Gait Posture. 2015 Feb;41(2):459-64
Theeffectof levodopaonpostural stabilityevaluated bywearable inertialmeasurement unitsforidiopathic andvascularParkinson’s disease
MiguelF.Gagoa,b,c,*,VitorFernandesd,JaimeFerreirad,He´lderSilvad, MariaL.Rodriguesa,b,Luı´sRochad,EstelaBichod,NunoSousab,c
aNeurologyDepartment,CentroHospitalardoAltoAve(CHAA),EPE,Guimara˜es,Portugal
bLifeandHealthSciencesResearchInstitute(ICVS),SchoolofHealthSciences,UniversityofMinho,Braga,Portugal
cICVS-3BsPTGovernmentAssociateLaboratory,Braga,Guimara˜es,Portugal
dAlgoritmiCenter,DepartmentofIndustrialElectronics,SchoolofEngineering,UniversityofMinho,Braga,Portugal
1.Introduction
Posturalcontrolencompassestheactsofaligningthebodywith respecttogravityandmaintaining,achievingorrestoringthebody centerofmass(COM)relativetothebaseofsupportor,more
generally,withinthelimitsofstabilityduringdailyactivities.
Postural control is achieved by the complexintegration and coordinationofmultiplebodysystems,includingthevestibular, visual,auditory,motor,andhigherlevelpremotorsystems[1], oftenunconsciously[2].Posturalinstability(PI)isoneofthemost disabling featuresof idiopathic Parkinson’sdisease (IPD)and, generally,itisamanifestationofthelatestagesofthedisease [3].Yet,thereissomeevidencethatposturalcontrolisalready impairedinearlystageofIPDwithoutovertclinicalPI[4].Postural controlcanbecharacterizedbythefollowingfourmainpostural controlsystems: (1)balance duringquietstance,(2) reactive Gait&Posture41(2015)459–464
ARTICLE INFO Articlehistory:
Received2May2014
Receivedinrevisedform11November2014 Accepted17November2014
Keywords:
Posturalstability IdiopathicParkinson’sdisease VascularParkinson’sdisease Wearableinertialmeasurementunits Kinematicanalysis
ABSTRACT
Background:Posturalstabilityanalysishasshownthatposturalcontrolisimpaired inuntreated idiopathicParkinson’sdisease(IPD),evenintheearlystagesofthedisease.VascularParkinson’sdisease (VPD)lacksconsensusclinicalcriteriaordiagnostictests.Moreover,thelevodopaeffectonpostural balanceremainsundefinedforIPDandevenlesssoforVPD.
Objective:To characterize postural stability, using kinematic analysis with wearable inertial measurementunits,inIPDandVPDpatientswithoutclinicalPI,andtosubsequentlyanalyzethe responsetolevodopa.
Methods:Tenpatientswithakinetic-rigidIPDandfivepatientswithVPDwereincluded.Clinicaland posturalstabilitykinematicanalysiswasperformedbeforeandafterlevodopachallenge,ondifferent standingtasks:normalstance(NS),Rombergeyesopen(REO)andRombergeyesclosed.
Results:Inthe‘‘offstate’’,VPDpatientshadhighermeandistancesandhighermaximaldistanceof posturalswayonNSandREOtasks,respectively.VPDpatientsmaintainedahigherrangeofanterior–
posterior(AP)posturalswayafterlevodopa.IntheabsenceofPIandnon-significantdifferencesin UPDRS-III,ahighermPIGDscoreintheVPD patientswasmainlyduetogaitdisturbance.Gait disturbance,andnotUPDRS-III,influencedthedegreeofposturalswayresponsetolevodopaforVPD patients.
Conclusion:Quantitativeposturalswayevaluation isusefulintheinvestigationofParkinsonian syndromes.VPDpatientshavehigherAPposturalswaythatiscorrelatedwiththeirgaitdisturbance burdenandalsonotresponsivetolevodopa.Theseobservationscorroboratetheinterconnectionof posturalcontrolandlocomotornetworks.
!2014TheAuthors.PublishedbyElsevierB.V.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/3.0/).
* Correspondingauthorat:NeurologyDepartment,CentroHospitalardoAlto Ave.RuadosCutileiros,Creixomil,4835-044Guimara˜es,Portugal.
Tel.:+351919490689/+351253540330.
E-mailaddress:[email protected](M.F.Gago).
ContentslistsavailableatScienceDirect
Gait& Posture
j our na lho me pa g e :w ww . e l se v i e r . com / l oca t e / ga i t po st
http://dx.doi.org/10.1016/j.gaitpost.2014.11.008
0966-6362/!2014TheAuthors.PublishedbyElsevierB.V.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/
3.0/).
posturaladjustmentstoexternalperturbations,(3)anticipatory posturaladjustmentsinpreparationforvoluntarymovements,and (4)dynamicbalanceduringmovements,suchasgait[5].Inthis sense, postural control has a fundamental role in gait of establishingandmaintainingappropriateposturalorientationof bodysegmentsrelativetoeachanotherandtotheenvironmentas wellastoensuredynamicstabilityofthemovingbody[6].
VascularParkinsonism(VPD)isaParkinsoniansyndromethatis typicallycharacterizedbylowerbodyparkinsonism,markedgait difficulty,lesstremor,lessrigidity,betterhanddexterity,relatively symmetricalsymptomaticdistribution,associationwithpyrami- daltractsigns,morefrequentdementia,andpoorresponseto levodopatreatmentcomparedtoIPD[7].However,thereareno consensusclinicalcriteriaforVPDoritsspecificclinicalfeatures;
additionally,thereisalackofdiagnosticteststodifferentiateVPD fromIPD[8].Intermsoftreatment,althoughitisrecognizedthat thedopaminergicbenefittendstofadeawaywiththeprogression ofIPD,theobjectiveeffectofdopaminergictherapyonpostural balanceremainscontroversialforIPDandisevenmorequestion- ableforVPD.Thereisincreasingresearchtounderstandwhatand hownetworksofposturalcontrolandgait,bothdopaminergicand non-dopaminergic, interact [9]. VPD, which is pathologically differentfromParkinsoniansyndromebutwithclinicalsimilarities toIPD[8],mayserveasagoodcomparisonmodelforinvestigating theposturalstabilityondifferentandincreasinglydemanding posturalandcognitivetasksanditsresponsetolevodopa.
Objectivemeasuresofbalanceusingwearableinertialsensors aresensitive,specificandresponsivetoposturalbalancetestingon clinical practice [10] and act as a diagnostic tool that is complementary to the traditional force plate measurements [4].TocharacterizeposturalstabilityinIPDandVPDpatients and to subsequently analyze the response to levodopa, we evaluatedposturalstabilityusingkinematicanalysisderivedfrom wearableinertialmeasurementunitsonearlydiseaseakinetic- rigidIPDandVPDpatientswithoutclinicalPI.
2.Materialsandmethods 2.1. Subjectsandclinicalassessment
Patients wereconsecutively recruitedfromourMovement Disordersoutpatientconsult,fulfillingcriteriaforIPD(UKPDS BrainBankcriteria)orVPD[8].IPDandVPDpatientshadnormal clinicalposturalstabilitymeasuredbytheretropulsiontest(item 12onMDS-UPDRS-III),andtheyhadnodyskinesia.IPDpatients hadanHoehn&Yahrof!2(‘‘offstate’’)andanakinetic-rigidprofile.
VPDpatientspredominantlypresentedwithlowerbodyParkin- sonism withindependentbut impairedgait; theywereshort steppedandstooped,whichwasrelatedtoanacuteorchronic cerebrovasculardisease,fulfillingtheproposedcriteriaforVPD [8].VPDpatientshadsubcorticalorbasalgangliafocallesions withoutlargevesselsstrokethatwerequalitativelyclassifiedfrom theneuroradiologist’sreports.Patientswereconsideredasbeing ontheirbest‘‘on’’dopaminergicregimeninthethreeprevious months. The exclusion criteria were dementia, orthopedic, musculoskeletal,vestibulardisorder,significantvisualorauditory deficit, and alcoholabuse. VPD patientswithmotor deficits, whetherrelatedtostrokeornot,werealsoexcluded.
Agehasbeenassociatedwithkineticperformanceforpostural stability[11].Therefore,VPDandIPDage-matchedpatientswere included. The collected variables consisted of demographic (gender, age, andeducation) and biometric datareportedas influencingkineticperformance,suchasweight,height,bodymass index.Thecenterofmass(COM)wasdeterminedat55%ofa patient’sheightabovetheground[12].Clinicaldatawerealso collected,includingyearsofdiseaseduration;MovementDisorder
Society-UnifiedParkinson’sDiseaseRatingScaleIII(MDS-UPDRS III)(scored aseitheran on‘‘off’’oron‘‘on’’state); Levodopa EquivalentLevodopaDailyDose[13];Levodopasuprathreshold challengedose;andmotorbenefit(percentageofthedifference between‘‘off’’and‘‘on’’states).ThemodifiedPosturalInstability GaitDisorder(PIGD)scorepartIIIwasderivedfromthesumof MDS-UPDRS items(3.9 (arising from chair),3.10 (gait), 3.11 (freezingofgait),3.12(posturalstability),3.13(posture),and3.14 (globalspontaneityofmovement))[14].Abriefneuropsychologi- calexaminationwasperformedusingthePortugueseversionof the Montreal Cognitive Assessment test (MoCA) with scores normalized to thePortuguesepopulation [15]no more than 1monthpriortothekineticassessment.Thelevelsofeducation werecategorizedbyyearsofschoolingasfollows:0(analphabetic), 1(1–4years),2(5–9years),3(10–12years),and4(>12years).The studyprotocolderivedfromtheICVS-3BsandtheAlgoritmiCenter andwasapprovedbyhospitallocalethicscommittee.Written informedconsentwasreceivedfromallparticipantsinthestudy.
2.2.Kinematicposturaltasks
Fivekineticsensingmodules,harboringan8051microprocessor embeddedinCC2530TexasInstrumentSoC(SystemonChip),anda wearableinertialmeasurementunitMPU6000(tri-axialaccelerom- eterandgyroscope)[16]operatingwithasampleratefrequencyof 113HzonaSDcardwereattachedtothefollowingfivebody segments:trunk(ontheCOM);bothlegs(middleofankle-knee)and boththighs(middleofknee-iliaccrest)by Velcrobands.Video capture(samplerateof60fps)anddataloggingweresynchronized byabidirectionalradiosignaltransmissionthroughaUSBcoordina- tornodeconnectedtoaPCwithcustomdesignedMatlab!software.
Ourmethodologyandmathematicalformulasforkinematic acquisitionhavebeenpreviouslypublished[17].Wefocusedon some kinematic measurements that were derived from the wearable sensorunit placedat theCOM, includingthe total lengthofsway(cm);maximalandmeandistanceofsway(cm) withrespecttotheorigin;maximallinearvelocity(cm/s);and rangeofmedial-lateral(ML)andanterior–posterior(AP)sway(cm) (ontheXandYaxistransverseplanes,respectively).Asoneofthe human’smechanismsofmaintainingbalanceistovarytheheight andCOMbybendingthekneesandtrunk,kinematicdatawas constantlyadjustedtorealheightadjustedfromthewearable sensorunitsplacedontheshanksandthighs.
Subjects were instructed to perform the following three differenttasks,firstinthe‘‘off’’andtheninthe‘‘onstate’’:normal comfortablestanding,Rombergtestwitheyesopen,andRomberg with eyes closed. Patients were clinically and kinematically evaluatedinthe‘‘offstate’’,inthemorning,aftera12-hperiod without any dopaminergicmedication.Afterwards, theywere givenasuprathresholddopaminergicmedicationof150%oftheir usualmorningdoseandwerere-examined90minlaterregardless oftheintensityoftheirsubjectiveresponse.
SubjectsperformedtheRombergtestbarefootwiththemedial aspectsofthefeettouchingeachother.Duringthetasks,subjects stoodquietlywiththeirarmshangingattheirsidesandtheirheadin anormalforward-lookingeyepositiondirectedtoanobjectplacedat 2maway.Alltaskswereexplained,andsubjectshadthechanceto trainbeforethedefinitivetrial.Eachtaskwasperformedfor30s;
duringthattime,thekinematicdatawererecorded.Thetrialwas invalidatedandstartedagainifsubjectsmovedanypartoftheirbody, spoke,openedtheireyesforvisualaidorperformedacorrectivestep.
2.3.Statisticalanalysis
Gendercomparisonswereanalyzedbythex2Fisherexacttest.
Giventhesmallnumberofsubjects,statisticalanalysiswascarried M.F.Gagoetal./Gait&Posture41(2015)459–464
460
outwithanon-parametricexacttest,theMann–Whitneytest (comparisonbetweengroups),andbyaWilcoxonmatchedpair test forthemagnitude ofchange (intragroup)afterlevodopa challengeand forthe effectof thevisual suppressioneffect.
Intragroupcorrelationofthebasal(‘‘offstate’’)mPIGDscoreand thetotalMDS-UPDRSIIIscorewithachangeinposturalsway variables after levodopa challenge was evaluated with the Spearmantest.Statisticalanalyseswereconductedwithsoftware (SPSS20.0)usinga95%levelofsignificance.
3.Results
FivepatientswithVPDandtenpatientswithIPDwereincluded.
ThirteenpatientsfulfillingthecriteriaforVPDwereexcludeddueto dementia(sevenpatients)and/ormotordeficitand/ororthopedic problems(six patients). The demographic andanthropometric characteristicsofthetwogroupsaresummarizedinTable1.
AllVPDpatientsweremales,butgenderhasnotbeendescribed toinfluenceposturalsway[18].Groupsdidnotdifferinageor anthropometric characteristics. Additionally, baseline clinical characteristics(yearsofdiseaseduration,‘‘offstate’’MDS-UPDRS IIIscore,EquivalentLevodopaDailyDose;Levodopachallenge dose;andMotorBenefit)werenotsignificantlydifferentbetween groups.VPDpatientshadahighermPIGDscore8[5,10],(U=4.0;
z=!2.602;p=0.006)dueessentiallytoahigherscoreonposture andgait.Afterlevodopachallenge,bothgroupsdifferedsignifi- cantlyontheMDS-UPDRSIII(U=0.0;z=!3.062;p=0.001))and mPIGD score (U=1.5; z=!2.907; p=0.002), reflecting, as expected,alowermotorbenefitoflevodopaforpatientswith VPD(U=0.0;z=!3.067;p=0.001).
Concerning postural sway analysis (Table 2, Fig. 1), we observedthatinbothgroups,therequirementforposturalcontrol
increasedforthedifferenttasks.Thiswasevidentinthehigher valuesoftotalswaylengthanddistanceofswayintheMLandAP planes.
On‘‘offstate’’,inthenormalstance,VPDpatientshadahigher meandistanceofsway(U=7.0;z=!2.205;p=0.028),andonthe REOtask,theyhadahighermaximaldistance(U=8.0;z=!2.08;
p=0.04)andhigherrangeofanterior–posteriorsway(U=8.0;
z=!2.082;p=0.04).Inthe‘‘onstate,’’VPDpatientsontheREO taskalsohadahigherrangeofanterior–posteriorsway(U=5.0;
z=!2.449;p=0.013).Ofnote,inthe‘‘onstate,’’therewereno significantdifferencesinthedistanceofswaybetweenthetwo groups.
Inintragroupanalysisofthelevodopaeffect,onlyIPDpatients hadsignificantchangesinthenormalstancetask.Thetotallength (IPD:6.07[!5.98,10.81];VPD:1.05[!7.39,7.39])(z=!2.191, p=0.027), maximal distance (IPD: 0.65 [!0.18, 2.57]; VPD:
0.14 [!2.63, 1.18]) (z=!2.497, p=0.01), range of ML (IPD:
0.63[!0.01,2.03];VPD:1.19[!1.18,1.88])(z=!2.701,p=0.04) and AP sway (IPD: 0.64 [!0.73, 2.15]; VPD: !0.17 [!5.11,1.15])(z=!1.988;p=0.049)weresignificantlyincreased in onlythe IPD group. Whenanalyzing the effect of visual suppression, only IPD patients, and only in the ‘‘off state’’, registeredasignificanteffect,andtherewasanincreaseinthe totallength(z=!2.191,p=0.027)andmaximaldistanceofsway (z=!1.988,p=0.049).FortheIPDgroup,therewerenosignificant correlationsinthebasalmPIGDscore(‘‘offstate’’)withthechange inposturalswayvariablesafterlevodopachallenge.Incontrast, VPD patientshadasignificant correlationbetweenthebasal mPIGDscore(OFFstate)andthetotallengthofswayinnormal stance(rho=!0.949,p=0.014)andrangeofAPswayontheREC task(rho=0.9,p=0.037).ThebasalMDS-UPDRS-IIItotalscore (‘‘offstate’’)hadnosignificantcorrelationwithanyofthepostural swayvariablesineithergroup.
Table1
Demographics,anthropometricandclinicalvariablesinidiopathicParkinson’sdiseaseandvascularParkinson’sdiseasepatients.
IPD(n=10) VPD(n=5) Inter-groupcomparison
Gender(female/male) 6/4 0/5 *p=0.044
Age 73[61,79] 77[63,84] U=18.0;z=!0.086;p=0.418
Height(m) 1.61[1.52,1.71] 1.61[1.55,1.68] U=24.5;z=!0.062;p=0.981
Weight(kg) 73.2[55,85] 76.5[68,89] U=15;z=!1.225;p=0.254
BodyMassIndex(kg/m2) 29[24,32] 31[27,34] U=11.5;z=!1.673;p=0.098
Centerofmass(cm) 88.3[84,94] 88[85,92] U=24.5;z=!0.062;p=0.981
LevelofEducation 1[1,4] 1[1,1] x2=2.359;p=0.267
MOCA 23[16,30] 12[10,15] U=0.0;z=!3.067;p=0.001
Diseasedurationinyears 6[5,10] 5[3,9] U=25.0;z=!0.0;p=1.0
MDS-UPDRSIIIOffstage 30[16,53] 44[33,57] U=10.0;z=!1.839;p=0.075
mPIGDoffstage 3[1,7] 8[5,10] *U=4.0;z=!2.602;p=0.006
Arisingfromchair 0[0,1] 1[0,2] p=0.059*
Gait 0[0,2] 2[1,2] p=0.005*
Freezingofgait 0[0,0] 0[0,0] p=1.0
Posturalstability 0[0,0] 0[0,0] p=1.0
Posture 1[0,3] 3[1,3] p=0.067
Globalspontaneityofmovement 2[0,3] 2[2,3] p=0.114
MDS-UPDRSIIIOnstage 13.5[1,24] 39[26,46] *U=0.0;z=!3.062;p=0.001
mPIGDonstage 2[0,6] 7[5,8] *U=1.5;z=!2.907;p=0.002
Arisingfromchair 0[0,1] 1[0,2] p=0.032*
Gait 0[0,0] 1[1,2] p=0.001*
Freezingofgait 0[0,0] 0[0,0] p=1.0
Posturalstability 0[0,0] 0[0,0] p=1.0
Posture 1[0,3] 2[1,3] p=0.121
Globalspontaneityofmovement 1[0,2] 2[1,3] p=0.017*
Levodopaequivalentdailydose 685[300,1532] 750[500,1124] U=24;z=!0.123;p=0.931
Levodopachallengedose 300[150,400] 350[200,400] U=18.5;z=!0.82;p=0.458
Motorbenefit(%) 57.5[47,94] 19[11,26] *U=0.0;z=!3.067;p=0.001
Dataispresentedasmedian[minimum,maximum].
IPD—idiopathicParkinson’sdisease;VPD—vascularParkinson’sdisease;COM–55%ofindividual’sheight;mPIGD—modifiedposturalinstabilityandgaitdisorderscore (mPIGD)derivedfromthesumoftheMDS-UPDRSitems(arisingfromchair,gait,freezingofgait,posturalstability,posture,globalspontaneityofmovement).
*SignificantatexactFishertest.
M.F.Gagoetal./Gait&Posture41(2015)459–464 461
Table2 PosturalkinematicvariablesondifferentposturaltasksinidiopathicParkinson’sdiseaseandvascularParkinson’sdisease. KinematicvariablesNormalstanceRombergtestwitheyesopen(REO)Rombergtestwitheyesclosed(REC)REOvs. RECoffstageREOvs. REConstage OffstageOnstagep-ValueaOffstageOnstagep-ValueaOffstageOnstageap-Valueap-Valueap-Valuea Totallengthofsway(cm) IPD13.4[8.3,21.1]19.4[12.8,25.4]p=0.027*21.0[10.5,36.8]22.1[8.9,32.8]p=0.92224[13.8,39.6]23.2[12.5,47.2]p=0.846p=0.027*p=0.064 VPD13.7[12.8,41.2]20.2[10.3,33.9]p=1.020.9[18.7,35.7]21.3[16.0,50.0]p=0.3121.8[14.4,38.4]23.3[16.2,57.3]p=0.313p=0.625p=0.625 p-Valuebp=0.254p=0.953p=0.679p=0.513p=0.953p=0.768 Maximaldistanceofsway(cm) IPD1.56[0.92,2.93]2.46[1.60,3.55]p=0.01*2.04[1.36,3.66]2.5[1.4,4.3]p=0.232.43[1.46,4.70]2.43[1.13,8.4]p=0.625p=0.049*p=0.695 VPD1.82[1.46,6.50]3.0[1.8,4.0]p=0.813.7[1.9,9.2]3.2[2.0,5.9]p=0.812.4[1.64,6.25]3.26[1.8,5.4]p=0.625p=0.188p=0.438 p-Valuebp=0.206p=0.440p=0.04*p=0.129p=0.953p=0.594 Meandistanceofsway(cm) IPD0.57[0.45,1.32]1.03[0.42,1.98]p=.0841.15[0.71,2.04]1.2[0.65,2.24]p=0.4921.17[0.48,2.79]1.22[0.53,4.18]p=0.432p=0.57p=0.77 VPD1.15[0.61,2.50]0.98[0.5,2.6]p=0.6231.8[0.78,4.3]1.6[0.82,2.5]p=0.0811.1[0.7,2.3]1.64[0.8,3.2]p=0.438p=0.313p=0.625 p-Valuebp=0.028*p=.953p=0.129p=0.165p=0.679p=0.513 Maximallinearvelocity(cm/s) IPD0.85[0.22,2.78]1.3[0.24,1.77]p=0.430.6[0.28,2.6]1.27[0.37,1.82]p=0.2750.65[0.43,2.9]1.64[0.46,3.72]p=0.064p=0.275p=0.084 VPD0.79[0.5,7.20]1.5[0.5,8.2]p=0.431.46[0.58,2.8]2.2[0.41,5.5]p=0.1881.48[0.17,3.8]1.1[0.06,5.7]p=0.813p=1.0p=0.31 p-Valuebp=0.371p=0.59p=0.679p=0.055p=0.254p=0.859 RangeofMLsway(cm) IPD0.8[0.33,3.4]1.82[0.86,3.96]p=0.004*2.68[1.64,5.29]2.03[1.04,5.39]p=0.2752.49[1.33,5.47]2.28[1.23,7.3]p=0.695p=0.625p=0.105 VPD1.75[0.67,2.0]2.38[0.36,3.63]p=0.1882.4[1.76,3.20]3.24[2.38,3.72]p=0.0632.4[1.9,2.5]2.4[1.8,5.9]p=0.625p=1.0p=1.0 p-Valuebp=0.165p=0.44p=0.679p=0.129p=.768p=0.768 RangeofAPsway(cm) IPD1.96[0.99,2.70]2.86[1.89,3.78]p=0.049*2.32[1.3,3.87]2.45[0.9,4.2]p=0.772.24[1.77,3.85]2.04[1.30,4.40]p=0.492p=0.557p=1.0 VPD2.5[1.6,12.0]2.74[2.16,6.9]p=0.6254.14[1.75,9.96]5.3[2.7,10.9]p=0.1253.0[1.7,6.2]3.3[2.2,7.3]p=1.0p=0.18p=0.063 p-Valuebp=0.371p=0.44p=0.04*p=0.013*p=0.371p=0.055 Dataispresentedasmedian[minimum,maximum].IPD—idiopathicParkinson’sdisease;VPD—vascularParkinson’sdisease;ML—medial-lateral;AP—anterior–posterior. aWilcoxonstatisticalanalysis(intragroupanalysis). bMann–Whitneystatisticalanalysis(intergroupanalysis). *SignificantatexactFishertest.
M.F.Gagoetal./Gait&Posture41(2015)459–464 462
4.Discussion
Thepresentresultsindicatedsubclinicaldifferencesinpostural sway between VPD and AR-IPD patients. This finding is in agreement withclinical evidence, diagnosticcriteria and the differentetiopathologyofthesetwoentities[8].Inagreementwith the data from previous force platforms andIMUstudies, we alsofoundasignificantincreaseinthedisplacementofswayfrom theoriginafterlevodopa[19].Thisisrelevantbecausetherole attributedtolevodopaonposturalcontrolinIPDremainsunclear due to conflicting results. Herein, we alsodemonstrate that levodopaonlyhadasignificanteffectonIPDbutnotonVPD.Sway inpatientswithIPDwhoareinthe‘‘onstate’’arelargerandfaster thanwheninthe‘‘offstate’’,whichisperhapsbecauselevodopa reduces the rigidity without improving controlofposture or becausesubclinicaldyskinesiaincreasesbodymotion[20].Addi- tionally,thedecreaseinswayafterdopaminergicmedicationhas beencorrelatedwithasmallerriskoffalling,whereasnochangeor increasedposturalswaycorrelatedwithhigherrisk[21].Inour study,levodopadidnothaveapositiveeffectontherangeoftheAP posturalswayinVPDpatients.Interestingly,themaindifference betweenIPDandVPDwasintheAPswaymeasuresbothinthe
‘‘off’’and‘‘on’’states.APswayinvolvestheinvertedpendulumand anklemuscleswaystrategyofposturalcontrol,whichmaybeless affectedinIPDthaninVPD.
Theetiologyoftheposturalmisalignmentandflexedposturein IPDisnotclear,butbackgroundmuscletoneislarger,especiallyin flexormuscles.Inspiteoftheirforwardinclinationintheupright posture,IPDpatientstendtofallbackwardsveryeasily,withboth axialrigidityandpoortrunkcoordinationcontributingtothepoor stability ofIPD patients inresponseto backward bodysway [22].ThemoreflexedpostureofVPDpatients,demonstratedin theirmPIGDscores,mayhavecontributed,butthelargerAPrange ofswaycanalsorepresentadistinctivevariableofVPDandhigher riskoffallingevenwithoutovertclinicalPI.
Moredemandingposturalcontroltasks,suchastheRomberg undervisualsuppression,mayhaveputourpatientsonhigher cognitivealertandefforttocontrolCOMunderstablelimits.This mayhave attenuatedthe subclinicaldyskinesiaandincreased posturalswaythatwasonlyobservedinthenormalrelaxedstance.
Visualsuppressionincreasestheposturalinstability,makingthe patientmoredependentonothersystems,includingthevestibu- lar,proprioceptiveinputsandposturalcontrolsnucleussuchasthe
pedunculopontinenucleus[5].Weobservedasignificanteffectof visualsuppressionontheposturalswayofourIPDpatients,which isconcordantwithotherstudiesonearlystageIPD[19].This vulnerabilitywasonlypresentforIPDpatients,whichwasevident inthe‘‘offstate’’andshowedapositiveresponsetolevodopa,as previouslyreported[19];importantly,wefailedtofindapositive responseinVPDpatients.
Increasingevidencesuggests animportantroleofcognitive factors,suchasexecutivefunctionandattention,inthecontrolof balanceduringstandingandwalking[23,24].Manystudieshave shownthatgaitinIPDismoredependentonfocusedattentionand externalcuesandthatthefrontalcortexmayplayacrucialrolein controllinggaitpatterns[14].Thedisruptionofthemicrostructural organizationofthefrontallobewhitematterhasbeenassociated withtheseverityofVPD,reinforcingthehypothesisofthefrontal lobedisconnectionforgaitproblemsandthattheinvolvementof fibersrelatedtotheprefrontalcortexiscrucialforthecorefeatures ofVPD.Inthisrespect,wecannotexcludethatsomefindingsinVPD patientscanalsobeexplainedbytheirlowercognitiveperformance (lowervaluesonMoCa),albeitwithoutthecriteriaofdementia.
Intheabsenceofclinicalposturalinstability,thehighermPIGD scoreinbothgroupswasmainlyduetogaitdisturbance,especially prevalent inthe VPD patients.After levodopa challenge, VPD patientshadahigherbasalmPIGDbasalscore,whichiscorrelated withthelowertotallengthposturalswaychangeinnormalstance;
interestingly,thislowerswayapparentlypersistedintheAPplane.
InmostcasesofVPD,gaitandposturalstabilityaresimultaneously impaired[25]. InthisparticularcohortofVPDpatients,inthe absenceofclinicallyassessedposturalinstability,gaitimpairment influencedthedegreeoftheposturalswayresponsetolevodopa.
Locomotorgeneratorsandposturalcontrolareinterconnected[26], andifposturalcontrolisstillmodulatedbydopamineatleastinthe earlystagesofIPDwithoutPI,thiswasnotevidentinVPD.Unlikefor mPIGD,theUPDRS-IIIItotalscoredidnotinfluencethepostural swayresponseafterlevodopachallenge.Apuremechanicalprocess, withlessrigidityafterlevodopainfluencingposturalsway,isnotthe soleexplanationforthis;centralposturalcontrolcircuits,both dopaminergicandnon-dopaminergic,couldbeinvolved[27].
4.1.Studylimitations
Itisimportant tonotethatwe opted toincludeonly the akynetic-rigid IPD subtype and age-matched VPD patients.
Fig.1.Displacementonx-axis(medial-lateral)andy-axis(anterior–posterior)ofinertialmeasurementunitoncenterofmass(55%ofHeight),plottedondifferentconditions (before(off)andafterlevodopachallenge(on)),forallsubjects(idiopathicParkinson’sdisease(IPD);vascularParkinson’sdisease(VPD)patients).
M.F.Gagoetal./Gait&Posture41(2015)459–464 463