Migraine Disorders: Castillo J

Láinez JM, Castillo J, González VM, Otero M, Mateos V, Leira R, Pascual J, Anonymous00353. · Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología. · Rev Clin Esp. · Pubmed #17475183 No free full text.

Abstract: Migraine is the most frequent neurological reason for consultation. The differences regarding health care system, type of professional seeing these patients and therapeutic armamentarium available in the different countries are important, which makes it very recommendable to have an action guide that reflects the local clinical practice. Following the year 2005 WHO recommendations in its "Global Campaign" against migraine, the coordinators of the Headache Study Groups of the Spanish Society of Neurology, the Spanish Society of Family and Community Medicine, the Spanish Society of Rural and General Medicine, the Spanish Society of General Medicine and the Global Campaign decided to jointly make this guide. To do so, they made a search in MEDLINE, using the terms "migraine", "migraine treatment" and "headache guidelines" and "migraine guidelines". The most relevant articles were analyzed, including the references that we considered to be of interest. Furthermore, we reviewed the most important textbooks on headache and migraine. In this paper, we detail the recommendations agreed on, according to the evidence grade, on symptomatic and preventive treatment of migraine.

Pascual J, Colás R, Castillo J. · Service of Neurology, University Hospital Marqués de Valdecilla, Santander 39008, Spain. · Curr Pain Headache Rep. · Pubmed #11676887 No free full text.

Abstract: Daily or near-daily headache is a widespread problem in clinical practice. The general term of chronic daily headache (CDH) encompasses those primary headaches presenting more than 15 days per month and lasting more than 4 hours per day. CDH includes transformed migraine (TM), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). Around 40% of patients attending a specialized headache clinic meet CDH diagnostic criteria, of which 80% are women. In these clinics about 60% of patients suffer from TM, 20% from CTTH, and 20% meet NDPH criteria. Most, some 80%, overuse symptomatic medications. One should be very cautious on extrapolating these numbers to the general population. CDH prevalence in the general population seems to be around 4% to 5% (up to 8% to 9% for women). Regarding the prevalence of CDH subtypes, NDPH is rare (0.1%), whereas the prevalence of TM (1.5% to 2%) and CTTH (2.5% to 3%) is clearly higher. In contrast to data from specialized clinics, only around a quarter of CDH subjects in the general population overuse analgesics; the prevalence of CDH subjects with analgesic overuse being 1.1% to 1.9% of the general population. Most of these patients with analgesic overuse are TM patients.

Quintela E, Castillo J, Muñoz P, Pascual J. · Health Centre of Astillero, University Hospital, Salamanca, Spain. · Cephalalgia. · Pubmed #16919055 No free full text.

Abstract: 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.

Oterino A, Toriello M, Cayón A, Castillo J, Colas R, Alonson-Arranz A, Ruiz-Alegria C, Quintela E, Monton F, Ruiz-Lavilla N, Gonzalez F, Pascual J. · University Hospital Marqués de Valdecilla-Neurology, Santander, Spain. · Headache. · Pubmed #19093296 No free full text.

Abstract: 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. METHODS: We investigated 5 polymorphisms implicated in female hormone metabolism (FSHR, CYP19A1, ESR1, NRIP1, and ESR2) in a cohort of 730 subjects matched for age and sex. The effect of gene-gene interaction was assessed using the set association approach, and the corresponding haplotypes were studied with PM Plus software. To corroborate initial results, we analyzed the selected markers using a cohort of 134 families in which 168 trios were suitable for transmission-disequilibrium test (TDT) analysis under the migraine with aura (MA) phenotype. RESULTS: A total of 356 consecutive migraine patients (198 with MA [76% females] and 158 migraine without aura [MO, 74% females], and 374 matched controls [71% females]) were genotyped. In the 2-point analyses, the ESR1 and ESR2 polymorphisms showed nominal association under MA/MO phenotype, and this association was higher with the FSHR polymorphism in MA females (P = .004, uncorrected). Using the SUMSTAT program, we observed ESR2-ESR1-FSHR significant gene-gene interaction, suggesting association with the MA/MO phenotype (P = .005; P = .003 in females), and with MA alone (P = .021; P = .030 for females).We corroborated that ESR2-ESR1-FSHR haplotypes interacted for migraine under a model-free hypothesis (empirical P = .010 for the whole sample; P = .001 for females), and the association was stronger for the MA phenotype alone (empirical P = 5.0e-4, under the heterogeneity model; P = .001 for females). These results were corroborated using family-based association approaches. We observed nominal association for ESR2 and ESR1 (P = .031 and .034, respectively) in the TDT study, and significant association for ESR1 using family-based association test statistics. Haplotype-TDT analyses showed further significant gene-gene interaction for ESR1-ESR2 (global P = .009), ESR2-FSHR (global P = .011), and nominally significant interaction for ESR2-ESR1-FSHR genes (global P = .037). CONCLUSION: We found significant association of female hormone metabolism polymorphisms under the perspective of multigene approach.

Castillo J, Láinez MJ, Domínguez M, Palacios G, Díaz S, Rejas J. · Primary Care Health Center of Camargo, Muriedas, Cantabria, Spain. · J Occup Environ Med. · Pubmed #18695448 No free full text.

Abstract: OBJECTIVE: To estimate the impact of migraine on labor productivity and health resources utilization in an active population attending Primary Care settings in Spain. METHODS: An observational, cross-sectional, and multicenter study was designed. Productivity, loss workdays equivalents and previous 3-months health resources utilization were calculated. RESULTS: Four thousand four hundred twenty six patients were evaluated. The migraine group showed the lowest productivity, highest loss workdays equivalents and health resources utilization compared with non-migraine headaches and subjects without headaches (P < 0.05 in all cases). Within the migraine group, lower productivity values were observed in female patients compared to male (64.04 vs 59.69; P < 0.05), while emergency room visits were more frequent for male patients (0.71 vs 076; P < 0.05). CONCLUSIONS: Subjects with migraine showed higher impact on health resources utilization and productivity when evaluated at Primary care level.

Oterino A, Castillo J, Pascual J, Cayon A, Alonso A, Ruiz-Alegria C, Valle N, Monton F, Ruiz-Lavilla N. · Service of Neurology, University Hospital Marques de Valdecilla, E-39008, Santander, Spain. · J Headache Pain. · Pubmed #17901921 No free full text.

Abstract: 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.

Leira R, Sobrino T, Rodríguez-Yáñez M, Blanco M, Arias S, Castillo J. · Headache and Stroke Unit and Neurovascular Research Laboratory, Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Spain. · Headache. · Pubmed #17501851 No free full text.

Abstract: OBJECTIVE: To examine the role of matrix metalloproteinase 9 (MMP-9) in migraine during headache and asymptomatic periods. METHODS: Thirty-four patients with migraine with and without aura (according to International Headache Society criteria) were studied. Clinical characteristic of headache were recorded. Blood samples for measurement of MMP-9 were drawn during headache attacks and during asymptomatic periods in all patients and in 10 healthy controls. RESULTS: We found higher plasma MMP-9 levels in migraine patients than in control group (129.3 [78.0-258.9] vs. 49.6 [39.1-64.3] ng/mL; P < .001). Migrainous patients showed higher MMP-9 plasma levels during headache attacks than in asymptomatic periods, both in migraine without aura (338.4 [275.1-396.2] vs. 118.2 [75.3-137.5] ng/mL; P < .0001), and migraine with aura (389.3 [273.4-487.1] vs. 139.3 [107.3-191.4] ng/mL; P < .0001). CONCLUSIONS: Our study showed an increased production of MMP-9 during migraine attacks. These data suggest a possible role of inflammation or blood-brain barrier disruption during the migraine attack.

Oterino A, Ruiz-Alegría C, Castillo J, Valle N, Bravo Y, Cayón A, Alonso A, Tejera P, Ruiz-Lavilla N, Muñoz P, Pascual J. · Service of Neurology, University Hospital Marqués de Valdecilla (UC), Santander, Spain. · Cephalalgia. · Pubmed #17388805 No free full text.

Abstract: 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.

Oterino A, Pascual J, Ruiz de Alegría C, Valle N, Castillo J, Bravo Y, González F, Sánchez-Velasco P, Cayón A, Leyva-Cobián F, Alonso-Arranz A, Muñoz P. · Services of Neurology, Universitary Hospital Marqués de Valdecilla, Santander, Spain. · Neuroreport. · Pubmed #16361951 No free full text.

Abstract: Migraine is a genetically complex disorder in which sexual hormones influence the phenotype. ESR1 G594A polymorphism has been associated with migraine in Australians. We performed a case-control study with G594A and G325C polymorphisms to determine whether ESR1 is associated with migraine in our population. An association between G594A and migraine could not be demonstrated here. By contrast, we observed that the C325 allele conferred a 1.6 (95% confidence interval=1.1-2.4) higher risk for suffering from migraine in women than the G allele. Women carrying the C352C genotype were over 3 times more likely to suffer from migraine than those carrying the G325G genotype. Therefore, we conclude that ESR1 G325C polymorphism is associated with migraine in our population.

Oterino A, Valle N, Pascual J, Bravo Y, Muñoz P, Castillo J, Ruiz-Alegría C, Sánchez-Velasco P, Leyva-Cobián F, Cid C. · Services of Neurology, University Hospital Marqués de Valdecilla (UC), Santander-39008, Spain. · Brain Res Mol Brain Res. · Pubmed #15953655 No free full text.

Abstract: There is growing evidence that folate metabolism is involved in migraine pathophysiology, mainly in migraine with aura. Even though folate metabolism is regulated by a number of enzymes, only two functional polymorphisms have been tested in association studies with migraine. Here, we have explored the possible role in migraine of other folate-metabolizing enzymes which are in close interdependency with 5',10'-methylenetetrahydrofolate reductase analyzing functional polymorphisms of these enzymes in a case-control study. Individually, thymidylate synthase (TS), methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthase (MTHFD1), or methionine synthase (MS) polymorphisms did not modify the general risk for suffering migraine. Nevertheless, we observed a strong interaction between TS and MTHFR mutated genotypes, which increased over 8-fold the risk for experiencing aura among migraineurs; MTHFD1 and MTHFR mutated genotypes also increased together the risk for migraine in general (OR = 3.08; 95% CI = 1.3-7.4). We conclude that the pathogenetic role of the MTHFR T677 allele in migraine is modulated by functional polymorphisms of TS and MTHFD1.

Castillo J, Muñoz P, Guitera V, Pascual J. · Health Center of Camargo, Santander, Spain. · Headache. · Pubmed #15613213 No free full text.

Abstract: 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. METHODS: A questionnaire exploring headache frequency was distributed to 2252 unselected subjects. Those having headache 10 or more days per month were given a headache diary and were seen by a neurologist who classified their headaches. The varieties of chronic daily headache were classified according to the second revision of IHS criteria proposed by Silberstein et al published in Neurology 1996;47:871. RESULTS: The questionnaire was returned by 1883 subjects (83.5%). One hundred thirty-five admitted to headache 10 or more days per month. Chronic daily headache criteria were fulfilled by 89 individuals (4.7%). Eighty were women. Forty-two (47.2% of subjects with chronic daily headache and 2.2% of all subjects) had chronic tension-type headache. Analgesic overuse was found in 8 (17%). Transformed migraine was diagnosed in 45 (50.6% of subjects with chronic daily headache and 2.4% of all subjects). Fourteen (31.1%) individuals with this form of chronic daily headache overused ergots or analgesics. The remaining 2 cases in this series met the criteria of new daily persistent headache. No one was diagnosed as having hemicrania continua. CONCLUSIONS: Almost 5% of the general population (9% of women) suffers from chronic daily headache, the proportion of chronic tension-type headache and transformed migraine being quite similar. Less than one third overuse analgesics. The prevalence of chronic daily headache subtypes shown here differs from data obtained from headache clinics, emphasizing that caution is needed in extrapolating data from specialized units to the general population.

Oterino A, Valle N, Bravo Y, Muñoz P, Sánchez-Velasco P, Ruiz-Alegría C, Castillo J, Leyva-Cobián F, Vadillo A, Pascual J. · Service of Neurology, University Hospital Marqués de Valdecilla, Santander, Spain. · Cephalalgia. · Pubmed #15154859 No free full text.

Abstract: 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.

Guitera V, Muñoz P, Castillo J, Pascual J. · Service of Neurology, University Hospital Marqués de Valdecilla, Santander, Spain. · Neurology. · Pubmed #11940693 No free full text.

Abstract: OBJECTIVE: To analyze the quality of life (QoL) of subjects with chronic daily headache (CDH) in the general population. METHODS: QoL 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). RESULTS: CDH 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. CONCLUSIONS: In 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.

Guitera V, Gutiérrez E, Muñoz P, Castillo J, Pascual J. · Departamentos de Medicina y Psiquiatría, y Neurología, Hospital Universitario Marqués de Valdecilla, Santander. · Neurologia. · Pubmed #11234657 No free full text.

Abstract: BACKGROUND AND AIMS: The prevalence and type of personality disorders in unselected patients with chronic daily headache (CDH) are unknown. The aim of this study was to analyze the personality profile of patients with CHD is the general population. PATIENTS AND METHODS: Eighty-nine patients with CDH taken from a sample of 1,883 unselected subjects from the general population completed the EPQ-A (Eysenck Personality Questionnaire-Adult). RESULTS: Sixty percent of the patients with CDH presented a personality profile with high values in the scales measuring both the neurotic component (N scales) and the psychotic component (P scale). No significant differences were observed in the percentage of patients with high scores in these scales according to the diagnoses of transformed migraine (TM) or chronic tension headache (CTH). However, the percentage of questionnaires with high or not adapted scores was significantly greater in the patients abusing of analgesic drugs than is the non-abusers (82% versus 53%). With regard to the personality profile, we found a greater, but not significant, percentage of patients with CDH with a high grade of neuroticism in comparison with psychoticism (52% versus 36%). There were no significant differences in the personality profile between the two main subgroups of CCH, TM and CTC: 56% of the patients with TM showed high grade of neuroticism and 47% psychoticism versus 52% and 30%, respectively in the case of the patients with CTC. Sixty-eight percent of the analgesic abusers presented neurotic features and 50% psychotic features versus 47% and 32%, respectively, for the non abusers. CONCLUSIONS: There is a high percentage of subjects with CDH in the general population who present high scores in the scales measuring the two basic components of the personality, such as neuroticism and psychoticism. This personality profile is still found more frequently in patients presenting symptomatic medication abuse.

Guitera V, Muñoz P, Castillo J, Pascual J. · Department of Medicine and Psychiatry, University Hospital Marqués de Valdecilla, Santander, Spain. · Cephalalgia. · Pubmed #10668102 No free full text.

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