Homocysteine levels and cardiovascular disease in migraine with aura

Abstract Clinical studies suggest that hyperhomocysteinemia could be considered an independent risk factor for premature cerebral, peripheral and vascular diseases. A number of authors found an epidemiological correlation between increased risk of cerebrovascular disease and migraine with aura. In this study, 34 patients suffering from migraine with aura and 36 healthy controls were evaluated with respect to total plasma homocysteine levels, measured with FPIA immunoassay in the fasting state and after methionine load. Moreover, vitamin B12, folate and other classic biochemical indicators of atherosclerosis disease were evaluated. In this study, homocysteine levels, both at basal and after load, and other cardiovascular risk factors such as vitamin B12 and apo-LpA were within the normal range. Other multicentric randomised trials are needed to carry on and confirm these data.     

The natural course of migraine attacks. A prospective analysis of untreated attacks compared with attacks treated with a triptan

This study was designed to document prospectively and explore scientifically the natural course of untreated migraine attacks in detail. A new, integrated, time-intensity method for self-assessment of the intensity of symptoms was tested on 18 adult International Headache Society migraineurs who volunteered to refrain from treatment during one attack. The area under the curves (AUC) during 72 h of untreated attacks was compared with attacks treated with a triptan. Migraine attacks are heterogeneous both inter- and intra-individually. In untreated attacks, the pain can stabilize and fluctuate around a plateau with a wavelength of hours. In general, the symptoms of each separate migraine attack follow a similar temporal course, with only moderate deviations. In some cases photo- and/or phonophobia (hyperexcitability) were not experienced at all, despite severe pain and nausea. Moreover, there was sometimes no nausea despite severe pain and hyperexcitability. Vomiting does not always correlate to the intensity of nausea and is not always followed by decreased headache intensity. Treatment with a triptan usually only temporarily distorts the basic pattern of attacks. Hyperexcitability can respond before pain to treatment. These genuine findings of the classic symptoms of migraine attacks support the notion of a mutual underlying pathophysiological mechanism.     

Review of clinical trials using early acute intervention with oral triptans for migraine management

Most of the data on triptan use are from clinical trials in which patients were instructed to wait until migraine headache pain was moderate/severe in intensity. In the real world, patients may hesitate to use a triptan until headache pain is moderate/severe because of the cost of these agents or limited supply allowed by their health service organisation. However, accumulating data indicate that early intervention with an oral triptan when headache pain is still mild may be the most effective acute treatment strategy. Economic analyses also support early triptan intervention in migraine attacks. Tolerability is expected to be particularly important in early intervention, as patients treating mild migraine pain may be more reluctant to risk adverse events. Thus, an agent selected for use as early intervention should have both a demonstrated efficacy in treating mild migraine headache and placebo-like tolerability. This article reviews retrospective and prospective clinical trials which investigated the use of triptans for early acute migraine therapy.     

Switching patients with migraine from sumatriptan to other triptans increases primary care costs

Treatment of migraine with triptans is highly effective, although cost considerations may prompt a change in therapy. This retrospective database analysis of 3196 patients with migraine, established on sumatriptan therapy, found that 54% of the 292 experiencing a triptan switch returned to sumatriptan within 15 months, suggesting that the alternative was less acceptable. Excluding patients with unusually high use of triptans (> or = 208 tablets/year), switching therapy resulted in a significant increase of pounds sterling 53/patient in total costs, compared with patients continuing on sumatriptan (p = 0.014). Cost savings (pounds sterling 17/patient over 15 months) were observed only among the 41% of patients in whom the initial switch was successful and did not result in a further switch or return to sumatriptan. Among patients who were relatively low cost initially, switching resulted in increased costs, irrespective of the outcome. This study suggests that there is no economic justification for switching from sumatriptan to another triptan.     

Effects of berberine on lipid profile in subjects with low cardiovascular risk

Objective: To evaluate the efficacy as antihypercholesterolemic agent of berberine in patients with low cardiovascular risk.

Research design and methods: 144 Caucasian subjects were enrolled. After a 6-month run-in period following diet and practicing physical activity, patients were randomized to take placebo or berberine 500 mg twice a day, for 3 months, in a double-blind, placebo-controlled design. Berberine and placebo were then interrupted for 2 months (washout period), and all patients continued with only diet and physical activity. At the end of the washout period, patients restarted berberine or placebo twice a day for further 3 months. Anthropometric and metabolic parameters were assessed during the run-in period, at randomization, before and after the washout period.

Results: A decrease of body weight and BMI was observed after the run-in period. Berberine reduced total cholesterol, triglycerides and LDL cholesterol and increased HDL cholesterol after 3 months from randomization and compared with placebo. After the washout period, lipid profile worsened; afterward, when berberine was reintroduced, lipid profile improved again both compared with the washout period, and with placebo.

Conclusions: Berberine is effective and safe to mildly improve lipid profile in subjects with low risk for cardiovascular disease.     

The similarities and differences of migraine with aura and migraine without aura: a preliminary study

A preliminary study was undertaken to provide clinical evidence to support the hypothesis that: "Migraine with aura, migraine without aura and aura alone are the same condition, which differ in degree rather than pathophysiology." At the City of London Migraine Clinic, 50 patients consecutively attending the clinic with a past or present history of migraine with aura were questioned. Of the 50 patients questioned 36 (70%) had a combination of migraine with aura, migraine without aura and/or aura alone; i.e. 70% had had more than one type of migraine attack. The duration, severity and frequency of attacks did not differ between migraine with and migraine without aura. Conclusion--the results support the hypothesis that migraine with and migraine without aura, and aura alone are not separate conditions, because: (1) most patients suffer from more than one type of migraine attack; (2) there are no significant differences in the characteristics of the migraine attacks in the different groups; (3) there are no significant differences in the characteristics of the subjects.     

A review of evidence-based medicine and meta-analytic reviews in migraine

The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the 'gold standard' and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.     

Cerebrovascular risk factors in migraine with prolonged aura and without aura

The role of cerebrovascular risk factors such as mitral valve prolapse, platelet aggregation, platelet activation and cardiac arrythmias in migraine was investigated in a total of 44 migraineurs (32 migraineurs without aura and 12 with prolonged aura) and 32 controls. Comparing the total of migraineurs and the two subgroups with controls, mitral valve prolapse, a raised thromboxane B2 level, at least one platelet aggregation dysfunction or an abnormality in 24-h ECG was statistically seen no more often than in the control group. Neither did combinations of the variables occur more frequently. Altogether, this study showed no increased coincidence of migraine with prolonged aura and migraine without aura with the above parameters. The absence of cardiac and haematological abnormalities in migraine with prolonged aura focuses attention on the control of the cortical microcirculation.     

Elevated audiovisual temporal interaction in patients with migraine without aura

Background

Photophobia and phonophobia are the most prominent symptoms in patients with migraine without aura. Hypersensitivity to visual stimuli can lead to greater hypersensitivity to auditory stimuli, which suggests that the interaction between visual and auditory stimuli may play an important role in the pathogenesis of migraine. However, audiovisual temporal interactions in migraine have not been well studied. Therefore, our aim was to examine auditory and visual interactions in migraine.

Methods

In this study, visual, auditory, and audiovisual stimuli with different temporal intervals between the visual and auditory stimuli were randomly presented to the left or right hemispace. During this time, the participants were asked to respond promptly to target stimuli. We used cumulative distribution functions to analyze the response times as a measure of audiovisual integration.

Results

Our results showed that audiovisual integration was significantly elevated in the migraineurs compared with the normal controls (p < 0.05); however, audiovisual suppression was weaker in the migraineurs compared with the normal controls (p < 0.05).

Conclusions

Our findings further objectively support the notion that migraineurs without aura are hypersensitive to external visual and auditory stimuli. Our study offers a new quantitative and objective method to evaluate hypersensitivity to audio-visual stimuli in patients with migraine.     

Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine

BACKGROUND: Health care providers frequently cite concerns about cardiovascular safety of the triptans as a barrier to their use. In 2002, the American Headache Society convened the Triptan Cardiovascular Safety Expert Panel to evaluate the evidence on triptan-associated cardiovascular risk and to formulate consensus recommendations for making informed decisions for their use in patients with migraine. OBJECTIVE: To summarize the evidence reviewed by the Triptan Cardiovascular Safety Expert Panel and their recommendations for the use of triptans in clinical practice. PARTICIPANTS: The Triptan Cardiovascular Safety Expert Panel was composed of a multidisciplinary group of experts in neurology, primary care, cardiology, pharmacology, women's health, and epidemiology. EVIDENCE AND CONSENSUS PROCESS: An exhaustive search of the relevant published literature was reviewed by each panel member in preparation for an open roundtable meeting. Pertinent issues (eg, cardiovascular pharmacology of triptans, epidemiology of cardiovascular disease, cardiovascular risk assessment, migraine) were presented as a prelude to group discussion and formulation of consensus conclusions and recommendations. Follow-up meetings were held by telephone. CONCLUSIONS: (1) Most of the data on triptans are derived from patients without known coronary artery disease. (2) Chest symptoms occurring during use of triptans are generally nonserious and are not explained by ischemia. (3) The incidence of serious cardiovascular events with triptans in both clinical trials and clinical practice appears to be extremely low. (4) The cardiovascular risk-benefit profile of triptans favors their use in the absence of contraindications.     

Treatment of migraine and tension-type headache in Croatia

The aim of this study was to assess the treatment patterns of migraine and tension-type headache in the Croatian population. Analysis included the proportion of patients who were taking specific antimigraine therapy and the number of tablets per attack per month, the proportion of patients who were taking prophylactic therapy or using alternative treatment methods and their satisfaction with the treatment. The design of the study was a cross-sectional survey. Self-completed questionnaires were randomly distributed to adults >18 years of age in the Croatian population. A total of 616 questionnaires were analyzed: 115 patients with migraine (M), 327 patients with tension-type headache (TTH), and 174 patients with probable migraine (PM) and TTH. Specific antimigraine therapy was taken by half of patients with migraine: 35.7% of patients used triptans and 21.7% ergotamines. Prophylactic treatment had been used by 13.9% of M, 1.2% of TTH, and 6.9% of PM patients. Alternative methods of treatment were tried by 27% of M and TTH patients. Only 16.8% of patients with M pay regular visits to physicians, while 36.3% never visited a physician. More than half of TTH patients have never visited a physician. The majority of patients are only partially satisfied with their current treatment, and almost one-third are not satisfied. Results of this study indicate that the treatment of primary headaches in Croatia should be improved.     

Analysis of the relationship between age and treatment response in migraine

In migraine, headache severity varies with age. As a consequence, the effectiveness of medication may also depend on a patient's age. The purpose of this study was to assess the combined effect of age and drug treatment on headache characteristics. Using data from clinical trials of sumatriptan in adolescents and adults, we show how the interaction between age and drug exposure can be parameterised as a covariate on a Markov model that describes the decline of headache severity over three clinically defined stages (no relief, relief and pain-free status). The model explains important clinical observations: (i) the rates at which the pain relief and pain-free status were attained were found to be inversely related to age; (ii) in placebo-treated patients, the mean transit time from 'no relief' to 'relief' is 3 h for young adolescents and increases to 6 h for patients aged ≥ 30 years; and (iii) sumatriptan reduces the transit time to 2 h, irrespective of age. These findings indicate that the therapeutic gain over placebo increases with age. Prospective studies of antimigraine drugs should take this relationship into account when extrapolating efficacy data from adults to adolescents.     

Increased risk for coeliac disease in paediatric patients with migraine

The aim was to determine the prevalence of coeliac disease (CD) in paediatric patients with migraine. Serum tissue transglutaminase IgA (tTGA) antibodies and IgA concentrations were measured in 73 patients with migraine (age range 6–17 years) and the control group ( n  = 147). Patients having positive tTGA antibodies underwent duedonal biopsy. Four patients (5.5%) from the study group and one (0.6%) from the control group had positive tTGA antibody titres ( P  < 0.05). Three patients with migraine had normal duedonal histology and were considered as potential CD. One patient from the study group and one from the control group declined to have biopsy. tTGA antibody is considered as a reliable indicator for the presence of CD. However, some patients with positive antibodies may have normal biopsy initially and are classified as having potential CD. Our finding of a higher prevalance of tTGA antibodies in paediatric migraine patients suggests that an association between migraine and CD might exist.     

动脉血乳酸水平在心血管急症患者风险评估及预后判断中的价值

目的 探讨动脉血乳酸水平在心血管急症(急性心肌梗死、急性主动脉夹层A型、急性肺栓塞)患者风险评估及预后判断中的价值.方法 回顾性分析上海交通大学附属第六人民医院109例住院期间确诊的心血管急症患者的相关临床资料.根据入院时动脉血乳酸水平分为升高组和正常组,分析两组患者临床特征、生化及血气分析参数、住院期间病死率及随访1...     

Desialylated transferrin in plasma of patients with migraine without aura

Patients with migraine, without aura (MO), either during or between attacks, present elevated histamine levels in platelet-poor plasma but normal whole blood histamine levels, compared with controls. This finding is usually interpreted as an increased histamine release from basophils due to unidentified histamine-releasing factors. Compared with 10 control plasma samples, each sample from 12 MO patients (5 during and 7 between in attacks) contained normal amounts of iron and immunologically reactive transferrin but decreased transferrin iron-binding capacity. As transferrin inhibits histamine release in vitro, such as functional abnormality, probably due to modifications of the transferrin glycan moiety (desialylated transferrin), may well account for the increased histamine release observed in MO patients. We suggest that glycan-modified transferrin may be related to migraine histamine-releasing factors. Received: 7 August 2000, Accepted in revised form: 22 September 2000     

Perceived psychosocial stress and cardiovascular risk factors in obese and non-obese patients

Background Patients after their first myocardial infarction are characterized by increased levels of perceived stress and abdominal obesity compared to a matched control group. In the setting of primary prevention, the association of stress and cardiovascular risk factors in obese and non-obese individuals is not known. Methods and results: For this prospective cross-sectional study, primary care physicians recruited consecutive patients with BMI >30 and the next two individuals presenting with a BMI <30 as controls (n=414). The 10-year risk of death from cardiovascular disease determined by the European Society of Cardiology Heart- Score Germany was associated with BMI (p<0.0001). However, waist circumference and waist-tohip ratio predicted the calculated cardiovascular risk better than BMI. Psychosocial risk factors were determined using the INTERHEART questionnaire. Obesity was positively associated with depression (p=0.005) but not with perceived stress. In contrast to obesity or depression, the extent of perceived general stress inversely correlated with cardiovascular risk (never stress: 4.4±2.8%, some period: 2.4±2.7%, several periods: 1.4±2.3% and permanent: 0.65±0.5%; p=0.0001). Similarly, additional parameters of stress (stress at home, stress at work, financial stress, stressful life events) as well as locus of control were inversely associated with cardiovascular risk factors. A medical history of general stress was correlated with younger age and increased smoking. Conclusions Waist to hip ratio powerfully predicts the cardiovascular risk estimated by HeartScore in primary prevention. Perceived stress assessed by a standardized questionnaire does not positively correlate with traditional cardiovascular risk factors and warrants further evaluation as a routine tool for primary care physicians.     

History of migraine and the risk of spontaneous cervical artery dissection

The pathophysiology of spontaneous cervical artery dissection (sCAD) is largely unknown. An association with migraine has been suggested, but not definitively proven. In the setting of a hospital-based prospective case-control study we assessed personal and family history of migraine in 72 patients with sCAD, 72 patients with cerebral infarct unrelated to a CAD (non-CAD) and 72 control subjects. Personal history of migraine was significantly associated to sCAD compared to non-CAD (59.7% vs. 30.6%; OR 3.14; 95% CI 1.41-7.01) and controls (18.1%; OR 7.41; 95% CI 3.11-17.64). As opposed to migraine with aura, migraine without aura was significantly more frequent among sCAD than among non-CAD (56.9% vs. 25.0%; OR 3.91; 95% CI 1.71-8.90) and controls (12.5%; OR 9.84; 95% CI 3.85-25.16). Similar results were observed when the frequencies of family history of migraine were compared. These findings are consistent with the hypothesis that migraine may represent a predisposing condition for sCAD.