Posterior cerebral hypoperfusion in migraine without aura

In cerebral blood flow studies, migraine aura is characterized by a posterior cortical hypoperfusion. In contrast, only rare and mild changes in brain perfusion have been demonstrated in migraine without aura, suggesting two different haemodynamic patterns in migraine with and without aura. Our aim was to study hypoperfusion with positron emission tomography (PET) as early as possible during spontaneous migraine without aura attacks. We used H₂¹⁵O PET to investigate seven patients (six female, one male) with migraine without aura (International Classification of Headache Diseases-II code 1.1) in three situations: during the headache phase, after headache relief following sumatriptan injection, and during an attack-free interval. Statistical analysis was performed with SPM2. Within 4 h after the attack onset, significant relative bilateral posterior cortical hypoperfusion was found and persisted after headache relief following sumatriptan injection. A posterior cortical hypoperfusion demonstrated in migraine without aura could suggest a common pathogenesis in migraine with and without aura. The significance of relative posterior hypoperfusion in migraine without aura is discussed according to the current knowledge of migraine pathogenesis.     

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling

BackgroundMigraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine.MethodsThis study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated.ResultsIn comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R.ConclusionsOur results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.     

Abnormal platelet trace amine profiles in migraine with and without aura

Trace amines, including tyramine, octopamine and synephrine, are closely related to classic biogenic amines. In one study, where these substances were found elevated in plasma of migraineurs, it was hypothesized that trace amine metabolism is deranged in migraine. To confirm these findings, we studied, using a multichannel electrochemical high-performance liquid chromatography system, the concentrations of trace amines in platelets of migraine without aura (MoA) and migraine with aura (MA) patients in headache-free period, compared with controls. Platelet concentrations of trace amines, although elevated in both migraine types, showed a different profile in MoA and MA. Octopamine was significantly higher in MoA sufferers (0.69 +/- 0.43 ng/10(8) platelets) compared with both control subjects (0.22 +/- 0.16 ng/10(8) platelets) and MA patients (0.39 +/- 0.37 ng/10(8) platelets). Synephrine was significantly higher in MA patients (0.72 +/- 0.44 ng/10(8) platelets) with respect to both controls (0.33 +/- 0.25 ng/10(8) platelets) and MoA sufferers (0.37 +/- 0.29 ng/10(8) platelets). These results strengthen the hypothesis that tyrosine metabolism is deranged in migraine and may participate in its pathophysiology.     

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.     

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.     

Exaggerated interictal cerebrovascular reactivity but normal blood flow velocities in migraine without aura

Interictal cerebrovascular reactivity and blood flow velocities were tested in 23 patients with migraine without aura and 10 age- and sex-matched healthy controls by using the breath holding index (BHI). The mean systolic, diastolic and mean velocities and pulsatility indices were not different in the controls and patients. The BHI was found to be significantly greater (P=0011) in the patients (1.64 +/- 0.33) compared with the controls (1.26 +/- 0.37), showing an exaggerated reactivity to hypercapnia in migraineurs. Reactivity to pCO2 theoretically depends on pre-existing arteriolar tone and thereby on baseline velocity. Our finding of similar blood flow velocities in controls and patients suggests that the underlying cause for this high reactivity may not be an increased vasotonus but an increased sensitivity to changes in blood CO2 levels.     

Transient visual disturbances during migraine without aura attacks

OBJECTIVE: To evaluate the prevalence and clinical features of transient visual disturbances (TVDs) during migraine without aura (MO) attacks and to point out any similarities with the disturbances listed among the diagnostic criteria of the International Headache Society (IHS) classification for migraine with aura (MA). METHODS: We studied a sample of 191 patients (145 women and 46 men) with MO and no other associated forms of primary headache who had been referred to the University of Parma Headache Centre between December 1, 1999 and December 1, 2000. RESULTS: A total of 165 patients reported that they had never experienced TVDs during their MO attacks. In the remaining 26 patients (19 women and 7 men), MO attacks were at times accompanied by TVDs, which were present in over 30% of MO attacks in 65.4% of patients. In about 60% of cases, TVDs lasted less than half a minute. TVDs consisted of phosphenes in most patients, general blurring of vision in about one-fourth, and scintillating scotomas in 15%. In 73% of cases, TVDs occurred during the headache phase, whereas in the remainder they preceded it. Strict application of the IHS diagnostic criteria would have led to a diagnosis of MA in 12 cases, corresponding to 46% of our MO patients with TVDs and to 6.3% of all patients with an established clinical diagnosis of MO. CONCLUSION: The results of our study suggest that current IHS diagnostic criteria for MA may lead to an overestimation of MA cases.     

The similarities and differences of migraine with aura and migraine without aura: a preliminary study

A preliminary study was undertaken to provide clinical evidence to support the hypothesis that: "Migraine with aura, migraine without aura and aura alone are the same condition, which differ in degree rather than pathophysiology." At the City of London Migraine Clinic, 50 patients consecutively attending the clinic with a past or present history of migraine with aura were questioned. Of the 50 patients questioned 36 (70%) had a combination of migraine with aura, migraine without aura and/or aura alone; i.e. 70% had had more than one type of migraine attack. The duration, severity and frequency of attacks did not differ between migraine with and migraine without aura. Conclusion--the results support the hypothesis that migraine with and migraine without aura, and aura alone are not separate conditions, because: (1) most patients suffer from more than one type of migraine attack; (2) there are no significant differences in the characteristics of the migraine attacks in the different groups; (3) there are no significant differences in the characteristics of the subjects.     

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)     

Family-based analysis of serotonin transporter gene polymorphisms in migraine with and without aura

Genetic epidemiological twin studies have demonstrated a significant heritability for migraine, with > 60% of liability to migraine either with or without aura coming from additive genetic factors. Because of the essential role of serotonin in the pathophysiology and treatment of migraine, genes of the serotonin system are candidates for involvement in migraine. Consequently, we examined two functional VNTR polymorphisms in the serotonin transporter gene, the 5-HTTLPR and the intron 2 VNTR, in a sample of 212 family trios each with a proband with childhood migraine, 153 with migraine without aura (MoA) and 59 with migraine with aura (MA). For the first time, we used transmission disequilibrium test analysis with the program TDTPHASE to examine the transmission of these two markers and their haplotypes to offspring affected by migraine. We found no significant transmission distortion of any marker, with the common L allele of the 5-HTTLPR transmitted 170 times and not transmitted 178 times, and the S allele 130 vs. 122 times. Likewise, the common 12 allele of the intron 2 VNTR was transmitted 201 times and not transmitted 188 times, and the 10 allele 107 vs. 120 times. The markers were not associated with MoA and MA and none of the haplotypes was associated with overall migraine, MoA or MA. The 5-HTTLPR and the intron 2 VNTRs do not play a major role in susceptibility to migraine.     

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.     

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.     

Desialylated transferrin in plasma of patients with migraine without aura

Patients with migraine, without aura (MO), either during or between attacks, present elevated histamine levels in platelet-poor plasma but normal whole blood histamine levels, compared with controls. This finding is usually interpreted as an increased histamine release from basophils due to unidentified histamine-releasing factors. Compared with 10 control plasma samples, each sample from 12 MO patients (5 during and 7 between in attacks) contained normal amounts of iron and immunologically reactive transferrin but decreased transferrin iron-binding capacity. As transferrin inhibits histamine release in vitro, such as functional abnormality, probably due to modifications of the transferrin glycan moiety (desialylated transferrin), may well account for the increased histamine release observed in MO patients. We suggest that glycan-modified transferrin may be related to migraine histamine-releasing factors. Received: 7 August 2000, Accepted in revised form: 22 September 2000     

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.     

Stereotyped topography of different elevated contingent negative variation components in children with migraine without aura points towards a subcortical dysfunction

Increased negativity during contingent negative variation (CNV) is thought to reflect abnormal neural activation in adult migraineurs' attention related processing. Findings in childhood and adolescence have yielded less clear results. This study characterizes the age-dependent development of CNV topography in migraine during childhood in order to elucidate the origin and cerebral generators of described CNV elevations. A large sample of children with primary headache (migraine with/without aura, tension type headache) and healthy controls aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution DC-EEG. Patients were tested for diagnose-related topographic group differences of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation (PINV). All three CNV components of 6-11-year-old migraineurs without aura showed elevated negativity over the supplementary motor area (SMA) and around the vertex. Migraine children lacked age-dependent development of late CNV around Cz as previously reported. However, they showed a normal development of late CNV over pre-/primary motor cortex (MI). There was no marked elevation of iCNV amplitude over frontal areas (orienting reaction) nor specific amplitude elevations over "motor" or "sensory" areas during sustained attention (late CNV). Additional "pre-mature" activation e.g., in the locus coeruleus (leading to diffuse cortical activation summing up to a maximum over the vertex) or the basal ganglia (interacting with SMA) explained the rather stereotyped CNV elevation around the vertex better than a specific implication of the cortical systems responsible for orienting, motor preparation or sensory attention.     

Functional H-MRS findings in migraine patients with and without aura assessed interictally

The present study was aimed at investigating changes in brain metabolites due to visual cortex activation in migraineurs and normal subjects by (1)H-magnetic resonance spectroscopy (MRS). Twenty-two migraine patients with aura, 22 migraine patients without aura, and 10 control subjects were assessed. The volume of interest (about 8 cm(3)) was placed on the visual cortex area and the visual stimulus was applied using MR-compatible goggles with a flashing red light at a frequency of 8 Hz and an intensity of 14 lx. Data were acquired over 36'40". The experimental time course was: baseline phase, from 0 to 3'40" (1 spectrum); on phase (flashing light condition), from 3'40" to 29'20" (1540") (7 spectra), and off phase, from 29'20" to the end of the experiment at 36'40" (2 spectra). The main result of photic stimulation in patients with migraine with aura is the more consistent decrease (-14.61%) of the N-acetylaspartate (NAA) signal, which is significantly greater than that found in migraine patients without aura and control subjects. A parallel slight increase in the lactate peak was also detected. The above findings support little differences in brain metabolites between the two patient groups assessed in interictal periods, which suggests a less efficient mitochondrial functioning in migraine with aura patients.     

Clinical characteristics of migraine in a population-based twin sample: similarities and differences between migraine with and without aura

OBJECTIVE: To look into clinical differences between migraine with and without aura in a population-based sample of migraineurs. BACKGROUND: Migraine presents in two major forms, migraine with and migraine without aura. With the exception of the aura phase, the clinical characteristics of these entities are very similar. Despite this, however, the recent epidemiological data underline differences between migraine with and without aura. We tried to examine whether other features besides the aura differ between these two major forms of migraine. METHODS: We studied 321 twins suffering from migraine with aura and 166 twins with migraine without aura from the population-based Finnish Twin Cohort. Migraine was diagnosed according to the criteria of the International Headache Society (IHS). Analysis was based on the combination of a mailed questionnaire and a telephone interview by a neurologist. Special attention was paid to differences between migraine with and without aura. RESULTS: Some qualities of headaches differed between IHS defined migraine with and without aura. Unilateral headache (Chi-squared p = 0.039) and photophobia (Chi-squared p = 0.010) were more typical for migraine with aura, while nausea was more typical for migraine without aura (Chi-squared p = 0.002). Duration of headache in migraine without aura was also longer than in migraine with aura (Mann-Whitney U-test 0.007). CONCLUSIONS: There are clinical differences between IHS defined migraine with and without aura; even the headache phase between the two entities differs. It is worthwhile distinguishing between them when looking for the elusive genes for these more common forms of migraine.     

MRI观察无先兆偏头痛患者大脑活动异常

目的 以MRI观察无先兆偏头痛(MowA)患者大脑异常活动。方法 前瞻性纳入50例MwoA患者(MwoA组)及46名健康志愿者(对照组),以功能MRI(fMRI)观察其脑区动态局部一致性(dReHo);提取组间dReHo值存在差异脑区,与临床量表行相关性分析。结果 相比对照组,MwoA组双侧距状裂周围皮层、右枕中回dReHo值增高,右颞中回、右额中回、左楔叶dReHo值减低(GRF校正,体素水平P均<0.005,簇水平P均<0.05);权重分析显示,权重绝对值排名前3位脑区分别为右距状裂周围皮层、左楔叶及右枕中回。MwoA患者左距状裂周围皮层dReHo值与抑郁自评量表(SDS)呈负相关(r=-0.28,P=0.04)。结论 MwoA患者视觉信息上行传递通路存在异常,特别是右距状裂周围皮层、左楔叶及右枕中回。     

Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized,double blind,placebo controlled study

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of migraines in Brazil. Some investigators have found it to be a highly effective medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a randomized, placebo controlled, double blind study to assess the effect of dipyrone on the pain and symptoms associated with migraine without aura or with aura and the adverse effect profile of this medication. METHODS: For the migraine without aura group, 44 patients were assigned at random to receive 1 g intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline. For the migraine with aura group, 30 patients received both dipyrone or placebo. We used seven parameters of analgesic evaluation and an analog scale to assess nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is an effective drug for the relief of acute migraine pain and associated symptoms.     

Power spectral analysis of heart rate and diastolic blood pressure variability in migraine with and without aura

Autonomic function in migraineurs during headache-free periods was studied by means of cardiovascular reflexes and power spectral analysis of heart rate and diastolic blood pressure variability. We examined 56 patients: 37 suffering from migraine without aura and 19 from migraine with aura. Cardiovascular responses to the tilt test and Valsalva manoeuvre showed a normal function of the overall baroreceptor reflex arc. Normal heart rate responses to valsalva manoeuvre and deep breathing suggested an intact parasympathetic function. Power spectral analysis of both heart rate and diastolic blood pressure variability in basal conditions and during orthostatic test showed similar sympathovagal interactions modulating cardiovascular control in migraine patients and in controls.