Cross, Anne H

Multiple Sclerosis Partners Advancing Technology and Health Solutions Investigators#,

Naismith, Robert T

Shirani, Afsaneh

English

Digital Commons@Becker

Washington University School of MedicineDigital Commons@BeckerOpen Access Publications2019The association between handedness andclinicodemographic characteristics in people withmultiple sclerosis: A brief reportAfsaneh ShiraniWashington University School of Medicine in St. LouisAnne H. CrossWashington University School of Medicine in St. LouisRobert T. NaismithWashington University School of Medicine in St. LouisMultiple Sclerosis Partners Advancing Technology and Health Solutions Investigators#Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubsThis Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in OpenAccess Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationShirani, Afsaneh; Cross, Anne H.; Naismith, Robert T.; and Multiple Sclerosis Partners Advancing Technology and Health SolutionsInvestigators#, ,"The association between handedness and clinicodemographic characteristics in people with multiple sclerosis: A briefreport." Multiple Sclerosis Journal- Experimental, Translational and Clinical.5,1. 2055217319832031. (2019).https://digitalcommons.wustl.edu/open_access_pubs/7564Short reportThe association between handedness andclinicodemographic characteristics in peoplewith multiple sclerosis: a brief reportAfsaneh Shirani , Anne H Cross and Robert T Naismith; for the Multiple Sclerosis PartnersAdvancing Technology and Health Solutions Investigators#AbstractA relationship between handedness and clinicodemographic profiles of people with multiple sclerosiswas sought using data from the Multiple Sclerosis Partners Advancing Technology Health Solutionsnetwork of 10 multiple sclerosis centers in the USA and Europe. Handedness data were available for8888 multiple sclerosis patients, of which 917 (10.3%) were left-handed. Clinicodemographic profiles ofright versus left-handed multiple sclerosis patients were similar except for a slightly increased propor-tion of men who were left-handed, and slightly reduced performance on the manual dexterity test usingthe non-dominant hand in left-handed patients. We found no evidence to suggest a prognostic implica-tion of handedness in multiple sclerosis.Keywords: Multiple sclerosis, handedness, epidemiologyDate received: 22 December 2018; Revised received 23 January 2019; accepted: 28 January 2019IntroductionThe relationship between handedness and autoim-mune diseases such as multiple sclerosis (MS) isdebated.1–3 A previous study of female US nursessuggested a modest increase in the risk of MS amongleft-handed women.1 It has also been proposed thatHLA-alleles associated with an increased risk of MSand circulating autoantibodies may be morecommon among left-handed individuals.4Approximately 11% of the general population isleft-handed.5 Few population-based studies haveexamined the relationship between handedness anddemographic or clinical characteristics of peoplewith MS (PwMS). Multiple Sclerosis PartnersAdvancing Technology Health Solutions (MSPATHS)6 is a collaborative network including 10MS centers in the USA and Europe and providesaccess to a large cohort of PwMS. In this study,we investigated the association between handednessand clinicodemographic profile of enrollees inMS PATHS.MethodsThis cross-sectional study utilized data from the MSPATHS network. MS PATHS is a collaborative net-work sponsored by Biogen which includes sevencenters in the USA and three centers in Europe,and is based on the concept of a learning healthsystem.6 During routine clinic visits, people withMS undergo the multiple sclerosis performance test(MSPT) which is an iPad-based assessment includ-ing structured patient history, electronic adaptationsof the multiple sclerosis functional composite, andthe neuro-quality of life (neuro-QoL) outcomeinstrument.7We queried MS PATHS for PwMS recruited fromthe inception of the database (11/2015) through3/2018. Requested variables included sex, age atMS onset and diagnosis, MS subtype, level of edu-cation, handedness, patient determined disease steps(PDDS) and relevant components of MSPT assess-ment including manual dexterity test (MDT), walk-ing speed time (WST), contrast sensitivity testCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0License (http://www.creativecommons.org/licenses/by-nc/4.0/)which permits non-commercial use, reproduction anddistribution of theworkwithout furtherpermission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Multiple Sclerosis Journal—Experimental, Translationaland ClinicalJanuary—March 2019, 1–4DOI: 10.1177/2055217319832031! The Author(s), 2019.Article reuse guidelines:sagepub.com/journals-permissionsCorrespondence to:Afsaneh Shirani,Afsaneh Shirani, The John LTrotter Center andNeuroimmunology Section,Department of Neurology,Washington UniversitySchool of Medicine, CampusBox 8111, 660 S EuclidAvenue, St Louis 63110,MO, USA.ashirani@wustl.eduAfsaneh Shirani,Anne H Cross andRobert T Naismith,for the Multiple SclerosisPartners AdvancingTechnology and HealthSolutions Investigators#,The John L Trotter MultipleSclerosis Center andNeuroimmunology Section,Washington UniversitySchool of Medicine, USA#Data used in preparation ofthis article were obtainedfrom Multiple SclerosisPartners AdvancingTechnology and HealthSolutions (MS PATHS)database. As such, the(CST), processing speed time (PST), and the Neuro-QoL’s upper extremity function and cognitivedomains. Handedness data in MS PATHS is system-atically collected by asking the patients which handthey learned to write with.We compared right and left-handed patients for dif-ferences in demographic and clinical profiles usingthe chi-square test to examine the associationbetween categorical variables, t-test for continuousvariables, and Mann–Whitney U test for ordinal var-iables. P values less than 0.05 were considered sta-tistically significant. The institutional review boardat Washington University in St Louis approvedthe study.ResultsA total of 9618 PwMS were identified (73.2%women). Handedness data were available for 8888patients, of which 917 (10.3%) were left-handed.Table 1 shows the demographic and clinical profilesof the patients. Among women with MS, 9.5% wereleft-handed whereas 12.4% of men with MS wereleft-handed. Women comprised a greater proportionof right-handed than of left-handed PwMS (74.0%vs. 67.8%, P< 0.001). Overall, right and left-handed patients had a similar age at MS diagnosis,PDDS, and MS subtype. Approximately 65% ofPwMS had relapsing–remitting MS in both handed-ness groups. The mean time to complete MDT withthe left hand was not associated with handedness.The mean time to complete MDT with the righthand was slightly longer in left-handed comparedto right-handed PwMS (28.9 8.3 vs. 27.6 7.6seconds, P<0.001). Results for WST, CST, PST,and neuro-QoL upper extremity and cognitivedomain scores were similar between right and left-handed PwMS. Stratification by sex did not changeour findings.To examine if any major underlying upper extremitydysfunction might have impacted our findings (byaffecting patient-reported handedness), we per-formed a sensitivity analysis by including a subsetof patients whose MDT performance values were inthe best performance quartile (<23 seconds) thushaving minimal functional impairment of upperextremities. In this subset (n=1393, 10.1% left-handed), the meanSD time to complete MDTwith the dominant hand was 20.01.7 seconds forright-handed patients and 20.01.8 in left-handedpatients. Time to complete MDT with the non-dom-inant hand was 20.81.6 in right-handed patients,and 20.01.8 in left-handed patients. These resultsdid not change our interpretation of the findings.We also investigated if right-handed and left-handedpatients might have been differentially impactedwhen MDT performance is more severely impaired.To examine this, we performed another sensitivityanalysis by including a subset of patients whoseMDT performance values were in the worst perfor-mance quartile (>32 seconds). In this subset(n=1184, 10.1% left-handed), the meanSD timeto complete MDT with the dominant hand was40.66.4 seconds for right-handed patients and40.36.2 for left-handed patients. Time to completeMDT with the non-dominant hand was 38.96.2 inright-handed patients, and 40.06.8 in left-handedpatients. These results did not change our interpre-tation of the findings, either.DiscussionIn this large cross-sectional study using data fromMS PATHS, 10.3% of PwMS were left-handed,close to the estimated 11% prevalence of left-handedness or mixed-handedness in the US generalpopulation.5 The higher prevalence of left-handedness among male PwMS compared towomen (12.4% vs. 9.5%) in our study is consistentwith the general population. A meta-analysis found ahigher prevalence of left-handedness in men in thegeneral population, with an estimated male to femaleodds ratio of 1.23 (95% confidence interval (CI)1.19–1.27).8A previous cohort study using data from theNurses’ Health Study reported a 62% increasedrisk of MS among women who were naturallyleft-handed as compared to those who were right-handed (relative risk=1.62, 95% CI 1.04–2.53)1and suggested that prenatal exposure to sex hor-mones may possibly play a role in MS risk.9,10That study included only women, and was notdesigned to examine the clinical characteristics ofincident MS cases. We compared the clinical pro-files of right versus left-handed PwMS to seek anyevidence to support that left-handed MS patientsmay have an earlier MS onset or altered clinicalseverity. No strong evidence to suggest this wasfound. However, we found a slightly longer meantime to complete MDT with the non-dominant hand(right hand) in left-handed PwMS. The mean timeto complete MDT with the left hand was similarbetween right-handed and left-handed MS patients.The mean age at MS onset in left-handedPwMS was minimally higher than right-handedinvestigators within MSPATHS contributed to thedesign and implementationof MS PATHS and/orprovided data but did notparticipate in analysis orwriting of this report.Multiple Sclerosis Journal—Experimental, Translational and Clinical2 www.sagepub.com/msjetcPwMS. The implications of these subtle differencesare unclear.We were unable to examine the relationship betweenhandedness and MS onset symptom lateralitybecause MS PATHS does not capture the details ofonset symptoms. Future studies should examine thispotential relationship, given that the brain networksresponsible for controlling the less dexterousnon-dominant hand may have a lower reserve capac-ity, and therefore impairments of the fine motor con-trol of the non-dominant hand may be discernable atan earlier stage of MS.Overall, we found no evidence to suggest a prognos-tic implication of handedness in MS. Our study alsoencourages using MS PATHS for conducting clini-cal research in MS.Table 1. Demographic and clinical profile of right-handed versus left-handed patients with MS (n¼ 8888).CharacteristicsRight-handed(n¼ 7971)Left-handed(n¼ 917) P valueSex,a n (%)Women 5898 (74.0) 622 (67.8) <0.001bMen 2068 (25.9) 294 (32.1)Age at MS symptom onset,c years, meanSD 32.3 11.2 32.6 11.8 0.008dAge at MS diagnosis, years, mean SD 35.2 11.0 35.6 11.5 0.066dEducation,f years, median (IQR) 14 (12–16) 14 (12–16) 0.068gDisease subtype,h n (%)Relapsing–remitting 4764 (64.3) 549 (65.5) 0.20bSecondary progressive 1381 (18.6) 164 (19.6)Primary progressive 595 (8.0) 50 (6.0)Progressive relapsing 665 (9.0) 75 (8.9)Patient determined disease steps,i median (IQR) 1 (0–3) 1 (0–3) 0.279gManual dexterity test for right hand,j seconds, mean SD 27.6 7.6 28.9 8.3 <0.001dManual dexterity test for left hand,k seconds, meanSD 29.0 7.7 28.7 8.0 0.333dNeuro-QoLl upper extremity function t-score,m meanSD 45.5 9.5 45.1 9.5 0.95dWalking speed time,n seconds, meanSD 7.4 4.9 7.7 5.2 0.187dContrast sensitivity testo at high (100%) contrast,p meanSD 57.0 6.3 56.6 6.1 0.248dContrast sensitivity testo at low (2.5%) contrast,p mean SD 33.7 13.0 32.9 13.5 0.174dProcessing speed test,q seconds, meanSD 46.9 12.9 46.6 12.9 0.613dNeuro-QoLl cognitive function t-score,m meanSD 46.2 9.1 45.6 8.9 0.91daData for sex were missing for six patients.bChi-square testcData for age at MS symptoms onset were missing for 414 patients.dStudent’s t-testeDate for age at MS diagnosis were missing for 538 patients.fData for education were missing for 310 patients.gMann–Whitney U test.hData for MS disease subtype were missing for 645 patients.iData for patient determined disease steps were missing for 75 patients.jData for manual dexterity test for the right hand were missing for 890 patients.kData for manual dexterity test for the left hand were missing for 922 patients.lScores for neuro-quality of life (Neuro-QoL) are reported using a t distribution, with the mean of the reference population set to 50 and thestandard deviation set to 10 units. Lower t scores indicate less of the concept being measured. For instance, a t score of 45 for upper extremityfunction, is 0.5 standard deviation worse than the average.mData for Neuro-QoL were missing for 2083 patients.nData for walking speed time were missing for 1068 patients.oThe contrast sensitivity testing is based on the Sloan low contrast letter acuity test and evaluates binocular acuity with a maximum numbercorrect of 60 at high (100%) and low (2.5%) contrast.pData for contrast sensitivity test were missing for 3814 patients.qData for processing speed test were missing for 625 patients.Shirani et al.www.sagepub.com/msjetc 3AcknowledgementsWe would like to express our thanks to the MS PATHSclinical research coordinators at Washington University inSt. Louis including Courtney Dula, MS, Dana Perantie,MPH, and Shannon Sides, BA, as well as all the otherMS PATHS research coordinators at other sites. Wewould also like to thank Dana Perantie, MPH for herhelp with IRB preparation and submission.Conflict of InterestsThe author(s) declared the following potential conflicts ofinterest with respect to the research, authorship, and/orpublication of this article: AS is funded through a clinicianscientist development award from the National MultipleSclerosis Society (USA), and a clinical research trainingscholarship from the American Academy of Neurology.AHC has been a paid consultant for Biogen, Celgene,EMD-Serono, Genzyme, Genentech, and Novartis. AHCwas funded in part by the Manny and Rosalyn Rosenthal –Dr John L Trotter MS Center Chair in Neuroimmunologyof Barnes-Jewish Hospital Foundation. RTN has receivedhonoraria for consulting for Alkermes, Biogen, Celgene,Novartis; and for speaking for EMD Serono, Genzyme,Genentech, and Novartis.FundingThe author(s) disclosed receipt of the following financialsupport for the research, authorship, and/or publication ofthis article: The Multiple Sclerosis Partners AdvancingTechnology and Health Solutions (MS PATHS) databasewas funded by Biogen..ORCID iDAfsaneh Shirani http://orcid.org/0000-0002-8866-6426References1. Gardener H, Munger K, Chitnis T, et al. The relation-ship between handedness and risk of multiple sclero-sis. Mult Scler 2009; 15: 587–592.2. McManus IC, Naylor J and Booker BL. Left-handed-ness and myasthenia gravis. Neuropsychologia 1990;28: 947–955.3. Morris DL, Montgomery SM, Galloway ML, et al.Inflammatory bowel disease and laterality: is lefthandedness a risk? Gut 2001; 49: 199–202.4. Lengen C, Regard M, Joller H, et al. Anomalous braindominance and the immune system: do left-handershave specific immunological patterns? Brain Cogn2009; 69: 188–193.5. Gilbert AN and Wysocki CJ. Hand preference and agein the United States. Neuropsychologia 1992;30: 601–608.6. MS PATHS: Multiple Sclerosis Partners AdvancingTechnology Health Solutions. https://www.mspaths.com (accessed 16 November 2018).7. Rudick RA, Miller D, Bethoux F, et al. The MultipleSclerosis Performance Test (MSPT): an iPad-BasedDisability Assessment Tool. J Vis Exp 2014;88: e51318.8. Papadatou-Pastou M, Martin M, Munafo` MR, et al.Sex differences in left-handedness: a meta-analysisof 144 studies. Psychol Bull 2008; 134: 677–699.9. Geschwind N and Galaburda AM. Cerebral lateraliza-tion. Biological mechanisms, associations, and pathol-ogy: II. A hypothesis and a program for research. ArchNeurol 1985; 42: 521–552.10. Bouman A, Heineman MJ and Faas MM. Sex hor-mones and the immune response in humans. HumReprod Update 2005; 11: 411–423.Multiple Sclerosis Journal—Experimental, Translational and Clinical4 www.sagepub.com/msjetc

The association between handedness and clinicodemographic characteristics in people with multiple sclerosis: A brief report

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The association between handedness and clinicodemographic characteristics in people with multiple sclerosis: A brief report

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