Incidence of migraine and tension-type headache in three different populations at risk within the German DMKG headache study.

BACKGROUND: Unlike the prevalence, the incidence of headache disorders has attracted only little attention in epidemiological research. Different definitions of the 'population at risk' among the few published migraine and tension-type headache incidence studies limit their comparability and warrant further research. Therefore, we analysed data from the German Migraine and Headache Society (DMKG). METHODS: Incidences were assessed in the general population in Germany via standardized headache questions using the International Classification of Headache Disorders, 2nd Edition (ICHD-2). The population was drawn from a 5-year age-group- stratified and gender-stratified random sample from the population register. RESULTS: Of the 1312 baseline participants examined between 2003 and 2004, 1122 (85.5%) participated in the follow-up in 2006 and were the basis for three different populations at risk. We found that the three populations differed in size, age, gender and incidence estimate. The total sample incidence of migraine ranged between 0% and 3.3% and of tension-type headache between 5.3% and 9.2% depending on the definition of 'at risk'. CONCLUSION: We concluded that one significant problem in headache incidence estimation is the definition of 'at risk', limiting comparability. Thus, this study supports the need for a common definition for prospective headache incidence estimations.

A case-control study on cortical thickness in episodic cluster headache.

OBJECTIVE: This study aims at investigating cortical thickness in cluster headache patients as compared with a healthy control group. BACKGROUND: The pathobiology of cluster headache is not yet fully understood, although a dysfunction of the hypothalamus has been suggested to be causal. Previous studies in migraine and trigeminal neuropathic pain have demonstrated changes in cortical thickness using cortex segmentation techniques, but no data have been published on cluster headache. METHODS: We investigated 12 men with episodic cluster headache during a phase without acute headache as well as age and sex-matched healthy controls using high resolution T1-weighted magnetic resonance imaging acquired at 3T and performed a categorical whole-brain surface-based comparison of cortical thickness between groups. Furthermore, a correlation analysis of disease duration and cortical thickness was conducted. RESULTS: In comparison with control subjects, we found a reduction of cortical thickness in the angular gyrus and the precentral gyrus in cluster headache patients contralaterally to the headache side. These reductions did not correlate with disease duration. The cortical thickness of an area within the primary sensory cortex correlated with disease duration. CONCLUSIONS: This study demonstrates alterations in cortical thickness in cluster headache patients suggesting a potential role of cortical structures in cluster headache pathogenesis. However, it cannot be determined from this study whether the changes are cause or consequence of the disorder. The correlation of cortical thickness with disease duration in the somatosensory cortex may suggest disease-related plasticity in the somatosensory system.

Association between lifestyle factors and headache.

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required.

A high-density association screen of 155 ion transport genes for involvement with common migraine.

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

OTC analgesics in headache treatment: open-label phase vs randomized double-blind phase of a large clinical trial.

OBJECTIVE: To compare the superior efficacy of the fixed combination of acetylsalicylic acid, paracetamol, and caffeine over the single substances, which was observed in the randomized, double-blind phase of the clinical trial, with the efficacy of the respective usual nonprescription medication taken by the patients in the open-label pre-phase of the same study. BACKGROUND: The "Thomapyrin Study" showed significant superiority of the fixed combination containing acetylsalicylic acid, paracetamol, and caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. METHODS: Prior to the randomized treatment phase, a headache episode treated with the patient's usual nonprescription medication was recorded (open-label pre-phase). Patients assessed their pain intensity on a 100-mm visual analog scale. For the 1734 patients included in the efficacy analysis, we compared the time course of the pain intensity difference (PID) to baseline after the patients took their usual medication with the time course of the PID after intake of the randomized study medication. RESULTS: Time course of PID after intake of the patient's usual medication was very similar to the time course of PID after intake of the randomized study medication. After 2 hours, pain reduction was on average 43.0, 38.2, 38.1, and 37.7 mm as assessed on the visual analog scale in the group of patients who took their usual triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, paracetamol, and ibuprofen, respectively, in the open-label phase. The corresponding mean pain reduction was 44.7, 40.7, and 39.5 mm in patients allocated to the triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, and paracetamol, respectively, in the randomized, double-blind phase.

Clinical relevance of efficacy endpoints in OTC headache trials.

OBJECTIVE: This analysis evaluates and ranks efficacy endpoints often used in headache trials concerning their clinical relevance in relation to the patient-related criterion "global assessment of overall efficacy" based on data gained in a large trial investigating different over-the-counter drugs in the treatment of headache. BACKGROUND: The original study showed a significant superiority of the fixed combination of acetylsalicylic acid+paracetamol+caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. METHODS: For 1734 patients included in the efficacy analysis we investigated the correlation of patient's global efficacy assessment with the endpoints "time to 50% pain relief" (primary endpoint), "time to be pain-free," pain intensity difference, sum of pain intensity difference, and extent of impairment of daily activities. Patients recorded pain intensity on a visual analog scale. Efficacy, tolerability, and extent of impairment of daily activity were assessed on verbal rating scales.A logistic regression, proportional odds model was adapted to the time to event data. RESULTS: The highest correlation with patient's global efficacy assessment was demonstrated for the primary endpoint time to 50% pain relief (r = 0.6727) and the sum of pain intensity difference (r = 0.7037). The frequency distribution of patient's global efficacy assessment depended primarily on the time to 50% pain relief and similarly, but to a somewhat lesser extent, on the reduction of pain intensity to 10 mm as assessed on the visual analog scale. More than 86% of the patients assessed efficacy as very good or good when their pain was reduced by 50% at least within 1 hour after drug intake. The patients accept a longer time span than 2 hours for reaching no pain to give a positive global evaluation of efficacy.

Botulinum toxin as preventive treatment for migraine: a randomized double-blind study.

AIM: To determine if botulinum toxin type A (BoNT-A) injections can reduce the frequency and severity of migraines. METHODS: Patients (n = 127) were randomized to receive placebo or two doses of BoNT-A (Dysport). The primary endpoint was reduction in number of migraine attacks up to week 8 and between weeks 8 and 12 after injection. Patient diaries were used to record secondary endpoints, including frequency, severity and duration of migraine attacks. RESULTS: There was a mean reduction of 0.54 and 0.94 attacks/month with placebo and BoNT-A, respectively, and absolute attack count was less in the verum group (3.6 vs. 4.2 attacks/month), but this was not statistically significant. The patients' global assessment of efficacy was significantly better than placebo in the high-dose group (p = 0.02) but no effects were seen for the other secondary efficacy parameters. CONCLUSION: Our study showed a trend towards a reduced attack rate with verum but did not show any statistically significant efficacy of BoNT-A in the prophylactic treatment of migraine.

SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a primary head-pain syndrome, which is often refractory to any medical treatment. Concerning the pathophysiology of SUNCT, hypothalamic involvement ipsilaterally to the pain has been suggested based on the clinical features and one functional imaging case report. Here we now report a new case with SUNCT and the concomitant cerebral activation pattern (fMRI) during the pain attacks. In addition to an activation of several brain structures known to be generally involved in pain processing, bilateral hypothalamic activation occurred during the pain attacks, arguing for a central origin of the headache. Interestingly, this patient became completely pain free after surgical decompression of the ipsilateral trigeminal nerve. We hypothesize that in this case with a central predisposition for trigeminal autonomic cephalgias, a peripheral trigger with ectopic excitation might have contributed to the clinical picture of SUNCT.

Acupuncture for patients with migraine: a randomized controlled trial.

CONTEXT: Acupuncture is widely used to prevent migraine attacks, but the available evidence of its benefit is scarce. OBJECTIVE: To investigate the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in patients with migraine. DESIGN, SETTING, AND PATIENTS: Three-group, randomized, controlled trial (April 2002-January 2003) involving 302 patients (88% women), mean (SD) age of 43 (11) years, with migraine headaches, based on International Headache Society criteria. Patients were treated at 18 outpatient centers in Germany. INTERVENTIONS: Acupuncture, sham acupuncture, or waiting list control. Acupuncture and sham acupuncture were administered by specialized physicians and consisted of 12 sessions per patient over 8 weeks. Patients completed headache diaries from 4 weeks before to 12 weeks after randomization and from week 21 to 24 after randomization. MAIN OUTCOME MEASURES: Difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after randomization. RESULTS: Between baseline and weeks 9 to 12, the mean (SD) number of days with headache of moderate or severe intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of 5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a baseline if 5.4 (3.0) days in the waiting list group. No difference was detected between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence interval, -0.7 to 0.7 days; P = .96) while there was a difference between the acupuncture group compared with the waiting list group (1.4 days; 95% confidence interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group. CONCLUSION: Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control.

Neurometabolic correlates of depression and disability in episodic cluster headache.

A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering.

Effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis.

OBJECTIVES: In a randomized controlled multicenter trial extending over 24 weeks, we investigated whether acupuncture is as effective and safe as metoprolol in the prophylactic treatment of migraine under conditions similar to routine care. METHODS: One hundred fourteen migraine patients could be randomized to treatment over 12 weeks either with acupuncture (8 to 15 sessions) or metoprolol (100 to 200 mg daily). Main outcome measure was the difference in the number of migraine days between baseline and the weeks 9 to 12 after randomization (derived from a headache diary). RESULTS: Two of 59 patients randomized to acupuncture withdrew prematurely from the study compared to 18 of 55 randomized to metoprolol. The number of migraine days decreased by 2.5 +/- 2.9 days (baseline 5.8 +/- 2.5 days) in the acupuncture group compared to 2.2 +/- 2.7 days (baseline 5.8 +/- 2.9 days) in the metoprolol group (P= .721). The proportion of responders (reduction of migraine attacks by > or =50%) was 61% for acupuncture and 49% for metoprolol. Both physicians and patients reported fewer adverse effects in the acupuncture group. CONCLUSIONS: Due to missing the recruitment target (480 patients) and the high drop-out in the metoprolol group the results must be interpreted with caution. Still, they suggest that acupuncture might be an effective and safe treatment option for patients unwilling or unable to use drug prophylaxis.

Acupuncture for chronic headaches--an epidemiological study.

OBJECTIVE: To investigate the characteristics and outcomes of patients undergoing acupuncture treatment for chronic headaches under conditions of routine care provided within the framework of statutory health insurance in Germany. Furthermore, we investigated correlations between different outcomes. PATIENTS AND METHODS: Patients with migraine, episodic or chronic tension-type headache (TTH), or several other forms of chronic headache (cluster, vascular, drug-induced headache; other specific headaches) treated with acupuncture (mean number of sessions 8.6 +/- 3.0) were included into an observational study. Detailed questionnaires including questions on headache days and instruments measuring disability (Pain Disability Index) and quality of life (SF-36) were completed before treatment, after treatment, and at 6 months after inclusion. RESULTS: A total of 2,022 patients (732 with migraine, 351 with episodic and 440 with chronic TTHs, and 499 with other diagnoses) treated by 1,418 physicians were included in the main analysis. Sociodemographic and baseline characteristics differed considerably in the four diagnostic groups. Statistically highly significant and clinically relevant improvements were seen for all clinical outcome measures in all diagnostic groups. In 52.6% of patients headache frequency decreased by at least 50% compared to baseline. The comparison of headache frequency, pain intensity, and generic outcome measures showed that some of these outcomes correlate only weakly. CONCLUSIONS: In this epidemiological study, headache patients reported clinically relevant improvements after receiving acupuncture. Randomized trials performed in parallel to this study confirm the relevant overall effect, however, the effect may largely be due to potent unspecific needling and placebo effects.

Acupuncture in patients with tension-type headache: randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache. DESIGN: Three armed randomised controlled multicentre trial. SETTING: 28 outpatient centres in Germany. PARTICIPANTS: 270 patients (74% women, mean age 43 (SD 13) years) with episodic or chronic tension-type headache. INTERVENTIONS: Acupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or waiting list control. Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks. MAIN OUTCOME MEASURE: Difference in numbers of days with headache between the four weeks before randomisation and weeks 9-12 after randomisation, as recorded by participants in headache diaries. RESULTS: The number of days with headache decreased by 7.2 (SD 6.5) days in the acupuncture group compared with 6.6 (SD 6.0) days in the minimal acupuncture group and 1.5 (SD 3.7) days in the waiting list group (difference: acupuncture v minimal acupuncture, 0.6 days, 95% confidence interval -1.5 to 2.6 days, P = 0.58; acupuncture v waiting list, 5.7 days, 3.9 to 7.5 days, P < 0.001). The proportion of responders (at least 50% reduction in days with headache) was 46% in the acupuncture group, 35% in the minimal acupuncture group, and 4% in the waiting list group. CONCLUSIONS: The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache. TRIAL REGISTRATION NUMBER: ISRCTN9737659.