bluuebunny/crossref_metadata_2025 huggingface dataset:
Sumatriptan Nasal Spray in the Acute Treatment of Migraine: A Review of Clinical Studies
Authors: Dahlöf C
Published: March 2003

Sumatriptan nasal spray is a single-dose device that delivers 5 mg, 10 mg, or 20 mg of sumatriptan (dosage availability dependent upon country) in a 0.1 ml aqueous solution to one nostril. The efficacy and tolerability of sumatriptan nasal spray have been assessed in a number of studies. It has been demonstrated that administering sumatriptan as a divided dose in both nostrils confers no advantage over administration in a single nostril. It appears from these studies that sumatriptan nasal spray is rapidly effective (with an onset of efficacy as early as 15 min postdose). The 20 mg dose is superior to the lower doses (5 mg, 10 mg) in terms of both time to onset of efficacy and the extent of migraine symptom relief. Sumatriptan nasal spray is consistently effective in the treatment of multiple migraine attacks (with 67% of patients treated with the 20 mg dose responding in at least two of three treated attacks) and with long-term use for up to 1 year. Apart from a bitter taste, the adverse event profile of sumatriptan nasal spray is comparable to that of placebo.
Acupuncture for Recurrent Headaches: A Systematic Review of Randomized Controlled Trials
Authors: Melchart D , Linde K , Fischer P , White A , Allais G , Vickers A , Berman B
Published: March 2003

Objective: To assess whether there is evidence that acupuncture is effective in the treatment of recurrent headaches.

Design: Systematic review.

Study selection: Randomized or quasi-randomized clinical trials comparing acupuncture with any type of control intervention for the treatment of recurrent headaches.

Data sources: Electronic databases (Medline, Embase, Cochrane Field for Complementary Medicine, Cochrane Controlled Trials Register), personal communications and bibliographies.

Data collection and analysis: Information on patients, interventions, methods, and results were extracted by at least two independent reviewers using a pretested form. A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group) was calculated as a crude indicator of trial results as meta-analysis of more specific outcome data was impossible due to heterogeneity and insufficient reporting.

Results: Twenty-two trials, including a total of 1042 patients (median 36, range 10-150), met the inclusion criteria. Fifteen trials were in migraine patients, six in tension-headache patients, and in one trial patients with various headaches were included. The majority of the 14 trials comparing true and sham acupuncture showed at least a trend in favor of true acupuncture. The pooled responder rate ratio was 1.53 (95% confidence interval 1.11 to 2.11). The eight trials comparing acupuncture and other treatment forms had contradictory results.

Conclusions: Overall, the existing evidence suggests that acupuncture has a role in the treatment of recurrent headaches. However, the quality and amount of evidence is not fully convincing. There is urgent need for well-planned, large-scale studies to assess effectiveness and efficiency of acupuncture under real life conditions.
Headache in Intracranial Tumors
Authors: Pfund Z , Szapáry L , Jászberényi O , Nagy F , Czopf J
Published: March 2003

The clinical data of 279 consecutive patients with brain tumors were analyzed pre- and postoperatively in the period of 1994-95. No headache had been recorded in the history of 115 patients, neither pre- nor postoperatively. Only in 139 of the remaining 164 headache patients was there a probable connection between headache and intracranial neoplasm. In the headache group the most frequent findings were metastatic brain tumors and different astrocytomas. Hypophysis adenomas and glioblastoma multiforme were frequent in the no-headache group. Progressive headache was found in 110 patients (67% of the headache group). The progressive character of the headache showed a close relationship with the prevailing edema, but not with the size of the tumor. Infratentorial and intraventricular tumors were more frequently accompanied by headache than those located supratentorially, probably due to the disturbance of CSF circulation and midline dislocation with increased intracranial pressure. Only in one-third of the patients did the site of the tumor coincide with the lateralization of headache. In half of the headache patients, pain was the first complaint. Headaches caused by tumor were characterized by pain lasting for hours, developing for weeks or months. The headache was never permanent and there was no regular daily recurrence.
Headache in Ehlers—Danlos Syndrome
Authors: Jacome DE
Published: March 2003

Objective: Ehlers—Danlos Syndrome (EDS) is a complex hereditary connective tissue disorder with neurologic manifestations that include cerebrovascular disorders and chronic pain. The clinical data collected on 18 patients with EDS and chronic headaches is reported.

Procedure: Clinical history, neurologic examination, computerized tomography of the head, magnetic resonance imaging (MRI) of the brain, and electroencephalogram (EEG). Headaches were classified according to the International Headache Society and the patients were followed by the author for a minimum of 2 years.

Findings: Four patients had migraine with aura, four had migraine without aura, four had tension headaches, four had a combination of migraine and tension headaches, and two had post-traumatic headaches. Nine patients exhibited blepharoclonus but none had history of seizures and their EEGs were normal, ruling out eye closure epilepsy. Although one patient had a small right frontal angioma, a second had Arnold Chiari malformation type I, and a third had an old stroke, headaches did not clinically correlate with their central nervous system (CNS) lesions.

Conclusion: Chronic recurrent headaches may constitute the neurologic presentation of EDS in the absence of structural, congenital, or acquired CNS lesions that correlate with their symptoms. Individuals with EDS may be prone to migraine due to an inherent disorder of cerebrovascular reactivity or cortical excitability. Additional studies are needed to elucidate the pathogenesis of headaches in EDS.
Cervicogenic Headache: Long-Term Postoperative Follow-Up
Authors: Fredriksen TA , Salvesen R , Stolt-Nielsen A , Sjaastad O
Published: March 2003

The patient, a 50-year old female had been suffering from right-sided head- and neck pain since she was 31 years of age. It started in connection with an indirect neck trauma. Analgesics were of little or no avail and operative procedures, including liberation of the greater occipital nerve (GON) ( n = 2) and decompression of the C2 ganglion/root, had only a transitory effect. At 42, a magnetic resonance scan of the cervical spine demonstrated a degenerated disk C5–C6, with encroachment on the foramina and the cord. At 42 years of age, a stabilization operation at C5–C6 (Robinson-Smith) alleviated her discomfort—only some motor complaints in the ipsilateral upper extremity remaining and only in the first 12–18 months.
Migraine Patients Show an Increased Density of Dopamine D3 and D4 Receptors on Lymphocytes
Authors: Barbanti P , Fabbrini G , Ricci A , Pascali M Paola , Bronzetti E , Amenta F , Lenzi GL , Cerbo R
Published: March 2003

Recent studies have revealed peculiar functional and genetic features of dopamine receptors in migraine. As peripheral blood lymphocytes (PBL) may represent a tool for peripheral detection of neuroreceptors, we compared the expression of dopamine D3 (DRD3) and D4 (DRD4) receptors on PBL in migraine patients and in healthy controls using radioligand binding assay techniques in the presence of antidopamine D2-like receptor antibodies. The dopamine D2-like receptor agonist [3H]7-OH-DPAT was used as a radioligand. An increased density of both DRD3 ( P = 0.0006) and DRD4 ( P = 0.002) on PBL was observed in migraineurs compared with controls. This up-regulation might reflect central and/or peripheral dopamine receptor hypersensitivity due to hypofunction of the dopaminergic system. These findings support the view that dopamine D2-like receptors are involved in the determination of the so-called migraine trait, which may help to elucidate several clinical features of the disease.
Migraine and Stroke in Young Women
Authors: Tzourio C , Kittner S J , Bousser M-G , Alpérovitch A
Published: March 2003

In this paper we review the evidence that migraine is associated with ischaemic stroke in young women, emphasizing potential biases, factors that may influence the association, potential mechanisms, and potential public health impact. Consistency of case-control findings from several countries and supporting evidence from prospective data suggest that the association is not an artifact of study design or execution, although, due to methodological limitations, none of the studies mentioned can be considered definite proof of the association. However, it is less clear whether migraine without aura is associated with stroke or whether the association is restricted to migraine with aura. Similarly, there are few data examining the magnitude of the association among non-users of oral contraceptives compared with those who use low oestrogen oral contraceptives. As a consequence, there is a lack of data concurrently stratifying both by the presence vs. the absence of aura and by the use of low oestrogen oral contraceptives vs. non-use of oral contraceptives. Moreover, there is still no convincing evidence on the mechanisms that would be implied and on the groups of migraineurs really at risk of ischaemic stroke. Despite the considerable advances in our understanding of the relationship between migraine and stroke, there are many gaps in the data needed for public health recommendations.
Head-HUNT: Validity and Reliability of a Headache Questionnaire in a Large Population-Based Study in Norway
Authors: Hagen K , Zwart J-A , Vatten L , Stovner LJ , Bovim G
Published: March 2003

We have assessed the validity and reliability of a self-administered headache questionnaire used in the 'Nord-Trøndelag Health Survey 1995-97 (HUNT)' in Norway, by blindly comparing questionnaire-based headache diagnoses with those made in a clinical interview of a sample of the participants. Restrictive questionnaire-based diagnostic criteria for migraine, assessed according to modified criteria of the International Headache Society, performed excellently in selecting 'definite' migraine patients (100% positive predictive value). The best agreement concerning migraine diagnoses was achieved by using a liberal set of criteria (k 0.59). Similar agreement was found evaluating patient status as headache sufferers, and as sufferers from frequent headaches (>6 days per month) (k 0.57 and 0.50, respectively). The k values of nonmigrainous headache and chronic headache (>14 days per month) were 0.43 and 0.44, respectively. The results suggest that our self-administered questionnaire may be suitable in identifying a population with 'definite' migraine, and the questionnaire is an acceptable instrument in determining the prevalence in Nord-Trøndelag of headache sufferers, migraine, non-migrainous headache, and frequent or chronic headache sufferers.
Cortical Hyperexcitability is Cortical Under-Inhibition: Evidence From a Novel Functional Test of Migraine Patients
Authors: Palmer JE , Chronicle EP , Rolan P , Mulleners WM
Published: March 2003

Recent studies of the visual cortex in patients with migraine have generally concluded that migraine (particularly migraine with aura) is associated with a state of functional cortical hyperexcitability. The mechanisms giving rise to this hyperexcitability have hitherto been unclear. This paper reports two studies that used a novel investigative technique, derived from basic research in vision science, to examine specific deficits of inhibitory processing in primary visual cortex. The technique is termed the metacontrast test, and it examines visual masking under highly specified conditions. In Study 1 , 12 migraine with aura patients (MA), 12 age-matched migraine without aura patients (MO) and 12 age- and sex-matched headache-free control subjects (C) were compared using the metacontrast test. MA patients were significantly less susceptible to visual masking in the metacontrast test than both MO and C groups: this result is highly consistent with a deficit in cortical inhibitory processing in MA patients. Study 2 examined MA patients taking a variety of migraine prophylactics, again using the metacontrast test. Test results normalized in those MA patients taking sodium valproate, but not in those taking other prophylactics. Sodium valproate is a GABA-A agonist that is known to cross the blood–brain barrier: GABA-ergic networks act as the primary inhibitory mechanism in visual cortex. Taken together, the results of these studies argue that cortical hyperexcitability, at least in MA patients, is likely to be a result of deficient intracortical inhibitory processes.
The Potential Anti-Migraine Compound SB-220453 does not Contract Human Isolated Blood Vessels or Myocardium; A Comparison with Sumatriptan
Authors: Maassen VanDenBrink A , van den Broek RWM , de Vries R , Upton N , Parsons AA , Saxena PR
Published: March 2003

The mechanistically novel benzopyran derivative SB-220453, which is undergoing clinical evaluation in migraine, exhibits a high affinity for a selective, but not yet characterized, binding site in the human brain. It inhibits nitric oxide release and cerebral vasodilatation following cortical spreading depression as well as carotid vasodilatation induced by trigeminal nerve stimulation in the cat. The aim of our study was to investigate the contractile properties of SB-220453 on a number of human isolated blood vessels (coronary artery, saphenous vein and middle meningeal artery) as well as atrial and ventricular cardiac trabeculae. While sumatriptan induced marked contractions in three blood vessels investigated, SB-220453 was devoid of any effect. In atrial and ventricular cardiac trabeculae, neither SB-220453 nor sumatriptan displayed a positive or negative inotropic effect. Since SB-220453 did not contract the middle meningeal artery, we conclude that potential anti-migraine effects are not mediated via a direct cerebral vasoconstriction. The lack of activity of SB-220453 in coronary artery, saphenous vein and cardiac trabeculae demonstrates that the compound is unlikely to cause adverse cardiac side-effects.
Prevalence of Migraine in Taipei, Taiwan: A Population-Based Survey
Authors: Wang S-J , Fuh J-L , Young Y-H , Lu S-R , Shia B-C
Published: March 2003

We conducted the first population-based migraine survey in Taipei, Taiwan, using a validated questionnaire administered by interviewers during the period from August 1997 to June 1998. Our target population comprised all individuals (age ≥ 15 years) in 1400 randomly selected households. Migraine diagnoses were made according to the classification criteria of migraine without aura proposed by the International Headache Society, 1988, except that attacks with a duration of between 2 h and 4 h were also included. Of the 4434 eligible subjects in the 1211 respondent households, 3377 (76%) completed the questionnaire. After adjustment for age and sex distribution according to the population structure, the prevalence of migraine was 9.1% (F/M 14.4%/4.5%). Fifty-four percent of the subjects with migraine had consulted a physician about their headaches in the past year. However, only 18% of them reported that their migraine had been diagnosed by physicians. This study found that Taipei residents have the highest migraine prevalence of all Chinese populations studied, although it is still in the low range of prevalence compared with the results from Western countries.
Intranasal Civamide for the Acute Treatment of Migraine Headache
Authors: Diamond S , Freitag F , Phillips SB , Bernstein JE , Saper JR
Published: March 2003

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 μg or 150 μg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.
Evidence-Based Analysis of a Migraine Treatment Drug Comparison Trial
Authors: Gawel M , Wiebe S
Published: March 2003

Patients present with specific problems against a background of their particular situation. The applicability of a treatment to a specific case may be difficult to assess in the light of the information available on that treatment. Evidence-based medicine is a discipline developed to achieve the best informed treatment decisions in clinical situations. In this paper, we illustrate a logical approach to reaching a decision regarding which of two migraine treatments should be used in a clearly defined patient. The information evaluated is a comparative trial between sumatriptan (100 mg), rizatriptan (5 and 10 mg) and placebo. The use of the analytical tools of evidence-based medicine is demonstrated in this exercise. The example was chosen because this is an area of great current interest in the field of neurology.
Polysomnographic Findings in Nights Preceding a Migraine Attack
Authors: Göder R , Fritzer G , Kapsokalyvas A , Kropp P , Niederberger U , Strenge H , Gerber WD , Aldenhoff JB
Published: March 2003

Sleep recordings were performed in eight patients to analyse sleep alterations preceding migraine attacks. Polysomnographic recordings from nights before an attack were compared with nights without following migraine. We analysed standard sleep parameters and electroencephalogram (EEG) power spectra. The main findings preceding migraine attacks were a significant decrease in the number of arousals, a decrease in rapid eye movement (REM) density, a significant decrease of beta power in the slow wave sleep, and a decrease of alpha power during the first REM period. The results suggest a decrease in cortical activation during sleep preceding migraine attacks. According to the models of sleep regulation, alterations in the function of aminergic or cholinergic brainstem nuclei have to be discussed.
New-Onset Cluster Headache in Middle-Age and Elderly Women
Authors: Mosek A , Hering-Hanit R , Kuritzky A
Published: March 2003

Cluster headache is usually considered to affect young men. We hereby report on new-onset cluster headache in middle-aged and elderly women. We performed a retrospective chart review of female patients diagnosed with cluster headache (IHS criteria), and studied the charts of women in whom the headache started after the age of 50 years. Out of 168 patients (26 women, 15%) diagnosed with cluster headache, the headache started after the age of 50 years in seven women, of whom three reported past tension-type or migraine headaches. The mean age at the beginning of the headache was 61 ± 8 years (range 52–72 years). In all cases, the pain was severe, strictly unilateral, and accompanied by at least one autonomic symptom. The average duration of the pain was 70 min (range 20 min−3 h), recurring daily for an average period of 7 weeks (range 1–16 weeks). Five patients had 1–2 pain attacks each day, while the other two experienced up to eight episodes of pain in 1 day. In two patients the periodicity of the pain was currently undetermined. In the remainder, the headache periods recurred every 1–4 years. Cluster headache is commonly considered to be a young-male disorder, but middle-aged and elderly women may also be affected. The characteristics of the pain and its manner of occurrence were similar in our cases to those reported in the young-male population.
Supraorbital Neuralgia: A Clinical Study
Authors: Caminero AB , Pareja JA
Published: March 2003

A series of 18 patients suffering from supraorbital neuralgia have been studied through a seven year period. Appropriate investigations ruled out other headaches.

There was a female (67%) preponderance. Mean age at onset was 51.6 years. The mean headache duration was 5.9 years. Five patients had a history of ipsilateral forehead trauma. The main areas of pain were the forehead and orbit. The pain was dull with short sharp or burning exacerbations. The temporal pattern was either remitting ( n = 7) or chronic continuous ( n = 11). Autonomic accompaniments were generally lacking. Neurological assessment was normal in all but 4 patients who were found to have signs/symptoms of sensory dysfunction in the forehead of the symptomatic side. Trials of different drugs, including migraine and anti-neuralgic drugs, only provided slight relief. Anaesthetic nerve blocks of the supraorbital nerve provided an absolute but transitory relief of pain.

Although aetiology and pathogenesis of supraorbital neuralgia is largely unknown, entrapment of the supraorbital nerve at its outlet and successful decompressive surgery have been previously reported. This and other pathogenic hypotheses are discussed.
Diagnosis of Migraine: Empirical Analysis of a Large Clinical Sample of Atypical Migraine (IHS 1.7) Patients and Proposed Revision of the IHS Criteria
Authors: Rains JC , Penzien DB , Lipchik GL , Ramadan NM
Published: March 2003

The International Headache Society (IHS) diagnostic criteria for headache improved the accuracy of primary headache diagnoses, including migraine. However, many migraineurs receive an ‘atypical migraine’ diagnosis according to the IHS nosology (IHS 1.7), indicating that they approximate but do not fully meet all IHS criteria. This study characterized and sub-classified patients with atypical migraine. Within a clinical sample of 382 headache sufferers, 83 patients met IHS criteria for ‘atypical migraine’. Patients receiving the IHS 1.7 designation did not converge to form a homogeneous group. Rather, distinct and clinically relevant subgroups were empirically derived (e.g. migraine with atypical pain parameters, brief migraine, chronic migraine). The results call for revisions of the IHS diagnostic criteria for migraine that would minimize the number of patients receiving an atypical diagnosis. Revisions would include decreasing the minimum headache duration criteria from 4 h to 2 h, and developing a classification for ‘chronic migraine’ for migraine greater than 15 days per month. The proposed revision provides a means of diagnosing the daily and near-daily headache commonly observed in clinical populations.
Headache Caused by Drinking Cold Water is Common and Related to Active Migraine
Authors: Mattsson P
Published: March 2003

The primary aim of this study was to estimate the prevalence of cold-induced headache and to test if it is associated with migraine. Women attending a population-based mammography screening programme were asked to participate in the study. Fifty-one of 669 women (7.6%) experienced a headache after ingesting 150 ml of ice-cold water through a straw. Women who had experienced one or more migraine attacks in the last year (active migraine) were twice as likely to experience a headache from ingesting the cold water as women who had never suffered from migraine. Ninety-five women who had experienced their most recent migraine attack more than 1 year ago (inactive migraine) were not at increased risk. The prevalence of active and inactive migraine was 19.4 and 14.2%, respectively. Headache caused by drinking cold water is common in women. The results indicate that active migraine facilitates the perception of forehead pain induced by a cold palatal stimulus.
Patterns of Ergotamine and Sumatriptan Use in the Netherlands from 1991 to 1997
Authors: Rahimtoola H , Egberts ACG , Buurma H , Tijssen CC , Leufkens HG
Published: March 2003

The objective of this study was to assess usage patterns of ergotamine and sumatriptan over a period of 6 years, primarily to evaluate the impact that sumatriptan has had on the prescription of ergotamine. This study used ergotamine and sumatriptan prescription data representing inhabitants of eight cities in the Netherlands and covering the period of 1991–1997. The yearly incidence of new users between 1991 and 1997 was estimated for both drugs as well as for the drug of first choice to be prescribed to patients initiating specific abortive migraine treatment with either ergotamine or sumatriptan. Intra-individual ergotamine and sumatriptan usage patterns, characterized by single (incidental), continuous (rate of retention) or switch use, were examined for five patient cohorts, each for a follow-up period of 1 year. During the year of sumatriptan introduction (1991–1992), the overall incidence of new use for both drugs was highest (5.4 per 1000 inhabitants). Hereafter, a substantial reduction of more than 50% was observed. From 1992 to 1996, the yearly incidence of ergotamine first-time use was significantly higher than that of sumatriptan and up to 1996 ergotamine was more than twice as likely than sumatriptan to be prescribed to patients initiating specific abortive treatment. Hereafter, sumatriptan was as likely as ergotamine to be prescribed as the drug of first choice, which coincided with the full reimbursement of sumatriptan tablets. Overall, neurologists were more likely than general practitioners (GPs), to prescribe sumatriptan as the drug of first choice. Approximately half of the total study population were identified as single-time users. This phenomonen occurred more frequently in the ergotamine cohorts. The sumatriptan cohorts displayed a slight yet significant stronger retention rate compared with the ergotamine cohorts. The overall impact of sumatriptan on ergotamine use in The Netherlands was marginal, predominantly due to GP's adherence to migraine treatment guidelines and reimbursement policies concerning sumatriptan tablets. Overall, incidental use was relatively high and may reflect the reported difficulties in diagnosing migraine, lack of patient–doctor consultation, or that anticipated benefits of the drug were not achieved. Further study is required to clarify these issues.
Are There Predictive Factors for Long-Term Outcome after Withdrawal in Drug-Induced Chronic Daily Headache?
Authors: Tribl GG , Schnider P , Wöber C , Aull S , Auterith A , Zeiler K , Wessely P
Published: March 2003

Objectives

To investigate prognostic factors for long-term outcome of patients after inpatient withdrawal because of drug-induced chronic daily headache.

Procedures

Fifty-five patients (36 females) were re-examined by means of a standardized interview after inpatient withdrawal. The mean observation period was 9.28 ± 2.85 years (mean ± sd; median 8.58; range 5.00–13.50).

Results

Five years after withdrawal, one-third of the patients (34.6%) had an overall favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported a clear-cut improvement of headache, and one-third (32.7%) developed recurrent drug overuse. Most relapses occurred within 2 years, and a small percentage within 5 years. No predictors for long-term outcome after inpatient withdrawal were found.

Conclusions

All patients with drug-induced chronic daily headache should be considered as good candidates for inpatient withdrawal, and no patient should be excluded from that therapy.
Hemicrania Continua: Diagnostic Criteria and Nosologic Status
Authors: Pareja JA , Vincent M , Antonaci F , Sjaastad O
Published: March 2003

Proposals for the diagnostic criteria for hemicrania continua (HC) and also for the nosological status of HC are set forth. The clinical constellation of symptoms and signs making up HC consists of: unilaterality without side shift; absolute indomethacin effect; and long-lasting repetitive attacks of varying duration, eventually with a chronic pattern, the pain being mild to severe. For the typical clinical picture of HC, including a positive ‘indotest’, we propose the term hemicrania continua vera. More or less analogous, but ‘indotest-negative’ clinical pictures have provisionally been termed hemicrania generis incerti (of undetermined nature). At the present level of knowledge, the diagnosis of hemicrania generis incerti should be made mostly by exclusion. HC may possibly best be classified along with chronic paroxysmal hemicrania (CPH) as this is the only other headache absolutely responsive to indomethacin. The bond between these two headaches on the one hand and cluster headache on the other should, at most, be a loose one. Interrelationships of these four classifiable headaches are briefly discussed.
Recurrent Lilliputian Hallucinations as Visual Aura Symptom in Migraine
Authors: Podoll K , Robinson D
Published: March 2003

Since her early 30s a 72-year-old female migraine sufferer has experienced recurrent episodes of Lilliputian hallucinations occurring at the peak of her severe migraine attacks and lasting between 2 min and 5 min, suggesting that her miniature hallucinations represent a visual migraine aura symptom. The existence of Lilliputian hallucinations of a migrainous nature is confirmed by four similar case reports reviewed from the migraine literature. The occurrence of similar Lilliputian hallucinations in the syndrome of peduncular hallucinosis, due to mesencephalic and/or thalamic lesions, supports the notion that the patient's recurrent Lilliputian hallucinations might have been aura symptoms of basilar migraine.
Increased Plasma Nitrites in Migraine and Cluster Headache Patients in Interictal Period: Basal Hyperactivity of L-Arginine-No Pathway?
Authors: D'Amico D , Ferraris A , Leone M , Catania A , Carlin A , Grazzi L , Bussone G
Published: March 2003

Nitrite concentrations in plasma were investigated in a population of migraine and cluster headache patients and a group of healthy non-headache controls. A hundred migraine patients and 69 cluster headache patients in the interictal period, and 112 controls, were studied. Significantly higher nitrite concentrations were found in migraine patients, with and without aura, and cluster headache patients, in remission and cluster phase, than in controls. These findings suggest that a basal dysfunction in the L-arginine-NO pathway may be involved in the peripheral mechanisms predisposing subjects with neurovascular headaches to individual attacks.
A Neural Network Model of Sensitization of Evoked Cortical Responses in Migraine
Authors: Thomas E , Sándor PS , Ambrosini A , Schoenen J
Published: March 2003

Migraine patients show abnormalities of cerebral electrophysiology that manifest themselves mainly during the attack interval. Cortical-evoked potentials of migraineurs fail to habituate to repetitive presentations of visual stimuli, and the amplitude of components of their auditory cortical-evoked potentials have a higher dependence on the stimulus intensities than in healthy subjects. A computer model of a neural network has been developed that is able to reproduce both these neurophysiological dysfunctions. It predicts a positive correlation between the magnitudes of both these dysfunctions. The model also offers an explanation of why mutations in the same ion channel gene with opposite consequences on channel function, e.g. P/Q Ca2+ channels in migraine, may lead to similar electrophysiological abnormalities.
Neurovascular Headache and A Midbrain Vascular Malformation: Evidence for A Role of the Brainstem in Chronic Migraine
Authors: Goadsby PJ
Published: March 2003

Migraine is a common, disabling form of primary headache that has been linked by functional imaging studies to activation in the rostral brainstem. In specialty clinics migraine is most commonly seen in association with frequent less feature full headache that has been called transformed migraine or more recently termed chronic migraine. A patient is described with frequent migraine, 3 days per week, and less feature full headaches on other days. The patient has a cavernoma in the midbrain that has bled. She was previously headache free and now has contralateral daily headache. The patient supports the functional imaging observations from positron emission tomography (PET) that the rostral brainstem is pivotal in migraine pathophysiology, particularly the contralateral midbrain periaqueductal grey matter. Moreover, the patient's lesion provides biologically plausible support that a single entity causes her clinical presentation: chronic migraine, not two-disorders, migraine and tension-type headache.
The Movement-Related Potential in Children with Migraine and Tension-Type Headache
Authors: Müller BW , Sartory G , Tackenberg A
Published: March 2003

Migraine is characterized by an elevated contingent negative variation (CNV) in adults and children. In the present study the movement-related potential preceding self-initiated movements, the Bereitschaftspotential, was investigated in 30 children (mean age 12 years) who were suffering from migraine and tension-type headache and in 16 healthy age-matched controls. Children pressed a button 80 times with the right index finger while movement-related potentials were recorded from frontal and central electrodes. Whereas healthy children evidenced positive movement-related potentials at left and midline positions, children with migraine and tension-type headache showed negative movement-related potentials at midline leads without lateralization. Negativity was even more pronounced in cases of migraine with than without aura symptoms.
Motion Sickness and Migraine: Optokinetic Stimulation Increases Scalp Tenderness, Pain Sensitivity in the Fingers and Photophobia
Authors: Drummond PD
Published: March 2003

The aim of this study was to determine whether scalp tenderness and photophobia, two well-recognized symptoms of migraine, develop during the motion sickness induced by optokinetic stimulation. To investigate whether motion sickness has a general influence on pain perception, pain was also assessed in the fingertips. After optokinetic stimulation, nausea increased more and headache persisted longer in 21 migraine sufferers than in 15 non-headache controls. Scalp tenderness increased during optokinetic stimulation in nauseated subjects, and pain in the fingertips increased more and photophobia persisted longer in migraine sufferers than controls. These findings suggest that the disturbance responsible for nausea also sensitizes trigeminal nociceptive neurones or releases inhibitory controls on their discharge. A low nausea threshold and a propensity for sensitization to develop rapidly in nociceptive pathways may increase susceptibility to migraine.
Acute and Chronic Hypertensive Headache and Hypertensive Encephalopathy
Authors: Spierings ELH
Published: March 2003

Three patients are described who experienced headache from hypertension: one had acute headache from acute hypertension, one had daily, morning headaches from chronic hypertension, and one had acute headache with generalized tonic-clonic seizure from hypertensive encephalopathy. The presumed pathophysiological mechanisms involved in the three hypertensive headache conditions are reviewed.
Cox-2 Inhibitor for the Treatment of Idiopathic Stabbing Headache Secondary To Cerebrovascular Diseases
Authors: Piovesan EJ , Zukerman E , Kowacs PA , Werneck LC
Published: March 2003

The idiopathic stabbing headache (ISH) is characterized by a stabbing pain of short duration, variable localization and an errant evolution pattern. As its biological mechanisms are unknown and the treatment options are little effective, this disorder shows a strong impact on the patient's life. Two females and one male, aged 76, 66 and 72 years, respectively, started presenting ISH within 20 days after the onset of a stroke. All the patients were treated for the ISH with celecoxib, a COX-2 specific inhibitor, with full recovery from ISH up to 6 days after it was first administered. The interruption of the drug 60 days after the treatment with celecoxib induced again the appearance of algic symptoms in two patients. We concluded that cerebrovascular diseases (CD) can lead to ISH and that the COX-2 inhibitor can be an effective prophylactic drug for ISH after CD.
Exaggerated Interictal Cerebrovascular Reactivity But Normal Blood Flow Velocities in Migraine Without Aura
Authors: Dora B , Balkan S
Published: March 2003

Interictal cerebrovascular reactivity and blood flow velocities were tested in 23 patients with migraine without aura and 10 age- and sex-matched healthy controls by using the breath holding index (BHI). The mean systolic, diastolic and mean velocities and pulsatility indices were not different in the controls and patients. The BHI was found to be significantly greater ( P = 0011) in the patients (1.64 ± 0.33) compared with the controls (1.26 ± 0.37), showing an exaggerated reactivity to hypercapnia in migraineurs. Reactivity to pCO2 theoretically depends on pre-existing arteriolar tone and thereby on baseline velocity. Our finding of similar blood flow velocities in controls and patients suggests that the underlying cause for this high reactivity may not be an increased vasotonus but an increased sensitivity to changes in blood CO2 levels.
Sudden Onset Headache: A Prospective Study of Features, Incidence and Causes
Authors: Landtblom A-M , Fridriksson S , Boivie J , Hillman J , Johansson G , Johansson I
Published: March 2003

Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.
An Epidemiological Survey of Hemiplegic Migraine
Authors: Thomsen L Lykke , Eriksen M Kirchmann , Romer S Faerch , Andersen I , Ostergaard E , Keiding N , Olesen J , Russell MB
Published: March 2003

The objective of the present study was to use systematic nation-wide case-finding methods to establish the prevalence and sex ratio of hemiplegic migraine (HM) in the entire Danish population of 5.2 million inhabitants. Affected patients were identified from three different recruitment sources: the National Patient Register, case records from private practising neurologists and advertisements. Based on the observed number of affected patients from each case-finding method, it was attempted to estimate the total number of affected patients by means of the statistical method known as capture- recapture. Two hundred and ninety-one affected patients were identified; 147 were familial HM from 44 different families, 105 were sporadic HM and 39 were unclassifiable HM. The HM sex ratio (M: F) was 1: 3. Based on the identified number of affected patients the prevalence of HM at the end of 1999 was estimated to be 0.01% in Denmark, where the familial and sporadic form were equally frequent.
Zolmitriptan is Effective and Well Tolerated in Japanese Patients with Migraine: A Dose-Response Study
Authors: Sakai F , Iwata M , Tashiro K , Itoyama Y , Tsuji S , Fukuuchi Y , Sobue G , Nakashima K , Morimatsu M
Published: March 2003

This phase II study investigated the efficacy, tolerability and dose-response relationship of oral zolmitriptan in the treatment of a single migraine attack in Japanese patients. A bridging analysis then assessed the validity of extrapolating western clinical data to these Japanese patients. In this multicentre, randomized, double-blind, placebo-controlled study, patients received a single dose of placebo or zolmitriptan 1, 2.5 or 5 mg. The primary endpoints were 2-h headache response and the tolerability of zolmitriptan. A statistically significant dose-response relationship was observed for the 2-h headache response ( P = 0.003). The 2.5 mg group had significantly greater 2-h headache response than the placebo group ( P = 0.032). The adverse event profile was similar to that reported in western patients, and no adverse events unique to the Japanese population were observed. The bridging analysis report confirmed similar efficacy and tolerability of zolmitriptan in Japanese and western populations. In the Japanese patients, the estimated response rates were 34.3%, 45.2%, 57.7% and 66.2% for placebo, and zolmitriptan 1, 2.5 and 5 mg, respectively, while in the western population the corresponding rates were 39.9%, 49.6%, 61.2% and 71.7%. Zolmitriptan is effective and well tolerated in the acute treatment of migraine in Japanese patients. The optimal dose was 2.5 mg, although the 5 mg dose may provide further benefit for some patients. The bridging analysis supports extrapolation of data from western to Japanese patients.
Spontaneous Csf Leaks Mimicking Benign Exertional Headaches
Authors: Mokri B
Published: March 2003

Spontaneous CSF leaks are increasingly recognized, and a broader clinical and imaging spectrum of the disorder is emerging. The headaches of CSF leaks are typically orthostatic, but sometimes especially with chronicity the orthostatic features are blurred into lingering chronic daily headaches. Additional types of headache are also increasingly recognized. Two patients with spontaneous CSF leaks presented with intermittent transient severe headaches provoked by Valsalva-type manoeuvres. Orthostatic features were absent and the patients were asymptomatic if they avoided the provoking manoeuvres. One patient had been treated for 6 years for benign exertional headaches and had failed many medical treatments, including courses of indomethacin. He was found to have a leak from cribriform plate. The second patient had been symptomatic for several months, had diffuse pachymeningeal gadolinium enhancement on head magnetic resonance imaging, spinal meningeal diverticula, and CSF leak at the thoracic spine level. Headaches that mimic benign exertional headaches are yet another mode of the still broadening clinical presentation of spontaneous CSF leaks.
Benign Cough Headache
Authors: Boes CJ , Matharu MS , Goadsby PJ
Published: March 2003

Benign cough headache is an uncommon primary headache disorder marked by short- lasting attacks of pain triggered by coughing. Magnetic resonance imaging of the brain is required to assure that the cough headache is truly benign. The aetiology of the pain is unclear, but is probably associated with the brief increased intracranial pressure that attends coughing. We have reviewed the clinical features, aetiology, differential diagnosis, management, and prognosis of benign cough headache.
Brain Blood Flow in the Nitroglycerin (Gtn) Model of Migraine: Measurement Using Positron Emission Tomography and Transcranial Doppler
Authors: Bednarczyk EM , Wack DS , Kassab MY , Burch K , Trinidad K , Haka M , Gona J
Published: March 2003

Nitroglycerin has been widely used as a model of experimental migraine. Studies combining measurement of flow velocity using transcranial Doppler (TCD) concurrently with measures of cerebral blood flow (CBF) are uncommon. We report the results of a study combining TCD and positron emission tomography (PET). Healthy volunteers with no personal or family history of migraine underwent measurement of CBF using H215O PET, and velocity using TCD. Measurements were done at baseline, and following i.v. nitroglycerin at 0.125, 0.25 and 0.5 μg/kg per min. Subcutaneous sumatriptan (6 mg) was injected, with CBF and velocity measured 15, 30, and 60 min later. Nitroglycerin was terminated and measurements obtained 30 min later. Six male and six female subjects were studied. Nitroglycerin increased global CBF while flow velocities decreased. Sumatriptan did not have a significant effect on these values. Regions of increased flow included the anterior cingulate, while regions of decreased flow included the occipital cortex. Our data suggest that nitroglycerin induces regional changes in CBF that are similar to changes reported in spontaneous migraine, but produces distinctly different effects on global CBF and velocity.
Preclinical Studies Characterizing the Anti-Migraine and Cardiovascular Effects of the Selective 5-HT1D Receptor Agonist PNU-142633
Authors: McCall RB , Huff R , Chio CL , TenBrink R , Bergh CL , Ennis MD , Ghazal NB , Hoffman RL , Meisheri K , Higdon NR , Hall E
Published: March 2003

The present study describes the preclinical pharmacology of a highly selective 5-HT1Dreceptor agonist PNU-142633. PNU-142633 binds with a Ki of 6 nM at the human 5-HT1Dreceptor and a Ki of > 18 000 nM at the human 5-HT1B receptor. The intrinsic activity of PNU-142633 at the human 5-HT1D receptor was determined to be 70% that of 5-HT in a cytosensor cell-based assay compared with 84% for that of sumatriptan. PNU-142633 was equally effective as sumatriptan and a half-log more potent than sumatriptan in preventing plasma protein extravasation induced by electrical stimulation of the trigeminal ganglion. Like sumatriptan, PNU-142633 reduced the increase in cat nucleus trigeminal caudalis blood flow elicited by electrical stimulation of the trigeminal ganglion compared with the vehicle control. The direct vasoconstrictor potential of PNU-142633 was evaluated in vascular beds. Sumatriptan increased vascular resistance in carotid, meningeal and coronary arteries while PNU-142633 failed to alter resistance in these vascular beds. These data are discussed in relation to the clinical findings of PNU-142633 in a phase II acute migraine study.