Evaluating the effects of spatial frequency on migraines by using pattern-reversal visual evoked potentials.

OBJECTIVE: To clarify the effects of contrast and spatial frequency in patients with migraine by means of pattern-reversal visual evoked potentials (PVEPs). METHODS: PVEPs were obtained from 14 patients who had migraine without aura (MO), 11 patients who had migraine with aura (MA), and 25 age-matched, healthy controls (CO). PVEPs were binocularly recorded with a reversal rate of 1Hz (2 reversal/s) at 3 spatial frequencies (0.5, 1.0 and 4.0 cpd) at high (98%), medium (83%) and low (29%) contrast. N75, P100 and N135 latency and the amplitudes of P50-N75, N75-P100 and P100-N135 were analyzed. RESULTS: Increased amplitude of PVEPs in patients with migraines were revealed at 3 different spatial frequencies in all components. The MO and the MA showed increased amplitudes mostly in high contrasts (98%). These findings were detected more at a high spatial frequency (4.0 cpd) than at a low spatial frequency (0.5 cpd). Increased amplitude with prolonged latency of N135 were found both in MO and MA at 4.0 cpd. CONCLUSIONS: We conclude that pattern stimuli of high contrasts may be particularly effective in uncovering abnormal cortical reactivity which may be modified in the primary and secondary visual cortex in the interictal state of migraine. SIGNIFICANCE: These findings indicate that there is abnormal visual cortex processing in patients with migraine.     

Comparison of visual and auditory evoked cortical potentials in migraine patients between attacks.

OBJECTIVE: As both habituation of pattern reversal visual evoked potentials (PR-VEP) (Schoenen J, Wang W, Albert A, Delwaide PJ. Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks. Eur J Neurol 1995;2:115-122) and intensity dependence of auditory evoked cortical potentials (IDAP) (Wang W, Timsit-Berthier M, Schoenen J. Intensity dependence of auditory evoked potentials in migraine: an indication of cortical potentiation and low serotonergic neurotransmission? Neurology 1996;46:1404-1409) were found abnormal in migraine between attacks, we have searched for intraindividual correlations between both tests in 59 migraine patients (22 with aura [MA], 37 without aura [MO]) and in 23 healthy volunteers (HV). METHODS: Amplitude change of the PR-VEP N1-P1 was measured between the 1st and 5th block of 50 sequential averagings during continuous stimulation at 3.1 Hz. IDAP was computed from N1-P2 amplitudes of 100 averagings during stimulations at 40, 50, 60 and 70 dB SL. Amplitude-stimulus intensity function (ASF) slopes and amplitude changes between 40 and 70 dB were calculated. MO and MA differed from HV in PR-VEP amplitude change (P=0.007) and IDAP slope (P = 0.0004). RESULTS: There was no significant correlation between VEP amplitude changes and IDAP slopes, nor between the latter two and attack frequency or disease duration. A negative correlation was found between the amplitude of the first block of averaged responses and potentiation of VEP in all subject groups (P = 0.03) as well as between the amplitude of the auditory evoked potential, at 40 dB, and the percentage of amplitude increase between 40 and 70 dB in MO (P = 0.004) and MA (P = 0.007). ASF slopes and 40 dB amplitudes were significantly correlated only in the MA group (P = 0.002). These results confirm the interictal deficit of habituation in cortical processing of repetitive visual and auditory information in migraine. Since there is no intraindividual correlation between the cortical responses to these sensory modalities they are complementary tools for the study of migraine and may help to identify subgroups of patients with distinct pathophysiological mechanisms. CONCLUSIONS: The strong negative correlation between the initial amplitude of evoked potentials and their amplitude increase during subsequent averaging confirms that the response potentiation in migraine is likely to be due to a reduced preactivation level of sensory cortices.     

The effect of spatial frequency on chromatic and achromatic steady-state visual evoked potentials.

OBJECTIVE: Little is known about the physiological properties of the major components of steady-state visual evoked potentials (VEPs). Based on the hypothesis that isoluminant color and high contrast pattern differentially activate the parvo- and magnocellular pathways, we studied difference in spatial frequency function between chromatic and achromatic VEPs to sinusoidal gratings. METHODS: Steady-state VEPs to isoluminant chromatic (red-green) and high contrast (90%) achromatic (black-white) sinusoidal gratings with nine spatial frequencies (0.5 to 8.0 cycles/degrees (cpd)) at 4 Hz (8 reversals/s) were recorded in 13 normal subjects. VEPs were Fourier analyzed to obtain phase and amplitude of the second (2F) and fourth (4F) harmonic responses. RESULTS: The 2F amplitude of chromatic VEPs decreased above 4.0 cpd in a low-pass function while that of achromatic VEPs showed a band-pass function with a peak at 4.0 cpd. The 4F amplitude of chromatic VEPs was not affected significantly by spatial frequency whereas that of achromatic VEPs exhibited a high-pass function. The phases of 2F and 4F showed a non-monotonic function of spatial frequency in both chromatic and achromatic stimuli with peaks at middle spatial frequencies. CONCLUSION: Chromatic and achromatic visual stimuli differently affected 2F and 4F components, which thus suggests that 2F and 4F components are generated from different neuronal subgroups largely in the parvocellular pathway.     

Median nerve somatosensory evoked potentials in migraine

In visual evoked potential studies, habituation during stimulus repetition with the same stimulus at a constant intensity has been found to be abnormal in migraineurs between attacks. The purpose of this study was to investigate habituation of somatosensory evoked potentials (SEPs) and the effects of migraine on them. Eighty-five subjects were included in the study: 30 healthy volunteers (HVs) and 55 migraineurs [30 with migraine without aura (MO), 25 with migraine with aura (MA)]. During continuous stimulation at 3 Hz, four blocks of 100 responses were sequentially averaged of Erb's point (N9), cervical (N13), and cortical (N20) median nerve SEPs. Mean amplitude changes in the second, third and fourth blocks are expressed as percentages of the first block. There was habituation to N13 and N20 in the second, third and fourth blocks in HVs. In the migraine groups, there was no habituation; on the contrary, potentiation was found. This potentiation was statistically significant only in the second blocks for N13 (MO P=0.007, MA P=0.01 versus HVs). However, in both migraineur groups, the rate of N20 potentiations was statistically significant versus that in HVs for all blocks (all P < 0.05). It is concluded that whilst physiological habituation occurs in HVs for cervical and cortical SEPs, in migraine patients there is an interictal deficit of habituation of this sensory modality.     

Auditory cognitive event-related potentials in migraine with and without aura in children and adolescents

BACKGROUND AND PURPOSE: Cognitive Event-Related Potentials (CERP) reflect sensory information processing: cognitive function and early memory. Studies of CERP in adult migraneurs yielded contradictory results. The aim of our study was to evaluate CERP in children and adolescents with migraine with and without aura during the interictal period. MATERIAL AND METHODS: The study was carried out on 111 children aged 7-18 years (mean 12.92 (2.78) with idiopathic attack headaches. In this group migraine with aura (MA) was diagnosed in 27 patients, migraine without aura (MO) in 36 children and episodic tension-type (TH) headaches in 48 patients. RESULTS: The latencies N2 and P3 were significantly longer (p < 0.05 and p < 0.01, respectively) in the group of all migraneurs (MA + MO, n = 63) as compared with the TH group. In the MO group not only N2 and P3 latency, but also P2 latency (p < 0.05) were longer, if particular types of migraine were compared with tension-type headaches. There were no statistically significant differences between mean latencies in MA and TH groups. Analyzing CERP amplitudes, the N1/P2 amplitude was significantly higher in MO patients than in the TH group only. We found longer P2, N2 and P3 latencies and higher N1/P2 amplitude in MO patients in comparison with MA patients. We found correlation between P3 latency and the age of patients with migraine. There were no statistically significant correlations for either headache type between CERP parameters and illness duration, sex of patients and unilateral localisation of headache. CONCLUSIONS: The CERP parameter changes in children with migraine point out the disturbances of cognitive functions also for auditory modalities. It suggests generalized dysfunction of cortical information processing in the interictal period of migraine.     

Visual evoked potential latency, amplitude and habituation in migraine: a longitudinal study.

OBJECTIVE: It has not been previously studied with a paired longitudinal design if visual excitability changes occur in the preattack period across the migraine cycle, or how excitability and habituation relate to migraine-attack severity, clinical photophobia and serotonin metabolism. METHODS: Monocular 62' check reversals were applied in 33 adult migraine patients without aura (MwoA), 8 with aura (MA) and 31 controls. VEP was recorded in four blocks of 50 stimuli. P1 (P100) and N2 (N145) latency and N1P1 and P1N2 amplitude were measured. Serotonin was measured in plasma and platelets sampled before each session. Sessions were classified as preattack, attack, postattack or interictal. RESULTS: Migraine patients had significantly higher P1N2 amplitude before the attack compared to a paired interictal recording (n=13, p=0.03), but habituation difference was not found. MA patients had significantly higher P1N2 and N1P1 amplitude than controls and MwoA. P1 latency correlated positively with headache history duration. During attack, a positive correlation between P1N2 amplitude habituation and serotonin emerged in MA patients. CONCLUSIONS: Increased VEP P1N2 amplitude was observed within a few days before the attack. Visual cortex excitability seems to be generally increased in MA as compared to MwoA patients and controls. SIGNIFICANCE: Increased excitability of the visual cortex seems to be detectable in the preattack state, supporting the concept of a cyclic CNS dysfunction in migraine.     

Investigation of an LDLR gene polymorphism (19p13.2) in susceptibility to migraine without aura

We performed a genetic association study with the LDL receptor gene (LDLR) on chromosome 19p13.2 in 360 migraine patients, 220 with migraine without aura (MO) and 140 with migraine with aura (MA), and 200 controls, by analysing two polymorphic markers, a G142A transition in exon 10 and a triallelic (TA)n repeat in exon 18. The allelic distribution of the (TA)n polymorphism was significantly different between migraine without aura (MO) and both controls and migraine with aura (MA). We suggest a possible predisposition to MO in the studied population through this polymorphism or another polymorphism in linkage disequilibrium with (TA)n.     

Increased Cortical Excitability in Female Migraineurs: A Transcranial Magnetic Stimulation Study Conducted in the Preovulatory Phase

Background and PurposeThe cerebral cortex has been the focus of investigations of the pathogenesis of migraine for a long time. Transcranial magnetic stimulation (TMS) is a safe and effective technique for evaluating cortex excitability. Previous studies of the duration of the cortical silent period (CSP)—a measure of intracortical inhibition—in migraine patients have yielded conflicting results. We aimed to characterize cortical excitability by applying TMS to female migraineurs during the preovulatory phase of the menstrual cycle, in order to eliminate the effects of variations in sex hormones.MethodsWe enrolled 70 female subjects: 20 migraine with aura (MA) patients, 20 migraine without aura (MO) patients, and 30 healthy controls. We measured the CSP, resting motor threshold (rMT), and motor evoked potential (MEP) induced by TMS to evaluate cortical excitability during the preovulatory phase of the menstrual cycle.ResultsThe CSP was shorter in MA patients (88.93±3.82 ms, mean±SEM) and MO patients (86.98±2.72 ms) than in the control group (109.06±2.85 ms) (both p=0.001), and did not differ significantly between the MA and MO groups (p=0.925). The rMT did not differ significantly among the groups (p=0.088). MEP_max was higher in MA patients than in healthy controls (p=0.014), while that in MO patients did not differ from those in MA patients and healthy controls (p=0.079 and p=0.068).ConclusionsWe detected a shorter CSP in both MA and MO patients. This finding may indicate the presence of motor cortex hyperexcitability, which is probably due to reduced GABAergic neuronal inhibition in migraine.     

Chromosome 1p36 in migraine with aura: association study of the 5HT(1D) locus

Migraine with aura (MA) may share some but not all risk factors with other forms of migraine. As common migraine without aura (MO) has been associated with the chromosome 1p36 locus, we tested its involvement in MA by using two-point parametric linkage analysis to analyze 64 multiplex MA families. A logarithm of the odds score of 1.9 was suggestive of chromosome 1p36 linkage to MA. The transmission disequilibrium test analysis was then performed in 79 nuclear families with one MA parent and one MA offspring. We identified the presence of genetic association at chromosome 1p36 with MA (P=0.045, Bonferroni corrected): the locus encoding the 5HT(1D) receptor gene. Although these data suggest that the 1p36 locus may protect against MA, consistent with the role of the 5HT(1D) receptor in migraine treatment with triptan drugs, the study is subject to the limitations associated with studying a small number of affected families. As a result, we contrast evidence suggesting that the chromosome 1p36 locus is strongly MO associated with our finding that 1p36 has a more limited contribution to MA in the families we analyzed. Further work using a genome-wide association study approach in familial typical migraine, consisting of those affected by MO or MA, will serve to further distinguish how and why MA differs from MO.     

Increased risk of migraine with typical aura in probands with familial hemiplegic migraine and their relatives

We investigated the occurrence of migraine without aura (MO) and migraine with typical aura (MA) amongst probands with familial hemiplegic migraine (FHM) and their first degree relatives in order to evaluate the relations between these syndromes. A total of 44 FHM probands and 240 first degree relatives were identified in the Danish population. The pattern of familial aggregation was assessed by population relative risk (PRR) calculations. Amongst FHM probands the PRR of MO was 1.5 (95% CI: 0.8-2.2), whereas the PRR of MA was 7.1 (95% CI: 5.0-9.2). Thus, compared with the general population, FHM probands had no increased risk of MO but a significantly increased risk of MA. A similar pattern was seen amongst their first degree relatives, who had no increased risk of MO, whereas the risk of MA was significantly increased; 7.6 times in FHM-affected first degree relatives and 2.4-times in non-FHM-affected first degree relatives. These results are contrary to a sharing of genetic mechanisms between FHM and MO. Furthermore, they suggest that the genetic abnormality causing FHM may also cause attacks with the symptomatology of MA.     

Transcranial magnetic stimulation of visual area V5 in migraine

OBJECTIVE: To examine visual cortical excitability in persons with migraine using transcranial magnetic stimulation (TMS) over an extrastriate area of the brain, area V5. BACKGROUND: Previous studies found that persons with migraine have a lower phosphene threshold than healthy control subjects with TMS delivered over the primary visual cortical area V1. The result suggests that the occipital cortex in migraineurs between migraine attacks is hyperexcitable. However, it is not known whether interictal cortical hyperexcitability is also present in areas of the association visual cortex. METHOD: To investigate this, single-pulse TMS was delivered over visual area V5, the motion cortex, to 16 persons with migraine and visual aura, nine migraineurs without visual aura, and 16 healthy control subjects. TMS was delivered at intensities ranging from 30 to 100% of maximum stimulator output or until the participant reported seeing phosphenes (visual illusions characterized by flashes of light). Thresholds to phosphenes were obtained for each participant using a staircase procedure. RESULT: Significantly lower phosphene thresholds for TMS delivered over V5 were found in migraineurs as compared with control subjects. Qualitatively, the migraineurs' experience of phosphenes were more vivid, florid, and sustained compared with that of control subjects. CONCLUSION: Results of this study indicate that hyperexcitability of the visual cortex in migraine goes beyond visual area V1 and demonstrates for the first time a significant difference in threshold for excitability of visual area V5 in persons with migraine.     

The genetics of migraine

Clinical, pathophysiological and genetic studies indicate that migraine without aura (MO) and migraine with aura (MA) are distinct entities. Compared with the general population, first degree relatives of probands with MO have a two-fold increased risk of MO. The mode of inheritance is most likely multifactorial inheritance without generational difference, but genetic heterogeneity can not be excluded. Compared with the general population, first degree relatives of probands with MA have a four-fold increased risk of MA. The mode of inheritance is most likely multifactorial inheritance without generational differences. Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of MA. A gene for FHM maps to chromosome 19. Some families with FHM do not link to this locus, indicating genetic heterogeneity of FHM. The gene for FHM is soon to be cloned. Loci for the more common types of migraine MO; and MA will problably be identified in the near future.     

Treating migraine with contraceptives

At least 18% of women suffers from migraine. Clinically, there are two main forms of migraine: migraine with aura (MA) and migraine without aura (MO) and more than 50% of MO is strongly correlated to the menstrual cycle. The high prevalence of migraine in females, its correlation with the menstrual cycle and with the use of combined hormonal contraceptives (CHCs) suggest that the estrogen drop is implicated in the pathogenesis of the attacks. Although CHCs may trigger or worsen migraine, their correct use may even prevent or reduce some forms of migraine, like estrogen withdrawal headache. Evidence suggested that stable estrogen levels have a positive effect, minimising or eliminating the estrogenic drop. Several contraceptive strategies may act in this way: extended-cycle CHCs, CHCs with shortened hormone-free interval (HFI), progestogen-only contraceptives, CHCs containing new generation estrogens and estrogen supplementation during the HFI.     

Vector analysis of visual evoked potentials in migraineurs with visual aura.

OBJECTIVE: To assess the capability of vector analysis of visual evoked potentials (VEPs) for revealing alterations in posterior visual pathways in migraineurs with visual aura. METHODS: VEPs to pattern reversal (PR) and LED goggle stimulation were obtained in 23 patients suffering from migraine with visual aura, in an orthogonal Fpz-Oz and T3-T4 montage and displayed as a two-channel Lissajous' trajectory. VEP latency and amplitude at Fpz-Oz, bc segment amplitude (V) and bc vector orientation angle (theta) were compared with a previously collected normative database for individual assessment, and group comparisons with the previously collected normal sample were made. Electrophysiological measures were also correlated with time from onset of disease and from the last crisis, and with the side of symptoms. RESULTS: No individual alterations in VEP latency or amplitude were observed. However, 36.4% of patients showed alterations in vector orientation to PR and 78% to LED goggles. Group differences with respect to normal subjects were found not only in vector orientation but also in midline VEP and V, only for PR stimulation. A significant relationship was found between the laterality of vector deviation and the laterality of symptoms. CONCLUSIONS: Vector analysis of VEP revealed alterations possibly corresponding to asymmetrical visual cortex activation in migraineurs with visual aura, mainly to diffuse light stimulation. SIGNIFICANCE: An electrophysiological parameter of individual value for revealing asymmetric activation of visual cortex in migraineurs is proposed.     

Chlordimeform produces contrast-dependent changes in visual evoked potentials of hooded rats

Previous experiments found that acute exposure to the insecticide/acaricide, chlordimeform (CDM), produced large increases in the amplitude of pattern reversal evoked potentials (PREPs) without changing the amplitude of flash evoked potentials (FEPs) in the same rats (W. K. Boyes and R. S. Dyer, Exp. Neurol. 86: 434-447, 1984). Current work investigated the influence of physical characteristics of the evoking stimuli on the action of CDM. Adult male Long-Evans rats with epidural visual cortex electrodes were used. In experiment 1, PREPs were elicited with alternating gratings having equal contrast (99%) and a square wave spatial luminance profile at several spatial frequencies. Rats treated 1 h previously with 40 mg/kg CDM had increased PREP amplitudes at 0.1, 0.2, and 0.4 cycles per degree (cpd), but not at 0.8 cpd. No changes were found after 5 mg/kg CDM. In experiment 2, PREPs were elicited with gratings oriented at 0 degrees (horizontal), 45 degrees, 90 degrees, or 135 degrees. Treatment with 40 mg/kg CDM increased PREP amplitudes and latencies regardless of orientation. In experiment 3, FEPs elicited with strobe flashes spanning four log units of intensity showed a small but significant CDM dose X intensity interaction on P2N2 peak-to-peak amplitude. In experiment 4, PREPs were elicited with alternating gratings having a sinusoidal spatial luminance profile, spatial frequency of 0.2 or 0.8 cpd, and contrast ranging from noise levels to 65%. Rats treated with 40 mg/kg CDM showed increased peak-to-peak amplitudes only at 0.2 cpd and only at contrast values above 10%. The failure of CDM to alter PREPs at 0.8 cpd was attributed to low contrast sensitivity at that spatial frequency. The results demonstrated that the action of CDM on visual evoked potentials was dependent on the amount of contrast in the stimulus pattern, and suggested that CDM alters the encoding of visual contrast.     

Association of MTHFR gene polymorphisms with migraine in North Indian population

Polymorphisms in MTHFR gene are mostly associated with increased levels of homocysteine in the absence of dietary folate and are a risk factor for complex neurovascular diseases like migraine. The aim of present case-control study was to determine the association between MTHFR gene polymorphisms (C667T; rs 1801133, A1298C; rs 1801131) with migraine susceptibility. In total, 100 patients with migraine (23with MA and 77 with MO) and age-sex matched 100 healthy controls were included in this study from OPD of ESIC Medical College & Hospital, Faridabad. Genotyping was done by PCR-RFLP method. Genotypic and allelic frequencies were compared by SPSS 24 version. Genotypic results indicated a non-significant increase in frequencies of CT and TT in C667T SNP in migraine patients with control (52 and 10% vs. 42 and 7%: p?>?0.05), but CC genotype in A1298C was found to be a risk factor in migraine patients than controls (30 vs. 17% respectively: p?<?0.05). On comparing migraine subclasses, migraine with aura (MA) and without aura (MO) with control groups, the present study suggests that in MTHFR polymorphisms, the prevalence of 677CT genotype and T allele in C667T SNP influences susceptibility to MA (p?<?0.05) but not to MO. Meanwhile, CC genotype in A1298C SNP could be a risk factor for migraine patients without aura (p?<?0.05).     

Steady-state visual evoked potential temporal dynamics reveal correlates of cognitive decline

ObjectiveA central concern in aging is the preservation of cognitive skills. Tools to detect cognitive decline are sparse. The aim of this study was to ascertain whether cognitive decline is accompanied by alterations in the temporal dynamics of steady-state visual evoked potentials (SSVEPs).MethodsWe included 162 men from the Danish Metropolit birth cohort. Their cognitive trajectory was based on their intelligence test score at youth (age ~18), middle age (age ~56), and late middle age (age ~62). Subjects underwent cognitive tests and steady-state visual stimulation. Temporal dynamics of SSVEPs were assessed in terms of amplitude and phase coherence.ResultsThe latency and magnitude of the amplitude modulation of the 36-Hz response correlated negatively with subjects’ cognition indices. Furthermore, negative cognition index was associated with loss of SSVEPs at 36 Hz, and both 8 Hz and 36 Hz in severe cases.ConclusionLatency and magnitude of gamma frequency SSVEPs increase with cognitive decline. This suggests that the facilitation of SSVEPs first becomes problematic at gamma frequencies, then at alpha frequencies.SignificanceOur data suggests that the temporal dynamics of SSVEPs can be used as an indicator of cognitive impairment. Furthermore, evoked gamma oscillations are especially vulnerable in cognitive decline.     

Clinical review of headache in pregnancy

Headache is a common disorder in the general population. Among women, the primary headache form that is more heavily affected by the physiologic hormonal variations occurring through a woman’s lifetime is migraine. Migraine without aura (MO) and migraine with aura (MA) show a different clinical pattern during pregnancy. MO improves or disappears while it is not infrequent for women to have their first attack of MA during this period; usually, during pregnancy MA do not improve. In MO women who continue to suffer from migraine during pregnancy, clinical observation and the few data currently available from the literature suggest that in the gestational period their attacks are nonetheless less disabling than those occurring outside this period. Even though the duration of the attacks is unchanged, their severity tends to be mild or moderate. Treatment of migraine during pregnancy is discussed.     

Validation of the deCODE Migraine Questionnaire (DMQ3) for use in genetic studies

We assessed the reliability of the diagnosis of migraine with aura (MA) and migraine without aura (MO) based on the third edition of the deCODE Migraine Questionnaire (DMQ3) using a physician-conducted interview as an empirical index of validity. Amongst Danish migraine families recruited from specialist practice we selected 200 cases diagnosed according to the International Classification of Headache Disorders 2nd Edition in a validated physician-conducted telephone interview: 50 patients with exclusively MA, 50 with both MA and MO, 50 with exclusively MO and 50 controls. A written copy of the DMQ3 was mailed to the participant. The DMQ3-based diagnosis was compared with the interview-based diagnosis. Overall, the DMQ3 diagnosed migraine (MA, MO or both) with a sensitivity of 99% (109/110), a specificity of 86% (32/37) and a kappa statistic of 0.89. The most reliable subtype of migraine was MA (with or without co-occurring attacks of MO) which was diagnosed with a sensitivity of 92% (71/77), a specificity of 93% (65/70) and a kappa statistic of 0.85. Exclusively MO was diagnosed with a sensitivity of 91% (30/33), a specificity of 93% (106/114) and a kappa statistic of 0.80. Weakest was the diagnosis of both MO and MA which was diagnosed with a sensitivity of 63% (24/38), a specificity of 92% (100/109) and a kappa statistic of 0.57. In conclusion, the DMQ3 is a valid tool for diagnosing patients with migraine for genetic studies.     

Investigation of the low-density lipoprotein receptor gene and cholesterol as a risk factor for migraine

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an association analysis in 244 typical migraine-affected patients, 151 suffering from migraine with aura (MA), 96 with migraine without aura (MO) and 244 unaffected controls. The populations consisted of Caucasians only, and controls were age- and sex-matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine-affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al. who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine-affected population.