Sex-hormone-related events in migrainous females. A clinical comparative study between migraine with aura and migraine without aura

In this study, the relationship between hormonal-related events and migraine with aura (MA) and without aura (MO) was investigated. Subjects included 268 women suffering from MA (88) and MO (180). Data were collected on the relationship between sex-hormone-related events and migraine. Migraine during menses was observed in a significantly higher percentage of MO than MA patients ( p < 0.03). Menstrual migraine was significantly more common in MO than in MA patients ( p < 0.01). Migraine began during pregnancy in a significantly higher percentage of MA than of MO patients ( p < 0.01). No significant difference was observed between the two groups of patients regarding the onset of migraine at menarche, after menopause, in the postpartum period or during the early cycles of oral contraceptives. Also, both groups of patients showed a similar migraine course during pregnancy, oral contraceptive use and menopause. Eight patients with coexisting migraine with aura and migraine without aura attacks reported the appearance of the aura symptom for the first time in the early cycles of oral contraceptive intake. These findings suggest that gonadal hormone fluctuation may influence both types of migraine.     

Improved description of the migraine aura by a diagnostic aura diary

We present a diagnostic aura diary for prospective recordings of migraine with aura. Three questionnaires are supplemented with sheets for drawings and plottings of visual and sensory auras. Twenty patients recorded 54 attacks of migraine with aura and 2 attacks of migraine aura without headache. The visual and sensory aura were usually gradually progressive, reaching maximum development in 15 and 25 min (median) respectively and had a total duration of 20 and 55 min (median) respectively. Approximately 13% of the attacks had acute onset of visual aura associated with other features more typical of migraine. The visual and sensory auras always preceded typical migraine headache, and headache occurring before aura symptoms was always of the tension type, The migraine headache was milder than in attacks of migraine without aura and often did not have migraine characteristics. In attacks with unilateral head pain, headache and aura symptoms were contralateral in 90% and ipsilateral in 10%.     

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.     

Cytochrome P-450-dependent hydroxylation in migraine

The hypothesis was tested that an acute oxidation deficiency related to potential dietary trigger factors plays a role in the migraine attack. Migraine sufferers (14F and 4M), fulfilling the criteria for migraine with and without aura according to the classification of the International Headache Society, were coadministered oral mephenytoin (100 mg) and debrisoquine (10 mg) during the initial phase of a typical migraine attack. This was repeated during a period without migraine. The hydroxylation of mephenytoin and debrisoquine hydroxylation did not differ during and without the migraine attack. We conclude that hydroxylation, via cytochrome P-450 (2D6, 2C8 and 9), is not reduced during the migraine attack. The results do not support the hypothesis that oxidation deficiency is involved in the pathophysiology of migraine.     

A prospective study of migraine with aura attacks in a headache clinic population

In order to investigate the prevalence of migraine with aura (MA) attacks according to the criteria set by the International Headache Society (IHS) for diagnosis down to the three-digit level of classification, and to determine the recurrence and possible variability of MA attacks over time, we conducted a 6-15-month-long prospective study on 64 MA patients (42 women and 22 men) consecutively referred for the first time to the University of Parma Headache Centre. At the end of the follow-up period, diagnosis was the same as at the first visit for 80.0% of patients, while it was changed for 20.0%. Throughout the duration of the study, the average number of attacks for each patient was 5.3 +/- 6.2 (range 0-30). Attacks of migraine with typical aura were the most frequent (69.1% of patients), but migraine aura without headache (29.1%) and migraine with prolonged aura (20.0%) were also common; by contrast, basilar migraine and migraine with acute onset aura were reported only by one patient in either case. Migraine aura without headache was statistically significantly more frequent in males than in females. Our study results suggest that in most cases the frequency of recurrent MA attacks is relatively low and provide interesting indications about the prevalence of the different MA subtypes listed in the IHS classification, albeit in a headache clinic population.     

Cerebral blood flow velocities are reduced during attacks of unilateral migraine without aura

It has been disputed whether or not large intracranial arteries are dilated during migraine attacks. In order to answer this question the present transcranial Doppler study focused on side-to-side differences of middle cerebral artery blood velocity during unilateral attacks of migraine without aura in 25 patients. Blood velocity in the middle cerebral artery was lower on the headache side (59 cms) than on the non-headache side (65 cms) during the migraine attack. No such difference was found outside of attack (65 cms both sides). The difference (headache side minus non-headache side) was on average −6.1 cms during attack compared to −0.4 cms outside of attack ( p = 0.01). Assuming that rCBF is unchanged during attacks of migraine without aura, our results suggest a 9% increase in middle cerebral artery lumen (cross-sectional area) on the affected side during unilateral attacks of migraine without aura. The findings, however, do not necessarily mean that arterial dilatation is the only or even the most significant cause of pain.     

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.     

Visual field loss after attacks of migraine with aura

Visual fields were mapped with kinetic are perimetry in 23 migraine with aura subjects and, for comparison, in 20 migraine without aura subjects and in 21 non-headache controls. Central vision on the Amsler eye chart and visual perception threshold on a computer task were also investigated. Measures were obtained at least seven days after an episode of migraine. In addition, 10 of the migraine with aura subjects and 10 migraine without aura subjects were studied the day after an attack. The day after migraine with aura, visual sensitivity in the periphery of the visual fields was depressed, central vision was blurred, and visual perception threshold was elevated. These visual disturbances had resolved 7 to 10 days later. With the exception of a minor increase in visual perception threshold, vision was normal after attacks of migraine without aura. Residual effects of the migraine aura could mediate the subclinical visual disturbances which persist for at least one day after attacks of migraine with aura.     

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.     

Depression, migraine with aura and migraine without aura: their familiality and interrelatedness

Migraine is frequently comorbid with depression. There appear to be common aetiological factors for both disorders, but the aetiology of migraine within depressed patients, in particular the significance of aura, has been little studied. A large sample of concordantly depressed sibling pairs [the Depression-Network (DeNT) sample] was assessed as having migraine with aura (MA), migraine without aura (MoA), probable migraine or no migraine according to International Headache Society guidelines. Correlations between siblings' migraine status were used to assess the nature of familial liability to migraine. A multiple threshold isocorrelational model fit best, in which different syndromes are conceptualized as different severities of one underlying dimension rather than as having separate aetiologies. Thus, MA and MoA were found to be different forms of the same disorder, with MA occupying the more extreme end of the spectrum of liability. Implications for our understanding of the relationship between migraine and depression are discussed.     

Evidence for activation of the coagulation system in migraine with aura

Migraine with aura has been shown to be an independent risk factor for stroke. Although the precise mechanism of migraine-related stroke is not known, risk factors for hypercoagulability have been found in migraineurs. Prothrombin factor 1.2 (F1.2) is a cleavage product of prothrombin. Elevated plasma F1.2 has been shown to be a sensitive and a specific marker of ongoing thrombin generation, and thus may serve as an indicator of hypercoagulability. In this study we determined plasma F1.2 levels in 35 patients with migraine (22 with aura and 13 without aura) and in 24 healthy age- and sex-matched volunteers. Elevated F1.2 levels were found in 11 of 22 (50%) patients with migraine with aura (1.25-3.5 nmol/l). None of the patients with migraine without aura nor any of the healthy volunteers had elevated plasma F1.2 levels (normal < 1.1 nmol/l). We conclude that prothrombin F1.2 levels are elevated in a significant number of patients with migraine with aura but not in patients with migraine without aura. This finding suggests that there is activation of the clotting system in certain patients with migraine with aura.     

Changes in functional vasomotor reactivity in migraine with aura

Migraine with aura (MA) is associated with cerebral hyper- and hypoperfusion during and after the attacks. Several attempts to estimate individual perfusion changes and asymmetries in patients with MA using transcranial Doppler (TCD) have not been consistent. In 70 patients with MA and 40 controls with migraine without aura (MoA) or without any history of migraine, interictally recorded TCD sequences were prospectively analysed. Formal curve analysis of the visually evoked flow response (VEFR) was performed semiautomatically. As a main parameter for functional vasomotor reactivity (fVMR), the visually evoked flow rate (VEFR%) was calculated. The VEFR% showed a significantly higher mean difference of 14.7 ± 12% in MA patients vs. 5.8 ± 4.4% ( P  < 0.001) in controls. The significant asymmetry of fVMR in MA patients is suggested to reflect interattack persisting vasomotor changes which are of pathophysiological interest and may be used as a monitoring tool under prophylactic medication.     

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.     

Transient global amnesia occurring as migraine aura

We describe a case of transient global amnesia (TGA) occurring as migraine aura. TGA prevalence is higher among migraineurs and has been ascribed to spreading depression in the hippocampus. Our patient, a 38-year-old physician, developed migraine without aura in early adolescence and from age 20 years, had experienced rare attacks of migraine with aura,. At ages 36 and 38 years, he suffered two attacks of sudden-onset anterograde amnesia, which lasted 5 hours and were immediately followed by unilateral right-sided pounding headaches. Ictal neurological examination was normal except for fixation amnesia. Interictal brain magnetic resonance imaging (MRI) and neurological examination were normal. Thus, in our patient affected with migraine with and without aura, TGA occurred as the aura phase of two migraine attacks. Our case report suggests that TGA shares common mechanisms with migraine. Received: 22 December 1999 / Accepted in revised form: 16 February 2000     

Some clinical comparisons between common and classical migraine: a questionnaire-based study

In a questionnaire-based study we compared the clinical features of migraine with aura (classical migraine) and migraine without aura (common migraine) in 354 and 397 patients, respectively, attending The Princess Margaret Migraine Clinic. Other than those related to the aura, no significant differences were seen in any clinical features of the attack (e.g. frequency or duration of attacks, time of day at onset, location of headache at onset, severity of headache, or nausea and vomiting). Common migraine attacks were significantly more likely to occur at weekends (p = 0.002). Dietary triggers tended to be more troublesome in classical migraineurs while pregnancy and the menstrual cycle affected both migraine types equally. Classical migraine patients were twice as likely to have a history of hypertension (p less than 0.05) and showed a slightly but not significantly greater tendency to depression. Family histories of migraine were similar in each migraine type. We conclude that classical and common migraine are fundamentally similar in their clinical characteristics and that the occurrence of focal neurological symptoms during a migraine attack has little influence on the rest of the attack.     

Prognosis of migraine with aura

The present study is a 16-year follow-up study assessing the long-term outcome of migraine with aura (MA). Additionally possible predictive factors in the prognosis of MA were evaluated. Patients were recruited from the files of Danish headache clinics. A total of 53 patients (11M:42F) with MA (IHS criteria) participated in a follow-up interview. At follow-up attacks had ceased (no MA for 2 years) in 36% of patients. Attacks had ceased in 55% of males and 31% of females (P = 0.17). Attacks had ceased in 41% of patients with visual aura without other aura symptoms and in 25% of those with sensory or aphasic aura besides their visual aura (P = 0.36). Among those with attacks of MA at follow-up frequency of attacks and headache intensity was improved in 44% and 41% of the patients, respectively. The results point to a favourable evolution of MA and suggest possible predictive factors.     

Sumatriptan in the treatment of acute migraine with aura

The efficacy of the selective 5HT1-like agonist sumatriptan in acute treatment of classical migraine (i.e. migraine with aura) was assessed in a double-blind, placebo-controlled, parallel group randomized trial. An oral dose of 200 mg was chosen on the basis of the efficacy rates achieved (70-85%) with 70-280 mg in open studies (1, 2). The dose of 200 mg was also chosen for the study because preliminary data from an oral pilot study indicated that efficacy increased with increasing dose up to 200 mg. Each patient was treated for a maximum of three separate attacks of migraine with aura within a three months' period. Three attacks were treated so that we could examine consistency of response across more than one attack. For attack 1, 200 mg sumatriptan was significantly more effective, safe and well tolerated than placebo at relieving headache 2 h after treatment was given (p = 0.023). In subsequent attacks, i.e. in attacks 2 and 3, there was no such significant effect of sumatriptan compared with placebo in relieving headache. This reduced efficacy of sumatriptan in the second and third attacks may be due to a high incidence of vomiting induced by the high dose of dispersible formulation and also by the bitter taste of the tablets. In addition, there was an increase in placebo response in attacks 2 and 3 compared to the first attack.     

Concepts and mechanisms of migraine chronification

Migraine is a chronic recurrent disorder with episodic manifestations that is progressive in some individuals. Migraine progresses clinically, physiologically, and anatomically. Progression may be a consequence of the mechanisms that generate the migraine attacks (eg, cortical spreading depression) or it may be a function of the activations generated by the attacks (eg, lesions in the periaqueductal gray area), a hypothesis supported by the increase in lesions with attack frequency. Progression may also be partially explained by common genetic or environmental risk factors. Finally, migraine with aura is associated with an elevated Framingham score and with risk factors for cardiovascular disease. Research on this issue is in its infancy and cautions are necessary before extrapolating this information into clinical practice.     

Motor cortex excitability in patients with migraine with aura and hemiplegic migraine

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls (n=17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.     

Leukocyte subsets and cortisol serum levels in patients with migraine without aura and chronic tension-type headache

Leukocyte subsets, serum cortisol and immunoglobulin production were investigated in a group of 12 migraine without aura patients, 12 chronic tension-type headache patients and compared with findings in 12 healthy controls. Chronic tension-type headache patients had statistically significant increased levels of B-lymphocytes (CD19 + cells) ( p < 0.05), while migraine sufferers had a similarly significant decrease in CD8 + T-lymphocytes ( p < 0.05). Migraine patients also had an increased percentage of B-lymphocytes although this failed to reach statistical significance. Immunoglobulin production and cortisol serum levels did not differ in the two headache groups. We conclude that the observed abnormalities in tension-type headache and migraine are unlikely to be a consequence of pain or of hypothalamic-pituitary-adrenal axis dysfunction.