Ali Manouchehrinia

Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study

Tobacco smoking has been linked to an increased risk of multiple sclerosis. However, to date, results from the few studies on the impact of smoking on the progression of disability are conflicting. The aim of this study was to investigate the effects of smoking on disability progression and disease severity in a cohort of patients with clinically definite multiple sclerosis. We analysed data from 895 patients (270 male, 625 female), mean age 49 years with mean disease duration 17 years. Forty-nine per cent of the patients were regular smokers at the time of disease onset or at diagnosis (ever-smokers). Average disease severity as measured by multiple sclerosis severity score was greater in ever-smokers, by 0.68 (95% confidence interval: 0.36–1.01). The risk of reaching Expanded Disability Status Scale score milestones of 4 and 6 in ever-smokers compared to never-smokers was 1.34 (95% confidence interval: 1.12–1.60) and 1.25 (95% confidence interval: 1.02–1.51) respectively. Current smokers showed 1.64 (95% confidence interval: 1.33–2.02) and 1.49 (95% confidence interval: 1.18–1.86) times higher risk of reaching Expanded Disability Status Scale scores 4 and 6 compared with non-smokers. Ex-smokers who stopped smoking either before or after the onset of the disease had a significantly lower risk of reaching Expanded Disability Status Scale scores 4 (hazard ratio: 0.65, confidence interval: 0.50–0.83) and 6 (hazard ratio: 0.69, confidence interval: 0.53–0.90) than current smokers, and there was no significant difference between ex-smokers and non-smokers in terms of time to Expanded Disability Status Scale scores 4 or 6. Our data suggest that regular smoking is associated with more severe disease and faster disability progression. In addition, smoking cessation, whether before or after onset of the disease, is associated with a slower progression of disability.

Mortality in multiple sclerosis: meta-analysis of standardised mortality ratios

Objective There are inconsistent data on mortality in people with multiple sclerosis (MS). We performed a meta-analysis of all-cause, cause-specific and gender-specific crude mortality rates (CMRs), and standardised mortality ratios (SMRs) in MS, and estimated the rate of change of CMR and SMR over the past 50u2005years. Methods Medline, Embase and the Cochrane Library were searched. Keywords: ‘Multiple Sclerosis’ and (‘standardised mortality’ or ‘standardized mortality’). Inclusion criteria: availability of data on the number of deaths; mean or median patient follow-up or reports of SMRs; being a longitudinal study. 12 studies were included covering the period 1949–2012 (27u2005423 patients; 6628 deaths; 437u2005832 person-years follow-up). CMR was calculated. SMRs were extracted. CMRs and natural logarithm of SMRs were pooled by the method of the inverse of the variance. Meta-regression models were used to investigate the secular trends. Results Pooled CMR was 9.78/1000 person-years (95% CI 6.81 to 14.02). Pooled all-cause SMR was 2.80 (95% CI 2.74 to 2.87). All-cause SMR was 2.56 (95% CI 2.47 to 2.66) in males and 3.06 (95% CI 2.97 to 3.17) in females. SMR due to cancer was 0.89 (95% CI 0.83 to 0.97). SMRs due to cardiovascular diseases, suicide, infection and respiratory diseases were 1.29 (95% CI 1.20 to 1.38), 2.13 (95% CI 1.80 to 2.51) and 2.91 (95% CI 2.60 to 3.26). There was no trend in CMRs, all-cause, and gender-specific SMRs. Conclusions The excess mortality in MS relative to the general population has not changed over the past 50u2005years. Female patients with MS have higher survival disadvantage compared to that of males. Death due to cardiovascular diseases, suicide and infection is higher in patients with MS compared to the general population.

Tobacco smoking and excess mortality in multiple sclerosis: a cohort study

Objective As patients with multiple sclerosis (MS) have more than 2.5-fold increased mortality risk, we sought to investigate the impact of tobacco smoking on the risk of premature death and its contribution to the excess mortality in MS patients. Methods We studied 1032 patients during the period 1994–2013 in a UK-based register. Cox regression model was used to investigate the impact of smoking on the risk of premature death, controlling for confounders. Smoking-specific mortality rates were compared with the UK general population. Results Of 923 patients with clinically definite MS, 80 (46 males and 34 females) had died by December 2012. HRs for death in current smokers and ex-smokers relative to never smokers were 2.70 (95% CI 1.59 to 4.58, p<0.001) and 1.30 (95% CI 0.72 to 2.32; pu2009=u20090.37). The standardised mortality ratio, compared with the UK general population, when stratified by smoking status was 3.83 (95% CI 2.71 to 5.42) in current smokers, 1.96 (95% CI 1.27 to 3.0) in ex-smokers and 1.27 (95% CI 0.87 to 1.86) in non-smokers. Never smokers and ex-smokers with MS had similar mortality rates compared with never smokers and ex-smokers without MS in the male British doctors cohort (1.12 (95% CI 0.63 to 1.97) and 0.54 (95% CI 0.26 to 1.14), respectively), while current smokers with MS had 84% higher rate of death compared with current smokers without MS (95% CI 1.24 to 2.72). Conclusions Tobacco smoking can account for some of the excess mortality associated with MS and is a risk determinant for all-cause and MS-related death.

Cost-effectiveness of disease-modifying therapies in multiple sclerosis.

Multiple sclerosis (MS) is a leading cause of disability among young adults and has a significant economic impact on society. Although MS is not currently a curable disease, costly treatments known as disease-modifying therapies (DMTs) are available to reduce the disease impact in certain types of MS. In the current economic downturn, cost-effectiveness analysis (CEA) of therapies in MS has become an important part of the decision-making process in order to use resources efficiently in the face of the rapidly escalating costs of MS. While some studies have reported costs of DMTs at the level of cost-effectiveness thresholds, some have estimated their costs beyond the tolerance level of health care systems. On the basis of the current literature and given the difficulties in accurately assessing cost-effectiveness in diseases like MS, it is challenging to determine whether DMTs are cost-effective. Further population-based studies are required regarding the cost-effectiveness of therapies in MS.

Multiple sclerosis course and clinical outcomes in patients with comorbid asthma: a survey study

Objective To determine if comorbid asthma is associated with accumulation of multiple sclerosis (MS)-related impairment and disability. Method We sent a comprehensive questionnaire to a cohort of patients with MS and examined the association between comorbid asthma and reaching Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0. Multiple Sclerosis Impact Scale (MSIS-29) scores were compared between patients with MS with and without comorbid asthma. Results 680 patients participated in our study of whom 88 (12.9%) had comorbid asthma. There was no difference in the prevalence of asthma between our MS cohort and the England general population (OR: 0.89, 95% CI 0.68 to 1.17). We did not observe a significant association between having asthma and the risk of reaching EDSS scores 4.0 and 6.0 (HR: 1.29, 95% CI 0.93 to 1.77, and HR: 1.33, 95% CI 0.93 to 1.89, respectively) after controlling for confounders. Patients with MS with asthma reported higher level of psychological impairments (coefficient: 2.29, 95% CI 0.1 to 4.49). Conclusions Asthma is a prevalent condition among patients with MS and it may contribute to the psychological impairment in MS. Although we did not observe significant association between comorbid asthma and physical disability in MS, it seems that the two conditions influence one another.

Reduced EDSS progression in multiple sclerosis patients treated with modafinil for three years or more compared to matched untreated subjects.

BACKGROUNDnModafinil is a wakefulness-promoting drug used to treat narcolepsy, obstructive sleep apnoea, and shift-work sleep disorder. Modafinil has also been used for the treatment of fatigue and excessive sleepiness in other neurological disorders including multiple sclerosis, psychiatric disorders, and for cognitive enhancement. Recent preclinical studies suggest a potential neuroprotective effect of modafinil in neurodegenerative diseases. Therefore, we investigated its neuroprotective potential in multiple sclerosis.nnnOBJECTIVEnTo retrospectively assess disease progression in a group of MS patients that had received treatment with modafinil, and a matched group that received no treatment with modafinil.nnnMETHODSnWe assessed the expanded disability status scale (EDSS) score change, over at least three years, in 30 patients with MS treated with modafinil, and in 90 patients who did not receive modafinil. The two groups were matched for initial EDSS, age, sex, type of disease, disease duration, duration of follow-up, and concomitant disease modifying therapies. Statistical analysis was performed using a general linear regression model.nnnRESULTSnIn relapsing-remitting (RR) patients treated with modafinil there was no significant EDSS change over the follow-up period. In RR patients not treated with modafinil, the mean EDSS increased significantly (0.94; p=0.0001) over the follow-up period. Independent of modafinil treatment status, our model indicated an additional mean EDSS increase of 1.1 point (p=0.0002) for progressive patients i.e. mean EDSS change was 1.1 point for modafinil treated, and 1.1+0.94=2.04 points for modafinil-untreated patients.nnnCONCLUSIONnOur results support the hypothesis that modafinil has neuroprotective potential, and may play a role in the treatment of multiple sclerosis. A prospective study will need to confirm this finding.

Effects of cigarette smoke on immunity, neuroinflammation and multiple sclerosis

Cigarette smoking is the most prominent significant cause of death and morbidity. It is recognised as a risk factor for a number of immune mediated, inflammatory diseases including multiple sclerosis (MS). Here, we review the complex immunological effects of smoking on the immune system, which include enhancement of inflammatory responses with a parallel reduction of some immune defences, resulting in an increased susceptibility to infection and a persistent proinflammatory environment. We discuss the effect of smoking on the susceptibility, clinical course, disability, and mortality in MS, the likely benefits of smoking cessation, and the specific immunological effects of smoking in MS. In conclusion, smoking is an important environmental risk factor for MS occurrence and outcome, and it acts in significant part through immunological mechanisms.

Prevalence of a history of prior varicella/herpes zoster infection in multiple sclerosis

Varicella zoster virus (VZV) infection has been implicated in multiple sclerosis (MS), but direct causal involvement has been disputed. Nevertheless, knowledge of VZV exposure is important, given the risk of serious complications of first exposure while undergoing immunosuppressive treatment, in particular with fingolimod. We distributed questionnaires to MS clinic patients, requesting information about history of chickenpox, sibling/household/occupational exposure, history of zoster (shingles), and disease-modifying treatment. A random, proportionally representative sample of 51 patients that included patients with positive, negative, and unknown chickenpox history were selected for determination of VZV IgG by ELISA. Of 1206 distributed questionnaires, 605 were returned (50% response rate). Of these, 86% reported history of chickenpox, 5.6% gave negative history, and 8.5% did not know. Of 594 who answered the zoster question, 78% gave a negative response, 4% did not know, and 104 (17%) answered yes. Of these, 83 reported 1 episode; 12 had 2; 5 had 3; and 1 each reported 5, 6, and 15 episodes. Of 51 patients tested for VZV IgG (44 “yes,” 4 “no,” and 3 “I don’t know” answers to the question of whether they had chickenpox), 48 were seropositive; the 3 seronegative all had reported having had chickenpox. The high rate of MS patients reporting prior chickenpox infection is comparable with previous reports. A substantial proportion of MS patients, estimated to be higher than an age-matched general population, report single or multiple episodes of zoster. These data are useful for consideration of immunosuppressive treatments and/or VZV and zoster vaccination.

Association of Multiple sclerosis with Other Autoimmune Diseases

Since its first comprehensive clinico-pathological description by Charcot, Multiple sclerosis (MS) has remained a mysterious clinical entity and has represented a fascination to scientists and clinicians of the most diverse disciplines. With an incompletely known pathogenesis and aetiology, it has given rise to numerous theories including the more plausible ones of infection, autoimmunity and primary neurodegenerative disease to the more daring ones of vascular disease, psychological abnormality or even neurocristopathy.