Migraine with and without aura share the same pathogenic mechanisms

Migraine with aura and without aura share the same clinical features with respect to the headache, and differ nosologically in the presence or absence of aura. The mechanisms of aura generation are now becoming clearer, based on imaging studies, and a common migraine pathophysiology for all subtypes of migraine headaches now seems reasonable, as it would seem implausible that all of these neurological events have different pathogenic mechanisms. Both major subtypes of migraine clearly represent a perturbation of normal physiology and employ normal anatomic pathways to generate the aura and headache, similar to aura and a seizure. So what is the mechanism of migraine aura? Do migraine without aura patients have clinically silent aura? Migraine is after all defined as a clinical disorder and is the prototypic primary headache and thus its uniform pathogenesis must underlie all that we know about migraine clinically. This presentation will take the resolve that the migraine with and without aura share the same pathogenic mechanisms.

     

Cognitive functions and psychological symptoms in migraine: a study on patients with and without aura

Aim: Migraine is neurological disorder with a complex pathophysiology. We described the neuropsychological profile of 100 migraineurs (50 with visual aura and 50 without aura), in interictal phase, compared to 50 matched healthy controls.

Materials and methods: A battery of standardized neuropsychological tests was used to assess attention, memory and executive functions. Beck Depression Inventory and Hamilton Rating Scale for Anxiety were used to evaluate anxiety and depressive symptoms. Severity of disability during daily activities was assessed by Migraine Disability Assessment.

Results: Migraine without aura showed a significant difference in comparison to healthy controls in semantic verbal fluency (p?=?0.02), delayed memory (p?<?0.001) and set-shifting (p?<?0.001). Migraine with aura showed a significant difference in delayed memory (p?=?0.001) and set-shifting (p?=?0.005) if compared to healthy controls. No significant correlation between cognitive functions and mood was found (HAM-A p?=?0.67) (BDI-II p?=?0.42).

Conclusions: Our data showed isolate and specific cognitive deficit during interictal phase in migraine patients. Future studies are need to identify if specific migraine characteristics may affect cognitive functions.     

Predictors of Triptan Response in Pediatric Migraine

BackgroundMigraine is common in children and adolescents and can be disabling. Being able to predict which patients will respond to triptans based on their clinical phenotype would be helpful. Adult data suggest cranial autonomic symptoms and aura predict triptan response. This study examined clinical predictors of triptan response in pediatric migraineurs.MethodsThis chart review study included all patients less than 18 years old with migraine who were seen at the University of California, San Francisco Headache Center in 2014. Univariate χ² analyses were performed, followed by multivariate logistic regression modeling.ResultsOf 127 pediatric migraineurs, 70 (55%) had chronic migraine and 24 (19%) had aura. The majority (55%) had at least one cranial autonomic symptom. Of 65 with triptan outcome data, 47 (73%) benefitted from a triptan. In univariate analyses, triptan benefit was seen in 65% with chronic migraine versus 88% with episodic migraine (P = 0.048), 67% with aura versus 74% without (P = 0.66), and 70% with cranial autonomic symptom versus 74% without (P = 0.76). In a multivariate logistic regression model, chronic migraine, aura, and cranial autonomic symptom were not statistically significant predictors of triptan benefit: chronic migraine: 0.25 (0.06-1.04); aura: 0.65 (0.09-4.45); cranial autonomic symptom: 0.75 (0.22-2.52).ConclusionsIn univariate analysis, individuals with chronic migraine were less likely to benefit from triptans. In contrast to what has been documented in adults, cranial autonomic symptoms and aura did not predict triptan response, although our small sample size limited the study's power. Larger pediatric studies are needed, and future pediatric triptan trials should provide response rates stratified by clinical variables such as aura.     

Is ocular vascularity affected in young migraine patients? A pilot study

ObjectiveThis study aimed to evaluate ocular vascularity in young adult migraine patients with visual aura and without visual aura.Material and MethodsThe study included 30 patients with migraine with visual aura (MWVA), 30 patients with migraine without visual aura (MWOVA), and 30 healthy control subjects, all between ages ≥18 and <45. Migraine patients were applied Headache Impact Test (HIT) and Migraine Disability Assessment Scale (MIDAS). Retinal nerve fiber layer thickness and ocular vascularity of all participants were evaluated with optical coherence tomography (OCT) and OCT angiography (OCTA).ResultsThe MWVA group had significantly lower superficial and deep foveal vascular density values compared to the control group (p = 0.039, p = 0.028, respectively). The foveal avascular zone was significantly enlarged in the MWVA group compared to the control group (p = 0.033). MWVA patients had significantly lower whole optic disc, optic disc inside, peripapillary, superior hemisphere, inferior hemisphere, superior quadrant, and temporal quadrant vascular density values compared to the control group (p < 0.05 all), while there was no significant difference in the nasal quadrant (p = 0.083). Migraine attack frequency, MIDAS, and HIT were negatively correlated with ocular vascular density values.ConclusionThe results of our study indicate that young adult patients with MWVA are at risk of decreased ocular vascularity and that this risk may increase with frequency and severity of migraine attacks.     

Stroke in patients with migraine

Background and purposeMigraine with aura (MA) is considered as a risk factor for ischaemic stroke. The present observational retrospective study compares migraine patients admitted for a documented stroke with those presenting focal neurological symptoms and headache without a demonstrable lesion and in which the final diagnosis was a migraine attack with aura.Material and methodsThe study included 14 migraine patients with a stroke and 37 without a stroke. The clinical characteristics, the vascular risk factors and the results of the technical examinations were compared.ResultsStroke occurred in migraine patients with aura as well as without aura. Classical vascular risk factors were rather rare. Patent foramen ovale (PFO) with or without atrial septum aneurysm appeared to be the main risk factor for stroke in patients with a history of migraine. Infarcts were mainly located in the supratentorial territory of the posterior cerebral circulation. Also some lobar haematomas were observed, but their aetiology remained uncertain. The strokes were generally mildly severe with good outcome. Hyperintense signals in the cerebral white matter and cerebellum, on T₂-weighted magnetic resonance imaging, were more frequent in the migraine patients with stroke.ConclusionsThe presence of PFO, rather than of MA, appeared to be the main risk factor for stroke patients with migraine. No direct relation between migraine and stroke could be demonstrated.     

Evaluation of serum transforming growth factor β1 and C-reactive protein levels in migraine patients

Background and purposeMigraine is a frequent form of headache. Although many mechanisms describing onset of migraine with and without visual aura have been suggested, the aetiology of migraine headaches is still not clear. Neurogenic inflammation may play a key role in the development of migraine headaches. We evaluated the discriminative power of serum levels of C-reactive protein (CRP) and transforming growth factor beta 1 (TGF-β1) in patients who presented to our clinic with migraine headaches with or without visual aura.Material and methodsWe designed a prospective case-control study of 51 patients with migraine (27 with migraine with aura and 24 with migraine without aura; all had headache) and compared them with 27 healthy subjects during the study period. Demographic and clinical characteristics recorded were age, sex, marital status, occupation, characteristics of headache, laboratory values, and serum CRP and TGF-β1 levels. Statistical analyses used Student t-test, the χ² test, and ANOVA followed by the post-hoc Bonferroni test for multiple comparisons. Receiver operator characteristic (ROC)-curve analysis for CRP and TGF-β1 was also conducted.ResultsThere was no difference between the groups in terms of demographic characteristics, marital status, and socioeconomic status. Statistically, white blood cell levels, serum glucose levels, triglyceride levels, high-density lipoprotein levels, and serum CRP and TGF-β1 were significantly higher in patients with migraine (p < 0.05). The ROC curve results in this study identified that CRP and TGF-β1 may discriminate patients who have different types of migraine headache.ConclusionsThis study suggests that serum CRP and TGF-β1 levels may be diagnostic factors to differentiate migraine patients with and without aura. These findings show that neurogenic inflammation may have a role in the aetiology of migraines.     

Migraine with aura is a risk factor for unprovoked seizures in children

OBJECTIVE: Migraine is associated with epilepsy, but the time order and nature of the relationship are unclear. We conducted a population based case control study to clarify the time order to determine whether migraine is a risk factor for epilepsy. METHODS: Migraine symptoms were evaluated in a population-based case-control study of all incident epilepsy in Icelandic children and in matched controls (next two same sex births in the country). RESULTS: Migraine was associated with a fourfold increased risk for developing epilepsy, an association explained by migraine with aura (odds ratio, 8.1; 95% confidence interval, 2.7-24.3). Migraine without aura did not increase risk for epilepsy. INTERPRETATION: Children with migraine with aura have a substantial increased risk to develop subsequent epilepsy. This finding is consistent with the hypothesis that migraine with aura and migraine without aura may be different disorders.     

The prevalence of patent foramen ovale in patients with migraine

BACKGROUND AND PURPOSE: Migraine is a common neurologic disorder whose etiology remains unknown. Migraine has been reported as a possible risk factor for ischemic stroke, especially in young women. The relationship between migraine and stroke is stronger in patients suffering from migraine with aura compared to those with common migraine. Coexistence of migraine and patent foramen ovale (PFO) should be also considered. The aim of our study was to evaluate the frequency of PFO in patients with migraine with aura (MA) and compare it with the prevalence of PFO in migraine patients without aura (M) and in a healthy age-matched control group. MATERIAL AND METHODS: We assessed 62 patients (48 females) suffering from migraine with aura, 60 without aura (53 females) and 65 normal controls (51 females). In order to detect PFO the contrast transcranial Doppler was performed during Valsalva maneuver. RESULTS: The presence of PFO was found in 33/62 (53%) patients with MA compared to 15/60 (25%) without aura, and in 16/65 (25%) control subjects. The difference in PFO prevalence between MA patients and M patients and the difference between MA patients and the control group was statistically significant (p<0.05). CONCLUSIONS: Our findings suggest that at least some attacks of migraine with aura may be associated with paradoxical embolism.     

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 role of migraine headache severity,associated features and interactions with overweight/obesity in inhibitory control

Aim of the Study: While migraine and obesity are related and both conditions are associated with reduced executive functioning, no study has examined whether obesity exacerbates executive dysfunction in migraine. This cross-sectional study examined whether overweight/obesity moderated associations of migraine severity and associated features with inhibitory control, one aspect of executive function.

Materials and Methods: Women (n = 124) aged 18–50 years old with overweight/obesity body mass index (BMI) = 35.1 ± 6.4 kg/m² and migraine completed a 28-day smartphone-based headache diary assessing migraine headache severity (attack frequency, pain intensity) and frequency of associated features (aura, photophobia, phonophobia, nausea). They then completed computerized measures of inhibitory control during an interictal (headache-free) period.

Results: Participants with higher migraine attack frequency performed worse on the Flanker test (accuracy and reaction time; p < .05). Migraine attack frequency and pain intensity interacted with BMI to predict slower Stroop and/or Flanker Reaction Time (RT; p < .05). More frequent photophobia, phonophobia and aura were independently related to slower RT on the Stroop and/or Flanker tests (p < .05), and BMI moderated the relationship between the occurrence of aura and Stroop RT (p = .03).

Conclusions: Associations of migraine severity and presence of associated features with inhibitory control varied by BMI in overweight/obese women with migraine. These findings warrant consideration of weight status in clarifying the role of migraine in executive functioning.     

Spectral analysis of EEG in etiological assessment of patients with transient neurological deficits

ObjectiveDifferentiating transient ischemic attack from stroke mimics may be difficult. Besides clinical evaluation and brain imaging, electroencephalography (EEG) may be a useful diagnostic tool.MethodsWe conducted spectral analysis on 67 EEG of patients who had presented a transient neurological deficit (TND) within the previous seven days. Expert clinicians provided the final diagnosis: transient ischemic attack, migraine with aura, focal seizure or “other”. We first calculated the relative power of the four EEG frequency bands (delta, theta, alpha and beta), in the whole hemisphere, then, according to the clinical symptoms, in the relevant electrodes of the symptomatic hemisphere. Finally, we calculated the relative power ratio between symptomatic and asymptomatic hemispheres.ResultsMedian age was 60.6 years (57% females). The etiological diagnosis was transient ischemic attack (27%), migraine with aura (11%), focal seizures (22%) and “other” (40%). We did not find significant differences in the theta and delta relative power analysis between groups. Over the symptomatic hemisphere only, we found a significant increase of the alpha relative power (p = 0.0026, p < 0.0001, p = 0.0014) in the migraine group compared to transient ischemic attack, migraine and focal seizures groups, and a significant decrease of the beta relative power (p = 0.0034, p = 0.0016, p = 0.0005) compared to the same groups.ConclusionsMigraine with aura presents a discriminative EEG relative power in comparison to transient neurological deficits of other origins. To further investigate the additive diagnosis value of EEG in other TND, future studies should be performed with an EEG obtained within the first 24 h after the onset of symptoms.SignificanceSpectral EEG analysis discriminates migraine with aura groups from other groups, but not at the individual level.     

Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆

ObjectiveTo examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects.MethodsAcute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype.ResultsOur primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01–0.03) and decreased risk of ACiS (p=0.010–0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008–0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001–0.010) and migraine without aura (p=0.032–0.048). Migraine with aura PRS did not show a differential association in our analyses.ConclusionsOur results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.     

Interictal “patchy” regional cerebral blood flow patterns in migraine patients. A single photon emission computerized tomographic study

In 92 migraine patients and 44 healthy control subjects we recorded regional cerebral blood flow (rCBF) with single photon emission computerized tomography and ¹³³Xe inhalation or with i.v. ^99mTc-HMPAO. Migraine patients were studied interictally. A quantitated analysis of right-left asymmetry indices in a fixed set of regions of interest was compared with the normal asymmetry indices in the healthy controls. An asymmetry index deviating more than ± 2.5 S.D.s in normals was defined as pathological asymmetry. By quantitated analysis 47% of images from patients with aura attacks and 48% of images from patients without aura attacks were established to contain higher rate of asymmetries, the difference being statistically significant (p < 0.05, Wilcoxon). A blinded visual analysis and scoring by a four level scale were done by four experienced observers. rCBF images from 18% of patients having attacks with aura and from 19% of patients without aura attacks was scored as containing abnormal right-left asymmetries by the visual analysis. Images from healthy controls were all scored to be normal. In 37% of the images (all from patients) there was lack of consensus among observers (κ = 0.28). There was no correlation between visual or quantitated abnormalities and age, duration of migraine, frequency of attacks or prophylactic medication. No correlation could be established between asymmetries and the usual side of headache or aura symptoms. Two conclusions emerged: (1) visual evaluation of interictal migraine rCBF images is insufficient to pick up abnormalities; (2) almost 50% of the migraine sufferers had abnormal rCBF/asymmetries. However, these are discrete compared with those typically seen during the aura phase of a migraine attack. One explanation to the patchy rCBF patterns might be that they reflect interictal cerebrovascular dysregulation which might to be a common feature in both types of migraine.     

An innovative approach for migraine prevention in young age: a preliminary study

Headache is one of the commonest conditions to affect children and adolescents in industrialized countries. Effective pharmacological treatments without side effects are still lacking. Ginkgolide B, an herbal constituent extract from ginkgo biloba tree leaves, is a natural antiplatelet activating factor (PAF). PAF is a potent proinflammatory and nociceptive agent released during the inflammation process. Therefore, Ginkgolide B can be considered a promising non-pharmacological tool for treatment of migraine with and without aura. We propose to determine the efficacy of Ginkgolide B as preventive treatment in a group of young patients suffering from migraine without aura. A small sample of 24 young patients suffering from migraine without aura entered the open-label prospective trial. Migraine without aura was diagnosed according to International Headache Society criteria. The treatment was well tolerated and the compliance was good. These preliminary data show that Ginkgolide B seems to be effective as preventive treatment in reducing migraine attack frequency and in attenuating the use of symptomatic medication in our small series of children with primary headache.

     

Duration,frequency, recency,and type of migraine and the risk of ischaemic stroke in women of childbearing age

BACKGROUND: Migraine is recognised increasingly as a risk factor for ischaemic stroke in women of childbearing age. Migraine with aura poses a higher risk than migraine without aura. OBJECTIVE: To investigate further the effect of duration, frequency, recency, and type of migraine on the risk of ischaemic stroke. METHODS: Additional analyses of a previously reported multicentre case-control study of the relation between stroke and migraine in women aged 20-44 years. RESULTS: Among 86 cases of ischaemic stroke and 214 controls, the adjusted risk of ischaemic stroke was significantly associated with: (1) migraine of more than 12 years duration, odds ratio (OR) 4.61 (1.27-16.8); (2) initial migraine with aura, OR 8.37 (2.33-30.1); (3) particularly if attacks were more frequent than 12 times per year, OR 10.4 (2.18-49.4). In no case did correction for oral contraception usage significantly alter these odds ratios. Increasing risk of ischaemic stroke was related to a change to increased frequency of headaches (trend p 相似文献   

Patent foramen ovale, stroke, and cardiovascular disease in migraine

PURPOSE OF REVIEW: We will review the literature on the association between migraine with patent foramen ovale, stroke, and coronary heart disease. RECENT FINDINGS: The prevalence of patent foramen ovale in patients with migraine with aura is significantly higher than in nonmigraine controls and migraineurs without aura. However, there is currently no evidence to support a causal relationship. Migraine with aura has been consistently associated with increased risk of ischemic stroke in several epidemiologic studies. Migraine with aura is associated with a more unfavourable cardiovascular risk profile and recent data suggest that the association between migraine with aura and stroke may extend to overall cardiovascular disease. Identification of migraine patients at particular risk for stroke or other vascular events is impossible based on current knowledge. SUMMARY: Migraine with aura and patent foramen ovale have higher coincidences than expected by chance only. It is possible that both conditions are inherited together. Until now there has been no evidence from placebo-controlled randomized trials that closure of patent foramen ovale improves migraine with aura. There is increasing evidence that migraine with aura is not only a risk factor for ischemic stroke but also for myocardial infarction and other ischemic vascular events.     

Migraine with aura: conventional and non-conventional treatments

Migraine with aura (MwA) is a primary headache that affects up 30% of migraine patients. Although the frequency of MwA attacks is usually low and the majority of migraine sufferers do not need prophylactic treatment(s), same particular patients do. This occurs when the neurological symptoms, that characterize the auras, determine anxiety to the migraine sufferers and when the frequency of MwA attacks is or becomes high. In this study, we review the few therapeutic conventional options specifically devoted to cure MwA attacks present in the literature together with those, recent, non-conventional.

     

Contrasts in cortical magnesium, phospholipid and energy metabolism between migraine syndromes

BACKGROUND: Previous single voxel (31)P MRS pilot studies of migraine patients have suggested that disordered energy metabolism or Mg(2+) deficiencies may be responsible for hyperexcitability of neuronal tissue in migraine patients. These studies were extended to include multiple brain regions and larger numbers of patients by multislice (31)P MR spectroscopic imaging. METHODS: Migraine with aura (MWA), migraine without aura (MwoA), and hemiplegic migraine patients were studied between attacks by (31)P MRS imaging using a 3-T scanner. RESULTS: Results were compared with those in healthy control subjects without headache. In MwoA, consistent increases in phosphodiester concentration [PDE] were measured in most brain regions, with a trend toward increase in [Mg(2+)] in posterior brain. In MWA, phosphocreatine concentration ([PCr]) was decreased to a minor degree in anterior brain regions and a trend toward decreased [Mg(2+)] was observed in posterior slice 1, but no consistent changes were found in phosphomonoester concentration [PME], [PDE], inorganic phosphate concentration ([Pi]), or pH. In hemiplegic migraine patients, [PCr] had a tendency to be lower, and [Mg(2+)] was significantly lower than in the posterior brain regions of control subjects. Trend analysis showed a significant decrease of brain [Mg(2+)] and [PDE] in posterior brain regions with increasing severity of neurologic symptoms. CONCLUSIONS: Overall, the results support no substantial or consistent abnormalities of energy metabolism, but it is hypothesized that disturbances in magnesium ion homeostasis may contribute to brain cortex hyperexcitability and the pathogenesis of migraine syndromes associated with neurologic symptoms. In contrast, migraine patients without a neurologic aura may exhibit compensatory changes in [Mg(2+)] and membrane phospholipids that counteract cortical excitability.     

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.     

Alexithymic features in migraine patients

Abstract. The aims of the present study were 1) to investigate the alexithymic features in migraine patients and, 2) if alexithymia has any relation with the results of other psychological scales that are widely used in clinical practice to describe the psychopathologies, such as depression and anxiety. Demographic and clinical data of 50 cases with migraine without aura and 50 normal volunteers were supplied. All cases completed the Beck Depression Inventory, Hamilton Depression Rating Scale, State and Trait Anxiety Inventory and Toronto Alexithymia Scale. Migraine patients were significantly more depressive, anxious and alexithymic than the control group; there was no correlation between TAS scores and demographic variables; not depression but anxiety was significantly correlated with alexithymia in the migraine group, whereas none of the scores were found to be related to alexithymia in controls. According to our results, alexithymia is a frequent finding in migraine patients and is associated with anxiety to a considerable extent but not with depression.