Lack of age-dependent development of the contingent negative variation (CNV) in migraine children?

Increased negativity of contingent negative variation (CNV) in adult migraineurs is thought to reflect cortical hyperexcitability. CNV amplitude changes with age in healthy adults. Recently, evidence emerged that this might not be the case for migraineurs. Our study investigates age-dependency of CNV during childhood age. Seventy-six healthy controls and 61 children with migraine without aura (IHS code 1.1) between 6 and 18 years were examined using an acoustic S1-S2-CNV-paradigm with a 3-s inter-stimulus interval. The amplitude of the late component of CNV, as well as total CNV at the vertex (Cz according to the international 10-20 system), were significantly higher in migraineurs without aura than in controls. Healthy controls showed increasing amplitudes of CNV with age, whereas in migraine children without aura amplitudes did not change. Thus group differences were reduced during adolescence. Increased CNV negativity might reflect a biological vulnerability to migraine, rather than being a result of chronification. Migraineurs seem to lack age-dependent development of CNV also during early age, which supports the hypothesis of migraine as a maturation disorder.     

Longitudinal assessment of response preparation and evaluation in migraine gives evidence for deviant maturation

Evidence for deviant maturation of sensory processing in migraine has come recently from cross-sectional studies during childhood. Age-dependent development of response preparation and evaluation is characterized using a longitudinal design in school-aged migraine patients and controls in order to challenge the hypothesis of migraine as a maturation disorder. Forty-six children with migraine and 57 healthy controls aged 6–18 years were investigated and followed up 4 years later using a simple acoustic contingent negative variation (CNV) paradigm. Maturation in controls was characterized by increasing negativity of late and total CNV and stability of initial CNV (iCNV) and the motor postimperative negative variation (mPINV). Migraine patients showed a lack of development for late and total CNV and decreasing iCNV and mPINV negativity. This first longitudinal study confirms cross-sectional results of deviant CNV maturation in migraine. Altered maturation was not correlated with clinical improvement and may represent a vulnerability marker for migraine.     

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.     

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.     

Developmental changes of the contingent negative variation in migraine and healthy children

It has been hypothesized that abnormalities of information processing in migraine may be attributed to impairment of cerebral maturation. However, the most evidences for this hypothesis have come from cross-sectional studies during childhood. We performed a longitudinal study and recorded contingent negative variation (CNV), an event-related slow cortical potential, in migraine children (n = 27) and age-matched healthy individuals (n = 23) in 1998 and 8 years later (2006). Amplitudes of all CNV components were reduced and habituation of the initial CNV (iCNV) increased in the observed time. However, the reduction of the iCNV amplitude was more pronounced in migraine patients who were in remission in 2006 and in healthy subjects and less pronounced in migraineurs with persisting headaches. Patients with the worsened migraine demonstrated the most pronounced loss of iCNV habituation in 1998 and significantly increased iCNV amplitudes in 2006. This longitudinal study supports the hypothesis of impaired cerebral maturation in migraine and shows that migraine manifestation is a key factor interfering with the natural maturation process of central information processing.     

Contingent Negative Variation in Migraine

The Contingent Negative Variation (CNV) is an event-related slow potential. It was recorded in healthy volunteers (n = 8) and in patients suffering from migraine without (n = 12) or with (n = 5) aura, during one (CNV1) and three second (CNV3) foreperiods in a forewarned reaction time task. CNV1 was recorded at the vertex while CNV3 was recorded at multiple electrode sites to assess topographical differences. Seven out of twelve migraine patients without aura had increased CNV1 amplitudes. CNV3 amplitudes were increased as well, but only at electrode positions C3 and C4 and not at Fz. CNV3, which allows for analysis of both an early and a late CNV component, could improve the discrimination of migraine without aura beyond that of CNV1. In migraine with aura all CNV parameters were at control levels, confirming previous results. The data obtained are discussed in terms of arousal, activation and stress and the "biobehavioral model of migraine" (Welch, 1986).     

Contingent negative variation in patients with chronic daily headache

The aim of this study was the investigation of amplitude and habituation of contingent negative variation (CNV) in migraine and chronic daily headache (CDH) patients in order to describe possible neurophysiological features responsible for the clinical transformation and worsening of the headache. Fifteen females suffering from migraine without aura and 15 females diagnosed with CDH evolved from migraine without aura with interparoxysmal chronic tension-type headache (transformed migraine), underwent CNV recording. Fifteen healthy females matched for age served as controls. CNV was obtained from C3 and C4 using the standard reaction time paradigm and 3 sec ISI. The amplitudes and habituation of total CNV, early and late components, and of post-imperative negative variation (PINV) were calculated. The migraine patients were characterized by significantly more pronounced negativity of the early component and total CNV, compared to CDH sufferers and controls. CDH patients demonstrated significantly reduced negativity of the late component and pronounced PINV compared to the other groups. The early component of CNV did not habituate in migraine or CDH patients. However, the impaired habituation in CDH was related to significantly lower amplitudes. These results support the diagnostic and scientific value of habituation in migraine research and therapy. Late components of CNV and PINV can be considered as predictive variables for transformation of migraine. The results are discussed in terms of the relationship between late CNV, PINV, environment control abilities and susceptibility for development of depression.     

Contingent negative variation in subjects at risk for migraine without aura.

Migraine is a complex disease with a significant genetic background. One possible strategy to investigate the genetics of migraine is the evaluation of functional vulnerability markers or biological elementary endophenotypes in individuals with the greatest probability of developing the disorder (high-risk design). In this study the contingent negative variation (CNV) was recorded in 35 high-risk subjects with a positive family history of migraine without aura (FHP), 35 low-risk individuals without a positive family history (FHN), and 35 migraineurs (migraine without aura). FHP subjects and migraine patients differed significantly from FHN individuals with regard to amplitude and habituation slope of the early CNV component (initial CNV or iCNV). FHP participants demonstrated the same iCNV abnormalities and distribution among iCNV characteristics as migraineurs. The amplitude of the iCNV correlated significantly with the relative number of subjects suffering from migraine among first- and second-degree relatives. The higher the density of affected individuals in the family, the more pronounced were the CNV abnormalities in relatives. This study provides evidence that the familial factor contributes to the abnormal amplitude, and to a lesser degree, habituation of the iCNV, and that the iCNV may be used as a functional-genetic vulnerability marker in further research of migraine genetics.     

Frontal lobe involvement in the processing of meaningful auditory stimuli develops during childhood and adolescence

Auditory event-related N1b reflects attention-related processing in bilateral temporal auditory cortex. Frontal contributions indicating an orienting reaction have been suggested. We analyzed the maturation of frontal contributions to the auditory event-related potential following the warning stimulus in a contingent negative variation (CNV) task by high-resolution current source density mapping and spatio-temporal source analysis in 80 healthy subjects and 121 primary headache patients (migraine with/without aura, tension type headache) from 6 to 18 years; as increased orienting responses and disturbed maturation have been described in migraineurs. A selective local increase of N1b with age occurred at mid-frontocentral leads. This increase could not be explained sufficiently by overlapping bilateral temporal sources but pointed towards additional frontal activation over the supplementary motor area (SMA) in adolescents which was absent in children. A second frontal N1 component peaked about 50 ms later, showed an earlier maturation and has been suggested to reflect early response selection processes in the anterior cingulate. Primary headache patients showed the same component structure and developmental trajectory as healthy subjects without significant influences of differential diagnosis. We conclude that: (1) Brain maturation crucially influences N1b. (2) Two frontal lobe N1 components can be dissociated in their maturational trajectory. (3) Early SMA activation could be elicited by rare auditory stimuli from about 12 years on, allowing fast sensory-motor coupling without previous categorical stimulus classification. (4) Primary headache patients did not differ in their maturation of frontal or temporal contributions to N1b when elicited by moderately loud short tone bursts.     

Effects of visual pathway lesions on the visual aura of migraine

The aim was to to determine if the visual aura of migraine is altered by disease of the afferent visual pathways and if visual aura changes are associated with pre- or postgeniculate lesions. Functional neuroimaging during migraine demonstrates primary visual/extrastriate cortex as an anatomical substrate of visual aura. Neuro-ophthalmological records (including kinetic and static perimetry) of 25 patients with visual loss and typical aura with or without migraine headache were reviewed. Twenty-five patients (16 women, nine men) (mean age 59.8 years) with typical aura had visual loss from pregeniculate (72%) or postgeniculate lesions (28%). Eight patients (four postgeniculate cerebrovascular accidents or arteriovenous malformations, two lifelong optic neuropathy/retinopathy, one childhood ocular trauma, one anisometropic amblyopia) reported absence or alteration of visual aura. Postgeniculate lesions were significantly associated ( P  = 0.017) with visual aura changes. The association of postgeniculate lesions with altered auras points to a postgeniculate effect on aura appearance (consistent with functional neuroimaging findings). Although statistically significant, this series' association of postgeniculate disease and aura changes is even more robust ( P  = 0.0002) when structural changes of ocular dominance columns are posited in three patients with optic neuropathy, retinopathy and keratopathy of congenital or childhood origin.     

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.     

Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic tension-type headache–a placebo-controlled study

Acute headache is a very frequent symptom, responsible for significant demand at primary care units and emergency rooms. In such sets in Brazil, metamizol is easily found but, on the other hand, neither ergotics nor triptans are available. The aim of this study is to compare intravenous metamizol with placebo in the acute treatment of migraine with aura, migraine without aura and episodic tension-type headache. Fifty-four migraine with aura patients, 95 migraine without aura patients and 30 tension-type headache patients were treated with metamizol. Ninety patients (30 migraine with aura, 30 migraine without aura and 30 tension-type headache patients) received placebo. Pain intensity, nausea, aura, photo- and phonophobia were investigated at 30 min and 60 min after the administration of the drug. Significant improvement of pain after 30 min and 60 min post-dosage was achieved from metamizol groups compared with placebo groups. Significant improvement of all other symptoms was achieved after 60 min post-dosage. Side-effects were mild and with small incidence. Metamizol is an effective, safe and low price drug. It may be regarded as a good alternative drug for the treatment of common acute primary headaches.     

The prevalence of migraine in women aged 40-74 years: a population-based study

The objective of this study was to investigate the age-dependence of the prevalence and characteristics of migraine headache and migraine visual aura. A neurologist interviewed 728 women attending a mammography screening programme. International Headache Society (IHS) criteria were used. The lifetime prevalence of migraine headache was 31.5% and the 1-year prevalence 18.0%. The magnitude of the decline of the prevalence of active (one or more attacks in the previous year) migraine headache was estimated to 50% per decade. The prevalence of active migraine visual aura was 3.8%. This did not vary by age. Except for the pain intensity and the presence of nausea, other characteristics and concomitant symptoms did not change with age. Active migraine headache and migraine visual aura in middle-aged and older women are common and modified differently by age. We suggest that the decline of prevalence of active migraine headache with age is caused by a decrease in pain intensity.     

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.     

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.     

Migraine with aura in the locker room: three case reports

It is well known that physical activity can aggravate the intensity of the headache, but the pathophysiological relationship between exertion and aura is still unknown. Anecdotal reports describe episodes of migraine preceded by head trauma and visual symptoms, migraine prodrome symptoms after unusually strenuous running with no subsequent head pain or recurrent attacks of hemiplegic migraine induced only by exertion. We describe the cases of three young men with recurrent episodes of migraine with aura occurring in the locker room shortly after a football match. Since the symptoms could mimic important pathologies in approximately 10% of these of headaches, it was mandatory to exclude a secondary form of headache in these patients. Several theories exist regarding the cause of primary exertional headache, but the pathogenesis of migraine triggered by physical activity has still not been identified. The present International Classification of Headache Disorders does not mention sport/exercise-induced migraine with aura episodes as primary headache. Since there are many cases described in the literature of migraine with aura triggered only by exercise, it may be helpful to specify, in the typical aura with migraine headache comments, that in some cases it can be exclusively triggered by sport/exercise.     

An Association Between Migrainous Aura and Hereditary Haemorrhagic Telangiectasia

SYNOPSIS
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by a variety of abnormalities of the vasculature.
This study investigated by questionnaire an unselected group of 58 patients suffering from HHT to identify and diagnose any headache history. These were compared with a control group comprising 40 patients with an unrelated autosomal dominant disorder, familial adenomatous polyposis.
Fifty percent of the HHT patients reported attacks of headache which fulfilled current diagnostic criteria for migraine with aura. This was over four times the figure for the control group and at least 10 times the expected level for a normal population. The auras described by all the affected patients were classic visual disturbances preceding the headaches. Two patients also described typical visual auras unassociated with headache symptoms.
The reason for such a clear association between migraine with aura and HHT is uncertain but cerebral arteriovenous malformations seem to be the likely link. A greater understanding of the reasons for the relationship may provide an insight into the pathophysiology of both conditions.     

Association of benign recurrent vertigo and migraine in 208 patients

The aim of this study was to determine the association of benign recurrent vertigo (BRV) and migraine, using standardized questionnaire-based interview of 208 patients with BRV recruited through a University Neurotology clinic. Of 208 patients with BRV, 180 (87%) met the International Classification of Headache Disorders 2004 criteria for migraine: 112 migraine with aura (62%) and 68 without aura (38%). Twenty-eight (13%) did not meet criteria for migraine. Among patients with migraine, 70% experienced headache, one or more auras, photophobia, or auditory symptoms with some or all of their vertigo attacks, meeting the criteria for definite migrainous vertigo. Thirty per cent never experienced migraine symptoms concurrent with vertigo attacks. These met criteria for probable migrainous vertigo. Among patients without migraine, 21% experienced either photophobia or auditory symptoms with some or all of their vertigo attacks; 79% experienced only isolated vertigo. The age of onset and duration of vertigo attacks did not differ significantly between patients with (34 ± 1.2 years) and patients without migraine (31 ± 3.0 years). In patients with migraine, the age of onset of migraine headache preceded the onset of vertigo attacks by an average of 14 years and aura preceded vertigo by 8 years. The most frequent duration of vertigo attacks was between 1 h and 1 day. Benign recurrent vertigo is highly associated with migraine, but a high proportion of patients with BRV and migraine never have migraine symptoms during their vertigo attacks. Other features such as age of onset and duration of vertigo are similar between patients with or without migraine.     

Clinical characteristics of 362 patients with familial migraine with aura

The objectives of the present study were to describe the clinical characteristics of patients with severe familial non-hemiplegic migraine with aura (NHMA) and to compare these data to those from cases in previous population-based Danish studies using the same methodology. NHMA families were recruited from the Danish patient registry and from Danish neurology practices. A total of 362 NHMA patients were diagnosed according to the 1988 International Headache Society criteria using a validated semistructured physician-conducted interview. Visual aura occurred in almost every NHMA attack. In aura without headache visual aura occurred primarily in isolation. Aura without headache was most common in older, male patients. Several clinical characteristics of familial NHMA differed from migraine with aura in the general population: firstly, the age at onset was lower, secondly, the age at cessation was higher, thirdly, aura symptoms were more severe and finally, the co-occurrence of migraine without aura was higher in familial NHMA. There seems to be a correlation between more severe symptoms and familial aggregation. These results have both clinical and scientific implications.     

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.