Cortical spreading depression and calcitonin gene-related peptide: A brief review of current progress

Although detailed disease mechanisms of migraine remain poorly understood, migraine is known to have a complex pathophysiology with both vascular and neuronal mechanisms. The neuronal mechanisms of migraine may be attributed to cortical spreading depression (CSD); consequently, CSD has been widely studied for understanding the pathophysiology of migraine. Well validated CSD models have been developed for evaluating anti-migraine drugs. Neuropeptides, mainly, calcitonin gene-related peptide (CGRP), have been proposed as an emerging class of effective drugs against migraine headache. The central role of this neuropeptide has led to research into CSD for understanding disease mechanisms of migraine. This review briefly summarizes our current understanding of CSD and CGRP involvement in CSD. Although CSD can also worsen strokes, this brief paper has excluded the possible connection between the neuropeptide and CSD associated with them. Instead it has focused solely on CGRP in CSD associated with migraine.     

The Prevalence of Migraine Headaches in an Anxiety Disorders Clinic Sample

The association between migraine and psychiatric disorders has been reported in both clinical and epidemiological studies. The prevalence of psychiatric disorders has been found to be increased among individuals with migraine. Studies assessing migraine in psychiatric patients are limited and the majority of these studies have focused solely on examining patients with major depression. In the present study, we examined the prevalence and characteristics of migraine headache in an anxiety disorders clinic sample in order to better understand the relationship between these commonly associated conditions. We evaluated 206 consecutive outpatients to an Anxiety Disorders Clinic for the prevalence of migraine. The presence of migraine was established using International Headache Society Criteria. Subjects completed a modified self‐report version of the Headache Diagnostic Questionnaire. In order to assess the relationship between migraine and anxiety disorder symptom severity, subjects completed standardized measures of symptom severity. The prevalence of migraine in our anxiety disorder clinic sample was 67%. Anxiety disorder patients with migraine presented with a significantly greater number of comorbid psychiatric disorders than patients without migraine (P= 0.012). The prevalence of migraine was significantly higher in patients with a diagnosis of either panic disorder with agoraphobia (P= 0.048) or major depressive disorder/dysthymia (P= 0.008) compared to other psychiatric disorders. The severity of anxiety disorder symptoms was significantly higher in patients with migraine compared to patients without migraine. This study suggests that there is an increased prevalence of migraine headaches among anxiety disorder patients as compared to the general population. Migraine comorbidity may have important clinical implications, such that the treatment of one condition could potentially ameliorate the development or progression of the other. Further research is required to better understand the nature and implications of the association between migraine and psychiatric disorders.     

Non pharmaceutical treatments for migraine

The target of non-drug treatment of migraine is to reduce attack frequency and intensity. To reach this goal, the general relationship between the patient and the physician, i.e. the drug consumer and prescriber, has to be changed fundamentally. To understand migraine attacks the patient must learn to distinguish between the cause of migraine, a special readiness of the brain to react, and the triggers of a headache attack. Today, we have access to effective methods that prevent inherited migraine from coming to an effect, or to effectively arrest an attack if it has nevertheless broken out. There are three available strategies: prevention by avoiding trigger factors, prevention via reduction of attack readiness and treatment of the acute effects of the migraine attack.     

Migraine associated with menstruation

Many women report increased frequency of migraine in association with menstruation. The term 'menstrual' migraine is often used despite lack of an agreed definition. The International Headache Society has classified most headaches but not 'menstrual' migraine. A proposed definition is based on the finding that the prevalence of migraine increases on day 1 +/- 2 of the menstrual cycle. Attacks occurring at this time of the cycle are typically without aura. Effective acute therapy is the mainstay of management for menstrual and non-menstrual attacks although there is some evidence that attacks linked to menstruation are less responsive to treatment compared with migraine at other times of the cycle. If several attacks occur throughout the cycle, standard prophylactic agents should be used. Women with exclusive 'menstrual' migraine may benefit from perimenstrual prophylaxis but this should only be instigated once the association between migraine and menstruation has been confirmed with prospective records kept for a minimum of three cycles. NSAIDs are the treatment of choice in reducing migraine associated with menorrhagia and/or dysmenorrhoea, otherwise perimenstrual oestrogen supplements using percutaneous or transdermal oestrogens are recommended. Combined oral contraceptives are useful for women requiring contraception although there is a tendency for attacks to occur during the pill-free interval. If these are contraindicated, depot progestogen is an alternative as it also inhibits ovulation and can improve migraine, provided amenorrhoea is achieved. Oral progestogen-only contraception has little place in the management of 'menstrual' migraine as it does not inhibit ovulation and is often associated with a disrupted menstrual cycle. Some women consulting with menstrual migraine are menopausal and may be considering hormone replacement therapy. Studies suggest that non-oral routes of delivery of oestrogen, which provide stable levels, are more likely to improve migraine than oral oestrogens, which produce variable day-to-day levels. Too low a dose of oestrogen is ineffective at controlling symptoms but too high a dose, particularly if coupled with surges of endogenous oestrogen, can trigger migraine aura. Once the route and dose has been optimised, continuous oestrogens can control migraine as well as menopausal symptoms. Additional progestogen, necessary for unhysterectomised women, can exacerbate migraine. To minimise this, progesterone derivatives or non-oral routes of delivery are recommended, with continuous regimens used where possible.     

MRI findings in migraine

INTRODUCTION: For long time, migraine has been considered to be an episodic, multifactorial, neurovascular disorder, without long-term consequences to the brain, although an association between migraine and clinical stroke and white matter hyperintense lesions has been suggested in numerous studies. Due to various methodological problems no definite conclusion could be drawn from these studies. STATE OF THE ART: Recently, data from a population-based cross-sectional MRI study were published, establishing migraine to be a true and independent risk factor for white matter lesions (in female migraine patients) and subclinical posterior circulation territory infarcts. PERSPECTIVES: The methodology and results of previous investigations of a relationship between migraine and clinical ischemic stroke, silent infarction and white matter lesions are reviewed, and integrated in the results from the new population-based MRI study. CONCLUSION: Brain infarction occurs far more frequently than expected in migraine patients, most pronounced in migraine with aura (8 percent have subclinical cerebellar infarcts), although most infarcts remain clinically silent. Female migraine patients are at increased risk of deep white matter lesions, independent of the effects of cardiovascular risk factors. The influence of migraine severity (attack frequency) on the risk of both types of lesions suggests a causal relationship between migraine severity and lesion load. Future studies are needed to assess whether these (probably) ischemic lesions have relevant (long-term) functional correlates.     

A positron emission tomographic study in spontaneous migraine

BACKGROUND: Functional brain imaging in acute migraine has proved challenging because of the logistic problems associated with an episodic condition. Since the seminal observation of brainstem activation in migraine, there has been only a single case substantiating this finding. OBJECTIVE: To test the hypothesis that brainstem activation could be detected in migraine and to refine the anatomic localization with higher-resolution positron emission tomography than previously used. DESIGN: Using positron emission tomography with radioactive water (H(2)15O), we studied acute migraine attacks occurring spontaneously. Five patients underwent imaging in ictal and interictal states, and the differences were analyzed by means of statistical parametric mapping. SETTING: Tertiary referral center. PATIENTS: Six volunteers with episodic migraine were recruited from advertisements in migraine newsletters. One patient was excluded because of use of preventive medication. MAIN OUTCOME MEASURE: Brainstem activation during migraine state vs interictal state. RESULTS: Two patients had a typical migrainous aura before the onset of the headache. All of the attacks studied fulfilled standard diagnostic criteria for migraine. Comparing the migraine scans with interictal scans, there was significant activation in the dorsal pons, lateralized to the left (small volume correction, P = .003). Activation was also seen in the right anterior cingulate, posterior cingulate, cerebellum, thalamus, insula, prefrontal cortex, and temporal lobes. There was an area of deactivation in the migraine phase also located in the pons, lateralized to the right. CONCLUSIONS: Our findings provide clear evidence of dorsal pontine activation in migraine and reinforce the view that migraine is a subcortical disorder modulating afferent neural traffic.     

Migraine and headache in systemic lupus erythematosus and their relationship with antibodies against phospholipids

Summary It has been reported that migraine is common in systemic lupus erythematous (SLE) and an association with phospholipid antibodies has been suggested. The incidence of migraine and non-migrainous headache was prospectively studied in 90 patients with SLE and 90 age-and sex-matched controls. A history of migraine was commoner in SLE patients than in controls [31(34%) vs 15(16%);P<0.05], and the mean age of onset was higher in the SLE group (26.8 vs 17.2 years). Within the SLE group an association was found between migraine and SLE disease activity. Non-migrainous headaches were also more common (non-significant) in the SLE group, and there was a close temporal relationship between onset of both headache and SLE in many patients. Both migraine and non-migrainous headaches in SLE patients often responded to specific SLE treatment. No association was found between migraine or other headaches and antibodies to phospholipids.     

Menstrual migraine

Migraine is a common disorder that is disproportionately prevalent in women, especially during the reproductive years. Hormonal changes may play a role in the etiology of migraine, as many women note that their migraine attacks occur in temporal relationship with their menses. The Headache Classification Subcommittee of the International Headache Society has recently defined menstrual and menstrually related migraine. We review the most relevant and recent literature on menstrual migraine, with a special focus on pathophysiology and therapy. Although the pathogenesis of menstrual and menstrually related migraine is not well understood, estrogen withdrawal seems to play an important role as a trigger for menstrual migraine attacks. The therapeutic approach also may differ from the treatment of nonmenstrual migraine. Some patients do not require prophylaxis when they can abort their attacks effectively, whereas others may benefit from perimenstrual prophylaxis or standard migraine prophylaxis.     

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.     

Efficacy of lisinopril in migraine prophylaxis – an open label study

The ACE-inhibitor lisinopril has previously been shown to be effective in migraine prophylaxis at a daily dose of 20 mg. To test the effect of a low dose of lisinopril (5 mg daily) in migraine prevention, we performed an open label study in 21 migraineurs. The primary outcome measure was frequency of migraine attacks. Secondary efficacy measures were migraine hours, intake of acute migraine drugs, pain intensity and responder rate. Compared with baseline conditions, the attack frequency of migraine attacks was significantly reduced ( P  < 0.0005). The number of acute migraine drugs dropped significantly ( P  = 0.002). Three patients dropped out because of intolerable cough. Our study suggests that even low doses of lisinopril may be effective in migraine treatment. However, its use may be limited by intolerable side-effects.     

Arterial mechanisms in the pathophysiology of migraine headache—implications for modern therapy

Studies of the cephalic vascular system have markedly contributed towards an understanding of the mechanisms of migraine pain. Whereas cerebral blood flow changes, and thereby changes in the arterioles, correlate poorly with migraine headache, abnormal regulation of the large cranial arteries seems to play a significant role in relation to migraine pain. Thus, vasodilation of extra- and intracranial conductance arteries has been described both during spontaneous migraine attacks and during experimentally provoked vascular headaches. Whether dilation of these arteries is the key mechanism of migraine nociception or is merely associated with another more important nociceptive mechanism remains to be shown. Studies of vascular regulatory mechanisms have not only pointed towards a possible locus of migraine pain, but have also been helpful in demonstrating a new molecular mechanism of migraine—the key effect of the small messenger molecule nitric oxide. It is likely that nitric oxide is the most important molecule responsible for the induction of migraine attacks.     

Progress in clinical neurosciences: Migraine-stroke: a causal relationship, but which direction?

A significant association between migraine and ischemic stroke has been demonstrated in population and case-control studies. The risk of ischemic stroke appears to be higher in migraine with aura (MWA) than migraine without aura (MwoA). Migraine-stroke comprises a number of distinct entities, including migrainous infarction, in which ischemic stroke occurs during an attack of MWA and migraine-related stroke, in which the causal link is less clear. Migrainous infarction accounts for only one-third of migraine-stroke, strokes may occur during attacks of MwoA, and a number of cerebrovascular disorders may present as MWA or MwoA. Migraine may occur as a consequence of conditions that are known to cause stroke; therefore it remains to be determined whether migraine predisposes to stroke in the absence of any known disease associations, if it is an epiphenomenon of an underlying stroke diathesis, or if it requires the presence of another stroke risk factor to produce cerebral ischemia. Furthermore, it is unclear if ischemia results in migraine more often than migraine results in ischemia. Careful clinical studies that evaluate this bidirectional relationship are needed to determine why migraine patients are subject to a higher risk of ischemic stroke.     

Cyclic vomiting with generalized epileptiform discharges responsive to topiramate therapy

Cyclic vomiting syndrome is a disorder characterized by recurrent attacks of vomiting and intervals of normal health between vomiting episodes averaging 2-4 weeks. It has been described by a variety of names such as abdominal migraine, abdominal epilepsy, and periodic syndrome but now has been classified in the subgroup of childhood periodic syndromes that are commonly precursors of migraine. Topiramate is an antiepileptic drug used both in the treatment of epilepsy and in migraine prophylaxis. This report presents a child with cyclic vomiting syndrome with generalized epileptiform discharges who responded to topiramate therapy. The common features of epilepsy, migraine, and cyclic vomiting syndrome are discussed.     

Intensity dependence of auditory evoked cortical potentials in migraine. Changes in the peri-ictal period

The presence of premonitory symptoms in about 20% of patients suggest that the migraine attack is initiated long before the occurrence of the aura or headache symptoms. Recording of evoked and event-related potentials has revealed a strong intensity dependence of auditory evoked potentials (IDAP) in migraine with and without aura. We studied changes in IDAP in the peri-ictal period in 63 migraine patients (55 presenting migraine without aura, four migraine with aura, and four both types) and compared findings with interictal controls. The results of this study indicated that cortical processing of sensory information tends to normalize just before and during an attack. The normalization of IDAP may reflect an increase in central serotonergic activity. The study has been published in Cephalalgia (Afra J, Sándor PS, Schoenen J. Cephalalgia 2000;20:714-719).     

Sumatriptan: a decade of use and experience in the treatment of migraine

The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Sumatriptan (Imitrex) has been available for the longest time within the class, is most flexible in form and has been given successfully to the most number of patients. It is useful for the full range of attacks experienced by a migraine suffer. The aim of this review is to provide an overview of the first 10 years of the use of sumatriptan.     

偏头痛导致脑卒中的机制研究进展

偏头痛和脑卒中是常见的神经系统疾病,都是严重致残的疾病,多项研究认为偏头痛尤其是先兆性偏头痛,与脑卒中风险增加有关。文中主要就偏头痛导致脑卒中的相关性及可能机制进行综述。     

Platelet–leukocyte interaction and platelet activation in migraine: a link to ischemic stroke?

OBJECTIVES: Migraine has been identified as an independent risk factor for ischemic stroke. Both neurogenic inflammation and platelet activation have been linked to the pathophysiology of migraine. Increased platelet activation results in up-regulation of specific binding to leukocytes which promotes pro-inflammatory leukocyte secretion and their tethering to endothelium, a mechanism that has been demonstrated in stroke and which could provide a link to migraine. We aimed to determine whether platelet-leukocyte aggregation is increased in migraine patients outside an acute attack. METHODS: Seventy two patients with migraine according to IHS criteria were compared to a control group (n = 72). Whole blood flow cytometry was used to quantify the activation dependent P selectin on the platelet, and to assess the fraction of platelets bound to the different leukocyte subsets. RESULTS: Migraine patients showed significantly more platelet-leukocyte aggregates compared to the control subjects (p = 0.003). This effect was driven by an increased polymorphonuclear cell-platelet aggregation (p = 0.003) whereas platelet aggregation with monocytes and lymphocytes was not. Platelet activation was also increased (p = 0.001). CONCLUSIONS: In migraine pro-inflammatory platelet adhesion to leukocytes occurs during the headache free interval similar to that seen in acute coronary and cerebrovascular syndromes. This may suggest a link between migraine and stroke on a cellular level.     

Migraine with aura: new understanding from clinical epidemiologic studies

PURPOSE OF REVIEW: To discuss the consequences of recent clinical data on migraine with aura for clinical practice and future research in the light of new diagnostic criteria for migraine with aura. RECENT FINDINGS: Migraine with aura is now distinguished from hemiplegic migraine and from basilar migraine. Migraine with typical aura has an aura consisting of visual, sensory, or speech symptoms. The aura symptoms typically develop gradually over 5 or more minutes, last between 5 and 60 minutes and, when more than one symptom is present, they occur in succession. Half-sidedness is typical of visual and sensory symptoms, whereas speech symptoms are typically aphasic, primarily of the Broca type. A visual aura rating scale with a high sensitivity and specificity has been developed to standardize the diagnosis of visual aura. The new classification, the new criteria, and the new knowledge about clinical features of migraine with aura are important both for routine clinical diagnosis and for future research studies. SUMMARY: Recent studies of the clinical features of migraine with aura allow a more precise diagnosis and classification than previously possible. A clear distinction between migraine with typical aura, hemiplegic migraine, and basilar migraine is important for genetic and other research studies.     

Remission of migraine attacks in a patient with depression who is taking pregabalin

Antiepileptic drugs (AED) are increasingly used in the treatment of migraine. Pregabalin (PGB) is an AED that has been used in the treatment of partial seizures, of various types of pain, and of certain anxiety disorders, but to the best of our knowledge, there has been no report on the use of PGB in the treatment of migraine. We report the case of a 60-year-old female inpatient with depression, long experiencing migraine, whose migraine symptoms improved markedly after receiving PGB in combination with escitalopram administered for her depression. The PGB mechanism of action in conjunction with its structural similarity with gabapentin, already successfully tested in the treatment of migraine, provide additional supportive evidence, theoretical and clinical, respectively, for PGB potential to alleviate migraine symptoms. However, only carefully randomized, controlled studies, or at the very least, open-label series of large patient samples treated in a similar fashion could establish the efficacy of PGB in migraine treatment.     

Most cases labeled as "retinal migraine" are not migraine.

BACKGROUND: Monocular visual loss has often been labeled "retinal migraine." Yet there is reason to believe that many such cases do not meet the criteria set out by the International Headache Society (IHS), which defines "retinal migraine" as attacks of fully reversible monocular visual disturbance associated with migraine headache and a normal neuro-ophthalmic examination between attacks. METHODS: We performed a literature search of articles mentioning "retinal migraine," "anterior visual pathway migraine," "monocular migraine," "ocular migraine," "retinal vasospasm," "transient monocular visual loss," and "retinal spreading depression" using Medline and older textbooks. We applied the IHS criteria for retinal migraine to all cases so labeled. To be included as definite retinal migraine, patients were required to have had at least two episodes of transient monocular visual loss associated with, or followed by, a headache with migrainous features. RESULTS: Only 16 patients with transient monocular visual loss had clinical manifestations consistent with retinal migraine. Only 5 of these patients met the IHS criteria for definite retinal migraine. No patient with permanent visual loss met the IHS criteria for retinal migraine. CONCLUSIONS: Definite retinal migraine, as defined by the IHS criteria, is an exceedingly rare cause of transient monocular visual loss. There are no convincing reports of permanent monocular visual loss associated with migraine. Most cases of transient monocular visual loss diagnosed as retinal migraine would more properly be diagnosed as "presumed retinal vasospasm."