Acaseseriesinindividualswithmultiple sclerosisusingdirectcurrentelectrical stimulationtoinhibitspasticityandimprove functionaloutcomes
CourtneyLEllerbusch ,KristinaMChappleandJulieBSeibert
Abstract
BackgroundandPurpose: Multiplesclerosis(MS)hasahighincidenceofdebilitatingspasticity.Central NervousSystem(CNS)intrafusalsettingshaveanimpactonspasticitylevel.Mechanoreceptorsofthe PeripheralNervousSystem(PNS)communicatemonosynapticallywiththecentralnervoussystem (CNS).ThiscaseseriesassessesfeasibilityofmultimodaltreatmentofindividualswithMSusinga directcurrentelectricalstimulation(DC)toinfluencemechanoreceptors.
CaseDescriptionandIntervention: SevenMSdiagnosedparticipantswithExpandedDisabilityStatus Scale(EDSS) = 6.0–8.0completed18visitsover6weeksofusingDCcombinedwithneuromuscular reeducation.Designincludedpre-,post-outcomemeasuresofEDSS,12-itemMSWalkingScale (MSWS-12),RangeofMotion(ROM),ManualMuscleTesting(MMT),ModifiedAshworthTest (MAT),Timed25-Footwalk(T25WT),TimedUpandGo(TUG)andtheMultipleSclerosisImpact Scale-29(MSIS-29).
Outcome: 125outofapossible126visitswerecompleted,demonstratingahighleveloftolerance. Individualresultsincludedtrendstowardsimprovementinspasticityandagonists.
Discussion: ThiscaseseriesdesignofsevenheterogenoussubjectswithMSisalowsamplesizeforstatisticalanalysisandshouldbeconsideredapilot.Thestudydemonstratesahighleveloffeasibilityand possiblecorrelationstoconsider.Furtherresearchiswarranted.
Keywords: multiplesclerosis,spasticity
Datereceived:30March2023;accepted:20June2023
Introduction
Approximately66%1–84%2,3 ofindividualswith multiplesclerosis(MS)experiencespasticity. 1 The pathophysiologyofspasticitybestunderstood, demonstratesanimbalancebetweeninhibitory dorsalreticulospinaltract(RST) fibersandexcitatory bulbopontinetegmentum.RSTneuronsreceivedirect somatic,vestibular,tectal,cerebellarandmotorexcitatoryinputandarescatteredintheventraland lateralspinalcordcolumnsintermingledwithpropriospinal fi bers. 2 TheperipheralGolgitendon organofmuscletendonandmusclespindleintrafusal fi bersubiquitousthroughoutthemusculoskeletal systemhavemonosynapticconnectiontothiscentral
nervoussystem(CNS)propriospinal fi bersandin fl uencethedegreeofspasticityandoveractivestretch re fl exes. 2,4
Whenmechanoreceptorsfunctionnormallywithina fullyintactneurologicalsystem,theyareprotective againststretchinmuscle,tendonand/orboneinjury causingreflexivecounterforcesuchasdroppinga weightthatistooheavy.2 InanindividualwithMS theCNScausesthethresholdforstretchreflexand muscletightnesstobesetlowerthannormal.2 This inhibitsnormalmovementandcausesabnormalities inambulation,posture,stiffnessandattimesjoint contractures.
MultipleSclerosisJournal Experimental,Translational andClinical
July-September2023,1–12
DOI:10.1177/ 20552173231186512
©TheAuthor(s),2023. Articlereuseguidelines: sagepub.com/journalspermissions
Correspondenceto: CourtneyLEllerbusch,PT, DPT,CenturaHealthat Home. courtneyellerbusch@ centura.org
CourtneyLEllerbusch, AmbulatoryDepartment, CenturaHealthat Home,Denver,Colorado, USA
KristinaMChapple, DepartmentofSurgery, UniversityofArizonaSchool ofMedicine,Phoenix, Arizona,USA
JulieBSeibert, MultipleSclerosis,
permissionprovidedtheoriginalworkisattributedasspecifiedontheSAGEandOpenAccesspage(https://us.sagepub.com/en-us/nam/open-access-at-sage).
OverseeingNeurologist, Littleton,Colorado,USA
Ifdirectcurrentelectricalstimulation(DC)isableto altertheproprioceptionoftheperipheralnervous system(PNS)withinputtomechanoreceptors,it maybepossibleto findmeasurablechangeinCNS drivenspasticityduringtreatmentandaftertreatment.5 IfindividualswithMScanexperienceanormalizedstretchresponse,itmaybepossibleto createCNSlevelchangeswithinthebulbopontine tegmentum.Thispilotstudycaseseriesisdesigned withmeasuresofspasticity,rangeofmotion,muscle strength,gaitspeedandbalancetoassessfeasibility. ThepurposeofthisPilotcaseseriesistoassessif treatmentofindividualswithprogressiveMSatthe PNSlevelthroughtargetingmechanoreceptorsusing theNeuBie(NeurologicalFitnessEquipmentand EducationLLC,AustinTXmanufacturedbyJohari ElectroTechCompanyinJodhpurIndia),aDCelectricalstimulationdevice,hasfeasibilitytoinhibit spasticityandimprovefunctionalmobilityinclinicallysignificantmeasures. 6
Patientinformation
CourtneyEllerbusch,PT,DPTdesignedandimplementedarepeatablestudydesignofhomehealth visitsforprogressiveMSinpartnershipwithDrJulie Seibert,MD.DrEllerbuschcompletedallassessments andinterventions.Acaseseriesof7participantswith progressiveMSwithmobilityimpairment(Expanded DisabilityStatusScale = 6.0–8.0)completed18visits over6weeksofhomehealth-deliveredphysical therapyfromJuly22,2021throughJune3,2022. ThedesignutilizedDCcombinedwithneuromuscular reeducationinmanualactivations,7 flexibilitytraining, neuromuscularreeducationandfunctionaltraining.Dr Seibertcompletedeachsubject’sofficevisitpriorto participation,consentsandEDSS;thenrepeated EDSSuponinterventiontimelinecompletion.(See Table1fordemographics).
Assessmentandinterventiontimeline
Thestudyassessmentandinterventiontimeline (Table2)detailstheassessmentsandinterventionparametersprovidedforallsevensubjectsoveraperiodof 6weeksofhomehealthphysicaltherapy.Theonly exceptionissubject7whodevelopedurinarytract infection(UTI)symptomsonthe18thvisitandwas notabletotolerate finalambulatoryassessments.
InitialPTvisitincludedmedicalhistory,goals, assessmentoffunctionalimpairmentsandoutcomemeasures.Subjects1–7wereaheterogenousgroupofnonambulatoryandambulatory.Afour-partintervention wasusedwitheachsubject.Part1***targetedneuropathywithaDCfootbathprotocol,whenneuropathy
wasreported.Part2**targetedareasofmeasuredspasticitythrough flexibilitycombinedwithDCtoarange thatelicitedastretchwithoutcreatingaspasmorspasticityresponse.Part3**combinedDCwithagonist strengtheningthroughtoleratedrangeswithoutidentified compensatorymovements.Subjectsweregivenworkto restratioof1:2upto1:4dependingonfatigueresponse withinvisitorreportedatthenextappointment.Part4 appliedDCwhiletraining subjectstothehighest degreeoffunctionaltrainingsafelytoleratedwhilereducingoreliminatingcompensatorypatterns.
Groupclinical findings
APhDlevelstatisticianprovidedquantitativeanalysis MATandMMT(seeTable3).Individualcases showedavarietyofquantitativechanges,withtrends towardsimprovementinplantar flexor(PF)spasticity perMAT(71.4%ofsubjectsimprovedinPFMAT). SubjectstrendedtowardimprovementinMMTofbilateralpsoas,bilateralquadratuslumborum,bilateral vastuslateralisandmedialis,bilateralgluteusmedius, bilateralhipadductorgroup,bilateraltibialisanterior (TA)andbilateralbicepsfemoris.Therearenotrends acrosssubjectsdemonstratingworseningmeasurements inspasticity,MMTorROM.Therearenocleartrends identifiedfromsubjectivemeasuresMSIS-29or MSWS-12acrosssubjects.Outofapossible126total visitsforsevensubjectsatotalof125visitswerecompleted,demonstratingahighleveloftolerance.One missedvisitoccurredduetopre-existingcomorbidities insubject7withUTIsymptoms.Allsubjectswereeducatedtothepotentialforneurologicalfatiguewith carefulassessmentofresponse.8 Subjects1and5 requiredinterventionmodificationindosingandintensityduetofatigueresponse,butabletotoleratemodifiedintensity.Subject7hadhypertensionattimesand UTIsymptomsrequiringmodifications.Noothersubjectsrequiredinterventionmodificationindosingor exerciseintensity.Therewerenoknownadverse responsestotheinterventionsprovided.
Individualclinical findings
Subject1(non-ambulatorypowerchairdependent) demonstratedimprovementsinrightsidehip flexor lengthimprovingfrominitialassessment(IA)of four fingersinpronefromASIStomatsurfaceand 0degreeshipinternalrotationassociatedwithright 0/5psoasMMTtoa finalassessment(FA)ofthree fingersinpronefromASIStomatsurface,5 degreeshipinternalrotationand1+/5rightpsoas MMT.Subject1alsodemonstratedimprovement from3/4hipextensionMATatinitialassessmentto finalassessmentof0/4hipextensionMATwith abilitytocontractpsoasmusclesforthe firsttime
Table1. Demographics.
Subjectmain impairmentsandgoalsMedicationListComorbidities
Supportat home
Assistivedevicefor mobilityandrelated impairments
Type ofMS
Age(age ofMS diagnosis)Sex
SN
depression,backpain, continuousbilateral lowerlegclonusin weightbearing; musclespasms
Ambien;Baclofen10mg (40mgdaily); clonazepam;Gilenya; Inhaler;Lipitor; oxycodone;paxil; valium;vitaminD3; wellbutrin
Impairments: hyposensationT10 levelanddistally, clonus,spasticityand spasms,backpainand weaknesslimiting transfers.Goals: Reducetone manisfestations, reducebackpainand improvestrengthfor transfers
Liveswith spousewho worksfull time availableto supportin morningand evening.
150(39)MSPMSCustomlightweight manualwheelchair. Unabletoambulate duetoweakness, andclonus.
acetaminophen; amlodipine;amoxicillin potassium;baclofen 10mg(40mgdaily); cholecalciferol; fl uticasone;furosemide; gabapentin;ibuprofen; lorazepam;rosuvastatin; stoolsoftner;sertraline; spironolactone;tylenol PM bilateralknee fl exion contracture; hypertension; hyperlipidemia;neck pain;backpain;knee pain;formersmoker; ataxia
Impairments:bilateral knee fl exion contractures, spasticity,weakness limitingtransfersand bedmobilityGoals: reducebilateralknee fl exioncontractures, improvestrengthfor bedmobilityand transfers
Liveswith daughter whois primary caregiver andworking fulltime fromhome
269(40)FPPMScustompowerchair. Unabletoambulate duetobilateralknee contracturesand weakness.
formersmoker, depression (untreated),anxiety (untreated)
Impairments:spasticity, severebilateral neuropathy; depression,bilateral legweaknessworseon leftsidewithfoot drop.Goals:Improve balance,reduced spasticity,reduce neuropathy,improve walkingqualityand distance baclofen10mg(30mg daily);cyclobenzaprin; dalfampridine; ergocalciferol;Ocrevus
Liveswith parentswho supportas needed.
330(23)MPPMSSinglePointCanewith ambulationdistance andqualitylimited byataxia, neuropathyand spasticity.
Subjectmain impairmentsandgoalsMedicationListComorbidities
Supportat home
Assistivedevicefor mobilityandrelated impairments
Type ofMS
Age(age ofMS diagnosis)Sex
Table1. Continued. SN
Myrbetriqseizures,tornLACL, shorttermmemory loss
Impairments:cognitive de fi cit,leftleg weaknessand spasticity,fatigue Goals:Improvemental clarity,improve energy,improveleft legstrengthand walkingdistanceas wellasquality
liveswith daughters takingturns between theirhomes; parttime paid caregiver support
464(27)FPPMSSinglePointCanewith ambulationdistance limitedbyLside footdropand spasticity.
overactivebladder; musclespasms
atorvastatin;baclofen 20mg(80mgtotal); B-complex;benadryl; magnesium; fi shoil; ibuprofen;juiceplus supplement;niacin; Ocrevus;omeprazole; ropinirole;saw palmento;tadala fi l; tamsulosin;tizanidine; valium;vitaminD
Impairments:bilateralleg weaknessand hypertonicitywith greaterweaknessleft legandpainfulspasms rightleg,limited walkingqualityand distanceGoals:restore anymobilityor strengthtolegs,reduce footdrop,reduce spasms
Liveswithwife andsome childrenat home; spouseis primary caregiver andworking fulltime
559(44)MSPMSThreeWheeledwalker indoormobilityand powerchairfor community distances. Limitationin bilaterallower extremityweakness, spasticityandspasm impacting ambulation.
2009RTibialSpiral Fracture;ataxic movements;severe hyperre fl exia bilaterally;sustained bilateralclonus (continued)
baclofen10mg(30mg daily);dalfampridine; vitaminD3;medical marijuana;Ocrevus
Impairments:Rleg weakness,severe hyperre fl exia, sustainedbilateral clonus,lowerlegand footneuropathy, spasticgaitwithRfoot drop.Goals:Improve walkingtoleranceand quality,improveR anklemovement, reduceneuropathy
Liveswithout caregiver support; familyin areasupport asneeded butdonot knowhehas MS
639(35)MPPMSBilateralcaneswith intermittentRAFO usewithweakness andspasticity limitingambulation.
Subjectmain impairmentsandgoalsMedicationListComorbidities
Supportat home
Assistivedevicefor mobilityandrelated impairments
Age(age ofMS diagnosis)Sex Type ofMS
anxiety/depression; frequentUTIs; hypertension; dizziness;dysarthria; urinaryfrequency/ urgency;diploplia; ataxicrapid alternating movements
atoravastatin;carvedilol; chlorthalidone; hydralazine;lexapro; losartan
Impairments:Rleg spasticity,weakness andfootdrop;fatigue, limitedwalking distanceanddizziness Goals:ImproveRleg strength,improve walkingqualityand distance
Liveswith spousewho isprimary caregiver
775(53)FSPMSFourWheeledwalker withRAFOdueto footdropand spasticityforall walkinginhome andmanual wheelchairfor community distances.
sinceinitialassessmentat1+/5MMT.TheseimprovementscombinedwithabilitytoplaceelectricalstimulationonbilateralPFtopreventclonusinweightbearing allowedthissubjecttostandwithoutclonus,requiring maximumassistancefromtheinvestigator,while holdingthesink.Priortostudyparticipation,subject 1wasunabletostandduetoweakness,clonusand spasticity.Subject1reportsdisappointmentinhis results,expressinghopetohaveimprovedhisstanding andcontrolofspasmsmoresubstantially.
Subject2(non-ambulatorypowerchairdependent withbilateralknee flexioncontractures)demonstrated reductioninbilateralPFspasticityfrom3/4MAT bilaterallyatIAreducedto1+/4atFAandabletotoleraterollingfromsupinetoprone.Pronepositioning wasnottoleratedpriortostudyparticipationdueto weaknessandbilateralknee flexioncontractures puttinghip flexorsintoashortenedposition.Subject 2improvedknee flexioncontracturesfrombilateral IA0-70-130improvedtoFA0-20-130passive rangeofmotion.Duetoimprovedkneerangeof motionandeliminationofclonusinweight-bearing duringapplicationofelectricalstimulationtobilateral gastrocnemiusandsoleusregion,Subject2wasable toinitiatestandingtrainingforthe firsttimein10 years(perself-reportofthesubject)atsinkwithbilateralupperextremitysupportandmaximumassistance fromprimaryinvestigator.Subject2reportsfeeling looserinherlegsandstrongerfortransfers.
Subject3(bilateralspasticgaitpatternwithunilateral cane)demonstratedmixedresultsinspasticity, strength,ambulationtestsandsubjectivereporting onMSWS-12andMSIS-29withadiagnosisof untreateddepression.Thissubjectdemonstrated ninthvisitreassessment(RA)ofspasticityasworse insomecategoriesandimprovedinothersbutsignificantimprovementinmusclelengthandstrengthin mostcategorieswhichisassociatedwithimprovementinT25WTfrom15.86sandTUG15.38sat IAtoT25WT14.52sandTUG14.5satRA. However,atFA,hedemonstratesincreasedPFspasticityandstrengthastrendingworseassociatedwith slowerT25WTtimeof17.8sandTUGtimeof 16.06s.AtFA,Subject3experiencedanincreasein bilateralpedaledema,spasticityinlowerlegsand feetseeninincreasedPFspasticityanddecreased gaittestingspeedbutwasabletogenerallymaintain progressinspasticityandstrengthofhipsandknees atFA.Subject3reportsfrustrationwithhisdiagnosis anddisappointmentthattheinterventiondidnot improvehisneuropathyspasticityandwalking beyonda24-hperiodofimprovement. Table1. Continued.
Table2. Studyassessmentandinterventiontimeline.
JS: study wrapup visit
CE:PTdischarge fi nal visit18
CE: PTvisits10 –17
CE:PTre-assessment visit9
3.EDSS
6.ObjectiveOutcome measures: MSWS-12;ROM; MMT;MAT;T25WT; TUG; 7.SubjectiveOutcome measures:MSIS-29; MSWS12 (afterdatacollection performedtreatmentas detailedbelow)
9.duplicateofstep9 (manualactivations) 10.**duplicateofstep 10(DCcombined with fl exibility,ROM andfunctional training) 11.duplicateofstep11 (DCwithfootbath)
6.ObjectiveOutcome measures: MSWS-12;ROM; MMT;MAT;T25WT; TUG
9.duplicateofstep9 (manualactivations)
JS:InitialvisitCE:InitialPTvisit1CE:PTvisit2CE:PTvisits3 –8
9.duplicateofstep9 (manualactivations)
10.**duplicateofstep10 (DCcombinedwith fl exibility,ROMand functionaltraining) 11.***duplicateofstep 11(DCwithfootbath)
8.*NeuBieelectrical stimulationre-mapping (seeappendix) 10.**duplicateofstep10 (DCcombinedwith fl exibility,ROMand functionaltraining)
11.***duplicateofstep 11(DCwithfootbath)
9.duplicateofstep9 (manualactivations)
8.*NeuBieelectricalstimulation mapping(seeappendix)
4.HomeHealth admission
10.**duplicateofstep 10(DCcombined with fl exibility,ROM andfunctional training) 11.duplicateofstep11 (DCwithfootbath)
9.Manualactivationstoimpaired musclesandareasof hypertonicity
10.**Electrodeplacements × 8 based onmappingcombinedwith fl exibilityopposingspasticity, agonistROMcorrecting compensatorypatternsrepeated forqualityastolerated; functionaltrainingbasedon subject ’ sability(bedmobility, transfers,ambulation)
11.***Incasesofneuropathy providedelectricalstimulation footbathwithmanualactivations andagonistROMtraining × 10 –15min
5.PTdetailedstudy explanation 6.Objective Outcome measures: MSWS-12; ROM;MMT; MAT;T25WT; TUG; 7.Subjective Outcome measures: MSIS-29; MSWS12
1.NeuBiepilot study explanation
2.NeuBiepilot study consent form 3.EDSS
Legend:JS = DrJulieSeibert;CE = DrCourtneyEllerbusch.
*Seeappendix1forNeuBiemappingexplanation. **Seeappendix2fordetailsonDCparametersanddosing. ***Seeappendix3fordetailsonDCfootbathprotocol.
Table3. QuantitativechangesinMATandMMT.
MATRhip flexionchange0520.0%71.4%28.6% MATLhip flexionchange0610.0%85.7%14.3% MATRhipextensionchange12414.3%28.6%57.1% MATLhipextensionchange24128.6%57.1%14.3% MATRknee flexionchange14214.3%57.1%28.6% MATLknee flexionchange0340.0%42.9%57.1% MATRkneeextensionchange15114.3%71.4%14.3% MATLkneeextensionchange0340.0%42.9%57.1% MATRankledorsiflexionchange16014.3%85.7%0.0% MATLankledorsiflexionchange0700.0%100.0%0.0% MATRAnkleplantarflexionchange11514.3%14.3%71.4% MATLankleplantarflexionchange20528.6%0.0%71.4% MMTRpsoasChange0340.0%42.9%57.1% MMTLpsoasChange0250.0%28.6%71.4% MMTRectusabdominuschange0330.0%50.0%50.0% MMTRquadratuslumborumchange0250.0%28.6%71.4% MMTLquadratuslumborumchange0340.0%42.9%57.1% MMTRRectusfemorischange12414.3%28.6%57.1% MMTLrectusfemorischange13314.3%42.9%42.9% MMTRvastuslateralis&medialischange11514.3%14.3%71.4% MMTRvastuslateralis&medialischange0070.0%0.0%100.0% MMTRgluteusmediuschange0070.0%0.0%100.0% MMTLgluteusmediuschange0340.0%42.9%57.1% MMTRhipadductorchange11514.3%14.3%71.4% MMTLhipadductorchange0250.0%28.6%71.4% MMTR fibulariichange32242.9%28.6%28.6% MMTL fibulariichange23228.6%42.9%28.6% MMTRtibialisanteriorchange0250.0%28.6%71.4% MMTLtibialisanteriorchange11514.3%14.3%71.4% MMTRtibialisposteriorchange32242.9%28.6%28.6% MMTLtibialisposteriorchange23228.6%42.9%28.6% MMTRtoeextensionchange12414.3%28.6%57.1% MMTLtoeextensionchange23228.6%42.9%28.6% MMTRtoe flexionchange22328.6%28.6%42.9% MMTLtoe flexionchange14214.3%57.1%28.6% MMTlumbarextensionbilateralchange10420.0%0.0%80.0% MMTRgluteusmaximuschange0340.0%42.9%57.1% MMTLgluteusmaximuschange22328.6%28.6%42.9% MMTRbicepsfemorischange0240.0%33.3%66.7% MMTLbicepsfemorischange0150.0%16.7%83.3% MMTRsemitendinosissemimembranosischange0250.0%28.6%71.4% MMTLsemitendinosissemimembranosischange14214.3%57.1%28.6%
Legend:MAT = ModifiedAshworthTest;MMT = ManualMuscleTest.
Subject4(spasticleftlowerextremityimpactinggait withunilateralcane)demonstratedimprovementin leftlowerextremityMAT,MMT,T25WTandTUG testsfromIAtoFA.Subject4improvedTUGIAof
19.34sandT25WT17.64stoFATUG15.6sand T25WT16.36s.Shealsodemonstratedimprovement inanklespasticityfrom3/4MATPFtonewithTA MMTof3+/5atIAtoFAof2/4LankleMAT
associatedwithimprovedFA4/5TAMMT.Subject4 reportswalkingfurtherthanshehadbeenabletoin years,correctingherleftanklefootdropattimes andfeelingencouraged.
Subject5(Leftlowerextremityspasticityandright lowerextremityspasmimpactedgaitusing3WW indoorhouseholddistancesforambulation)demonstratedimprovementbilaterallyinMAT,MMT, T25WTandTUGtestsfromIAtoFA.Subject5 improvedfromIATUG19.5sandT25WT15.34s toFATUG17.37sandT25WT13.53s.Healso demonstratedimprovementinanklespasticityfrom 3/4MATPFtonewithTAMMTof2/5atIAtoFA of2/4LankleMATassociatedwith2+/5TAMMT strength.Subject5alsodemonstratedreductionin allcategoriesofmeasuredspasticityatIAdownto 0/4exceptresidualbutreducedspasticityofbilateral PF(right1+/4andleft2/4)MAT.Subject5reports feelinghisleftlegimprovedslightlyinabilityto loosenhisleftkneeduringthetoe-offportionof walkingwhichallowedhimtousehishipbetterand walkfurther.Subject5statesplantoinvestina versionofelectricalstimulationduetohisresponse.
Subject6(Bilateralcaneswithintermittentrightankle footorthoticusewithweaknessandspasticitylimitingambulation)demonstratedsignificantimprovementinPFMAT,TAMMT,T25WTandTUG testsfrominitialassessmentto finalassessment. Subject6improvedTUGfrom54.75satinitial assessmentto16.81sat finalassessmentand T25WTfrominitialassessmentof36.88sto12.15s at finalassessment.Healsodemonstratedimprovementinanklespasticityfrom3/4MATPFtone withTAMMTof1+/5atinitialassessmentto final assessmentof2/4LankleMATassociatedwith improved2/5TAMMTstrength.Subject6reports feelingverysupportedbythevisitsandlearning howtoworkwithhisbodyaswellasimproved walkingespeciallyfrom10pmto11pmwithsignificantlyreducedspasticity.
Subject7(Rightlowerextremityspasticityassociated footdropcorrectedwithRAFOand4WWforhouseholdambulation)demonstratedimprovementinMAT inPF,MMTandmusclelengthbutwasunabletotolerateambulationtestingat finalassessmentdueto intoleranceinprobableurinarytractinfection.At RAsubject7demonstratesimprovementinspasticity, strengthandmusclelengthhoweveradeclinewith worsenedambulationspeed.AtIATUG46.15s andT25WT27.94swithRATUG47.5sand T25WT47.05s.AtIA,rightlowerextremityPF
spasticity3/4withassociatedrightTAstrengthof2/ 5.AtRArightPFspasticitydownto1+/4withassociated3/5TAMMT.AtFArightPFspasticity remains1+/4associatedwithtrendingimprovement rightankledorsiflexionof3+/5MMT.Subject7 reportsdespitethe finalappointmentbeingdisappointingduetohernewurinarytractinfectionsymptoms,thatshefeelsstrongerinherrightlegandmore comfortablewithwalkinginherhomeoverall.
InTable3,MATimprovementisdefinedasatleast1 gradedifferencefromIAtoFAonascaleof1+/4,2/ 4,3/4,and4/4.MMTimprovementisdefinedasat least1/2gradeimprovement.FromIAtoFAona scaleof0/5,1+/5,2/5,2+/5,3/5,3+/5,4/5,4+/5, 5/5.PertheAmericanPhysicalTherapyAssociation MultipleSclerosisOutcomeMeasureTaskforce, intraraterreliabilityforlowerextremityassessment insubjectswithMSis71.1%butneitherofthese assessmentshaveMCIDorMDCdatatoreference.9
Table3containsassessmentsforcategoricalmeasures shownbythecountandpercentageofpatientswho improved,stayedthesame,andworsenedovertime (frompretopost).
Discussion
Thiscaseseriesofsevenheterogenoussubjectswith MSisalowsamplesizeforstrongstatisticalanalysis ofresultsandshouldbeconsideredapilotstudy.The designisamulti-modaltreatmentapproachwhich demonstratesahighleveloffeasibilityandtolerance butcannotconcludecauseandeffectrelationships, onlypossiblecorrelationstofurtherinvestigate. Possibleotherexplanationsforresultsmeasured includeantispasmodic(baclofen)medicationin5 outof7subjects,thehighfrequencyofPTvisits, rapportwiththeprimaryinvestigatorandmultimodal interventions.Therearenoknownadverseresponses ofDCandantispasmodics.Baclofencombinedwith therapyinterventionsincludingelectricalstimulation improvefunctionaloutcomesinneurological patients.10
Trendsacrosssubjectsinspasticityandagonist strengthshowapossiblecorrelationbetweenmechanoreceptorinputfromDCallowinggreaterstretch andimprovedagoniststrength.71.4%ofsubjects demonstratedreductioninbilateralPFspasticity. 71.4%ofsubjectsimprovedMMTofbilateralTA. Twosubjectsstoodforthe firsttimeinmorethan3 yearswitheliminationofclonustheynormallyexperience.Subject6demonstratedsignificantimprovementinrightlowerextremityneuropathyand spasticityallowingsigni ficantimprovementingait
mechanicsandvelocityover25to50feet.Subject4 and5alsodemonstratedimprovementingait mechanicsandgaitvelocitywithreductioninspasticityandimprovementinagoniststrength.Subject3 experiencedFAworseningsymptomswhichcaused adeclineingaitmechanicsandvelocity.Impacton gaitisinconclusiveduetosamplesizeandtimeline.
Per findingsbyEtoometal.(SystematicReviewand MetaAnalysis)11 spasticitymaybebeneficialfunctionallybycounteractingmuscleweakness.11 The goalinspasticityreductioninterventionsneedstobe focusedonpreservingsafelevelsoffunction,while simultaneouslyimprovinganindividuals’ accessto normalizedanti-gravitysagittalandfrontalplane functionalmuscles.Thearticleindicatesthatthe bestavailablequalityofevidenceisforrobotassisted gaittrainingandoutpatientexerciseprogramson hypertonicity.This findingisinlinewithprevious research.12 Robotassistedgaittrainingcombines functionaltrainingwithelectricalstimulationdemonstratingreductioninspasticity.Thiselucidatesthe benefitofcombiningfunctionaltrainingwithelectricalstimulationtraining.1,6,11,13 Thereviewedarticlesdemonstratebenefitsinmuscletone,EMG muscleactivity,biomechanicalpropertiesofmovementandself-reportedspasmbutnoeffecton clonusordeeptendonreflex. 11 Per findingsinthis pilot,subjects1and2demonstratedeliminationof clonusduringandtemporarilyaftertreatment.This findingmaydistinguishthisversionofelectrical stimulation(DC)fromtheTENS(AC)assessedin thesystematicreview.Clonusisaphasicjerk responseasaresultofastretchattheextrafusal muscle fibersdetectedbythemusclespindleand transmittedtotheCNSbyIaafferentsthatconnect topropriospinal fibers.2 Inorderforclonusto reduce,themechanoreceptorsand/orCNSIa pathwayneedstohaveinputthatallowsnormalized stretch.
Summary
Basedonliterature findings,theuseofelectricalstimulationintheformofFESbikeandNMESisfeasiblefor personswithprogressiveMS.Thesetreatmentsmay reducefalls,improvemobility,reducephysiological deconditioningandreducespasticity.Inalloftheseoutcomes,furtherstudiesareindicatedtomakemoredefinitiveconclusions.3,14–17 Inthispilotwecanconclude thatinindividualswithprogressiveMS,DCisfeasible andwelltoleratedwhencloselymonitoredandmodified.ThisformofDCdemonstratesthepotentialto reducehypertonicityinformsofspasticityandclonus. Insomecases,thistreatmentalsodemonstrates
improvementinagonistmusclestrengthwithtrends towardimprovementinfunctionaloutcomemeasures.
TraditionalTENSapplicationmayreducespasticity throughthe1binhibitorypathwayshort-term1,18,19 and theformofDC5 usedinthiscaseseriesshowspotential toreducespasticityduringtreatmentandcarryoverafter treatments.Inthispilot,thisisdemonstratedintrendsof improvingagoniststrengthespeciallydorsiflexionwhile simultaneouslyreducingspasticity,especiallyatPF.Due tosubjects1and2beingnon-ambulatoryandsubject7 nottoleratingFAambulatorygaitspeedtesting,inconclusiveevidenceforgaitspeedimprovementisavailable. However,3/5ofambulatorysubjectsshowedtrends towardsimprovinggaitbiomechanicsandspeed.Most subjectsshowtrendstowardsimprovementinspasticity, strengthandROM.Subjects1and2withEDSS7.5–8.0 wereunabletoambulateorchangetheirdependenceona chairformobility,however,abletoinitiatefunctional standingduringtheirstudyparticipation.Thecase series findingssuggestfurtherresearchiswarranted.
Limitations
Theprimarylimitationsofthiscaseseriespilotstudy includeasmallsamplesizeandtreatmentscope limitedto18visitsover6weeks,whichlimitsgeneralizabilityofthe findingsandpotentialtherapeutic effectofthestudydesignonsubjectswithprogressive MS.Thestudyincludedaheterogenousmixofnonambulatoryandambulatoryindividualswithmultiple comorbiditieslimitingtoleranceoftreatmentand impactingassessments.Inherenttothestudyisa multi-modaltreatmentapproachwhichdemonstrates ahighleveloffeasibilityandtolerancebutcannot concludedirectcauseandeffectrelationships,only possiblecorrelationstofurtherinvestigate.Inherit biasmayoccurwiththestudydesignoftheprimary investigatorasprimaryauthorwithinacaseseries.
Futureresearchwouldbenefitfromisolatingtheeffect ofDConspasticityusingasingleordoubleblindrandomizedcontroltrialwithDCasthemaintherapyand alargersamplesizelimitingallsubjectstoeither ambulatoryornon-ambulatoryandperformedovera longerdurationtoincreasegeneralizabilityandvalidityof findings.Thisunfundedstudywaslimitedin scopetooneprimaryinvestigatorandone Neurologist.AllexpensesinInstitutionalReview Boardapprovalfeesandpublicationfeeshavebeen coveredbyNeurologicalFitnessEquipmentand EducationLLC,AustinTX.
Futurestudydesignsofelectricalstimulationorthis specificversionofDCshouldconsidercontinued
emphasisonfunctionalapplicationperformedsimultaneouslywithelectricalcurrentassessedwithobjectivemeasurementsinspinalreflex,spasticityand biomechanicalpropertiesofthegaitcycleinorder tobestunderstandquantityanddurationofreduced spasticitywithcorrelationintofunctionalchanges.1,6
Theauthorsdeclarenopotentialconflictsofinterest withrespecttotheresearch,authorship,and/orpublicationofthisarticle.TheuseoftheNeuBiewas approvedbyCenturaHealthbiomedicaldepartment. ThisDCunitisanFDAapprovedunit(AP439; HILLIFCInterferentialUnit;Neubie;Neuro-M TrainerModelA).CommonSpiritHealthResearch InstituteInstitutionalReviewBoardprovided approvalofthisstudydesignandconsentform (FWANumber:FWA00019514OHRPIRB Number:IRB00009715).
Declarationofconflictinginterests
Theauthorsdeclarednopotentialconflictsofinterestwith respecttotheresearch,authorship,and/orpublicationof thisarticle.
Funding
Theauthorsreceivedno financialsupportfortheresearch, authorship,and/orpublicationofthisarticle.
Disclosurestatement
NeuFithascoveredtheexpensesrequiredforinstitutional reviewboardapprovalprocessaswellasthefeesassociated withathird-partystatistician.Theinvestigatorshavenot receivedanyreimbursementforthisstudy.Theauthors declarenopotentialconflictsofinterestwithrespecttothe research,authorshiporpublicationofthisarticle.
NeuBiebyNeurologicalFitnessEquipmentandEducation LLC,AustinTX.
Manufacturer:JohariElectroTechCo.(Jodhpur,India).
ORCIDiD
CourtneyLEllerbusch https://orcid.org/0009-00071702-3574
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Appendix1(NeuBiedirectcurrentmapping)
AuniqueapplicationofNeuBiedirectcurrentis mapping.Thepractitionerplacesaredelectrode onthedistallumbosacralregionofthesubjectand usestheblackelectrodeleadattachedtoacarbon fi berelectrodewithwetspongeandscansacross thesurfaceoftheskinatcontinuous500Hz current.Thegoalistolocateareasofinterestindicatingorthopedichotspots,locationsthatallow increasedrangeofmotionfrombaseline,locations thatdemonstrateincreasedspasticityorspasm responseandlocationsthathavelowersensation thantheestablishedbaseline.Oncetheselocations areidenti fi ed,thepractitionercanplaceelectrodes tospeci fi callytargetorthopedicconcerns,range ofmotionimprovements,hypertonicregionsand neuropathy.
Appendix2(NeuBiedirectcurrentelectrical stimulationparametersusedinstudy interventions)
NeuBiedirectcurrentelectricalstimulationutilized forneuromuscularre-education,spasticityreduction andstrengtheningoflowerextremityandtrunk regionbasedonmappingandmotorpoints.Direct Currenttreatmentisalwayscombinedwith PT-basedinterventionsandfunctionaltraining lasting15–45mindependingontolerancewiththe followingparameters:
• Frequencyisadjustedbasedonpatientresponse from35–500Hzwithgoalofincreasingtime with500Hz.Inmid-rangefrequencyof35–75Hzthesubjectwasgivena1:4–1:2ratioof currentontocurrentofftimetoallowforrepolarization.Inhighfrequenciesof100–500Hzthe currentwasusedcontinuously.
• Intensityistobeadjustedtoremain70%–80% clientreportedperceivedintensityand/ortobe underthresholdofanyspasticityorpain.With electrodesinplaceemphasizingreductionin
spasticityandimprovementinrangeofmotion outofhypertonicpatterns,subjectsweregiven fl exibilitytreatmentforgastrocnemius,soleus, hamstrings,adductors ,quadratuslumborum, quadricepsandhip fl exors.Following fl exibility trainingsubjectsgivenAROM,AAROMand manualcuestoguidenon-compensatory agonistmovementtogreatestdegreepossible inmovementssuchasdorsi fl exionandeversion, kneeextension,knee fl exion,hip fl exion,hip bridging,hipexternalrotation.Next,subjects trainedathighestfunctionalmobilitychallenge theywereabletoperformwithcontrolledcompensationpossibleinbedmobility,sitting posture,sittostand,ambulationandstanding balance.
Appendix3(NeuBiedirectcurrentfootbath neuropathyprotocolusedinstudyinterventions) FootBathformultiplesclerosisperformedfor8–15minfortheaffectedside(ifbothaffectedthen treatedbothsimultaneouslywithdifferentchannels).Use500Hzcontinuouscurrent.**Assessed withtheclientoncomfortablerangeoftemperature forwaterandadjustedtemperatureaccordinglyfor comfort**
• Immersedtheentirefootandankleandhighankle inthewater.
• Providedthefollowingelectrodeplacementstarget thelocationsnerve fibersareclosesttothesurface. Thelumbarnerverootsto filloutasmuchofthe sciaticandfemoralnervepathwaysandmany bifurcationsaspossible
• channel1:Lumbarnerverootstotheaffected sideverticalelectrodeplacement(red)
• channel2:Midadductorverticallyplacedelectrode(red)
• channel3:Poplitealfossahorizontallyplaced electrode(red)
• channel4:Distalquadhorizontallyplacedelectrode(red)(allblackelectrodeswere floating carbon fibersinthewater,keptoutoftheway ofthetreatedfoot/feet.)
Duringfootbathprovidedmanualactivationsfor lowerlegmuscles;talocruralglides(toencourage thecalcaneousremainincontactwith floorsurface) grade2–4dependingontolerance,metatarsalglides, proximalphalanxglidesandbilateraltendon massagejustlateraltoachilles.Withlocationsthat allowedforgreaterdesiredankleorfootROMcontinuedtoworkandhaveclientmovethroughimproved rangeastolerated.Withareasthatcausereflexive response,decreasedtheintensityofmanualwork belowathresholdthatelicitedthereflexand workedwithclientondiaphragmaticbreathingwith
thework.Aftermanualworkassessforqualityof movementespeciallyintoankledorsiflexionand eversion.Whennoticingcompensationintoinversion orweaknesswaspresent,thenprovidedeither AAROM,isometricholdoreccentriccontrolinto
dorsiflexionandeversionandhadtheclientmove withcorrectionorsustainaposition.Throughout thisprocessensuredthecurrentwasatjustbelow thelevelthatwouldcausespasticityand/or7/10 intensity.