Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis.

OBJECTIVES: Reports of increased amyotrophic lateral sclerosis (ALS) with hyperlipidaemia and elevated plasma homocysteine levels as well as cigarette-smoking and polymorphisms in angiogenic genes suggest a role for altered vascular homeostasis in ALS pathogenesis. The authors assessed the association between vascular risk factors and ALS. METHODS: Traditional cardiovascular risk factors (smoking, hypertension, hypercholesterolaemia, diabetes and body mass index (BMI)) and cardiovascular disease prior to ALS onset established by a questionnaire were compared in 334 patients and 538 age- and sex-matched controls. Biochemical assessments (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and homocysteine) at diagnosis were measured in blood samples of 303 patients with ALS and compared with prospectively collected data from 2100 population-based controls. RESULTS: Patients with ALS used cholesterol-lowering agents less frequently (OR=0.6, p=0.008) and had a lower BMI (OR=0.9, p=0.001), a lower LDL/HDL ratio (women: OR=0.5, p<0.001; men: OR=0.4, p<0.001) and lower homocysteine levels (women: OR=0.9, p=0.02; men: OR=0.9, p<0.001). The mean LDL and TC levels were significantly lower among patients with a lower functional vital capacity percentage of predicted (FVC). In the univariate analysis, a higher LDL/HDL ratio correlated with increased survival (HR=0.9, p=0.04); after adjusting for the confounders age, site and FVC, no difference was observed. CONCLUSIONS: Vascular risk factors, measured clinically and biochemically, were not associated with increased ALS. Instead, patients reported less use of cholesterol-lowering medication and had a lower premorbid BMI and favourable lipid profile-all findings consistent with the hypothesis that a higher metabolic rate plays a role in ALS.

Increased frequency of HLA-DRB1*15 in patients with multifocal motor neuropathy.

OBJECTIVES: The favorable response to treatment with IV immunoglobulins and the presence of IgM antibodies to the glycolipid GM1 are indications that inflammation underlies multifocal motor neuropathy (MMN) pathogenesis. We investigated the association of MMN with human leukocyte antigen (HLA) class I and II antigens. METHODS: HLA class I and II antigens of 74 Dutch patients with MMN and 700 controls were determined in a case-control study. Associations of HLA types with MMN disease characteristics were investigated. RESULTS: Compared with controls, patients with MMN had higher frequencies of HLA-DRB1*15 (41 vs 24%, p = 0.0017). Disease characteristics were not associated with specific HLA types. CONCLUSIONS: Similar associations were found in patients with multiple sclerosis and women with chronic immune-mediated demyelinating neuropathy, which may suggest that these demyelinating disorders share pathogenic mechanisms.

Lifetime occupation, education, smoking, and risk of ALS.

OBJECTIVE: To investigate the association between cigarette smoking, level of education, occupation, and the occurrence of sporadic amyotrophic lateral sclerosis (ALS). METHODS: A total of 364 patients and 392 controls completed a questionnaire covering smoking habits, level of education, and occupational history. Main occupations were coded according to the International Standard Classification of Occupations and compared between patients and controls. RESULTS: The univariate analysis showed an increased risk of developing ALS among current cigarette smokers (OR = 1.7; 95% CI = 1.1 to 2.6; p = 0.01), those with a low level of education (elementary school) (OR = 2.2; 95% CI = 1.2 to 3.8; p < 0.01), and among women whose main occupation was classified as crafts and related trades workers (OR = 8.4; 95% CI = 1.0 to 70.1; p = 0.05). Multivariate analysis (with covariates age, smoking, education, and occupation) showed an increased risk for current smokers of cigarettes (OR = 1.6; 95% CI = 1.0 to 2.5; p = 0.04). CONCLUSIONS: Occupation, education, and cigarette smoking are risk factors for amyotrophic lateral sclerosis, but only smoking appeared independently associated.

Lack of association between VEGF polymorphisms and ALS in a Dutch population.

Sequence alterations in the promoter region of the vascular endothelial growth factor (VEGF) gene have been implicated in increasing the risk of developing ALS. VEGF promoter haplotypes were determined in 373 patients with sporadic ALS and 615 matched healthy controls in The Netherlands. No significant association between the previously reported at-risk haplotypes and ALS was found. Pooling our results with the previously studied population still showed a significant association with the AAG haplotype.