French general practitioners' management of children's migraine headaches

OBJECTIVES: This study sought to examine the treatment of children with migraine headaches in a prospective sample of children referred to a tertiary center for headaches. BACKGROUND: Despite the wide diffusion of guidelines for headache management in children, their application in general practice is far from optimal. METHODS: This prospective study analyzed previous headache treatment by general practitioners in 151 consecutive children (F/M: 0.82; mean age 10.4 +/- 3.2 years) referred for migraines to the Lille University Hospital Neuropediatric department between October 1, 2003, and November 30, 2005. The physician completed a questionnaire according to the parents' responses to questions about previous advice about life-style adjustments (diet, exercise, and sleep hygiene) and abortive and prophylactic treatment. Questions about abortive treatment covered ergot derivatives, triptans, and 3 aspects of ibuprofen use-appropriate dose (ie, more than 7.5 mg/kg), recommendation to administer the drug early in attacks, and warnings about drug abuse. Under the topic of prophylactic treatment, we asked about information from general practitioners about preventive therapy and advice to keep a headache diary. RESULTS: Fewer than 15% of patients had received advice about life-style adjustments. Only 30.3% had received ibuprofen at a correct dose (more than 7.5 mg/kg); only 26.5% were told to use it early during the headache; and only 9.1% were warned about drug abuse. Ergot derivatives were prescribed to 4.6% of children and triptans to 9.1%. Families of 17.9% reported that the general practitioners gave them information about prophylactic treatment. Only 8.0% were advised to keep a headache diary. CONCLUSION: This study shows the need to increase the role and the involvement of family doctors in the management of primary headache in children in general, and of pediatric migraine in particular.     

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-na?ve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.     

Frequent triptan use: observations on safety issues

OBJECTIVE: To examine the safety of frequent triptan use over extended periods. For a small group of patients with refractory migraine plus chronic daily headache, triptans are effective. METHODS: This retrospective study primarily evaluated the cardiac safety of daily triptan use in 118 patients and, in addition, hematologic tests were assessed. Each patient had utilized a triptan for a minimum of 4 days per week for at least 6 months. Patients with rebound headache had been withdrawn from the triptans. Most patients (97 of 118) averaged 1 tablet daily; most would occasionally go for several days without a triptan. Forty patients had taken a triptan for 6 months to 2 years, 37 patients from 2 to 4 years, and 41 for 4 or more years. RESULTS: Routine hematologic tests were performed periodically on all patients, and no abnormalities were attributable to triptans. Almost all patients had an electrocardiogram, and no abnormal electrocardiograms were felt to be related to triptans. Cardiac echocardiography was performed in 57 patients. The 10 abnormal echocardiograms were not due to triptans. All 20 cardiac stress tests revealed normal findings. Adverse events were minimal; 9 patients described fatigue due to triptans, and 5 had mild chest tightness. CONCLUSION: This long-term study of 118 patients indicates that frequent triptan use may be relatively safe.     

An MMPI Control Study: Chinese Migraineurs During Frequent Headache Attack Intervals

The investigation of personality traits of migraineurs with the Minnesota Multiphasic Personality Inventory (MMPI) is an important line of research, but so far has led to diverse conclusions. In this study, the MMPI (Chinese edition) responses of 50 Chinese subjects (10 men, 40 women) with migraine (4 migraine with aura, 46 without aura), during frequent headache attacks were compared with 30 nonheadache healthy control subjects (6 men, 24 women). Statistical analysis was made between the two groups. The results revealed that subjects in the migraine group had significantly higher scores on subtests of neurotic, (hypochondriasis, depression, hysteria, and psychasthenia), schizophrenia, and social introversion ( P <0.05 to 0.001). Utilizing the American T-score, we found the migraine group's MMPI profile was a typical 1.2.3.7 model. These results suggest migraineurs with frequent headache attacks have multiphasic personality abnormalities and partial cerebral function disturbances.     

Disrupted resting‐state functional connectivity and its changing trend in migraine suffers

Chronic pain has been linked with learning and memory processes and functional changes in brain plasticity in its development and maintenance via neuroimaging studies. However, the principle of reorganization of the migraine brain network as the brain progresses into chronic pain remain poorly understood. Here, using resting‐state functional magnetic resonance imaging (rs‐fMRI) and graph theory approaches, we aimed to investigate the dynamic dysfunctional connectivity in 108 patients with migraine without aura (MWoA) and 30 gender‐matched healthy controls (HC). All patients were divided into 40 groups using a sliding boxcar grouping of subjects in disease duration order. As compared with HC, nonparametric permutation tests were applied for between‐group comparisons of functional connectivity strength in each patient group. We focused only on the between‐group differences of functional connections in MWoA, and the situation how these different connections were organized along with the changing trend. As the disease duration increased, the presence of chronic headache altered the functional connectivity from the local central nervous system (CNS) to a disruption in the whole‐brain networks. These dysfunctional connections integrated into a connected component in relatively longer migraine duration groups, suggesting an abnormal integrated network configuration with ongoing central changes for long‐term migraine. Within these between‐group differences of the connected component, there were contained a small number of brain regions that had disproportionately numerous connections. Moreover, these brain regions exhibited a tendency to link to each other were organized into a strongly interconnected community. These interconnected brain regions were mainly located in the sensory‐discriminative brain areas. Our results exhibited a working model of the central mechanisms of migraine where the brain functional connectivity was altered from the local central nervous system to a densely interconnected center, which may extend our understanding of the role of learning mechanisms which are likely involved in maintenance of chronic pain. Hum Brain Mapp 36:1892–1907, 2015. © 2015 Wiley Periodicals, Inc .     

细胞膜色谱法筛选川芎-白芷中5-HT受体激动剂的研究

偏头痛是临床的常见病和多发病,研究表明,5-羟色胺(5-HT)受体在偏头痛的发病中起重要作用。实验通过大鼠纹状体组织制备得到色谱固定相,并利用细胞膜色谱与液相色谱的离线联用来特异性地识别川芎-白芷药对中可与固定相上受体相互作用的配体,发现了欧前胡素是其中潜在的活性成分。以不同浓度(2.42×10-8~4.84×10-7mol·L-1)的5-HT1D受体激动剂舒马普坦为模型药物,记录样品在模型中的容量因子,测得欧前胡素与5-HT1D受体作用的平衡解离常数为(4.59±0.33)×10-6mol·L-1,并采用硝酸甘油致大鼠偏头痛模型验证其药理活性。该研究为体外快速有效地研究药物与受体之间的相互作用提供了一种新方法。     

Therapeutic antibodies against CGRP or its receptor

CGRP is an extensively studied neuropeptide that has been implicated in the pathophysiology of migraine. While a number of small molecule antagonists against the CGRP receptor have demonstrated that targeting this pathway is a valid and effective way of treating migraine, off-target hepatoxicity and formulation issues have hampered the development for regulatory approval of any therapeutic in this class. The development of monoclonal antibodies to CGRP or its receptor as therapeutic agents has allowed this pathway to be re-investigated. Herein we review why CGRP is an ideal target for the prevention of migraine and describe four monoclonal antibodies against either CGRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine. We describe what has been publically disclosed about their clinical trials and future clinical development plans.     

Drug safety and tolerability in prophylactic migraine treatment

Introduction: Migraine is a frequent, disabling primary headache disorder, whose pathomechanism is not yet fully understood. Prophylactic treatment is advisable for migraineurs with severe or highly frequent attacks, which impair the quality of life.

Areas covered: The different types of prophylactic migraine drugs are discussed, with particular regard to potential adverse effects and safety issues. β-Adrenergic blockers, antiepileptic drugs and calcium-channel blockers are drugs widely used for migraine prevention, whereas complementary medicine and onabotulinumtoxin A can be used in selected cases.

Expert opinion: The background of the recurrence and chronification of migraine attacks has not been fully clarified, and causative preventive therapy is therefore not currently available. The tolerability and adverse effects of the currently used medications often limit their use. β-Adrenergic receptor blockers may induce adverse cardiovascular events, whereas flunarizine is frequently associated with a weight gain and depression. As most migraine sufferers are young women of child-bearing age, the use of valproate is limited. Topiramate is associated with central nervous system-related side effects. There is a need for future development of pathomechanism-based preventive drugs, and personalized therapy tailored to the patient.