Habituation of visual and intensity dependence of auditory evoked cortical potentials tends to normalize just before and during the migraine attack

Between attacks, migraine with (MO) or without aura (MA) patients show deficient habituation of pattern-reversal visual evoked potentials (PR-VEP) and a strong intensity dependence of auditory evoked cortical potentials (IDAP). Clinical observations of migraine prodromes and previously published electrophysiological studies suggest that cortical information processing may vary in close temporal relationship to the attack. We studied PR-VEP and IDAP just before (11 MO pts), during (23 MO, 3 MA), 1 day following (27 MO, 1 MA) and 2 days following (14 MO) a migraine attack. The results were compared with a large group of MO patients recorded at a distance of at least 3 days from an attack (n = 66 for IDAP; n = 39 for VEP). Patients recorded the day before the attack had on average an habituation of -13.6+/-20.5% (mean +/- SD) between the 5th and 1st block of 100 averaged VEP responses and a flat (0.38+/-1.06 microV/10 dB) amplitude-stimulus intensity function (ASF) slope of the auditory evoked cortical potential. Both values were significantly different from those obtained in the attack interval (P=0.003; P=0.020). During the attack, VEP habituation was less pronounced (-0.17+/-26.2%) and ASF slopes remained flat (0.32+/-1.44 microV/10 dB; P=0.002 compared to interval). During the 2 days following the attack, VEP habituation was replaced by potentiation (+0.09+/-29.1% the 1st day; 19.5+/-45.7% the 2nd day) and ASF slopes increased markedly (0.87+/-1.39 and 1.14+/-1.12 microV/10 dB). The normalization of evoked cortical responses just before and during the attack, might reflect an increase in the cortical preactivation level due to enhanced activity in raphe-cortical serotonergic pathways.     

C-reactive protein in migraine sufferers similar to that of non-migraineurs: the Reykjavik Study

C-reactive protein (CRP), a marker of inflammation, has been associated with cardiovascular disease. Risk of cardiovascular disease is increased in migraineurs with aura. Results from a clinical report, case–control and a cohort study suggest that CRP is elevated in migraineurs compared with non-migraineurs. We examined the proposed association in a case–control study nested within two large population-based studies. The relationship between migraine and CRP (high-sensitivity CRP) was studied in 5906 men and women aged 55.0 ± 8.5 years in the Reykjavik Study and 1345 men and women aged 27.7 ± 5.5 years from the Reykjavik Study for the Young. A modified version of the International Headache Society's criteria was used to categorize people into migraineurs (two or more symptoms) or non-migraineurs. Migraineurs with visual or sensory symptoms were further defined as having migraine with aura (MA) or without aura (MO). Multivariable-adjusted CRP levels were similar in migraineurs and non-migraineurs for men (0.83 vs. 0.79 mg/l, P  = 0.44) and for women (0.87 vs. 0.87 mg/l, P  = 0.90). When further stratified by migraine aura and age, no differences were found between non-migraineurs, MO and MA among men. In women, CRP levels were borderline higher in those with MO compared with non-migraineurs and those with MA (1.01 mg/l vs. 0.81 and 0.75 mg/l, P  = 0.08 and P  = 0.08) in age group 19–34 years, but significantly lower in age group 60–81 years (0.52 mg/l vs. 1.07 and 1.01 mg/l, P  = 0.007 and P  = 0.03). CRP levels were not increased among migraine sufferers compared with non-migraineurs. Older women migraineurs without aura had lower CRP values than non-migraineurs and migraineurs with aura.     

Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypofunctioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.     

Interictal potentiation of passive "oddball" auditory event-related potentials in migraine

We have studied habituation of the P3a component of the passive "oddball" auditory event-related potential which reflects automatic processing of a "novel" stimulus in 24 patients suffering from migraine without aura and in 21 healthy volunteers. Three blocks of responses to 160 standard and to 40 novel tones were sequentially averaged at Cz and analyzed for latencies and peak-to-peak amplitudes. Latencies of components N1 and P2 elicited by standard tones and of components N1, P2, N2, and P3a elicited by novel tones were not significantly different between sequential blocks or between subject groups, nor were mean N1-P2 amplitudes. The N2-P3a amplitude tended to be lower in migraine, but not significantly so. The most striking result in migraineurs was a significant potentiation of N2-P3a in successive blocks, contrasting with an habituation in controls. Our previous evoked- and event-related potential studies and the present one suggest that deficient habituation, or even potentiation, represents interictally a fundamental dysfunction of cortical information processing in migraine, which might increase energy demands and play a role in etiopathogenesis.     

Nociceptive blink reflex and visual evoked potential habituations are correlated in migraine

BACKGROUND: Lack of habituation, as reported in migraine patients between attacks for evoked cortical responses, was also recently found for the nociceptive blink reflex (nBR) mediated by brainstem neurons. It is not known if both brain stem and cortical habituation deficits are correlated in the same patient, which would favor a common underlying mechanism. OBJECTIVE: To search for intraindividual correlations between habituation of pattern reversal-visual evoked potentials and that of the nociception-specific blink reflex in migraineurs and in healthy volunteers (HV). METHODS: We recorded 15 HV and 15 migraine without aura patients between attacks. Habituation for visual evoked potentials was measured by comparing the N1-P1 amplitude change (%) between the first and sixth block of 100 sequential averaged responses. Habituation for the nBR was defined as the percentage change of the R2 response area between the 1st and 10th block of five averaged EMG responses, elicited by stimulating the right side every 2 minutes for 32 minutes. We also calculated the slope of N1-P1 amplitude and R2 response area changes from the first to the last response and the correlation with attack frequency. RESULTS: A significant habituation deficit in both cortical and brain stem evoked activity characterized on average the group of migraineurs compared to controls. In migraine patients, but not in HV, we found a significant positive correlation between habituation of pattern reversal-visual evoked potentials and that of the nociception-specific blink reflex both for the degree of habituation between first and last blocks of averagings (r = 0.703; P = .003) and for the habituation slope (r = 0.751; P = .001). Moreover, nBR habituation was positively correlated with attack frequency (r = 0.548; P = .034). CONCLUSION: The positive correlation between visual evoked potential and nBR habituations is consistent with the idea that in migraine the same neurobiological dysfunction might be responsible for the habituation deficit both in cortex and brain stem. As nBR habituation increases with attack frequency, its interictal deficit is unlikely to be due to trigeminal sensitization.     

Effects of fluoxetine on habituation of pattern reversal visually evoked potentials in migraine prophylaxis

OBJECTIVE: To investigate the effects of fluoxetine in migraine prophylaxis on habituation of visually evoked potentials. BACKGROUND: Habituation of pattern reversal visually evoked potentials was found to be abnormal in migraine between attack, and this abnormality was most likely due to serotonergic pathway dysfunction in the brain stem. METHODS: One hundred nineteen subjects were included in the study: 40 healthy volunteers and 79 migraineurs not taking any prophylactic migraine medication (44 without aura and 35 with aura). Visually evoked potentials in migraineurs were recorded in the headache-free interval. Amplitude change of the visually evoked potentials (N1-P1) was measured between the first and fifth block of 50 sequential averagings during continuous stimulation at 3.1 Hz. All migraineurs were placed on fluoxetine 20 mg/day for prophylaxis of migraine. One month later, visually evoked potentials were recorded again. RESULTS: Mean amplitude changes in the fifth block expressed as percentages of the first block were -13.4% +/- 19.2% in healthy volunteers, 9.8% +/- 23.3% in migraine without aura, and 4.4% +/- 8.7% in migraine with aura during the baseline period. The difference was significant between migraineurs and healthy volunteers (both P= 0.0001), but not between migraineur groups. After treatment, amplitude changes were -9.3% +/- 14.5% in migraine without aura and -10.1% +/- 11.5% in migraine with aura. Habituation pattern tended to normalize with prophylactic treatment, and mean amplitude changes were not significant between migraineurs and healthy volunteers (both P = 0.4). CONCLUSIONS: We concluded that the fluoxetine prophylaxis corrects the interictal deficit of habituation in migraineurs.     

Maturation of early visual processing investigated by a pattern-reversal habituation paradigm is altered in migraine

Evidence for a disturbed maturation of information processing in migraine came recently from evoked and event-related potential studies during childhood. In adult migraineurs, deficient habituation is proposed as principal interictal abnormality and was found inter alia for Visual Evoked Potentials (VEPs). This study investigated response and habituation to pattern-reversal VEPs and its maturation in 102 children with primary headache (migraine with and without aura, tension-type headache) and 79 healthy controls from 6 to 18 years. A reduction of N180 latency from pre- to postpubertal age reflects maturation and was clearly present in controls but lessened in migraineurs. N180 latency was prolonged in migraineurs without aura from 12 years onwards. Habituation did not differ between groups. In conclusion, diminished N180 latency reduction with age in migraineurs gives further evidence that maturation of visual information processing is altered in migraine. Deficient habituation to pattern-reversal VEPs could not be confirmed during childhood migraine.     

Is increased amplitude of contingent negative variation in migraine due to cortical hyperactivity or to reduced habituation?

The aim of this study was to compare the habituation kinetics of contingent negative variation (CNV) between 12 migraineurs without aura and matched healthy controls. CNV was studied with a 3 sec interval between the warning stimulus (WS) and the imperative stimulus (IS). The data from (a) the total interval (WS-IS), (b) early component, and (c) late component were analyzed. During successive trials the habituation kinetics were determined using regression analysis. On CNV averaged over 32 trials, migraine patients had a significantly higher negativity in the total interval compared to controls. When sequential blocks of four trials were analyzed, the most significant finding in migraineurs was lack of habituation of the early CNV component. The present study indicates that a delayed habituation, rather than a general increased cortical activity, is responsible for the CNV abnormalities in migraine without aura. We suggest that migraineurs between attacks not only have a cortical hyperexcitability, but also a lack of cortical inhibition causing delayed habituation.     

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.     

The vestibulo-collic reflex is abnormal in migraine

Interictal evoked central nervous system responses are characterized in migraineurs by a deficit of habituation, at both cortical and subcortical levels. The click-evoked vestibulo-collic reflex (VCR) allows the assessment of otolith function and an oligosynaptic pathway linking receptors in the saccular macula to motoneurons of neck muscles. Three blocks of 75 averaged responses to monaural 95-dB normal hearing level 3-Hz clicks were recorded over the contracted ipsilateral sternocleidomastoid muscle in 25 migraineurs between attacks and 20 healthy subjects, without vestibular symptoms. Amplitudes, raw and corrected for baseline electromyography, were significantly smaller in migraine patients. Whereas in healthy volunteers the VCR habituated during stimulus repetition (-4.96% +/- 14.3), potentiation was found in migraineurs (4.34% +/- 15.3; P = 0.04). The combination with a reduced mean amplitude does not favour vestibular hyperexcitability as an explanation for the habituation deficit in migraine, but rather an abnormal processing of repeated stimuli in the reflex circuit.     

Search for correlations between genotypes and electrophysiological patterns in migraine: the MTHFR C677T polymorphism and visual evoked potentials

Interictally, migraineurs have on average a reduction in habituation of pattern-reversal visual evoked potentials (PR-VEP) and in mitochondrial energy reserve. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and its C677T polymorphism may be more prevalent in migraine. The aim of this study was to search in migraineurs for a correlation between the MTHFR C677T polymorphism and the PR-VEP profile. PR-VEP were recorded in 52 genotyped migraine patients: 40 female, 24 without (MoA), 28 with aura (MA). Among them 21 had a normal genotype (CC), 18 were heterozygous (CT) and 13 homozygous (TT) for the MTHFR C677T polymorphism. Mean PR-VEP N1-P1 amplitude was significantly lower in CT compared with CC, and tended to be lower in TT with increasing age. The habituation deficit was significantly greater in CC compared with TT subjects. The correlation between the cortical preactivation level, as reflected by the VEP amplitude in the first block of averages, and habituation was stronger in CC than in CT or TT. The MTHFR C677T polymorphism could thus have an ambiguous role in migraine. On one hand, the better VEP habituation which is associated with its homozygosity, and possibly mediated by homocysteine derivatives increasing serotoninergic transmission, may protect the brain against overstimulation. On the other hand, MTHFR C677T homozygosity is linked to a reduction of grand average VEP amplitude with illness duration, which has been attributed to brain damage.     

Visual, long-latency auditory and brainstem auditory evoked potentials in migraine: relation to pattern size, stimulus intensity, sound and light discomfort thresholds and pre-attack state

We aimed to estimate primary sensory evoked potential (EP) amplitude, amplitude-intensity functions and habituation in migraine patients compared with healthy control subjects and to investigate the possible relation to check size, sound and light discomfort thresholds, and the time to the next attack. Amplitudes of cortical visual evoked potentials (VEP, check size 8' and 33'), cortical long latency auditory evoked potential (AEP NIP1; 40, 55 and 70 dB SL tones) and brainstem auditory evoked potential (BAEP wave IV-V; 40, 55 and 65 dB SL clicks) were recorded and analysed in a blind and balanced design. The difference between the response to the first and the second half of the stimulus sequence was used as a measure of habituation. Twenty-one migraine patients (16 women and five men, mean age 39.3 years, six with aura, 15 without aura) and 22 sex- and age-matched healthy control subjects were studied (18 women and four men, mean age 39.5 years). Low sound discomfort threshold correlated significantly with low levels of BAEP wave IV-V amplitude habituation (r = -0.30, P = 0.05). VEP an AEP amplitudes, habituation, and amplitude-intensity function (ASF) slopes did not differ between groups when ANOVA main factors were considered. Control group VEP habituation was found for small check stimuli (P = 0.04), while potentiation was observed for medium sized checks (P = 0.02). The eight migraine patients who experienced headache within 24 h after the test tended to have increased BAEP wave IV-V ASF slopes (P = 0.08). This subgroup did also have a significant VEP habituation to small checks (P = 0.04). No correlation was found between different modalities. These results suggest that: (i) VEP habituation/potentiation state and brainstem activatio state may depend on the attack-interval cycle in migraine; (ii) VEP habituation/ potentiation may depend on spatial stimulus frequency; (iii) phonophobia (and possibly photophobia) may depend more on subcortical (brainstem) function than on cortical mechanisms; (iv) low cortical preactivation in migraine could not be confirmed; (v) EP habituation and ASF analysis may reflect sensory modality-specific, not generalized, central nervous system states in migraine and healthy control subjects.     

Abnormalities of the vestibulo-collic reflex are similar in migraineurs with and without vertigo

The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR) was found reduced between attacks in migraineurs without complaints of ictal or interictal vertigo or dizziness, compared with healthy subjects. As a next step we recorded VCR in 17 migraine patients (eight with migraine without aura and nine with migraine with aura) who presented ictal migrainous vertigo according to the criteria defined by Neuhauser et al., using a method described previously. Migraineurs with migrainous vertigo have similar VCR abnormalities as patients without vertigo, i.e. a decreased global amplitude and absence of habituation. Potentiation seemed more pronounced in migraineurs with vertigo (7.46 ± 18.6), but the difference was not significant.     

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5 Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5 Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5 Hz-rTMS in the three groups tested. The 5 Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5 Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.     

Performances in cerebellar and neuromuscular transmission tests are correlated in migraine with aura

In previous studies, we described subclinical abnormalities of neuromuscular transmission and cerebellar functions in migraineurs. The aim of this study was to search if these two functions are correlated in the same patient. Thirteen migraineurs [five without aura (MO) and eight with aura (MA)] underwent both stimulation-SFEMG and 3D-movement analysis. Single fiber EMG (SFEMG) results were expressed as the “mean value of consecutive differences” (mean MCD). Precision of arm-reaching movements (measured with an infrared optoelectronic tracking system) was expressed as the average deviation in the horizontal plane. Median values of mean MCD and mean horizontal deviation were not different between MO and MA. However, in MA, but not in MO, both variables were positively correlated. Thus, we conclude that neuromuscular transmission and cerebellar functions are correlated in the same patient when affected by migraine with aura. We suggest that this correlation might be due to a common molecular abnormality.     

Is migraine associated with right-to-left shunt a separate disease? Results of the SAM study

Migraine with aura (MA) is associated with the persistence of patent foramen ovale (PFO) in about 50% of cases, and migraineurs tend to have larger shunts than controls, suggesting that right-to-left shunt (RILES) determined by PFO could play a role in triggering migraine attacks. Moreover, some preliminary reports have suggested that PFO closure may give relief to both migraine and aura attacks. The aim of this study was to clarify if shunt-associated migraine (SAM) has clinical features that allow a distinction from shunt-unrelated migraine (SUM), in a prospective, multicentre, observational study (SAM study). We enrolled consecutive MA patients, who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. All were systematically screened for RILES with transcranial Doppler, and for coagulation disorders. Overall, 460 patients were included; the SUM and SAM classes comprised 58% and 42% of patients, respectively. SAM patients were significantly younger (34.1 ± 10 vs. 37.1 ± 11 years), had a more frequent family history of migraine (76% vs. 66%) and a higher frequency of sensory symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of SAM with other cardiac abnormalities and with coagulation disorders. The SAM study suggests that the effect of RILES on migraine features is not relevant. The higher family history of migraine in SAM suggests a possible genetic linkage between migraine and RILES.     

Personality and response to repeated visual stimulation in migraine and tension-type headaches

Migraine sufferers potentiate their visual evoked potentials (VEPs) from a short period of 2 min to a longer period of 15 min. As a lack of habituation is linked to higher level arousal, we thus hypothesized that short-term VEP potentiation might he correlated with an arousal-related personality trait. We therefore carried out short-term VFPs, Plutchik-van Praag's Depression Inventory, Zuckerman's Sensation-Seeking Scales (Form V), and Zuckerman- Kuhlman's Personality Questionnaire in 26 healthy subjects, 22 patients suffering from migraine without aura between attacks, 13 episodic and 20 chronic tension-type headaches. The chronic tension-type headache sufferers showed increased depression compared with other groups, which might be a consequence of the headache itself. Migraines, however, showed steeper habituation slopes of N1-P1 and P1-N2, decreased thrill and adventure-seeking, and general sensation-seeking than healthy controls; in addition, the habituation slope of P1-N2 was positively correlated with experience-seeking in migraine. The short-term VEP potentiation and the decreased thrill and adventure-seeking and general sensation-seeking in migraine might be related to a high level of cortical arousal and a low 5HT neurotransmission. In compliance with the long-term VEP study, the positive correlation between the P1-N2 habituation slope and experience-seeking in migraine suggests a continuous metabolic overload for the brain interictally, which can trigger the activation of a migraine attack.     

Influence of MTHFR genotype on contingent negative variation and MRI abnormalities in migraine

BACKGROUND: The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper-homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke. OBJECTIVE: The first aim of the present study was to examine the Contingent Negative Variation (CNV) amplitude and habituation pattern in a migraine sample versus non-migraine subjects, at the light of the MTHFR genotype, according to an unrelated and clinical based case-control panel. The second aim was to compare the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions across the different C677 genotypes in the same migraine sample, selected for the young age and the absence of any cardiovascular risk factor. METHODS: One hundred and five 18-45 year old out-patients, 90 affected by migraine without aura (MO) and 15 by MA, and 97 non-migraine healthy subjects, age and sex matched, were selected for the genetic analysis. All subjects had a common ethnic origin from Puglia. Sixty-four migraine subjects and 33 control subjects were submitted to the recording of the CNV. All migraine subjects underwent the MRI evaluation. RESULTS: The frequency of homozygosis was 14.33% in normal subjects, versus 25.7% in MA + MO group (chi2-test: 10.80 P= .001). The frequency of homozygosis in MO patients, was 25.5% (MA versus N: chi2-test: 9 P= .003), in MA group it was 26.6%. Considering the MTHFR genotype in migraine patients and controls, the C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in respect with both C677TC and C677CC; in the migraine group, there was a significant decrease of CNV habituation in patients with homozygosis and a positive correlation between the habituation index values and the homocysteine levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): patients with C677T homozygosis did not exhibit a higher risk for MRI abnormalities. CONCLUSIONS: This unrelated and clinical based case-control study showed that genetically induced hyper-homocysteinemia may favor the neuronal factors predisposing to migraine, while it does not influence the presence of subclinical vascular brain lesions probably linked with increased risk of stroke.     

Lack of cold pressor test-induced effect on visual-evoked potentials in migraine

In patients with migraine, the various sensory stimulation modalities, including visual stimuli, invariably fail to elicit the normal response habituation. Whether this lack of habituation depends on abnormal activity in the sub-cortical structures responsible for processing incoming information as well as nociception and antinociception or on abnormal cortical excitability per se remains debateable. To find out whether inducing tonic pain in the hand by cold pressure test (CPT) alters the lack of visual-evoked potential (VEP) habituation in migraineurs without aura studied between attacks we recorded VEPs in 19 healthy subjects and in 12 migraine patients during four experimental conditions: baseline; no-pain (hand held in warm water, 25°C); pain (hand held in cold water, 2–4°C); and after-effects. We measured P100 amplitudes from six blocks of 100 sweeps, and assessed habituation from amplitude changes between the six sequential blocks. In healthy subjects, the CPT decreased block 1 VEP amplitude and abolished the normal VEP habituation (amplitude decrease to repeated stimulation) in patients with migraine studied between attacks; it left block 1 VEP amplitude and abnormal VEP habituation unchanged. These findings suggest that the interictal cortical dysfunction induced by migraine prevents the cortical changes induced by tonic painful stimulation both during pain and after pain ends. Because such cortical changes presumably reflect plasticity mechanisms in the stimulated cortex, our study suggests altered plasticity of sensory cortices in migraine. Whether this abnormality reflects abnormal functional activity in the subcortical structures subserving tonic pain activation remains conjectural.     

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.