Autonomic Nervous System Function in Migraine Without Aura

Autonomic nervous system functions were studied in 13 females with migraine without aura during headache-free intervals, using physiological, pharmacological and biochemical methods. Heart-rate in the resting condition and blood pressure rises in the cold-face and isometric handgrip tests were higher than in controls. Normal cardiovascular responses to the Valsalva manoeuvre and to noradrenaline infusion suggest that the baroreflex arc is intact. Normal heart rate responses to the Valsalva manoeuvre, to the cold-face test and to deep breathing confirmed a normal cardiac parasympathetic function. Clonidine infusion showed a sedative and depressor effect and an inhibition of plasma NA similar to those occurring in controls, suggesting a normal central sympathetic tone. As a whole, the physiological, pharmacological and biochemical tests were consistent with a non-specific sympathetic hyperactivity, but do not confirm any impairment of the autonomic control of the cardiovascular system in migraine patients in headache-free intervals.     

Migraine without aura and migraine with aura are distinct clinical entities: a study of four hundred and eighty-four male and female migraineurs from the general population

The clinical characteristics of migraine without aura (MO) and migraine with aura (MA) were compared in 484 migraineurs from the general population. We used the criteria of the International Headache Society. The lifetime prevalence of MO was 14.7% with a M:F ratio of 1:2.2; that of MA was 7.9% with a M:F ratio of 1:1.5. The female preponderance was significant in both MO and MA. The female preponderance was present in all age groups in MA, but was first apparent after menarche in MO, suggesting that female hormones are an initiating factor in MO, but not likely so in MA. The age at onset of MO followed a normal distribution, whereas the age at onset of MA was bimodally distributed, which could be explained by a composition of two normal distributions. The estimated separation between the two groups of MA was at age 26 years among the females and age 31 years among the males. The observed number of persons with co-occurrence of MO and MA was not significantly different from the expected number. The specificity and importance of premonitory symptoms are questioned, but prospective studies are needed. Bright light was a precipitating factor in MA, but not in MO. Menstruation was a precipitating factor in MO, but not likely in MA. Both MO and MA improved during pregnancy. The clinical differences indicate that MO and MA are distinct entities.     

A report of cranial autonomic symptoms in migraineurs

The presence of cranial autonomic symptoms in migraine is well known and thought to represent activation of the trigeminal parasympathetic reflex pathway similar to trigeminal autonomic cephalalgias. However, studies regarding the prevalence of these symptoms are few. The characteristics of migraineurs with cranial autonomic symptoms and the association of cranial autonomic symptoms with laterality of headache have never been studied in a clinic population. Seventy-eight consecutive subjects with migraine were recruited from the Headache Clinic of the Department of Psychiatry after exclusion of subjects with secondary headache. Their demographic data and detailed history of headache were noted and leading questions were asked regarding cranial autonomic symptoms. chi(2) test and Fisher's exact test was used for categorical variables, whereas an independent sample t-test was applied on numerical data. Spearman's correlation was used for correlational analysis of categorical variables. Female subjects (78.2%) outnumbered males and the average duration of illness in the whole sample was 3.81 years. Migraine without aura (53.8%) was the commonest diagnosis, followed by migraine with aura (24.4%). Cranial autonomic symptoms were present in 73.1% of subjects and, commonly, they were ipsilateral to headache. Moreover, strictly unilateral cranial autonomic symptoms were reported by only 32% of patients. The anatomical side of headache did not affect the presence of autonomic symptoms. Those with or without autonomic symptoms did not differ with respect to gender, diagnosis, laterality of headache or associated symptoms except phonophobia, which was more common in subjects with autonomic symptoms (P = 0.05). Those with autonomic symptoms had longer duration of illness (P = 0.03) and longer headache episodes (P = 0.04). In addition, sleep was ineffective in relieving their headache (P = 0.02). Cranial autonomic symptoms are frequent in migraineurs and are common in subjects with long duration of illness and longer headache episodes. Clinical evidence in the present study suggests that subjects with cranial autonomic symptoms have a hyperactive efferent arm of trigeminal autonomic reflex. The connections of trigeminal nucleus with the locus coeruleus and dorsal raphe nucleus may account for the observed phenotypic differences between the two groups. Further research, however, is required to elucidate the underlying neural mechanisms of cranial autonomic symptoms in migraine.     

Consecutive transcranial magnetic stimulation: phosphene thresholds in migraineurs and controls

OBJECTIVE: To characterize the temporal course of transcranial magnetic stimulation-induced phosphene thresholds in subjects with migraine and in controls. METHODS: Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study. RESULTS: Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P <.001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P <.10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold. CONCLUSIONS: Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold.     

Migraine‐Like Headache With Autonomic Symptoms in Midbrain Malformation

We report a case of midbrain malformation characterized by right deviation of the medulla oblongata associated with elongation and ectasia of the basilar and left vertebral arteries in a patient with a long history of migraine‐like headache with autonomic symptoms.     

Autonomic Function Testing in Patients with Migraine

SYNOPSIS
Autonomic nervous system function was studied in 62 patients with migraine. The Valsalva maneuver, deep breathing test, sustained handgrip test, orthostatic test and spectral analysis of heart rate variability in the supine and standing positions were performed in a group of 62 patients of both sexes, aged 21 to 50 years, and in an age-matched control group of 45 healthy volunteers.
Heart rate increase during sustained handgrip was significantly reduced in the headache group, when compared to the control group, while the results of the remaining cardiovascular tests did not significantly differ between the control and headache groups. In standing patients, the integrals of middle frequency bands of amplitude spectra were smaller in patients than in controls because the increase induced by standing was smaller in migraine patients. The results in patients with migraine with aura (21 patients) and migraine without aura (41 patients) did not differ significantly from each other. The same was true for the results of the female and male patients.
It is concluded that sympathetic function is impaired in migraine patients.     

MTHFR T677 homozygosis influences the presence of aura in migraineurs

It has been suggested that folate metabolism could be involved in migraine pathogenesis. We analysed the 5',10'-methylenetetrahydrofolate reductase (MTHFR) genotypic distribution in a large migraine sample. We genotyped 230 migraine patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 nonheadache controls. The incidence of TT homozygosis for migraine in general (12%), MO (9%) and MA (18%) did not significantly differ from that found in healthy controls (13%). Differences were significant when the frequency of TT homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was compared. There was a tendency for a higher frequency of the MTHFR T allele in the MA group (42%) as compared to MO (29%) and controls (36%). These differences were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI = 1.15-2.65). These results could indicate that the MTHFR C677T polymorphism, causing mild hyperhomocystinaemia, might be a genetic risk factor for experiencing aura among migraineurs. Overall, however, there was no association between migraine and the C677T MTHFR polymorphism.     

Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks

Subjects with migraine are at increased risk of subcortical white matter lesions (WML). Reports of cognitive testing in adults with migraine have yielded inconsistent results. We performed a cross-sectional study to assess whether migraine without aura (MwA) is associated with impairment in executive functioning, a typical cognitive correlate of subcortical WML. Forty-five subjects with MwA and 90 controls, matched for age and education, underwent a cognitive battery of tests evaluating executive functions. The following migraine characteristics were collected: age at onset and length of migraine history, and frequency, duration and intensity of attacks. Subjects with MwA performed significantly lower than controls in tests evaluating complex, multifactorial executive functions. After multiple adjustments, the duration and intensity of migraine attacks significantly predicted cognitive disturbances. In the interictal phase of MwA there is evidence of mild executive dysfunction. The cumulative effects of repeated migraine attacks on prefronto-cerebellar loop probably account for our results.     

Evidence for Instability of the Autonomic Nervous System in Patients With Migraine Headache

Autonomic impairment in migraine is well documented. In order to evaluate the autonomic control in migraine, spectral analysis of heart rate fluctuations was performed on ten migraine patients, drug-free and during the inter-headache phase. They were compared to nine healthy controls and eight tension headache patients. A 24h Holter recording of ECG was performed for each subject. Every half hour, a short ECG subtrace was digitized and submitted to R wave detection, followed by computation of heart rate power spectrum. The spectral analysis of heart rate fluctuations disclosed significant differences between control subjects and patients with migraine. The migraine patients displayed markedly enhanced low frequency fluctuations (below 0.1 sec-1), during day hours (p less than 0.01) and especially at night (p less than 0.0006). In the respiratory frequency band (between 0.2 and 0.4 sec-1) no significant change was observed. Tension headache patients however, resembled the controls in that they did not display enhanced low frequency fluctuations. The enhancement at low frequencies fluctuations only, a frequency range known to be related to vasomotor control, suggests that the migraine patients are characterized by a clear sympathetic instability. This finding supports the hypothesis that migraine is of neural origin and is consistent with the observation of large variations in regional cerebral flow. Spectral analysis of heart rate fluctuations allows us to specify and quantitate this autonomic imbalance and may provide a useful tool for the evaluation of drug therapy in migraine.     

Persistent and Repetitive Visual Disturbances in Migraine: A Review

Visual disturbances in migraineurs, such as visual aura, are typically episodic, that is, associated with the headache attack, and overlaid by head pain and other symptoms that impact the patient. In some patients, however, visual symptoms are dominant due to frequency (migraine aura status), duration (persistent migraine aura and other persistent positive visual phenomena), or complexity (visual snow syndrome). These syndromes are more rare and challenging to classify in clinical practice resulting in a lack of systematic studies on pathophysiology and treatment. We aim at describing clinical features and pathophysiological concepts of typical migraine aura with a focus on cortical spreading depression and differentiation from non‐typical migraine aura. Additionally, we discuss nomenclature and the specifics of migraine aura status, persistent migraine aura, persistent positive visual phenomena, visual snow, and other migrainous visual disturbances. The term migraine with prolonged aura might be a useful bridge between typical aura and persistent aura. Further studies would be necessary to assess whether a return of the classification category eventually helps diagnosing or treating patients more effectively. A practical approach is presented to help the treating physician to assign the correct diagnosis and to choose a medication for treatment that has been successful in case reports of these rare but disabling conditions.     

Sympathetic skin response in migraineurs and patients with medication overuse headache

BACKGROUND: Autonomic dysfunction has been reported in patients with migraine, and it may play a role in promoting attacks. OBJECTIVE: To investigate changes in the autonomic function of migraineurs and patients with medication overuse headache via sympathetic skin response, and to determine whether psychiatric comorbidity is related to any changes recorded. METHODS: A consecutive series of patients with migraine (n = 45) and medication overuse headache (n = 53) were studied. Patients with other chronic diseases requiring medication were excluded. Sympathetic skin response latencies and amplitudes from the patients with headache (N = 98) and 40 healthy controls were compared statistically. RESULTS: Sympathetic skin response latencies in patients with medication overuse headache and in migraineurs were significantly longer than in controls. To analyze the effect of psychiatric comorbidity, patients with medication overuse headache and migraineurs were each divided into 2 groups: those with psychiatric comorbidity and those without comorbidity. When the sympathetic skin response results of these 4 groups were compared with controls, the only statistically significant difference was between the sympathetic skin response latencies of controls and the latencies of patients with psychiatric comorbidity. We could not find any difference between the results from patients without psychiatric comorbidity and those of controls. CONCLUSION: Psychiatric disease may affect the results of autonomic function testing in migraineurs and patients with medication overuse headache. Consideration should be given to excluding patients with psychiatric comorbidity from studies investigating autonomic dysfunction in patients with headache.     

Migraine with prolonged aura

We present the case of a 29-year-old man with a long history of migraine with aura, in whom migraine with prolonged aura was induced after the sudden withdrawal of prophylactic therapy.     

Characteristics of Migraine Visual Aura

Visual auras (VAs) of 100 patients with migraine with aura were studied by questionnaire. Visual auras accompanied the patients' first headache (HA) in 39% of patients. Only 19% had VAs with every attack. Patients with VAs over the entire HA history had a high frequency (greater than 50%) of attacks with VA; patients with VA during only part of the HA history had a low frequency (less than 50%} of attacks with VA. The auras occurred exclusively prior to the HA in 57%. The free interval between the end of the VA and the start of the HA was usually (75%) shorter than 30 minutes. Most (59%) patients had VAs that lasted from 1 to 30 minutes. They started in the periphery of the visual fields in 56%. The most common phenomena described were: small bright dots (42%), flashes of light (39%), "blind spots" (32%), and "foggy vision" (27%). Fortification spectra was reported by only 20%. Although most (65%) patients had a combination of phenomena, the majority (72%) had only one uniform constellation of manifestations. There was no clear-cut relationship between side of VA and side of HA.
Migraine VA is a pleomorphic and complex symptom. Many patients not qualifying for the diagnostic criteria of migraine with aura, as proposed by the International Headache Society (IHS) unequivocally present with visual phenomena that strongly suggest this diagnosis.     

Red blood cell magnesium levels in migraine patients

In the last few years, it has been suggested that magnesium plays a central role in establishing a threshold for migraine attacks and in intervening with the pathogenetic mechanisms involved in their onset. Accordingly, we determined red blood cell magnesium levels in adult migraine patients with and without aura interictally and in some of them also ictally. In comparison with normal subjects, migraineurs with and without aura had significantly lower red blood cell magnesium levels in the interictal period. Ictal red blood cell magnesium levels did not differ from the interictal values. Low red blood cell magnesium levels could be a peripheral expression of the reduced brain magnesium concentration observed in migraine patients.