Pathophysiology of migraine attack with prolonged aura revealed by transcranial Doppler and near infrared spectroscopy

The aim of this study is to identify the pathophysiology of migraine attack with prolonged aura (between 1 h and 7 days) not clearly understood. We studied cortical cerebral microcirculation by an innovative near infrared spectroscopy system (NIRS) and cerebral macrocirculation by trancranial Doppler (TCD) in eight subjects (3 M and 5 F, age range 21–41 years) during spontaneous prolonged migraine aura and after 1, 2, 4, 6, 12 and 24 h since the end of aura and compared the results with the headache-free periods. During aura NIRS showed a significant decrease of the arterial pulse wave of cerebral microcirculation (APWCM) amplitude (−35%), p < 0.002, and an increase of cerebral tissue oxygen saturation (SctO₂) (+15%), p < 0.008 ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods; TCD showed a significant increase of pulsatility index (+38%), p < 0.001 and a significant decrease of the diastolic velocity in the posterior and middle cerebral artery ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods. During prolonged migraine aura we found areas of cortical hypoperfusion corresponding to the topography of aura symptoms that were the result of a decreased metabolic demand rather than ischemic mechanism.

     

Multimodal tests of cerebrovascular reactivity in migraine: a transcranial Doppler study

Summary Altered cerebral vasoreactivity (CVR) has been implicated in migraine. To test this hypothesis, we studied CVR as measured by transcranial Doppler ultrasound (TCD) in 11 migraineurs and 12 healthy controls of similar age. Mean flow velocities (MFV) in the middle cerebral artery (MCA) were recorded during a cognitive and two motor tasks. MFV in the posterior cerebral artery (PCA) were measured during photic stimulation and observation of complex images. The increase of MFV in the MCA during the cognitive task was greater in migraineurs than in controls (9.1% vs 5.0% ;P = 0.06). The increase of MFV in both tests for PCA reactivity was significantly greater in migraineurs than in controls: 17.4% vs 9.9% for photic stimulation (P < 0.05) and 20.3% vs 10.2% for observation of complex images (P<0.05). Owing to overlap of individual results, the discriminative value of both tests was unsatisfactory. The variability of flow velocities as measured by standard deviations of MFV was significantly greater in migraineurs than in controls during all tests of PCA vasoreactivity. Differences in CVR between migraineurs and normal controls may be detected by TCD testing, in particular in the PCA territory. For individual diagnostic purposes, CVR tests proved to be insufficient.     

Cerebrovascular CO2 reactivity in migraine with aura and without aura. A transcranial doppler study

Inntroduction – We studied by means of Transcranial Doppler (TCD) recordings the CO₂ cerebrovascular reactivity in migraine patients during the headache-free period. Material & methods - In three groups of subjects (15 controls, 15 suffering from migraine with aura and 15 from migraine without aura) the middle cerebral artery (MCA) mean flow velocity (MFV) was recorded under basal condition and hypocapnia induced by hyperventilation. Relative MFV, PI (Pulsatility Index) changes and Reactivity Index (RI) were calculated. Results - Reactivity Index values were: 0.019 ± 0.007 (mean ± SD) in control subjects: 0.029 ± 0.008 in migraine with aura; 0.022 ± 0.008 in migraine without aura. Statistical analysis showed a significantly (P < 0.05) increased RI in migraine with aura group. Conclusion – Cerebrovascular CO₂ reactivity is increased during the interictal period in migraine with aura patients.     

Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes. Received: 28 December 2001, Received in revised form: 19 March 2002, Accepted: 21 March 2002     

Gender-related differences in acetazolamide-induced cerebral vasodilatory response: a transcranial Doppler study.

Cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration can be easily and reliably assessed by measuring acetazolamide-induced changes using transcranial Doppler. The authors' aim was to determine whether there are gender-related differences in these parameters. Fifty-six healthy subjects (27 males, 29 females) were examined using transcranial Doppler. Velocities in the middle cerebral artery on both sides were recorded before and at 5, 10, 15, and 20 minutes after intravenous administration of 1 g acetazolamide. The baseline mean flow velocity in the middle cerebral artery was significantly higher in women than in men (p < 0.02). After acetazolamide administration, significantly higher cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration were observed in females than in males (p < 0.001 in all cases). Subgroup analysis showed that women before menopause responded with higher cerebrovascular reserve capacity and velocity acceleration than age-matched men (p < 0.01 and p < 0.001, respectively), but no significant difference was found between females after menopause and men of similar age.     

Decreased vasoreactivity to right cerebral hemisphere pressure in migraine without aura: a near-infrared spectroscopy study.

OBJECTIVE: Several studies have reported changes in cerebrovascular reactivity during the interictal period of migraine. To characterize mechanisms of migraine, we compared changes in total haemoglobin (THbl) and regional oxygen saturation (rSO(2)) of the right and left frontal lobes in response to intracranial pressure changes during the interictal period of migraine. METHODS: Twelve right-handed migraineurs without aura and twelve age- and sex-matched healthy volunteers were asked to perform a head-down maneuver to increase intracranial venous pressure. Initial THbl was designated as 1.0, and all subsequent THbl measurements, which was proportional to the change in cerebral blood flow, were expressed as a value relative to this baseline. RESULTS: The head-down maneuver resulted in a significantly smaller increase in right-sided THbl in migraineurs when compared to volunteers (migraineurs, -0.1+/-0.04; volunteers, 30+/-13; P=0.027), but there was no significant difference in left-sided THbl when comparing migraineurs and volunteers. Further, the head-down maneuver produced a significantly smaller increase in right-sided THbl than in left-sided THbl in migraineurs (right side, -0.1+/-0.04; left side, 0.35+/-0.08; P<0.0001), but produced a significantly greater increase in right-sided THbl than in left-sided THbl in volunteers (right side, 30+/-13; left side, 0.44+/-0.13; P=0.030). The head-down maneuver resulted in a smaller decrease in right-sided rSO(2) in migraineurs when compared to volunteers (migraineurs, -4.1+/-2.2%; volunteers, -16+/-9.1%), but produced a significantly greater decrease in left-sided rSO(2) in migraineurs when compared to volunteers (migraineurs, -1.3+/-1.1%; volunteers, 2.8+/-0.63%; P=0.0037). CONCLUSIONS: These data indicate that pressure-related vasoreactivity is suppressed in the right hemisphere of migraineurs during the interictal period. SIGNIFICANCE: The suppression of vasoreactivity in the right hemisphere might be related to the pathogenesis of migraine.     

Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura

This study examined the efficacy of lamotrigine in the prevention of migraine aura. Fifty nine patients suffering from migraine with aura received lamotrigine in a controlled three year prospective open study. Treatment response was defined as a reduction of aura frequency each month by at least 50%. Primary endpoint was reached by three quarters of the patients. Lamotrigine significantly reduced both frequency of migraine aura (mean, 1.5 (SD, 0.6) each month before v 0.4 (0.7) after treatment; p < 0.001) and aura duration (mean, 27 (SD, 11) minutes before v 8 (14) after treatment; p < 0.001). Furthermore, more than three quarters of those patients with a reduction of aura symptoms experienced a significant reduction of frequency of migraine attacks (mean, 2.1 (SD, 1.0) each month before v 1.2 (1.1) after treatment; p < 0.001). Lamotrigine was highly effective in reducing migraine aura and migraine attacks. The strong correlation between reduction of aura symptoms and migraine attacks stresses the potential role of aura-like events and possibly cortical spreading depression as a trigger for trigeminal vascular activation, and subsequently the development of migraine headaches.     

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。     

Serial contrast saline transcranial Doppler examination in a patient with paradoxical brain embolism associated with pulmonary embolism.

We report a patient with paradoxical brain embolism due to patent foramen ovale (PFO) associated with pulmonary embolism (PE). The number of microembolic signals, as detected by contrast saline transcranial Doppler (c-TCD) exam, drastically decreased with improvement of increased right atrial pressure due to PE. In a patient with paradoxical brain embolism associated with PE, c-TCD may be useful for both diagnosis of the presence of right-to-left shunting and evaluation of cardio-pulmonary circulation.     

Oscillations in cerebral blood flow detected with a transcranial Doppler index.

Although transcranial Doppler ultrasound (TCD) has been used to detect oscillations in CBF, interpretation is severely limited, since only blood velocity and not flow is measured. Oscillations in vessel diameter could, therefore, mask or alter the detection of those in flow by TCD velocities. In this report, the authors use a TCD-derived index of flow to detect and quantify oscillations of CBF in humans at rest. A flow index (FI) was calculated from TCD spectra by averaging the intensity weighted mean in a beat-by-beat manner over 10 seconds. Both FI and TCD velocity were measured in 16 studies of eight normal subjects at rest every 10 seconds for 20 minutes. End tidal CO2 and blood pressure were obtained simultaneously in six of these studies. The TCD probe position was meticulously held constant. An index of vessel area was calculated by dividing FI by velocity. Spectral estimations were obtained using the Welch method. Spectral peaks were defined as peaks greater than 2 dB above background. The frequencies and magnitudes of spectral peaks of FI, velocity, blood pressure, and CO2 were compared with t tests. The Kolmogorov-Smirnov test was used to further confirm that the data were not white noise. In most cases, three spectral peaks (a, b, c) could be identified, corresponding to periods of 208+/-93, 59+/-31, and 28+/-4 (SD) seconds for FI, and 196+/-83, 57+/-20, and 28+/-6, (SD) seconds for velocity. The magnitudes of the spectral peaks for FI were significantly greater (P<0.02) than those for velocity. These magnitudes corresponded to variations of at least 15.6%, 9.8%, and 6.8% for FI, and 4.8%, 4.2%, and 2.8% for velocity. The frequencies of the spectral peaks of CO2 were similar to those of FI with periods of 213+/-100, 60+/-46, and 28+/-3.6 (SD) seconds. However, the CO2 spectral peak magnitudes were small, with an estimated maximal effect on CBF of (+/-) 2.5+/-0.98, 1.5+/-0.54, and 1.1+/-0.31 (SD) percent. The frequencies of the blood pressure spectral peaks also were similar, with periods of 173+/-81, 44+/-8, and 26+/-2.5 (SD) seconds. Their magnitudes were small, corresponding to variations in blood pressure of (+/-) 2.1+/-0.55, 0.97+/-0.25, and 0.72+/-0.19 (SD) percent. Furthermore, coherence analysis showed no correlation between CO2 and FI, and only weak correlations at isolated frequencies between CO2 and velocity, blood pressure and velocity, or blood pressure and FI. The Kolmogorov-Smirnov test distinguished our data from white noise in most cases. Oscillations in vessel flow occur with significant magnitude at three distinct frequencies in normal subjects at rest and can be detected with a TCD-derived index. The presence of oscillations in blood velocity at similar frequencies but at lower magnitudes suggests that the vessel diameters oscillate in synchrony with flow. Observed variations in CO2 and blood pressure do not explain the flow oscillations. Ordinary TCD velocities severely underestimate these oscillations and so are not appropriate when small changes in flow are to be measured.     

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...     

Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label study

OBJECTIVE: To evaluate the efficacy of levetiracetam as prophylactic treatment for migraine with aura with high frequency of attacks. BACKGROUND: Migraine with aura with high frequency of attacks could represent a very demanding therapeutic problem. Efficacy of the antiepileptic drug, lamotrigine, has been reported in this form of migraine. Levetiracetam is a new antiepileptic drug with an excellent tolerability profile. Mechanisms of action of this drug remain largely unknown, but recently, it has been shown to exert inhibitory effects on neuronal-type calcium channels. METHODS: We performed a small open-label trial treating 16 patients affected by migraine with aura with high frequency of attacks. After a 1-month run-in period, patients were treated with levetiracetam at a dosage of 1000 mg/d for 6 months. RESULTS: The number of attacks per month was significantly reduced during the first month (compared with run-in; P < 0.001), and it was reduced further during the second (second month vs first month; P < 0.001) and the third months (third month vs second month; P < 0.001) of the treatment. This improvement persisted unchanged for the remaining 3 months of treatment. In 7 (44%) of the 16 patients, the attacks were completely abolished after 3 months of treatment. Severity of headache and duration of headache and aura were also significantly reduced at the third and sixth months of treatment (P < 0.001). Levetiracetam was well tolerated (6 patients complained of slight dizziness, nervousness, and somnolence). CONCLUSIONS: Levetiracetam seems to be a safe and effective treatment for migraine with aura. Controlled trials are needed to confirm the observed results.     

Silent brain embolism during transcatheter closure of patent foramen ovale: a transcranial Doppler study

Abstract The aim of this report is to quantify the amount of spontaneous microembolism detected in brain vessels by transcranial Doppler (TCD) during transcatheter closure of right-to-left shunt (RLS). We examined 29 patients who had had a stroke or a transient ischaemic attack (17 females and 12 males; mean age 45±15 years). They all underwent TCD monitoring during the procedure and microembolic signals (MES) were recorded. Detection of MES was distributed as follows: during femoral catheterisation in 8 patients (25%), during atrial catheterisation in 5 patients (17%), during transeptal crossing in 14 patients (48%), during left disc opening in 28 patients (96%) and during right disc opening in 7 patients (24%). The highest rates of MES were observed during left disc opening and less during transeptal crossing with an average count of 31 (range 3–135) and 3 (range 1–18) respectively. Brain embolism occurs throughout the procedure after femoral catheterisation for PFO closure. Our results indicate that the majority of MES reached the brain during the opening of the left disc in the left atrium: 28/29 patients exhibited MES with an average of 31 (3–135), thus supporting the notion that gas embolism accounted for the findings.     

Reduced vasomotor reactivity in cerebral microangiopathy : a study with near-infrared spectroscopy and transcranial Doppler sonography

BACKGROUND AND PURPOSE: Reduction of cerebral blood flow and vasomotor reactivity (VMR) are thought to play an important role in the pathogenesis of cerebral microangiopathy. The aim of our study was to determine whether near-infrared spectroscopy (NIRS) can detect a reduced VMR in patients with microangiopathy, whether NIRS reactivities correlate with VMR assessed by transcranial Doppler sonography (TCD), and whether the differing extents of patients' microangiopathy demonstrated on MRI or CT can be distinguished by both noninvasive techniques. METHODS: We compared the VMR of 46 patients with cerebral microangiopathy with 13 age-matched control subjects. Patients were classified with the Erkinjuntti scale. We monitored cerebral blood flow velocity (CBFV) in both middle cerebral arteries by TCD, changes in concentration of oxyhemoglobin (HbO(2)), deoxyhemoglobin (Hb) and blood volume (HbT) by NIRS, mean arterial blood pressure, and end-tidal CO(2) (EtCO(2)) during normocapnia and hypercapnia. VMRs were calculated as percent change of CBFV (NCR) and as absolute change in concentration of HbO(2), Hb, and HbT per 1% increase in EtCO(2) (CR-HbO(2), CR-Hb, CR-HbT). RESULTS: NCR and NIRS reactivities were significantly reduced in patients with cerebral microangiopathy. CR-HbO(2) and CR-Hb showed a close correlation with NCR, and NCR and NIRS reactivities were related to the severity of cerebral microangiopathy according to the Erkinjuntti scale. Validity of NCR and NIRS reactivities were similar. CONCLUSIONS: VMR is reduced in patients with cerebral microangiopathy and can be noninvasively assessed in basal arteries (with TCD) and brain parenchyma (with NIRS). Reduction of CO(2)-induced VMR, as measured by NIRS and TCD, may indicate the severity of microangiopathy.     

中国南方人偏头痛CACNAlA基因多态性相关研究

研究目的:通过检测偏头痛患者和FHM家族外周血CACNAlA基因三个常见的突变位点,分析探讨中国南方人FHM与CACNAlA基因突变之间的关系。2.方法:采用SSCP方法对2个FHM家族10个受试者及12个无症状亲属和53个无FHM家族史的有先兆偏头痛及10个健康对照的外周血标本进行检测,分析CACNAlA基因的三个常见突变位点(T666M、R583Q和D715E)在FHM家族中的表现形式。3.结果:CACNAlA基因三个常见的突变T666M、R5830和D715E在2个FHM家族10个受试者12个无症状亲属和53个无FHM家族史的有先兆偏头痛及10个健康对照中均未检测到。4.结论:在中国人FHM家族中未发现有T666M、R583Q和D715E三个突变。FHM以及有先兆偏头痛与CACNAlA基因的相关性有待进一步研究。     

Acute effects of smoking on human cerebral blood flow: a transcranial Doppler ultrasonography study.

Middle cerebral artery (MCA) flow velocity was continuously monitored during smoking in an observational study (n = 14) using transcranial Doppler (TCD) ultrasonography. Cerebral autoregulatory vasodilator capacitance under inspired CO2 challenge was also measured before smoking and at peak smoking effect. Several puffs on a single lighted cigarette over a period of five minutes acutely increased MCA mean flow velocity in every subject (group mean increase: 19%, individual increases ranged 2-64%) with a response onset and offset detectable within several seconds of beginning and ending smoking. The mechanism for the increase in MCA flow velocities appeared to be independent of the CO2 autoregulatory mechanism. Gender subgroup analysis showed smoking acutely suppressed the CO2 vasodilator capacitance by 56% in men but only by 5% in women (p = 0.05). The magnitude of the acute smoking-induced increases in MCA flow velocities appeared to be independent of the estimated cigarette yields for nicotine, carbon monoxide, and "tar." Smoking in healthy subjects acutely increased MCA mean flow velocity, which may reflect a global increase in cerebral blood flow via complex influences on the cerebral autoregulation.