Platelet and plasma levels of glutamate and glutamine in migraine with and without aura

We evaluated plasma and platelet glutamate and glutamine levels in migraine with and without aura during headache-free periods and compared the results with those of normal controls. The plasma and platelet levels of glutamine in migraine with and without aura were normal. Migraine without aura patients had higher glutamate levels in plasma, and normal platelet levels. In migraine with aura patients, glutamate levels were high in platelets, but not in plasma. This suggests different profiles of excitatory amino acid metabolism in migraine with and without aura.     

Migraine without aura and migraine with aura are inherited disorders

The familial occurrence and mode of inheritance were analysed in families with migraine without aura (MO) and migraine with aura (MA). The probands were found among 4000 persons from the general population. All persons with MA were included as probands, and an equivalent number of probands with MO was selected as a random sample among those with MO. Spouses and first-degree relatives were blindly interviewed. All interviews were performed by one neurological research fellow. The distinct familial patterns indicate that MO and MA have a different aetiology. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO, indicating that both genetic and environmental factors are important in MO. The first-degree relatives of probands with MA had a four-fold increased risk of MA while spouses had no increased risk of MA, indicating that MA is determined largely by genetic factors. The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference.     

Pattern reversal visual evoked potentials in migraine with aura and migraine aura without headache

Pattern reversal visual evoked potentials (PVEPs) were recorded in 20 patients with migraine with aura (MA), 19 patients with migraine without headache (migraine equivalent; ME.) during interictal periods, and 34 normal subjects. All migraine patients had hemianopsia or fortification spectra during attacks. In both MA and ME patients of less than 49 years of age, there were significant ( p <0.01) differences in amplitude of PVEPs at the mid-occipital and contralateral to visual aura electrode sites compared to normal subjects. Amplitude of PVEPs in MA and ME showed significant ( p <0.001) increases when recorded soon after attacks, especially within 10 days. There was a significant ( p <0.0l) correlation between percentage asymmetries and the duration of illness in both MA and ME. We conclude from our PVEP findings that cortical spreading depression remains the most likely explanation for the migraine visual aura.     

Migraine with aura and migraine without aura: an epidemiological study

In a cross-sectional study of headache disorders in a representative general population of 1,000 persons the epidemiology of migraine with aura (MA) and migraine without aura (MO) was analysed in relation to sex and age distribution, symptomatology and precipitants. The headache disorders were classified on the basis of a clinical interview as well as a physical and a neurological examination using the operational diagnostic criteria of the International Headache Society (IHS). Lifetime prevalence of MA was 5%, male:female ratio 1:2. Lifetime prevalence of MO was 8%, M:F ratio 1:7. Women, but not men, were significantly more likely to have MO than MA. Neither MA nor MO showed correlation to age in the studied age interval (25-64 years). Premonitory symptoms occurred in 16% of subjects with MA and in 12% with MO. One or more precipitating factor was present in 61% with MA and in 90% with MO. In both MA and MO the most conspicuous precipitating factor was stress and mental tension. Visual disturbances were the most common aura phenomenon occurring in 90% of subjects with MA. Aura symptoms of sensory, motor or speech disturbances rarely occurred without coexisting visual disturbances. The pain phase of MA fulfilled the criteria for MO of the IHS. Headache was, however, less severe and shorter lasting in MA than in MO. Onset at menarche, menstrual precipitation, menstrual problems, influence of pregnancy and use of oral contraceptives all showed some relationship with the presence of MO and less with MA. The present findings suggest that MA and MO share the pain phase.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Ovarian steroid levels in migraine with and without aura

Radioimmunoassays were used to measure interictal levels of ovarian steroids (oestradiol, total oestrogens and progesterone) in migraine patients at the onset of menses and coincident with the luteinizing hormone surge preceding ovulation. Results of these verified biochemically-contrasting points of the ovarian cycle were used to compare 13 migraine patients without aura and 6 migraine patients with aura with 17 non-migraine women. No group differences were found for physiological basal levels of ovarian steroids measured at menses. Preceding ovulation elevation in oestradiol levels relative to normal was found in migraine patients with aura but not in migraine patients without aura. These results suggest that a variation in oestradiol levels is an important factor in the different clinical expressions of migraine.     

Intracellular and plasma magnesium in familial hemiplegic migraine and migraine with and without aura

Familial hemiplegic migraine (FHM) is an autosomal dominant type of migraine and probably represents the most extreme end of migraine with aura. Reduced magnesium facilitates the development of spreading depression and possibly aura. Cellular magnesium levels are under genetic control. We hypothesized that FHM patients would have significantly reduced intracellular magnesium levels. We determined intracellular and plasma magnesium levels in blood of 38 afflicted and 11 non-afflicted members of three families with FHM and, in 32 migraine patients (9 with and 23 without aura) and 32 age and sex matched healthy controls. We found no significant differences between the magnesium levels in the five study groups. We conclude that reduced blood magnesium is unlikely to be related to migraine pathophysiology.     

Immunocyte enumeration in duodenal biopsies of migraine without aura patients with or without food-induced migraine

The possibility of an IgE-mediated allergic mechanism in food-induced migraine remains controversial. Twenty consecutive migraine patients, 11 with food-induced migraine, 9 without, were investigated for determination and counting of immunocyte populations (IgA, IgM, IgE, IgG containing cells) by biopsies at duodenum 2 level. Conventional histology and plasmocyte populations were not significantly different between the two groups of migraine patients. This study does not support the existence of an IgE-mediated allergic mechanism in food-induced migraine.     

Objective assessment of cortical excitability in migraine with and without aura

Recent progress in the genetics of migraine has refocused attention on cortical dysfunction as an important component of the pathophysiology of this disorder. In previous work, we have demonstrated functional changes in the visual cortex of migraine patients, using an objective transcranial magnetic stimulation technique, termed magnetic suppression of perceptual accuracy (MSPA). This study aimed to replicate previous findings in migraine with aura (MA) and to use the technique to examine migraine without aura (MoA). Eight MA patients, 14 MoA patients and 13 migraine-free controls participated. MSPA assessments were undertaken using a standardized protocol in which computer-presented letter targets were followed at a variable delay interval by a single magnetic pulse delivered over the occiput. MSPA performance is expressed as a profile of response accuracy across target-pulse delay intervals. The profiles of migraine-free controls exhibited a normal U-shape. MA patients had significantly shallower profiles, showing little or no suppression at intermediate delay intervals. MoA patients had profiles that were similar to controls. Recent animal evidence strongly indicates that the U-shape of the normal MSPA function is caused by preferential activation of inhibitory neurons. Shallower MPSA profiles in MA patients are therefore likely to indicate a functional hyperexcitability caused by impaired inhibition. The finding of normal MPSA profiles in MoA patients is novel and will require further investigation.     

Platelet serotonin uptake and migraine

Platelet serotonin uptake characteristics (K_m, V_max, y) were determined in platelet-rich plasma for 11 common migraineurs and 15 healthy volunteers. All three parameters were decreased only for the three patients having a migraine attack during blood collection. Migrainous platelets isolated on dextran or resuspended in control plasma exhibited normal serotonin uptake. This finding suggests that plasmatic factor(s) may be responsible for the decrease of platelet serotonin uptake observed during migraine attacks.     

Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally

We measured, by RIA methods, ictal and interictal levels of substance P (SP), calcitonin-gene related peptide (CGRP) and neurokinin A (NKA) in the plasma of 30 young migraine patients with aura (MPA) and 45 migraine patients without aura (MWA), and compared the results with those of 30 age-matched controls. There were no significant differences between the levels of these vasoactive peptides in the control group and the levels in both migraine groups studied in headache-free periods. An elevation of CGRP levels in plasma was found during attacks in MPA and, to a lesser extent, in MWA ( p < 0.03 and p < 0.05, respectively). A significant increase in NKA levels was also demonstrated in the MPA and MWA groups ( p < 0.02 and p < 0.04, respectively). These data suggest, although indirectly, that CGRP and NKA could be involved in the pathogenesis of migraine attacks in juvenile migraine patients.     

Cerebrovascular risk factors in migraine with prolonged aura and without aura

The role of cerebrovascular risk factors such as mitral valve prolapse, platelet aggregation, platelet activation and cardiac arrythmias in migraine was investigated in a total of 44 migraineurs (32 migraineurs without aura and 12 with prolonged aura) and 32 controls. Comparing the total of migraineurs and the two subgroups with controls, mitral valve prolapse, a raised thromboxane B2 level, at least one platelet aggregation dysfunction or an abnormality in 24-h ECG was statistically seen no more often than in the control group. Neither did combinations of the variables occur more frequently. Altogether, this study showed no increased coincidence of migraine with prolonged aura and migraine without aura with the above parameters. The absence of cardiac and haematological abnormalities in migraine with prolonged aura focuses attention on the control of the cortical microcirculation.     

MicroRNA profiling in migraine without aura: Pilot study

Background and purpose. MicroRNAs (miRNAs) are short, non-coding RNAs whose deregulation has been shown in several human diseases, including pain states and diseases associated with increased cardiovascular (CV) risk. This study aimed at identifying differentially expressed circulating miRNAs in patients with ‘migraine without aura’ (MO), a pain condition whose link with CV risk remains debated.

Methods. Fifteen female MO patients and 13 matching healthy controls underwent a circulating microRNA expression profiling. MiR-22, miR-26a, miR-26b, miR-27b, miR-29b, let-7b, miR-181a, miR-221, miR-30b, and miR-30e were selected for validation by quantitative real-time polymerase chain reaction.

Results. In migraineurs versus controls, four miRNAs were differentially expressed: miR-27b was significantly up-regulated (q < 0.004), while miR-181a, let-7b, and miR-22 were significantly down-regulated (q ≤ 0.01). MiR-22 and let-7b down-regulation was also confirmed in circulating blood monocytes. A logistic regression model based on microRNA expression profile showed a high accuracy for identifying migraine (AUC of ROC curve: 0.956; P < 0.001).

Conclusion. A specific circulating miRNAs profile is associated with migraine without aura. Remarkably, the same miRNAs are known to be modulated in the setting of atherosclerosis and stroke in humans. This study represents a first step towards further characterization of MO diagnosis/pathophysiology, also in relation to its link with cardiovascular risk.     

Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey

OBJECTIVE: To investigate the co-occurrence of migraine without aura (MWOA) and migraine with aura (MWA) in a population-based twin survey. BACKGROUND: Migraine without aura and MWA are multifactorial disorders. If MWOA and MWA share common genes, co-occurrence should be observed more frequently than expected, ie, the product of the prevalence in the general population. MATERIAL AND METHODS: The study population included all living Danish monozygotic (MZ) and same-gender dizygotic (DZ) twin pairs born between 1953 and 1960: 5360 twins (2026 MZ, 3334 DZ). The sample included 2840 men and 2520 women. All received a posted questionnaire, and those with possible migraine were interviewed via telephone by trained physicians (V.U. or M.G.). Twins who did not respond to the questionnaire and who had a co-twin with possible migraine were contacted by telephone. The questionnaire response rate was 87% (4660 of 5360), and the telephone interview was participated in by 90% (2035 of 2272). The physician interviewers were unaware of questionnaire answers, zygosity, and the clinical diagnosis of the co-twin. The criteria of the International Headache Society were used to establish a diagnosis of migraine. RESULTS: Lifetime prevalence in the twin sample: 7% of men and 19% of women had MWOA, while 7% of men and 8% of women had MWA. Lifetime prevalence of MWA in twin pairs with MWOA: MZ men, 2% (1 of 47); MZ women, 6% (5 of 90); DZ men, 9% (7 of 75); and DZ women, 10% (19 of 182). Lifetime prevalence of MWOA in twin pairs with MWA: MZ men, 3% (1 of 33); MZ women, 5% (3 of 58); DZ men, 9% (4 of 44); and DZ women, 13% (10 of 76). The observed and the expected numbers of twins with co-occurrence of MWOA and MWA based on the prevalence in the general population were not significantly different in either men or women (men, P=.1 and women, P=.5). CONCLUSION: The results strongly suggest that MWOA and MWA are distinct disorders, and identification of common genes for MWOA and MWA, thus, should not be expected to result from future genetic research.     

Prevalence of migraine in schoolchildren and some clinical comparisons between migraine with and without aura

OBJECTIVES: To determine the prevalence of migraine and its association with age, gender, and social class and to find out whether or not the headache and nonheadache characteristics differ between children with migraine, with and without aura, using the diagnostic criteria of the International Headache Society for childhood migraine. DESIGN: Population-based study in two stages comprising an initial screening questionnaire followed by telephone interviews of children with symptoms. SETTING: Eighteen kindergarten and 39 primary and secondary schools in Thessaloniki and its semiurban areas. SUBJECTS: Four thousand children, aged 4 to 15 years, representing a random sample of 5% of schoolchildren in Thessaloniki and its semiurban areas. MAIN OUTCOME MEASURES: (1) The prevalence of migraine, (2) the connection of migraine with social class, (3) differences in the occurrence of individual symptoms between migraine with and without aura. RESULTS: The results of the present study show that migraine prevalence was 6.2% (95% confidence interval [CI], 5.4 to 7.0). The estimated prevalences of migraine with and without aura were 2.8% (95% CI, 2.3 to 3.4) and 3.4% (CI, 2.8 to 4.0), respectively. The prevalence of migraine increased with age and it was found to be almost equal in boys and girls aged 7 to 9 years or younger, but in older age groups the prevalence was higher in girls than in boys. The data showed no evidence that connected migraine with social class. It also showed that except for the aura, the headache (e.g., frequency, duration, location, quality, and severity) and nonheadache (e.g., nausea, vomiting, phonophobia, and photophobia) characteristics were no different between children with migraine, with and without aura. In conclusion, our findings indicate that migraine is a common underdiagnosed cause of severe recurrent headache in children. The findings show that childhood migraine is not connected with social class and varies with age and gender, and that except for the aura, both migraine with and without aura are so similar in their headache and nonheadache clinical characteristics that a common pathogenesis is plausible.     

Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord

Peripheral nerve injury provokes heightened excitability of primary sensory afferents including nociceptors, and elicits ectopic activity in lesioned and neighboring intact nerve fibers. The major transmitter released by sensory afferents in the superficial dorsal horn of the spinal cord is glutamate. Glutamate is critically involved in nociceptive signaling and the development of neuropathic pain. We recorded miniature excitatory postsynaptic currents (mEPSCs) from neurons in lamina II of the rat dorsal horn to assess spontaneous synaptic activity after spared nerve injury (SNI), a model of chronic neuropathic pain. Following SNI, the frequency of mEPSCs doubled, indicating heightened glutamate release from primary afferents or spinal interneurons. Consistent with this finding, glutamate concentrations in the cerebrospinal fluid were elevated at 1 and 4 weeks after SNI. Transmitter uptake was insufficient to prevent the rise in extracellular glutamate as the expression of glutamate transporters remained unchanged or decreased. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride, an antagonist of metabotropic glutamate receptor 5 (mGluR5), reduced the frequency of mEPSCs to its preinjury level, suggesting a positive feedback mechanism that involves facilitation of transmitter release by mGluR5 activation in the presence of high extracellular glutamate. Treatment with the β-lactam antibiotic ceftriaxone increased the expression of glutamate transporter 1 (Glt1) in the dorsal horn after SNI, raised transmitter uptake, and lowered extracellular glutamate. Improving glutamate clearance prevented the facilitation of transmitter release by mGluR5 and attenuated neuropathic pain-like behavior. Balancing glutamate release and uptake after nerve injury should be an important target in the management of chronic neuropathic pain.     

Migrainous disorder and its relation to migraine without aura and migraine with aura. A genetic epidemiological study

Migrainous disorder was analysed in a large population-based study of 4000 forty-year-old males and females. All interviews were conducted by one physician and the diagnostic criteria of the International Headache Society were used. Of the 48 people with migrainous disorder, 40 had migrainous disorder without aura and 9 had migrainous disorder with aura One person had co-occurrence of migrainous disorder with and without aura. The lifetime prevalence of migrainous disorder was 2.5% with a male: female ratio of 1:1.2. The first-degree relatives of probands with migrainous disorder were blindly interviewed. Compared with the general population, first-degree relatives of probands with migrainous disorder without aura had a slightly but less increased risk of migraine without aura than first-degree relatives of probands with migraine without aura. First-degree relatives of probands with migrainous disorder with aura had no increased risk of migraine with aura. We conclude that migrainous disorder without aura in some people is a type of migraine without aura and in other people not. Migrainous disorder with aura may be unrelated to migraine with aura.     

Migraine with aura versus migraine without aura: pain intensity and associated symptom intensities after placebo

OBJECTIVE: To compare the intensity of pain and associated symptoms after placebo administration in patients with migraine with aura and migraine without aura. BACKGROUND: Studies that evaluate drugs used in the acute treatment of migraine ideally should include a placebo arm. The International Headache Society also recommends stratification according to age and sex but not by the presence versus absence of aura. METHODS: The study was conducted as part of a placebo controlled randomized survey comparing four active drugs against placebo in the acute treatment of migraine. Patients were blinded as to treatment received. Placebo consisted of 10 mL of normal saline (0.9%) intravenously. Pain intensity was evaluated by a 10-point analogical-verbal scale. Nausea, photophobia, and phonophobia were evaluated by a four-point analogical-verbal scale. For statistical analysis, unpaired t-test with Welch correction was used. RESULTS: After placebo administration, reduction of symptom intensity (pain, nausea, photophobia, and phonophobia) in patients with migraine without aura was significantly greater than that observed in patients with migraine with aura. CONCLUSIONS: Our findings suggest that studies comparing placebo against an active drug should use stratification according to the presence versus absence of aura.