Smoking and disease progression in multiple sclerosis.

BACKGROUND: Although cigarette smokers are at increased risk of developing multiple sclerosis (MS), the effect of smoking on the progression of MS remains uncertain. OBJECTIVE: To establish the relationship between cigarette smoking and progression of MS using clinical and magnetic resonance imaging outcomes DESIGN: Cross-sectional survey and longitudinal follow-up for a mean of 3.29 years, ending January 15, 2008. SETTING: Partners MS Center (Boston, Massachusetts), a referral center for patients with MS. PATIENTS: Study participants included 1465 patients with clinically definite MS (25.1% men), with mean (range) age at baseline of 42.0 (16-75) years and disease duration of 9.4 (0-50.4) years. Seven hundred eighty patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers, and 257 (17.5%) were current smokers. MAIN OUTCOME MEASURES: Smoking groups were compared for baseline clinical and magnetic resonance imaging characteristics as well as progression and sustained progression on the Expanded Disability Status Scale at 2 and 5 years and time to disease conversion to secondary progressive MS. In addition, the rate of on-study change in the brain parenchymal fraction and T2 hyperintense lesion volume were compared. RESULTS: Current smokers had significantly worse disease at baseline than never-smokers in terms of Expanded Disability Status Scale score (adjusted P < .001), Multiple Sclerosis Severity Score (adjusted P < .001), and brain parenchymal fraction (adjusted P = .004). In addition, current smokers were significantly more likely to have primary progressive MS (adjusted odds ratio, 2.41; 95% confidence interval, 1.09-5.34). At longitudinal analyses, MS in smokers progressed from relapsing-remitting to secondary progressive disease faster than in never-smokers (hazard ratio for current smokers vs never-smokers, 2.50; 95% confidence interval, 1.42-4.41). In addition, in smokers, the T2-weighted lesion volume increased faster (P = .02), and brain parenchymal fraction decreased faster (P = .02). CONCLUSION: Our data suggest that cigarette smoke has an adverse influence on the progression of MS and accelerates conversion from a relapsing-remitting to a progressive course.

Rate of brain atrophy in benign vs early multiple sclerosis.

BACKGROUND: Benign multiple sclerosis (MS) is defined by minimal or no disability after many years of observation, therefore a less degenerative disease process is suspected to be present in this subset of patients. OBJECTIVE: To compare brain atrophy rates in patients with long-standing benign MS vs typical early MS. DESIGN: A longitudinal prospective cohort study and a retrospective database review. SETTING: An academic MS center. PATIENTS: Thirty-nine patients with clinically defined benign MS and an age-matched group of 40 patients with early relapsing-remitting MS. MAIN OUTCOME MEASURES: Baseline demographic, treatment, brain magnetic resonance imaging measures, and annualized atrophy rates, derived from serial brain parenchymal fraction measurements across 2 years, were compared. RESULTS: In the baseline analysis, patients with benign MS were matched to the early MS group on age, sex, treatment with immunomodulatory therapy, T2 lesion volume, and brain parenchymal fraction. The mean (SD) annualized brain atrophy rate in patients with benign MS (-0.16% [0.51%]) was lower than that in patients with early MS (-0.46% [0.72%]) (P = .02). The difference remained significant after controlling for age, sex, and treatment (P = .04). CONCLUSIONS: Serial magnetic resonance imaging revealed a low 2-year rate of brain atrophy in patients with clinically benign MS, suggesting a less prominent degenerative component in its pathogenesis than in patients with typical early MS. Identification of patients with a low rate of brain atrophy may indicate a benign course.

Genetic polymorphisms in venous thrombosis and pulmonary embolism after total hip arthroplasty: a pilot study.

UNLABELLED: Deep venous thrombosis (DVT) after major orthopaedic surgery is a substantial concern. We asked whether the single or combined presence of thrombophilic genetic polymorphisms might further increase the already high risk for venous thrombosis and pulmonary embolism (PE) after THA. We therefore compared the prevalence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and plasminogen activator inhibitor 4G/5G polymorphisms between 50 patients with symptomatic DVT within 3 weeks after elective THA and an asymptomatic control group of 85 patients. We found no major difference for the presence of a single mutation between the groups. Factor V Leiden and homozygous MTHFR C667T mutations were of borderline significance with odds ratios (95% confidence intervals) of 3.73 (0.89-15.63) and 2.93 (0.92-9.29), respectively. Patients with homozygous or combined heterozygous status of MTHFR C677T and A1298C mutation had a higher frequency of DVT after elective THA (odds ratio, 2.86; 95% confidence interval, 1.32-6.35) than those with wild-type. The presence of a single mutation may not further increase the already high risk for symptomatic DVT after THA, whereas combinations of mutations of distinct polymorphisms might be important. However, prospective studies with a larger number of patients are needed before we would recommend preoperative screening. LEVEL OF EVIDENCE: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.