bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial and Behavioral Characteristics in Chronic Headache Patients: Support for a Continuum and Dual-Diagnostic Approach
Authors: Scharff L , Turk DC , Marcus DA
Published: March 2003

The present study attempted to identify psychological differences among different headache diagnoses defined by IHS criteria as well as psychological differences by headache intensity and frequency. Differences between diagnostic categories reflected characteristics used to assign diagnoses, namely the constancy of pain and distracting behaviors of significant others due to isolating behavior from photophobia and phonophobia. A rating of headache intensity and frequency was a more powerful predictor of psychological ratings than diagnosis. Diagnosis was related to headache frequency but not intensity. The results suggest that a continuum diagnosis based on severity can be useful in conceptualizing headaches, and a dual-diagnostic system integrating headache characteristics with perceptions and coping ability would be helpful in determining treatment options.
Classification of Chronic Daily Headache by International Headache Society Criteria: Limits and New Proposals
Authors: Manzoni GC , Granella F , Sandrini G , Cavallini A , Zanferrari C , Nappi G
Published: March 2003

We conducted a retrospective study of 150 patients with chronic daily headache (CDH) to determine how to categorize their headache according to the classification of the International Headache Society (IHS). All patients were first evaluated at Parma and Pavia Headache Centres (from January 1992 to March 1993) and had had headache for at least 15 days a month during the previous 6 months. Four patients were thereafter excluded due to poor reliability. The 146 patients who met our CDH criteria (92 with and 54 without clear-cut migraine attacks) could be classified into four groups: (i) chronic tension-type headache (CTTH)-27 patients; (ii) coexisting migraine plus CTTH-65 patients; (iii) unclassifiable daily headache-27 patients; and (iv) migraine and an unclassifiable interval headache-27 patients. Seventy-two percent of patients with CDH had migraine as the initial form of their headache. We therefore propose to revise the IHS classification for migraine, taking into account its evolution, and add two subcategories, migraine with interparoxysmal headache and chronic migraine.
Clinical Neurophysiology and Neurotransmitters
Authors: Noordhout A Maertens de , Wang W , Schoenen J
Published: March 2003

Clinical neurophysiology allows non-invasive assessment of neurotransmitter function in various regions of the central and peripheral nervous system. In this review, we describe examples of functional evaluation of neurotransmission at the neuromuscular junction, in some spinal interneurons and intracortical circuits as well as evaluation of pharmacological modulation of some electrophysiological tests. These investigations are carried out to help our understanding of the pathophysiology of brain diseases. Finally, we discuss possible relationships between electrophysiological tests (evoked/event-related potentials and exteroceptive suppression of temporalis muscle activity) and neurotransmitter function in headache.
Migraine, Chronic Tension-Type Headache, and Cluster Headache in An Ethiopian Rural Community
Authors: Haimanot R Tekle , Seraw B , Forsgren L , Ekbom K , Ekstedt J
Published: March 2003

Fifteen-thousand-five hundred adults (320 years) in a rural district in Ethiopia with a population of 250 000 were studied for chronic headache. Door-to-door survey was performed by trained lay health workers using a questionnaire with a high degree or reliability and validity. The 1-year prevalence of migraine headache was 3.0% (4.2% for females and 1.7% for males) with the peak age specific rate in the fourth decade. Migraine headache was about three times more common in females than in males at any decade. Two-thirds of migraine sufferers had rather frequent attacks. The most frequent trigger factors were emotional stress (90%), changes of weather (78%), physical exhaustion (75%), and smell (70%). Migraine with aura was rare. Family occurrence of migraine in first-degree relatives was 30%. The 1-year prevalence of chronic tension-type headache was 1.7%, while cluster headache was found to be extremely rare. Compared to similarly performed surveys, the prevalence of migraine among rural Ethiopians was less than among Nigerian Africans.
Migraine Trigger Factors in a Non-Clinical Mexican-American Population in San Diego County: Implications for Etiology
Authors: Turner LC , Molgaard CA , Gardner CH , Rothrock JF , Stang PE
Published: March 2003

We conducted an investigation of migraine headache in a general population of Mexican-Americans living in San Diego county. Specific headache triggers were reported and analyzed, the most frequently reported for females with migraine being missing meals (58.9%), weather changes (54.4%), menstruation (53.6%), post-crisis letdown (52.7%), and fatigue (51.8%). The most frequently reported trigger factors for migraines reported by males were fatigue (58.8%), sleep (as a precipitating factor) (56.3%), post-crisis letdown (41.2%), and weather changes (37.5%). Trigger factors were further evaluated using stratification by presence or absence of Raynaud's phenomenon (RP), menstrual migraine, family history of migraine, and by migraine type. Odds ratios and 95% confidence intervals were calculated. These results suggest that subjects with migraine and RP (perhaps indicative of a systematic vascular tone disorder) and those with menstrual migraine (indicative of sensitivity to hormonal changes) may overall be more sensitive to certain environmental stimuli, particularly those involving change in the internal environment.
Red Wine-Induced Release of [14C]5-Hydroxytryptamine from Platelets of Migraine Patients and Controls
Authors: Jarman J , Pattichis K , Peatfield R , Glover V , Sandler M
Published: March 2003

Red wine-induced release of [14C]5-hydroxytryptamine (5HT) from platelets of red wine-sensitive migraine patients, migraine patients not sensitive to red wine and controls, was determined in vitro. No significant differences in platelet [14C]5HT release were found between any of the groups investigated.
Demographic and Clinical Characteristics of Patients With Episodic Migraine Versus Chronic Daily Headache
Authors: Rothrock J , Patel M , Lyden P , Jackson C
Published: March 2003

We compared data from 243 patients with episodic migraine (EM) and 132 patients with chronic daily headache (CDH). We divided the matter group into those with tension-type headache only (CDH Type 1) and those with headaches having migrainous features (CDH Types 2+3) and compared each with the EM group and all three groups with one another. CDH Type l patients differed from those in the other groups by virtue of gender (more often male) and mean age at headache onset (older). The CDH Types 2+3 and EM groups differed only in that the former were more likely to have undergone a brain-imaging study. These data suggest that CDH Type 1 may represent a distinct headache syndrome, while CDH Types 2+3 closely resemble episodic migraine.
Muscular Disorders in Tension-Type Headache
Authors: Jensen R , Rasmussen BK
Published: March 2003

In order to evaluate the diagnostic criteria for muscular disorders in tension-type headache, pericranial muscle tenderness and pressure pain thresholds were studied in a random sample population of 735 adults aged 25–64. In addition, quantitative EMGs were recorded in 547 of these subjects. The correlation between the three diagnostic tests was assessed and the discriminality and cut-off points were analysed using Receiver Operating Characteristics analysis. Local tenderness from the temporal muscles was closely related to the total tenderness scores from 14 pairs of muscles. In chronic tension-type headache, tenderness was positively related to EMG and inversely related to pain thresholds. In the episodic form the total tenderness score was inversely related to pain thresholds, whereas no significant relation to EMG was noted. The Receiver Operating Characteristics curves indicated that tenderness recorded by manual palpation was the most specific and sensitive test, whereas EMG and pain thresholds were of limited diagnostic value. Eighty-seven percent of subjects with the chronic, and 66% of subjects with the episodic form were found to have a “muscular disorder” defined as increased tenderness recorded by either manual palpation or pressure algometry and/or increased EMG levels. However, muscle tenderness increased significantly during pain, so the headache state should be considered in future studies. Suggestions for revision of the present diagnostic criteria for muscular disorders are given.
Initiating Mechanisms of Experimentally Induced Tension-Type Headache
Authors: Jensen R , Olesen J
Published: March 2003

To elucidate possible myofascial mechanisms of tension-type headache, the effect of 30 min of sustained tooth clenching (10% of maximal EMG-signal) was studied in 58 patients with tension-type headache and in 30 age- and sex-matched controls. Pericranial tenderness, mechanical and thermal pain detection and tolerance thresholds and FMG levels were recorded before and after the clenching procedure. Within 24 h, 69% of patients and 17% of controls developed a tension-type headache. Shortly after clenching, tenderness was increased in the group who subsequently developed headache, whereas tenderness was stable in the group of patients who remained headache free. Mechanical pain thresholds evaluated by pressure algometry remained unchanged in the group which developed headache, whereas thresholds increased in the group which did not develop headache Thermal pain detection and tolerance thresholds remained unchanged in both groups. These findings indicate that, though there may be several different mechanisms of tension-type headache, one of them is sustained muscle contraction. A peripheral mechanism of tension-type headache is therefore possible, whereas a secondary segmental central sensitization seems to be involved in subjects with frequent, tension-type headache. Finally, the increase in pressure pain thresholds in patients who did not develop headache suggested that clenching activated their antinociceptive system, whereas those developing headache were, unable to do so.
Cluster Headache Syndrome Associated With Middle Cerebral Artery Arteriovenous Malformation
Authors: Muoz C , Diez-Tejedor E , Frank A , Barreiro P
Published: March 2003

Cluster headache (CH) is an idiopathic cephalagic syndrome, although several pathological processes have been described in association with this syndrome. We report two cases of cluster headache in hospitalized patients with middle cerebral artery dependent arteriovenous malformation (AVM). After surgical removal of the AVM the headache completely resolved, suggesting that complementary studies and treatment of the underlying actinology may be indicated for secondary forms of cluster headache.
Risk Factors for Headache Recurrence After Sumatriptan: A Study in 366 Migraine Patients
Authors: Visser WH , Jaspers NMWH , de Vriend RHM , Ferrari MD
Published: March 2003

Headache recurrence (HR) is the major limitation of sumatriptan in the acute treatment of migraine attacks. The risk of HR is mainly patient dependent. We analyzed, in 366 migraine patients, clinical differences between patients who always have HR and patients who never have HR. We found remarkably few differences. HR more frequently occurred in patients with more severe attacks and longer untreated attack duration; in patients who experienced a sensation of a subclinically ongoing attack, despite headache relief after sumatriptan; and in females, mainly with menstruation-related migraine, most probably due to the more severe and longer lasting attacks these patients suffer, rather than due to hormonal factors. The incidence of HR was, among other factors, not related to the (other) clinical effects of sumatriptan, the timing of administration within the attack, the duration of use of sumatriptan, pharmacokinetic factors, or whether patients were experiencing HR after use of ergot alkaloids.
Recurrent Ophthalmoplegia in Childhood: Diagnostic and Etiologic Considerations
Authors: Østergaard JR , Møller HU , Christensen T
Published: March 2003

We present two patients with recurrent painful ophthalmoplegia starting in early childhood. Clinically, both patients fulfilled the criteria for ophthalmoplegic migraine. In one case, magnetic resonance investigations were performed following the second attack, between the third and fourth and during the fourth attack. The left third cranial nerve was significantly thickened in its course from the brainstem through the prepontine cistern to the cavernous sinus during the attacks and moderately thickened between the attacks. In the second case, magnetic resonance imaging was performed during the 14th attack, when the oculomotor nerve dysfunction was almost permanent, and the imaging demonstrated a swollen oculomotor nerve. Whether these findings are pathognomonic of ophthalmoplegic migraine awaits further reports using magnetic resonance imaging in infants showing recurrent painful ophthalmoplegia of early onset.
Migrainous Disorder and its Relation to Migraine Without Aura and Migraine with Aura. A Genetic Epidemiological Study
Authors: Russell MB , Olesen J
Published: March 2003

Migrainous disorder was analysed in a large population-based study of 4000 forty-year-old males and females. All interviews were conducted by one physician and the diagnostic criteria of the International Headache Society were used. Of the 48 people with migrainous disorder, 40 had migrainous disorder without aura and 9 had migrainous disorder with aura One person had co-occurrence of migrainous disorder with and without aura. The lifetime prevalence of migrainous disorder was 2.5% with a male: female ratio of 1:1.2. The first-degree relatives of probands with migrainous disorder were blindly interviewed. Compared with the general population, first-degree relatives of probands with migrainous disorder without aura had a slightly but less increased risk of migraine without aura than first-degree relatives of probands with migraine without aura. First-degree relatives of probands with migrainous disorder with aura had no increased risk of migraine with aura. We conclude that migrainous disorder without aura in some people is a type of migraine without aura and in other people not. Migrainous disorder with aura may be unrelated to migraine with aura. œ
Migraine Association and Linkage Analyses of the Human 5-Hydroxytryptamine (5HT2A) Receptor Gene
Authors: Nyholt DR , Curtain RP , Gaffney PT , Brimage P , Goadsby PJ , Griffiths LR
Published: March 2003

5-Hydroxytryptamine (5HT), commonly known as serotonin, which predominantly serves as an inhibitory neurotransmitter in the brain, has long been implicated in migraine pathophysiology. This study tested an Mspl polymorphism in the human 5HT2A receptor gene ( HTR2A) and a closely linked microsatellite marker (D13S126), for linkage and association with common migraine. In the association analyses, no significant differences were found between the migraine and control populations for both the Mspl polymorphism and the D13S126 microsatellite marker. The linkage studies involving three families comprising 36 affected members were analysed using both parametric (FASTLINK) and non-parametric (MFLINK and APM) techniques. Significant close linkage was indicated between the Mspl polymorphism and the D13S126 microsatellite marker at a recombination fraction (θ) of zero (lod score=7.15). Linkage results for the Mspl polymorphism were not very informative in the three families, producing maximum and minimum lod scores of only 0.35 and 0.39 at recombination fractions (θ) of 0.2 and 0.00, respectively. However, linkage analysis between the D13S126 marker and migraine indicated significant non-linkage (lod2) up to a recombination fraction (θ) of 0.028. Results from this study exclude the HTR2A gene, which has been localized to chromosome 13q14-q21, for involvement with common migraine.
Evaluation of Non-Invasive Techniques to Assess Vasoconstriction in Healthy Volunteers Using Methoxamine as a Probe Drug
Authors: Dixon RM , Meire HB , Leigh C , Posner J , Rolan PE
Published: March 2003

Non-invasive methods for assessment of the vascular effects of antimigraine drugs were evaluated with respect to their utility, variability and sensitivity in a double-blind, placebo-controlled, three-period crossover study in six healthy volunteers using an intravenous vasoconstrictor, methoxamine, as a probe drug. Changes in the internal diameter of the brachial and radial arteries were measured using ultrasound which had low between-day and within-day coefficients of variation. Peak systolic velocity (PSV), time-averaged velocity (TAV), total flow, resistance (RI) and pulsatility indices (PI) were measured by Doppler from one arterial wave form. Whilst PSV and TAV increased with methoxamine, because of bradycardia, changes in PI and RI were difficult to interpret. An automatic oscillametric cuff, a mercury-in-silastic strain gauge method and the “Finapres”, finger arterial blood pressure monitor were used to follow changes in systolic blood pressure (SBP). The strain gauge technique underestimated arm SBP compared to the oscillometric method but clearly showed drug-related increases whilst the Finapres did not reflect changes in blood pressure detected by the other methods.
How do the Currently Used Prophylactic Agents Work in Migraine?
Authors: Goadsby PJ
Published: March 2003

Since migraine attacks are often frequent they require management with agents that reduce their number. Such agents, although often effective, are mechanistically ill-understood, They have been suggested to work through four main mechanisms, 5HT2 antagonism, modulation of plasma protein extravasation, modulation of central aminergic control mechanisms and membrane stabilizing effects through actions at voltage-sensitive channels. The evidence for these mechanisms, except plasma protein extravasation (see Cutrer, this supplement) is examined in the light of current thoughts concerning the pathophysiology of migraine.

The understanding of the action of preventative drugs is at a relatively immature stage. Recent developments in pharmacology and studies of the pathophysiology of migraine have provided a substrate around which concepts can be developed. The actions and indeed the locus of action of the preventatives is crucial since these drugs are likely to point to the basic defect which underlies the process responsible for a migraine attack. Understanding this process can only facilitate patient management both in terms of explaining the disease and its implications and in controlling its clinical manifestations.
Possible Mechanisms of Valproate in Migraine Prophylaxis
Authors: Cutrer FM , Limmroth V , Moskowitz MA
Published: March 2003

Valproate has been shown to be an effective prophylactic treatment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. There is experimental evidence that it suppresses neurogenic inflammation and directly attenuates nociceptive neurotransmission. In addition, valproate reportedly alters levels of excitatory and inhibitory neurotransmitters and exerts direct effects on neuronal membranes in vitro. Valproate's observed effect may ultimately result from a combination of actions at different loci.

Our understanding of valproate's mechanism in migraine is made more difficult by the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. It lowers aspartate levels and NMDA receptor activity which may suppress aura related cortical processes, or may modulate nociceptive transmission within TNC. The significance of valproate-induced changes in serotonin, dopamine, glycine, taurine and enkephalin levels is not known. There is experimental evidence that it suppresses neurogenic inflammation and directly attenuates nociceptive neurotransmission. Direct action on pain transmission is unlikely to be the only relevant action since the number as well as severity of attacks is decreased Valproate's observed effect may ultimately result from a combination of actions at different loci.
Safety, Tolerability, and Pharmacokinetics of Sumatriptan Suppositories Following Single and Multiple doses in Healthy Volunteers
Authors: Kunka RL , Hussey EK , Shaw S , Warner P , Aubert B , Richard I , Fowler PA , Pakes GE
Published: March 2003

A suppository formulation of file 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind, randomized clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of sumatriptan suppositories following ascending single dose. (four different dose levels) and multiple doses. In the four-period, crossover, single-dose study, 24 healthy male subjects were randomized to receive a suppository containing 12.5, 25, 50, or 100 mg on separate occasions 3–14 days apart. The suppositories were generally well tolerated; transient asthenia, drowsiness, and headache were the most frequently reported adverse events, and these were not close-related. Peak plasma concentrations (Cmax) of sumatriptan were proportional to close from 25 to 100 mg; area under the plasma concentration-time curve (AUCx) values were proportional to dose except at the highest doses, when they were greater than those predicted from lower doses. For all doses, the tmax of sumatriptan occurred within 2.5h, and the t1/2 was approximately 2h. In the two-period, placebo-controlled, crossover, repeat-dose study, 12 healthy adult male subjects were randomized to receive either a 50-mg sumatriptan suppository or placebo suppository, administered rectally twice a day, for 11 doses (5 1/2 days). Adverse events were no more frequent with sumatriptan than with placebo, and stool guaiac, rectal examinations, and physical examinations remained normal. No significant differences were noted between Day 1 and Day 6 values in the AUC, Cmax, time of peak serum concentration (tmax), elimination half-life (t1/2), fraction of the dose excreted in the urine (fe), or renal clearance (Clr) of sumatriptan or its pharmacologically inactive indole acetic acid metabolite. Serum metabolite concentrations were two to threefold higher than corresponding sumatriptan concentrations. No clinically significant accumulation of sumatriptan or its metabolite occurred. Overall, these studies show that sumatriptan administration via a suppository formulation is well tolerated, allows rapid absorption of sumatriptan, results in sumatriptan Cmax values that are proportion I to dose from 25 to 100 mg, and is not associated with accumulation of sumatriptan or its nnetabolite.
A CPH-Like Picture in Two Patients with an Orbitocavernous Sinus Syndrome
Authors: Foerderreuther S , Maydell R v , Straube A
Published: March 2003

Two patients with retroorbital pain syndromes with or without paresis of cranial nerves developed weeks after ipsilateral headache resembling chronic paroxysmal hemicrania (CPH) but without autonomic features. These findings might support the hypothesis that CPH may be caused by a pathological process in the region of the cavernous sinus, as has been proposed for the Tolosa-Hunt syndrome (THS).
Double-Blind, Placebo-Controlled, Dose-Finding Study of Rizatriptan (MK-462) in the Acute Treatment of Migraine
Authors: Gijsmant H , Kramer MS , Sargent J , Tuchman M , Maczura-Wolfe D , Polis A , Teall J , Block G , Ferrari MD
Published: March 2003

Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical elficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Fatients with moderate or severe migraine ( n=417) were treated with placebo ( n=67), rizatriptan 2.5 mg ( n=75), 5 mg ( n=130), or rizatriptan 10 mg ( n=145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e placebo initiallyrizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initiallyplacebo as optional second dose). An upward dose-response relationship was observed among placebo rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to “no pain or mild pain” at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for pacebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2n post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.
Double-Blind Placebo-Controlled Trial of Lithium in Episodic Cluster Headache
Authors: Steiner TJ , Hering R , Couturier EGM , Davies PTG , Whitmarsh TE
Published: March 2003

Lithium is widely used in the prophylaxis of episodic cluster headache without formal evidence of efficacy. Placebo-controlled clinical trials are not easy in conditions characterized by frequent severe pain. In this study, it was assumed that lithium would work quickly if at all, and placebo response would be zero. Strict diagnostic criteria excluded uncertain or atypical cases Patients were male in so-far untreated episodes expected to last for at least 3 weeks more. In a double-blind, placebo-controlled comparison of matched parallel groups, treatment was either slow-release lithium carbonate, 800 mg/day, or placebo. After 7 days, compliance was estimated by tablet count, blood was taken for lithium assay, efficacy was assessed (attacks stopped or substantially improved) and adverse reactions were recorded. The study was stopped after planned sequential analysis of the 27th patient (13 on lithium, 14 on placebo). Estimated compliance was usually but not always good. Plasma lithium levels were mostly in the range 0.5–0.6 mmol/1 on lithium, zero on placebo. Cessation of attacks within 1 week occurred in two patients in each group, substantial improvement in 6/14 (43%) on placebo, 8/13 (62%; NS) on lithium. Only minor adverse events were reported. Lithium treatment was therefore associated with a useful subjective improvement rate but the assumptions made at outset had proved wrong. The trial was stopped because superiority over placebo could not be demonstrated. There were lessons for future trials. □ Episodic cluster headache, lithium, placebo response, randomized controlled trial, treatment
Cluster Headache after Orbital Exenteration
Authors: Evers S , Sörös P , Brilla R , Gerding H , Husstedt I-W
Published: March 2003

A 37-year old man developed an ipsilateral headache which fulfilled the criteria for cluster headache after orbital exenteration because of traumatic lesion of the bulb. The headache could be treated successfully by drugs usually applied in the therapy of cluster headache. Six similar cases of cluster headache after orbital exenteration could be identified in the literature suggesting that the eye itself is not necessarily part of the pathogenesis of cluster headache. We hypothesize that orbital exenteration can cause cluster headache by lesions of sympathetic structures. Possibly, these mechanisms are similar to those of sympathetic reflex dystrophy (Sudeck-Leriche syndrome) causing pain of the limbs
Headache and the Cervical Spine: A Critical Review
Authors: Pöllmann W , Keidel M , Pfaffenrath V
Published: March 2003

Headache related to the cervical spine is often misdiagnosed and treated inadequately because of confusing and varying terminology. Primary headaches such as tension-type headache and migraine are incorrectly categorized as “cervicogenic” merely because of their occipital localization. Cervicogenic headache as described by Sjaastad presents as a unilateral headache of fluctuating intensity increased by movement of the head and typically radiates from occipital to frontal regions. Definition, pathophysiology, differential diagnoses and therapy of cervicogenic headache are demonstrated. Ipsilateral blockades of the C2 root and/or greater occipital nerve allow a differentiation between cervicogenic headache and primary headache syndromes such as migraine or tension-type headache. Neither pharmacological nor surgical or chiropractic procedures lead to a significant improvement or remission of cervicogenic headache. Pains of various anatomical regions possibly join into a common anatomical pathway, then present as cervicogenic headache, which should therefore be understood as a homogeneous but also unspecific pattern of reaction.
Furosemide Inhibits Regenerative Cortical Spreading Depression in Anaesthetized Cats
Authors: Read SJ , Smith MI , Benham CD , Hunter AJ , Parsons AA
Published: March 2003

Ionic perturbations occur during cortical spreading depression (SD), a phenomenon implicated in migraine pathophysiology. We studied the effect of 0.2,2 and 20 mg kg-1 iv ( n=4) furosemide on cortical direct current (d.c.) potential, cerebrovascular laser Doppler flux (rCBFLDF), artery diameter and NO concentration in the parietal cortex of the anaesthetized cat during repetitive SD. In vehicle treated animals ( n=4), SD activity was sustained for 50 1.8 min. However, duration of SD activity was significantly reduced when compared to vehicle to 39 6.6 ( n=4), 3.1 8.3 ( n = 4) and 27.3 11.3 min ( n=4), at 0.2, 2 and 20 mg kg-1 iv furosemide respectively. It is hypothesized that the mechanism of inhibition of SD d.c. activity by furosemide may be through alterations in cortica ion buffering capacity or inhibition of cell swelling in neurones or glia. These mechanisms may represent potential novel drug targets in future migraine therapy.
Intensity Dependence of the Cortical Auditory Evoked Potentials as A Surrogate Marker of Central Nervous System Serotonin Transmission in Man: Demonstration of A Central Effect for the 5Ht1B/1D Agonist Zolmitriptan (311C90, Zomig®).
Authors: Proietti-Cecchini A , Áfra J , Schoenen J
Published: March 2003

As shown in animal studies, 5HT1B/1D agonists can inhibit activity in the trigeminal nucleus caudalis, which may be advantageous for their antimigraine effect. To demonstrate a possible central nervous system (CNS) action of these compounds in man we studied their effect on the intensity dependence of the cortical auditory evoked potentials (IDAPs), thought to be inversely related to central serotonergic transmission. An amplitude/stimulus intensity function (ASF) slope was computed in healthy volunteers and migraine patients between attacks before and 2 h after oral 311C90 (zolmitriptan “Zomig”) 10 mg ( n=14), 311C90 5 mg ( n=7), sumatriptan 100 mg ( n=14), dexfenfluramine 15 mg ( n=4), lorazepam 1.25 mg ( n=4) and placebo ( n=14). 311C90 10 mg and, to a lesser degree, 5 mg significantly increased the mean ASF slope ( p=0.007 and 0.05 vs placebo). There was a significant positive correlation between plasma levels of 311C90 and ASF slope changes. Sumatriptan and lorazepam had little effect, but dexfenfluramine produced a significant ASF slope decrease. 311C90 is able to modify a CNS activity that is modulated by serotonin, i.e. the IDAP. This effect is probably the consequence of its super or lipophilicity compared to sumatriptan and of activation of prejunctional 5HT1B/1D autoreceptors, which lowers central serotonin release and thus the preactivation level of sensory cortices.
Premonitory and Prodromal Symptoms in Cluster Headache
Authors: Blau JN , Engel HO
Published: March 2003

Warning symptoms in 150 cluster headache patients were studied by focusing on attacks occurring during waking hours. Warnings were divided into prodromes that started minutes before the pain of individual attacks (122 patients) and premonitory symptoms preceding the onset of cluster periods by days to weeks (12 patients). Pathogenetic and therapeutic implications are discussed.
Measurement of Muscle Hardness: A Methodological Study
Authors: Ashina M , Bendtsen L , Jensen R , Sakai F , Olesen J
Published: March 2003

The aim of the present study was to determine the intra- and interobserver variation during measurement of muscle hardness with a new instrument, a so-called hardness meter. In addition, we investigated the factors which may influence the recording of muscle hardness and whether the hardness differs within the same muscle. Hardness was measured at a standardized point on the trapezius muscle in 20 volunteers by 2 observers in random order and again by 1 of the observers after 30 min. Muscle hardness was then measured at 3 different locations on the trapezius muscle. In addition, the muscle hardness at the standard point was measured in 10 volunteers by both observers at 3 different speeds of the applied pressure. The intraobserver variation was 10% and the interobserver variation was 12% for recording of muscle hardness. There was no significant difference in hardness values from time to time within the same observer ( p=0.12), while there was a significant difference in hardness measurements between observers ( p=0.007). Muscle hardness differed significantly among the 3 anatomical locations ( p=0.03). For both observers, there was a significant difference among hardness recordings obtained at 3 different speeds ( p=0.01 and p=0.0001). In conclusion, we have shown that the hardness meter can measure muscle hardness reliably if the same observer is used throughout a study. The speed factor was a major source of variability. In addition, we have demonstrated that muscle hardness differs within the same muscle. We suggest that the muscle hardness meter will be an important tool in future research of the mechanisms leading to myofascial pain.
Dopamine and Migraine: A Review of Pharmacological, Biochemical, Neurophysiological, and Therapeutic Data
Authors: Mascia A , Qqaacute;fra J , Schoenen J
Published: March 2003

The dopamine theory of migraine pathogenesis, first proposed by F. Sicuteri in 1977, has attracted renewed interest after an increased frequency of the dopamine D2 receptor (DRD2) gene allele NcoI C was found in patients with migraine with aura. Therefore we reviewed the relevant literature. The most compelling argument favoring an interictal hypersensitivity of dopamine receptors in migraineurs stems from pharmacologic studies of the gastric and autonomic effects of dopaminergic agents such as apomorphine, but none of these studies was blinded and placebo-controlled. Various DRD2 antagonists abort migraine attacks after parenteral administration, while mere is circumstantial evidence that dopamine agonists may be useful for prophylaxis. Most drugs used in these trials, however, lack selectivity for dopamine receptors. Both in pharmacological and therapeutic studies most patients had migraine without aura. We conclude that data suggesting a primary role for the dopaminergic system in migraine pathogenesis are unconvincing. Based on well established interactions between central amines, a reduced release of serotonin between attacks could lower dopamine release which would lead to receptor hypersensitivity.
Headache as the Initial Manifestation of Acute Aortic Dissection Type A
Authors: Stöllberger C , Finsterer J , Fousek C , Waldenberger FR , Haumer H , Lorenz W
Published: March 2003

The most common initial symptom of aortic dissection is chest pain. Other initial symptoms include pain in the neck, throat, abdomen and lower back, syncope, paresis, and dyspnoea. Headache as the initial symptom of aortic dissection has not been described previously. A 61-year-old woman with a history of migraine and arterial hypertension developed continuous bifrontal headache. Two hours later, right-sided thoracic pain and a diastolic murmur were suggestive of aortic dissection that was confirmed by echocardiography and subsequent surgery. The dissection commenced in the ascending aorta and involved all cervical arteries until the base of the skull. Headache as the initial manifestation of aortic dissection was assumed due to either vessel distension or pericarotid plexus ischemia. Aortic dissection has to be considered as a rare differential diagnosis of frontal headache, especially in patients who develop aortic regurgitation or chest pain for the first time.
Incremental Absenteeism Due to Headaches in Migraine: Results from the Mig-Access French National Cohort
Authors: Michel P , Dartigues JF , Duru G , Moreau J , Salamon R , Henry P
Published: March 2003

Objective

To assess the costs of headache-related absenteeism of community-dwelling migraineurs, and to compare the amount of absenteeism between migraineurs aged 18 and older and age, sex, and occupation-matched nonheadache-prone subjects.

Design

Follow-up over a 3-month period.

Samples

385 migraineurs and 313 nonheadache subjects representative of the setting.

Methods

Every day, the participants recorded the presence of headache, if any, and the work situation (unemployment, holiday, weekend, medical reason, nonmedical reason). Sickness-related absenteeism was the number of workdays missed or interrupted for medical reasons. Headache-related absenteeism was the sickness-related absenteeism during workdays with headaches. The annual headache-related absenteeism costs in France were extrapolated from these data in accordance with the mean income per occupational category. The incremental absenteeism and related costs were the difference between the two samples.

Results

Of working migraineurs, 20% had at least one period of absenteeism. During the 3 months, they missed or interrupted on average 1.4 days for medical reasons, 0.25 of which for headaches. Sickness-related absenteeism was statistically higher in migraineurs than in nonheadache-prone subjects. This difference was due to a higher absenteeism for comorbidity reasons, not for headache reasons, representing 20% of all sickness-related absenteeism. Migraineurs avoided sick leave for headache reasons. As an incremental total, 1.68 days or approximately 0.7% of the annual number of working days are lost on average per individual with migraine. The annual incremental headache-related absenteeism cost was 5.22 billions, i.e. 1,551 FF (US$240) per migraineur.
Coincidence of Familial Hemiplegic Migraine and Hemicrania Continua? A Case Report
Authors: Evers S , Bahra A , Goadsby PJ
Published: March 2003

A case is presented of a 39-year-old woman with a history of simultaneous Familial hemiplegic migraine (FHM) and hemicrania continua (HC). The family history of the patient revealed different types of migraine and cyclic syndromes in childhood in four generations. The possible links between FHM and HC are discussed. The pedigree gives further evidence that cyclic syndromes in childhood belong to the spectrum of migraine.
Resolution of Mri Abnormalities of the Oculomotor Nerve in Childhood Ophthalmoplegic Migraine
Authors: Prats JM , Mateos B , Garaizar C
Published: March 2003

Ophthalmoplegic migraine is an uncommon disorder, usually starting in older childhood. Its physiopathology remains obscure and diagnosis is reliant on clinical grounds and exclusion of other disorders. We report four cases of childhood ophthalmoplegic migraine, one of them starting in infancy. Association with other types of migraine is common. Two of the three patients studied by magnetic resonance imaging (MRI) showed enhancement and enlargement of the cisternal portion of the oculomotor nerve, which spontaneously resolved after 2 and 4 years, respectively. Persistence of clinical recurrences was associated with long-lasting presence of the MRI finding, and possibly with mild sequelae. These radiological abnormalities suggest a common physiopathological mechanism with other inflammatory diseases, except for a benign evolution which, added to its specific anatomic site, seems to be the only neuroradiological marker, besides normality, in ophthalmoplegic migraine. The very long potential duration of MRI changes and the scarcity of clinical episodes make feasible its incident discovery once the migraine attack has become a remote memory.
Treatment of Severe, Disabling Migraine Attacks in an Over-The-Counter Population of Migraine Sufferers: Results From Three Randomized, Placebo-Controlled Studies of the Combination of Acetaminophen, Aspirin, and Caffeine
Authors: Goldstein J , Hoffman HD , Armellino JJ , Battikha JP , Hamelsky SW , Couch J , Blumenthal H , Lipton RB
Published: March 2003

Objective: To examine the benefits of acetaminophen, aspirin, and caffeine (AAC) in the treatment of severe, disabling migraine attacks, in a population of migraine sufferers for whom over-the-counter (OTC) medications are appropriate.

Background: Subjects ( n = 1220) who met the International Headache Society criteria for migraine with or without aura were included in three independent clinical studies.

Designl Methods: Post-hoc analysis of 172 subjects who met the criteria for severe, disabling migraine reported a history of migraine attacks characterized by at least severe pain and severe disability, and treated attacks with severe pain and at least severe disability. Subjects who usually vomited with 20% or more of their migraine attacks, and those with incapacitating disability (subjects who required bed rest for more than 50% of their attacks) were not eligible for enrollment.

Results: From 1 h and continuing through 6 h postdose, the proportion of responders was significantly greater ( p≤0.01) for AAC than placebo. The pain intensity difference from baseline was significantly greater ( p≤0.05) for AAC than placebo from 0.5 h through 6 h. The proportion of subjects reporting improvement in functional disability, photophobia, and phonophobia was significantly greater for AAC than placebo from 2 h through 6 h postdose.

Conclusions: The nonprescription combination of AAC was well tolerated and effective.
Loss of Topographic Memory and Prosopagnosia During Migraine Aura
Authors: Martins IP , Sá M Cunhae
Published: March 2003

We report the case of a 28-year-old woman with a past history of acephalalgic migraine. She had a complex migraine aura with left-sided scintillating scotomas, hemianopia, left-sided paresthesias, a loss of topographic and procedural memory, and prosopagnosia. The rarity of right hemisphere cognitive dysfunction during the aura, its diagnostic difficulties, and differential diagnosis are discussed.
Serotonin 5HT1B/1D Receptor Agonists Abolish NMDA Receptor-evoked Enhancement of Nitric Oxide Synthase Activity and cGMP Concentration in Brain Cortex Slices
Authors: Stȩpień A , Chalimoniuk M , Strosznajder J
Published: March 2003

Our previous studies indicating that the function of excitatory amino acids, NMDA type receptor, is modulated by serotonin focused on the interaction between serotonin 5HT1B/1D and glutamate, NMDA receptor in brain cortex. The effect of agonists of 5HT1B/1D receptor, sumatriptan, and zolmitriptan on NMDA receptor-evoked activation of nitric oxide (NO) and cGMP synthesis in adult rat brain cortex slices was investigated. Two kinds of experiment were carried out using adult rats. In one of them, sumatriptan or zolmitriptan was administered in vivo subcutaneously (s.c.) in a dose of 0.1 mg per kg body weight. Brain slices were then prepared and used in the experiments or, in the other exclusively in vitro studies, both agonists at 10 μM concentration were added directly to the incubation medium containing adult rat brain cortex slices. The data obtained from these studies indicated that stimulation of NMDA receptor in brain cortex slices. The data obtained from these studies indicated that stimulation of NMDA receptor in brain cortex slices leads to a large increase in calcium, calmodulin-dependent NO synthase (NOS) activity and to significant enhancement of the cGMP level. This NMDA receptor-dependent NO and cGMP release was completely blocked by competitive and noncompetitive NMDA receptor antagonists APV (10 μM) or MK-801 (10 μM.), respectively. The specific inhibitor of Ca2+-dependent isoforms of NOS (N-nitro-1-arginine NNLA and 7-nitroindozole (7-N1)) eliminated the NMDA receptor-mediated enhancement of NO and cGMP release. Moreover, the serotonin 5HT1B/1D receptor agonists sumatriptan and zolmitriptan administrated in vivo (s.c.) or in vitro abolished NMDA receptor-evoked NO signalling in brain cortex. The potency of both agonists investigated directly in vitro was similar to their effect after in vivo administration. These results suggest that both serotonin 5HT1B/1D receptor agonists may play an important role in modulating the NO and cGMP-dependent signal transduction pathway in the brain. This effect of sumatriptan and zolmitriptan on NO signaling in the brain system should be taken into consideration when investigating their mechanism of action in the migraine attack.
Molecular Genetics of Migraine Headaches: A Review
Authors: Montagna P
Published: March 2003

Following the recent discovery of neural calcium channel mutations in familial hemiplegic migraine, genetic linkage and association studies have been performed world-wide in an effort to unveil the genetic basis of the more common types of migraine too. Mutations in neural calcium channels, rnitochondrial DNA, serotonin receptors and transporter, dopamine receptors and genetic prothrombotic risk factors have been especially investigated and are discussed here. No unambiguous conclusions have, however, been reached. FHM remains an isolated success story in the quest for the genetic basis of migraine.
Prevention of Migraine During Prodrome With Naratriptan
Authors: Luciani R , Carter D , Mannix L , Hemphill M , Diamond M , Cady R
Published: March 2003

Objective To determine the role of naratriptan in preventing migraine headache when administered during prodrome. Procedures Baseline phase: patients recorded prodrome symptoms and time of onset, time when patient knew that headache was inevitable, time of onset and severity of headache. Treatment phase: patients given naratriptan 2.5 mg to take at the time they knew headache was inevitable. Patients recorded prodrome symptoms and time of onset, time they knew headache was inevitable, time naratriptan administered, time of onset and severity of any headache. Patients treated three prodromes separated by at least 48 h. Findings Twenty patients completed both phases. During baseline phase, 59 prodromes were reported and all were followed by headache. Severity of headache: 5% mild, 51% moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of these, 38/63 (60%) were not followed by headache. Among headaches that occurred, the majority occurred within 2 h of naratriptan administration, suggesting that naratriptan is more effective in preventing headache if taken early in prodrome. Severity of 25 headaches: 44% mild, 24% moderate, 32% severe. Conclusions Naratriptan 2.5 mg appears to prevent migraine headache when given early in prodrome. If headache occurs, severity appears to be reduced. □ Prodrome, premonitory, aura, naratriptan, migraine