Pakpoor J, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Alcohol Misuse Disorders and Multiple Sclerosis Risk. JAMA Neurol. 2014;71(9):1088-1189. doi:10.1001/jamaneurol.2014.1795
Multiple sclerosis (MS) is a complex neurologic disease caused by both genetic and environmental risk factors. To our knowledge, few studies have investigated the relationship between alcohol and MS risk, and these have been limited by small sample sizes and inconsistent results.1- 3 Hedström and colleagues4 reported that alcohol consumption exhibits a dose-dependent inverse association with MS risk. We aimed to determine whether individuals with alcohol misuse disorders, presumed to consume large quantities of alcohol, have a lower MS risk than the general population.
We conducted a record-linkage study using linked data sets of anonymized English Hospital Episode Statistics (records of every episode of day-case care or hospital admission in all English National Health Service hospitals) and death registrations for England from 1999 to 2011. The English National Research Ethics Service approved use of the data sets (ref 04/Q2006/176).
The methods have been described fully elsewhere.5 Three cohorts of people with a record of day-case care or inpatient admission for alcohol abuse, alcohol dependence, and alcohol use (International Statistical Classification of Diseases, 10th Revision codes F10.1, F10.2, and F10.9) were constructed by identifying the first recorded episode in which each condition was diagnosed in a National Health Service hospital during the study period. A reference cohort was constructed by identifying people admitted for various other, mainly minor, medical and surgical conditions and injuries (Table 1, footnotes). None of the control conditions within the reference cohort, when studied separately, had unusually high or low rates of MS when compared with other conditions in the reference cohort.
We then searched for any subsequent episode of day-case care or hospital admission for, or death from, MS in these cohorts. We considered that rates of MS in the reference cohort would approximate those in the general population while allowing for migration in and out of it. The standardized rate ratio was then calculated (Table 1, footnotes).
The number of people in the reference cohort was more than 6.7 million (50% women). The number of people in the alcohol use, alcohol abuse, and alcohol dependence cohorts were 10 156 (35% women), 255 827 (29% women), and 281 305 (29% women), respectively. There was a significantly increased risk for MS following alcohol abuse, alcohol dependence, and alcohol use (Table 1). We considered the possibility of reverse causality or that the increased risk for MS may be related to the alcohol-related care itself (eg, increased surveillance). Therefore, we analyzed the data for whether the occurrence of the first record of MS was within, or after, 1 year following the first admission for each alcohol misuse disorder. There was a significantly elevated risk for MS within 1 year of first admission for alcohol abuse only (Table 1). For all alcohol misuse disorders, there was a significantly elevated risk for MS with an interval of more than 1 year from first admission with the alcohol misuse disorder (Table 1). The association between alcohol misuse disorders and the risk for MS was more evident in men than women (Table 2).
This study supports the presence of a significant positive association between alcohol misuse disorders and MS risk, particularly in men. The strengths of this study were the longitudinal design and the size of the Hospital Episode Statistics database. We consider it likely that most people with MS would be seen as a day case or admitted at least once. Whereas Hedström et al4 observed a negative association between alcohol consumption and MS risk, the likely much higher levels of toxicity and alcohol dependency in the patients in our study may be associated with MS or might be associated with risk factors or other comorbidities that may, in turn, be associated with MS. We cannot exclude any influence of smoking. Interestingly, Hedström et al4 observed that the effect of smoking on MS risk was attenuated with greater alcohol consumption. Clinical advice with regard to alcohol consumption and MS remains largely speculative, and long-term follow-up studies are required to ascertain the relationship.
Corresponding Author: Michael J. Goldacre, FFPH, FRCP, Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, England (firstname.lastname@example.org).
Author Contributions: Dr M. J. Goldacre had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Pakpoor, Giovannoni, M. J. Goldacre.
Acquisition, analysis, or interpretation of data: Pakpoor, R. Goldacre, Disanto, M. J. Goldacre.
Drafting of the manuscript: Pakpoor, Giovannoni.
Critical revision of the manuscript for important intellectual content: R.Goldacre, Disanto, M. J. Goldacre.
Statistical analysis: R.Goldacre, M. J. Goldacre.
Obtained funding: M. J. Goldacre.
Study supervision: Giovannoni, M. J. Goldacre.
Conflict of Interest Disclosures: Dr Giovannoni serves on scientific advisory boards for Merck Serono, Biogen Idec, and Vertex Pharmaceuticals; has served on the editorial board of Multiple Sclerosis; and has received speaker honoraria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Pfizer Inc, Teva Pharmaceutical Industries Ltd, sanofi-aventis, Vertex Pharmaceuticals, Genzyme Corp, Ironwood, and Novartis. Dr Giovannoni has also served as a consultant for Bayer Schering Pharma, Biogen Idec, GlaxoSmithKline, Merck Serono, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, sanofi-aventis, UCB, Vertex Pharmaceuticals, GW Pharma, Novartis, and FivePrime; serves on the speakers bureau for Merck Serono; and has received research support from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, UCB, Merz Pharmaceuticals LLC, Teva Pharmaceutical Industries Ltd, sanofi-aventis, GW Pharma, and Ironwood. No other disclosures were reported.
Funding/Support: The building of the linked datasets and the development of the analytical software used to study disease associations were funded by the UK National Institute for Health Research.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed in this article do not necessarily reflect those of the funding body.