The course of change differed between groups, and suggested that improvement reversed in the last month of treatment on placebo. On this evidence we cannot recommend homoeopathy for migraine prophylaxis, but cannot conclude that it is without effect.
The Factor V Leiden Mutation (R506Q) is not a Major Risk Factor for Migrainous Cerebral Infarction
Authors: Haan J , Kappelle LJ , de Ronde H , Ferrari MD , Bertina RM
Published: March 2003

The etiology of migrainous cerebral infarction is unknown, but may involve prothrombotic coagulation abnormalities. Therefore, we studied resistance to activated protein C and the presence of the Arg506Gln factor V Leiden mutation in 20 patients, with migrainous cerebral infarction. Only one heterozygous carrier of the mutation was found, whereas other patients did not carry the mutation. This indicates that the factor V Leiden mutation is not a major risk factor for migrainous cerebral infarction.
Endozepine Stupor in Children
Authors: Soriani S , Carrozzi M , De Carlo L , Plazzi G , Provini F , Rothstein JD , Tinuper P , Bouquet F , Lugaresi E , Montagna P
Published: March 2003

Recurring episodes of stupor in adults have been shown to be related to increased levels of endozepines, which are endogenous ligands for the GABAA receptors. We report here two children presenting with recurrent episodes of stupor associated with fast EEG activity who had increased levels of endozepine-4 in plasma. Mass spectroscopy did not reveal commercially available benzodiazepines. Interictal endozepine-4 levels were normal. In one of the patients, administration of flumazenil (0.25 mg i.v.), a benzodiazepine inverse agonist, induced improvement of consciousness and attenuation of EEG fast activity. In conclusion, children presenting with recurrent episodes of stupor and EEG fast activity should be evaluated for endozepine levels and can be effectively treated with i.v. flumazenil.
Power Spectral Analysis of Heart Rate and Diastolic Blood Pressure Variability in Migraine with and Without Aura
Authors: Pierangeli G , Parchi P , Barletta G , Chiogna M , Lugaresi E , Cortelli P
Published: March 2003

Autonomic function in migraineurs during headache-free periods was studied by means of cardiovascular reflexes and power spectral analysis of heart rate and diastolic blood pressure variability. We examined 56 patients: 37 suffering from migraine without aura and 19 from migraine with aura. Cardiovascular responses to the tilt test and Valsalva manoeuvre showed a normal function of the overall baroreceptor reflex arc. Normal heart rate responses to valsalva manoeuvre and deep breathing suggested an intact parasympathetic function. Power spectral analysis of both heart rate and diastolic blood pressure variability in basal conditions and during orthostatic test showed similar sympathovagal interactions modulating cardiovascular control in migraine patients and in controls.
Epidemiology of Migraine Headache in Santiago, Chile
Authors: Lavados PM , Tenhamm E
Published: March 2003

Objective. To describe the importance of migraine in Santiago, Chile, by analyzing its prevalence, clinical features and impact by age, gender and socioeconomic status. Methods. In 1993, a representative sample of 1,540 adults of the province of Santiago were interviewed using a standard questionnaire. A total of 1,385 (89.9%) subjects responded to the survey. Initially, a designated member of each household responded to the questionnaire. Subsequently, each household member with headaches was asked to respond to questions about severity, frequency, location, duration, associated symptoms and impact in work and social activities of their most frequent headaches. Migraine diagnoses were determined in accordance with the International Headache Society (IHS) criteria of 1988. Results. Recurrent headaches in the past year were found in 516 (36.82%) respondents, 145 (28.1%) males and 371 (71.9%) females. Total prevalence of migraine was found to be 7.3% (95%, CI 5.9–8.6); 11.9% (95% CI 9.6–14.2) in females and 2.0% (95% CI 0.9–3.0) in males. Overall, migraine constituted 19.6% (101/516) of all headaches reported in this sample. The prevalence did not vary significantly by age groups or socioeconomic status (SES). Migraine with aura had an overall prevalence of 3.5% (CI 0.8–7.1), and was significantly more frequent in females. In 60–70% of cases the attacks lasted 2–6 h and the frequency was 3.3 and 3.4 per month in females and males respectively. Both males and females reported significantly high percentages of attacks during work. Conclusions. Migraine prevalence in a sample of adults of Santiago is similar to that reported in previous studies using IHS criteria. Women of all socioeconomic levels are at an increased risk.
Sumatriptan Blocks Spreading Depression in Isolated Chick Retina
Authors: Maranhâo-Filho PA , Martins-Ferreira H , Vincent MB , Ribeiro LJC , Novis SAP
Published: March 2003

Spreading depression is a neurohumoral phenomenon that has been related to the pathophysiology of migraine. The recently introduced 5HTID agonist anti-migraine compound sumatriptan blocks neurogenic extravasation and induces cerebral vasoconstriction, but the actual mechanism of action against migraine remains obscure. Retinal spreading depression (RSD) velocity has been measured in isolated chick retinas in the presence of 0.05-2.00:nM sumatriptan. This drug reversibly blocks RSD in a concentration-dependent manner. Since the preparation is blood-vessel free, this effect must be related to the nervous tissue.
Improvement in Migraine-Specific Quality of Life in A Clinical Trial of Rizatriptan
Authors: Santanello NC , Polis AB , Hartmaier SL , Kramer MS , Block GA , Silberstein SD
Published: March 2003

A validated migraine-specific questionnaire (24-h Migraine Quality of Life Questionnaire1: 24-h MQoLQ) was used to assess the impact of migraine and migraine therapy on health related quality of life during an acute migraine attack. Male and female migraineurs aged 18-55 years were randomized to placebo ( n = 41), rizatriptan 2.5 mg ( n = 47), 5 mg ( n = 74), or 10 mg ( n = 85) in a triple-blind, placebo-controlled clinical trial. Rizatriptan 5 mg and 10 mg were significantly more efficacious than placebo on pain relief and functional disability. After accounting, for multiple comparisons to placebo, rizatriptan 10 mg showed significantly better responses compared to placebo on three of five domains of 24-h MQoLQ (social functioning, migraine symptoms, and feelings/concerns). The O'Brien's Rank Sum Test statistic showed a statistically significant overall difference on the 24-h MQoLQ between the 10 mg rizatriptan and placebo groups ( p = 0.005) and for the overall close trend ( p 0.001).
Ketoprofen (25 Mg) in the Symptomatic Treatment of Episodic Tension-Type Headache: Double-Blind Placebo-Controlled Comparison with Acetaminophen (1000 Mg)
Authors: Steiner TJ , Lange R
Published: March 2003

Therapies in current use for episodic tension-type headache (ETTH) are often unsatisfactory. Few trials have been conducted to demonstrate efficacy of any of them. This multicenter placebo-controlled randomized parallel-groups study compared the analgesic efficacy of single oral doses of ketoprofen 25 mg and acetaminophen 1000 mg as outpatient treatment of 1 attack of ETTH. Efficacy was assessed by patients as pain relief on a diary-entered 7-point categorical scale. A total of 457 patients treated 348 attacks, 330 of which were evaluable. There were no serious adverse events (AEs); gastrointestinal AEs were most common on all treatments. Total relief from pain after 2 h was recorded by 16% of patients on placebo, 28% on ketoprofen, and 22% on acetaminophen. Worthwhile effect or total relief (all other responses were regarded as treatment failures) were recorded by 36% on placebo, 70% on ketoprofen ( p <0.001), 61% on acetaminophen ( p <0.001). The difference between ketoprofen and acetaminophen was not significant ( p=0.24). Various secondary efficacy measures confirmed superiority of both active treatments over placebo, with some trends for slightly better outcome on ketoprofen than on acetaminophen This study demonstrates that ketoprofen is an effective alternative to standard therapy in ETTH.
Noncompliance May Render Migraine Prophylaxis Useless, But Once-Daily Regimens Are Better
Authors: Mulleners WM , Whitmarsh TE , Steiner TJ
Published: March 2003

Medicines work better if taken, which must be true of migraine prophylaxis. There is evidence that compliance with regular medication can be badly deficient. To assess how serious the problem might be in routine migraine management, we undertook a covert observational 2-month survey in a specialist headache clinic using objective measures of compliance. Subjects were 38 patients needing prophylaxis with medication prescribed once (od), twice (bd), or three times daily (tds). Medication was dispensed, unknown to them, in Medication Event Monitoring Systems (MEMS) to record openings in real time. Number, timing, and pattern of actual openings were compared with what was expected. Compliance rates averaged 66%, although returned pill counts indicated 91%. A substantial and significant difference was shown between od and bd or tds regimens. Measures of dosing interval—used-on-schedule rate and therapeutic coverage—averaged between 44% and 71%. Once-daily treatment was associated with a used-on-schedule rate more than double those of multiple daily dosing, but still only 66%. We conclude that routine use of drug prophylaxis in migraine may be so seriously undermined by poor compliance that it has little chance of efficacy. Returned-pill counting is inadequate for compliance assessment.
Serotonin Metabolism in Cluster Headache
Authors: D'Andrea G , Granella F , Alecci M , Manzoni GC
Published: March 2003

Despite some evidence of the involvement of the serotonergic system in cluster headache (CH) pathophysiology, the serotonin (5HT) metabolism has so far been poorly studied. The aim of this study was to investigate plasma and platelet levels of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in CH patients in the active period of the disease. Nineteen CH sufferers and 17 sex- and age-matched healthy controls were studied. CH patients showed significantly higher plasma levels of 5HT and 5HIAA compared to controls (5HT: 5.7±6.1 ng/ml vs 0.2±0.2 ng/ml; p=0.02; 5HIAA: 34.7±46.1 ng/ml vs 0.6±0.7 ng/ml; p=0.004). In platelet 5HT levels were slightly reduced in CH patients in comparison with those of control subjects (662.4±522.3 ng/10-8 platelets vs 832.4±587.9 ng/10-8 platelets; n.s.) and 5HIAA levels resulted significantly lower in CH sufferers than in control subjects (3.2±2.6 ng/10-8 platelets vs 6.7±4.8 ng/10-8 platelets; p=0.04). Our data suggest that CH is characterized by an increase of plasma serotonergic metabolism that could reflect an involvement of the central serotonergic system in the pathogenesis of CH.
The Psychological Profiles of Patients with Whiplash-Associated Headache
Authors: Wallis BJ , Lord SM , Barnsley L , Bogduk N
Published: March 2003

Headache often compounds chronic neck pain following whiplash injury. To better understand post-traumatic headache, the SCL-90-R symptom checklist was used to determine the psychological profiles of patients with whiplash-associated headache and of patients with whiplash-associated neck pain without headache. The psychological profiles of these patients were compared with previously published SCL-90-R profiles of patients with post-traumatic and nontraumatic headache, and of the normal population. Patients with whiplash-associated headache were not significantly different from those with other forms of post-traumatic headache or with whiplash-associated neck pain without headache. However, when patients with whiplash-associated headache and patients with nontraumatic headache were compared to normal data, significant differences emerged. Patients with nontraumatic headache exhibited higher scores on all subscales, whereas patients with whiplash-associated headache differed from the normal sample only on somatization, obsessive-compulsive, depression and hostility subscales, and the global severity index. These differences imply that patients with whiplash-associated headache suffer psychological distress secondary to chronic pain and not from tension headache and generalized psychological distress.
Craniometric Measures in Cluster Headache Patients
Authors: Áfra J , Cecchini A Proietti , Schoenen J
Published: March 2003

Blockade of venous drainage in the cavernous sinus, which may play a pivotal role in the pathophysiology of cluster headache (CH), could be triggered by local inflammation. It could also be favored by a constitutional narrowness of the cavernous sinus region. Before exploring the latter with magnetic resonance imaging (MRI), we determined whether external morphometric skull measures are different among CH patients ( n=25), healthy volunteers ( n=21), and migraine patients ( n=20). All subjects were males of comparable age distribution. Six measures were taken: inion-nasion perimeter, inion-nasion distance over the vertex; distance between the upper ends of tragus; diameter at the level of the temporal fossa; diameter at mid inion-nasion perimeter at ear level; and inion-nasion diameter. CH patients had significantly smaller values than healthy subjects and/or migraine patients in all but one measure (ANOVA and Duncan's post-hoc analysis). This may suggest mat they have a narrower anterior/middle cranial fossa, and possibly a narrower cavernous sinus loggia, which needs to be confirmed by a quantitative MRI study.
The Hypnic (“Alarm Clock”) Headache Syndrome
Authors: Dodick DW , Mosek AC , Campbell JK
Published: March 2003

Hypnic headache syndrome is a rare, sleep-related, benign headache disorder. We report 19 new cases (84% females) with follow-up data. The mean age at headache onset was 60.5 ± 9 years (range 40–73 years). Headache awakened the patients from the night's sleep at a consistent time, usually between 1.00 and 3.00 a.m. (63%); three patients (16%) reported that identical headaches could occur also during daytime naps. Headache frequency was high, occurring more than 4 nights/week in 68% of the patients. Headache resolution occurred within 2 h in 68% of patients. Neurologic examination, laboratory studies, and brain imaging were unrevealing at the time of diagnosis. Headache severity largely remains unchanged or attenuates over time, but frequency may vary in either direction. Only one patient had spontaneous relief from headache. Four patients (24%) achieved permanent suppression of headache with medication, and two were able to abort individual headache attacks. Caffeine in a tablet or beverage was helpful in four patients. Lithium carbonate therapy caused side effects requiring cessation of treatment in four patients.