Reliability of assessing lifestyle and trigger factors in patients with migraine--findings from the PAMINA study.

BACKGROUND AND PURPOSE: Numerous lifestyle factors are blamed for triggering migraine attacks. The reliability of assessing these factors retrospectively is unknown. Therefore, retrospective and prospective assessments of lifestyle in general and of migraine triggers in particular were compared in patients with migraine. METHODS: At baseline, the patients filled in two questionnaires covering the previous 90 days. Thereafter they kept a prospective 90-day diary. Questionnaires and diary included the same set of 45 factors. In the first questionnaire the patients assessed their lifestyle, in the second they rated for each factor the likelihood of triggering a migraine attack, and in the diary they recorded the daily presence of these factors irrespective of headache. Five categories were used for comparing frequencies in questionnaire and diary, defining agreement as identical categories in diary and questionnaire, minor disagreement and major disagreement as overestimation or underestimation by one category and two or more categories, respectively. RESULTS: In all, 327 patients (283 women, age 41.9 ± 12.1 years) who recorded 28,325 patient days were included. Calculating for each factor the percentage of patients with major disagreement the mean proportion was larger for trigger factors than for lifestyle (38.7% ± 6.6% vs. 16.9% ± 6.4%, P < 0.001). The proportion of factors showing major disagreement in more than 20% of the patients was 8.8% for lifestyle but 94.1% for trigger factors (P < 0.001). CONCLUSION: Comparing questionnaire and diary assessments of lifestyle and trigger factors in patients with migraine shows that questionnaire assessment of lifestyle is reliable, whereas trigger factors are overestimated and/or underestimated in retrospective questionnaires.

The course of migraine-a diary study in unselected patients.

The course of disease and the predictive value of depression and anxiety in patients with migraine were prospectively examined. We recruited 393 migraineurs through articles in newspapers and performed a follow-up examination 30 months later. At baseline and follow-up, patients underwent a semistructured interview, filled out the Headache Impact Test (HIT-6), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) and they kept a headache diary for 30 days. One hundred and fifty-one patients (38.6%) were seen at follow-up. The baseline data of patients with and without follow-up were comparable. At follow-up the number of headache days per month had decreased from 9.6 +/- 5.8 to 8.1 +/- 6.3 (P < 0.001) and the proportion of patients with chronic headache (15.4%) and medication overuse (13%) had remained stable. SDS and SAS scores were associated with a high migraine frequency and high initial SDS scores predicted high migraine frequency at follow-up. This longitudinal study in unselected patients with migraine not excluding subjects with chronic headache, medication overuse, depression or anxiety does not point towards migraine as a progressive disease in the vast majority of patients and confirms the importance of psychiatric comorbidity.

Quality of sleep, fatigue and daytime sleepiness in migraine - a controlled study.

The objective of this study was to evaluate whether the quality of sleep and the degree of fatigue and daytime sleepiness are related to migraine. We investigated 489 subjects comprising 97 patients with eight or more, 77 patients with five to seven and 196 patients with one to four migraine days per month, and 119 migraine-free controls with fewer than six headache days per year. The patients were recruited via articles in newspapers not stressing the subject of the study. All participants underwent a semistructured interview and completed the Pittsburgh Sleep Quality Index (PSQI), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS) and the Self-rating Depression Scale and the Self-rating Anxiety Scale. For statistical analysis we used two way manovas, post hoc univariate two-way anovas and Hochberg's GT2 tests as well as three-way mixed design anovas. The PSQI total score was highest in patients with frequent migraine (5.9 +/- 4.3) and lowest in controls (4.3 +/- 2.5, P = 0.04). Four subscores of the PSQI showed similar statistically significant differences. The FSS and ESS scores did not differ in the four study groups. Analysing depression and anxiety revealed a significant impact on PSQI, FSS and ESS, but did not demonstrate interactions with migraine, thus suggesting that the impact of migraine is similar in patients without and with psychiatric comorbidity. In conclusion, the quality of sleep is decreased in patients with migraine, whereas fatigue and daytime sleepiness do not differ from healthy controls. The decreased quality of sleep in migraineurs is also a consequence of migraine itself and cannot be explained exclusively by comorbidity with depression or anxiety.

Family-based association analysis of functional VNTR polymorphisms in the dopamine transporter gene in migraine with and without aura.

Because of the role of dopamine in triggering migraine attacks, genes of the dopamine system are candidates for involvement in migraine. We examined three VNTR polymorphisms in the dopamine transporter, the 5'UTR VNTR, the intron 8 VNTR and the intron 14 VNTR, in a sample of 205 family trios. We used the transmission disequilibirium test (TDT) to examine the transmission of these three markers and their haplotypes to offspring affected by migraine. We found no significant transmission distortion of any marker. Likewise haplotypes of the three markers did not show significant overall or individual association with migraine. Finally we examined migraine with and without aura, and likewise found no association between dopamine transporter VNTRs or their haplotypes and either classification of the disease. We conclude that functional genetic variation in the dopamine transporter does not act as a significant risk factor for migraine.

Family-based analysis of serotonin transporter gene polymorphisms in migraine with and without aura.

Genetic epidemiological twin studies have demonstrated a significant heritability for migraine, with > 60% of liability to migraine either with or without aura coming from additive genetic factors. Because of the essential role of serotonin in the pathophysiology and treatment of migraine, genes of the serotonin system are candidates for involvement in migraine. Consequently, we examined two functional VNTR polymorphisms in the serotonin transporter gene, the 5-HTTLPR and the intron 2 VNTR, in a sample of 212 family trios each with a proband with childhood migraine, 153 with migraine without aura (MoA) and 59 with migraine with aura (MA). For the first time, we used transmission disequilibrium test analysis with the program TDTPHASE to examine the transmission of these two markers and their haplotypes to offspring affected by migraine. We found no significant transmission distortion of any marker, with the common L allele of the 5-HTTLPR transmitted 170 times and not transmitted 178 times, and the S allele 130 vs. 122 times. Likewise, the common 12 allele of the intron 2 VNTR was transmitted 201 times and not transmitted 188 times, and the 10 allele 107 vs. 120 times. The markers were not associated with MoA and MA and none of the haplotypes was associated with overall migraine, MoA or MA. The 5-HTTLPR and the intron 2 VNTRs do not play a major role in susceptibility to migraine.

Prospective analysis of factors related to migraine attacks: the PAMINA study.

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.

Clinical features, classification and prognosis of migraine and tension-type headache in children and adolescents: a long-term follow-up study.

We performed a long-term follow-up examination in children and adolescents with migraine and tension-type headache (TTH) in order to investigate the evolution of clinical features and headache diagnoses, to compare International Classification of Headache Disorders (ICHD)-I and ICHD-II criteria and to identify prognostic factors. We re-examined 227 patients (52.4% female, age 17.6 +/- 3.1 years) 6.6 +/- 1.6 years after their first presentation to a headache centre using identical semistructured questionnaires. Of 140 patients initially diagnosed with migraine, 25.7% were headache free, 48.6% still had migraine and 25.7% had TTH at follow-up. Of 87 patients with TTH, 37.9% were headache free, 41.4% still had TTH and 20.7% had migraine. The number of subjects with definite migraine was higher in ICHD-II than in ICHD-I at baseline and at follow-up. The likelihood of a decrease in headache frequency decreased with a changing headache location at baseline (P < 0.0001), with the time between baseline and follow-up (P = 0.0019), and with an initial diagnosis of migraine (P = 0.014). Female gender and a longer time between headache onset and first examination tended to have an unfavourable impact. In conclusion, 30% of the children and adolescents presenting to a headache centre because of migraine or TTH become headache-free in the long-term. Another 20-25% shift from migraine to TTH or vice versa. ICHD-II criteria are superior to those of ICHD-I in identifying definite migraine in children and adolescents presenting to a headache centre. The prognosis is adversely affected by an initial diagnosis of migraine and by changing headache location, and it tends to be affected by an increasing time between headache onset and first presentation.

[Non-alimentary trigger factors of migraine and tension-type headache]. / Nichtalimentäre Triggerfaktoren bei Migräne und Kopfschmerz vom Spannungstyp.

Based on an overview of the literature, this contribution critically discusses the importance of non-alimentary trigger factors of migraine and tension-type headache. Menstruation, environmental factors, psychological effects as well as sleep disorders and fatigue are mentioned most frequently. According to controlled studies, menstruation is indubitably associated with an increased risk of headache. Although a correlation between specific meteorological parameters and the appearance of headaches was established in some patients, the subjective observations of the patients did not however correlate with the objective weather data. Sensory stimuli function as triggers particularly for migraine with aura. Psychological factors, especially stress and everyday pressures, have been confirmed as trigger factors, but further prospective trials addressing this issue would be advantageous. Additional studies are also needed to elucidate the significance of sleep (disorders) and fatigue since their importance as triggers or symptoms of a headache attack has not been conclusively determined.

[Alimentary trigger factors that provoke migraine and tension-type headache]. / Alimentäre Triggerfaktoren bei Migräne und Kopfschmerz vom Spannungstyp.

Based on a review of the literature the authors discuss the role of nutrition in the precipitation of migraine and tension-type headache (TTH). The available information relies largely on the subjective assessment of the patients. Controlled trials suggest that alcohol and caffeine withdrawal are the most important nutritional precipitating factors of migraine and TTH. In addition, there is some evidence that missing meals is also an important factor. Dehydration seems to deserve more attention. A selective sensitivity to red wine has been shown in some patients, the importance of chocolate has been doubted seriously, and scientific evidence for cheese as a precipitating factor is lacking. Despite a series of experimental studies demonstrating that NO donors such as nitroglycerin and parenteral histamine cause headache the role of histamine, nitrates, and nitrites in food remains unclear. Similarly, other biogenic amines and aspartame have not been proven to precipitate headache. Sodium glutamate causes adverse reactions including headache probably at large doses ingested on an empty stomach. Therefore, patients should be advised that food plays a limited role as a precipitating factor of migraine and TTH. Subjective sensitivity to certain foods should be examined critically, and proven precipitating factors should be avoided. General dietary restrictions have not been proven to be useful.

Facial pain in a neurological tertiary care centre--evaluation of the International Classification of Headache Disorders.

The aim of this study was to examine the diagnostic spectrum of facial pain and to evaluate the clinical features relevant to the differential diagnosis in a neurological tertiary care centre. This is the first investigation comparing the first with the second edition of the International Classification of Headache Disorders (ICHD-I, ICHD-II) in consecutively referred patients comprising a broad spectrum of disorders without restricting the inclusion to certain diagnoses. Studying 97 consecutive patients referred for facial pain, we found trigeminal neuralgia or other types of cranial neuralgia in 38% and 39% according to ICHD-I and ICHD-II, respectively; persistent idiopathic facial pain was diagnosed in 27% and 21%, respectively. The proportion of patients who could not be classified was 24% in ICHD-I and 29% in ICHD-II. Six per cent of the patients had cluster headache or chronic paroxysmal hemicrania, the remaining 5% had various other disorders. The agreement between ICHD-I and ICHD-II was very good to perfect. In ICHD-II, sensitivity and specificity were similar to ICHD-I, the specificity and negative predictive value were imrpoved in single features of trigeminal neuralgia, but were widely unchanged in persistent idiopathic facial pain. The number of patients who could not be classified was larger in ICHD-II than in ICHD-I. Modifying the diagnostic criteria for different types of facial pain, in particular changes in the criteria of persistent idiopathic facial pain, might be helpful in reducing the number of patients with unclassifiable facial pain.

Familial hemiplegic migraine: follow-up findings of diffusion-weighted magnetic resonance imaging (MRI), perfusion-MRI and [99mTc] HMPAO-SPECT in a patient with prolonged hemiplegic aura.

Familial hemiplegic migraine (FHM) is a rare inherited autosomal dominant disorder. Migraine aura may last up to several weeks and then resolve without sequel. We report a 21-year-old male with FHM since the age of 3 years. Diffusion-weighted magnetic resonance imaging (DWI), perfusion-MR imaging (P-MRI) and [99mTc] hexamethyl-propyleneamine-oxime-single photon emission tomography (HMPAO-SPECT) were performed on day 2, when he was somnolent with right-sided hemiplegia, on day 9 when a mild hemiparesis was still present and on day 24 after recovery. The right central region showed normal findings in DWI, whereas P-MRI and SPECT revealed hyperperfusion on day 2, less marked on day 9, and normal findings on day 24. In conclusion, this case report indicates for the first time, by means of SPECT, P-MRI and DWI studies, that even extremely long-lasting migraine aura is not associated with cerebral ischaemia. Therefore, it supports the revised International Headache Society criteria where the term 'persistent' aura is proposed.

Clinical features of migraine: a cross-sectional study in patients aged three to sixty-nine.

We investigated 260 consecutive patients classified as migraine cases aged 3-69 at two tertiary headache centres, one for children and adolescents and the other for adults to evaluate the relationship between age and clinical features of migraine cross-sectionally. We only included subjects with definite migraine without or with aura and we excluded subjects with coexisting tension-type headache, medication overuse and/or other clinically relevant disorders. The percentage of males decreased markedly from childhood to adulthood and this affected the evaluation of age-related changes in male patients, as only large differences reached the level of statistical significance. In females, the headache duration and the prevalence of unilateral, pulsating pain, photophobia and phonophobia increased, whereas the prevalence of aggravation by physical activity decreased with age. In conclusion, this cross-sectional, clinic-based study on a strictly defined sample of 260 consecutive patients with definite migraine covering a wide range of age from the very young to the old suggests marked age-related differences of the clinical features of migraine in females and failed to demonstrate similar differences in males due to the small number of adult male migraineurs.

Establishing principles for migraine management in primary care.

Published guidelines for the management of migraine in primary care were evaluated by an international advisory board of headache specialists, to establish evidence-based principles of migraine management that could be recommended for international use. Twelve principles of migraine management were identified, covering screening, diagnosis, management and treatments: Almost all headaches are benign/primary and can be managed by all practising clinicians. Use questions/a questionnaire to assess the impact on daily living and everyday activities, for diagnostic screening and to aid management decisions. Share migraine management between the clinician and the patient. Provide individualised care for migraine and encourage patients to manage their migraine. Follow up patients, preferably with migraine calendars or diaries. Regularly re-evaluate the success of therapy using specific outcome measures and monitor the use of acute and prophylactic medications regularly. Adapt migraine management to changes that occur in the illness and its presentation over the years. Provide acute medication to all migraine patients and recommend it is taken at the appropriate time, during the attack. Provide rescue medication/symptomatic treatment for when the initial therapy fails. Offer to prescribe prophylactic medications, as well as lifestyle changes, to patients who have four or more migraine attacks per month or who are resistant to acute medications. Consider concurrent co-morbidities in the choice of appropriate prophylactic medication. Work with the patient to achieve comfort with mutually agreed upon treatment and ensure that it is practical for their lifestyle and headache presentation. Using these principles, practising clinicians can screen and diagnose their headache patients effectively and manage their migraine patients over the long-term natural history of the migraine process. In this way, the majority of migraine patients can be well treated in primary care, ensuring a structured and individualised approach to headache management, and conserving valuable healthcare resources.

The effect of calisthenic home exercises on postmenopausal fractures--a long-term observational study.

OBJECTIVES: To evaluate the long-term effects of calisthenic home exercises on the incidence of fractures in postmenopausal women. DESIGN: Controlled long-term observational study. METHODS: Postmenopausal women between 45 and 75 years of age who had been randomly assigned to an exercise or control group in the course of a previous study conducted 5-10 years ago, were invited for follow-up. The number of fractures before and during the observation time were recorded by means of a questionnaire. Vertebral deformities due to fractures were diagnosed by X-rays at entry and at follow-up. Walking speed, muscle strength, static posturography, and maximum oxygen uptake were measured in addition. RESULTS: After an average follow-up time of 7.6+/-1.1 years, 73 women of the exercise group and 64 subjects of the control group were investigated. Thirty-three per cent (n=24) of the exercise group reported to have exercised continuously at least three times a week for 20 min. No intergroup differences between the compliant and non-compliant exercisers and the control group were seen in the number of fractures. However, the incidence of fracture was lowest in women with a baseline bone mass less than one standard deviation (SD) below the mean for young adults (high BMC) and highest in those with more than 2.5 SD below the mean for young adults (low BMC) (P<0.001, odds ratio 2.9 [95% CI, 1.59-5.39]). CONCLUSION: This long-term follow-up did not produce any evidence that prescription of a calisthenic home exercise program may prevent fractures in postmenopausal women aged between 61+/-6.4 and 68+/-6.5 years.

Amantadine in Parkinson's disease: lymphocyte subsets and IL-2 secreting T cell precursor frequencies.

The antiviral drug amantadine, that is effective in idiopathic Parkinson's disease (PD), may affect the composition and function of peripheral blood lymphocytes. In an explorative study, we therefore compared lymphocyte subpopulations and IL-2 secreting T cell precursors frequencies (HTLp-frequencies) in 15 PD patients without amantadine and six patients on long-term treatment. Five patients were investigated before and three months after the start of treatment. Group comparisons for long-term amantadine treatment showed no differences in subpopulations of B-, T-, and NK cells, and HTLp-frequencies. However, three months after initiation of treatment we noted in all five patients an increase of CD3+CD4+ and decrease of CD3+CD8+ cells, associated with an increase of the CD3+CD4+/CD3+CD8+ ratio. These changes had no effect on the HTLp-frequencies. Thus, at least for a short period of time, amantadine improves the T cell mediated immune system in PD patients.

Are there predictive factors for long-term outcome after withdrawal in drug-induced chronic daily headache?

OBJECTIVES: To investigate prognostic factors for long-term outcome of patients after inpatient withdrawal because of drug-induced chronic daily headache. PROCEDURES: Fifty-five patients (36 females) were re-examined by means of a standardized interview after inpatient withdrawal. The mean observation period was 9.28 +/- 2.85 years (mean +/- SD; median 8.58; range 5.00-13.50). RESULTS: Five years after withdrawal, one-third of the patients (34.6%) had an overall favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported a clear-cut improvement of headache, and one-third (32.7%) developed recurrent drug overuse. Most relapses occurred within 2 years, and a small percentage within 5 years. No predictors for long-term outcome after inpatient withdrawal were found. CONCLUSIONS: All patients with drug-induced chronic daily headache should be considered as good candidates for inpatient withdrawal, and no patient should be excluded from that therapy.

Migrainous disorder and headache of the tension-type not fulfilling the criteria: a follow-up study in children and adolescents.

In this follow-up study in children and adolescents with recurrent headaches classified as migrainous disorder (IHS 1.7) and headache of the tension-type not fulfilling the criteria (IHS 2.3), 28.6% were headache-free and 71.4% still had headaches 2-5 years after the first examination. The majority remained in the same one-digit IHS diagnosis, whereas 20% changed from migraine to tension-type headache or vice versa. The number of IHS criteria fulfilled increased significantly from the first to the second examination. The reason for diagnosing IHS 1.7 and IHS 2.3 most often was a short headache duration or headache characteristics not meeting the criteria. By reducing the minimum headache duration to 1 h, 11 of 58 patients could be diagnosed as migraine without aura. There was a remarkable overlap in the diagnostic criteria for migraine without aura and tension-type headache. In IHS 1.7 and IHS 2.3 this overlap exceeded 80%, with a trend to decrease at the second examination.