Jesus Castillo

Epidemiology of Chronic Daily Headache in the General Population

Background and Objectives.—Although chronic daily headache, mainly transformed migraine, is an important reason for consultation in headache clinics, its actual prevalence is unknown. This study analyzes the prevalence of the different types of chronic daily headache in an unselected population.

Quality of life in chronic daily headache A study in a general population

ObjectiveTo analyze the quality of life (QoL) of subjects with chronic daily headache (CDH) in the general population. MethodsQoL was studied, using the generic instrument Short Form-36 (SF-36), in 89 unselected subjects from an epidemiologic study in the general population who fulfilled CDH criteria. SF-36 scores were adjusted for comorbid conditions. A total of 89 healthy matched subjects were recruited as a control group. An additional matched group of 89 otherwise healthy subjects with episodic migraine was recruited as controls only to those with transformed migraine (TM). ResultsCDH subjects showed a significant decrease in each health-related concept of the SF-36 as compared with healthy subjects. The highest decreases were seen for role physical, bodily pain, vitality, and social functioning. There was no significant difference in SF-36 scores in subjects with chronic tension-type headache as compared with TM subjects. TM individuals showed lower values in each health-related concept when compared with patients with episodic migraine, these decreases being significant for general health, vitality, and mental health. Finally, CDH subjects without analgesic overuse showed higher values in each concept of the SF-36 than those with analgesic overuse. Despite the low proportion of abusers in this study, differences were significant for physical functioning and bodily pain. ConclusionsIn the general population, CDH reduced all QoL aspects studied with the SF-36. This reduction in QoL was most marked in subjects with analgesic overuse. QoL was affected more by the chronicity than by the intensity of pain.

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.

Premonitory and resolution symptoms in migraine: a prospective study in 100 unselected patients.

The nosology of migraine premonitory (PS) and resolution (RS) symptoms was studied in 100 migraineurs consulting their general physician. They were asked to fill in, for three attacks, a PS and RS questionnaire. ‘True’ PS/RS were those experienced the day before (or the day after) the headache had started only if they were not present in a questionnaire completed in a pain-free period. True PS and RS were experienced by 84± and 80±, respectively, of subjects for the first attack. The mean and range (per patient) of PS were 6.8 and 0–21 and of RS 4.7 and 0–15. Anxiety, phonophobia, irritability, unhappiness and yawning were the commonest PS, whereas asthenia, tiredness, somnolence and concentration difficulties were the most common RS. Gender, age and Migraine Disability Assessment scores did not influence PS and RS. Both PS and RS were more frequent in migraine with aura subjects. Patients on preventatives showed a decreased frequency of PS and, to a lesser degree, of RS. Severity of headache was associated with a higher frequency of RS. Individual RS and especially PS were quite consistent after three attacks. Almost two-thirds of the symptoms were noticed in at least two out of three attacks, while more than a half of PS and more than a quarter of RS repeated in three out of three attacks. In conclusion, around 80± of unselected migraineurs experience RS and PS. Migraine with aura and severe pain are risk factors for experiencing PS and RS, while preventatives were protective, especially for PS.

Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in migraine.

Objective.— Female hormone genes have been investigated in migraine in recent years. Research in this field has been controversial, especially in regard to ESR1 gene findings. None of the reports have yet to approach the problem from a multigenic point of view.

The Relationship Between Homocysteine and Genes of Folate-Related Enzymes in Migraine Patients

(Headache 2010;50:99‐168)

Lack of Association of Endothelial Nitric Oxide Synthase Polymorphisms and Migraine

Objective.— The aim of this study was to evaluate if 2 functional endothelial nitric oxide synthase (eNOS) gene polymorphisms might be risk factors for migraine.

Analysis of endothelial precursor cells in chronic migraine: A case-control study

Background: Migraine has been considered a vascular risk factor especially in young women. Factors predisposing to endothelial damage in migraine are still being debated. The insufficiency of circulating endothelial precursor circulating cells (EPCs) suggested a link between migraine and cardiovascular risk. This research aimed to study a subtype of EPCs, those expressing e-selectin, to assess endothelial activation and, therefore, endothelial dysfunction in migraine. Methods: Consecutive headache patients (n = 99) and 35 adjusted controls were recruited. Total EPCs, defined as CD34+/KDR+ cells, and EPC colony-forming units (CFUs) were assayed. We identified as “early” EPCs those CD62E– EPCs, and “late” EPCs, CD62E+, a surrogate marker for endothelial damage. Plasmatic calcitonin-gene related protein (CGRP) and vascular-endothelial growth factor (VEGF) were analyzed. Results: We did not find differences in the total number of CFUs among clinical groups. Means of total CD34+/KDR+ and “early” EPCs were not significant among clinical groups. Nevertheless, the mean of “late” EPCs was lower (log10-transformed mean = 1.715; SD = 0.393) in the control group than in the migraine patients (log10-transformed mean = 2.167; SD = 0.685), even after adjustment by VEGF plasma level and other confounding factors. Linear regression analyses disclosed significant predictors for “late” EPCs for controls vs migraine (β = 0.452 SE ± 0.13; p = 0.001). We did not observe differences between migraine with or without aura. Conclusion: We observed higher number of activated EPCs in migraine patients than in controls. CD62E+ EPCs might be considered a marker for vascular damage in migraine patients.

GNAS1 T393C polymorphism is associated with migraine

Migraineurs have an interictal sympathetic nervous system (SNS) hypofunctionality and hypersensitivity to adrenergic amines. The GNAS1 T393C polymorphism has been associated with a distinct SNS sensitivity in healthy subjects. We tested GNAS1 T393C variant in two independent sets of subjects. In the case-control subset, 365 migraine patients [194 with aura (MA)] vs. 347 healthy controls were studied. A significant excess of the CC genotype was found in migraneurs (31.2%) as opposed to controls (20.2%; P = 0.003). Using a logistic regression model corrected for sex, the CC genotype conferred a general risk for migraine twice [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.27-2.53; P = 0.001] higher than CT/TT genotypes. Using parents from 117 migraine families, a marginally significant trend for association could be observed (P = 0.025), but the transmission disequilibrium test for alleles maternally transmitted failed to demonstrate familial association. In this subgroup, CC genotype conferred a risk for migraine over twice (OR 2.20; 95% CI 1.14-4.40; P = 0.019) higher than TT/TC genotypes. In conclusion, the GNAS1 T393C variant is associated with migraine, which suggests a genetic basis for its higher SNS sensitivity.

Genetic association study and meta-analysis of the HTR2C Cys23Ser polymorphism and migraine

The objectives of this study were to determine if the HTR2C Cys23Ser polymorphism is associated with migraine in a case-control study, and to perform a meta-analysis with present and previous available studies. The HTR2C gene is located at the Xq24-q28 chromosomal band. This band was linked to migraine with aura (MA) in two Australian families. Using the HTR2C Cys23Ser allelic variant, this gene has been ruled out as a migraine gene in 3 out of 4 studies. Only the Japanese study reported a higher risk for MA (OR=6.11; 95% CI=1.70−21.97, p trend<0.01). We performed a case-control study with 335 migraine subjects and 335 sex- and age-matched controls, and a meta-analysis pooling the results of the available data from MA subsets of patients. In the association study we found no significant differences among migraine and MA patients for this polymorphism. In the meta-analysis, under the fixed-effect model, the Ser allele did not confer higher risk for suffering MA (pooled OR=1.1; 99% CI=0.8−1.5, p=0.499). Our study did not confirm the HTR2C Cys23Ser polymorphism as a risk factor for migraine and MA.