Telomere length and Parkinson's disease in men: a nested case-control study.

BACKGROUND AND PURPOSE: Telomere shortening has been implicated in neurodegenerative disorders. However, available data on the association between telomere length and Parkinson's disease (PD) are inconclusive. METHODS: A nested case-control design was used amongst men participating in the prospective Physicians' Health Study. A large proportion of participants provided blood samples in 1997 and they were followed through 2010. Men with self-reported PD were age-matched to controls in a 1:2 ratio. Quantitative PCR was used to determine the telomere repeat copy number to single gene copy number ratio (TSR) in genomic DNA extracted from peripheral blood leukocytes. TSR was used as a measure for relative telomere length (RTL) in our analyses. Conditional logistic regression was used to determine the risk of PD associated with RTL. RESULTS: Data on RTL were available from 408 cases and 809 controls. Median TSR was shorter in controls than in cases (47.7 vs. 50.2; P = 0.02). The age-adjusted odds ratio (OR) for PD was 0.66 [95% confidence interval (CI) 0.46-0.95; Ptrend over quartiles 0.02] comparing the lowest to the highest quartile. The pattern of association was unchanged when comparing RTL below versus above the median (age-adjusted OR 0.75; 95% CI 0.59-0.96). Associations were similar after additional adjustment for many covariates. CONCLUSION: Contrary to what was expected, in this large nested case-control study amongst men shorter telomeres were associated with reduced PD risk. Future research on the nature of this counterintuitive association is warranted.

Telomere length and ischaemic stroke in women: a nested case-control study.

BACKGROUND AND PURPOSE: Telomere shortening has been implicated in cardiovascular disease (CVD). However, prospective data on the association between relative telomere length (RTL) and ischaemic stroke are scarce and inconclusive. METHODS: We used a nested case-control design among women participating in the prospective Nurses' Health Study. Participants provided blood samples in 1990 and were followed till 2006. Women with confirmed incident ischaemic stroke were matched to controls by age, smoking, postmenopausal status and postmenopausal hormone use. Quantitative polymerase chain reaction was used to determine RTL in genomic DNA extracted from peripheral blood leukocytes. Conditional logistic regression was used to determine the risk of ischaemic stroke associated with RTL, using RTL quartiles and as dichotomous according to the median. RESULTS: Data on RTL were available from 504 case-control pairs. Results did not suggest an association between RTL and ischaemic stroke. The odds ratio (OR) for ischaemic stroke was 0.82 [95% confidence interval (CI) 0.52-1.32] comparing lowest with the highest RTL quartile and 0.90 (95% CI 0.65-1.24) comparing RTL below the median with RTL above the median. Associations were unchanged after additional adjustment for cardiovascular risk factors. Further analyses suggested an association between RTL and fatal ischaemic stroke (54 case-control pairs; lowest versus highest quartile OR = 1.99, 95%CI 0.26-14.9); however, results were statistically insignificant. CONCLUSION: In this large nested case-control study among women RTL was not associated with ischaemic stroke. In light of the varying study results in the literature on the association between telomere length and stroke, additional research is warranted.

Multiple sclerosis and restless legs syndrome: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) has been reported to occur more frequently in patients with multiple sclerosis (MS) than in people without MS. METHODS: Systematic review and meta-analysis of studies investigating RLS in patients with MS published through April 2012. We calculated the prevalences and 95% confidence intervals (CIs) of RLS in patients with MS and people without MS as well as odds ratios (ORs) and 95% CIs of the association between MS and RLS based on data from the publications. We then calculated pooled effect estimates for the association between MS and RLS. RESULTS: We identified 24 studies. RLS prevalence amongst patients with MS ranged from 12.12% to 57.50% and from 2.56% to 18.33% amongst people without MS. Heterogeneity amongst studies was high (RLS prevalence in patients with MS I(2) =94.4%; RLS prevalence amongst people without MS I(2) =82.2%). Hence, we did not pool the prevalence data for meta-analysis. Heterogeneity amongst studies investigating the association between MS and RLS was moderate (I(2) =53.6%). Pooled analysis indicates that MS is associated with a fourfold increased odds for RLS (pooled OR=4.19, 95% CI 3.11-5.66). This association was smaller amongst studies published as full papers (pooled OR=3.94, 95% CI 2.81-5.54) than amongst studies published as abstracts only (pooled OR=6.23, 95% CI 3.25-11.95). CONCLUSION: This systematic review indicates that RLS prevalence amongst patients with MS ranges from 12.12% to 57.50% in different populations. Pooled analysis further indicates that the odds of RLS amongst patients with MS are fourfold higher compared to people without MS.

MTHFR 677C->T and ACE D/I polymorphisms and migraine attack frequency in women.

Data on the association of the MTHFR 677C→T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 ≥ weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 ≥ weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA.

Agreement of self-reported migraine with ICHD-II criteria in the Women's Health Study.

Migraine is a common headache disorder that is increasingly being evaluated in population-based studies. The American Migraine Study II and the Women's Health Study (WHS) have successfully used 'modified' International Classification of Headache Disorders, 1st edition (ICHD-I) criteria to classify patients. Investigating agreement of self-reported migraine in large epidemiological studies with the criteria of the revised version [International Classification of Headache Disorders, 2nd edition (ICHD-II)] is sparse. We have investigated 1675 women with self-reported migraine participating in the WHS, who provided additional information on a detailed migraine questionnaire that allowed us to apply all ICHD-II criteria. In this sub-cohort, we confirmed self-reported migraine in > 87% of women when applying the ICHD-II criteria for migraine (71.5%) and probable migraine without aura (16.2%). In conclusion, there is excellent agreement between self-reported migraine and ICHD-II-based migraine classification in the WHS. In addition, questionnaire-based migraine assessment according to full ICHD-II criteria in large population-based studies is feasible.

[What is migraine?]. / Was ist Migräne?

Migraine is a multifactorial and heterogeneous disorder. Diagnostic criteria have been established by the International Headache Society, however these are only supportive in terms of definition. The pathophysiology involves neuronal and vascular phenomena. The former is supported by the cortical spreading depression being the aura correlate and by brainstem and hypothalamic activation during the pain phase; the latter is suggested by the association between migraine and cardiovascular disease and findings of pathological vasoreactivity and endothelial dysfunction. Triptans and calcitonin gene-related peptide receptor antagonists show only a relative migraine-specific action; up to 30% of patients are nonresponders. Despite a clear genetic component, the discovery of specific genes for common forms of migraine remains elusive. Electrophysiological studies consistently indicate a characteristic "dyshabituation" concurring with clinical features of altered sensory perception. The age- and sex-specific pattern along with the effect of external factors on the course of migraine argue in favor of the involvement of epigenetic mechanisms. Knowledge about migraine is still limited, which hampers a definition.

ACE D/I polymorphism, migraine, and cardiovascular disease in women.

BACKGROUND: Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial. METHODS: Association study among 25,000 white US women, participating in the Women's Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship among genotype, migraine, and incident CVD. RESULTS: At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, ischemic stroke, and myocardial infarction. Migraine with aura doubled the risk for CVD, but only for carriers of the DD (multivariable-adjusted relative risk [RR] = 2.10; 95% CI = 1.22-3.59; p = 0.007) and DI genotype (multivariable-adjusted RR = 2.31; 95% CI = 1.52-3.51; p < 0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke. CONCLUSIONS: Data from this large cohort of women do not suggest an association of the ACE deletion/insertion (D/I) polymorphism with migraine, migraine aura status, or cardiovascular disease (CVD). The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.

Migraine, allodynia, and implications for treatment.

Allodynia--perception of pain from non-noxious stimuli--is a common clinical feature in various pain syndromes. The significance for migraine has increasingly been recognized and the pathophysiology has been investigated in detail. Allodynia is a marker for sensitization of central trigeminal neurons. Intensity and persistence of allodynic symptoms are a function of duration of migraine attacks, frequency of attacks, and migraine history. It has been hypothesized that treatment success with triptans may be severely impaired in the presence of allodynia. However, randomized controlled trials did not confirm that. Treatment with cyclooxygenase inhibitors and dihydroergotamine does not seem to be limited by allodynia; these medications may be able to reverse allodynia. Data on the new class of calcitonin-gene related-peptide antagonists are not yet available. Additional and more refined randomized controlled trials, focusing on methodological issues pertaining to the determination of allodynia, are warranted to resolve the true relationship between allodynia and treatment response. Regardless--based on available randomized controlled trials--the recommendation prevails to initiate abortive treatment as soon as possible after attack onset when pain is still mild.

[Pathophysiology of migraine and clinical implications]. / Pathophysiologie der Migräne im klinischen Kontext.

Migraine pathophysiology is determined by genetic and environmental factors. Based on altered cerebral habituation and low serotonin levels, certain triggers can elicit a migraine attack. Following initial unspecific prodromi, an aura follows in many patients which most often consists of visual symptoms. Cortical spreading depression is the electrophysiological correlate of the aura and can activate the trigemino-vascular system. This is one potential mechanism initiating the pain process. The characteristic unilateral pulsating headache is caused by a neurogenic inflammation in the meninges. Neck pain as reported by some patients is a migraine-specific feature, the anatomical basis being the trigemino-cervical complex. Functional changes in the pain processing system maintain the headache. Among these are sensitization of trigeminal nucleus caudalis neurons and an altered antinociception descending from the periaquaductal grey. Triptans have a peripheral and central mode of action, but they are no longer effective once central sensitization has occurred.