Summary of Focal Article 1.1.. Focal Article WangF,SunL,ZhangXZ,JiaJ,LiuZ,HuangXY,YuSY,Zuo LJ, CaoCJ, Wang XM,Zhang W.Effect and Potential Mech-anismofElectroacupunctureAdd-OnTreatment i
Trang 1integrmedres xxx (2016)xxx–xxx
Available online at www.sciencedirect.com
Integrative Medicine Research
jo u rn al h o m e p a g e :w w w i m r - j o u r n a l c o m
Commentary
Jungtae Leema,b, ∗ ,1
aKorean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul, Korea
bDepartment of Clinical Research of Korean Medicine, College of Korean Medicine, Kyung Hee University,
Seoul, Korea
a r t i c l e i n f o
Article history:
Received21May2016
Receivedinrevisedform
25June2016
Accepted28June2016
Availableonlinexxx
Keywords:
Acupuncture
ParkinsonDisease
Responder
Observationalstudy
1 Summary of Focal Article
1.1 Focal Article
WangF,SunL,ZhangXZ,JiaJ,LiuZ,HuangXY,YuSY,Zuo
LJ, CaoCJ, Wang XM,Zhang W.Effect and Potential
Mech-anismofElectroacupunctureAdd-OnTreatment inPatients
withParkinson’sDisease EvidBasedComplement Alternat
∗ Corresponding Author. Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Hoegi-dong, Dongdaemun-gu,Seoul,KoreaTelephone:+82-2-958-9490(Office)Fax:+numbers:none
E-mailaddress:julcho@naver.com
1 M.DofKoreanMedicineandMasterdegreeofInternalMedicineofKoreanMedicine
Med.2015;2015:692795 doi:10.1155/2015/692795 Epub2015 Aug131
1.2 Corresponding author of the focal article
WeiZhang Address:DepartmentofGeriatrics,BeijingTiantan Hospi-tal,CapitalMedicalUniversity,Beijing100050,China
E-mail:ttyyzw@163.com
http://dx.doi.org/10.1016/j.imr.2016.06.006
2213-4220/©2016KoreaInstituteofOrientalMedicine.PublishedbyElsevier.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense
Trang 2The authors aimed to evaluate the effectiveness of
elec-troacupuncture(EA)andexploreitsmechanisms in
Parkin-son’sdisease(PD)patientswhenusedasanadjunctivetherapy
toconventionaldrugs
3 Design
Thisstudywasarandomized,controlled(EA+drugvs.drug
alone),assessor-blind,single-center,pilottrial
4 Setting
PDpatientswererecruitedfromMay2011toMay2012inthe
Departmentof Geriatricsand Neurology ofBeijing Tiantan
HospitalatCapitalUniversity
5 Participants
FiftyPDpatientsusingastabledosageofanti-PDmedication
foratleasttwomonthswithoutadverseeffectswererecruited
PatientswerediagnosedbyaneurologistaccordingtotheUK
Parkinson’sDiseaseSocietyBrainBankcriteria2.Patientswith
ParkinsonplussyndromeorsecondaryParkinsonsyndrome
werenotincluded
Thirtypatientswereallocatedtothetreatmentgroup(EA
+drug).Twentypatientswereallocatedtothecontrolgroup
(drugonly).Duringtheclinicaltrialperiod,patientswerenot
allowedtochangetheirmedication.Twopatientsdroppedout
duetoPDmedicationchanges
6 Intervention
Needles0.25mmindiameterand40mminlength(Huatuo)
wereinsertedintothefollowing6acupointsbasedon
previ-ousstudies:3,4 bilateralGB20(Pungji)andLI4(Hapgok),and
centralGV16(Pungbu)andGV14(Daechu).Theneedleswere
stimulatedusingthefollowingparametersfor30minutes:9V,
1A,9W,and100Hz(KWD-808-II;Yingdi,China).One
acupunc-turetreatmentcourseiscomposedof10sessionsthatoccur
every3days.Two treatmentcourses,equatingtoatotalof
20sessionsofacupuncturetreatment,wereperformedover
2months.Participantswhoskippedmorethan2sessionsof
treatmentwereeliminatedfromthetrial
7 Main Outcome Measures
7.1 Assessment schedule
Assessmentswereperformed12hoursafterthelatestintake
ofPDmedication.Treatment grouppatients were assessed
afterthecompletionoftheentireEAtreatmentcourse
Con-trolgrouppatientswereassessed2monthsafterthebaseline
assessmentdate
7.2 Motor symptoms and motor complications
ThefollowingitemsfromtheUnifiedParkinson’sDisease Rat-ing Scale (UPDRS) III were used: total score, items 20 and
21 (tremor), item 22 (rigidity), and items 23-26 (bradykine-sia).Hoehn–Yahr(H-Y)stageratingswereusedtoindicatethe severityofPDandtheUPDRSIVwasusedtoassessmotor complications
7.3 Non-motor symptoms
Non-motor symptoms were assessed using the following tests: Nonmotor Symptoms Quest (NMSQ), including the Montreal Cognitive Assessment (MoCA); Mini-Mental State Examination(MMSE)fortheassessmentofcognitivefunction; Hamilton
DepressionScale(HAMD)24-itemtestfortheassessment
ofdepression,HamiltonAnxietyScale(HAMA)14–itemtestfor theassessmentofanxiety,andPittsburghSleepQualityIndex (PSQI)fortheassessmentofsleepquality.1
7.4 Activity of Daily Life (ADL) and Quality of Life (QOL)
TheUPDRSIIandtheADLscalewereusedtoassessADL.QOL wasevaluatedusingthe Parkinson’sDiseaseQualityofLife Questionnaire(PDQ)39itemtest
7.5 Neuroinflammatory factors and Neurotransmitters in Serum
The following neuroinflammatory factors were measured: nitricoxide(NO),tumornecrosisfactor-␣(TNF-␣), interleukin-1(IL-1),andprostaglandin(PG)E2
The following neurotransmitters were measured: dopamine (DA), acetylcholine (Ach), norepinephrine (NE), and5-hydroxytryptamine(5-HT)
8 Main Results
8.1 Comparison between treatment and control groups
TheUPDRSIIIscorechangesweresignificantlydifferentbefore andaftertreatment.ThechangeintheUPDRSIIIscorewas 4.9±4.8inthetreatment groupand2.3±3.0inthecontrol group.ThechangeinthePSQIwas1.0(0.0-2.0)inthe treat-mentgroup,whichwassignificant,whileitwas0inthecontrol group However, the H-Y stage, HAMD, HAMA, MMSE, and MoCAwerenotdifferentbetweenthetwogroups.Theonly biomarkerthatwassignificantlydifferentfollowingthe treat-ment wastheNOlevel(treatmentgroup,53.18[6.42-64.51]; controlgroup,80.49[62.15-107.57])
8.2 Within-group comparisons (before vs after comparison in the treatment group)
The motor symptoms evaluatedusing the UPDRSIII score (25.6±2.8to20.6±2.7),andthetremor(4.9±4.4to3.4±3.9),
Trang 3rigidity (4.6±3.4to 3.6±3.2),and bradykinesia(9.0±6.3 to
7.4±5.9) sub-items were significantly improved following
treatment Subgroup analysis revealed that the UPDRS III
scoresweredecreasedinpatientswithrigidity-bradykinesia
typeormixedtypePD,butnotinthosewithtremortypePD
UPDRSIIIscoresofpatients withmildseverity groupwere
significantlyimproved(20.2±2.6to14.7±2.0),whereasthose
withmoderate severity groupdid notshow the significant
improvement(33.5±3.9to29.1±4.1).Thenon-motor
symp-tomsassessedusingthePSQIandHAMDwereimproved,but
noimprovementswereseeninothervariables
9 Authors’ conclusion:
ThemotorsymptomsofPDwere significantlydecreasedby
the addition of EA tostandard treatment These
improve-mentswere measured using the UPDRSIII scoreand were
especially evidentin patients with mixed type or
rigidity-bradykinesiatypePDandinthosewithmildPDsymptoms.EA
treatmentalsoimprovedthequalityofsleepanddepressionin
PDpatients.ElevatedNOlevelsmaybeapossiblemechanism
underlyingtheeffectsofEA
10 Comment/Critique
The focal article indicates that EA improves motor
symp-toms,asassessedbytheUPDRSIII,andanon-motorsymptom
(quality ofsleep), asmeasured bythe PSQI Several
previ-ousreportsontheuseofacupuncturedidnotindicatemotor
symptomimprovementfollowingthistreatment.5,6However,
positivereportsontheuseofacupunctureforPDtreatmentare
increasing.Choetal.,3reportedthat16sessionsof
acupunc-tureorbeevenomtreatmentimprovetheUPDRSIIIscorein
treatedpatientsincomparisontopatientsinthenotreatment
controlgroupina3-armpilotrandomizedcontrolledtrial.In
anotherprospectiveopen-labelstudy,11participants
under-went12consecutiveweeksofconventionaltreatmentand12
weeksofconventionaltreatmentcombinedwithacupuncture
andbeevenomtreatment.UPDRSIIandIIIscoreswere
signif-icantlyimprovedinthecombinedtreatmentphasecompared
totheconventionaltreatmentphase.7Inanotherrandomized
study,36 sessions ofadjunctiveacupuncture therapy
com-binedwithwesternmedicationover18weeksledtoahigher
UPDRStotalscoreimprovementratio(55%vs.15%,p=0.019)
comparedtomedication-only group.8 Acupunctureis also
showntohavelong-termeffects.PatientsinanL-dopa-only
group(control group)andthoseinanL-dopaand
acupunc-turecombinationgroup(treatmentgroup)werefollowedfor
60months.Patientsinthetreatmentgroupreceived
acupunc-turetreatment2to4timesamonth.Overthecourseof5years,
UPDRSIIIscoresworsenedby18.2±9.8pointsinthecontrol
group,buttheonlyworsenedby11.9±6.8pointsinthe
treat-mentgroup(p=0.043).9Arecentmeta-analysisofcombined
traditionaleastAsianmedicinetherapies,including
acupunc-ture,moxibustion,herbalmedicine,patentmedicine,manual
therapy,andqigongindicatedthatthesetreatmentsimproved
theUPDRSIIIscoreby2.45points(95%confidenceinterval(CI)
[2.03to2.86])anddiminished38%ofthesideeffectsassociated withconventionaldrugs(riskratio,0.6295%CI[0.40-0.96]).10
Theoriginalfocalarticlecontainsaconsiderableamountof discussionregardingthemechanismsunderlyingtheeffects
ofacupunctureinPDtreatment.Thereareseveralarticles dis-cussingthesemechanisms.AnoriginalarticlepointstoGABA activityinthesubstantianigraasafactormediatingchanges
inmotorsymptoms,suggestsNEand5-HTdecreasesas fac-tors underlyingchanges indepression, and DAchanges as factorsmediatingchangesintheincidenceofsleepdisorders
1However,inthefocalarticle,therewerenosignificant dif-ferencesinthesemarkersbetweenthetreatmentandcontrol groups, exceptforchangesinserumNOlevels.Therewere onlywithin-groupbeforeandafterdifferencesinseveralof the neuroinflammatory factors and neurotransmitters.The authorsthusfailedtofindapossiblemechanismunderlying theeffectsofEAtreatmentinpatientswithPDinthistrial What ismoreinterestingin thisarticle isthat itidentifies potential responders toEAtreatmentinPD Inthis article, themildseveritygroup(H-Ystage1to2)showedsignificant improvementaftertreatment.Thiseffectwasnotobservedin themoderateseveritygroup(H-Ystage2.5to3).Thisindicates thatearlyEAtreatmentinPDmay behelpfulinalleviating motorsymptoms.Inapreviousstudy,H-Ystageandagewere predictive oftheeffectsofintegrated Chineseand western therapyasevaluatedusingtheUPDRSIIIscore.11Theauthors thushypothesizethattheseverityofPDisadeterminantof
EAtreatmentresponse.Anothersubgroupanalysisrevealed that participantswithtremor typePDdidnotimprove fol-lowingtreatment.Howeverthosewithrigidity–bradykinesia typeormixedtypePDshowedimprovementsafterEA treat-ment.ThisindicatesthattheEAeffectmaynotbethesamein thedifferentsubtypesofthedisease.Thesehypothesesmay
besupportedbyseveralobservationalstudies.Observational studiesareappropriatewhendesigningfeasibleclinicaltrial protocols withlarge samplesizes.12 Thereare insufficient resources, suchasfundingandmanpower,foracupuncture research As a result, there will not be any well-designed researchexploringtheresponsetoacupunctureinthe foresee-ablefuture.However,knowingtheresponsetoacupuncture
isa veryimportantfactor indesigning appropriateclinical trialprotocolsandisacriticalfactorinthesuccessofsuch clinical trials A retrospective chart review or a retrospec-tivecohort studyusing nationalhealthinsurancedatawill
behelpfulinidentifyingpatientwhowillimprovefollowing acupuncturetreatment.Thus,themostvaluablediscoveryof thisfocalarticleisthepotentialidentificationofresponders
tothistreatment.Irecommendthattheauthors definethe responderandthenon-respondergroupandcompare base-linecharacteristics,severity,symptomsubtype,andthelevels
ofneuroinflammatoryfactorsandneurotransmittersbetween thesegroupsdespitethesmallsamplesize
This article indicates that acupuncture improves motor symptoms and quality ofsleep inpatients withPD Lower
NOlevelsinthetreatmentgroupindicatethatacupuncture suppressesneuroinflammation,ahypothesisthatshouldbe tested by further research The most interestingaspect of thefocalarticleisthepotentialidentificationofresponders
toacupuncturetreatment.Atthispoint,moreobservational studies are needed, and not clinical trials, to study the
Trang 4characteristics of acupuncture treatment responders with
PD
Conflict of Interest
Nonedeclared
r e f e r e n c e s
1 WangF,SunL,ZhangX-Z,JiaJ,LiuZ,HuangX-Y,etal.Effect
andPotentialMechanismofElectroacupunctureAdd-On
TreatmentinPatientswithParkinson’sDisease.Evid-Based
Complement Altern Med ECAM2015;2015:692795,
1993;56(8):938–9
3 ChoS-Y,ShimS-R,RheeHY,ParkH-J,JungW-S,MoonS-K,
etal.Effectivenessofacupunctureandbeevenom
acupunctureinidiopathicParkinson’sdisease.Parkinsonism
Relat Disord2012;18(8):948–52,
4 ZengB-Y,SalvageS,JennerP.Currentdevelopmentof
acupunctureresearchinParkinson’sdisease.Int Rev
Neurobiol2013;111:141–58,
5 ShulmanLM,WenX,WeinerWJ,BatemanD,MinagarA,
DuncanR,etal.Acupuncturetherapyforthesymptomsof
Parkinson’sdisease.Mov Disord Off J Mov Disord Soc
2002;17(4):799–802,http://dx.doi.org/10.1002/mds.10134
6 CristianA,KatzM,CutroneE,WalkerRH.Evaluationof
acupunctureinthetreatmentofParkinson’sdisease:a
double-blindpilotstudy.Mov Disord Off J Mov Disord Soc
2005;20(9):1185–8,http://dx.doi.org/10.1002/mds.20503
7 DooK-H,LeeJ-H,ChoS-Y,JungW-S,MoonS-K,ParkJ-M,
etal.AProspectiveOpen-LabelStudyofCombined TreatmentforIdiopathicParkinson’sDiseaseUsing AcupunctureandBeeVenomAcupunctureasanAdjunctive Treatment.J Altern Complement Med N Y N
2015;21(10):598–603,
8 ChenF-P,ChangC-M,ShiuJ-H,ChiuJ-H,WuT-P,YangJ-L,
etal.Aclinicalstudyofintegratingacupunctureand WesternmedicineintreatingpatientswithParkinson’s disease.Am J Chin Med2015;43(3):407–23,
9 MizushimaT.TreatmentResultsbetweenMatchedPairof L-dopaMedicationTreatmentandAcupunctureTreatment CombinationonParkinsonDisease.Kampo Med
2011;62(6):691–4,
10 ZhangG,XiongN,ZhangZ,LiuL,HuangJ,YangJ,etal EffectivenessoftraditionalChinesemedicineasanadjunct therapyforParkinson’sdisease:asystematicreviewand meta-analysis.PloS One2015;10(3):e0118498,
11 LiM,YangM-H,LiuY,LuoX-D,ChenJ-Z,ShiH-J.Analysisof clinicalevaluationofresponsetotreatmentofParkinson’s diseasewithintegratedChineseandWesternmedicine therapy.Chin J Integr Med2015;21(1):17–21,
12 DreyerNA,TunisSR,BergerM,OllendorfD,MattoxP, GliklichR.Whyobservationalstudiesshouldbeamongthe toolsusedincomparativeeffectivenessresearch.Health Aff Proj Hope2010;29(10):1818–25,