Motor cortex excitability in patients with migraine with aura and hemiplegic migraine

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls (n=17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.     

Objective assessment of cortical excitability in migraine with and without aura

Recent progress in the genetics of migraine has refocused attention on cortical dysfunction as an important component of the pathophysiology of this disorder. In previous work, we have demonstrated functional changes in the visual cortex of migraine patients, using an objective transcranial magnetic stimulation technique, termed magnetic suppression of perceptual accuracy (MSPA). This study aimed to replicate previous findings in migraine with aura (MA) and to use the technique to examine migraine without aura (MoA). Eight MA patients, 14 MoA patients and 13 migraine-free controls participated. MSPA assessments were undertaken using a standardized protocol in which computer-presented letter targets were followed at a variable delay interval by a single magnetic pulse delivered over the occiput. MSPA performance is expressed as a profile of response accuracy across target-pulse delay intervals. The profiles of migraine-free controls exhibited a normal U-shape. MA patients had significantly shallower profiles, showing little or no suppression at intermediate delay intervals. MoA patients had profiles that were similar to controls. Recent animal evidence strongly indicates that the U-shape of the normal MSPA function is caused by preferential activation of inhibitory neurons. Shallower MPSA profiles in MA patients are therefore likely to indicate a functional hyperexcitability caused by impaired inhibition. The finding of normal MPSA profiles in MoA patients is novel and will require further investigation.     

Effects of topiramate on migraine frequency and cortical excitability in patients with frequent migraine

We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 ± 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 ± 1.3 to 5.8 ± 3.2 migraine days per month; P  = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 ± 7.5% to 47.7 ± 9.2% ( P  = 0.049) and on the left side from 43.4 ± 7.0% to 47.2 ± 9.6% ( P  = 0.047), and phosphene thresholds increased from 58.9 ± 11.1% to 71.2 ± 11.2% ( P  = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.     

Visual cortex excitability in migraine evaluated by single and paired magnetic stimuli

OBJECTIVE: To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses. METHODS: Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms. RESULTS: The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001). CONCLUSIONS: PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.     

Assessing cortical excitability in migraine: reliability of magnetic suppression of perceptual accuracy technique over time

OBJECTIVES: To examine test-retest reliability of magnetic suppression of perceptual accuracy (MSPA) prior to its use as a marker of cortical excitability in a trial of migraine prophylactic agents. BACKGROUND: MSPA is a relatively novel avenue of research in headache, providing an opportunity to study cortical responsiveness objectively and noninvasively. However, little is known about the reliability of magnetic stimulation protocols such as MSPA in longitudinal research designs. METHODS: We tested 10 healthy headache-free volunteers who had no family history of migraine. In 54 trials, they were briefly presented different three-letter combinations, flashed on a computer screen for 24 ms (target). After a brief interval, each target was followed by a single magnetic pulse through a 90-mm circular coil centered 7 cm above inion in the midline. The interval between target and magnetic pulse was systematically varied. Volunteers were requested to report as many letters as they had possibly identified. After 2 weeks, all volunteers were retested using identical methods. RESULTS: MSPA performance is expressed as a profile of response accuracy (ie, percentage of correctly identified letters) across target-pulse intervals. Profiles were characteristic of normal headache-free subjects at the first test. Analysis of variance revealed no significant difference in profiles between test and retest (F= 2.05; P= .136): the retest profiles are almost coincidental with the test profiles. CONCLUSIONS: MSPA is a safe and objective measure of cortical excitability, which is reliable over time. MSPA, therefore, shows excellent promise as a biological marker of cortical response in trials of migraine prophylactics.     

Relationship between migraine and epilepsy in pediatric age

OBJECTIVE: Many studies have supported the hypothesis of alteration of cortical hyperexcitability as a possible pathological mechanism underlying the onset of migraine and epileptic attacks. Different biochemical pathways involving cellular structures may increase or decrease the excitability of neuronal membranes. The aim of this study was to identify a possible link between migraine and epilepsy from a clinical and neurophysiologic point of view. METHODS: One-hundred thirty-seven children and adolescents consecutively diagnosed for tension-type headache and idiopathic migraine with and without aura were studied. Anamnestic, clinical, and instrumental data were collected by a neurological examination, a specific questionnaire, and awake electroencephalogram (EEG) registrations. EEG features of nonheadache and nonseizures control group were compared. RESULTS: Fourteen cases (10.2%) had a positive history for seizures with fever, isolated seizures, or epilepsy. Distribution differed according to headache diagnosis; migraine with aura (MWA) was largely prevalent. Specific electroencephalographic abnormalities were present in 11.7% of the sample, with a significant different distribution across the groups of children with headache and the control group: specific interictal abnormalities were found in 10 of 23 (43.5%) children with MWA. Two factors, seizures and specific interictal electroencephalographic abnormalities, showed a different distribution in patients with MWA compared to other classes of headache and control group (P < or = .01). CONCLUSION: The present study supports the hypothesis of a possible clinical continuum between some types of MWA and epileptic syndromes as entities due to altered neuronal excitability with similar genetic substrates.     

脑老化过程中的白质损害与P300变化的关系

目的观察脑白质变化(WML)与事件相关电位P300变化关系,认识P300是否能够反映WML时认知功能改变。方法观察35例老龄及老龄前期个体的MRI及事件相关电位P300变化,并对WML与P300潜伏期变化进行相关分析。结果轻度WML11例,中度17例,重度7例,P300潜伏期明显延长,随WML的程度加重而加重,相关分析提示两者呈正相关。结论观察老年性WML主要依靠T像或质子密度加权像。WML能引起事件相关电位P300延长,其损害程度与P300潜伏期变化呈正相关。     

利用事件相关电位探索三种听觉Oddball范式脑加工机制的研究

目的:开发一组新的听觉Oddball范式,通过事件相关电位观察其在健康受试者中的脑加工反应。方法:社会招募健康志愿者15名(男8名,女7名,平均年龄40±9岁),分别进行纯音-正名(TS),其他名字-正名(OS)和反名-正名(RS)三组难度依次增大的听觉Oddball范式的事件相关电位检查,分析比较各组MMN和P300潜伏期和波幅的差异。结果:三组实验范式在所有健康志愿者中均诱发得到失匹配负波(mismatch negativity,MMN)和P300,TS组MMN和P300的潜伏期最短,OS组次之,RS组最长(P0.05),但OS组和RS组统计学分析无显著性差异(P0.05);MMN的波幅TS组最大,OS组次之,RS组最小(P0.05),但OS组和RS组统计学分析无显著性差异(P0.05);各组之间P300波幅比较未发现显著性差异(P0.05)。结论:三组听觉Oddball实验范式有一定的区分难度,有望进一步应用于植物状态/无反应觉醒综合征患者和最小意识状态患者的鉴别诊断和预后预测。     

急性脑梗死事件相关电位与认知障碍

目的 分析脑梗死患者的事件相关电位与认知障碍的关系。方法 应用简易精神状态检查量表（MMSE）和相关事件电位（ERP）的检测,分析脑梗死患者的认知功能变化。结果 脑梗死组（32例）与对照组（32例）之间P300潜伏期（P300PL）的比较有非常显著性差异（P＜0．01）。从波形看,脑梗死组波幅较低,P300波变异大,波形不规则。两组MMSE评分亦有非常显著性差异（P＜0．01）。脑梗死组P300潜伏期与MMSE评分呈负相关（r=-0.28,P＜0．01）。结论 P300潜伏期可客观地反映急性期脑梗死患者的认知功能障碍。     

MRI观察无先兆偏头痛患者大脑活动异常

目的 以MRI观察无先兆偏头痛(MowA)患者大脑异常活动。方法 前瞻性纳入50例MwoA患者(MwoA组)及46名健康志愿者(对照组),以功能MRI(fMRI)观察其脑区动态局部一致性(dReHo);提取组间dReHo值存在差异脑区,与临床量表行相关性分析。结果 相比对照组,MwoA组双侧距状裂周围皮层、右枕中回dReHo值增高,右颞中回、右额中回、左楔叶dReHo值减低(GRF校正,体素水平P均<0.005,簇水平P均<0.05);权重分析显示,权重绝对值排名前3位脑区分别为右距状裂周围皮层、左楔叶及右枕中回。MwoA患者左距状裂周围皮层dReHo值与抑郁自评量表(SDS)呈负相关(r=-0.28,P=0.04)。结论 MwoA患者视觉信息上行传递通路存在异常,特别是右距状裂周围皮层、左楔叶及右枕中回。     

Plasma calcitonin gene-related peptide in diagnosing and predicting paediatric migraine

To investigate the role of plasma calcitonin gene-related peptide (CGRP) in paediatric migraine, we prospectively collected 134 blood samples during or between attacks from 66 migraine, 33 non-migraine headache (non-migraine) and 22 non-headache patients, aged 4–18 years. Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment (PedMIDAS) questionnaire. Migraineurs had higher plasma CGRP levels than non-migraine patients ( P  = 0.007). The attack level was higher than the non-attack level in migraine ( P  = 0.036), but not in non-migraine, patients. This was also revealed in paired comparison ( n  = 9, P  = 0.015 vs. n  = 4, P  = 0.47). Using a threshold of 55.1 pg/ml, the sensitivity of the attack level in predicting migraine was 0.81, and specificity 0.75. The PedMIDAS score tended to be higher in the high CGRP (> 200 pg/ml, n  = 7) group than in the low (< 200 pg/ml, n  = 33) group (26.07 vs. 19.32, P  = 0.16) using Mann–Whitney test. Plasma CGRP is useful for diagnosis in paediatric migraine.     

Cortical inhibition is reduced in chronic and episodic migraine and demonstrates a spectrum of illness

BACKGROUND: The pathophysiological relationship between episodic migraine and chronic migraine is not fully understood. We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical excitability in patients with episodic migraine (EM) and probable chronic migraine (PCM), and matched controls. METHODS: Cortical excitability was assessed at baseline with two well-established methods: phosphene thresholds (PT) and magnetic suppression of perceptual accuracy (MSPA) profiles. Five EM patients, five PCM patients, and five normal controls participated in the main study. In addition, two patients were reassessed after 30 days of treatment with topiramate. RESULTS: Both PT and MPSA measures were consistent in indicating a continuum of excitability across the three groups: PCM patients had the highest excitability, followed by EM, then controls. In the two treated patients MPSA profiles appeared to normalize at a 100 mg dosage. CONCLUSIONS: Patients with PCM appear to be characterized by very high cortical excitability. This may contribute to their greatly increased attack frequency. TMS-based methods will be important for future research examining the evolution of chronic migraine from episodic migraine over time.     

Interictal potentiation of passive "oddball" auditory event-related potentials in migraine

We have studied habituation of the P3a component of the passive "oddball" auditory event-related potential which reflects automatic processing of a "novel" stimulus in 24 patients suffering from migraine without aura and in 21 healthy volunteers. Three blocks of responses to 160 standard and to 40 novel tones were sequentially averaged at Cz and analyzed for latencies and peak-to-peak amplitudes. Latencies of components N1 and P2 elicited by standard tones and of components N1, P2, N2, and P3a elicited by novel tones were not significantly different between sequential blocks or between subject groups, nor were mean N1-P2 amplitudes. The N2-P3a amplitude tended to be lower in migraine, but not significantly so. The most striking result in migraineurs was a significant potentiation of N2-P3a in successive blocks, contrasting with an habituation in controls. Our previous evoked- and event-related potential studies and the present one suggest that deficient habituation, or even potentiation, represents interictally a fundamental dysfunction of cortical information processing in migraine, which might increase energy demands and play a role in etiopathogenesis.     

Genetic risk factors in primary paediatric versus adult headache: complexities and problematics

Numerous candidate genes for migraine have been proposed on the basis of their possible functional role in its pathogenesis. Genetic polymorphisms have been evaluated in association studies, some of which have been suggested to be susceptibility markers for adult migraine. To date, however, none of the identified polymorphisms in adult migraine susceptibility have been investigated in children, raising the possibility that they may not be necessarily involved in paediatric migraine susceptibility. This paper reviews studies of the genetic basis of migraine and summarises our experience in genetic association studies in primary paediatric headache susceptibility.     

Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers

OBJECTIVE: To investigate whether colored glasses influence the habituation of visual evoked potentials. BACKGROUND: We have previously shown that during pattern-reversal stimulations lasting 2 minutes the amplitude of the visual evoked potential increases in migraine with and without aura between attacks, whereas it decreases in healthy volunteers. Red light was found to increase visually evoked EEG fast activity only in children with migraine with aura. Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel with a reduction of the visually evoked EEG fast activity. METHODS: We compared the change in amplitude of the visual evoked potential using five different tinted glasses in 12 patients with migraine with aura and in 10 healthy volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses were sequentially averaged using red, yellow, green, blue, and grey glasses and without glasses in a random order and analyzed in terms of latencies and N1-P1 amplitudes. Amplitude changes were calculated for each block by comparison with the first block in every condition and analyzed statistically using Zerbe's method. RESULTS: In healthy volunteers, the visual evoked potential amplitude increased with red glasses compared to without glasses (P = .05) or with green glasses (P = .03). In patients with migraine with aura, no significant difference was detected using colored glasses. Our findings in healthy volunteers are in line with earlier reports of increased excitability of the human visual cortex when exposed to red light. The lack of such a pattern in patients with migraine with aura suggests that the visual cortex is interictally hypoexcitable rather than hyperexcitable, which is consistent with studies of transcranial magnetic stimulation.     

Change of excitability in brainstem and cortical visual processing in migraine exhibiting allodynia

BACKGROUND: Clinical and neurophysiological manifestations of information processing associated with central sensitization are little known. Allodynic migraine (AM) can be caused by the sensitization of trigeminal neuron, but no study has reported on AM between attacks using blink reflex (BR) and pattern-reversal visual evoked potentials (PVEPs). OBJECTIVE: We explored the characteristics of AM between attacks associated with central sensitization using BR and PVEP. METHODS: We recruited 13 patients with interictal AM and 15 patients with nonallodynic migraine (NA), and 30 healthy subjects (HS). BRs were obtained using paired pulses delivered at the interstimulus interval (ISI) of 150, 300, and 500 ms. The ratio of the area in the R2 of the second to R2 of the first shock was measured for each ISI. PVEP were recorded with 2 spatial frequencies (0.5 and 4.0 cpd) and 2 low and high contrasts (29% and 98%, respectively). Amplitudes of P100 were measured. RESULTS: For BR, there were no significant differences in the ratio of the area of the R2 between the sides of stimulation, and the sides of headache. AM patients had less suppression of the R2 at the ISI of 150 and 300 ms when compared with the NA patients and HS. For PVEP, at 0.5, there were significant differences of amplitude between AM patients and HS, and between NA patients and HS in low and high contrast. At 4.0 cpd, there were significant differences of amplitude between AM patients and HS in low contrast, and between AM patients and HS, and NA patients and HS in high contrast. In AM patients, there was a significant difference of amplitude ratio between 0.5 and 4.0 cpd. Conclusions.-Our BR and PVEP study showed that migraine patients exhibiting allodynia may show central sensitization of brainstem trigeminal neuron and have contrast modulating dysfunction during the cortical visual processing of striate and extrastriate on visual cortex in-between attacks.     

慢性意识障碍患者昏迷恢复量表与事件相关电位的相关性分析

摘要目的：探讨慢性意识障碍患者昏迷恢复量表（CRS-R）与事件相关电位MMN、P300的相关性,从而确立CRS-R量表联合事件相关电位评估慢性意识障碍患者意识水平的临床价值。方法：按照入选标准纳入意识障碍患者61例,所有纳入患者在同一时间段（即72h内）完成CRS-R评定及事件相关电位（MMN和P300）检查。先对所收集的数据行正态性检验,符合正态分布的数据采用Pearson相关性分析,不符合正态分布的数据采用Spearman相关性分析,然后将具有相关性的两组数据在考虑年龄、性别、病程、病因、BMI、意识水平等多因素响的情况下进行线性回归多因素分析。结果：在考虑年龄、性别、病程、病因、BMI、意识水平等混杂因素的情况下,CRS-R（听觉）与MMN（F4潜伏期）、CRS-R（视觉）与MMN（CZ波幅）、MMN（FZ波幅）、MMN（F3波幅）,CRS-R（运动）与MMN（CZ波幅）和MMN（F4波幅）,CRS-R（唤醒度）与MMN（F4潜伏期）,CRS-R（总分）与MMN（CZ波幅）存在相关性,其中CZ（波幅）与CRS-R（运动）相关系数为0.759、F4（波幅）与CRS-R（运动）相关系数为0.689、FZ（波幅）与CRSR（视觉）相关系数为0.685,为显著相关。而CRS-R（听觉）与P300（F3波幅）、CRS-R（视觉）与P300（CZ波幅）、CRS-R（口部运动）与P300（F4潜伏期、FZ潜伏期）均存在相关性。结论：CRS-R量表各评分项目与MMN、P300电极点的波幅、潜伏期存在相关性,为慢性意识障碍的临床行为学评估提供电生理检测的客观、直接证据。     

Iron deposition in pain-regulatory nuclei in episodic migraine and chronic daily headache by MRI

Background.— Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks. Methods.— This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension‐type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by‐products of frequent attacks or long duration of illness with these changes. Results.— The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2′ shortening. Conclusions.— Because iron accumulation should cause shortening of both T2 and T2′, although the lack of significance in observed T2′ difference could be due to increased variance in T2′ the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.     

Prevalence of migraine in schoolchildren and some clinical comparisons between migraine with and without aura

OBJECTIVES: To determine the prevalence of migraine and its association with age, gender, and social class and to find out whether or not the headache and nonheadache characteristics differ between children with migraine, with and without aura, using the diagnostic criteria of the International Headache Society for childhood migraine. DESIGN: Population-based study in two stages comprising an initial screening questionnaire followed by telephone interviews of children with symptoms. SETTING: Eighteen kindergarten and 39 primary and secondary schools in Thessaloniki and its semiurban areas. SUBJECTS: Four thousand children, aged 4 to 15 years, representing a random sample of 5% of schoolchildren in Thessaloniki and its semiurban areas. MAIN OUTCOME MEASURES: (1) The prevalence of migraine, (2) the connection of migraine with social class, (3) differences in the occurrence of individual symptoms between migraine with and without aura. RESULTS: The results of the present study show that migraine prevalence was 6.2% (95% confidence interval [CI], 5.4 to 7.0). The estimated prevalences of migraine with and without aura were 2.8% (95% CI, 2.3 to 3.4) and 3.4% (CI, 2.8 to 4.0), respectively. The prevalence of migraine increased with age and it was found to be almost equal in boys and girls aged 7 to 9 years or younger, but in older age groups the prevalence was higher in girls than in boys. The data showed no evidence that connected migraine with social class. It also showed that except for the aura, the headache (e.g., frequency, duration, location, quality, and severity) and nonheadache (e.g., nausea, vomiting, phonophobia, and photophobia) characteristics were no different between children with migraine, with and without aura. In conclusion, our findings indicate that migraine is a common underdiagnosed cause of severe recurrent headache in children. The findings show that childhood migraine is not connected with social class and varies with age and gender, and that except for the aura, both migraine with and without aura are so similar in their headache and nonheadache clinical characteristics that a common pathogenesis is plausible.     

Clinical characteristics of migraine in a population-based twin sample: similarities and differences between migraine with and without aura

OBJECTIVE: To look into clinical differences between migraine with and without aura in a population-based sample of migraineurs. BACKGROUND: Migraine presents in two major forms, migraine with and migraine without aura. With the exception of the aura phase, the clinical characteristics of these entities are very similar. Despite this, however, the recent epidemiological data underline differences between migraine with and without aura. We tried to examine whether other features besides the aura differ between these two major forms of migraine. METHODS: We studied 321 twins suffering from migraine with aura and 166 twins with migraine without aura from the population-based Finnish Twin Cohort. Migraine was diagnosed according to the criteria of the International Headache Society (IHS). Analysis was based on the combination of a mailed questionnaire and a telephone interview by a neurologist. Special attention was paid to differences between migraine with and without aura. RESULTS: Some qualities of headaches differed between IHS defined migraine with and without aura. Unilateral headache (Chi-squared p = 0.039) and photophobia (Chi-squared p = 0.010) were more typical for migraine with aura, while nausea was more typical for migraine without aura (Chi-squared p = 0.002). Duration of headache in migraine without aura was also longer than in migraine with aura (Mann-Whitney U-test 0.007). CONCLUSIONS: There are clinical differences between IHS defined migraine with and without aura; even the headache phase between the two entities differs. It is worthwhile distinguishing between them when looking for the elusive genes for these more common forms of migraine.