Serum lipid abnormalities in migraine: A meta-analysis of observational studies.

BACKGROUND: The association of migraine with vascular comorbidities is long-established. The contribution of the "traditional" cardiovascular risk factors to this connection remains unclear. OBJECTIVE: To determine-quantify the differences in the serum lipid concentrations between lipid-lowering agents-naïve individuals with migraine and healthy controls (HC). METHODS: The study protocol was not preregistered with an online systematic review-protocol registry. A literature search involving MEDLINE, EMBASE, CENTRAL, Google Scholar, and the OpenGrey database was performed. Case-control, cross-sectional, or cohort studies involving HC and participants with migraine (with and without aura regardless of the use of prophylactic treatment) that quantitatively assessed serum low-density lipoprotein cholesterol (LDL-C) (primary index) and/or total cholesterol (TC) and/or high-density lipoprotein cholesterol (HDL-C) and/or triglycerides (TG) (secondary indices) were retrieved. Articles including participants with known dyslipidemia (or under lipid-lowering medications) or with secondary causes of dyslipidemia (aside from the subjectively assessed lifestyle parameters) were excluded. Studies with abstracts and full texts not published in English and articles reporting the implementation of other study designs (reviews, meta-analyses, commentaries, case reports, etc.) were excluded as well. Conference abstracts and English abstracts from studies with full texts not published in English were evaluated as part of the gray literature. Each step of the review process was performed by two investigators independently, and relevant data were abstracted based on standardized extraction forms. Any discrepancies were resolved by a third investigator. RESULTS: Seventeen studies (16 case-control and 1 cross-sectional) fulfilled the eligibility criteria. Retrieved articles involved adult participants, principally during the fourth decade of life. Results were compatible with higher LDL-C levels in migraine individuals (1370) than in HC (1215) [12 studies, mean difference (MD) = 10.4 mg/dl, 95% confidence interval (CI) = (1.6, 19.2)]. Similarly, higher TC levels were determined in migraine patients [14 studies, migraine = 1325, HC = 1213, MD = 10.6 mg/dl, 95% CI = (1.8, 19.3)], as were TG levels [15 studies, migraine = 1526, HC = 1262, MD = 11.8 mg/dl, 95% CI = (3.6, 20.0)]. HDL-C concentrations were not different between the two groups [14 studies, migraine = 1488, HC = 1328, MD = -0.4 mg/dl, 95% CI = (-2.2, 1.5)]. Prespecified sensitivity analysis following the exclusion of studies not presenting comparable body mass index values between the groups nullified the significant difference regarding LDL-C levels [MD = 5.3 mg/dl, 95% CI = (-0.1, 10.8)]. Subgroup analyses as well as the direct comparison of migraine with aura and migraine without aura individuals were compatible with no difference regarding lipid concentrations, but only a small fraction of the retrieved studies presented relevant figures. CONCLUSIONS: Although our results are of limited generalizability, since most retrieved studies were performed in Turkey (nine studies), TC abnormalities may provide part of the explanation for the unfavorable cardiovascular profile of migraine patients. Lifestyle may be partly or entirely accountable for the determined increased serum TC. Additional studies that will completely address the effect that lifestyle parameters exert on lipid concentrations are required to better capture existing abnormalities.

Genetic Risk Factors for Essential Tremor: A Review.

Highlights: In the current review, we thoroughly reviewed 74 identified articles regarding genes and genetic loci that confer susceptibility to ET. Over 50 genes/genetic loci have been examined for possible association with ET, but consistent results failed to be reported raising the need for collaborative multiethnic studies. Background: Essential tremor (ET) is a common movement disorder, which is mainly characterized by bilateral tremor (postural and/or kinetic) in the upper limbs, with other parts of the body possibly involved. While the pathophysiology of ET is still unclear, there is accumulating evidence indicating that genetic variability may be heavily involved in ET pathogenesis. This review focuses on the role of genetic risk factors in ET susceptibility. Methods: The PubMed database was searched for articles written in English, for studies with humans with ET, controls without ET, and genetic variants. The terms "essential tremor" and "polymorphism" (as free words) were used during search. We also performed meta-analyses for the most examined genetic variants. Results: Seventy four articles concerning LINGO1, LINGO2, LINGO4, SLC1A2, STK32B, PPARGC1A, CTNNA3, DRD3, ALAD, VDR, HMOX1, HMOX2, LRRK1,LRRK2, GBA, SNCA, MAPT, FUS, CYPsIL17A, IL1B, NOS1, ADH1B, TREM2, RIT2, HNMT, MTHFR, PPP2R2B, GSTP1, PON1, GABA receptors and GABA transporter, HS1BP3, ADH2, hSKCa3 and CACNL1A4 genes, and ETM genetic loci were included in the current review. Results from meta-analyses revealed a marginal association for the STK32B rs10937625 and a marginal trend for association (in sensitivity analysis) for the LINGO1 rs9652490, with ET. Discussion: Quite a few variants have been examined for their possible association with ET. LINGO1 rs9652490 and STK32B rs10937625 appear to influence, to some extent, ET susceptibility. However, the conflicting results and the lack of replication for many candidate genes raise the need for collaborative multiethnic studies.

Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis.

BACKGROUND: Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies. OBJECTIVE: The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO). METHODS: Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias. RESULTS: Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2  = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2  = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2  = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I2  = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2  = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I2  = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I2  = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I2  = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2  = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I2  = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I2  = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I2  = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2  = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I2  = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO. CONCLUSIONS: Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.

Pyridoxine, folate and cobalamin for migraine: A systematic review.

There is a possible relationship between migraine and hypercoagulability inducing factors, such as hyperhomocysteinemia. In this context, homocysteine (Hcy)-lowering vitamins (B6-folate-B12) may prove beneficial in the management-prophylaxis of migraine. We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6, folate and B12 (alone or as adjunctive therapies) to migraine patients, as well as patients suffering from other primary headache disorders. MEDLINE, EMBASE, CENTRAL, Google Scholar, trial registries and OpenGrey were searched. Twelve relevant articles were retrieved. The management of acute migraine attacks with Hcy-lowering vitamins has not provided promising results (one randomized controlled trial-RCT-and one prospective uncontrolled trial). On the contrary, significant benefits were registered for the use of B6 alone, in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura (MA) in adults compared to placebo (five RCTs, only one did not obtain significant results). Folate supplementation alone was not more efficacious than placebo (one RCT). Limited data for the prophylaxis of migraine without aura (MO) in children (two prospective uncontrolled trials) and adults (two prospective uncontrolled trials involving both MA and MO participants) impede the extraction of safe conclusions. An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common. Overall, a potential beneficial effect regarding the administration of B6, folate and/or B12 in the prophylaxis of MA in adults was indicated. Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted.

Does the CD33 rs3865444 Polymorphism Confer Susceptibility to Alzheimer's Disease?

Alzheimer's disease (AD) is a complex genetic disorder. To date, published data have reported conflicting results on the role of CD33 rs3865444 polymorphism in AD. The present study aimed at evaluating the effect of rs3865444 on AD in a large cohort of Greek native patients with AD. We also conducted a meta-analysis by pooling information from different studies on the same topic. Patients with AD (n = 327) and healthy controls (n = 327) were analyzed and genotyped for rs3865444. Single locus analyses were run to explore possible associations between CD33 rs3865444 polymorphism and AD. Our analysis yielded no significant interaction between AD and the CD33 rs3865444 polymorphism. The lack of interaction between the two variables persisted even after a pooled meta-analysis of 8 studies (with 13 datasets), with 4015 AD cases and 7981 controls. The overall results do not support the hypothesis that CD33 rs3865444 polymorphism increases the risk of AD. The results also suggest that the identification of functional variants in CD33 that are indisputably correlated with AD may be an important factor to investigate in future genetic screening studies.

TREM2 R47H (rs75932628) variant is unlikely to contribute to Multiple Sclerosis susceptibility and severity in a large Greek MS cohort.

BACKGROUND: Multiple Sclerosis is a multifactorial autoimmune disease of the central nervous system, characterized by focal inflammation, demyelination and secondary axonal injury. TREM2 is a signaling protein which participates in the innate immune system by implication to inflammation, proliferation and phagocytosis. The R47H (rs75392628) rare variant of the TREM2 gene has been related to various neurological diseases and leads to impaired signaling, lipoprotein binding, lipoprotein uptake and surface uptake. AIM: To assess the role of TREM2 rs75932628 on MS risk through a genetic candidate gene association case-control study in a Greek population. METHODS: 1246 MS cases and 398 controls were genotyped for this variant. RESULTS: No MS or healthy subjects carried the variant. CONCLUSION: This variant does not seem to play a determining role in the pathogenesis of MS, although further studies examining the presence of TREM2 mutations in other, phylogenetically different populations and the epigenetic regulation of this gene are needed in order to thoroughly investigate its role in MS.

Body mass index in patients with Multiple Sclerosis: a meta-analysis.

Background: The impact of nutrition and diet on the etiology of Multiple Sclerosis (MS) has been evaluated through a number of studies. Only a limited number reported findings on the association between body mass index (BMI) and MS. We systematically assessed whether BMI differs between MS patients and healthy individuals. Methods: The PubMed database was searched for available studies assessing the relationship between BMI and MS until April 2018. Random effects models were applied for evaluating the association of mean BMI between MS, relapsing-remitting MS (RRMS) patients, females, or males with MS, and their respective healthy control groups. Results: We included 25 studies. The mean BMI of MS patients during the course of the disease and RRMS patients was significantly different from the mean BMI of their healthy counterpart individuals [standardized mean difference (SMD) (95% confidence interval (CI)): -0.25 (-0.44, -0.06), PZ = 0.01 and SMD (95%): -0.27 (-0.54, -0.01), PZ = 0.04, respectively]. The mean BMI of females with MS was significantly differentfrom that of corresponding healthy females [SMD (95% CI): -0.52 (-0.96, -0.07), PZ = 0.02]. Moreover, the mean BMI was significantly different between males with MS and healthy males [SMD (95% CI): -0.75 (-1.33, -0.18), PZ = 0.01]. Conclusions: Statistically significantly lower mean BMI was revealed in the overall MS patients' group during the MS course than in healthy controls. The same difference was revealed in all parts of the meta-analysis demonstrating a significantly lower BMI in patients with RRMS, in females, and in males with MS, when compared to their respective healthy individuals.