Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 431986 8 pageshttpdxdoiorg1011552013431986
Research ArticleA Randomized Controlled Pilot Study ofthe Triple Stimulation Technique in the Assessment ofElectroacupuncture for Motor Function Recovery inPatients with Acute Ischemic Stroke
Feng Tan1 Xuewen Wang1 Hui-qin Li2 Lin Lu2 Ming Li1 Ji-huang Li2 Meifeng Fang1
Di Meng1 and Guo-qing Zheng2
1 Department of Neurology Foshan Hospital of TCM Affiliated Hospital of Guangzhou University of Chinese MedicineFoshan 528000 China
2The Center of Neurology and Rehabilitation The Second Affiliated Hospital of Wenzhou Medical College Wenzhou 325027 China
Correspondence should be addressed to Guo-qing Zheng gq zhengsohucom
Received 11 March 2013 Revised 21 May 2013 Accepted 26 May 2013
Academic Editor Shu-Ming Wang
Copyright copy 2013 Feng Tan et alThis is an open access article distributed under the Creative CommonsAttribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
The objective of this pilot study was to objectively assess electroacupuncture for motor function recovery in patients withacute ischemic stroke using the triple-stimulation technique (TST) The patients received either electroacupuncture plus westernconventional medication (WCM) (119899 = 32) or single WCM (119899 = 31) for 14 days The total clinical effective rate was statisticallysignificantly superior in electroacupuncture group to that in WCM group (119875 lt 001) Fugl-Meyer Assessment Scale (FMA) scoreNational Institutes of Health Stroke Scale (NIHSS) score and TSTratio were statistically more significant in electroacupuncturegroup than those in WCM group (119875 lt 001) There was positive correlation between TSTratio and NIHS score both before andafter treatment (119875 lt 001) and negative correlation between TSTratio and FAM score both before treatment and after treatment(119875 lt 001) Comparing between the two groups or between pretreatment and posttreatment adverse events electrocardiogramliver function and kidney function showed no statistically significant difference (119875 gt 005) In conclusion electroacupuncturewas beneficial for the motor function recovery of patients with acute ischemic stroke and was generally safe TST can be used forquantitative evaluation of electroacupuncture for motor function recovery in patients with acute ischemic stroke because it canobjectively analyze the injury and recovery of corticospinal tract impairments
1 Introduction
Stroke is the second most common cause of death aftercancer worldwide and low-income countries are the mostaffected by the high rates of stroke mortality and burden[1] Particularly stroke has become the leading cause ofdeath among all diseases in China which has one-fifth ofthe total population (13 billion) in the world However theonly Food and Drug Administration-approved therapy foracute ischemic stroke (AIS) remains the thrombolytic agentrecombinant tissue-type plasminogen activator (rtPA) withinthe limited 45-hour timeframe [2] In addition symptomaticintracranial hemorrhage (ICH) is a devastating complicationof intravenous thrombolysis treatment and is associated with
highmortality [3]Therefore complementary and alternativemedicine (CAM) therapies are increasingly used in patientswith stroke adjunct to conventional treatment Acupuncturea form of CAM is one of the oldest medical modality inthe world which has played an important role in the medicalcare of stroke patients for more than 3000 years [4] In thepast decades a number of randomized controlled trials wereconducted to address efficacy and safety of acupuncture forimprovingmotor function recovery of patients suffering fromischemic stroke but the results are not conclusive [5]
Motor impairment is a frequent complication after strokeThe ability to live independently after stroke depends largelyon the reduction of motor impairment and the recov-ery of motor function [6] Advances in neurophysiological
2 Evidence-Based Complementary and Alternative Medicine
assessments with transcranial magnetic stimulation (TMS)have provided newways tomeasure the extent of stroke dam-age and understand the anatomical and functional changesin the motor system at given time points during the courseof recovery [7] Recently a novel TMS technique involv-ing two collisions the triple-stimulation technique (TST)links the central to peripheral conduction and suppressesdesynchronization of the motor evoked potentials (MEPs)and this technique enabled a quantitative electrophysiologicalmeasurement of the central motor-conduction failure thatcauses the patientrsquos disability [8] The TST was reported tobe 15sim275 times more sensitive than conventional TMS fordetecting corticospinal conduction failure [9ndash11] NowadaysTST has been applied for various disorders to quantifyassessment of the central conduction failure suggesting thatTST was useful in quantifying the benefits of treatmentsin disorders such as multiple sclerosis amyotrophic lateralsclerosis and spondylotic myelopathies or cerebral plasticityin the course of rehabilitation programmes in disorders suchas stroke [10] Thus TST is a useful diagnostic tool andprovides an accurate objective quantification in follow-upstudies including assessment of the efficiency of treatmentsFurthermore the most important period of recovery is atthe acute and subacute stages during the clinical course ofischemic stroke [12] In the present study we thus conducteda randomized controlled pilot study using the TST to objec-tively evaluate electroacupuncture (EA) for motor functionrecovery in patients with the first-ever ischemic stroke andwithin the first three days of stroke onset
2 Methods
This clinical study was designed as a randomized controlledtrial and was conducted between June 2010 and March 2011in China The trial used the two-group parallel design where63 cases of AIS patients were randomized in a 1 1 ratio toreceive EA plus western conventional medication (WCM) orsingle WCM treatment for a total of 14 days The efficacy andsafety of EA was mainly assessed by using TST and severalneurological outcome scales after 14-day treatment Thestudy was conducted in accordance with the World MedicalAssociation Declaration of Helsinki and Chinarsquos regulationsand guidelines on good clinical practice Ethical approval forthe trial was obtained from the Ethics Committee of the localhospital Ethical ReviewBoardWritten informed consent wasobtained from all subjects
21 Participants Subjects were considered eligible to beenrolled in the study only when all of the following inclusioncriteria were met (1) a diagnosis of AIS according to theChinese national criteria in Diagnostic Essentials of VariousCerebrovascular Diseases revised at the Fourth NationalConference of China Society ofMedicine onCerebrovascularDiseases in 1995 [13]The diagnosis of AISmust be confirmedby both CT and MRI (2) within in 72 hours from the onsetof stroke (3) motor deficits in at least one limb and NationalInstitutes of Health Stroke Scale (NIHSS) score that is greaterthan or equals to 4 (4) the age ranged from 35 to 80 years (5)
all subjects must participate of their own free will and sign aninformed consent form
The following exclusion criteria were applied (1) con-traindication of TMS (2) suffering from neural or mus-culoskeletal disease that affects function recovery beforeAIS (3) more than 72 hours after the onset of stroke(4) patients suffering from transient ischemic attack sub-arachnoid hemorrhage ICH or cerebellar infarction (5)patients who presented with conscious disturbance aphasiaand dementia after stroke onset (6) emergency and criticalpatients who were not suitable for acupuncture such as acutemyocardial infarction serious infection active tuberculosishepatic failure andor renal failure and upper gastrointestinalbleeding (7) patients age lt 35 years old or gt80 years old (8)those who refuse to sign an informed consent form
The terminal criteria were as follows (1) those who didnot meet the inclusion criteria but were included in thetrial (2) patients who did not obey the trial plan to takemedication and affected the efficacy evaluation (3) patientswho withdraw from the trial if any of the serious adverseevents happened (4) patients whose condition deterioratedor when serious complications occurred (5) patients whostop participating due to onersquos own free will during the trialPatients could withdraw from the study at any time and forany reason
22 Participant Flow Baseline Evaluation and Randomiza-tion Based on inclusion criteria 95 patients were screenedand 32 patients were excluded due to not meeting inclusioncriteria declining to participate andor other reasons Afterthe patients have fully understood the study and have signedthe informed consent the baseline evaluation was recordedand assessed by a responsible doctor including age sexheight body weight history medication history drink-ingsmoking history risk factors (history of hypertensionstroke diabetes and cardiovascular disease) and type of limbparesis NIHSS score was carried out by a trained doctorBasic life signs such as breathing heart rate blood pressureand pulse were recorded The lesion site and volume ofcerebral infarction were also assessed by a CT and MRI scanThe infarct volume was divided into 3 types according tothe Pullicino formula (length times width times number of CT orMRT scanning positive layer2) They are large size infarct(gt10 cm3) medium size infarct (5sim10 cm3) and small sizeinfarct (lt5 cm3) All of the patients should take lab testsof liver and kidney function The qualified subjects finishedTSTtest level and Fugl-Meyer Assessment Scale (FMA) scoreSixty-three AIS patients signed informed consent finishedbaseline evaluation and entered random process Thesepatientswere randomly divided into EAplusWCMtreatmentgroup (EA group 119899 = 32) and WCM control group (WCMgroup 119899 = 31) by using a random number tableThe randomnumbers were sealed in opaque envelopes and the researcheropened the envelope only to start the intervention Duringthe trial 2 patients were transferred to intensive care unitfrom general ward and discontinued the intervention becauseof one cerebral hernia secondary to large size cerebral infarc-tion and the other severe pulmonary infection secondary toaspirations Ultimately statistical analyses were conducted on
Evidence-Based Complementary and Alternative Medicine 3
because of cerebral hernia secondary to large size cerebral infarction
Allocated to electroacupuncture plus
All patients received allocated intervention
because of severe pulmonary infection secondary to aspirations
Allocated to a single western conventional
All patients received allocated intervention
Allocation
Analysis
Assessed for eligibility (n = 95)
Excluded (n = 32)∙ Not meeting inclusion criteria (n = 21)∙ Declined to participate (n = 6)∙ Other reasons (n = 5)
western conventional medication (n = 32) medication (n = 31)
Followup
Figure 1 Participant flow diagram
the results from 31 patients of EA treatment group and 30patients of WCM control group (Figure 1 participant flowdiagram)
23 Interventions Based on the Standards for ReportingInterventions in Clinical Trials of Acupuncture (STRICTA)2010 checklist we reported interventions in present clini-cal trial of electroacupuncture as follows (1) acupuncturerationale the oldest and greatest extant classic TCM litera-ture Huangdi Neijing (Huangdirsquos Internal Classic) recordedWei Syndrome (flaccidity syndrome) Under this bookrsquosSuwen (Plain Questions) section chapter 44 Wei Syndromedescribed that the main acupoints for the treatment of Weisyndrome should be specifically selected from the Yang-ming Meridian in the following manner ldquoWhen treatingWei syndrome doctor should specifically target YangmingMeridian as Yangming is the source of nourishing forall the Zang-Fu internal viscera only with this nourishmentcan the tendons bones and joints be lubricatedrdquo Thereforewe mainly selected the acupoints of Yangming meridiansbecause they are full of qi and blood whose unblocked cir-culation is beneficial to recover the affected limbs includingparalysis of stroke (2) Details of needling acupoints weremainly selected in large intestine meridianchannel of handyang brightness (LI) and stomach meridianchannel of footyang brightness (ST) located on the subjectsrsquo hemiparetic
limbThey are upper limb Jianyu (LI 15) plus Jianliao (TE 14)Quchi (LI 11) plusHegu (LI 4) andChize (LU 5) plusNeiguan(PC 6) and lower limb Zusanli (ST 36) plus Yanglingquan(GB 34) Fenglong (ST 40) plus Xuanzhong (GB 39) andSanyinjiao (SP 6) plus Taichung (LR 3) The Huanqiu brandof sterile needles 15 inch in length (025mm times 10mm) wereperpendicularly inserted into 12 inches After the needlingsensation was attained the electrodes of G6805-2 electricstimulator were connected and electrostimulationwas addedThe intermittent wave was used with a frequency of 20Hzand an intensity that depended on the patientsrsquo toleranceThe electrical stimulation was given for 20 minutes oncedaily (3) Treatment regimen the total duration was 2 weekswith 6 days therapy followed by 1 day off each week (4)Other components of treatment the intervention of the sameWCM as the control group was also administered to the EAgroup (5) Practitioner background this entails an expertacupuncturist who has practiced acupuncture for more thanten years (6) Control interventions the patients at the controlgroup were given WCM based on the Chinese guideline fordiagnosis and management of acute ischemic stroke (version2010) [14] This stroke guideline is similar to the westerncountries [2] whichmeans that management of patients withAIS remains multifaceted and includes several aspects of carethat have not been tested in clinical trials briefly Bayaspirin01 g (H20065051) qd (Clopidogrel 50mg (H20000542) or
4 Evidence-Based Complementary and Alternative Medicine
Clopidogrel 75mg (J20040006) qd if there is contraindica-tion to aspirin treatment) Atorvastatin (Lipitor) 20mg qnand combination of needed therapies of the following aspectsfor 14 days (1) general supportive care mainly includes(A) airway ventilatory support and supplemental oxygen(B) cardiac monitoring and treatment (C) temperature (D)blood pressure (E) blood sugar and (F) nutrition (2) special-ized care mainly includes a variety of measures to improvecerebral blood circulation except thrombolytic agents andneuroprotective agents (3) treatment of acute complicationsmainly includes (A) brain edema and elevated intracranialpressure (B) seizures (C) dysphagia (D) pneumonia (E)voiding dysfunction and urinary tract infections and (F)deep vein thrombosis
24 Outcome Assessments The primary efficacy variableswere TST NIHSS and FAM that utilized blind assessmentat baseline and after 14 days of treatment (1) TST detailsof this technique are described previously by Magistris etal [8 10] Briefly the testing uses the Danish Dantec com-panyrsquos KeypointNet EMG and aMagPro Compact stimulator(Medtronic-Dantec Skovlunde Denmark) in the presentstudy TST consists of three stimuli a first magnetic pulseto the motor cortex and a second and third supramaximalelectrical pulse applied to a peripheral nerve that is theulnar nerve over the wrist and over the plexus respectivelyThe evoked antidromic and orthodromic responses collidein the nerve in a complex manner resulting in a com-pound muscle action potential (eg abductor digiti minimimuscle) providing a measure of the functional integrityof the corticospinal tract A control trial without a TMSpulse and a test trial carried out as described above arecompared The TST amplitude ratio was computed using theformula TSTratio = TSTtestTSTcontrol TST amplitude ratioand TST area ratio were used as a quantitative measurementof the central motor-conduction disorders The ratio valuesindicated the percentage of central motor-conduction failureand variation less than 10 was acceptable (TSTratio shouldbe gt90 indicating that the corticospinal tract is functionallyintact) In the present study we used 1-TSTratio as injury partof central motor-conduction impairment (2) NIHSS strokeoutcome was assessed by NIHSS score [15] (3) FMA FMAis a stroke-specific performance-based impairment index[16] Poststroke hemiplegia patients were graded by FMA inwhich the total score was 100 points and consisted of upperlimb score 0ndash66 points and lower limb score 0ndash34 points
The secondary efficacy variable was the clinical efficacyevaluation at the end of the treatment course by an appointeddoctor and safety assessments The criteria of neurologicaldeficit score were adopted based on theModified Edinburgh-Scandinavian Stroke Scale a nationwide accepted scoringsystem recommended at the Fourth National Cerebrovascu-lar Diseases Conference in China including consciousnessgaze facial paresis language walking ability and motorfunction of arms legs and hands The assessment wasconducted in accordance with the reduction in the scoresof basic nervous functional deficits and disability degree asfollows recovery scores the functional deficit scores weredecreased up to 91ndash100 and disability degree was at
Table 1 Baseline of demographic and clinical characteristics
EA electroacupuncture FMA Fugl-Meyer Assessment Scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication
grade 0 remarkable improvement the scores of functionaldeficit were decreased at 46ndash90 and disability degreewas at the grade 1ndash3 improvement the scores of functionaldeficit were decreased at 18ndash45 no change the scores offunctional deficit were decreased or increased at about 17deterioration the scores of functional deficit were increasedover 18 and death [13]
25 Safety Assessments Safety was assessed by the documen-tation of whole body reaction recorded whenever necessaryas well as by laboratory test of electrocardiogram (ECG) liverfunction and kidney function both at baseline time and at theend time of treatment
26 Statistics Analysis All data was processed by SPSS150Quantitative data was described by mean plusmn standard devi-ation (119909 plusmn 119904) An independent sample 1199051199051015840-test was usedfor comparing the means between two groups a paired119905-test was applied for comparing the change in outcomesbefore and after treatment Spearmanrsquos rho test was used forcorrelation analysis between the two quantitative variables(correlation coefficient 119903) Qualitative data was described bythe frequency (119891) and the percentage (119875) Fisherrsquos Exact Testis a test for independence in a 2 times 2 table and Pearson chi-square test for R times C table Statistical tests were completedblindly All tests were two-sided and were considered to bestatistically significant at 119875 lt 005
3 Results
31 Baseline Data Demographic characteristics and clinicalfeatures of participants in both groups are presented inTable 1 The differences in the demographics including
Evidence-Based Complementary and Alternative Medicine 5
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(a)
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(b)
Wrist-ADMErb-ADMCol W + E-Cortex-ADMTSTcontrol
TSTtest
(c)
Figure 2 (a) Triple stimulation technique (TST) tested in the right ulnar nerve of an adult healthy subject The TST amplitude ratio(TSTtestTSTcontrol) was 901 (b) TST tested in the right ulnar nerve of a patient with acute ischemic strokeTheTST amplitude ratio (TSTtestTSTcontrol) was 458 (c) TST tested in the right ulnar nerve of a patient with acute ischemic stroke after electroacupuncture treatment TheTST amplitude ratio (TSTtestTSTcontrol) was 839
age sex comorbid disease and infarct volume of the 2groups were insignificant (119875 gt 005) Moreover there is nostatistically significant difference in all the preintervention-selected outcome measures such as TST NIHSS and FAMbetween EA group and WCM group (119875 gt 005) (Table 1)
32 Clinical Effectiveness In the EA treatment group therewere 4 recovery cases 20 remarkable improvement cases 5improvement cases 1 no change case and 1 deterioration casethe total effective rate was 9350 In WCM control groupthere were 2 recovery cases 14 remarkable improvementcases 5 improvement cases 8 no change case and 1 worsecase the total effective rate was 7333The total effective ratewas statistically significantly superior in EA group to that inWCM group (1205942 = 572 119875 lt 001) (Table 2)
33 NIHSS Score FMA Score and TST119903119886119905119894119900
There was nostatistical difference between EA treatment group and WCMcontrol group inNIHSS score FMA score andTSTratio beforetreatment (119875 gt 005) After 14-day treatment NIHSS scoreFMA score and TSTratio between pretreatment and post-treatment were statistically more significant in EA treatmentgroup than those in WCM control group (119875 lt 001) Inaddition there were significant differences between the twogroups in all these three measure outcomes (119875 lt 005)(Table 3 Figure 2)
34 Correlation of TST119903119886119905119894119900
and NIHSS Score FMA ScoreThere was positive correlation between TSTratio and NIHSSscore before treatment (119903 = 0646 119875 lt 001) and after 14-day treatment (119903 = 0649 119875 lt 001) There was negative
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Comparison of the clinical efficacy between EA treatment group and WCM control group (119899 ())
Group 119899 Recovery Remarkable improvement Improvement No change Deterioration Death Total effective rate
WCM 30 2 (67) 14 (467) 5 (167) 8 (233) 1 (33) 0 (00) 7333EA electroacupuncture WCM western conventional medication Compared with WCM control group lowast119875 lt 005 Total effective rate = (recovery +Remarkable improvement + improvement) times 100 divide 119899
Table 3 Comparison of NIHSS score FMA score and TSTratiobetween EA treatment group and WCM control group (119909 plusmn 119904)
Items Group 119899
Assessment timePretreatment Posttreatment
NIHSS score EA 31 610 plusmn 261 252 plusmn 193lowast
WCM 30 630 plusmn 310 417 plusmn 340
FMA score EA 31 6848 plusmn 1981 8527 plusmn 1659lowast
WCM 30 6530 plusmn 2661 7417 plusmn 2416
TSTratio () EA 31 6354 plusmn 2820 3991 plusmn 3176lowast
WCM 30 6477 plusmn 2680 5645 plusmn 3149
EA electroacupuncture FMA Fugl-Meyer assessment scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication Compared with WCM controlgroup lowast119875 lt 005 Compared with pretreatment
119875 lt 001
Table 4 Correlation of TSTratio and NIHSS score FMA score (119903)
lowastlowast 1FMA Fugl-Meyer assessment scale NIHSS National Institutes of HealthStroke Scale TST triple-stimulation technique Correlation lowastlowast119875 lt 001
correlation between TSTratio and FMA score both beforetreatment (119903
119904= minus0570 119875 lt 001) and after treatment
(119903 = minus0572 119875 lt 001) There was also negative correlationbetween NIHSS and FMA scores both before treatment (119903 =minus0741 119875 lt 001) and after treatment (119903 = minus0769 119875 lt 001)(Table 4)
35 Complications No death of subjects or other seriousadverse events occurred during the treatment period Com-paring between two groups or between pretreatment andposttreatment adverse events ECG liver function andkidney function showed no significant difference (119875 gt 005)(Table 5) One patient in the EA group showed dizzinessand limb weakness for 2 times after the TST test Thesymptoms lasted for about half an hour and relieved bythemselves Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) slightly elevated in three patientsboth in EA group and in WCM group but the elevationswere not greater than 2 times the upper limit of normalSerum creatinine (SCr) level slightly elevated in two casesin WCM group (153 120583molL and 162 120583molL) and recoveredafter stopping use of the mannitol injection Two cases hadabnormal ECG with occasional atrial premature beats or the
first degree atrioventricular block in EA group and 1 patienthad abnormal ECGwith sinus arrhythmia inWCMgroup allthe above 3 patients with no requirement for clinical care
4 Discussion
To our knowledge to date this is the first randomized con-trolled study using the triple stimulation technique to objec-tively evaluate EA for motor function recovery in patientswith AIS The main findings in the present study were asfollows (1) EA had more beneficial effect on motor functionrecovery of AIS patients when compared with WCM controland was generally safe (2) the effect of EA formotor functioninjury and recovery of corticospinal tract impairments in AISpatients can be quantitatively evaluated by TST
Neurophysiological assessments have been used to mea-sure the extent of stroke damage to the motor system andto predict subsequent recovery of function An abnormalTST represents uppermotor neuron loss central axon lesionsor conduction blocks or inexcitability in response to TMS[17] In healthy Chinese subjects the TST amplitude ratio(TSTteatTSTcontrol) was 850 plusmn 67 and there was nodifference among genders age groups and arm length andsides [18] In the present study abnormal TSTratio wasobserved in all included stroke patients suggesting that TSTis effective to assess corticospinal tract impairment in AISTherefore TST can be a useful tool for quantitative diagnosisof corticospinal tract motor function in lesional defects ofconduction after acute ischemic stroke
Systematic reviews of the literature indicated that theinitial grade of paresis as measured on admission in thehospital is the most important predictor of early prognosisof motor recovery and special attention should be paid tothe clinical prognostic value of MEPs [19 20] Severity ofstroke measured by NIHSS score on admission is highlypredictive of excellent or devastating outcomes in ischemicstroke patients [21] FMA scale is a disease-specific objectiveimpairment index designed specifically as an evaluative mea-sure for assessment of recovery in the poststroke hemiplegicpatient [16] TST is a method improving the study of MEPs[8] In the present study TST and NIHSS score reducedand the FMA score improved after treatment in both groupsTST was positively correlated with NIHSS scores and wasnegatively correlated with FMA scores after both EA andWCM treatment These results showed that reduction ofNIHSS scores and improvement in FMA scores indicated theimprovement of motor function after treatment and TST canbe an indicator of prognosis for motor function recovery
Along the clinical course of ischemic stroke the mostcritical period of recovery is at the acute and subacute stages
Evidence-Based Complementary and Alternative Medicine 7
Table 5 Comparison of adverse events electrocardiogram liver function and kidney function between two groups or between pretreatmentand posttreatment
Group 119899
Pretreatment PosttreatmentALT SCr Adverse eventslowast ECGlowast ALT SCr
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
2 Evidence-Based Complementary and Alternative Medicine
assessments with transcranial magnetic stimulation (TMS)have provided newways tomeasure the extent of stroke dam-age and understand the anatomical and functional changesin the motor system at given time points during the courseof recovery [7] Recently a novel TMS technique involv-ing two collisions the triple-stimulation technique (TST)links the central to peripheral conduction and suppressesdesynchronization of the motor evoked potentials (MEPs)and this technique enabled a quantitative electrophysiologicalmeasurement of the central motor-conduction failure thatcauses the patientrsquos disability [8] The TST was reported tobe 15sim275 times more sensitive than conventional TMS fordetecting corticospinal conduction failure [9ndash11] NowadaysTST has been applied for various disorders to quantifyassessment of the central conduction failure suggesting thatTST was useful in quantifying the benefits of treatmentsin disorders such as multiple sclerosis amyotrophic lateralsclerosis and spondylotic myelopathies or cerebral plasticityin the course of rehabilitation programmes in disorders suchas stroke [10] Thus TST is a useful diagnostic tool andprovides an accurate objective quantification in follow-upstudies including assessment of the efficiency of treatmentsFurthermore the most important period of recovery is atthe acute and subacute stages during the clinical course ofischemic stroke [12] In the present study we thus conducteda randomized controlled pilot study using the TST to objec-tively evaluate electroacupuncture (EA) for motor functionrecovery in patients with the first-ever ischemic stroke andwithin the first three days of stroke onset
2 Methods
This clinical study was designed as a randomized controlledtrial and was conducted between June 2010 and March 2011in China The trial used the two-group parallel design where63 cases of AIS patients were randomized in a 1 1 ratio toreceive EA plus western conventional medication (WCM) orsingle WCM treatment for a total of 14 days The efficacy andsafety of EA was mainly assessed by using TST and severalneurological outcome scales after 14-day treatment Thestudy was conducted in accordance with the World MedicalAssociation Declaration of Helsinki and Chinarsquos regulationsand guidelines on good clinical practice Ethical approval forthe trial was obtained from the Ethics Committee of the localhospital Ethical ReviewBoardWritten informed consent wasobtained from all subjects
21 Participants Subjects were considered eligible to beenrolled in the study only when all of the following inclusioncriteria were met (1) a diagnosis of AIS according to theChinese national criteria in Diagnostic Essentials of VariousCerebrovascular Diseases revised at the Fourth NationalConference of China Society ofMedicine onCerebrovascularDiseases in 1995 [13]The diagnosis of AISmust be confirmedby both CT and MRI (2) within in 72 hours from the onsetof stroke (3) motor deficits in at least one limb and NationalInstitutes of Health Stroke Scale (NIHSS) score that is greaterthan or equals to 4 (4) the age ranged from 35 to 80 years (5)
all subjects must participate of their own free will and sign aninformed consent form
The following exclusion criteria were applied (1) con-traindication of TMS (2) suffering from neural or mus-culoskeletal disease that affects function recovery beforeAIS (3) more than 72 hours after the onset of stroke(4) patients suffering from transient ischemic attack sub-arachnoid hemorrhage ICH or cerebellar infarction (5)patients who presented with conscious disturbance aphasiaand dementia after stroke onset (6) emergency and criticalpatients who were not suitable for acupuncture such as acutemyocardial infarction serious infection active tuberculosishepatic failure andor renal failure and upper gastrointestinalbleeding (7) patients age lt 35 years old or gt80 years old (8)those who refuse to sign an informed consent form
The terminal criteria were as follows (1) those who didnot meet the inclusion criteria but were included in thetrial (2) patients who did not obey the trial plan to takemedication and affected the efficacy evaluation (3) patientswho withdraw from the trial if any of the serious adverseevents happened (4) patients whose condition deterioratedor when serious complications occurred (5) patients whostop participating due to onersquos own free will during the trialPatients could withdraw from the study at any time and forany reason
22 Participant Flow Baseline Evaluation and Randomiza-tion Based on inclusion criteria 95 patients were screenedand 32 patients were excluded due to not meeting inclusioncriteria declining to participate andor other reasons Afterthe patients have fully understood the study and have signedthe informed consent the baseline evaluation was recordedand assessed by a responsible doctor including age sexheight body weight history medication history drink-ingsmoking history risk factors (history of hypertensionstroke diabetes and cardiovascular disease) and type of limbparesis NIHSS score was carried out by a trained doctorBasic life signs such as breathing heart rate blood pressureand pulse were recorded The lesion site and volume ofcerebral infarction were also assessed by a CT and MRI scanThe infarct volume was divided into 3 types according tothe Pullicino formula (length times width times number of CT orMRT scanning positive layer2) They are large size infarct(gt10 cm3) medium size infarct (5sim10 cm3) and small sizeinfarct (lt5 cm3) All of the patients should take lab testsof liver and kidney function The qualified subjects finishedTSTtest level and Fugl-Meyer Assessment Scale (FMA) scoreSixty-three AIS patients signed informed consent finishedbaseline evaluation and entered random process Thesepatientswere randomly divided into EAplusWCMtreatmentgroup (EA group 119899 = 32) and WCM control group (WCMgroup 119899 = 31) by using a random number tableThe randomnumbers were sealed in opaque envelopes and the researcheropened the envelope only to start the intervention Duringthe trial 2 patients were transferred to intensive care unitfrom general ward and discontinued the intervention becauseof one cerebral hernia secondary to large size cerebral infarc-tion and the other severe pulmonary infection secondary toaspirations Ultimately statistical analyses were conducted on
Evidence-Based Complementary and Alternative Medicine 3
because of cerebral hernia secondary to large size cerebral infarction
Allocated to electroacupuncture plus
All patients received allocated intervention
because of severe pulmonary infection secondary to aspirations
Allocated to a single western conventional
All patients received allocated intervention
Allocation
Analysis
Assessed for eligibility (n = 95)
Excluded (n = 32)∙ Not meeting inclusion criteria (n = 21)∙ Declined to participate (n = 6)∙ Other reasons (n = 5)
western conventional medication (n = 32) medication (n = 31)
Followup
Figure 1 Participant flow diagram
the results from 31 patients of EA treatment group and 30patients of WCM control group (Figure 1 participant flowdiagram)
23 Interventions Based on the Standards for ReportingInterventions in Clinical Trials of Acupuncture (STRICTA)2010 checklist we reported interventions in present clini-cal trial of electroacupuncture as follows (1) acupuncturerationale the oldest and greatest extant classic TCM litera-ture Huangdi Neijing (Huangdirsquos Internal Classic) recordedWei Syndrome (flaccidity syndrome) Under this bookrsquosSuwen (Plain Questions) section chapter 44 Wei Syndromedescribed that the main acupoints for the treatment of Weisyndrome should be specifically selected from the Yang-ming Meridian in the following manner ldquoWhen treatingWei syndrome doctor should specifically target YangmingMeridian as Yangming is the source of nourishing forall the Zang-Fu internal viscera only with this nourishmentcan the tendons bones and joints be lubricatedrdquo Thereforewe mainly selected the acupoints of Yangming meridiansbecause they are full of qi and blood whose unblocked cir-culation is beneficial to recover the affected limbs includingparalysis of stroke (2) Details of needling acupoints weremainly selected in large intestine meridianchannel of handyang brightness (LI) and stomach meridianchannel of footyang brightness (ST) located on the subjectsrsquo hemiparetic
limbThey are upper limb Jianyu (LI 15) plus Jianliao (TE 14)Quchi (LI 11) plusHegu (LI 4) andChize (LU 5) plusNeiguan(PC 6) and lower limb Zusanli (ST 36) plus Yanglingquan(GB 34) Fenglong (ST 40) plus Xuanzhong (GB 39) andSanyinjiao (SP 6) plus Taichung (LR 3) The Huanqiu brandof sterile needles 15 inch in length (025mm times 10mm) wereperpendicularly inserted into 12 inches After the needlingsensation was attained the electrodes of G6805-2 electricstimulator were connected and electrostimulationwas addedThe intermittent wave was used with a frequency of 20Hzand an intensity that depended on the patientsrsquo toleranceThe electrical stimulation was given for 20 minutes oncedaily (3) Treatment regimen the total duration was 2 weekswith 6 days therapy followed by 1 day off each week (4)Other components of treatment the intervention of the sameWCM as the control group was also administered to the EAgroup (5) Practitioner background this entails an expertacupuncturist who has practiced acupuncture for more thanten years (6) Control interventions the patients at the controlgroup were given WCM based on the Chinese guideline fordiagnosis and management of acute ischemic stroke (version2010) [14] This stroke guideline is similar to the westerncountries [2] whichmeans that management of patients withAIS remains multifaceted and includes several aspects of carethat have not been tested in clinical trials briefly Bayaspirin01 g (H20065051) qd (Clopidogrel 50mg (H20000542) or
4 Evidence-Based Complementary and Alternative Medicine
Clopidogrel 75mg (J20040006) qd if there is contraindica-tion to aspirin treatment) Atorvastatin (Lipitor) 20mg qnand combination of needed therapies of the following aspectsfor 14 days (1) general supportive care mainly includes(A) airway ventilatory support and supplemental oxygen(B) cardiac monitoring and treatment (C) temperature (D)blood pressure (E) blood sugar and (F) nutrition (2) special-ized care mainly includes a variety of measures to improvecerebral blood circulation except thrombolytic agents andneuroprotective agents (3) treatment of acute complicationsmainly includes (A) brain edema and elevated intracranialpressure (B) seizures (C) dysphagia (D) pneumonia (E)voiding dysfunction and urinary tract infections and (F)deep vein thrombosis
24 Outcome Assessments The primary efficacy variableswere TST NIHSS and FAM that utilized blind assessmentat baseline and after 14 days of treatment (1) TST detailsof this technique are described previously by Magistris etal [8 10] Briefly the testing uses the Danish Dantec com-panyrsquos KeypointNet EMG and aMagPro Compact stimulator(Medtronic-Dantec Skovlunde Denmark) in the presentstudy TST consists of three stimuli a first magnetic pulseto the motor cortex and a second and third supramaximalelectrical pulse applied to a peripheral nerve that is theulnar nerve over the wrist and over the plexus respectivelyThe evoked antidromic and orthodromic responses collidein the nerve in a complex manner resulting in a com-pound muscle action potential (eg abductor digiti minimimuscle) providing a measure of the functional integrityof the corticospinal tract A control trial without a TMSpulse and a test trial carried out as described above arecompared The TST amplitude ratio was computed using theformula TSTratio = TSTtestTSTcontrol TST amplitude ratioand TST area ratio were used as a quantitative measurementof the central motor-conduction disorders The ratio valuesindicated the percentage of central motor-conduction failureand variation less than 10 was acceptable (TSTratio shouldbe gt90 indicating that the corticospinal tract is functionallyintact) In the present study we used 1-TSTratio as injury partof central motor-conduction impairment (2) NIHSS strokeoutcome was assessed by NIHSS score [15] (3) FMA FMAis a stroke-specific performance-based impairment index[16] Poststroke hemiplegia patients were graded by FMA inwhich the total score was 100 points and consisted of upperlimb score 0ndash66 points and lower limb score 0ndash34 points
The secondary efficacy variable was the clinical efficacyevaluation at the end of the treatment course by an appointeddoctor and safety assessments The criteria of neurologicaldeficit score were adopted based on theModified Edinburgh-Scandinavian Stroke Scale a nationwide accepted scoringsystem recommended at the Fourth National Cerebrovascu-lar Diseases Conference in China including consciousnessgaze facial paresis language walking ability and motorfunction of arms legs and hands The assessment wasconducted in accordance with the reduction in the scoresof basic nervous functional deficits and disability degree asfollows recovery scores the functional deficit scores weredecreased up to 91ndash100 and disability degree was at
Table 1 Baseline of demographic and clinical characteristics
EA electroacupuncture FMA Fugl-Meyer Assessment Scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication
grade 0 remarkable improvement the scores of functionaldeficit were decreased at 46ndash90 and disability degreewas at the grade 1ndash3 improvement the scores of functionaldeficit were decreased at 18ndash45 no change the scores offunctional deficit were decreased or increased at about 17deterioration the scores of functional deficit were increasedover 18 and death [13]
25 Safety Assessments Safety was assessed by the documen-tation of whole body reaction recorded whenever necessaryas well as by laboratory test of electrocardiogram (ECG) liverfunction and kidney function both at baseline time and at theend time of treatment
26 Statistics Analysis All data was processed by SPSS150Quantitative data was described by mean plusmn standard devi-ation (119909 plusmn 119904) An independent sample 1199051199051015840-test was usedfor comparing the means between two groups a paired119905-test was applied for comparing the change in outcomesbefore and after treatment Spearmanrsquos rho test was used forcorrelation analysis between the two quantitative variables(correlation coefficient 119903) Qualitative data was described bythe frequency (119891) and the percentage (119875) Fisherrsquos Exact Testis a test for independence in a 2 times 2 table and Pearson chi-square test for R times C table Statistical tests were completedblindly All tests were two-sided and were considered to bestatistically significant at 119875 lt 005
3 Results
31 Baseline Data Demographic characteristics and clinicalfeatures of participants in both groups are presented inTable 1 The differences in the demographics including
Evidence-Based Complementary and Alternative Medicine 5
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(a)
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(b)
Wrist-ADMErb-ADMCol W + E-Cortex-ADMTSTcontrol
TSTtest
(c)
Figure 2 (a) Triple stimulation technique (TST) tested in the right ulnar nerve of an adult healthy subject The TST amplitude ratio(TSTtestTSTcontrol) was 901 (b) TST tested in the right ulnar nerve of a patient with acute ischemic strokeTheTST amplitude ratio (TSTtestTSTcontrol) was 458 (c) TST tested in the right ulnar nerve of a patient with acute ischemic stroke after electroacupuncture treatment TheTST amplitude ratio (TSTtestTSTcontrol) was 839
age sex comorbid disease and infarct volume of the 2groups were insignificant (119875 gt 005) Moreover there is nostatistically significant difference in all the preintervention-selected outcome measures such as TST NIHSS and FAMbetween EA group and WCM group (119875 gt 005) (Table 1)
32 Clinical Effectiveness In the EA treatment group therewere 4 recovery cases 20 remarkable improvement cases 5improvement cases 1 no change case and 1 deterioration casethe total effective rate was 9350 In WCM control groupthere were 2 recovery cases 14 remarkable improvementcases 5 improvement cases 8 no change case and 1 worsecase the total effective rate was 7333The total effective ratewas statistically significantly superior in EA group to that inWCM group (1205942 = 572 119875 lt 001) (Table 2)
33 NIHSS Score FMA Score and TST119903119886119905119894119900
There was nostatistical difference between EA treatment group and WCMcontrol group inNIHSS score FMA score andTSTratio beforetreatment (119875 gt 005) After 14-day treatment NIHSS scoreFMA score and TSTratio between pretreatment and post-treatment were statistically more significant in EA treatmentgroup than those in WCM control group (119875 lt 001) Inaddition there were significant differences between the twogroups in all these three measure outcomes (119875 lt 005)(Table 3 Figure 2)
34 Correlation of TST119903119886119905119894119900
and NIHSS Score FMA ScoreThere was positive correlation between TSTratio and NIHSSscore before treatment (119903 = 0646 119875 lt 001) and after 14-day treatment (119903 = 0649 119875 lt 001) There was negative
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Comparison of the clinical efficacy between EA treatment group and WCM control group (119899 ())
Group 119899 Recovery Remarkable improvement Improvement No change Deterioration Death Total effective rate
WCM 30 2 (67) 14 (467) 5 (167) 8 (233) 1 (33) 0 (00) 7333EA electroacupuncture WCM western conventional medication Compared with WCM control group lowast119875 lt 005 Total effective rate = (recovery +Remarkable improvement + improvement) times 100 divide 119899
Table 3 Comparison of NIHSS score FMA score and TSTratiobetween EA treatment group and WCM control group (119909 plusmn 119904)
Items Group 119899
Assessment timePretreatment Posttreatment
NIHSS score EA 31 610 plusmn 261 252 plusmn 193lowast
WCM 30 630 plusmn 310 417 plusmn 340
FMA score EA 31 6848 plusmn 1981 8527 plusmn 1659lowast
WCM 30 6530 plusmn 2661 7417 plusmn 2416
TSTratio () EA 31 6354 plusmn 2820 3991 plusmn 3176lowast
WCM 30 6477 plusmn 2680 5645 plusmn 3149
EA electroacupuncture FMA Fugl-Meyer assessment scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication Compared with WCM controlgroup lowast119875 lt 005 Compared with pretreatment
119875 lt 001
Table 4 Correlation of TSTratio and NIHSS score FMA score (119903)
lowastlowast 1FMA Fugl-Meyer assessment scale NIHSS National Institutes of HealthStroke Scale TST triple-stimulation technique Correlation lowastlowast119875 lt 001
correlation between TSTratio and FMA score both beforetreatment (119903
119904= minus0570 119875 lt 001) and after treatment
(119903 = minus0572 119875 lt 001) There was also negative correlationbetween NIHSS and FMA scores both before treatment (119903 =minus0741 119875 lt 001) and after treatment (119903 = minus0769 119875 lt 001)(Table 4)
35 Complications No death of subjects or other seriousadverse events occurred during the treatment period Com-paring between two groups or between pretreatment andposttreatment adverse events ECG liver function andkidney function showed no significant difference (119875 gt 005)(Table 5) One patient in the EA group showed dizzinessand limb weakness for 2 times after the TST test Thesymptoms lasted for about half an hour and relieved bythemselves Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) slightly elevated in three patientsboth in EA group and in WCM group but the elevationswere not greater than 2 times the upper limit of normalSerum creatinine (SCr) level slightly elevated in two casesin WCM group (153 120583molL and 162 120583molL) and recoveredafter stopping use of the mannitol injection Two cases hadabnormal ECG with occasional atrial premature beats or the
first degree atrioventricular block in EA group and 1 patienthad abnormal ECGwith sinus arrhythmia inWCMgroup allthe above 3 patients with no requirement for clinical care
4 Discussion
To our knowledge to date this is the first randomized con-trolled study using the triple stimulation technique to objec-tively evaluate EA for motor function recovery in patientswith AIS The main findings in the present study were asfollows (1) EA had more beneficial effect on motor functionrecovery of AIS patients when compared with WCM controland was generally safe (2) the effect of EA formotor functioninjury and recovery of corticospinal tract impairments in AISpatients can be quantitatively evaluated by TST
Neurophysiological assessments have been used to mea-sure the extent of stroke damage to the motor system andto predict subsequent recovery of function An abnormalTST represents uppermotor neuron loss central axon lesionsor conduction blocks or inexcitability in response to TMS[17] In healthy Chinese subjects the TST amplitude ratio(TSTteatTSTcontrol) was 850 plusmn 67 and there was nodifference among genders age groups and arm length andsides [18] In the present study abnormal TSTratio wasobserved in all included stroke patients suggesting that TSTis effective to assess corticospinal tract impairment in AISTherefore TST can be a useful tool for quantitative diagnosisof corticospinal tract motor function in lesional defects ofconduction after acute ischemic stroke
Systematic reviews of the literature indicated that theinitial grade of paresis as measured on admission in thehospital is the most important predictor of early prognosisof motor recovery and special attention should be paid tothe clinical prognostic value of MEPs [19 20] Severity ofstroke measured by NIHSS score on admission is highlypredictive of excellent or devastating outcomes in ischemicstroke patients [21] FMA scale is a disease-specific objectiveimpairment index designed specifically as an evaluative mea-sure for assessment of recovery in the poststroke hemiplegicpatient [16] TST is a method improving the study of MEPs[8] In the present study TST and NIHSS score reducedand the FMA score improved after treatment in both groupsTST was positively correlated with NIHSS scores and wasnegatively correlated with FMA scores after both EA andWCM treatment These results showed that reduction ofNIHSS scores and improvement in FMA scores indicated theimprovement of motor function after treatment and TST canbe an indicator of prognosis for motor function recovery
Along the clinical course of ischemic stroke the mostcritical period of recovery is at the acute and subacute stages
Evidence-Based Complementary and Alternative Medicine 7
Table 5 Comparison of adverse events electrocardiogram liver function and kidney function between two groups or between pretreatmentand posttreatment
Group 119899
Pretreatment PosttreatmentALT SCr Adverse eventslowast ECGlowast ALT SCr
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
western conventional medication (n = 32) medication (n = 31)
Followup
Figure 1 Participant flow diagram
the results from 31 patients of EA treatment group and 30patients of WCM control group (Figure 1 participant flowdiagram)
23 Interventions Based on the Standards for ReportingInterventions in Clinical Trials of Acupuncture (STRICTA)2010 checklist we reported interventions in present clini-cal trial of electroacupuncture as follows (1) acupuncturerationale the oldest and greatest extant classic TCM litera-ture Huangdi Neijing (Huangdirsquos Internal Classic) recordedWei Syndrome (flaccidity syndrome) Under this bookrsquosSuwen (Plain Questions) section chapter 44 Wei Syndromedescribed that the main acupoints for the treatment of Weisyndrome should be specifically selected from the Yang-ming Meridian in the following manner ldquoWhen treatingWei syndrome doctor should specifically target YangmingMeridian as Yangming is the source of nourishing forall the Zang-Fu internal viscera only with this nourishmentcan the tendons bones and joints be lubricatedrdquo Thereforewe mainly selected the acupoints of Yangming meridiansbecause they are full of qi and blood whose unblocked cir-culation is beneficial to recover the affected limbs includingparalysis of stroke (2) Details of needling acupoints weremainly selected in large intestine meridianchannel of handyang brightness (LI) and stomach meridianchannel of footyang brightness (ST) located on the subjectsrsquo hemiparetic
limbThey are upper limb Jianyu (LI 15) plus Jianliao (TE 14)Quchi (LI 11) plusHegu (LI 4) andChize (LU 5) plusNeiguan(PC 6) and lower limb Zusanli (ST 36) plus Yanglingquan(GB 34) Fenglong (ST 40) plus Xuanzhong (GB 39) andSanyinjiao (SP 6) plus Taichung (LR 3) The Huanqiu brandof sterile needles 15 inch in length (025mm times 10mm) wereperpendicularly inserted into 12 inches After the needlingsensation was attained the electrodes of G6805-2 electricstimulator were connected and electrostimulationwas addedThe intermittent wave was used with a frequency of 20Hzand an intensity that depended on the patientsrsquo toleranceThe electrical stimulation was given for 20 minutes oncedaily (3) Treatment regimen the total duration was 2 weekswith 6 days therapy followed by 1 day off each week (4)Other components of treatment the intervention of the sameWCM as the control group was also administered to the EAgroup (5) Practitioner background this entails an expertacupuncturist who has practiced acupuncture for more thanten years (6) Control interventions the patients at the controlgroup were given WCM based on the Chinese guideline fordiagnosis and management of acute ischemic stroke (version2010) [14] This stroke guideline is similar to the westerncountries [2] whichmeans that management of patients withAIS remains multifaceted and includes several aspects of carethat have not been tested in clinical trials briefly Bayaspirin01 g (H20065051) qd (Clopidogrel 50mg (H20000542) or
4 Evidence-Based Complementary and Alternative Medicine
Clopidogrel 75mg (J20040006) qd if there is contraindica-tion to aspirin treatment) Atorvastatin (Lipitor) 20mg qnand combination of needed therapies of the following aspectsfor 14 days (1) general supportive care mainly includes(A) airway ventilatory support and supplemental oxygen(B) cardiac monitoring and treatment (C) temperature (D)blood pressure (E) blood sugar and (F) nutrition (2) special-ized care mainly includes a variety of measures to improvecerebral blood circulation except thrombolytic agents andneuroprotective agents (3) treatment of acute complicationsmainly includes (A) brain edema and elevated intracranialpressure (B) seizures (C) dysphagia (D) pneumonia (E)voiding dysfunction and urinary tract infections and (F)deep vein thrombosis
24 Outcome Assessments The primary efficacy variableswere TST NIHSS and FAM that utilized blind assessmentat baseline and after 14 days of treatment (1) TST detailsof this technique are described previously by Magistris etal [8 10] Briefly the testing uses the Danish Dantec com-panyrsquos KeypointNet EMG and aMagPro Compact stimulator(Medtronic-Dantec Skovlunde Denmark) in the presentstudy TST consists of three stimuli a first magnetic pulseto the motor cortex and a second and third supramaximalelectrical pulse applied to a peripheral nerve that is theulnar nerve over the wrist and over the plexus respectivelyThe evoked antidromic and orthodromic responses collidein the nerve in a complex manner resulting in a com-pound muscle action potential (eg abductor digiti minimimuscle) providing a measure of the functional integrityof the corticospinal tract A control trial without a TMSpulse and a test trial carried out as described above arecompared The TST amplitude ratio was computed using theformula TSTratio = TSTtestTSTcontrol TST amplitude ratioand TST area ratio were used as a quantitative measurementof the central motor-conduction disorders The ratio valuesindicated the percentage of central motor-conduction failureand variation less than 10 was acceptable (TSTratio shouldbe gt90 indicating that the corticospinal tract is functionallyintact) In the present study we used 1-TSTratio as injury partof central motor-conduction impairment (2) NIHSS strokeoutcome was assessed by NIHSS score [15] (3) FMA FMAis a stroke-specific performance-based impairment index[16] Poststroke hemiplegia patients were graded by FMA inwhich the total score was 100 points and consisted of upperlimb score 0ndash66 points and lower limb score 0ndash34 points
The secondary efficacy variable was the clinical efficacyevaluation at the end of the treatment course by an appointeddoctor and safety assessments The criteria of neurologicaldeficit score were adopted based on theModified Edinburgh-Scandinavian Stroke Scale a nationwide accepted scoringsystem recommended at the Fourth National Cerebrovascu-lar Diseases Conference in China including consciousnessgaze facial paresis language walking ability and motorfunction of arms legs and hands The assessment wasconducted in accordance with the reduction in the scoresof basic nervous functional deficits and disability degree asfollows recovery scores the functional deficit scores weredecreased up to 91ndash100 and disability degree was at
Table 1 Baseline of demographic and clinical characteristics
EA electroacupuncture FMA Fugl-Meyer Assessment Scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication
grade 0 remarkable improvement the scores of functionaldeficit were decreased at 46ndash90 and disability degreewas at the grade 1ndash3 improvement the scores of functionaldeficit were decreased at 18ndash45 no change the scores offunctional deficit were decreased or increased at about 17deterioration the scores of functional deficit were increasedover 18 and death [13]
25 Safety Assessments Safety was assessed by the documen-tation of whole body reaction recorded whenever necessaryas well as by laboratory test of electrocardiogram (ECG) liverfunction and kidney function both at baseline time and at theend time of treatment
26 Statistics Analysis All data was processed by SPSS150Quantitative data was described by mean plusmn standard devi-ation (119909 plusmn 119904) An independent sample 1199051199051015840-test was usedfor comparing the means between two groups a paired119905-test was applied for comparing the change in outcomesbefore and after treatment Spearmanrsquos rho test was used forcorrelation analysis between the two quantitative variables(correlation coefficient 119903) Qualitative data was described bythe frequency (119891) and the percentage (119875) Fisherrsquos Exact Testis a test for independence in a 2 times 2 table and Pearson chi-square test for R times C table Statistical tests were completedblindly All tests were two-sided and were considered to bestatistically significant at 119875 lt 005
3 Results
31 Baseline Data Demographic characteristics and clinicalfeatures of participants in both groups are presented inTable 1 The differences in the demographics including
Evidence-Based Complementary and Alternative Medicine 5
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(a)
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(b)
Wrist-ADMErb-ADMCol W + E-Cortex-ADMTSTcontrol
TSTtest
(c)
Figure 2 (a) Triple stimulation technique (TST) tested in the right ulnar nerve of an adult healthy subject The TST amplitude ratio(TSTtestTSTcontrol) was 901 (b) TST tested in the right ulnar nerve of a patient with acute ischemic strokeTheTST amplitude ratio (TSTtestTSTcontrol) was 458 (c) TST tested in the right ulnar nerve of a patient with acute ischemic stroke after electroacupuncture treatment TheTST amplitude ratio (TSTtestTSTcontrol) was 839
age sex comorbid disease and infarct volume of the 2groups were insignificant (119875 gt 005) Moreover there is nostatistically significant difference in all the preintervention-selected outcome measures such as TST NIHSS and FAMbetween EA group and WCM group (119875 gt 005) (Table 1)
32 Clinical Effectiveness In the EA treatment group therewere 4 recovery cases 20 remarkable improvement cases 5improvement cases 1 no change case and 1 deterioration casethe total effective rate was 9350 In WCM control groupthere were 2 recovery cases 14 remarkable improvementcases 5 improvement cases 8 no change case and 1 worsecase the total effective rate was 7333The total effective ratewas statistically significantly superior in EA group to that inWCM group (1205942 = 572 119875 lt 001) (Table 2)
33 NIHSS Score FMA Score and TST119903119886119905119894119900
There was nostatistical difference between EA treatment group and WCMcontrol group inNIHSS score FMA score andTSTratio beforetreatment (119875 gt 005) After 14-day treatment NIHSS scoreFMA score and TSTratio between pretreatment and post-treatment were statistically more significant in EA treatmentgroup than those in WCM control group (119875 lt 001) Inaddition there were significant differences between the twogroups in all these three measure outcomes (119875 lt 005)(Table 3 Figure 2)
34 Correlation of TST119903119886119905119894119900
and NIHSS Score FMA ScoreThere was positive correlation between TSTratio and NIHSSscore before treatment (119903 = 0646 119875 lt 001) and after 14-day treatment (119903 = 0649 119875 lt 001) There was negative
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Comparison of the clinical efficacy between EA treatment group and WCM control group (119899 ())
Group 119899 Recovery Remarkable improvement Improvement No change Deterioration Death Total effective rate
WCM 30 2 (67) 14 (467) 5 (167) 8 (233) 1 (33) 0 (00) 7333EA electroacupuncture WCM western conventional medication Compared with WCM control group lowast119875 lt 005 Total effective rate = (recovery +Remarkable improvement + improvement) times 100 divide 119899
Table 3 Comparison of NIHSS score FMA score and TSTratiobetween EA treatment group and WCM control group (119909 plusmn 119904)
Items Group 119899
Assessment timePretreatment Posttreatment
NIHSS score EA 31 610 plusmn 261 252 plusmn 193lowast
WCM 30 630 plusmn 310 417 plusmn 340
FMA score EA 31 6848 plusmn 1981 8527 plusmn 1659lowast
WCM 30 6530 plusmn 2661 7417 plusmn 2416
TSTratio () EA 31 6354 plusmn 2820 3991 plusmn 3176lowast
WCM 30 6477 plusmn 2680 5645 plusmn 3149
EA electroacupuncture FMA Fugl-Meyer assessment scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication Compared with WCM controlgroup lowast119875 lt 005 Compared with pretreatment
119875 lt 001
Table 4 Correlation of TSTratio and NIHSS score FMA score (119903)
lowastlowast 1FMA Fugl-Meyer assessment scale NIHSS National Institutes of HealthStroke Scale TST triple-stimulation technique Correlation lowastlowast119875 lt 001
correlation between TSTratio and FMA score both beforetreatment (119903
119904= minus0570 119875 lt 001) and after treatment
(119903 = minus0572 119875 lt 001) There was also negative correlationbetween NIHSS and FMA scores both before treatment (119903 =minus0741 119875 lt 001) and after treatment (119903 = minus0769 119875 lt 001)(Table 4)
35 Complications No death of subjects or other seriousadverse events occurred during the treatment period Com-paring between two groups or between pretreatment andposttreatment adverse events ECG liver function andkidney function showed no significant difference (119875 gt 005)(Table 5) One patient in the EA group showed dizzinessand limb weakness for 2 times after the TST test Thesymptoms lasted for about half an hour and relieved bythemselves Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) slightly elevated in three patientsboth in EA group and in WCM group but the elevationswere not greater than 2 times the upper limit of normalSerum creatinine (SCr) level slightly elevated in two casesin WCM group (153 120583molL and 162 120583molL) and recoveredafter stopping use of the mannitol injection Two cases hadabnormal ECG with occasional atrial premature beats or the
first degree atrioventricular block in EA group and 1 patienthad abnormal ECGwith sinus arrhythmia inWCMgroup allthe above 3 patients with no requirement for clinical care
4 Discussion
To our knowledge to date this is the first randomized con-trolled study using the triple stimulation technique to objec-tively evaluate EA for motor function recovery in patientswith AIS The main findings in the present study were asfollows (1) EA had more beneficial effect on motor functionrecovery of AIS patients when compared with WCM controland was generally safe (2) the effect of EA formotor functioninjury and recovery of corticospinal tract impairments in AISpatients can be quantitatively evaluated by TST
Neurophysiological assessments have been used to mea-sure the extent of stroke damage to the motor system andto predict subsequent recovery of function An abnormalTST represents uppermotor neuron loss central axon lesionsor conduction blocks or inexcitability in response to TMS[17] In healthy Chinese subjects the TST amplitude ratio(TSTteatTSTcontrol) was 850 plusmn 67 and there was nodifference among genders age groups and arm length andsides [18] In the present study abnormal TSTratio wasobserved in all included stroke patients suggesting that TSTis effective to assess corticospinal tract impairment in AISTherefore TST can be a useful tool for quantitative diagnosisof corticospinal tract motor function in lesional defects ofconduction after acute ischemic stroke
Systematic reviews of the literature indicated that theinitial grade of paresis as measured on admission in thehospital is the most important predictor of early prognosisof motor recovery and special attention should be paid tothe clinical prognostic value of MEPs [19 20] Severity ofstroke measured by NIHSS score on admission is highlypredictive of excellent or devastating outcomes in ischemicstroke patients [21] FMA scale is a disease-specific objectiveimpairment index designed specifically as an evaluative mea-sure for assessment of recovery in the poststroke hemiplegicpatient [16] TST is a method improving the study of MEPs[8] In the present study TST and NIHSS score reducedand the FMA score improved after treatment in both groupsTST was positively correlated with NIHSS scores and wasnegatively correlated with FMA scores after both EA andWCM treatment These results showed that reduction ofNIHSS scores and improvement in FMA scores indicated theimprovement of motor function after treatment and TST canbe an indicator of prognosis for motor function recovery
Along the clinical course of ischemic stroke the mostcritical period of recovery is at the acute and subacute stages
Evidence-Based Complementary and Alternative Medicine 7
Table 5 Comparison of adverse events electrocardiogram liver function and kidney function between two groups or between pretreatmentand posttreatment
Group 119899
Pretreatment PosttreatmentALT SCr Adverse eventslowast ECGlowast ALT SCr
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
4 Evidence-Based Complementary and Alternative Medicine
Clopidogrel 75mg (J20040006) qd if there is contraindica-tion to aspirin treatment) Atorvastatin (Lipitor) 20mg qnand combination of needed therapies of the following aspectsfor 14 days (1) general supportive care mainly includes(A) airway ventilatory support and supplemental oxygen(B) cardiac monitoring and treatment (C) temperature (D)blood pressure (E) blood sugar and (F) nutrition (2) special-ized care mainly includes a variety of measures to improvecerebral blood circulation except thrombolytic agents andneuroprotective agents (3) treatment of acute complicationsmainly includes (A) brain edema and elevated intracranialpressure (B) seizures (C) dysphagia (D) pneumonia (E)voiding dysfunction and urinary tract infections and (F)deep vein thrombosis
24 Outcome Assessments The primary efficacy variableswere TST NIHSS and FAM that utilized blind assessmentat baseline and after 14 days of treatment (1) TST detailsof this technique are described previously by Magistris etal [8 10] Briefly the testing uses the Danish Dantec com-panyrsquos KeypointNet EMG and aMagPro Compact stimulator(Medtronic-Dantec Skovlunde Denmark) in the presentstudy TST consists of three stimuli a first magnetic pulseto the motor cortex and a second and third supramaximalelectrical pulse applied to a peripheral nerve that is theulnar nerve over the wrist and over the plexus respectivelyThe evoked antidromic and orthodromic responses collidein the nerve in a complex manner resulting in a com-pound muscle action potential (eg abductor digiti minimimuscle) providing a measure of the functional integrityof the corticospinal tract A control trial without a TMSpulse and a test trial carried out as described above arecompared The TST amplitude ratio was computed using theformula TSTratio = TSTtestTSTcontrol TST amplitude ratioand TST area ratio were used as a quantitative measurementof the central motor-conduction disorders The ratio valuesindicated the percentage of central motor-conduction failureand variation less than 10 was acceptable (TSTratio shouldbe gt90 indicating that the corticospinal tract is functionallyintact) In the present study we used 1-TSTratio as injury partof central motor-conduction impairment (2) NIHSS strokeoutcome was assessed by NIHSS score [15] (3) FMA FMAis a stroke-specific performance-based impairment index[16] Poststroke hemiplegia patients were graded by FMA inwhich the total score was 100 points and consisted of upperlimb score 0ndash66 points and lower limb score 0ndash34 points
The secondary efficacy variable was the clinical efficacyevaluation at the end of the treatment course by an appointeddoctor and safety assessments The criteria of neurologicaldeficit score were adopted based on theModified Edinburgh-Scandinavian Stroke Scale a nationwide accepted scoringsystem recommended at the Fourth National Cerebrovascu-lar Diseases Conference in China including consciousnessgaze facial paresis language walking ability and motorfunction of arms legs and hands The assessment wasconducted in accordance with the reduction in the scoresof basic nervous functional deficits and disability degree asfollows recovery scores the functional deficit scores weredecreased up to 91ndash100 and disability degree was at
Table 1 Baseline of demographic and clinical characteristics
EA electroacupuncture FMA Fugl-Meyer Assessment Scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication
grade 0 remarkable improvement the scores of functionaldeficit were decreased at 46ndash90 and disability degreewas at the grade 1ndash3 improvement the scores of functionaldeficit were decreased at 18ndash45 no change the scores offunctional deficit were decreased or increased at about 17deterioration the scores of functional deficit were increasedover 18 and death [13]
25 Safety Assessments Safety was assessed by the documen-tation of whole body reaction recorded whenever necessaryas well as by laboratory test of electrocardiogram (ECG) liverfunction and kidney function both at baseline time and at theend time of treatment
26 Statistics Analysis All data was processed by SPSS150Quantitative data was described by mean plusmn standard devi-ation (119909 plusmn 119904) An independent sample 1199051199051015840-test was usedfor comparing the means between two groups a paired119905-test was applied for comparing the change in outcomesbefore and after treatment Spearmanrsquos rho test was used forcorrelation analysis between the two quantitative variables(correlation coefficient 119903) Qualitative data was described bythe frequency (119891) and the percentage (119875) Fisherrsquos Exact Testis a test for independence in a 2 times 2 table and Pearson chi-square test for R times C table Statistical tests were completedblindly All tests were two-sided and were considered to bestatistically significant at 119875 lt 005
3 Results
31 Baseline Data Demographic characteristics and clinicalfeatures of participants in both groups are presented inTable 1 The differences in the demographics including
Evidence-Based Complementary and Alternative Medicine 5
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(a)
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(b)
Wrist-ADMErb-ADMCol W + E-Cortex-ADMTSTcontrol
TSTtest
(c)
Figure 2 (a) Triple stimulation technique (TST) tested in the right ulnar nerve of an adult healthy subject The TST amplitude ratio(TSTtestTSTcontrol) was 901 (b) TST tested in the right ulnar nerve of a patient with acute ischemic strokeTheTST amplitude ratio (TSTtestTSTcontrol) was 458 (c) TST tested in the right ulnar nerve of a patient with acute ischemic stroke after electroacupuncture treatment TheTST amplitude ratio (TSTtestTSTcontrol) was 839
age sex comorbid disease and infarct volume of the 2groups were insignificant (119875 gt 005) Moreover there is nostatistically significant difference in all the preintervention-selected outcome measures such as TST NIHSS and FAMbetween EA group and WCM group (119875 gt 005) (Table 1)
32 Clinical Effectiveness In the EA treatment group therewere 4 recovery cases 20 remarkable improvement cases 5improvement cases 1 no change case and 1 deterioration casethe total effective rate was 9350 In WCM control groupthere were 2 recovery cases 14 remarkable improvementcases 5 improvement cases 8 no change case and 1 worsecase the total effective rate was 7333The total effective ratewas statistically significantly superior in EA group to that inWCM group (1205942 = 572 119875 lt 001) (Table 2)
33 NIHSS Score FMA Score and TST119903119886119905119894119900
There was nostatistical difference between EA treatment group and WCMcontrol group inNIHSS score FMA score andTSTratio beforetreatment (119875 gt 005) After 14-day treatment NIHSS scoreFMA score and TSTratio between pretreatment and post-treatment were statistically more significant in EA treatmentgroup than those in WCM control group (119875 lt 001) Inaddition there were significant differences between the twogroups in all these three measure outcomes (119875 lt 005)(Table 3 Figure 2)
34 Correlation of TST119903119886119905119894119900
and NIHSS Score FMA ScoreThere was positive correlation between TSTratio and NIHSSscore before treatment (119903 = 0646 119875 lt 001) and after 14-day treatment (119903 = 0649 119875 lt 001) There was negative
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Comparison of the clinical efficacy between EA treatment group and WCM control group (119899 ())
Group 119899 Recovery Remarkable improvement Improvement No change Deterioration Death Total effective rate
WCM 30 2 (67) 14 (467) 5 (167) 8 (233) 1 (33) 0 (00) 7333EA electroacupuncture WCM western conventional medication Compared with WCM control group lowast119875 lt 005 Total effective rate = (recovery +Remarkable improvement + improvement) times 100 divide 119899
Table 3 Comparison of NIHSS score FMA score and TSTratiobetween EA treatment group and WCM control group (119909 plusmn 119904)
Items Group 119899
Assessment timePretreatment Posttreatment
NIHSS score EA 31 610 plusmn 261 252 plusmn 193lowast
WCM 30 630 plusmn 310 417 plusmn 340
FMA score EA 31 6848 plusmn 1981 8527 plusmn 1659lowast
WCM 30 6530 plusmn 2661 7417 plusmn 2416
TSTratio () EA 31 6354 plusmn 2820 3991 plusmn 3176lowast
WCM 30 6477 plusmn 2680 5645 plusmn 3149
EA electroacupuncture FMA Fugl-Meyer assessment scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication Compared with WCM controlgroup lowast119875 lt 005 Compared with pretreatment
119875 lt 001
Table 4 Correlation of TSTratio and NIHSS score FMA score (119903)
lowastlowast 1FMA Fugl-Meyer assessment scale NIHSS National Institutes of HealthStroke Scale TST triple-stimulation technique Correlation lowastlowast119875 lt 001
correlation between TSTratio and FMA score both beforetreatment (119903
119904= minus0570 119875 lt 001) and after treatment
(119903 = minus0572 119875 lt 001) There was also negative correlationbetween NIHSS and FMA scores both before treatment (119903 =minus0741 119875 lt 001) and after treatment (119903 = minus0769 119875 lt 001)(Table 4)
35 Complications No death of subjects or other seriousadverse events occurred during the treatment period Com-paring between two groups or between pretreatment andposttreatment adverse events ECG liver function andkidney function showed no significant difference (119875 gt 005)(Table 5) One patient in the EA group showed dizzinessand limb weakness for 2 times after the TST test Thesymptoms lasted for about half an hour and relieved bythemselves Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) slightly elevated in three patientsboth in EA group and in WCM group but the elevationswere not greater than 2 times the upper limit of normalSerum creatinine (SCr) level slightly elevated in two casesin WCM group (153 120583molL and 162 120583molL) and recoveredafter stopping use of the mannitol injection Two cases hadabnormal ECG with occasional atrial premature beats or the
first degree atrioventricular block in EA group and 1 patienthad abnormal ECGwith sinus arrhythmia inWCMgroup allthe above 3 patients with no requirement for clinical care
4 Discussion
To our knowledge to date this is the first randomized con-trolled study using the triple stimulation technique to objec-tively evaluate EA for motor function recovery in patientswith AIS The main findings in the present study were asfollows (1) EA had more beneficial effect on motor functionrecovery of AIS patients when compared with WCM controland was generally safe (2) the effect of EA formotor functioninjury and recovery of corticospinal tract impairments in AISpatients can be quantitatively evaluated by TST
Neurophysiological assessments have been used to mea-sure the extent of stroke damage to the motor system andto predict subsequent recovery of function An abnormalTST represents uppermotor neuron loss central axon lesionsor conduction blocks or inexcitability in response to TMS[17] In healthy Chinese subjects the TST amplitude ratio(TSTteatTSTcontrol) was 850 plusmn 67 and there was nodifference among genders age groups and arm length andsides [18] In the present study abnormal TSTratio wasobserved in all included stroke patients suggesting that TSTis effective to assess corticospinal tract impairment in AISTherefore TST can be a useful tool for quantitative diagnosisof corticospinal tract motor function in lesional defects ofconduction after acute ischemic stroke
Systematic reviews of the literature indicated that theinitial grade of paresis as measured on admission in thehospital is the most important predictor of early prognosisof motor recovery and special attention should be paid tothe clinical prognostic value of MEPs [19 20] Severity ofstroke measured by NIHSS score on admission is highlypredictive of excellent or devastating outcomes in ischemicstroke patients [21] FMA scale is a disease-specific objectiveimpairment index designed specifically as an evaluative mea-sure for assessment of recovery in the poststroke hemiplegicpatient [16] TST is a method improving the study of MEPs[8] In the present study TST and NIHSS score reducedand the FMA score improved after treatment in both groupsTST was positively correlated with NIHSS scores and wasnegatively correlated with FMA scores after both EA andWCM treatment These results showed that reduction ofNIHSS scores and improvement in FMA scores indicated theimprovement of motor function after treatment and TST canbe an indicator of prognosis for motor function recovery
Along the clinical course of ischemic stroke the mostcritical period of recovery is at the acute and subacute stages
Evidence-Based Complementary and Alternative Medicine 7
Table 5 Comparison of adverse events electrocardiogram liver function and kidney function between two groups or between pretreatmentand posttreatment
Group 119899
Pretreatment PosttreatmentALT SCr Adverse eventslowast ECGlowast ALT SCr
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
Evidence-Based Complementary and Alternative Medicine 5
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(a)
Wrist-ADM
Erb-ADM
Col W + E-
Cortex-ADM
TSTcontrol
TSTtest
(b)
Wrist-ADMErb-ADMCol W + E-Cortex-ADMTSTcontrol
TSTtest
(c)
Figure 2 (a) Triple stimulation technique (TST) tested in the right ulnar nerve of an adult healthy subject The TST amplitude ratio(TSTtestTSTcontrol) was 901 (b) TST tested in the right ulnar nerve of a patient with acute ischemic strokeTheTST amplitude ratio (TSTtestTSTcontrol) was 458 (c) TST tested in the right ulnar nerve of a patient with acute ischemic stroke after electroacupuncture treatment TheTST amplitude ratio (TSTtestTSTcontrol) was 839
age sex comorbid disease and infarct volume of the 2groups were insignificant (119875 gt 005) Moreover there is nostatistically significant difference in all the preintervention-selected outcome measures such as TST NIHSS and FAMbetween EA group and WCM group (119875 gt 005) (Table 1)
32 Clinical Effectiveness In the EA treatment group therewere 4 recovery cases 20 remarkable improvement cases 5improvement cases 1 no change case and 1 deterioration casethe total effective rate was 9350 In WCM control groupthere were 2 recovery cases 14 remarkable improvementcases 5 improvement cases 8 no change case and 1 worsecase the total effective rate was 7333The total effective ratewas statistically significantly superior in EA group to that inWCM group (1205942 = 572 119875 lt 001) (Table 2)
33 NIHSS Score FMA Score and TST119903119886119905119894119900
There was nostatistical difference between EA treatment group and WCMcontrol group inNIHSS score FMA score andTSTratio beforetreatment (119875 gt 005) After 14-day treatment NIHSS scoreFMA score and TSTratio between pretreatment and post-treatment were statistically more significant in EA treatmentgroup than those in WCM control group (119875 lt 001) Inaddition there were significant differences between the twogroups in all these three measure outcomes (119875 lt 005)(Table 3 Figure 2)
34 Correlation of TST119903119886119905119894119900
and NIHSS Score FMA ScoreThere was positive correlation between TSTratio and NIHSSscore before treatment (119903 = 0646 119875 lt 001) and after 14-day treatment (119903 = 0649 119875 lt 001) There was negative
6 Evidence-Based Complementary and Alternative Medicine
Table 2 Comparison of the clinical efficacy between EA treatment group and WCM control group (119899 ())
Group 119899 Recovery Remarkable improvement Improvement No change Deterioration Death Total effective rate
WCM 30 2 (67) 14 (467) 5 (167) 8 (233) 1 (33) 0 (00) 7333EA electroacupuncture WCM western conventional medication Compared with WCM control group lowast119875 lt 005 Total effective rate = (recovery +Remarkable improvement + improvement) times 100 divide 119899
Table 3 Comparison of NIHSS score FMA score and TSTratiobetween EA treatment group and WCM control group (119909 plusmn 119904)
Items Group 119899
Assessment timePretreatment Posttreatment
NIHSS score EA 31 610 plusmn 261 252 plusmn 193lowast
WCM 30 630 plusmn 310 417 plusmn 340
FMA score EA 31 6848 plusmn 1981 8527 plusmn 1659lowast
WCM 30 6530 plusmn 2661 7417 plusmn 2416
TSTratio () EA 31 6354 plusmn 2820 3991 plusmn 3176lowast
WCM 30 6477 plusmn 2680 5645 plusmn 3149
EA electroacupuncture FMA Fugl-Meyer assessment scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication Compared with WCM controlgroup lowast119875 lt 005 Compared with pretreatment
119875 lt 001
Table 4 Correlation of TSTratio and NIHSS score FMA score (119903)
lowastlowast 1FMA Fugl-Meyer assessment scale NIHSS National Institutes of HealthStroke Scale TST triple-stimulation technique Correlation lowastlowast119875 lt 001
correlation between TSTratio and FMA score both beforetreatment (119903
119904= minus0570 119875 lt 001) and after treatment
(119903 = minus0572 119875 lt 001) There was also negative correlationbetween NIHSS and FMA scores both before treatment (119903 =minus0741 119875 lt 001) and after treatment (119903 = minus0769 119875 lt 001)(Table 4)
35 Complications No death of subjects or other seriousadverse events occurred during the treatment period Com-paring between two groups or between pretreatment andposttreatment adverse events ECG liver function andkidney function showed no significant difference (119875 gt 005)(Table 5) One patient in the EA group showed dizzinessand limb weakness for 2 times after the TST test Thesymptoms lasted for about half an hour and relieved bythemselves Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) slightly elevated in three patientsboth in EA group and in WCM group but the elevationswere not greater than 2 times the upper limit of normalSerum creatinine (SCr) level slightly elevated in two casesin WCM group (153 120583molL and 162 120583molL) and recoveredafter stopping use of the mannitol injection Two cases hadabnormal ECG with occasional atrial premature beats or the
first degree atrioventricular block in EA group and 1 patienthad abnormal ECGwith sinus arrhythmia inWCMgroup allthe above 3 patients with no requirement for clinical care
4 Discussion
To our knowledge to date this is the first randomized con-trolled study using the triple stimulation technique to objec-tively evaluate EA for motor function recovery in patientswith AIS The main findings in the present study were asfollows (1) EA had more beneficial effect on motor functionrecovery of AIS patients when compared with WCM controland was generally safe (2) the effect of EA formotor functioninjury and recovery of corticospinal tract impairments in AISpatients can be quantitatively evaluated by TST
Neurophysiological assessments have been used to mea-sure the extent of stroke damage to the motor system andto predict subsequent recovery of function An abnormalTST represents uppermotor neuron loss central axon lesionsor conduction blocks or inexcitability in response to TMS[17] In healthy Chinese subjects the TST amplitude ratio(TSTteatTSTcontrol) was 850 plusmn 67 and there was nodifference among genders age groups and arm length andsides [18] In the present study abnormal TSTratio wasobserved in all included stroke patients suggesting that TSTis effective to assess corticospinal tract impairment in AISTherefore TST can be a useful tool for quantitative diagnosisof corticospinal tract motor function in lesional defects ofconduction after acute ischemic stroke
Systematic reviews of the literature indicated that theinitial grade of paresis as measured on admission in thehospital is the most important predictor of early prognosisof motor recovery and special attention should be paid tothe clinical prognostic value of MEPs [19 20] Severity ofstroke measured by NIHSS score on admission is highlypredictive of excellent or devastating outcomes in ischemicstroke patients [21] FMA scale is a disease-specific objectiveimpairment index designed specifically as an evaluative mea-sure for assessment of recovery in the poststroke hemiplegicpatient [16] TST is a method improving the study of MEPs[8] In the present study TST and NIHSS score reducedand the FMA score improved after treatment in both groupsTST was positively correlated with NIHSS scores and wasnegatively correlated with FMA scores after both EA andWCM treatment These results showed that reduction ofNIHSS scores and improvement in FMA scores indicated theimprovement of motor function after treatment and TST canbe an indicator of prognosis for motor function recovery
Along the clinical course of ischemic stroke the mostcritical period of recovery is at the acute and subacute stages
Evidence-Based Complementary and Alternative Medicine 7
Table 5 Comparison of adverse events electrocardiogram liver function and kidney function between two groups or between pretreatmentand posttreatment
Group 119899
Pretreatment PosttreatmentALT SCr Adverse eventslowast ECGlowast ALT SCr
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
WCM 30 2 (67) 14 (467) 5 (167) 8 (233) 1 (33) 0 (00) 7333EA electroacupuncture WCM western conventional medication Compared with WCM control group lowast119875 lt 005 Total effective rate = (recovery +Remarkable improvement + improvement) times 100 divide 119899
Table 3 Comparison of NIHSS score FMA score and TSTratiobetween EA treatment group and WCM control group (119909 plusmn 119904)
Items Group 119899
Assessment timePretreatment Posttreatment
NIHSS score EA 31 610 plusmn 261 252 plusmn 193lowast
WCM 30 630 plusmn 310 417 plusmn 340
FMA score EA 31 6848 plusmn 1981 8527 plusmn 1659lowast
WCM 30 6530 plusmn 2661 7417 plusmn 2416
TSTratio () EA 31 6354 plusmn 2820 3991 plusmn 3176lowast
WCM 30 6477 plusmn 2680 5645 plusmn 3149
EA electroacupuncture FMA Fugl-Meyer assessment scale NIHSSNational Institutes of Health Stroke Scale TST triple-stimulation techniqueWCM western conventional medication Compared with WCM controlgroup lowast119875 lt 005 Compared with pretreatment
119875 lt 001
Table 4 Correlation of TSTratio and NIHSS score FMA score (119903)
lowastlowast 1FMA Fugl-Meyer assessment scale NIHSS National Institutes of HealthStroke Scale TST triple-stimulation technique Correlation lowastlowast119875 lt 001
correlation between TSTratio and FMA score both beforetreatment (119903
119904= minus0570 119875 lt 001) and after treatment
(119903 = minus0572 119875 lt 001) There was also negative correlationbetween NIHSS and FMA scores both before treatment (119903 =minus0741 119875 lt 001) and after treatment (119903 = minus0769 119875 lt 001)(Table 4)
35 Complications No death of subjects or other seriousadverse events occurred during the treatment period Com-paring between two groups or between pretreatment andposttreatment adverse events ECG liver function andkidney function showed no significant difference (119875 gt 005)(Table 5) One patient in the EA group showed dizzinessand limb weakness for 2 times after the TST test Thesymptoms lasted for about half an hour and relieved bythemselves Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) slightly elevated in three patientsboth in EA group and in WCM group but the elevationswere not greater than 2 times the upper limit of normalSerum creatinine (SCr) level slightly elevated in two casesin WCM group (153 120583molL and 162 120583molL) and recoveredafter stopping use of the mannitol injection Two cases hadabnormal ECG with occasional atrial premature beats or the
first degree atrioventricular block in EA group and 1 patienthad abnormal ECGwith sinus arrhythmia inWCMgroup allthe above 3 patients with no requirement for clinical care
4 Discussion
To our knowledge to date this is the first randomized con-trolled study using the triple stimulation technique to objec-tively evaluate EA for motor function recovery in patientswith AIS The main findings in the present study were asfollows (1) EA had more beneficial effect on motor functionrecovery of AIS patients when compared with WCM controland was generally safe (2) the effect of EA formotor functioninjury and recovery of corticospinal tract impairments in AISpatients can be quantitatively evaluated by TST
Neurophysiological assessments have been used to mea-sure the extent of stroke damage to the motor system andto predict subsequent recovery of function An abnormalTST represents uppermotor neuron loss central axon lesionsor conduction blocks or inexcitability in response to TMS[17] In healthy Chinese subjects the TST amplitude ratio(TSTteatTSTcontrol) was 850 plusmn 67 and there was nodifference among genders age groups and arm length andsides [18] In the present study abnormal TSTratio wasobserved in all included stroke patients suggesting that TSTis effective to assess corticospinal tract impairment in AISTherefore TST can be a useful tool for quantitative diagnosisof corticospinal tract motor function in lesional defects ofconduction after acute ischemic stroke
Systematic reviews of the literature indicated that theinitial grade of paresis as measured on admission in thehospital is the most important predictor of early prognosisof motor recovery and special attention should be paid tothe clinical prognostic value of MEPs [19 20] Severity ofstroke measured by NIHSS score on admission is highlypredictive of excellent or devastating outcomes in ischemicstroke patients [21] FMA scale is a disease-specific objectiveimpairment index designed specifically as an evaluative mea-sure for assessment of recovery in the poststroke hemiplegicpatient [16] TST is a method improving the study of MEPs[8] In the present study TST and NIHSS score reducedand the FMA score improved after treatment in both groupsTST was positively correlated with NIHSS scores and wasnegatively correlated with FMA scores after both EA andWCM treatment These results showed that reduction ofNIHSS scores and improvement in FMA scores indicated theimprovement of motor function after treatment and TST canbe an indicator of prognosis for motor function recovery
Along the clinical course of ischemic stroke the mostcritical period of recovery is at the acute and subacute stages
Evidence-Based Complementary and Alternative Medicine 7
Table 5 Comparison of adverse events electrocardiogram liver function and kidney function between two groups or between pretreatmentand posttreatment
Group 119899
Pretreatment PosttreatmentALT SCr Adverse eventslowast ECGlowast ALT SCr
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
ALT alanine aminotransferase EA electroacupuncture ECG electrocardiogram SCr serum creatinine WCM western conventional medication lowastOnepatient at 2 times in the EA group showed dizziness and limb weakness after the TST test which lasted about half an hour and relieved itself lowastlowastTwo caseshad abnormal ECG with occasional atrial premature beats or the first degree atrioventricular block in EA group and 1 patient had abnormal ECG with sinusarrhythmia in WCM group all with no requirement for clinical care
[12] Although the evidence was limited due to the lowmethodological quality at least 3 systematic reviews revealedthe potential benefits of acupuncture to patients with acuteischemic stroke [4 22 23] In the present pilot study EAis more effective in patients with first-ever AIS for motorfunction recovery when compared with a WCM controlusingNIHSS score for the neurologic severity assessment andFMA score for the motor-status evaluation This result wascompatible with the several previous studies [24ndash26] Partic-ularly we used TST to objectively quantify assessment of thecentral conduction failure after EA treatment Comparing theWCM control EA treatment during the acute phase of strokecan significantly improve corticospinal conduction failuresuggesting that EA had additional beneficial effects on motorfunctional outcome and TST can be an accurate and objectivequantification in assessment of the efficacy of EA treatments
Acupuncture appears to be a safe treatment when usedin the acute phase of stroke with rare serious adverse events[22] An NIH consensus report also stated that one of theadvantages of acupuncture was that the incidence of adverseeffects is substantially lower than that of many other acceptedmedical interventions [27] Although EA is a somewhatinvasive procedure with complications such as needle painfainting minor bleeding or infection few side effects werenoted in the present studyThus the present study supportedthe safety of EA for AIS patients
A few comments about the design methods and studylimitations deserve mention First one potential limitation ofthis pilot study is the small sample size evaluating the efficacyand safety of EA for AIS Trials with inadequate sample sizescould run the risk of overestimating intervention benefits[28] Another limitation is that the follow-up data after treat-ment were not available Lack of followups led to difficultyin accounting for the long-term efficacy of EA treatment forstroke Finally a true double-blinded acupuncture trial wouldbe very difficult to carry out because the acupuncturist alwaysknows which method is being applied and the patient caneasily distinguish between active and nonactive stimulationAlthough some placebosham acupuncture methods havebeen invented in the past decade [5] the use of thesemethodsin control groups remains controversial Therefore it cannotbe guaranteed that the placebo effect of the EA treatment hadbeen removed to some extent from the results even thoughWCM group was taken as control in the present study
In conclusion EA had more beneficial effect on motorfunction recovery of AIS patients after 14-day treatmentwhen
compared with WCM control and was generally safe TSTcan quantitatively evaluate EA for motor function recoveryin patients with AIS by objective analysis of the injury andrecovery of corticospinal tract impairment Further rigor-ously designed large sample size randomized double blindclinical trials are required
Conflict of Interests
All authors have no conflict of interests to disclose
Acknowledgments
Theauthors thankDr YanWang fromWenzhouMedical Col-lege for the excellent language improvement of the paperThisstudy was supported by Science and Technology PlanningProject ofGuangdongProvince China (no 2012B031800321)
References
[1] S C Johnston S Mendis and C D Mathers ldquoGlobal variationin stroke burden and mortality estimates from monitoringsurveillance and modellingrdquo The Lancet Neurology vol 8 no4 pp 345ndash354 2009
[2] H P Adams Jr G Del Zoppo M J Alberts et al ldquoAmericanHeart Association American Stroke Association Stroke Coun-cil Clinical Cardiology Council Cardiovascular Radiologyand Intervention Council Atherosclerotic Peripheral VascularDisease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Guidelines for the early managementof adults with ischemic strokerdquo Stroke vol 38 no 5 pp 1655ndash1711 2007
[3] R C Seet and A A Rabinstein ldquoSymptomatic intracra-nial hemorrhage following intravenous thrombolysis for acuteischemic stroke a critical review of case definitionsrdquo Cere-brovascular Diseases vol 34 no 2 pp 106ndash114 2012
[4] YWang J Shen XMWang et al ldquoScalp acupuncture for acuteischemic stroke a meta-analysis of randomized controlled tri-alsrdquo Evidence-Based Complementary and Alternative Medicinevol 2012 Article ID 480950 9 pages 2012
[5] J C Kong M S Lee B-C Shin Y-S Song and E ErnstldquoAcupuncture for functional recovery after stroke a systematicreview of sham-controlled randomized clinical trialsrdquo CMAJvol 182 no 16 pp 1723ndash1729 2010
[6] C Stinear ldquoPrediction of recovery of motor function afterstrokerdquoThe Lancet Neurology vol 9 no 12 pp 1228ndash1232 2010
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
8 Evidence-Based Complementary and Alternative Medicine
[7] P Talelli R J Greenwood and J C Rothwell ldquoArm functionafter stroke neurophysiological correlates and recovery mech-anisms assessed by transcranial magnetic stimulationrdquo ClinicalNeurophysiology vol 117 no 8 pp 1641ndash1659 2006
[8] M R Magistris K M Rosler A Truffert and J P MyersldquoTranscranial stimulation excites virtually all motor neuronssupplying the target muscle a demonstration and a methodimproving the study of motor evoked potentialsrdquo Brain vol 121part 3 pp 437ndash450 1998
[9] L Komissarow J D Rollnik D Bogdanova et al ldquoTriple stimu-lation technique (TST) in amyotrophic lateral sclerosisrdquoClinicalNeurophysiology vol 115 no 2 pp 356ndash360 2004
[10] M R Magistris K M Rosler A Truffert T Landis and C WHess ldquoA clinical study of motor evoked potentials using a triplestimulation techniquerdquo Brain vol 122 no 2 pp 265ndash279 1999
[11] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[12] H S Jorgensen H Nakayama H O Raaschou J Vive-Lar-sen M Stoier and T S Olsen ldquoOutcome and time courseof recovery in stroke Part II time course of recovery TheCopenhagen Stroke Studyrdquo Archives of Physical Medicine andRehabilitation vol 76 no 5 pp 406ndash412 1995
[13] Q T Chen ldquoClassification diagnostic criteria and evaluation ofneurological impairment for stroke patientsrdquoChinese Journal ofNeurology vol 29 pp 376ndash338 1996
[14] Chinese Medical Associationrsquos Neuropathy Credits ldquoChineseguideline for diagnosis and management of acute ischemicstroke 2010rdquoChinese Journal of Neurology vol 43 no 2 pp 146ndash153 2010
[15] T Brott H P Adams Jr C P Olinger et al ldquoMeasurements ofacute cerebral infarction a clinical examination scalerdquo Strokevol 20 no 7 pp 864ndash870 1989
[16] D J Gladstone C J Danells and S E Black ldquoThe Fugl-meyerassessment of motor recovery after stroke a critical review ofits measurement propertiesrdquo Neurorehabilitation and NeuralRepair vol 16 no 3 pp 232ndash240 2002
[17] K M Rosler A Truffert C W Hess and M R MagistrisldquoQuantification of upper motor neuron loss in amyotrophiclateral sclerosisrdquo Clinical Neurophysiology vol 111 no 12 pp2208ndash2218 2000
[18] J Y Zheng Y S Xu and D S Fan ldquoTriple stimulationtechnique normative value of Chinese adultsrdquo Chinese Journalof Neurology vol 44 no 11 pp 739ndash741 2011
[19] H T Hendricks J Van Limbeek A C Geurts and M JZwarts ldquoMotor recovery after stroke a systematic review of theliteraturerdquo Archives of Physical Medicine and Rehabilitation vol83 no 11 pp 1629ndash1637 2002
[20] J P Bembenek K Kurczych M Karli Nski and A Czlonkow-ska ldquoThe prognostic value of motor-evoked potentials in motorrecovery and functional outcome after stroke a systematicreview of the literaturerdquo Functional Neurology vol 27 no 2 pp79ndash84 2012
[21] H P Adams Jr P H Davis E C Leira et al ldquoBaseline NIHStroke Scale score strongly predicts outcome after stroke areport of the Trial of Org 10172 in Acute Stroke Treatment(TOAST)rdquo Neurology vol 53 no 1 pp 126ndash131 1999
[22] S H Zhang M Liu K Asplund and L Li ldquoAcupuncture foracute strokerdquo Cochrane Database of Systematic Reviews no 2Article ID CD003317 2005
[23] T Zhang L Zhang H M Zhang and Q Li ldquoSystematicreview of acupuncture therapy for acute ischemic strokerdquoChinaJournal of Traditional Chinese Medicine and Pharmacy vol 24no 1 pp 101ndash104 2009
[24] A M K Wong T-Y Su F-T Tang P-T Cheng and M-YLiaw ldquoClinical trial of electrical acupuncture on hemiplegicstroke patientsrdquo American Journal of Physical Medicine andRehabilitation vol 78 no 2 pp 117ndash122 1999
[25] R-L Hsieh L-YWang andW-C Lee ldquoAdditional therapeuticeffects of electroacupuncture in conjunction with conventionalrehabilitation for patients with first-ever ischaemic strokerdquoJournal of Rehabilitation Medicine vol 39 no 3 pp 205ndash2112007
[26] S Sallstrom A Kjendahl P E Oslashsten J H Stanghelle andC F Borchgrevink ldquoAcupuncture in the treatment of strokepatients in the subacute stage a randomized controlled studyrdquoComplementaryTherapies in Medicine vol 4 no 3 pp 193ndash1971996
[28] L L Kjaergard J Villumsen and C Gluud ldquoReported method-ologic quality and discrepancies between large and small ran-domized trials in meta-analysesrdquo Annals of Internal Medicinevol 135 no 11 pp 982ndash989 2001
