Evaluation of placebo use in migraine without aura, migraine with aura and episodic tension-type headache acute attacks

This study presents an evaluation of placebo response in the acute treatment of migraine with or without aura and episodic tension type headache. We studied patients admitted between March 1st,1997 and November 31st,1999 in two Emergency Room Units. Three groups had been defined, each one with 30 participants: migraine without aura (MWOA), migraine with aura (MWA) and episodic tension-type headache (ETTH). Patients were participating of a randomized study to evaluate efficacy of 4 different drugs; those randomized to receive placebo were included. We evaluated pain and associated symptoms. After one hour of placebo administration, 50% of MWOA patients, 23.3% of MWA and 26.7% of ETTH had presented pain relief. The mean of this relief, evaluated by the numerical pain scale, was 41.6%, 23.1% and 36%, respectively. Use of placebo is essential in evaluating the therapeutic role of drugs used in the treatment of acute headache.     

Regulation of regional cerebral blood flow during and between migraine attacks

Cerebrovascular reactivity to voluntary hyperventilation, moderate hypertension, and physiological activation was studied in nine patients during induced migraine attacks and in four patients between their attacks. Regional cerebral blood flow was measured by the xenon 133 injection technique in 254 areas of one hemisphere. The partly hypoperfused hemisphere allowed for comparison of adjacent hypoperfused and normally perfused brain areas. During attacks the carbon dioxide reactivity was decreased to 2.8 +/- 0.8% per mm Hg in the oligemic regions compared with 5.8 +/- 0.8% per mm Hg in the normally perfused brain. Blood pressure autoregulation was normal in all brain regions. Regional blood flow increase in response to physiological activation was severely impaired in the hypoperfused brain areas, whereas neighboring normally perfused regions reacted normally. Confinement of the regulation abnormalities to the area of the oligemia supports our suggestion that the blood flow changes are caused by a change in local metabolism. Between attacks of migraine, the patients had normal regulation of brain circulation.     

Rizatriptan does not change cerebral blood flow velocity during migraine attacks

Rizatriptan represents a major advance in the treatment of migraine attack: inhibition of peripheral trigeminal nerve and constriction of intracranial extracerebral blood vessels have been proposed as its main antimigraine mechanisms of action. Although many studies may suggest that rizatriptan causes highly selective vasoconstriction within intracranial extracerebral vessels (i.e., meningeal arteries), no literature data are available to date on possible cerebral hemodynamic changes in humans after treatment with rizatriptan. The aim of this study was to evaluate the effect of rizatriptan on cerebral blood flow velocity performing transcranial Doppler during spontaneous attacks of migraine without aura. Fourteen patients suffering from migraine without aura were monitored to evaluate mean flow velocity changes on both middle cerebral arteries during migraine attack 30 min before and 120 min after oral administration of rizatriptan 10mg. Monitoring was repeated for 30 min during the pain-free period. All patients turned out to be drug responders and no significant mean flow velocity changes were observed between the pain-free period and pre-treatment phase; besides no significant difference in mean flow velocity value have been detected between the periods after the drug administration during the attack versus both pre-treatment period and pain-free phase. These findings indicate that the antimigraine action of rizatriptan is not associated with clear intracranial cerebral hemodynamic changes and may support its cerebrovascular safety.     

Changes in regional cerebral blood flow during the course of classic migraine attacks

Regional cerebral blood flow (rCBF) following carotid arteriography was studied in thirteen patients with classic migraine. Using the 133xenon intraarterial injection method, rCBF was measured in 254 areas in one hemisphere. Nine patients developed a characteristic attack following arteriography and were examined by a series of rCBF studies, spaced by intervals of 5 to 10 minutes. A wave of reduced blood flow originating in the posterior part of the brain and progressing anteriorly was observed in eight of the nine patients. The oligemia advanced at a speed of 2 mm per minute over the hemisphere, progressing anteriorly but not crossing the rolandic or sylvian sulcus. Typically, the spreading oligemia reached the primary sensorimotor area after symptoms from that area had begun and persisted there long after the focal symptoms had disappeared. The observed time course suggests that the focal symptoms are not secondary to the oligemia. We suggest that focal symptoms and blood flow changes may be secondary to spreading depression of Leao.     

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.     

Animal models of migraine headache and aura

PURPOSE OF REVIEW: Over the past 30 years, animal models of migraine have led to the identification of novel drug targets and drug treatments as well as helped to clarify a mechanism for abortive and prophylactic drugs. Animal models have also provided translational knowledge and a framework to think about the impact of hormones, genes, and environmental factors on migraine pathophysiology. Although most acknowledge that these animal models have significant shortcomings, promising new drugs are now being developed and brought to the clinic using these preclinical models. Hence, it is timely to provide a short overview examining the ways in which animal models inform us about underlying migraine mechanisms. RECENT FINDINGS: First generation migraine models mainly focused on events within pain-generating intracranial tissues, for example, the dura mater and large vessels, as well as their downstream consequences within brain. Upstream events such as cortical spreading depression have also been modeled recently and provide insight into mechanisms of migraine prophylaxis. Mouse mutants expressing human migraine mutations have been genetically engineered to provide an understanding of familial hemiplegic migraine and possibly, by extrapolation, may reflect on the pathophysiology of more common migraine subtypes. SUMMARY: Animal models of migraine reflect distinct facets of this clinically heterogeneous disorder and contribute to a better understanding of its pathophysiology and pharmacology.     

Antimigraine drug sumatriptan increases blood flow velocity in large cerebral arteries during migraine attacks.

Sumatriptan, a novel selective 5-hydroxytryptamine1d (5-HT1d) receptor agonist, which is highly effective in the acute treatment of migraine attacks, blocks dural neurogenic plasma extravasation and constricts cranial blood vessels in animal experiments. We measured intra- and extracranial blood flow velocities (BFV) with a transcranial Doppler device in 67 patients during a spontaneous migraine attack, before and after treatment with 3 mg or 6 mg subcutaneous sumatriptan or placebo. Sumatriptan, but not placebo, significantly increased BFV (cm/sec) in the internal carotid and middle cerebral arteries on both sides, without detectably changing the BFV in the common and external carotid arteries. The rise in BFV increased with the dose of sumatriptan, parallel to an increase in proportion of patients improved. There were no significant changes in heart rate, blood pressure, or respiratory frequency after treatment with sumatriptan. The increase in BFV probably reflects vasoconstriction of the large basal intracranial arteries, which may be a mechanism for the antimigraine action of sumatriptan.     

Oestrogen and attacks of migraine with and without aura

During women's reproductive years, migraine is three times more common than in men of a similar age. Although this female preponderance is commonly assumed to be associated with the additional trigger of fluctuating sex hormones of the menstrual cycle, few studies have been done to confirm or refute this. This review is confined to the relation between oestrogen and attacks of migraine. The evidence for an association between oestrogen "withdrawal" and attacks of migraine without aura is presented, as well as evidence for an association between high oestrogen states and attacks of migraine with aura. Only clinical data are presented here.     

Precipitating factors of migraine attacks in patients with migraine without aura

To study the distribution of triggers of migraine in a selected population, 100 patients who fulfilled the diagnostic criteria for migraine without aura as proposed by the International Headache Society were evaluated by means of a personal interview. Stress was the most cited trigger, triggering migraine in 76%. Afterwards, in descending order of frequency, were cited sensorial stimuli (75%), sleep deprivation (49%), hunger (48%), environmental factors (47%), food (46%), menses (39%), fatigue (35%), alcohol (28%), sleep excess (27%), caffeine (22%), physical exertion (20%), head trauma (20%), trips (4%), sexual activity (3%), medications (2%), neck movements (2%), smoking (1%) and the use of a low pillow (1%). It is concluded that certain factors seem to play an important role in the triggering of migraine.     

Cerebral blood flow in a case of typical aura without headache

Journal of Neurology -     

Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura

The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been investigated. Studies of spontaneous migraine attacks are notoriously challenging due to their unpredictable nature and patient discomfort. We investigated 16 migraine patients with visual aura during attacks and in the attack‐free state using resting state fMRI. We applied a hypothesis‐driven seed‐based approach focusing on cortical visual areas and areas involved in migraine pain, and a data‐driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived aura symptoms. We found a marked increase in connectivity during attacks between the left pons and the left primary somatosensory cortex including the head and face somatotopic areas (peak voxel: P = 0.0096, (x, y, z ) = (?54, ?32, 32), corresponding well with the majority of patients reporting right‐sided pain. For aura‐side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, (x, y, z ) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity during attacks of migraine with aura, which may reflect consequences of cortical spreading depression, suggesting a link between aura and headache mechanisms. Hum Brain Mapp 38:2635–2642, 2017 . © 2017 Wiley Periodicals, Inc.     

偏头痛的临床、脑血流及影像学研究

目的 探讨偏头痛与脑白质变性的关系。方法 75例偏头痛患者的临床表现、分型、脑血流及头颅CT或MRI检测结果进行回顾分析。结果 75例偏头痛患者中62例TCD检查脑血流速度增加或降低各占50％。75例中有48例做头颅MRI检查，其中18例脑白质有多灶性小圆点状长T1长T2改变。结论 偏头痛患者MRI出现脑白质变性可能是偏头痛的一种新的特殊类型或者是伴有皮质下脑梗死或白质脑病的常染色体显性遗传性脑动脉病的早期改变。     

Effect of sumatriptan on cerebral blood flow during migraine headache: measurement by sequential SPECT used 99mTc-ECD background subtraction method]

The present study was designed to examine the effect of sumatriptan on regional cerebral blood flow (CBF) during migraine headache. Nine cases were examined by 99mTc-ECD background subtraction method for the absolute value measurement of regional CBF before and after sumatriptan injection. rCBF except for occipital and perioccipital lobes, were increased 10-20% during migraine headache and significant decreases were observed by sumatriptan injection. Two cases of nine had transiently increased systemic blood pressure and cardiac pulse rate, however, all cases improved migraine headache after injection of sumatriptan.     

三叉神经-颈反射在无先兆偏头痛和慢性紧张型头痛中的意义

目的 研究三叉神经-颈反射(trigemino-cervical reflex,TCR)在无先兆偏头痛(migraine without aura,MWOA)和慢性紧张型头痛(chronic tension-type headache,CTTH)中的意义.方法 选取2009年1月至2010年2月福建省级机关医院门诊25例单侧MWOA患者、25例CTTH患者及36名健康成年对照进行TCR检测.刺激一侧眶下神经(infraorbital nerve,ION),可在同侧胸锁乳突肌(sternocleidomastoid muscle,SCM)上记录到一个短潜伏期正-负波,即TCR.比较各组TCR参数[峰潜伏期(PL)、刺激前后波幅比率的平方根(A值)]的差异.结果 MWOA组和CTTH组双侧PLP19[MWOA右侧(19.81±1.79)ms,左侧(19.49±1.95)ms;CTTH右侧(19.16±1.67)ms,左侧(19.56±2.02)ms]、PLN31[MWOA右侧(30.75±2.35)ms,左侧(30.44±3.75)ms;CTTH右侧(30.32±3.47)ms,左侧(30.11±3.34)ms]较对照组缩短(t=2.027～3.654,P＜0.05);CTTH组和MWOA组双侧PLP19、PLN31及A值差异无统计学意义.结论 MWOA组和CTTH组的双侧PLP19、PLN31潜伏期较对照组缩短,提示三叉神经、脑干系统参与MWOA、CTTH的发病机制;但两组病例无明显差异,MWOA和CTTH在内源性疼痛调节系统的某个部位如三叉神经或脑干系统,存在共同的功能障碍.