Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.     

Blood flow velocity and pulsatility index differences in patients with unilateral migraine

OBJECTIVE: To evaluate blood flow velocity and pulsatility in unilateral migraine without aura during the headache-free period using transcranial Doppler (TCD) sonography. METHODS: Patients with unilateral headache were recruited during the headache-free period. Maximum mean flow velocity (MFV) and pulsatility index (PI) were measured in the middle cerebral (MCA) and basilar arteries. Controls were headache-free individuals without cerebrovascular disease. RESULTS: Twenty-five patients with right-sided migraine, 25 patients with left-sided migraine, and 19 controls were studied. The MCA PI was higher on the right headache side versus the left headache side (0.97 +/- 0.2 versus 0.86 +/- 0.1 cm/s, P =.02) and versus controls (0.9 +/- 0.2 cm/s, NS). The basilar artery MFV was higher in patients with right-sided headache versus left-sided headache (39.5 +/- 5.6 versus 34.7 +/- 8.2 cm/s, P =.02) and versus controls (38.2 +/- 8 cm/s, NS). No decrease in MFV with age was observed in patients with migraine. CONCLUSIONS: Middle cerebral artery flow pulsatility and basilar artery velocity are higher in patients with right-sided migraine compared with left-sided migraineurs, during the headache-free period. Although these parameters were similar to controls, the differences found during the headache-free period in migraineurs may indicate vascular involvement predisposing to the unilateral headache recurrence.     

Transcranial Doppler measurements in migraine and nitroglycerin headache

The objective of this study was to examine the cerebral circulation during spontaneous migraine attacks and to compare changes to an experimental headache model induced by nitroglycerin (NTG) infusion. This prospective study was carried out in a tertiary care hospital on migraineurs with or without aura. Healthy volunteers served as controls. There were no interventions. Flow velocity (FV) and pulsatility index (PI) were measured in migraineurs between and during headache attacks. In controls, FV and PI of the middle cerebral arteries were performed at baseline and after each IV infusion of 0.125, 0.25 and 0.5 μg/kg/min of NTG. In migraineurs, a significant increase in the mean flow velocity (MFV) in the left vertebral artery (VA) and the PI of the right VA during spontaneous migraine headache was found. In controls, all FV significantly decreased after infusion of NTG. The NTG model produces expected and substantially different vascular effects than those seen with spontaneous migraine headache.     

The cerebral hemodynamics of headache associated with sexual activity

Headache associated with sexual activity is an idiopathic headache disorder and regarded to be a vascular headache but no pathophysiological studies have been performed to date to elucidate the underlying mechanisms. We investigated 12 patients with the explosive type of sexual headache according to the criteria of the International Headache Society during a headache-free state by means of acetazolamide test and of stress Doppler sonography. Twelve age-matched migraine patients and 14 healthy subjects served as control groups. Changes of blood pressure, cerebral blood flow velocity (CBFV), and pulsatility index (PI) were evaluated. Patients with sexual headache showed a significantly higher increase of blood pressure during standardized physical exercise as compared to healthy subjects and migraine patients. Changes of CBFV by physical exercise were not different between the three examination groups. After 1g acetazolamide, CBFV showed a significantly higher increase in patients with sexual headache (plus 66%+/-16%) than in healthy subjects (plus 46%+/-18%), and PI showed a significantly lower decrease as compared to healthy subjects and migraine patients. These data suggest that in patients with sexual headache the metabolic rather than the myogenic component of the cerebral vasoneuronal coupling is impaired.     

The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs

We have previously proposed that histamine causes migraine via increased NO production. To test this hypothesis, we here examined if the NOS inhibitor, L-NG methylarginine hydrochloride (L-NMMA:546C88), could block or attenuate histamine induced migraine attacks and responses of the middle cerebral, temporal and radial arteries. In a double blind crossover design 12 patients were randomized to receive pretreatment with L-NMMA (6 mg/kg) or placebo i.v. over 15 min followed on both study days by histamine (0.5 microg/kg/min) i.v. for 20 min. Headache scores, mean maximal blood velocity (Vmean) in the middle cerebral artery (MCA) (transcranial doppler) and diameters of temporal and radial arteries (high resolution ultrasound) were repeatedly measured. Pre-treatment with L-NMMA, had no effect on histamine induced headache or migraine, but also had no effect on the magnitude of histamine induced-decrease in MCA blood velocity, or dilatation of neither the temporal nor the radial artery. L-NMMA constricted the temporal artery by 8% before histamine infusion, whereas the radial artery was unaffected. The temporal artery dilated 4-5 times more than the radial artery during histamine infusion. In conclusion the use of a NOS inhibitor in the highest possible dose did not block the histamine-induced headache response or arterial dilatation. Either the concentration of L-NMMA reaching the smooth muscle cell was insufficient or, histamine dilates arteries and causes headache via NO independent mechanisms. Our results showed for the first time a craniospecificity for the vasodilating effect of histamine and for the arterial effects of NOS inhibition.     

Nitric oxide synthase inhibition in the histamine headache model

Histamine has been widely used experimentally to induce headache in healthy subjects and migraine in migraineurs. There is evidence that the vascular effects of histamine are at least partially mediated by nitric oxide (NO). Hence we hypothesized that subjective symptoms and hemodynamic effects of histamine could be reduced by systemic NO-synthase inhibition. We therefore studied the effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO-synthase, or placebo on headache, flush and discomfort scores during histamine infusion. Additionally, blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA blunted the effect of histamine in the ophthalmic artery and the ocular circulation, NO-synthase inhibition did not mitigate subjective symptoms. Histamine did not affect mean blood flow velocities in the middle cerebral artery. Hence, we conclude that NO-synthase inhibition reduces the histamine-induced vascular effects in the ocular circulation, but is not sufficient to attenuate or abort the subjective symptoms provoked by histamine infusion.     

Acetazolamide Testing of Cerebral Vasodilator Capacity Provokes "Vascular" But Not Tension Headaches

Cerebrovascular capacitance was tested by measuring local cerebral blood flow (LCBF) by xenon-contrasted CT scanning before and after the oral administration of 14.3 mg/kg of acetazolamide among 45 subjects including 15 age-matched controls without history of headache, 20 migraineurs with and without aura, 3 patients with cluster headache, and 7 patients with tension-type headache. Percentage increases of LCBF were measured in 10 regions located throughout both hemispheres. Laterality indices for asymmetric LCBF increases were calculated. Local cerebral blood flow in cortical gray matter increased 5.9% in controls, 9.9% in patients with tension headaches, but 18.6% in both migraine and cluster headache patients; significantly greater LCBF increases than among controls or among patients with tension headaches (P<0.05). Increases in LCBF were significantly asymmetric among migraine and cluster patients and provoked typical unilateral vascular headaches which responded to sumatriptan. Maximal asymmetric LCBF increases also corresponded to the reported side of the induced headaches confirming their vascular pathogenesis. Patients with tension headaches and controls without history of headache did not develop head pain after acetazolamide.     

Spontaneous oscillations in cerebral blood flow velocity give evidence of different autonomic dysfunctions in various types of headache

OBJECTIVES: Our objectives were to determine if: (1) patients with migraine have B wave abnormalities in comparison to normal controls and patients with chronic tension headache and (2) patients with chronic tension headache have an imbalance in autonomic activity that is reflected in differences in Mayer wave activity in comparison to normal controls. BACKGROUND: B waves and Mayer waves are spontaneous oscillations in cerebral blood flow velocity with a frequency of 0.5 to 3 or 4 to 7 cycles per minute, respectively, and can be measured by transcranial Doppler sonography. There is experimental evidence that B waves are generated by certain brain stem nuclei which modulate the lumen of the small intracerebral vessels via monoaminergic nerve endings. In contrast, Mayer waves in cerebral blood flow velocity have no central generator but mirror the Mayer waves in arterial blood pressure which represent peripheral autonomic activity. Migraine may be attributed to a neurotransmitter imbalance in brain stem nuclei. Dysfunctions of the peripheral autonomic nervous system are known in patients with chronic tension headache. METHODS: Using bilateral transcranial Doppler monitoring of the middle cerebral artery B waves and Mayer waves were studied in 30 patients with migraine without aura, 28 subjects with tension-type headache, and 30 normal controls. Coefficient of variation as a quantitative parameter for amplitude of waves and the mean frequency were calculated from the envelope curves of the Doppler spectra. RESULTS: The coefficient of variation of B waves was higher in migrainous patients compared with patients with tension-type headache and normal controls (P<.05), indicating an increase in activity of brain stem nuclei in migraine only. Patients with chronic tension headaches had lower values for Mayer wave activity in comparison with normal controls (P<.05), a sign of an impairment of sympathetic activity. CONCLUSIONS: Our data support the dysfunction of the brain stem monoaminergic/serotonergic system in migraine. In contrast, patients with chronic tension headache have an autonomic dysfunction of peripheral origin presenting as a decrease of sympathetic activity.     

Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine

We hypothesized that intravenous infusion of the parasympathetic transmitter, vasoactive intestinal peptide (VIP), might induce migraine attacks in migraineurs. Twelve patients with migraine without aura were allocated to receive 8 pmol kg⁻¹ min⁻¹ VIP or placebo in a randomized, double-blind crossover study. Headache was scored on a verbal rating scale (VRS), mean blood flow velocity in the middle cerebral artery ( V _{mean MCA}) was measured by transcranial Doppler ultrasonography, and diameter of the superficial temporal artery (STA) by high-frequency ultrasound. None of the subjects reported a migraine attack after VIP infusion. VIP induced a mild immediate headache (maximum 2 on VRS) compared with placebo ( P  = 0.005). Three patients reported delayed headache (3–11 h after infusion) after VIP and two after placebo ( P  = 0.89). V _{mean MCA} decreased (16.3 ± 5.9%) and diameter of STA increased significantly after VIP (45.9 ± 13.9%). VIP mediates a marked dilation of cranial arteries, but does not trigger migraine attacks in migraineurs. These data provide further evidence against a purely vascular origin of migraine.     

Headache characteristics during the development of tolerance to nitrates: pathophysiological implications

Recent studies suggest that nitric oxide (NO) plays an important role in nitrate-induced headache and in spontaneous migraine attacks. Organic nitrates act as prodrugs for NO and headache is a predominant adverse effect of nitrates but often disappears during continuous treatment. Insight into tolerance to headache could lead to insight into vascular headache mechanisms in general. The specific aim of the present study was therefore to characterize the headache and accompanying symptoms during continuous nitrate administration until a state of tolerance to headache had developed. 5-isosorbide-mononitrate (5-ISMN) 30 mg three times daily was administered orally for 7 days in 11 healthy subjects in a double-blind, randomized placebo controlled cross-over design. Wash-out between periods was 14 days or more. Haemodynamic data from the present study were compared to the observed changes of headache over time. Headache during 5-ISMN was longer lasting and more severe compared to placebo (P<0.004). In 10 subjects the headache fulfilled the pain sub-criteria for migraine and in five subjects all diagnostic criteria for migraine without aura were fulfilled. Conversely, 20 min of intravenous infusion of glyceryl trinitrate caused a milder headache and no migraine. The present results therefore suggest that NO may elicit a migraine attack in many healthy subjects if a high enough dose is given for several hours. A close temporal association between the disappearance of headache and the attenuation of the 5-ISMN induced dilatation of the superficial temporal artery was observed. In contrast, tolerance in the middle cerebral artery already appeared after 24 h, which was earlier than the development of tolerance to headache. If vasodilatation is the cause of headache the results point to extracerebral arteries. However, cytotoxic and pain modulating central nervous system effects of NO, the time courses of which are unknown, may also play a role, involving both intra- and extracranial arteries.     

Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate

Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate cerebral arteries. The hypothesis tested here was that Az, by dilating cerebral arterioles but not arteries and thereby decreasing pulsatile stretching of the wall of the large arteries and their perivascular sensory nerves, would reduce or prevent the GTN-induced headache We tested this hypothesis in 14 healthy volunteers. In a randomized, double-blind, cross-over study, they were pretreated with Az or placebo followed on both study days by a GTN infusion of 0.5 µg kg⁻¹ min⁻¹ for 20 min. Headache was scored on a verbal rating scale and a headache diary was kept for 12 h. Mean blood velocity of the middle cerebral artery was measured (transcranial Doppler). Our hypothesis was disproved, as Az did not decrease GTN-induced headache. Unexpectedly but interestingly, GTN combined with Az induced more delayed headache than GTN alone. Furthermore, a migraine-like headache was observed in three volunteers, who did not develop migraine after GTN alone. The fact that a suitable pharmacological intervention may trigger migraine in individuals with no prior migraine may suggest that the ability to develop migraine without aura is a quantitative genetic trait.     

Sumatriptan and Cerebral Blood Flow Velocity Changes During Migraine Attacks

Transcranial Doppler studies on the effects of sumatriptan on cerebral hemodynamics have shown conflicting results. We evaluated blood flow velocity changes in 21 patients suffering from migraine with (n = 4) or without aura (n = 17) during a spontaneous attack, before and after treatment with sumatriptan. Flow velocity in the internal and external carotid, middle cerebral, and basilar arteries was measured by means of transcranial Doppler. During the attack, measurements were taken before subcutaneous sumatriptan injection, then after 30 minutes, 2 hours, and 24 hours. An additional measurement was taken 1 week later, in a headache-free state. We found a significant reduction of flow velocity during the attack in the middle cerebral artery on both sides (P < 0.05). After sumatriptan administration, flow velocity increased in the internal carotid artery on both sides (P < 0.05) and in the middle cerebral artery on the headache side (P = 0.0001), but not in the external carotid and basilar arteries (P > 0.05). Flow velocity changes may reflect the vasodilation present at the onset of the migraine attack followed by vasoconstriction in the internal carotid and middle cerebral arteries after sumatriptan treatment. Since vasoconstriction occurs in responders and nonresponders to treatment, it is unlikely to be the primary mechanism by which sumatriptan relieves headache.     

The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache

The most important primary headaches (i.e. independent disorders that are not caused by another disease) are migraine, tension-type headache and cluster headache. All primary headaches are in need of better treatments. Migraine has a prevalence of 10% in the general population and its societal costs are high. Although the precise mechanisms underlying the pathophysiology of migraine are still elusive, the last decades have witnessed some progress (e.g. involvement of serotonin, calcitonin gene-related peptide, nitric oxide, etc). Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-NMMA effectively treats attacks of migraine without aura. Similar results have been obtained for chronic tension-type headache and cluster headache. Inhibition of the breakdown of cGMP also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Several relationships exist between NO, calcitonin gene-related peptide and other molecules important in migraine. Also ion channels, particularly the K(ATP) channels, are important for the action of NO. In conclusion, inhibition of NO production or blockade of steps in the NO-cGMP pathway or scavenging of NO may be targets for new drugs for treating migraine and other headaches. Indeed, selective n-NOS and i-NOS inhibitors are already in early clinical development.     

Transcranial Doppler evaluation of common and classic migraine. Part I. Ultrasonic features during the headache-free period

To study vascular abnormalities in migraine, transcranial Doppler (TCD) was used for evaluation of 100 consecutive patients with either common or classic migraine during the headache-free period. We insonated the basal cerebral arteries and the internal carotid artery (ICA) in the neck. Particular ultrasonic features in migraineurs included intracranial elevations of mean flow velocity (MFV) above 3 standard deviations of normal values in 16%, probably reflecting increased vasotonus. Marked asymmetry of MFV in corresponding intracranial arteries was found in 12%, and could represent "asymmetrical" vascular tone. Characteristic vascular bruits of low frequency and sometimes harmonic quality were detected in 56%. When compared to TCD findings in 40 young controls, MFV were significantly higher in all intracranial arteries in migraineurs, but not in the cervical ICA. Marked differences were also found for incidence of MFV elevations and vascular bruits (p less than 0.0001). Vascular reactivity in response to eye closing as measured by flow changes in the posterior cerebral artery (visually evoked flow) was significantly greater in migraineurs than in controls (%MFV change, 14.1 +/- 5.4 vs 11.4 +/- 4.8; p = 0.004). TCD features did not discriminate common from classic migraine. Taken together, our results support the view of intracranial vascular abnormality in migraineurs reflecting, in particular, a narrower and more reactive arterial tree. The value of TCD in the differential diagnosis of "vascular headache" and in the study of migraine pathophysiology will have to be determined in the future.     

西比灵治疗儿童偏头痛频繁发作的脑血流状态研究

目的:探讨西比灵治疗儿童偏头痛频繁发作的脑血流状态变化及临床意义.方法:应用经颅多普勒超声技术(TCD)研究50例儿童偏头痛频繁发作患儿服药前及服药2周后脑血流改变及头痛发作变化情况.结果:(1)30例一侧偏头痛患儿服药前头痛侧与非头痛侧大脑中动脉(MCA)、大脑前动脉(ACA)的收缩期峰值流速(Vs)有显著性差异(P＜0.01),服药2周后双侧MCA、ACA的Vs无明显差异(P＞0.05),非头痛侧服药前与服药2周后Vs无显著性差异(P＞0.05);(2)20例双侧偏头痛患儿服药前与服药2周后的Vs有显著性差异(P＜0.01).结论:西比灵能明显改善偏头痛患儿的脑血流指标,可减少偏头痛的发作次数和头痛程度.     

Human migraine models

The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible for the induced headache and migraine. Perspectives are discussed.     

Dipyridamole may induce migraine in patients with migraine without aura

Dipyridamole inhibits phosphodiesterase 5 (PDE5) and adenosine re-uptake. The most prominent side-effect is headache. We examined the migraine-generating effects of dipyridamole as well as the cerebral blood velocity response in a single-blind study, including 10 patients with migraine without aura and 10 healthy subjects. Dipyridamole 0.142 mg/kg per min was administered intravenously. Headache intensity was scored on a verbal rating scale along with pain characteristics and accompanying symptoms. Blood velocity in the middle cerebral artery (V(mca)), blood pressure and heart rate were recorded repeatedly. Headache was induced in all migraine patients and in eight of 10 healthy subjects (P = 0.47) with no significant difference in headache intensity (P = 0.53). However, five patients but only one healthy subject experienced the symptoms of migraine without aura, according to ICHD-2 criteria, within 12 h (P = 0.14). Four patients reported photophobia after dipyridamole compared with no healthy subjects (P = 0.087). V(mca) decreased (P < 0.001) during and after dipyridamole infusion with no difference between groups (P = 0.15) coinciding with initiation, but not cessation of immediate headache. Thus, dipyridamole induces symptoms of migraine and an initial decrease in V(mca) in migraine patients, but not significantly more than in healthy subjects. This relatively low frequency of migraine induction, compared with nitric oxide donors and sildenafil, is probably due to the less specific action of dipyridamole on the cGMP signalling pathway as well as a possible bidirectional effect of adenosine on migraine induction.     

无先兆型偏头痛患者间歇期脑血流检测

采用经颅多普勒超声（ＴＣＤ），脑血管血液动力学分析仪（ＣＢＡ）和磁共振成像（ＭＲＩ）等多种先进检查手段对无先兆型偏头痛患者头痛间歇期进行检测。４０例患者进行了ＴＣＤ检查，结果示患者组双侧大脑中动脉平均血流速度增高，有９例患者颅内动脉平均流速不对称。４４例患者的ＣＢＡ检查显示，患者组脑血管外周阻力Ｒｖ，动态阻力ＤＲ和临界压力ＣＰ增高。这些结果提示患者间歇期颅内血管紧张性增高，血流状态仍呈现不稳定性，推测其发病机理以血管因素为主。另外，有１０例患者进行头颅ＭＲＩ检查，６例结果异常，其中５例是颅内多发性缺血灶，１例是腔隙性梗塞。这是否由于长期血管功能异常导致的形态学变化，尚待进一步研究。     

Role of K ATP channels in cephalic vasodilatation induced by calcitonin gene-related peptide, nitric oxide, and transcranial electrical stimulation in the rat

Objective.— The objective of this study was to explore the role of K_ATP channels in vasodilatation induced by calcitonin gene‐related peptide (CGRP), nitric oxide (NO), and transcranial electrical stimulation (TES) in intracranial arteries of rat. Background.— Dilatation of cerebral and dural arteries causes a throbbing, migraine‐like pain. Both CGRP and NO are potent vasodilators that can induce migraine. Their antagonists are effective in the treatment of migraine attacks. K_ATP channel openers cause headache in the majority of healthy subjects suggesting a role for K_ATP channels in migraine pathogenesis. We hypothesized that vasodilatation induced by CGRP and the NO donor glyceryltrinitrate (GTN) is mediated via K_ATP channels. Methods.— We examined the effects of the K_ATP channel inhibitor glibenclamide on dural and pial vasodilatation induced by CGRP, NO, and endogenously released CGRP by TES. A rat genuine closed cranial window model was used for in vivo studies and myograph baths for studying the effect in vitro. In the closed cranial window model the diameter of dural vessels was measured directly in anesthetized animals to investigate the vascular effects of infused CGRP, NO, and endogenous CGRP after electrical stimulation. Also diameter changes of pial arteries, mean arterial blood pressure and local cerebral blood flow by Laser Doppler flowmetry (LCBF_Flux) were measured. Results.— CGRP, NO, and TES caused dilatation of the 2 arteries in vivo and in vitro. In anesthetized rats glibenclamide significantly attenuated CGRP induced dural and TES induced dural/pial artery dilatation (P = .001; P = .001; P = .005), but had no effect on dural/pial vasodilatation induced by GTN. In vitro glibenclamide failed to significantly inhibit CGRP‐ and GTN‐induced vasodilatation. Conclusions.— These results show that a K_ATP channel blocker in vivo but not in vitro inhibits CGRP, but not GTN‐induced dilatation of dural and pial arteries, a mechanism thought to be important in migraine.     

Transcranial Doppler evaluation of common and classic migraine. Part II. Ultrasonic features during attacks

Transcranial Doppler (TCD) examinations were performed in 13 patients with common and 5 patients with classic migraine during attacks and compared to TCD findings during the headache-free period. Two distinct patterns of flow changes were detected to distinguish common from classic migraine on the basis of TCD findings. During attacks, patients with common migraine exhibited reduction of flow velocities associated with an increase of pulse wave amplitudes. Vascular bruits that were heard during the headache-free interval often disappeared. Opposite changes were found in attacks of classic migraine during the headache phase with increase of flow velocities, decrease of pulsatility and more prominent or newly appearing bruits. These findings were often diffuse and did not appear to correlate with side of headache or side of neurological aura. Uniform changes occurred in the cervical internal carotid artery and the basal cerebral arteries in either form of migraine. We propose that these changes represent caliber fluctuations of the large arteries, suggesting vasodilatation during attacks of common migraine and vasoconstriction during attacks of classic migraine. We do not intend to imply a casual role of these preliminary findings in migraine pathogenesis, but we suggest that TCD be used in combination with other methods to study vascular changes in migrainous disorders.