CGRP en migraña: de la fisiopatología a la terapéutica

IntroductionIt has been observed in recent years that levels of such molecules as calcitonin gene–related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase–activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients’ migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity.DevelopmentThe Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics.ConclusionsThe clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.     

癫痫及偏头痛相关诊断标准解读

国际头痛学会相继提出“偏头痛癫痫”和“发作性癫痫性头痛”等概念和诊断标准,并在临床上广泛应用。笔者认为上述诊断标准均有值得商榷之处。头痛可以作为癫痫发作的症状,也常见于癫痫发作后,偏头痛和癫痫可以共病。从癫痫专业角度来看,偏头痛癫痫也许是一种局灶性癫痫。医学观点百家争鸣,癫痫和头痛亚专业组应加强对话,科学地制订癫痫和偏头痛相关诊断标准。     

A review of clinical safety data for sumatriptan nasal powder administered by a breath powered exhalation delivery system in the acute treatment of migraine

Introduction: AVP-825 (sumatriptan nasal powder) is an FDA-approved intranasal medication delivery system containing low-dose sumatriptan powder for acute treatment of migraine with or without aura in adults. AVP-825 utilizes unique nasal anatomy features to avoid limitations of other intranasal delivery methods.

Areas covered: Literature search terms: ‘AVP-825’, ‘sumatriptan nasal powder’, ‘intranasal sumatriptan’, ‘sumatriptan safety’, ‘sumatriptan acute migraine’. Pharmacokinetic, Phase 2/3 studies, reviews (AVP-825) and metanalyses/reviews (sumatriptan) were evaluated.

Expert opinion: AVP-825 provides a more efficient sumatriptan delivery method versus other formulations. Pharmacokinetics showed that a single dose of AVP-825 (22 mg) delivers 15-16 mg sumatriptan and produces significantly lower exposure than oral or injectable formulations, which may translate into a better safety/tolerability profile. AVP-825 was well tolerated in controlled trials, with the most common adverse events localized at the administration-site (abnormal taste, nasal discomfort); these were mostly mild, leading to only one discontinuation. Compared to 100 mg oral sumatriptan, AVP-825 had a significantly lower rate of atypical sensations across multiple attacks. AVP-825 has the advantage of early efficacy onset associated with faster absorption at a lower delivered dose than liquid nasal spray or oral formulations. AVP-825 provided earlier efficacy (within 30 min) vs. 100 mg oral sumatriptan and similar sustained efficacy. AVP-825 offers the benefits of a non-oral, low-dose, tolerable acute migraine medication.     

Stereotyped topography of different elevated contingent negative variation components in children with migraine without aura points towards a subcortical dysfunction

Increased negativity during contingent negative variation (CNV) is thought to reflect abnormal neural activation in adult migraineurs' attention related processing. Findings in childhood and adolescence have yielded less clear results. This study characterizes the age-dependent development of CNV topography in migraine during childhood in order to elucidate the origin and cerebral generators of described CNV elevations. A large sample of children with primary headache (migraine with/without aura, tension type headache) and healthy controls aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution DC-EEG. Patients were tested for diagnose-related topographic group differences of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation (PINV). All three CNV components of 6-11-year-old migraineurs without aura showed elevated negativity over the supplementary motor area (SMA) and around the vertex. Migraine children lacked age-dependent development of late CNV around Cz as previously reported. However, they showed a normal development of late CNV over pre-/primary motor cortex (MI). There was no marked elevation of iCNV amplitude over frontal areas (orienting reaction) nor specific amplitude elevations over "motor" or "sensory" areas during sustained attention (late CNV). Additional "pre-mature" activation e.g., in the locus coeruleus (leading to diffuse cortical activation summing up to a maximum over the vertex) or the basal ganglia (interacting with SMA) explained the rather stereotyped CNV elevation around the vertex better than a specific implication of the cortical systems responsible for orienting, motor preparation or sensory attention.     

Validation of the eleven-point pain scale in the measurement of migraine headache pain

The four-point pain scale (none, mild, moderate, severe) and the 11-point pain scale (0 = no pain, 10 = pain as bad as it could be) have been used in migraine studies to assess treatment efficacy. The primary objective of this study was to investigate the validity and responsiveness of the 11-point pain scale using the four-point pain scale as a benchmark. Using data from 95 migraine patients recruited from headache clinics, this study found that 11-point pain scale scores were highly correlated with four-point pain scores. The correlations between the pain scales were significantly higher than the correlations with quality of life measures such as functional ability and emotional feelings. The 11-point pain scale was 55% more sensitive than the four-point pain scale in detecting clinically important differences. The strong linear relationship between the two pain scales allowed researchers to transform four-point pain scores to 11-point pain scores using regression weights.     

Migraine headache and obesity in women aged 40-74 years: a population-based study

This study investigates the associations between obesity and migraine. A neurologist clinically assessed 684 women aged 40-74 years attending a population-based mammography screening programme. Body height and weight were measured and body mass index (BMI) calculated. Obesity was defined as a BMI > or = 30 kg/m2. The proportion of obesity did not differ between women with active migraine, women with inactive migraine or women who had never experienced migraine (P = 0.96). The distribution of frequency, intensity, duration or severity of attacks did not differ between obese and non-obese women with migraine. In this study there were no significant associations between migraine or migraine characteristics on the one hand and obesity on the other.     

偏头痛患者血小板内环核苷酸含量的测定

运用放免法测定了１８例偏头痛间歇期患者血小板内ｃＧＭＰ含量及部分患者的血小板内ｃＡＭＰ含量，结果发现偏头痛患者血小板内ｃＧＭＰ含理增高，而ｃＡＭＰ含量无明显变化。要文讨论了偏头痛患者血小板内环核苷酸含量异常与其血小板功能异常的关系。     

足三阳经循经井穴刺血治疗偏头痛临床研究

目的:观察足三阳经循经井穴刺血法治疗偏头痛的临床疗效。方法:选取符合纳入标准的70例偏头痛患者作为研究对象,按数字奇偶法分为2组各35例。对照组给予常规针刺治疗,研究组在对照组治疗方案的基础上给予足三阳经循经井穴刺血治疗。观察2组治疗前后疼痛视觉模拟评分法(VAS)评分、偏头痛综合评分及临床疗效。结果:2组疼痛VAS评分、偏头痛综合评分治疗前后比较,差异均有统计学意义(P<0.01);治疗后研究组疼痛VAS评分、偏头痛综合评分均明显低于对照组,差异均有统计学意义(P<0.01)。临床疗效总有效率研究组91.43%,对照组80.00%,2组比较,差异无统计意义(P>0.05)。结论:相较于单纯常规针刺治疗,加用足三阳经循经井穴刺血治疗镇痛效果更佳。     

200例偏头痛患者急性发作期的经颅多普勒超声（TCD）检测及相关因素分析

目的探讨经颅多普勒超声（TCD）对偏头痛急性发作期的检测意义。方法将200例偏头痛患者按不同年龄段分成5组,在急性发作期进行TCD检测血流速度。结果偏头痛患者不同年龄段急性发作期脑血流速度和正常人血流速度与同名动脉比较,偏头痛患者MCA及PCA、VA血流速度和正常人血流速度比较有显著性差异（P〈0．05）。偏头痛患者TCD检测的总体表现脑血管血流速度增快。有先兆偏头痛与无先兆偏头痛的2组血流速度比较不明显（P〉0．05）。结论TCD能敏感地反映偏头痛患者在急性发作期颅脑血管舒缩功能及其血流动力学变化情况,TCD检测结果可作为偏头痛患者急性发作期的诊断依据。     

Lamotrigine for intractable migraine-like headaches in Sturge–Weber syndrome

We herein report that naratriptan remarkably improved intractable migraine-like headaches in a patient with Sturge–Weber syndrome (SWS) despite his past history of cerebral infarction. In addition, lamotrigine had a prophylactic effect on his visual aura and headaches. An 18-year-old male patient with SWS had intractable migraine-like headaches every several months from the age of 3 years. His migraine-like headaches were characterized by pulsating attacks preceded by left homonymous hemianopsia, which persisted after headache disappearance. In addition, after 14 years of age, the pulsating headaches were preceded by photophobia without homonymous hemianopsia and occurred almost daily. Headache pains were not improved by acetaminophen or loxoprofen sodium hydrate. Furthermore, various prophylactic drugs were ineffective. After obtaining informed consent, naratriptan was administered. The pain severity was reduced and the duration of headache with homonymous hemianopsia was shortened from several days to several hours. Interestingly, naratriptan also shortened the duration of homonymous hemianopsia to several hours. We confirmed that his headache attacks were not epileptic seizures by ictal electroencephalography. However, 25 mg/day of lamotrigine had a prophylactic effect on the frequency of headache. Moreover, lamotrigine led to complete remission of his headache without homonymous hemianopsia. Lamotrigine may have an advantage in terms of reducing the risk of cerebrovascular disease caused by migraine-like headaches and the use of triptans. The most effective management for migraine-like headaches in patients with SWS has not been established. Lamotrigine is a potentially effective option for patients with SWS with migraine-like headaches.