Persistent ocular motor disturbances in migraine without aura

Abstract. Activation in the brain stem during attacks of migraine has been detected with the use of functional imaging, suggesting an important role of the brain stem in this disorder. Recent findings showed permanent cerebellar signs in common forms of migraine. Both structures are involved in generating smooth pursuit eye movements. The aim of this study was to investigate migraine patients by electrooculography to identify persisting abnormalities that may provide a clinical sign of continuous dysfunction of these structures. We investigated 25 patients with migraine without aura and 15 controls. Smooth pursuit was pathologically changed, velocity gain was reduced and phase was significantly altered in migraineurs as compared to controls. The data provide clinical evidence of a persistent dysfunction in the brain stem and certain cerebellar structures in migraine patients. This is consistent with previous studies indicating an important role of the brain stem in generating migraine attacks.     

Familial migraine with and without aura: clinical characteristics and co-occurrence

Migraine with aura (MwA) and migraine without aura (MwoA) are the two common forms of migraine. Many migraine patients suffer from both kinds of attacks. In a questionnaire-based study using the current International Headache Society (IHS) criteria we determined the clinical characteristics and occurrence of MwA + MwoA in 1000 migraine patients belonging to 210 Finnish migraine families. Nine hundred and six patients were able to indicate whether they suffered from MwA (but not MwoA), migraine aura without headache (migraine equivalent) (but not MwA) or MwA and MwoA. Of these patients, 3.2% had experienced MwoA, 11.1% MwA, 40.6% MwA + MwoA, 23.5% MwoA and 20.3% MwA-like symptoms not meeting the IHS criteria. The high prevalence of MwA attacks in the families studied supports the belief that aura has a strong hereditary component. The MwA + MwoA patients had significantly more severe attacks, more typical headache and more prodromal symptoms than the MwA and MwoA subjects. Therefore, it is possible that there is a continuum with pure MwA at the neural and pure MwoA at the headache end of the spectrum, and MwA + MwoA lying in between the two. The MwA + MwoA patients would thus be liable to both types of migraine, making their attacks more characteristic and more severe. This would also explain why the co-occurrence of MwA and MwoA is more common in the clinic compared with population based epidemiological studies. These findings have consequences for future research on liability genes for migraine.     

A study of symptomatic drug use in migraine without aura

We assessed the attack drugs taken by 200 migraine without aura patients (International Headache Society criteria, 1988) between 1989 and 1991. A detailed pharmacological history regarding the acute attack therapy adopted up until our initial visit was gathered, including the type of drug used, dosage, administration route, the time of starting therapy, treatment efficacy, and the frequency and types of undesirable effects, all of which were subsequently compared with the guidelines (1993) of the Italian Society for the Study of Headache (SISC). The most commonly used are non steroidal anti-inflammatory drugs (NSAIDs). We observed a similar high frequency in the use of combinations, particularly prophyphenazone and barbituric acid. The pirazolones, such as noramidopyrine and prophyphenazone, are also widely used as single agents, even though they are not considered by the guidelines. Our study underlines the fact that current drug use differs in several respects from the guidelines.

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Sommario Abbiamo esaminato il trattamento farmacologico dell'attacco acuto, usato da 200 pazienti sofferenti di emicrania senza aura (criteri IHS 1988), visitati nel periodo 1989–1991. È stata raccolta una dettagliata analisi farmacologica sulle terapie d'attacco usate dai pazienti nel corso della loro storia cefalalgica precedentemente alla prima visita presso il nostro ambulatorio. Sono state studiate le seguenti variabili: tipo di farmaco usato, dosaggio e via di somministrazione, efficacia del trattamento, frequenza e tipo degli effetti indesiderati; questi parametri sono stati confrontati con le linee guida della Società Italiana per lo Studio delle Cefalee (SISC, 1993). I farmaci più comunemente usati sono gli antiinfiammatori non steroidei; abbiamo osservato un analogo uso delle associazioni, in particolare propifenazone ed acido barbiturico. I pirazolonici propifenazone ed amidopirina, non consigliati nelle linee guida, sono anch'essi largamente usati. Il nostro studio evidenzia il fatto che l'utilizzo corrente dei farmaci differisce in molti aspetti da quello suggerito dalle linee guida.

     

无先兆偏头痛发作间期的静息态功能磁共振研究

目的本研究采用静息态功能磁共振(rf MRI)方法通过对比无先兆偏头痛(Mwo A)患者与健康对照的大脑自发脑活动的局部一致性(Re Ho)差异,为偏头痛的发病机制提供新的见解。方法对23例发作间期的Mwo A患者和25例性别、年龄、受教育程度相匹配的健康被试者进行临床资料的采集及rf MRI检查。应用Re Ho方法分析每个被试者大脑的相邻体素的血氧水平依赖(BOLD)信号在同一时间序列中波动的一致性,并对两组被试者的Re Ho值的脑图行统计学分析。结果与对照组Re Ho脑图相比,偏头痛组右侧丘脑、右侧壳核、右侧前额叶皮质及右侧海马的Re Ho值显著高于对照组(P0.05)。结论 Mwo A患者发作间期疼痛处理及调节与应激反应相关的脑区存在功能异常。     

有先兆偏头痛患者发作间期的静息态功能磁共振变化

目的采用静息态功能磁共振成像技术探讨有先兆偏头痛患者的自发神经元活动,分析其脑功能网络的变化,以便更好地认识有先兆偏头痛的发病机制。方法对7例发作间期有先兆偏头痛患者和7例年龄、性别及受教育程度相匹配的健康对照行静息态功能磁共振成像扫描,分析原始数据,得出全脑低频振幅(ALFF),进行双样本t检验,并以ALFF差异脑区为感兴趣区(ROI)校正后行功能连接(FC)分析,比较两组之间影像学表现的差异。结果病例组双侧额上回、左侧眶额皮质低频振幅值显著高于对照组(t=2.18~5.12,P0.05)。病例组左侧颞中回、左侧颞下回、左侧尾状核、双侧丘脑、右侧运动前区低频振幅ALFF值显著低于对照组(t=-5.12~-2.18,P0.05);与对照组相比,病例组右侧眶额皮质、左侧额中回、双侧前扣带皮质、右侧缘上回与左侧额上回功能连接增强,病例组左侧小脑、右侧脑岛、脑干与左侧额上回之间的功能连接减弱。结论有先兆偏头痛患者头痛发作间期疼痛处理相关脑区功能异常,支持偏头痛并非单纯的发作性疾病。     

无先兆偏头痛患者的经颅多普勒和皮肤交感反应的对比分析

目的探讨无先兆偏头痛(MWA)患者发作间期的脑血管血液动力学异常和自主神经功能失常。方法对48例MWA患者和36例健康人群(HC)的经颅多普勒(TCD)和皮肤交感反应(SSR)进行对比分析。结果 MWA组的TCD大脑中动脉最高平均流速(MFV-MCA)异常率和SSR异常率分别为64.6%和58.3%,与HC组相比,均具有非常显著性差异(P<0.01);MWA组的SSR主要异常表现为潜伏期延长,与HC组相比,差异具有显著性(P<0.05)。MWA组TCD的异常改变和SSR的异常具有较好的一致性(总符合率=68.7%,Kappa值=0.343,P=0.017)。结论在发作间期无先兆偏头痛患者确实存在脑血液动力学的改变和自主神经功能的异常;TCD与SSR存在一致性异常有助于鉴别无先兆偏头痛患者的发病机制和原因。     

无先兆偏头痛患者大脑结构和功能异常的MRI研究

目的研究无先兆偏头痛患者大脑结构和功能异常的MRI表现。方法选取30例无先兆偏头痛患者作为观察组,同期25例健康志愿者作为对照组。Signa Excite 3.0 T磁共振扫描仪,采用平面回波成像序列采集对象静息态功能MRI图像,采用单次激发回波平面成像序列采集脑白质DTI图像。采用肯德尔系数评估静息态局部一致性,采用基于纤维束追踪空间统计分析技术(TBSS)分析脑白质纤维的分数各项异性(FA)、平行弥散系数(RD)、轴向弥散系数(AD)、以及平均弥散系数(MD)。结果与对照组比较,观察组患者多个脑区存在局部一致性降低,包括左侧前后扣带回、左侧颞下回、左侧梭状回、右侧中央前后回、右侧额中回、右侧舌回局部一致性减弱(FEW校正,P0.05)。观察组患者双侧大脑脚、双侧内囊后肢、右侧内囊前肢、右侧上纵束、右侧胼胝体体部和压部、右侧上放射冠和后放射冠、左侧扣带的FA值显著降低(FEW校正,P0.05);双侧上放射冠和后放射冠、双侧扣带、双侧丘脑后辐射、双侧上纵束、右侧大脑脚、右侧内囊前后肢以及右侧胼胝体体部和压部的RD值显著升高(FEW校正,P0.05);胼胝体体部和压部,右侧上放射冠和后放射冠,以及右侧上纵束的MD值显著升高(FEW校正,P0.05);两组各脑区的AD值无显著性差异(FEW校正,P0.05)。结论无先兆偏头痛患者大脑静息态局部一致性和脑白质纤维束存在改变,且明显区别于健康志愿者。     

Abnormal visual processing in migraine with aura: a study of steady-state visual evoked potentials

BACKGROUND: Although a number of studies reported different interictal findings between migraine with aura (MA) and migraine without aura (MO), the pathophysiology of the visual aura in migraine remains unclear. OBJECTIVE: To investigate the visual processing in patients who experience MA between attacks using steady-state visual evoked potentials (SSVEPs). METHODS: SSVEPs to high (98%) and low (29%) contrast black and white checkerboard gratings with two spatial frequencies (0.5 and 2.0 cpd) at 5 and 10 Hz (10 and 20 reversal/s) were recorded binocularly from 10 patients with MA, 10 patients with MO between attacks and 20 healthy controls (HC). The SSVEPs were Fourier analyzed to obtain the amplitude and phase of the second (2F) and fourth (4F) harmonic response. RESULTS: In the amplitude of 2F, at 0.5 cpd, there was significant increased amplitude in both MA and MO in comparison to HC at 5 Hz in high and low contrast. However, no significant differences were detected at 2.0 cpd in both 5 and 10 Hz in high and low contrast. In the amplitude of 4F, at 2.0 cpd, there was significant increased amplitude in MA in comparison to MO and HC at 10 Hz in high contrast. However, there were no significant differences at 0.5 cpd at both 5 and 10 Hz in high and low contrast. There were no significant phase differences between MA, MO, and HC. CONCLUSION: The high amplitude of the SSVEPs suggests that interictally migraine patients have abnormal excitability in the primary visual cortex, and this change in excitability may exist, at least partially, in the visual association cortex in MA.     

Is the CACNA1A gene involved in familial migraine with aura?

The discovery of mutations in the neural calcium channel (CACNA1A) gene in familial hemiplegic migraine (FHM), variant of migraine with aura, led to the suggestion that this gene might be involved in familial migraine with aura (FMA). We investigated whether the mutations in FHM are present in FMA patients, analyzing genomic DNA by PCR, single stranded conformation polymorphism, sequencing and restriction enzyme. No mutations were found. A known polymorphism (5682–14C>T) was found in exon 36. These findings suggest that the mutations found in FHM and the other known mutations of the CACNA1A gene are not the genetic basis of FMA. Genetic alterations in FMA patients may be localized on chromosome 19 but not in the CACNA1A exons we investigated. Received: 25 January 2002 / Accepted in revised form: 25 February 2002     

有先兆偏头痛发作间期的静息态功能磁共振研究

目的本研究采用静息态功能磁共振(rfMRI)技术描述有先兆偏头痛(MA)患者大脑自发脑活动的局部一致性(ReHo)的改变,为MA的发病机制提供新的见解。方法收集12例发作间期的MA患者和15例性别、年龄、受教育程度相匹配的健康被试,并进行临床资料的采集及rfMRI检查。计算每个被试大脑相邻体素的ReHo值,并对两组被试的ReHo值脑图行统计学分析。结果与对照组ReHo脑图相比,偏头痛组右侧丘脑、右侧壳核、右侧小脑、脑干的ReHo值显著降低,而右侧枕叶的ReHo值显著增高(P0.05)。结论MA患者发作间期疼痛处理及调节相关的脑区功能异常,中枢敏化作用及皮质高反应性在MA发病机制中可能占有重要作用。     

Gender ratio of migraine without aura: observations over time

Abstract Migraine without aura is typically considered a female condition. The purpose of this study was to determine if there have been any changes in the female-to-male ratio of the disease over time. We included in the study all patients with migraine without aura (n=3457) referred to the Parma University Headache Centre between 1976 and 1995. They were divided into subgroups with respect to gender and year-range of onset of migraine (before 1960, in the 1960s, in the 1970s, in the 1980s, and between 1990 and 1995). Gender ratio ranged from 3.6:1 (in patients with onset before 1960) to 2.8:1 (in patients with onset in the 1980s), with no statistically significant changes during the observation period.     

The extent of right-to-left shunt fails to correlate with severity of clinical picture in migraine with aura

Abstract Several investigations have documented an increased incidence of right-to-left shunt (RLS) in migraine with aura (MA) and have emphasised its role in the physiopathology of aura; so far, however, no data are available concerning a possible correlation between the extent of the RLS and the clinical picture of MA patients. To investigate the possible relationship between the extent of the RLS, revealed by the number of microbubbles (MB) detected during transcranial Doppler with IV injection of ultrasound contrast (TCDc), and the clinical characteristics of MA (age at first onset of migraine, mean annual frequency of attacks and mean duration of the aura phase), 30 consecutive patients with typical aura and migraine headache positive on TCDc evaluation for RLS were enrolled. Permanent RLS was found in 12 patients and latent RLS was found in 18 patients; of these, 6 had a high-grade RLS, 5 medium-grade RLS and 7 low-grade RLS. No correlation has been documented between the number of MBs and the clinical parameters of both patients with latent shunts and those with permanent ones, nor between the clinical parameters of the two groups of patients. These data show that RLS does not seem to affect the clinical manifestation of MA and that the extent of RLS fails to correlate with the severity of the clinical picture of the disorder.     

对比增强经颅多普勒对隐源性缺血性卒中和先兆性偏头痛患者与右向左分流不同分流量相关性的研究

目的 对隐源性缺血性卒中和先兆性偏头痛患者的右向左分流阳性率及分流量进行对比分析,研究二者之间右向左分流的特征及可能的发病机制.方法 连续入组48例隐源性缺血性卒中患者、42例先兆性偏头痛患者、33例健康志愿者做为对照组,使用对比增强经颅多普勒诊断右向左分流,并根据分流量进行分级,对3组的右向左分流阳性率和不同分级进行...     

Increased risk of migraine with typical aura in probands with familial hemiplegic migraine and their relatives

We investigated the occurrence of migraine without aura (MO) and migraine with typical aura (MA) amongst probands with familial hemiplegic migraine (FHM) and their first degree relatives in order to evaluate the relations between these syndromes. A total of 44 FHM probands and 240 first degree relatives were identified in the Danish population. The pattern of familial aggregation was assessed by population relative risk (PRR) calculations. Amongst FHM probands the PRR of MO was 1.5 (95% CI: 0.8-2.2), whereas the PRR of MA was 7.1 (95% CI: 5.0-9.2). Thus, compared with the general population, FHM probands had no increased risk of MO but a significantly increased risk of MA. A similar pattern was seen amongst their first degree relatives, who had no increased risk of MO, whereas the risk of MA was significantly increased; 7.6 times in FHM-affected first degree relatives and 2.4-times in non-FHM-affected first degree relatives. These results are contrary to a sharing of genetic mechanisms between FHM and MO. Furthermore, they suggest that the genetic abnormality causing FHM may also cause attacks with the symptomatology of MA.     

The genetics of migraine

Clinical, pathophysiological and genetic studies indicate that migraine without aura (MO) and migraine with aura (MA) are distinct entities. Compared with the general population, first degree relatives of probands with MO have a two-fold increased risk of MO. The mode of inheritance is most likely multifactorial inheritance without generational difference, but genetic heterogeneity can not be excluded. Compared with the general population, first degree relatives of probands with MA have a four-fold increased risk of MA. The mode of inheritance is most likely multifactorial inheritance without generational differences. Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of MA. A gene for FHM maps to chromosome 19. Some families with FHM do not link to this locus, indicating genetic heterogeneity of FHM. The gene for FHM is soon to be cloned. Loci for the more common types of migraine MO; and MA will problably be identified in the near future.     

Temporal–occipital glioblastoma presenting with Alice in Wonderland Syndrome in a patient with a long-time history of migraine without aura

ABSTRACT

Alice in Wonderland Syndrome (AIWS) is a rare perceptual disorder characterized by an erroneous perception of the body or the surrounding space. AIWS may be caused by different pathologies, ranging from infections to migraine. We present the case of a 54-year-old man, with a long-time history of migraine without aura, diagnosed with AIWS due to a glioblastoma located in the left temporal–occipital junction. To date, this is the first case of AIWS caused by glioblastoma. This case suggests that to exclude aura-mimic phenomena, a careful diagnostic workup should always be performed even in patients with a long-time history of migraine.     

偏头痛患者血浆P物质与神经激肽A的变化

为了探讨偏头痛与Ｐ物质（ＳＰ）、神经激肽Ａ（ＮＫＡ）含量之间的关系。本研究放射免疫法测定了６９例无先兆性砂痛患者组与３１例正常对照组血浆ＳＰ与ＮＫＡ含量。结果发现ＳＡＰ与ＮＫＡ在偏头痛患者组较正常对照组升高，且头痛发作期该两种神经肽较间歇期更高。提示ＳＰ与ＮＫＡ可能通过降低痛阈等机理偏头痛的发作。本组男女患者间ＳＰ与ＮＫＡ含量无明显临床上偏头痛了于女性，常于月经期发病，提示ＳＰ、ＮＫＡ等虽参予其发     

New international classification of migraine with aura (ICHD-2) applied to 362 migraine patients

The International Classification of Headache Disorders 2nd edition (ICHD-2) subdivides migraine with aura (MA) differently from the ICHD-1 and includes new diagnostic criteria. The aim of the present study was to evaluate how the new classification works in practice and in comparison with the ICHD-1. The patients were recruited from a screen of the Danish National Patient Registry and from Danish neurologists. We included 362 patients diagnosed with MA according to the ICHD-1 in a validated semistructured physician-conducted interview. According to the ICHD-2, 89% (322 of 362) had MA and 11% (40 of 362) had probable MA. The MA patients had one or more ICHD-2 subtype of MA: 54% (173 of 322) had typical aura with migraine headache (MA-MH), 40% (129 of 322) had typical aura with non-migraine headache (MA-NMH), 37% (120 of 322) had aura without headache (MA-WOH), and 7% (26 of 322) had basilar-type migraine (MA-B). Of patients with MA-MH 34% (59 of 173) had co-occurrence of MA-WOH, 9% (16 of 173) had co-occurrence of MA-B and 5% (8 of 173) had co-occurrence of both MA-WOH and MA-B. Of patients with MA-NMH 27% (35 of 129) had co-occurrence of MA-WOH. Only 6% (18 of 322) of the MA patients had exclusively MA-WOH and <1% (2 of 322) had exclusively MA-B. Patients with MA-MH had an earlier age at onset (P = 0.044), an increased lifetime number of MA attacks (P = 0.054) and a higher co-occurrence of migraine without aura (P = 0.002) than patients with MA-NMH. Patients with MA-B tended to have an earlier age at onset and more severe attacks and patients with MA-WOH had a higher age at onset and less severe attacks than patients with MA-MH. The variations between ICHD-2 subtypes of MA indicate that patients with similar subtype of MA share phenotype and very likely have similar underlying aetiology.