Letters COMMENT & RESPONSE
Multiple Sclerosis and Alcohol Misuse To the Editor I read with interest the article by Pakpoor and colleagues1 investigating the risk for hospital admission for multiple sclerosis (MS) after admission for alcohol misuse. While interesting, the study is far from proving a causal relationship of alcohol misuse on MS risk. As likely seen in another study by the same team,2 there is an issue of reverse causality that is not remedied by excluding admissions in the same year because MS risk factors likely act many years before the clinical onset of the disease.3 Furthermore, because MS has significant psychological impact, it is likely that alcohol misuse is a result of the impact of having MS.4 Therefore, the authors should test whether there is a risk for alcohol misuse admission in patients with MS. Furthermore, it is notable that the association is seen primarily in men, suggesting that the association is a result of having MS (as documented in the literature5) rather than reflecting confounding. Claudio Voci, BA Author Affiliation: University of Bologna, Bologna, Italy. Corresponding Author: Claudio Voci, BA, University of Bologna, Via Zamboni 33, 40126 Bologna, Italy ([email protected]). Conflict of Interest Disclosures: None reported. 1. Pakpoor J, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Alcohol misuse disorders and multiple sclerosis risk. JAMA Neurol. 2014;71(9):1188-1189. 2. Pakpoor J, Goldacre R, Schmierer K, Giovannoni G, Goldacre MJ. Testicular hypofunction and multiple sclerosis risk: a record-linkage study. Ann Neurol. 2014;76(4):625-628. 3. Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother. 2013;13(12)(suppl):3-9. 4. Stenager EN, Jensen B, Stenager M, Stenager K, Stenager E. Suicide attempts in multiple sclerosis. Mult Scler. 2011;17(10):1265-1268. 5. Beier M, D’Orio V, Spat J, Shuman M, Foley FW. Alcohol and substance use in multiple sclerosis. J Neurol Sci. 2014;338(1-2):122-127.
rate ratios were 0.84 (95% CI, 0.42-1.50; P = .65), 0.98 (95% CI, 0.86-1.11; P = .82), and 0.88 (95% CI, 0.77-1.00; P = .06) for alcohol use, abuse, and dependence, respectively. Although not significant, low rates of alcohol misuse disorders in the later years after first MS diagnosis lead us to speculate that perhaps, after a diagnosis of MS, people with it become more health conscious. These findings—combined with our previous results that there was a significantly elevated risk for MS within 1 year of first admission for alcohol abuse only and a significantly elevated risk for MS following all alcohol misuse disorders with an interval of more than 1 year between first recorded admission with the alcohol misuse disorder and firstrecorded admission with MS—make us consider reverse causality to be unlikely to explain our findings. Of note, Dr Voci’s comment that reverse causality is likely seen in another study reported from this data set is not supported by the results of that study where, as we have previously reported, the positive association was similarly only significant in 1 direction.2 We hope our study of a positive association between alcohol misuse disorders and subsequent MS, in combination with the findings reported by Hedström et al,3 stimulates further work to confirm or refute our findings in striving to establish the currently largely uncharacterized role of alcohol in MS pathophysiology. Julia Pakpoor, BA Raph Goldacre, BA Michael J. Goldacre, FFPH, FRCP Author Affiliations: Oxford University Medical School, John Radcliffe Hospital, Oxford, England (Pakpoor); Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, England (R. Goldacre, M. J. Goldacre). Corresponding Author: Michael J. Goldacre, FFPH, FRCP, Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, Oxfordshire OX3 7LF, England (michael.goldacre @dph.ox.ac.uk). Conflict of Interest Disclosures: None reported.
In Reply We thank Dr Voci for his comments on our article1 reporting a positive association between alcohol misuse disorders and subsequent multiple sclerosis (MS), particularly in men. The possibility of reverse causality whereby alcohol misuse may be a consequence of as yet undiagnosed MS is a necessary consideration. Using the same method and reference cohort as in our original study, we analyzed the data set for the risk for alcohol misuse disorders following an admission for MS. Comparing the MS cohort with the control cohort, the rate ratios were 1.04 (95% CI, 0.59-1.69; P = .98), 1.13 (95% CI, 1.021.25; P = .02), and 1.01 (95% CI, 0.91-1.13; P = .82) for alcohol use, alcohol abuse, and alcohol dependence, respectively. In reducing the possibility of surveillance bias and reverse causality, including only cases of alcohol misuse disorders observed at least 1 year following the first admission for MS, the 238
1. Pakpoor J, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Alcohol misuse disorders and multiple sclerosis risk. JAMA Neurol. 2014;71(9):1188-1189. 2. Pakpoor J, Goldacre R, Schmierer K, Giovannoni G, Goldacre MJ. Reply. Ann Neurol. 2014;76(5):765-766. 3. Hedström AK, Hillert J, Olsson T, Alfredsson L. Alcohol as a modifiable lifestyle factor affecting multiple sclerosis risk. JAMA Neurol. 2014;71(3): 300-305.
Autosomal Recessive Cerebellar Ataxia 3 Due to Homozygote c.132dupA Mutation Within the ANO10 Gene To the Editor With great interest we read the article by Renaud et al1 reporting a case series of 9 patients with autosomal recessive cerebellar ataxia type 3 due to ANO10 mutations. The authors discussed the previously reported c.132dupA mutation with a heterozygote carrier frequency of 1/184 and pos-
JAMA Neurology February 2015 Volume 72, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Multiple Sclerosis and Alcohol Misuse To the Editor I read with interest the article by Pakpoor and colleagues1 investigating the risk for hospital admission for multiple sclerosis (MS) after admission for alcohol misuse. While interesting, the study is far from proving a causal relationship of alcohol misuse on MS risk. As likely seen in another study by the same team,2 there is an issue of reverse causality that is not remedied by excluding admissions in the same year because MS risk factors likely act many years before the clinical onset of the disease.3 Furthermore, because MS has significant psychological impact, it is likely that alcohol misuse is a result of the impact of having MS.4 Therefore, the authors should test whether there is a risk for alcohol misuse admission in patients with MS. Furthermore, it is notable that the association is seen primarily in men, suggesting that the association is a result of having MS (as documented in the literature5) rather than reflecting confounding. Claudio Voci, BA Author Affiliation: University of Bologna, Bologna, Italy. Corresponding Author: Claudio Voci, BA, University of Bologna, Via Zamboni 33, 40126 Bologna, Italy ([email protected]). Conflict of Interest Disclosures: None reported. 1. Pakpoor J, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Alcohol misuse disorders and multiple sclerosis risk. JAMA Neurol. 2014;71(9):1188-1189. 2. Pakpoor J, Goldacre R, Schmierer K, Giovannoni G, Goldacre MJ. Testicular hypofunction and multiple sclerosis risk: a record-linkage study. Ann Neurol. 2014;76(4):625-628. 3. Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother. 2013;13(12)(suppl):3-9. 4. Stenager EN, Jensen B, Stenager M, Stenager K, Stenager E. Suicide attempts in multiple sclerosis. Mult Scler. 2011;17(10):1265-1268. 5. Beier M, D’Orio V, Spat J, Shuman M, Foley FW. Alcohol and substance use in multiple sclerosis. J Neurol Sci. 2014;338(1-2):122-127.
rate ratios were 0.84 (95% CI, 0.42-1.50; P = .65), 0.98 (95% CI, 0.86-1.11; P = .82), and 0.88 (95% CI, 0.77-1.00; P = .06) for alcohol use, abuse, and dependence, respectively. Although not significant, low rates of alcohol misuse disorders in the later years after first MS diagnosis lead us to speculate that perhaps, after a diagnosis of MS, people with it become more health conscious. These findings—combined with our previous results that there was a significantly elevated risk for MS within 1 year of first admission for alcohol abuse only and a significantly elevated risk for MS following all alcohol misuse disorders with an interval of more than 1 year between first recorded admission with the alcohol misuse disorder and firstrecorded admission with MS—make us consider reverse causality to be unlikely to explain our findings. Of note, Dr Voci’s comment that reverse causality is likely seen in another study reported from this data set is not supported by the results of that study where, as we have previously reported, the positive association was similarly only significant in 1 direction.2 We hope our study of a positive association between alcohol misuse disorders and subsequent MS, in combination with the findings reported by Hedström et al,3 stimulates further work to confirm or refute our findings in striving to establish the currently largely uncharacterized role of alcohol in MS pathophysiology. Julia Pakpoor, BA Raph Goldacre, BA Michael J. Goldacre, FFPH, FRCP Author Affiliations: Oxford University Medical School, John Radcliffe Hospital, Oxford, England (Pakpoor); Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, England (R. Goldacre, M. J. Goldacre). Corresponding Author: Michael J. Goldacre, FFPH, FRCP, Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, Oxfordshire OX3 7LF, England (michael.goldacre @dph.ox.ac.uk). Conflict of Interest Disclosures: None reported.
In Reply We thank Dr Voci for his comments on our article1 reporting a positive association between alcohol misuse disorders and subsequent multiple sclerosis (MS), particularly in men. The possibility of reverse causality whereby alcohol misuse may be a consequence of as yet undiagnosed MS is a necessary consideration. Using the same method and reference cohort as in our original study, we analyzed the data set for the risk for alcohol misuse disorders following an admission for MS. Comparing the MS cohort with the control cohort, the rate ratios were 1.04 (95% CI, 0.59-1.69; P = .98), 1.13 (95% CI, 1.021.25; P = .02), and 1.01 (95% CI, 0.91-1.13; P = .82) for alcohol use, alcohol abuse, and alcohol dependence, respectively. In reducing the possibility of surveillance bias and reverse causality, including only cases of alcohol misuse disorders observed at least 1 year following the first admission for MS, the 238
1. Pakpoor J, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Alcohol misuse disorders and multiple sclerosis risk. JAMA Neurol. 2014;71(9):1188-1189. 2. Pakpoor J, Goldacre R, Schmierer K, Giovannoni G, Goldacre MJ. Reply. Ann Neurol. 2014;76(5):765-766. 3. Hedström AK, Hillert J, Olsson T, Alfredsson L. Alcohol as a modifiable lifestyle factor affecting multiple sclerosis risk. JAMA Neurol. 2014;71(3): 300-305.
Autosomal Recessive Cerebellar Ataxia 3 Due to Homozygote c.132dupA Mutation Within the ANO10 Gene To the Editor With great interest we read the article by Renaud et al1 reporting a case series of 9 patients with autosomal recessive cerebellar ataxia type 3 due to ANO10 mutations. The authors discussed the previously reported c.132dupA mutation with a heterozygote carrier frequency of 1/184 and pos-
JAMA Neurology February 2015 Volume 72, Number 2 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a University of St. Andrews Library User on 05/21/2015
jamaneurology.com
