Showing papers in "Cephalalgia in 2007"
TL;DR: The calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine, which would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.
Abstract: This study, which is a part of the initiative 'Lifting The Burden: The Global Campaign to Reduce the Burden of Headache Worldwide', assesses and presents all existing evidence of the world prevalence and burden of headache disorders. Population-based studies applying International Headache Society criteria for migraine and tension-type headache, and also studies on headache in general and 'chronic daily headache', have been included. Globally, the percentages of the adult population with an active headache disorder are 46% for headache in general, 11% for migraine, 42% for tension-type headache and 3% for chronic daily headache. Our calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine. On the World Health Organization's ranking of causes of disability, this would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.
2,067 citations
TL;DR: Tiggers were more likely to be associated with a more florid acute migraine attack and differences were seen between women and men, aura and no aura, episodic and chronic migraine, and between migraine and probable migraine.
Abstract: The aim of this study was to evaluate and define the triggers of the acute migraine attack. Patients rated triggers on a 0-3 scale for the average headache. Demographics, prodrome, aura, headache characteristics, postdrome, medication responsiveness, acute and chronic disability, sleep characteristics and social and personal characteristics were also recorded. One thousand two hundred and seven International Classification of Headache Disorders-2 (1.1-1.2, and 1.5.1) patients were evaluated, of whom 75.9% reported triggers (40.4% infrequently, 26.7% frequently and 8.8% very frequently). The trigger frequencies were stress (79.7%), hormones in women (65.1%), not eating (57.3%), weather (53.2%), sleep disturbance (49.8%), perfume or odour (43.7%), neck pain (38.4%), light(s) (38.1%), alcohol (37.8%), smoke (35.7%), sleeping late (32.0%), heat (30.3%), food (26.9%), exercise (22.1%) and sexual activity (5.2%). Triggers were more likely to be associated with a more florid acute migraine attack. Differences were seen between women and men, aura and no aura, episodic and chronic migraine, and between migraine and probable migraine.
685 citations
TL;DR: This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.
Abstract: The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.
478 citations
TL;DR: The available data on cortical excitability obtained with different methodological approaches in patients over the migraine cycle are reviewed to show that these data congruently indicate that the sensory cortices of migraineurs react excessively to repetitive, but not to single, stimuli and that the controversy above hyper- versus hypo-excitability is merely a semantic misunderstanding.
Abstract: Although migraineurs appear in general to be hypersensitive to external stimuli, they maybe also have increased daytime sleepiness and complain of fatigue. Neurophysiological studies between attacks have shown that for a number of different sensory modalities the migrainous brain is characterised by a lack of habituation of evoked responses. Whether this is due to increased cortical hyperexcitability, possibly due to decreased inhibition, or to an abnormal responsivity of the cortex due a decreased preactivation level remains disputed. Studies using transcranial magnetic stimulation in particular have yielded contradictory results. We will review here the available data on cortical excitability obtained with different methodological approaches in patients over the migraine cycle. We will show that these data congruently indicate that the sensory cortices of migraineurs react excessively to repetitive, but not to single, stimuli and that the controversy above hyper- versus hypo-excitability is merely a semantic misunderstanding. Describing the migrainous brain as 'hyperresponsive' would fit most of the available data. Deciphering the precise cellular and molecular underpinnings of this hyperresponsivity remains a challenge for future research. We propose, as a working hypothesis, that a thalamo-cortical dysrhythmia might be the culprit.
297 citations
TL;DR: The original and most recent findings that support a role for altered serotonergic neurotransmission in the manifestation of migraine headache are presented and discussed.
Abstract: Migraine is the most frequent neurological disorder in the adult population worldwide, affecting up to 12% of the general population and more frequent in women (~25%). It has a high impact on our society due to its disabling nature and, therein, reduced quality of life and increased absenteeism from work. Headache is the primary clinical manifestation and it has been associated with ‘a hereditary or predisposed sensitivity of neurovascular reactions to certain stimuli or to cyclic changes in the central nervous system’ (1). Amongst the many neurotransmitters in the brain, the serotonergic (serotonin, 5-HT) system from the brainstem raphe nucleus has been most convincingly implicated in migraine pathophysiology. The documented changes in 5-HT metabolism and in the processing of central 5-HT-mediated responses during and in between migraine attacks have led to the suggestion that migraine is a consequence of a central neurochemical imbalance that involves a low serotonergic disposition. Although the exact c...
291 citations
TL;DR: Occipital nerve stimulation may be effective in some patients with intractable headache, and results from prospective, randomized, sham-controlled studies in patients with medically refractory headache are needed.
Abstract: The aim of this study was to examine the safety and efficacy of occipital nerve stimulation for medically intractable headache. Electrical stimulation of large sensory afferents has an antinociceptive effect. Occipital nerve stimulation may be effective for the treatment of medically intractable headache. Retrospective analysis was performed of 15 patients with medically refractory headache who underwent implantation of an occipital nerve stimulator. Pre- and postimplant data regarding headache frequency, severity, disability, depression and poststimulator complications were collected. Twelve patients were female and three male. Ages ranged from 21 to 52 years (mean 39 years). Eight patients had chronic migraine, three chronic cluster, two hemicrania continua and two had post-traumatic headache. Eight patients underwent bilateral and seven had unilateral lead placement. Patients were measured after 5-42 months (mean 19). All six mean headache measures improved significantly from baseline (P < 0.03). Headache frequency per 90 days improved by 25 days from a baseline of 89 days; headache severity (0-10) improved 2.4 points from a baseline of 7.1 points; MIDAS disability improved 70 points from a baseline of 179 points; HIT-6 scores improved 11 points from a baseline of 71 points; BDI-II improved eight points from a baseline of 20 points; and the mean subjective percent change in pain was 52%. Most patients (60%) required lead revision within 1 year. One patient required generator revision. Occipital nerve stimulation may be effective in some patients with intractable headache. Surgical revisions may be commonly required. Safety and efficacy results from prospective, randomized, sham-controlled studies in patients with medically refractory headache are needed.
258 citations
TL;DR: This is a review of the neurophysiological studies which have provided an insight to migraine pathogenesis supporting the theory of hyperexcitability.
Abstract: Migraine is a very common disorder occurring in 20% of women and 6% of men. Central neuronal hyperexcitability is proposed to be the putative basis for the physiological disturbances in migraine. Since there are no consistent structural disturbances in migraine, physiological and psychophysical studies have provided insight into the underlying mechanisms. This is a review of the neurophysiological studies which have provided an insight to migraine pathogenesis supporting the theory of hyperexcitability.
233 citations
TL;DR: An updated pain model for CTTH is proposed in which headache can at least partly be explained by referred pain from TrPs in the posterior cervical, head and shoulder muscles, and TrPs would be the primary hyperalgesic zones responsible for the development of central sensitization in CTTH.
Abstract: Present pain models for tension-type headache suggest that nociceptive inputs from peripheral tender muscles can lead to central sensitization and chronic tension-type headache (CTTH) conditions. Such models support that possible peripheral mechanisms leading to pericranial tenderness include activation or sensitization of nociceptive nerve endings by liberation of chemical mediators (bradikinin, serotonin, substance P). However, a study has found that nonspecific tender points in CTTH subjects were not responsible for liberation of algogenic substances in the periphery. Assuming that liberation of algogenic substances is important, the question arising is: if tender muscle points are not the primary sites of on-going neurogenic inflammation, which structure can be responsible for liberation of chemical mediators in the periphery? A recent study has found higher levels of algogenic substances, and lower pH levels, in active myofascial trigger point (TrPs) compared with control tender points. Clinical stud...
230 citations
227 citations
TL;DR: Of the headache disorders, migraine was rated the most disabling, with the highest average intensity, highest frequency, duration of headache often exceeding 2 h and more frequent use of medication.
Abstract: The aim of the present study was to assess the distribution and characteristics of headache in children aged 7-14 years in Lower Saxony (Germany). For the survey, 8800 households with children were randomly drawn from community registers. Parents received comprehensive questionnaires regarding various aspects of their child's headache history and general health by mail. The response rate was 63.5%. The 6-month prevalence of paediatric headache was 53.2% and increased with age (39% at 7 years to 63% at age 14). Overall, recurrent headache (≥/week) was experienced by 6.5% of the total sample and was significantly more common among older girls (≥11 years) than their male counterparts. Boys and girls did not differ markedly from one another regarding headache occurrence and frequency until the age of 11. Mean age of headache onset was 7.5 years, with onset occurring at a significantly younger age among boys than among girls. In accordance with International Classification of Headache Disorders-II criteria, mi...
204 citations
TL;DR: A dicriminant function analysis revealed that collectively, restricted movement, in association with palpable upper cervical joint dysfunction and impairment in the cranio-cervical flexion test had 100% sensitivity and 94% specificity to identify cervicogenic headache.
Abstract: Jull G, Amiri M, Bullock-Saxton J, Darnell R & Lander C. Cervical musculoskeletal impairment in frequent intermittent headache. Part 1: Subjects with single headaches. Cephalalgia 2007; 27:793-802. London. ISSN 0333-1024 Musculoskeletal disorders are considered the underlying cause of cervicogenic headache, but neck pain is commonly associated with migraine and tension-type headaches. This study tested musculoskeletal function in these headache types. From a group of 196 community-based volunteers with headache, 73 had a single headache classifiable as migraine (n = 22), tension-type (n = 33) or cervicogenic headache (n = 18); 57 subjects acted as controls. Range of movement, manual examination of cervical segments, cervical flexor and extensor strength, the cranio-cervical flexion test (CCFT), cross-sectional area of selected extensor muscles at C2 (ultrasound imaging) and cervical kinaesthetic sense were measured by a blinded examiner. In all but one measure (kinaesthetic sense), the cervicogenic headache group were significantly different from the migraine, tension-type headache and control groups (all P < 0.001). A dicriminant function analysis revealed that collectively, restricted movement, in association with palpable upper cervical joint dysfunction and impairment in the CCFT, had 100% sensitivity and 94% specificity to identify cervicogenic headache. There was no evidence that the cervical musculoskeletal impairments assessed in this study were present in the migraine and tension-type headache groups. Further research is required to validate the predictive capacity of this pattern of impairment to differentially diagnose cervicogenic headache.
TL;DR: Menstruation is most important in increasing the risk of occurrence and persistence of headache and migraine, and other factors increase the risk less markedly or decrease the risk.
Abstract: Migraine is related to numerous factors such as hormones, stress or nutrition, but information about their actual importance is limited. Therefore, we analysed prospectively a wide spectrum of factors related to headache in migraineurs. We examined 327 migraineurs recruited via newspapers who kept a comprehensive diary for 3 months. Statistical analysis comprising 28 325 patient days and 116 dichotomous variables was based on the interval between two successive headache attacks. We calculated univariate Cox regression analyses and included covariables with a P-value of <0.05 in two stepwise multivariate Cox regression analyses, the first accounting for a correlation of the event times within a subject, the second stratified by the number of headache-free intervals. We performed similar analyses for the occurrence of migraine attacks and for the persistence of headache and migraine. Menstruation had the most prominent effect, increasing the hazard of occurrence or persistence of headache and migraine by up to 96%. All other factors changed the hazard by <35%. The two days before menstruation and muscle tension in the neck, psychic tension, tiredness, noise and odours on days before headache onset increased the hazard of headache or migraine, whereas days off, a divorced marriage, relaxation after stress, and consumption of beer decreased the hazard. In addition, three meteorological factors increased and two others decreased the hazard. In conclusion, menstruation is most important in increasing the risk of occurrence and persistence of headache and migraine. Other factors increase the risk less markedly or decrease the risk.
TL;DR: It is concluded that PM is a frequent, undertreated, sometimes disabling disorder that has an epidemiological profile similar to migraine and is more prevalent in African-Americans than in Whites.
Abstract: Probable migraine (PM) is a prevalent migraine subtype fulfilling all but one criterion for migraine with or without aura. The aims of this study were: (i) to describe the epidemiology, medical recognition and patterns of treatment for PM in the USA; (ii) to compare the patterns of preventive PM treatment in the population with expert panel guidelines for preventive treatment. A validated self-administered headache questionnaire was mailed to a random sample of 120,000 US households. Subjects were classified as PM according to the second edition of the International Classification of Headache Disorders (ICHD-2). The questionnaire also assessed patterns of migraine treatment. Guidelines for preventive medication use were developed by a panel of headache experts, who used headache frequency and impairment to assess the need for preventive therapy and the gap between current and ideal use. Our sample consisted of 162 576 individuals aged > or = 12 years. The 1-year period prevalence of PM was 4.5% (3.9% in men and 5.1% in women). In women and men, prevalence was higher in middle life, between the ages of 30 and 59 years. The prevalence of PM was significantly higher in African-Americans than in Whites (female 7.4% vs. 4.8%; male 4.8% vs. 3.7%) and inversely related to household income. During their headaches, most (48.2%) had at least some impairment, while 22.1% were severely disabled. The vast majority (97%) of PM sufferers used acute treatments, although 71% usually treated with over-the-counter medication. Most PM sufferers (52.8%) never used a migraine-preventive treatment and only 7.9% were currently using preventive medication. According to the expert panel guidelines, prevention should be offered (16.9%) or considered (11.5%) for 28.4% of the PM sufferers in the survey. We conclude that PM is a frequent, undertreated, sometimes disabling disorder. It has an epidemiological profile similar to migraine. In contrast to migraine, which is less prevalent in African-Americans than in Whites, PM is more prevalent in African-Americans than in Whites. In the USA, many with PM do not receive adequate treatment.
TL;DR: Headache and migraine were more common in girls than in boys and in teenagers, especially in girls, aiming at higher education, especially among girls.
Abstract: This population-based cross-sectional study examined the 3-month prevalence of headache, migraine and tension-type headache (TTH) among adolescents aged 12-15 years in Germany. Students (n = 3324) from 20 schools completed a questionnaire on general and headache-specific pain which included a sociodemographic module. The headache-specific questionnaire complied with the respective revised criteria of the International Headache Society (IHS). 'Modified criteria' changed the item 'duration' in migraine (>30 min instead of > 4 h). The overall 3-month prevalence of headache was 69.4% (boys 59.5%, girls 78.9%), with 4.4% of the adolescents suffering from frequent (>or=14 days/3 months) and severe (grade 8-10 on a 10-point visual analogue scale) headache and 1.4% (boys 0.9%, girls 1.9%) from headache >or= 15 days/month. The 3-month prevalence of migraine was 2.6% (boys 1.6%, girls 3.5%) applying strict IHS criteria and 6.9% (boys 4.4%, girls 9.3%) with modified criteria; 12.6% (boys 8.3%, girls 16.7%) suffered from probable migraine, 0.07% fulfilled the criteria for chronic migraine, 4.5% (boys 4.6%, girls 4.3%) suffered from TTH, 0.2% from chronic TTH and 15.7% (boys 14.5%, girls 16.9%) from probable TTH. Headache and migraine were more common in girls than in boys and in teenagers, especially in girls, aiming at higher education. Recurrent headache and primary headache disorders are common complaints among German adolescents, especially among girls.
TL;DR: This is the first demonstration that a psychological response to migraines (catastrophizing) is associated with impaired Fn/QoL independent of migraine characteristics and other demographic and psychological variables.
Abstract: Migraine characteristics are associated with impaired functioning and quality of life (Fn/QoL), but the impact of other factors on Fn/QoL in headache patients is largely unexplored. We examined cat...
TL;DR: It is suggested that headache patients and TMD patients overlap considerably in diagnosis and oral parafunctional behaviours.
Abstract: To assess the diagnostic and behavioural overlap of headache patients with temporomandibular disorders (TMD), individuals recruited from the general population with self-described headaches were compared with non-headache controls. The examination and diagnostic procedures in the Research Diagnostic Criteria (RDC) for TMD were applied to both sets of subjects by a blinded examiner. Following their examination, subjects used experience sampling methods to obtain data on pain, tooth contact, masticatory muscle tension, emotional states and stress. Results showed that a significantly higher proportion of the headache patients received an RDC/TMD diagnosis of myofascial pain than non-headache controls. Headache patients also reported significantly more frequent and intense tooth contact, more masticatory muscle tension, more stress and more pain in the face/head and other parts of the body than non-headache controls. These results are similar to those reported for TMD patients and they suggest that headache patients and TMD patients overlap considerably in diagnosis and oral parafunctional behaviours.
TL;DR: The literature indicates that migraineurs are hypersensitive to dopamine agonists with respect to some of the premonitory symptoms of migraine, and dopamine receptors are present in the trigeminovascular system, the area believed to be involved in headache pain, and neuronal firing here is reduced by dopamine agonist.
Abstract: In the last 30 years dopamine has been considered as playing a role in the pathogenesis of migraine. The literature indicates that migraineurs are hypersensitive to dopamine agonists with respect to some of the premonitory symptoms of migraine such as nausea and yawning. There are various non-specific dopamine D(2) receptor antagonists that show good clinical efficacy in migraine, and also a number of polymorphisms of dopaminergic genes related to migraine. Animal studies have also shown that dopamine receptors are present in the trigeminovascular system, the area believed to be involved in headache pain, and neuronal firing here is reduced by dopamine agonists. There appears to be little effect of dopamine on peripheral trigeminal afferents. We assess some of the limitations of the clinical studies with regard to the therapeutics, and those found in the studies that discovered differences in genetic polymorphisms in migraine, and consider the implications of this on a dopaminergic hypothesis of migraine.
TL;DR: Cluster headache, although periodic in most cases, has considerable impact on social functions, quality of life and use of healthcare.
Abstract: The aim was to analyse the socioeconomic burden of cluster headache in patients from a tertiary headache centre. One hundred consecutive patients from the Danish Headache Centre were invited to an interview about the socioeconomic impact of cluster headache. Work absence and use of medical services were compared with a Danish population-based survey. Eighty-five patients participated; 78% reported restrictions in daily living and 13% also outside of cluster periods; 25% reported a major decrease in their ability to participate in social activities, family life and housework. The disease caused lifestyle changes for 96%, most frequently in sleeping habits and avoidance of alcohol. The absence rate among patients was 30%, which was significantly higher than 12% among the general population (P < 0.001). Use of health services due to headache was also higher among the patients (P < 0.001). Cluster headache, although periodic in most cases, has considerable impact on social functions, quality of life and use of healthcare.
TL;DR: The data suggests that there should be revised classification for SUNCT and SUNA, with an increased range of attack duration and frequency, cutaneous triggering of attacks, and a lack of refractory period.
Abstract: SUNCT (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing) and SUNA (Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms) are rare primary headache syndromes, classified as Trigeminal Autonomic Cephalalgias (TACs). Hypothalamic involvement in the TACs has been suggested by functional imaging data and clinically with deep brain stimulation. Fifty-two patients (43 SUNCT, 9 SUNA) were studied to determine the clinical phenotype of these conditions and response to medications. A functional imaging study explored activation of the posterior hypothalamus in attacks of SUNCT/SUNA. The clinical study characterised SUNCT and SUNA in terms of epidemiology, phenotype and clinical characteristics. Indomethacin is ineffective on single-blind testing. Intravenous lidocaine was effective in all cases. Open-label trails showed the effectiveness of lamotrigine, topiramate and gabapentin. On functional imaging there was hypothalamic activation bilaterally in 5/9 SUNCT patients, and contralaterally in two patients. Two SUNCT patients had ipsilateral negative activation. In SUNA the activation was bilaterally negative. There was no hypothalamic activation in a patient with SUNCT secondary to a brainstem lesion. The data suggests that there should be revised classification for SUNCT and SUNA, with an increased range of attack duration and frequency, cutaneous triggering of attacks, and a lack of refractory period. The concept of 'attack load' is introduced. The lack of response to indomethacin and the response to intravenous lidocaine, are useful in diagnostic and therapeutic terms, respectively. Preventive treatments include lamotrigine, gabapentin and topiramate. The role of hypothalamic involvement in SUNCT and SUNA as TACs is considered.
TL;DR: A population-based evaluation of the prevalence of unilateral autonomic features in migraine patients and an assessment of the expression of unilaterality of autonomic symptoms and head pain in patients with UAs compared to other migraine patients are provided.
Abstract: Epidemiological data on trigeminal unilateral autonomic symptoms in patients with migraine are scarce. The authors wanted to provide a population-based evaluation of the prevalence of unilateral autonomic features in migraine patients and an assessment of the expression of unilaterality of autonomic symptoms and head pain in patients with UAs compared to other migraine patients. A population based sample of 6000 inhabitants of the city of Essen in Germany was screened using a previously validated standard questionnaire. Three thousand three hundred and sixty subjects (56% of a total 6000) responded. 841 subjects had migraine, out of which 226 reported accompanying unilatral auetonomic symptoms (26.9%, CI 95% [23.9-30%]). Unilateral autonomic symptoms in patients with migraine are common and have been widely underestimated in the past. One out of four migraine patients regularly experiences one or more unilateral autonomic symptoms during their attack. Migraine patients with accompanying autonomic symptoms seem to experience their pain more unilateral and more severe than non-UA patients.
TL;DR: BoNTA treatment was safe and well tolerated but did not result in significantly greater improvement than placebo in this study, and several factors may have confounded the results.
Abstract: Our aim was to evaluate the safety and efficacy of botulinum toxin type A (BoNTA; BOTOX®) for prophylaxis of episodic migraine. In this double-blind, placebo-controlled study, patients were randomized to 225, 150 or 75 U of BoNTA or placebo after a 30-day placebo run-in for three 90-day treatment cycles. The primary efficacy end-point was the mean reduction from baseline in the frequency of migraine episodes at day 180 in the placebo non-responder stratum. All groups (N = 495) improved, with no significant differences. At day 180, the frequency of migraine episodes was reduced from baseline means of 4.3, 4.7, 4.7 and 4.4 by 1.6, 1.7, 1.5 and 1.4 for BoNTA 225 U, 150 U and 75 U and placebo, respectively. The primary end-point was not met. Treatment-related adverse events were transient and mild to moderate. BoNTA treatment was safe and well tolerated but did not result in significantly greater improvement than placebo in this study. Several factors may have confounded the results.
TL;DR: Interictal involvement indicates that MWA and MWoA are not completely silent outside attacks, and that both subforms of migraine may share common mechanisms.
Abstract: Migraine affects the cortical physiology and may induce dysfunction both ictally and interictally. Although visual symptoms predominate during aura, other contiguous cortical areas related to less impressive symptoms are also impaired in migraine. Answers from 72.2% migraine with aura and 48.6% of migraine without aura patients on human faces and objects recognition, colour perception, proper names recalling and memory in general showed dysfunctions suggestive of prosopagnosia, dyschromatopsia, ideational apraxia, alien hand syndrome, proper name anomia or aphasia, varying in duration and severity. Symptoms frequently occurred in a successively building-up pattern fitting with the geographical distribution of the various cortical functions. When specifically inquired, migraineurs reveal less evident symptoms that are not usually considered during routine examination. Spreading depression most likely underlies the aura symptoms progression. Interictal involvement indicates that MWA and MWoA are not completely silent outside attacks, and that both subforms of migraine may share common mechanisms.
TL;DR: It is hypothesize that the hypo-functioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.
Abstract: Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypofunctioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.
TL;DR: There is an association between RLS and migraine and, in addition, a co-association with depression; the underlying mechanism remains undetermined and might be related to a dysfunction of dopaminergic metabolism in migraine.
Abstract: In order to evaluate a possible association between migraine and restless legs syndrome (RLS), we performed a case-control study on the comorbidity of RLS and migraine. Patients with migraine (n = 411) and 411 sex- and age-matched control subjects were included. Migraine was diagnosed according to International Headache Society criteria, RLS according to the criteria of the International Restless Legs Syndrome Study Group. Furthermore, all patients had to fill out a self-assessment test performance on depression [Beck's Depression Inventory (BDI)]. RLS frequency was significantly higher in migraine patients than in control subjects (17.3% vs. 5.6%, P < 0.001; odds ratio 3.5, confidence interval 2.2, 5.8). In our sample, there was no significant association between migraine and depression as defined by the BDI score (9.6% in migraine vs. 4.0% in control subjects, P = 0.190). Depression was, however, not significantly more frequent in migraine patients with RLS (13.6%) than in migraine patients without RLS (8.7%). In addition, migraine patients with RLS had a significantly higher BDI score. RLS features did not differ significantly between migraine patients with RLS and control subjects with RLS. There is an association between RLS and migraine and, in addition, a co-association with depression. The underlying mechanism, however, remains undetermined and might be related to a dysfunction of dopaminergic metabolism in migraine.
TL;DR: It is found that after 1 year, those who had stopped their overuse had a reduction in the number of headache days of the order of 73.7%, vs. just 17.2% in those who continued to overuse.
Abstract: Dear Sir We read with great interest the paper by Zeeberg et al. (1), in which they describe the treatment outcomes in patients with medication overuse headache (MOH), who were simply withdrawn from the offending medication without any other pharmacological intervention. They identified 337 individuals in their headache clinic with an initial diagnosis of MOH. A total of 121 subjects were excluded because they did not remain medication free for 2 months, leaving 216 patients, of whom 45% had a reduction in headache frequency by mere discontinuation of the offending drug, 48% were unchanged following withdrawal and 7% had worsening headaches. Overall, there was a 46% decrease in headache frequency from the first visit to discharge (P < 0.0001). Patients with no improvement 2 months after complete drug withdrawal (n = 88) subsequently responded to pharmacological and/or non-pharmacological prevention with a 26% decrease in headache frequency as measured from the end of withdrawal to discharge (P < 0.0001). At discharge, 47% were on prevention. Former non-responders to medical prevention had a 49% decrease in headache frequency from first visit to discharge (P < 0.0001), whereas those who had never received prevention had a 56% reduction (P < 0.0001). Later in the paper, they report that ‘these results are somewhat smaller than the 74% decrease in headache frequency found by Bigal et al. (2) . . . in patients with so-called transformed migraine’. We would like, however, to emphasize that the data are not comparable. Although the definition of transformed migraine with medication overuse is very similar to the definition of medication overuse as used by Zeeberg et al., we assessed outcomes after 1 year, not 2 months, following detoxification. We found that after 1 year, those who had stopped their overuse had a reduction in the number of headache days of the order of 73.7%, vs. just 17.2% in those who continued to overuse. A similar trend was found regarding the headache score (frequency multiplied by severity— Fig. 1). However, different from Zeeberg, we used preventive medications at the very beginning. Therefore, this 73% improvement encompasses the long-term benefits of detoxification associated with 1 year of preventive medication. Because the subjects that received preventive medication but were not detoxified showed a much smaller magnitude of improvement, we indirectly demonstrated the importance of detoxification. Therefore, it seems to us that both papers are amazingly consistent and more similar than different, supporting the importance of detoxification in the treatment of medication overuse headache.
TL;DR: The study gave no evidence that RF fields from mobile phones may cause head pain or discomfort or influence physiological variables, and found the most likely reason for the symptoms is a nocebo effect.
Abstract: The objective was to test whether exposure to radio frequency (RF) fields from mobile phones may cause head pain or discomfort and whether it may influence physiological variables in individuals attributing symptoms to mobile phones, but not to electromagnetic fields in general. Seventeen eligible individuals, who experienced these symptoms in an open provocation test, took part in a double-blind, randomized provocation study with cross-over design. Sixty-five pairs of sham and mobile phone RF exposures were conducted. The increase in pain or discomfort (visual analogue scales) in RF sessions was 10.1 and in sham sessions 12.6 (P = 0.30). Changes in heart rate or blood pressure were not related to the type of exposure (P: 0.30-0.88). The study gave no evidence that RF fields from mobile phones may cause head pain or discomfort or influence physiological variables. The most likely reason for the symptoms is a nocebo effect.
TL;DR: Compared with healthy controls, migraine patients tended to show lower baseline PT values, but this decrease failed to reach statistical significance, strengthening the notion of deficient inhibitory processes in the cortex of migraineurs, which is selectively revealed by activity-modulating cortical input.
Abstract: The issue of interictal excitability of cortical neurons in migraine patients is controversial: some studies have reported hypo-, others hyperexcitability. The aim of the present study was to observe the dynamics of this basic interictal state by further modulating the excitability level of the visual cortex using transcranial direct current stimulation (tDCS) in migraineurs with and without aura. In healthy subjects anodal tDCS decreases, cathodal stimulation increases transcranial magnetic stimulation (TMS)-elicited phosphene thresholds (PT), which is suggested as a representative value of visual cortex excitability. Compared with healthy controls, migraine patients tended to show lower baseline PT values, but this decrease failed to reach statistical significance. Anodal stimulation decreased phosphene threshold in migraineurs similarly to controls, having a larger effect in migraineurs with aura. Cathodal stimulation had no significant effect in the patient groups. This result strengthens the notion of deficient inhibitory processes in the cortex of migraineurs, which is selectively revealed by activity-modulating cortical input.
TL;DR: Univariate analysis revealed that a positive family history of headache and the presence of meningiomas are risk factors for tumour-associated headache, and the use of β-blockers is prophylactic.
Abstract: Eighty-five brain tumour patients were examined for further characteristics of brain tumour-associated headache. The overall prevalence of headache in this population was 60%, but headache was the sole symptom in only 2%. Pain was generally dull, of moderate intensity, and not specifically localized. Nearly 40% met the criteria of tension-type headache. An alteration of the pain with the occurrence of the tumour was experienced by 82.5%, implying that the pre-existing and the brain tumour headaches were different. The classic characteristics mentioned in the International Classification of Headache Disorders (worsening in the morning or during coughing) were not found; this might be explained by the patients not having elevated intracranial pressure. Univariate analysis revealed that a positive family history of headache and the presence of meningiomas are risk factors for tumour-associated headache, and the use of beta-blockers is prophylactic. Pre-existing headache was the only risk factor according to logistic regression, suggesting that patients with pre-existing (primary) headache have a greater predisposition to develop secondary headache. Dull headache occurs significantly more often in patients with glioblastoma multiforme, and pulsating headache in patients with meningioma. In our study, only infratentorial tumours were associated with headache location, and predominantly with occipital but rarely frontal pain.
TL;DR: The median CRP level was 1.42 mg/l in patients with migraine and 0.90 mg/L in controls, supporting the role of inflammation in migraine, but needs confirmation in larger controlled studies.
Abstract: Interictal serum C-reactive protein (CRP) was measured in 50 young adult patients with migraine and compared with 50 controls. The median CRP level was 1.42 mg/l in patients with migraine and 0.90 mg/l in controls (P = 0.03). This finding supports the role of inflammation in migraine, but needs confirmation in larger controlled studies. Prospective studies may establish whether measurements of CRP can identify patients with migraine at risk for cardiovascular events.
TL;DR: Preliminary evidence is provided for the efficacy and safety of venlafaxine XR 150 mg/day in reducing the number of days with TTH and the primary efficacy variable was the decline in number of Days with headache.
Abstract: The aim of this study was to evaluate in a double-blind, randomized, placebo-controlled study the safety and efficacy of venlafaxine extended release (XR) in the prophylactic treatment of out-patients with tension-type headache (TTH) and no current depression or anxiety disorders. Sixty neurology and headache clinic out-patients meeting the International Headache Society diagnostic criteria for TTH were treated with venlafaxine XR (150 mg/day, n = 34) or placebo (n = 26) for 12 weeks. The primary efficacy variable was the decline in number of days with headache. At end-point, the venlafaxine XR group had a significantly greater decrease in the number of days with headache compared with placebo (P = 0.05). Differences with regard to secondary efficacy variables where not significant. The number needed to treat for responders (>or=50% reduction in days with headache) was 3.48. Six patients in the venlafaxine XR group interrupted therapy due to adverse events, while no patients in the placebo group did so for the same reason. The number needed to harm was 5.58. This study provides preliminary evidence for the efficacy and safety of venlafaxine XR 150 mg/day in reducing the number of days with TTH.