bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping Styles of Headache Sufferers
Authors: Siniatchkin M , Riabus M , Hasenbring M
Published: March 2003

Psychological factors are important in the chronification and aggravation of headaches. We studied 90 patients suffering from migraine, chronic daily headache (CDH) evolved from migraine, and episodic or chronic tension-type headache (TTH). Emotional, cognitive, and behavioral pain coping were assessed using the Kiel Pain Inventory (KPI), Beck's Depression Inventory, the State-Trait-Anxiety Inventory, and Quality of Life Questionnaire. In addition, the clinical course of headache was analyzed using a validated headache diary. The results were as follows. Firstly, the KPI is reliable internally for the assessment of pain-coping strategy employment among headache patients. Secondly, migraine sufferers were characterized by pronounced psychological abnormalities during the headache phase, demonstrating a less adaptive coping behavior. This was in contrast to the TTH patients, who showed more general distress manifesting in elevated anxiety and lower quality of life. The only factor which appeared to be essential for differentiating between migraine and TTH was the intensity of headache. Thirdly, chronic TTH and CDH evolved from migraine demonstrated more pronounced psychological disabilities and more severe clinical courses of headaches than episodic TTH or nontransformed migraine. The predictor variable for transformation of migraine was impairment of well-being/quality of life, and for transformation of TTH, the frequency of headaches and depression. Finally, analgesic misuse seems to be less important for chronification and transformation of headaches than the degree of psychological disability. This study draws attention to the role of psychological factors in the chronification of TTH and transformation of migraine and provides some recommendations for the behavioral treatment of chronic headaches.
Pressure Pain Threshold and Pain Tolerance in Episodic Tension-Type Headache Do Not Depend on the Presence of Headache
Authors: Bove GM , Nilsson N
Published: March 2003

Pressure pain thresholds and responses to painful mechanical stimuli were obtained from 20 subjects with episodic tension-type headaches (TTH). Tender points in the temporalis and trapezius muscles were studied, along with two nontender points, one in the temporalis and one on the Achilles tendon. Two examinations were performed, one during and one without a headache, and results were compared. No significant differences were found in either variable for any tested points. The data demonstrate that the sensitivity level of these points does not differ based on the presence or absence of TTH. This suggests that the muscle sensitivity in TTH is constant. The observation that the sensitivity levels of both tender and nontender points did not vary suggests that the underlying mechanism or effect of TTH is not restricted to tender muscles.
Tolfenamic Acid Decreases Migraine Recurrence When Used with Sumatriptan
Authors: Krymchantowski AV , Adriano M , Fernandes D
Published: March 2003

Although sumatriptan is an effective drug for the treatment of acute migraine attacks, recurrence has been cited as an important limitation for its use. Tolfenamic acid is also effective in the acute treatment of migraine attacks. We studied the recurrence rate of migraine attacks with the use of sumatriptan plus tolfenamic acid among patients who presented frequent recurrence with sumatriptan. Fifty migraineurs were retrospectively studied, all having treated at least 10 attacks with 100 mg P.O.; sumatriptan was effective in at least eight of them. The patients also presented recurrence in less than 24 h in at least five of the treated attacks. We then used sumatriptan 100 mg plus tolfenamic acid 200 mg P.O. during the first 60 min of the attack; 240 attacks were treated and there was recurrence in 57 (23.8%). With sumatriptan alone, 5 out of 8 attacks (62.5%) presented recurrence. We therefore conclude that the combination sumatritpan plus tolfenamic acid is effective in reducing the recurrence rate from 5 of 8 (62.5%) to 1.19 of 5 (23.8%). Further prospective studies with a double-blind design and a higher number of treated attacks are necessary to confirm these initial observations.
Migraine-Related Seizures in an Epileptic Population
Authors: Veliog;lu SK , Qqouml;zmenoglu M
Published: March 2003

A relationship between epilepsy and migraine has long been postulated, but the nature of this interaction is still debated. We studied adult patients with epilepsy and investigated the relationship between migraine and epilepsy. Fourteen percent ( n=412) of adult patients with seizures were identified with a diagnosis of migraine. We also found a direct relationship between migraine and epilepsy (a migraine-induced epilepsy) in 1.7% (seven patients) of the patients with seizures. Patients were at increased risk for both conditions if they had migraine with aura and catamenial epilepsy. The seizure began during or shortly after the migraine aura in all of the cases and preceded the headache. Three of four patients who were refractory to management with antiepileptic drugs using either mono or combination therapy improved seizure control with combination antimigraine and antiepileptic drugs.
Nitric Oxide Pathway, Ca2+, and Serotonin Content in Platelets from Patients Suffering from Chronic Daily Headache
Authors: Sarchielli P , Alberti A , Russo S , Codini M , Panico R , Floridi A , Gallai V
Published: March 2003

An alteration in serotonin concentration has been found in patients with chronic headache caused by abuse of analgesic substances as well as an up-regulation of 5HT2 platelet receptors, which has been correlated with chronicization of the headache. In a previous study we demonstrated an increase in L-arginine/nitric oxide (NO) pathway activity in platelets from patients affected by migraine with or without aura, particularly during attacks. In the present research we assessed the variations in platelet L-arginine/NO pathway and cyclic guanosine monophosphate (cGMP) levels in 32 patients affected by chronic daily headache (CDH) (8M, 24F, age range 34-50 years) both during and between attacks. In these same patients, the platelet aggregation to different collagen concentrations (0.3, 1, 3 μg/ml) was determined as well as the intracellular platelet calcium concentration using fluorescence polarization spectrometry. These parameters were compared with those of an age- and sex-matched control group ( n=25; n=10, n=15, age range 35 - 51 years). A reduction found in platelet aggregation response to each collagen concentration used ( p <0.001) was coupled with an increased NO and cGMP production (NO: p <0.0001; cGMP: p <0.001). This was accompanied by a significant increase in intracytosolic Ca2+ ( p <0.0001) concentration and a reduced platelet serotonin content compared to those in control individuals ( p <0.0002). Changes in the above platelet parameters were accentuated more in patients with analgesic abuse than in CDH patients with no drug abuse. These findings suggest the occurrence of an activation of cGMP-Ca2+ mediated events in CDH patients with analgesic abuse. This physiologic compensatory mechanism, which intervenes in overcoming the increase in cytosolic Ca2+ levels, is not as efficient at limiting serotonin depletion by platelet dense bodies. A similar depletion in the central serotoninergic pathway can be assumed in the same patients.
Migraine Consultation Patterns in Primary Care. Results From the Pcaom Study 1994-96
Authors: Krobot KJ , Schröder-Bernhardi D , Pfaffenrath V
Published: March 2003

In order to establish a basis for the planning of improved medical care of migraine in Germany, we report on the proportion of migraine patients under primary care and the continuity of consultations for migraine as determined by age, gender, and history of migraine and nonmigraine practice contact (Primary Care of Migraine, PCAOM Study). A primary-care-physician-based migraineurs' sample of 16,573 women and 4,636 men (MediPlus, IMS Health) was placed in relation to cases expected according to International Headache Society criteria in the base population, and was followed for up to 3 years for repeat consultations. Overall, no more than 51% and 37%, respectively, of female and male statutory health-insured migraine headache sufferers had a migraine diagnosis mentioned at least once a year in primary care. At younger ages, substantially less advantage was taken of available primary healthcare for migraine; 79% of the women and 74% of the men were estimated to present again to the same primary-care physician within 3 years because of migraine, the corresponding figures for patients with no history of migraine in the practice concerned being 41% and 31%, respectively. Following first migraine contacts, time to recontact and quarterly recontact prevalences for migraine did not differ, whether on the basis of an established nonmigraine primary care relationship or a first encounter with a medical practice. Trust evidenced by an existing nonmigraine doctor-patient relationship apparently did not carry over to migraine. Results indicate that one of the greatest challenges in relation to the care of migraine patients in Germany is to establish and maintain solid doctor-patient relationships.
Possible Antimigraine Mechanisms of Action of the 5HT1F Receptor Agonist LY334370
Authors: Shepheard S , Edvinsson L , Cumberbatch M , Williamson D , Mason G , Webb J , Boyce S , Hill R , Hargreaves R
Published: March 2003

This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10−5 M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg−1, iv) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg−1, iv) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg−1, iv), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg−1, iv. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.
Repeatability of the Intensity Dependence of Cortical Auditory Evoked Potentials in the Assessment of Cortical Information Processing
Authors: Sándor PS , Roon KI , Ferrari MD , van Dijk JG , Schoenen J
Published: March 2003

Data on repeatability and optimal settings are needed when studying the influence of drugs on the intensity dependence of auditory evoked cortical potentials (IDAP). IDAP was recorded at intervals of 1, 2, and 24 h at two centers in 22 healthy volunteers. Settings were modified to compare fixed versus randomly varied stimulus repetition rate, as well as 30 Hz and 100 Hz low pass filters. Repeatability was assessed for different intervals and different settings. Group means did not differ between centers, the 2-h or 24-h retest, or when using different settings. We observed an order effect for the 1 h retest. Fixed repetition rate and the 30 Hz filter improved repeatability with still high intraindividual variability. IDAP group means can be compared between centers for retest intervals of 2 h and 24 h and different settings. Variability is too large to compare individuals.
Out-of-Body Experiences and Related Phenomena in Migraine Art
Authors: Podoll K , Robinson D
Published: March 2003

In a collection of 562 migraine art pictures, seven pieces illustrate various elements of out-of-body experiences (OBEs) and related phenomena, including the somesthetic sensations of a duplicate or parasomatic body and the visual experiences of perceiving the own body, i.e. autoscopy, and its environment from a vantage point out of the body. Phenomenological features of the OBEs depicted are compared with 17 similar case reports reviewed from the literature. It is concluded that OBEs can occur as migraine aura symptom, which supports the notion that OBEs represent a preformed functional response of the brain. This neuropsychological theory supplements existing psychological theories of OBEs, which consider the said phenomena as representing hallucinatory experiences based on imagination and memory.
Are the Periodic Changes of Neurophysiological Parameters During the Pain-Free Interval in Migraine Related to Abnormal Orienting Activity?
Authors: Siniatchkin M , Gerber W-D , Kropp P , Voznesenskaya T , Vein AM
Published: March 2003

Objective and methods

Migraine patients are characterized by increased amplitude and reduced habituation of contingent negative variation (CNV). Furthermore, the CNV underlies periodic changes during the pain-free interval, being maximal before attack. The periodicity of CNV is related to periodic changes in habituation, probably due to variation of orienting activity during the pain-free interval. CNV and orienting response (OR) were studied in 20 females suffering from migraine without aura and in 12 matched healthy females. The neurophysiological recordings in the group of patients were performed 1–4 days before and 4 days after a migraine attack. The amplitudes and habituation of early and late components and total CNV were calculated. The OR was assessed using the habituation of the skin conductance response (SCR) and alpha blocking (AB). The non-parametric tests were employed for statistical analysis.

Results

There were no differences between the two groups for habituation of all CNV components and of SCR following an attack. However, the habituation of AB was significantly reduced in migraine. Before attack we observed a significantly reduced habituation of the early and total CNV and of the AB compared to controls and recordings performed after an attack. The habituation of the late component and of SCR remained unchanged.

Conclusions

The abnormal habituation could be explained by the periodic changes of physiological parameters during the pain-free interval. The impaired habituation of early CNV in migraine is associated with increased orienting activity seen only in the central component (AB) of OR.
Linked Activation of Nitric Oxide Synthase and Cyclooxygenase in Peripheral Monocytes of Asymptomatic Migraine Without Aura Patients
Authors: Stirparo G , Zicari A , Favilla M , Lipari M , Martelletti P
Published: March 2003

Many reports indicate that nitric oxide (NO) could be involved in migraine without aura (MWA), an extremely diffuse clinical event. Since monocyte may be a relevant source of NO, we analysed monocyte activation in MWA patients, in a period in which they were free of symptoms. NO basal production by MWA peripheral monocytes was significantly higher than in healthy subjects (91.25 ± 8.6 μm/106 cells vs. 22.6 ± 3.2 μm/106 cells). Interestingly, even the release of prostaglandin E2 (PGE2), was higher in MWA patients than in healthy subjects (3137 ± 320 pg/106 cells vs. 1531 ± 220 pg/106 cells). The incubation of monocytes from healthy subjects and MWA patients with N-nitro-l-arginine methyl ester caused a marked decrease of both NO and PGE2 release. We hypothesise that NOS and cyclooxygenase pathways in monocytes are linked and are, in MWA patients, up-regulated, even in a symptoms-free period. NO and PGE2 hyperproduction could therefore be involved in the neurovascular modifications leading to migraine attacks.
The Effect of Intranasal Cocaine and Lidocaine on Nitroglycerin‐Induced Attacks in Cluster Headache
Authors: Costa A , Pucci E , Antonaci F , Sances G , Granella F , Broich G , Nappi G
Published: March 2003

The administration of nitroderivatives in cluster headache (CH) sufferers is the most reproducible experimental paradigm to induce spontaneous‐like pain attacks. Previous uncontrolled studies have reported that the local use of anaesthetic agents in the area of the sphenopalatine fossa is able to extinguish nitroglycerin (NTG)‐induced pain in CH. The present study, carried out according to a double‐blind placebo‐controlled design, included 15 CH patients, six with episodic CH (mean ± sd age of 36.8 ± 5.6 years), and nine with chronic CH (37.8 ± 10.4 years). Patients had undergone a standard NTG test (0.9 mg sublingually), during which the intensity of pain was scored using a visuo‐analogic scale (VAS, range 0–10). Nine patients (two with the episodic form, seven with the chronic form) experienced a typical, spontaneous‐like attack on the usual side, occurring in all cases within 45 min. In these patients, the test was repeated with an interval of 2 days, and once pain intensity reached 5 on the VAS, a 10% solution of cocaine hydrochloride (1 ml, mean amount per application 40–50 mg), or 10% lidocaine (1 ml), or saline was applied using a cotton swab in the area corresponding to the sphenopalatine fossa, under anterior rhinoscopy. This was done in both the symptomatic and the non‐symptomatic side, for 5 min. Treatments were always performed randomly, in separate sessions. All patients responded promptly to both anaesthetic agents, with complete cessation of induced pain occurring after 31.3 ± 13.1 min for cocaine and 37.0 ± 7.8 min for lidocaine (M ± sd). In the case of saline application, pain severity increased thereafter, and extinction of the provoked attacks occurred with a latency of 59.3 ± 12.3 min ( P < 0.01 and P < 0.01 vs. cocaine and lidocaine, respectively, Mann–Whitney U‐test). While further suggesting that the sphenopalatine ganglion participates in the mechanisms of pain, these findings indicate that the local administration of the anaesthetic agents cocaine and lidocaine is effective on NTG‐induced CH attacks, and may be used in the symptomatic treatment of this disorder.
Prednisone as Initial Treatment of Analgesic-Induced Daily Headache
Authors: Krymchantowski AV , Barbosa JS
Published: March 2003

The majority of the patients who seek medical care in tertiary headache centres present with transformed migraine, and convert to daily headache, as a result of excessive intake of symptomatic medications (SM). This study aimed to analyse the possibility of using a short course of oral prednisone for detoxifying patients with chronic daily headache due to medication overuse in an out-patient setting. Four hundred patients with headache occurring more than 28 days per month for longer than 6 months were studied (mean baseline frequency of 0.96). Symptomatic medications were stopped suddenly and prednisone was initiated in tapering doses during 6 days, followed by the introduction of preventive treatment. Withdrawal symptoms and the frequency, intensity and duration of the headache, as well as the consumption of rescue medications, were analysed during the first 16 and 30 days of withdrawal. Eighty-five percent of the patients experienced a reduction in headache frequency and no patients presented severe attacks during the first 6 days. With regard to the following 10 days, 46% of the patients experienced at least 2 days without headache and 58% less intense attacks. Most of the patients noticed attacks with longer duration. After the 30-day period there was a significant decrease in headache frequency (mean 0.83, P < 0.001), and no patients returned to overuse of SM. This study demonstrates that it is possible to detoxify patients suffering from rebound headaches, using oral prednisone during the first days of withdrawal, in an out-patient setting.
Oral Contraceptives and Stroke
Authors: Bousser M-G , Kittner S J
Published: March 2003

Since 1962, more than 25 studies have been devoted to the relationship between oral contraceptives and stroke. They are all case-control or cohort epidemiological studies and thus contain the difficulties and biases that are inherent in these types of studies. The following conclusions can be drawn from these studies:

High oestrogen content (≥ 50 μg) increases the risk of stroke, all stroke subtypes, and stroke death. Low oestrogen content (< 50 μg) carries a very low or no risk of stroke. There are no data on progestogen only oral contraceptives. Stroke risk is greatly increased if associated risk factors are present, in particular hypertension, cigarette smoking and migraine. Oral contraceptives, even at low doses, significantly increase the risk of cerebral venous thrombosis, which is further enhanced if congenital thrombophilia is present. The attributable risk of stroke in young women using oral contraceptives is about 1 per 200 000 woman-years.

The contraceptive and non-contraceptive benefits of low dose oral contraceptives vastly outweigh their risks provided that other risk factors are absent or well controlled.
Amitriptyline Reduces Myofascial Tenderness in Patients with Chronic Tension-Type Headache
Authors: Bendtsen L , Jensen R
Published: March 2003

The tricyclic anti-depressant amitriptyline is widely used in the treatment of chronic tension-type headache. The aim of the present study was to investigate whether the analgesic effect is caused by a reduction of muscle pain or by a general reduction of pain sensitivity. Thirty-three non-depressed patients with chronic tension-type headache were treated with amitriptyline 75 mg/day and with the highly selective serotonin reuptake inhibitor citalopram 20 mg/day in a 32-week, double-blind, placebo-controlled, three-way crossover study. At the end of each treatment period, actual headache intensity and pericranial myofascial tenderness were recorded, pressure pain detection and tolerance thresholds were measured in the finger and in the temporal region and the electrical pain threshold was measured at the labial commissure. Amitriptyline reduced tenderness and headache intensity significantly more than placebo ( P = 0.01 and P = 0.04, respectively). The reduction in tenderness could be ascribed solely to the group of patients who responded to amitriptyline treatment by at least 30% reduction in headache while tenderness was unchanged in non-responders. Amitriptyline did not affect pressure or electrical pain thresholds at any of the examined locations. Citalopram had no significant effect on any of the examined parameters. These findings indicate that amitriptyline elicits its analgesic effect in chronic myofascial pain by reducing the transmission of painful stimuli from myofascial tissues rather than by reducing overall pain sensitivity. We suggest that this effect is caused by a segmental reduction of central sensitization in combination with a peripheral anti-nociceptive action.
Migraine Attacks and Sleep in Children
Authors: Aaltonen K , Hämäläinen ML , Hoppu K
Published: March 2003

Falling asleep as a means of ending migraine attack was studied in 133 4–16-year-old children in out-patient settings. Children registered 999 migraine attacks in headache diaries using a visual analogue scale (VAS) in 409 attacks and a five-face scale in 590 attacks. The distribution of maximal pain intensity was similar on both scales; on VAS 88% assigned grades between 63 and 100, and on the face scale 93% assigned grades of 4 or 5. Children fell asleep during 33% of the attacks ( n = 329), in 64% of these within the first hour ( n = 209). Of the children, 68% ( n = 91) had fallen asleep at least once during an attack. Falling asleep was more common in children under 8 years of age than in older children. In those under 8 years, 62% (95% confidence interval (CI) 49–75%) of attacks were resolved by sleep, in those aged 8–12 years 34% (26–41%), and in children > 12 years 24% (15–33%) (anova, P < 0.0001). Pain was relieved without sleep in 43% ( n = 431) of attacks, in 38% of these ( n = 383) within the first 4 h. The data on migraine resolution were missing for 24% ( n = 239) of the attacks, most often because the attack exceeded the 5-h observation period. This study confirms that migraine attacks in children are extremely painful and often resolve during an interval of sleep in children under 8 years of age.
Consistent Efficacy and Tolerability of Almotriptan in the Acute Treatment of Multiple Migraine Attacks: Results of a Large, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Pascual J , Falk RM , Piessens F , Prusinski A , Docekal P , Robert M , Ferrer P , Luria X , Segarra R , Zayas JM
Published: March 2003

In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher ( P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.
Visual, Long-Latency Auditory and Brainstem Auditory Evoked Potentials in Migraine: Relation to Pattern Size, Stimulus Intensity, Sound and Light Discomfort Thresholds and Pre-Attack State
Authors: Sand T , Vingen J Vanagaite
Published: March 2003

We aimed to estimate primary sensory evoked potential (EP) amplitude, amplitude–intensity functions and habituation in migraine patients compared with healthy control subjects and to investigate the possible relation to check size, sound and light discomfort thresholds, and the time to the next attack. Amplitudes of cortical visual evoked potentials (VEP, check size 8′ and 33′), cortical long latency auditory evoked potential (AEP N1P1; 40, 55 and 70 dB SL tones) and brainstem auditory evoked potential (BAEP wave IV–V; 40, 55 and 65 dB SL clicks) were recorded and analysed in a blind and balanced design. The difference between the response to the first and the second half of the stimulus sequence was used as a measure of habituation. Twenty-one migraine patients (16 women and five men, mean age 39.3 years, six with aura, 15 without aura) and 22 sex- and age-matched healthy control subjects were studied (18 women and four men, mean age 39.5 years). Low sound discomfort threshold correlated significantly with low levels of BAEP wave IV–V amplitude habituation ( r = –0.30, P = 0.05). VEP and AEP amplitudes, habituation, and amplitude–intensity function (ASF) slopes did not differ between groups when anova main factors were considered. Control group VEP habituation was found for small check stimuli ( P = 0.04), while potentiation was observed for medium sized checks ( P = 0.02). The eight migraine patients who experienced headache within 24 h after the test tended to have increased BAEP wave IV–V ASF slopes ( P = 0.08). This subgroup did also have a significant VEP habituation to small checks ( P = 0.04). No correlation was found between different modalities. These results suggest that: (i) VEP habituation/potentiation state and brainstem activation state may depend on the attack–interval cycle in migraine; (ii) VEP habituation/potentiation may depend on spatial stimulus frequency; (iii) phonophobia (and possibly photophobia) may depend more on subcortical (brainstem) function than on cortical mechanisms; (iv) low cortical preactivation in migraine could not be confirmed; (v) EP habituation and ASF analysis may reflect sensory modality-specific, not generalized, central nervous system states in migraine and healthy control subjects.
Slow Cortical Potentials in Migraine Families
Authors: Siniatchkin M , Kirsch E , Kropp P , Stephani U , Gerber W-D
Published: March 2003

Amplitude and habituation of event-related potentials are abnormal in migraine. We investigated 43 migraine and 41 healthy families to evaluate the influences of age, sex and familial contribution on the variance of amplitude and habituation of the contingent negative variation (CNV). Analysis of individual differences in relation to the CNV habituation was performed. The study demonstrated that habituation of the early CNV component characterizes migraine considerably better than the CNV amplitudes. Habituation, however, is strongly influenced by age. Migraine adults and children generally showed reduced habituation. Surprisingly, more than 30% of the healthy adults demonstrated a marked loss of habituation. The reduced CNV habituation represented a high sensitivity but low specificity to migraine, especially in children. CNV amplitude and habituation parameters revealed a considerable familial contribution associated with migraine. No familial influence on either morphology or habituation of the CNV in healthy families or between healthy members of migraine families was observed. The low specificity and familial transmission of CNV parameters in members of migraine families suggest that increased amplitudes and reduced habituation of CNV do not constitute a primary risk factor for migraine, but rather represent a predisposition. Genetic components probably affect variation of the CNV amplitude and habituation.
Possible Risk Factors and Precipitants for Migraine with Aura in Discordant Twin-Pairs: A Population-Based Study
Authors: Ulrich V , Olesen J , Gervil M , Russell MB
Published: March 2003

The aim of the present study was to detect possible risk factors in migraine with aura (MA) by analysis of discordant twin-pairs. In a recent population-based twin study we established that environmental factors account for approximately 50% of the variation in liability to MA. A cohort of 5360 same-gender twin-pairs from the general population was screened for migraine. All twin-pairs with possible migraine were interviewed by a physician. A questionnaire provided information about living conditions and lifestyle. Of the 169 discordant twin-pairs 51 were monozygotic and 118 were dizygotic twin-pairs. Several putative risk factors—schooling, education, marital status, smoking status and alcohol consumption—showed no association with MA. The presence of migraine without aura or tension-type headache did not increase the risk of MA. Stress and mental tension, and bright light precipitated attacks of MA in, respectively, 44% and 28% of the twins.
Prevalence of Migraine and Non-Migrainous Headache—Head-HUNT, A Large Population-Based Study
Authors: Hagen K , Zwart J-A , Vatten L , Stovner Lj , Bovim G
Published: March 2003

The objective of this study was to estimate the 1-year prevalence of the following categories of headache; migraine, non-migrainous headache, frequent headache (> 6 days/month), and chronic headache (> 14 days/month). Between 1995 and 1997, all 92 566 inhabitants 20 years and older in Nord-Trøndelag county in Norway were invited to a comprehensive health study. Out of 64 560 participants, a total of 51 383 subjects (80%) completed a headache questionnaire. The overall age-adjusted 1-year prevalence of headache was 38% (46% in women and 30% in men). The prevalence of migraine was 12% (16% in women and 8% in men), and for non-migrainous headache 26% (30% in women and 22% in men). For frequent headache (> 6 days per month) and for chronic headache (> 14 days per month), the prevalence was 8% and 2%, respectively. Women had a higher prevalence than men in all age groups and for all headache categories. Prevalence peaked in the fourth decade of life for both men and women, except for ‘frequent non-migrainous headache’, which was nearly constant across all age groups in both genders. In accordance with findings in other western countries, we found that headache suffering, including migraine, was highly prevalent, especially in younger women.
The Challenge of Evidence-Based Migraine Therapy
Authors: Becker WJ
Published: March 2003

It is important that physicians practise evidence-based medicine. Clinical experience is important, but there are a number of reasons why clinical experience can lead to the impression that ineffective treatments are effective. There are major educational and research challenges which must be met before clinicians can practice evidence-based migraine therapy more extensively than at present. Treating physicians will need to learn more about the principles of evidence-based medicine. Researchers will need to produce more and better clinical trials that address important clinical questions. The results of these trials will need to be reported clearly, and we need to improve the efficiency with which these results can be accessed. It is important that the pharmaceutical industry, clinicians, and academic health centres work together to meet these challenges.
Cyclandelate in the Prophylaxis of Migraine: A Placebo-Controlled Study
Authors: Diener HC , Krupp P , Schmitt T , Steitz G , Milde K , Freytag S ,   on behalf of the Study Group
Published: March 2003

The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients ( n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.
Referred Pain After Painful Stimulation of the Greater Occipital Nerve in Humans: Evidence of Convergence of Cervical Afferences on Trigeminal Nuclei
Authors: Piovesan EJ , Kowacs PA , Tatsui CE , Lange MC , Ribas LC , Werneck LC
Published: March 2003

Cranial sensory innervation is supplied mainly by the trigeminal nerves and by the first cervical nerves. Excitatory and inhibitory interactions among those nerve roots may occur in a mechanism called nociceptive convergence, leading to loss of somato-sensory spatial specificity. Three volunteers in an experimental trial had sterile water injected over their greater occipital nerve on one side of the neck. Pain intensity was evaluated 10, 30 and 120 s after the injection. Two of the patients reported intense pain. Trigeminal autonomic features, suggestive of parasympathetic activation, were seen associated with trigeminally distributed pain. These data add to and reinforce previous evidence of convergence of cervical afferents on the trigeminal sensory circuit.
Treatment of Migraine Attacks with Intranasal Alniditan: An Open Study
Authors: Diener HC , Louis P , Schellens R , De Beukelaar F ,   on behalf of the Study Group
Published: March 2003

In this open phase-II clinical tolerability trial 17 neurologists enrolled a total of 112 patients and instructed them to administer a maximum of two doses of intranasal alniditan, a 5-HT1B/D receptor agonist, for the treatment of three consecutive migraine attacks of moderate to severe intensity. A second dose of the trial medication was allowed within 1–24 h after the first administration. At 1 h after intranasal administration, 70/103 (68%) patients had responded to treatment (reduction from severe or moderate headache before treatment to mild or no headache) after their first migraine attack, 65/94 (69%) after their second and 52/75 (71%) after their third. In 187/270 (69%) of all attacks, patients were considered responders at 1 h. The median time to onset of effect was 30 min. The migraine headache recurred in 44% (attack 1), 55% (attack 2) and 44% (attack 3) after 4–5 h. Sixty-eight per cent of the patients reported nasal irritation, 19% taste disturbance and 44% throat irritation. Alniditan 2 mg, administered via the intranasal route, was effective in relieving migraine headaches in over two-thirds of the patients at 1 h.
Headache in the HIV Patient: A Review with Special Attention to the Role of Imaging
Authors: Graham CB , Wippold FJ
Published: March 2003

Headache is one of the most commonly encountered neurologically related complaints in HIV patients. The authors review the relationship between HIV infection and headache and discuss the role of neuroimaging in this select patient group.
The Lack of Vasoconstrictor Effect of the Pineal Hormone Melatonin in an Animal Model Predictive of Antimigraine Activity
Authors: Tom B , De Vries P , Heiligers JPC , Willems EW , Scalbert E , Delagrange P , Saxena PR
Published: March 2003

The pineal hormone, melatonin, has been implicated in the pathophysiology of migraine and several studies have demonstrated its vasoconstrictor properties. In the present study, systemic and carotid haemodynamic effects of melatonin, administered directly into the carotid artery, were investigated in anaesthetized pigs. Ten-minute intracarotid infusions of melatonin (1, 10 and 100 μg kg−1 min−1) produced slight decreases in blood pressure and total carotid and arteriovenous anastomotic blood flows, but nutrient blood flow was not affected. The decrease in carotid blood flow was entirely caused by the hypotension, since no changes in vascular conductance values were observed. It is concluded that melatonin itself is not capable of producing vasoconstriction in the cranial circulation of anaesthetized pigs. Thus, it appears that melatonin has no anti-migraine potential via a vasoconstrictor mechanism.
Altered Cerebrovascular Response Pattern in Interictal Migraine During Visual Stimulation
Authors: Bäcker M , Sander D , Hammes MG , Funke D , Deppe M , Conrad B , Tölle TR
Published: March 2003

A dysbalance of the cerebrovascular response during functional activation of the brain has been postulated as a factor in the pathophysiology of migraine. To determine the dynamic pattern of the cerebrovascular response in migraineurs compared with a control group, changes of the cerebral perfusion during cerebral activation were studied with high temporal resolution by functional transcranial Doppler sonography (fTCD). The cerebral blood flow velocity (CBFV) in the right posterior cerebral artery (PCA) and the left middle cerebral artery (MCA) was measured simultaneously during visual stimulation in 19 interictal migraineurs and in 19 age- and sex-matched control subjects. Data were analysed with a previously validated technique based on automated stimulus-related averaging of the CBFV. The MCA migraineurs exhibited a steady increase of CBFV during the stimulation, while normal subjects showed a habituation of the CBFV response. The lack of habituation in migraineurs was significantly ( P ≤ 0.05) more pronounced across patients with a high attack frequency (≥ 4 per month) compared with migraineurs with a low attack frequency (< 4 per month). In the PCA, compared with normal subjects, migraineurs showed significantly ( P ≤ 0.05) stronger CBFV changes at the beginning and after the end of stimulation, with a slower decline to baseline. Data are in accordance with electrophysiological findings in migraineurs. It is assumed that a lack of habituation of the cerebrovascular response in migraineurs might contribute to a disturbance of the metabolic homeostasis of the brain that might induce migraine attacks.
Headache in Magical and Medical Papyri of Ancient Egypt
Authors: Karenberg A , Leitz C
Published: March 2003

Despite the intensity with which many scholars have studied the evolution of Egyptian medicine, interdisciplinary studies on the history of headache are scarcely extant. Following a short discussion of historiographical issues, the main objective of this paper is to present a comprehensive and detailed overview on this subject. Scattered references to headache are extracted from so-called magical papyri and from medical texts of the New Kingdom. Although little is known about the quality of headache and about accompanying symptoms, four predominant localizations are distinguished. Due to the lack of precise descriptions it is impossible to establish the retrospective diagnosis of migraine. Explanations of the origin of cephalalgia and of the corresponding therapeutic actions differ according to the nature of the source. In magical papyri, headaches are attributed to the action of demons and supernatural forces, whereas medical papyri emphasize the role of head trauma and of ‘pain matter’ occurring in the body. Treatment could be magical, pharmacological or surgical. Examples of incantations and prescriptions are analysed in detail.
Dose, Efficacy and Tolerability of Long-Term Indomethacin Treatment of Chronic Paroxysmal Hemicrania and Hemicrania Continua
Authors: Pareja JA , Caminero AB , Franco E , Casado JL , Pascual J , del Río M Sánchez
Published: March 2003

Indomethacin has consistently been proven to provide complete and sustained relief of symptoms in hemicrania continua (HC) and chronic paroxysmal hemicrania (CPH), but is not devoid of side-effects. The goal of this retrospective study is to assess the dose and side-effects of prolonged indomethacin treatment of HC and CPH. Twenty-six patients with either HC or CPH were followed during an average of 3.8 years after onset of treatment with indomethacin. Relief of symptoms occurred within 3 days of treatment, with 84 ± 32 mg/day of indomethacin. With time, 42% of patients experienced a decrease of up to 60% in the dose of indomethacin required to maintain a pain-free state. Six (23%) patients showed adverse events, mostly gastrointestinal and relieved with ranitidine. No major side-effects were observed. These results indicate that prolonged indomethacin treatment of HC or CPH has a good safety and tolerability profile with a reduction of up to 60% in the initial dose.
Long-Term Follow-Up of Patients Treated for Chronic Headache with Analgesic Overuse
Authors: Pini L-A , Cicero AFG , Sandrini M
Published: March 2003

The study aim is to describe the long-term clinical outcome of 102 chronic headache patients with analgesic daily use. They were assessed for daily drug intake (DDI), headache index (HI) and quality of life (QoL) and compared with a parallel group of patients with active chronic daily headache but no analgesic overuse. For the primary study group, baseline 1995 DDI was 1.80 ± 1.87 and did not differ significantly in 1999. Patients who daily continued to use analgesics had a higher 1995 baseline DDI ( t = 2.275, P = 0.025), a longer drug abuse history ( t = 2.282, P = 0.025) and a higher DDI ( t = 4.042, P < 0.001) 4 years later. At 4 years of follow-up, only one-third of patients initially treated for chronic daily headache and analgesic overuse are successful in refraining from chronic overuse. Those subjects appear to have a persistence for combination analgesic agents; however, their QoL is slightly better than that of patients who revert to episodic headache or continue with chronic daily headache but do not overuse analgesic agents. Persistent analgesic overuse seems to be linked to the length of abuse and to the number of drugs ingested.
Leukocyte Mitochondrial DNA A to G Polymorphism at 11084 is not a Risk Factor for Japanese Migraineurs
Authors: Takeshima T , Fukuhara Y , Adachi Y , Ishizaki K , Kusumi M , Kowa H , Iigaya M , Sakai F , Nakashima K
Published: March 2003

Mitochondrial dysfunction has been reported in patients with migraine. We investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166 Japanese migraineurs and 483 Japanese controls. The migraine group consisted of 43 patients suffering from migraine with aura (MWA) and 123 from migraine without aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7% in MWA and 8.1% in MOA. There was no significant difference among the groups (chi-square test). The mitochondrial DNA 11084 A to G transition was more common in Japanese subjects than reported in Caucasians; however, this polymorphism is not a genetic risk factor for migraine in Japanese patients.
Effects of Donitriptan on Carotid Haemodynamics and Cardiac Output Distribution in Anaesthetized Pigs
Authors: Tom B , De Vries P , Heiligers JPC , Willems EW , Kapoor K , John GW , Saxena PR
Published: March 2003

We investigated the effects of donitriptan, which possesses a uniquely high affinity and efficacy at 5-HT1B/1D receptors, on carotid and systemic haemodynamics in anaesthetized pigs. Donitriptan (0.16-100 μg kg-1, i.v.) dose-dependently decreased total carotid blood flow and vascular conductance (maximum response: -25 ± 3%). This effect was entirely due to a selective reduction in the cephalic arteriovenous anastomotic fraction (maximum response: -63 ± 3%; ED50%: 92 ± 31 nmol/kg); the nutrient vascular conductance increased. Donitriptan did not decrease vascular conductances in or blood flow to a number of organs, including the heart and kidneys; in fact, vascular conductances in the skin, brain and skeletal muscles increased. Cardiac output was slightly decreased by donitriptan, but this effect was confined to peripheral arteriovenous anastomoses. The haemodynamic effects of donitriptan were substantially reduced by the 5-HT1B/1D receptor antagonist GR127935. These results show that donitriptan selectively constricts arteriovenous anastomoses via 5-HT1B receptor activation. The drug should be able to abort migraine headaches and it is unlikely to compromize blood flow to vital organs.
The Clinical Characteristics of New Daily Persistent Headache
Authors: Li D , Rozen TD
Published: March 2003

New daily persistent headache (NDPH) is a subtype of chronic daily headache. The literature on NDPH is scant and its true aetiology is unknown. A retrospective chart review was carried out from a computerized database at the Jefferson Headache Centre from August 1997 to May 2000 to identify patients with NDPH using the Silberstein et al. criteria. Forty women and 16 men were identified. Age of onset ranged from 12 to 78 years. The peak age of onset was the second and third decade in women and the fifth decade in men. Eighty-two per cent of patients were able to pinpoint the exact day their headache started. Onset occurred in relation to an infection or flu-like illness in 30%. A prior headache history was found in 38% of patients. A family history of headache was documented in 29%. The duration of daily headache ranged from 1.5 h to 24 h; 79% were continuous. Nausea occurred in 68% of patients, photophobia in 66%, phonophobia in 61%, and lightheadedness in 55%. Laboratory testing and neuroimaging in all patients was normal except for Epstein-Barr virus antibody titres, which were positive in 71% of seven patients tested, representing past infection. NDPH appears to be a female-predominant disorder, marked by a continuous daily headache with associated migrainous symptoms. Over 80% of patients could state the exact date their headache began. One-third of patients developed NDPH with a flu-like illness.