Funktionelle Elektrostimulation

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    Winfried Mayr, MedUni Wien 1

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

    1

    Center of Biomedical Engineering and PhysicsMedical University of Vienna, Austria

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

    2

    Technological Ressources

    Mechanics

    Microelectronics

    CAD/CAM

    Plastics Lab.

    Electronics

    Computer / Microcomputer

    Ph.D.Modeling/Simulation

    Digital SignalProcessing

    +PC-Measurement,

    CAD

    Sensor-/Actuator-applications

    +Sensors/

    Measurement

    FES-DDM

    +Co-operations

    Mechanics

    FES-Implants

    +Electronics

    FES-Walking

    +PCs, Network,

    -Computer

    PrecisionMechanics

    MechanicalEngineer

    CAD/CAM

    Mechanic Electrical EngineerMicroelectronics

    CAD/CAM

    SoftwareEngineer

    Ph.D.EMG-Feedback-FES

    Industry collaboration

    OUR TEAM Permanent Staff, Biomedical Engineering

    Temporary StaffUniversity Education:

    Sub-UniversityEducation:

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    CoCo--operationoperation partnerspartners

    ClinicsClinics & Departments,& Departments,ViennaVienna MedicalMedical Univ.Univ.

    TUTU BiomedBiomed

    externalexternal ClinicsClinics,,Departments &Departments & RehabRehabCenters:Centers:WilhelminenspitalWilhelminenspitalViennaVienna, University of, University ofGraz, Weier Hof A,Graz, Weier Hof A,BadBad HringHring A, BadA, BadMurnau D, BadMurnau D, BadWildungenWildungen D, Hamburg,D, Hamburg,Tbingen, Heidelberg,Tbingen, Heidelberg,PadovaPadova, Ljubljana,, Ljubljana,MoscowMoscow, Liverpool, . . ., Liverpool, . . .

    . . . . .. . . . .

    Industriekooperationen:Industriekooperationen: Otto BockOtto Bock

    MedMed--ElEl

    InsightInsight InstrumentsInstruments

    SeibersdorfSeibersdorf

    Przisionsteile GmbHPrzisionsteile GmbH

    PlanseePlansee

    SchottSchott

    . . . . .. . . . .

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    Examples for co-operations projects:

    EOG forremote control

    diagnosticERG

    Tool for gainingbrain samples

    Pruritometer

    Heater forlocal hyperdermia

    Force distribution measurement

    knee joint endo-prostheses

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    ISEK 2006ISEK 2006 -- TorinoTorino

    From Research to Clinical PracticeFrom Research to Clinical Practice

    FFunctionalunctional EElectricallectrical SStimulationtimulation

    Basic Research:Basic Research:-- indispensable for clinical applicationindispensable for clinical application-- explanation of clinical observationsexplanation of clinical observations

    Clinical Research:Clinical Research:-- part of Clinical Practicepart of Clinical Practice

    Clinical PracticeClinical Practice --> Clinical Routine> Clinical Routine-- routine component in rehabilitationroutine component in rehabilitation

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    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    CardiacPacemaker: First Prototyp 1958 the most successful FES-Product today

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    Auditory prostheses:

    Cochlea implants

    Visual prostheses:

    epiretinal

    subretinal optic nerve

    cortical

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    Practicallyall FES-applications are based onNERVE- and NOT on MUSCLE stimulation !

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    Vienna epineural elektrode

    Biocompatibility

    Electrochemical stability

    Mechanical stability

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    Electrode technology

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    RulesRules forfor constructingconstructing activeactive implantsimplants

    AllAll surfacessurfaces biomaterialsbiomaterials,, smoothlysmoothly

    structuredstructured, no, no edgesedges

    RobustRobust butbut lightweightlightweight

    ComponentsComponents andand DCDC--conductingconducting leadsleads inin

    hermetichermetic casecase (metal oder(metal oder ceramicsceramics))

    Pure metals, noPure metals, no alloysalloys

    PreferablyPreferably weldingwelding,, ifif unavoidableunavoidable acidacid--

    freefree solderingsoldering,, nevernever conductiveconductive bondingbonding

    AntennaAntenna coilscoils insideinside thethe casecase

    LongLong isolationisolation distancesdistances

    PolymerPolymer sealingsealing inin NitrogenNitrogen atmosphereatmosphere,,

    avoidingavoiding bubblesbubbles and fastand fast temperaturetemperature

    changeschanges duringduring curingcuring

    . . . . .. . . . .

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    Rf-powered8-channel implant Rf-powered20-channel implant bat terypowered 8-channel implant

    3 Generations of Vienna FES-Implants

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    Antenna coil

    Amplitude-limiter

    P ow er su pp ly D ec od er

    Impulseg enerator

    Current source

    Outputswitcharray

    DCdecoupling capacitors

    Hysol

    Electrodeconn ector

    8stimulation electrodes

    RF-link

    Antennacoil

    Rechargable battery

    Di sp la y C on tr ol s wi tc he s

    -controllerboard

    External supplyandcontrol unit

    Implant

    Covar case

    RF-link

    Antennacoil

    toaSECONDIMPLANT

    Stimulus Duration

    PhaseChange

    high,40 sm

    l ow ,5 sm

    CarrierSuppression,5 sm

    27MHz Carrier

    24 bit Data

    Antennacoil

    Telemetry circuit

    W G 8602 bat t ery -contro ll er

    Chargepumpe

    Current source

    Output switcharray

    DC decouplingcapacitors

    Hysol

    Electrode connector

    8stimulation electrodes

    Interfacebox

    Antennacoil

    ImplantTitanium case

    RS232

    RF datalink

    Electrodeconnector

    Recording

    electrodes

    Amplifier

    Rf-powered 8-channel State-of-the-art

    Battery powered 8-channel Next generation

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    Wien, 1983 Montpellier, 2000

    Locomotion pacemaker

    Vienna, 1983 Montpellier, 2000

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    Wien, 1983 Montpellier, 2000Montpellier, 2000

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    Vienna / Bad Wildungen, 1984

    Phrenic pacemaker - enormous improvement in quality of life

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    Phrenic pacemaker - enormous improvement in quality of life

    Atrotech / Finnland

    Avery / US

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    Brindleys sacral anterior root stimulator bladder control

    more than 2000 implantations

    more than 25 years lifetime

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    What decides about the survival of an FES implant ?What decides about the survival of an FES implant ?

    There should beThere should be

    a needa need

    a smart solutiona smart solution

    technology, application, handling sufficienttechnology, application, handling sufficient

    legal requirements fulfilledlegal requirements fulfilled

    fast reacting supportfast reacting support

    in application and in case of failurein application and in case of failure justification of costsjustification of costs

    unlimited financial room to moveunlimited financial room to move

    ..........

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    e

    a b

    c

    f

    POTENTIAL APPLICATIONS:

    Continence( Graciloplasty)

    Phrenic pacing

    Cardiac support (latissimus)

    Hand-/ arm-neuroprosthesis

    Peroneus-stimulator

    Walking aid

    Spinal cordstimulation

    - Chronic paintherapy

    - Treatment of spasticity

    - Locomotion

    .....

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    What is new and promising ?What is new and promising ?

    2 examples of novel implant applications:2 examples of novel implant applications: Activation of movement generatorsActivation of movement generators

    in the SCIin the SCI(Milan(Milan DimitrijevicDimitrijevic))

    Release of insulin via stimulation of theRelease of insulin via stimulation of theautonomic nervous systemautonomic nervous system((JanezJanez RozmanRozman))

    26

    FES of Spinal CordFES of Spinal Cord

    Movement pattern generatorsMovement pattern generators

    CPG, LLPGCPG, LLPG

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    Mimicking brain stem control of the lumbar network

    spinalspinalspinalcordcordcordinjuryinjuryinjury

    spinalspinal cordcord

    stimulationstimulation

    (SCS)(SCS)

    tonicsuprasegmental

    drive

    intermittentphasicafferent input

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    Methods: Epidural spinal cord stimulationMethods: Epidural spinal cord stimulation

    Continuous stimulationContinuous stimulation210 s pulse width210 s pulse width

    11 10 V10 V2.22.2 100 Hz100 Hz

    Cross-section at T12 vertebral level

    Posterior roots

    Dura mater

    Epidural space

    Spinal cord

    Anterior roots

    Vertebral bone Vertebral canal

    Epidural electrode site

    Electrode

    Spine

    Spinal cord

    Pulse generator

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    NonNon--patternedpatterned spinalspinal cordcord stimulationstimulation inducesinduces steppingstepping movementsmovements

    Electromyographic recording

    Electrode

    Spine

    Spinal cord

    Descendinginput

    Completespinal cord injury

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    2 mV

    1 mV

    1 mV

    1 mV

    2 s

    Q

    H

    TA

    TS

    KM

    2 mV

    Stimulus artifacts 0.05 s

    0.5 mV

    0.5 mV

    1.5 mV

    0.5 mV

    45

    2 s

    Q

    1 mV

    1.5 mV

    1 mV

    1.5 mV

    45

    Q

    H

    TA

    TS

    KJA

    2 s

    A

    B

    10 V, 6 Hz 10 V, 31 Hz

    90

    9 V, 30 Hz

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    CanCan thethe LLPGLLPG processprocess sensorysensory feedbackfeedback inputinput toto generategeneratefunctionalfunctional EMGEMG patternspatterns?? MethodsMethods

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    CanCan thethe LLPGLLPG processprocess sensorysensory feedbackfeedback inputinput toto generategeneratefunctionalfunctional EMGEMG patternspatterns?? ResultsResults

    33

    FES of Autonomic Nervous SystemFES of Autonomic Nervous System

    Insulin deliveryInsulin delivery

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    Experiments in dogs:

    39-electrode cuffaround left vagus

    biphasic rectangular:

    200s, 1mA, 20Hz

    increase of insulin releasein bothintact and partlydysfunctioned (alloxan)pancreas

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    P-system

    (HC16)

    stimulationmodule 1

    stimulationmodule 2

    stimulationmodul 3

    stimulationmodule 4

    I2C bus

    EMG-signals

    COM-Port

    surface electrodes

    I2C bus

    4 channel

    surface

    stimulator

    AD-board

    PC

    I2C Interface

    stimulationmodule 1

    stimulationmodule2

    stimulationmodul 3

    stimulationmodule4

    I2C bus

    EMG-signals

    surface electrodes

    I2C bus

    APPLICATIONS:

    Leg neural prosthesis

    Peroneus stimulator

    Remobilisation

    Continence therapy

    Pain therapy

    Therapy of spasticity

    Muscle training in space

    Long-term bed rest

    Chronic heart insufficiency

    Sports

    ..

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    Technical WP 3Technical WP 3

    stimulationmodule1

    stimulationmodule2

    stimulationmodul 3

    stimulationmodule4

    stimulationmodule1

    stimulationmodule2

    stimulationmodul 3

    stimulationmodule4

    I2C

    Control Unit

    RS232

    RS232

    433MHzFM

    RS232

    I2C Interface

    WirelessLAN

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    EMG-triggerte FES-training

    Relearning of lost movement functionsafter partial lesions

    University Clinic for Physical Medicine

    and Rehabilitation, MUW

    University Clinic for Neurology, AKH

    Rehabilitationscenters Weier Hof and

    Werner Wicker-Klinik, Bad W ildungenStiwell / Medel/ Otto Bock

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    Long-term space flights are associated withdegenerative changes in the neuromuscular system.

    Conventional exercising (treadmill, bicycle, expander...) at least 3-4 h per day required to be efficient.

    Problems: loss of working time, motivation

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    Alternative FES training: MYOSTIMisometric muscle training with low intensity,6h per day, during routine work

    easy to handle equipment:- electrode trousers (Patent D. Rafolt)- automized 8- channel stimulator

    in co- operation withIBMP Moscow

    First time in history application of FESfor muscle training in space

    Dec.98 Feb.99 und Feb.99 Aug.99

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    Very positive judgement by both cosmonauts

    Clear improvements in the functional tests:

    Test 108, Ergometric locomotion

    Equitest, sensomotoric coordination

    Indications of positive effects of FES trainingin the neuromuscular tests:

    Tendometry

    Dynamometry

    Reflex test

    Histological results, to interprete with reservation:

    Biopsyvom Vastus Lateralis

    No in relation to FES interpretable results:

    Bone density measurements

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    Preparation of potential application onboard ISS

    ISS

    Participation in the internationalterrestrialisolationstudy inMoscow(4 subjects)

    successfulapplicationof themethod inchronicheart insufficiencypatients

    Co- operation:University clinicfr Physical Medicineand Rehabilitation, Vienna

    Terrestrial application:

    French- russian crewan onboard of MIR

    23. March2001

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    NMES-Group (n=17)

    Age: 59 6

    BMI: 22,7 3,2

    LVEF: 15,1 3,1

    NHYA: II: 4

    III: 10

    IV: 3

    since, weeks: 24 6

    Control group (n=16)

    Age: 57 8

    BMI: 25,7 3,9

    LVEF: 18,1 5,2

    NHYA: II: 4

    III: 9

    IV: 3

    since, weeks: 26 5

    all on a waiting list for HTX

    stable medication

    voluntary training not possible

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    biphasic rectangular impulsesCV / 0,7ms / 50Hz

    2 s on / 6 s off

    Intensity: 25 - 30% MVC

    initially 30 min / day

    after 2 weeks increased to 60 min / day

    entire FES training period: 8 weeks

    FES training parameters

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    Force-Endurance-Test

    Stimulation group

    150

    170

    190

    210

    230

    250

    270

    290

    310

    0 5 10 15 20

    Minutes

    Extension

    force

    (N)

    before

    after

    *

    *

    * * *

    Control group

    150

    170

    190

    210

    230

    250

    270

    290

    310

    0 5 10 15 20

    Minutes

    Extension

    force

    (N)

    before

    after

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    NYHANMES-group

    8 patients + 1 class

    3: IV auf III

    5: III auf II

    9 patients unchanged

    Control group

    1 patient + 1 class

    1: IV auf III

    15 patients unchanged

    ADL

    10

    12

    14

    16

    18

    20

    22

    NMES Control

    SCOREpre

    postP

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    Population pyramids 1950/2000/2050

    male female

    0

    85year

    0

    85year

    0

    85year

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    FES ofFES ofDenervatedDenervated MusclesMuscles

    Direct muscle stimulationDirect muscle stimulation

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    Uppermotor neuron lesion

    Lowermotor neuron lesion

    Nerve stimulation Muscle stimulation

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    Stimulation parameterStimulation parameter surface electrodessurface electrodesNerve stimulation:Nerve stimulation: Amplitude rangeAmplitude range100V /100V /300mA300mA

    Pulse width (biphasic)Pulse width (biphasic)typtyp. 0.5. 0.5ms perms per phasephase

    FrequencyFrequency ((fusedfused contrcontr.).)25 Hz25 Hz

    Muscle stimulation:Muscle stimulation:

    Amplitude rangeAmplitude range100V /100V /300mA300mA

    Pulse width (biphasic)Pulse width (biphasic)typtyp.. 20ms (20ms (100ms) per100ms) per phasephase

    FrequencyFrequency ((fusedfused contrcontr.).)25 Hz25 Hz

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    Lomo 1985

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    Valencic et. al. 1985

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    Modulation/demodulation

    P ow er s up pl y -c on tr ol le r

    Current source

    Output endstage,

    channelselector

    Hysol

    Electrode connector

    Antennacoil

    Implant

    RS232

    RF

    datalink

    Electrodeconnector

    EMGrecordingelectrodes

    Amplifier

    External supplyand control unit

    Rechargablebattery

    Control switchesDisplay

    -controller board

    RF

    powerlink

    Titanium case

    Dual-channelstimulationelectrodes

    Antenna

    connector

    DC decoupling capacitors

    FES of the denervatedposterior cricoarytenoid musclefor glottis opening

    in synchrony with inspiration

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    Clinical program for FESClinical program for FES

    of subjects with lowerof subjects with lower

    motor neuron lesionmotor neuron lesion

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    5th Framework programme

    Quality of Life and Management of Living Resources

    Research relating to persons with disabilities

    R I S E

    Use of electrical stimulation to restore standingin paraplegics with long-term

    denervated degenerated muscles (DDM)

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    3 cm

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    per million EU citizens yearly:

    100 new spinal cord injuries 250 rehospitalisations

    500 outpatient treatments

    63 % paraplegics

    about 1/3 flaccid paraplegia

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    no adequate rehabilitation method available

    fast degeneration of muscles, skeleton, joints, skin, ...

    frequent secondary diseases

    problems with social and professional integration

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    Objectives of RISE

    New rehabilitation methode -- transfer to clinical practice

    Technical equipment -- new product family for biomedical industry

    Adaptation of EU-regulations for FES-devices -- scientific basis

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    Mayr, Vienna (Co-ordinator)

    Kern, ViennaSalmons, LiverpoolGirsch, ViennaCarraro, Padova

    Gruber, ViennaDimitrijevic, LjubljanaGerner, HeidelbergExner, HamburgKaps, Tbingen

    [Cerrel-Bazo, Vicenca][Helgason, Iceland][Protasi, Chieti]

    Schrei, KlosterneuburgJonas, Bad HringPotulski, MurnauSchmidt, ViennaLosert, ViennaGallasch, Graz

    Consortium:

    Subcontract: Rehabilitation CentreRehabilitation CentreRehabilitation CentreDermatologyAnimal DepartmentMuscle Function

    Biomedical Engineering

    Clinical StudyRabbit StudyPig StudyMuscle Regeneration

    Muscle HistologyNeurologyRehabilitation ClinicRehabilitation ClinicRehabilitation Clinic

    Rehabilitation ClinicRehabilitation ClinicMuscle Fibre Structure

    additional:

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    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

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    RISE Project Start Nov. 1, 2001

    Kick Off Meeting Jan. 2002 in Vienna

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    100 ms

    Twitch reaction

    Amplitude Fmax

    Duration at 50% Fmax

    0

    50

    100

    150

    0 20 40 60

    Pulse width [ms]

    [ms]

    Time to peak

    00,10,20,30,40,50,60,70,8

    0 20 40 60

    Pulse width [ms]

    [N]

    Amplitude Fmax

    I x t = const.

    Pilot Study on Rabbits

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    Rabbit Study

    STIMULATOR

    TRANSMITTER UNITNOTEBOOK

    ELECTRODES

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    Rabbit model ofRabbit model of denervationdenervation

    DenervatedDenervated ankleankle dorsiflexorsdorsiflexors 1010 -- 51 weeks (51 weeks ( 3314 years in humans)14 years in humans)

    Physiological propertiesPhysiological properties ExcitabilityExcitability

    Force generation and kineticsForce generation and kinetics

    Fatigue resistanceFatigue resistance

    Morphological propertiesMorphological properties Weight and CSAWeight and CSA

    MorphologyMorphology

    Fibre areasFibre areas

    Fibre typesFibre types

    Electron microscopyElectron microscopy

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    Conclusions: rabbit modelConclusions: rabbit model

    DenervationDenervation up to 1 year produced:up to 1 year produced:

    Profound muscle and individual fibre atrophyProfound muscle and individual fibre atrophy Little degeneration / regenerationLittle degeneration / regeneration

    Loss inLoss in tetanictetanic force generationforce generation

    Poor morphological structurePoor morphological structure

    No evidence of progressive changes; stable between 10No evidence of progressive changes; stable between 10and 51 weeksand 51 weeks denervationdenervation..

    Atrophy, NOT degeneration, inAtrophy, NOT degeneration, in denervateddenervated rabbit anklerabbit ankledorsiflexordorsiflexor muscles.muscles.

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    What was achievedWhat was achieved

    LongLong--term rabbit model ofterm rabbit model ofdenervationdenervation establishedestablished

    Selective motorSelective motor denervationdenervation avoided problems of selfavoided problems of self--harmharm

    Initial plan was toInitial plan was to denervatedenervate 10, 25 or 40 days10, 25 or 40 days

    By the end we hadBy the end we had denervateddenervated up to 357 days!up to 357 days!

    Safe envelope for stimulation establishedSafe envelope for stimulation established

    Temperature rise under electrodes less than 1 deg CTemperature rise under electrodes less than 1 deg C

    No damage under electrodes (other than thickened connective tissNo damage under electrodes (other than thickened connective tissue)ue)

    No damage in muscle, even with the most intensive longNo damage in muscle, even with the most intensive long--term stimulation regimesterm stimulation regimes

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    What was achieved (What was achieved (contdcontd))ExcitabilityExcitability Did not change afterDid not change after 4 d4 d

    Was not improved by stimulationWas not improved by stimulation

    Size and morphologySize and morphology

    Stimulation restored original weight and CSA (Stimulation restored original weight and CSA (~40% normal without)~40% normal without)

    Histological appearance substantially restoredHistological appearance substantially restored

    Electron microscopy (not yet liaised on stimulatedElectron microscopy (not yet liaised on stimulated--denervateddenervated))

    ConclusionsConclusions

    Any changes in excitability are not at cel lular level, or are deAny changes in excitability are not at cellular level, or are dependent on more atrophypendent on more atrophy

    or degeneration than we sawor degeneration than we saw

    Changes in SR and TChanges in SR and T--system suggest loss of Esystem suggest loss of E--C couplingC coupling

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    What was achieved (What was achieved (contdcontd))TensionTension--generating capacitygenerating capacity

    Stimulation increasedStimulation increased tetanic tensiontetanic tension fromfrom ~27%~27% to ~49% of normalto ~49% of normal Force recovery not commensurate with recovery in weight and CSAForce recovery not commensurate with recovery in weight and CSA

    Contractile speedContractile speed

    Time to peak twitch, halfTime to peak twitch, half--relaxation and speed of shortening all much slower (likerelaxation and speed of shortening all much slower (like

    soleussoleus!)!)

    Stimulation did not alter thisStimulation did not alter this

    ConclusionsConclusions

    Slowness and loss ofSlowness and loss oftetanictetanic tension could be due to loss of Etension could be due to loss of E--C couplingC coupling

    Disadvantage: reduction in power available from muscleDisadvantage: reduction in power available from muscle

    AAdvantage: fusion achievable at a lower frequencydvantage: fusion achievable at a lower frequency

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    What was achieved (What was achieved (contdcontd))EnduranceEndurance

    Denervation increases mitochondria (NADHDenervation increases mitochondria (NADH--TR, EM)TR, EM)

    But muscles, if anything, MORE susceptible to fatigueBut muscles, if anything, MORE susceptible to fatigue

    Fatigue resistance NOT improved by stimulationFatigue resistance NOT improved by stimulationworse with 40 Hz patterns!worse with 40 Hz patterns!

    Lack of degenerationLack of degeneration

    Major difference between rabbit (motor branches) an d rat (wholeMajor difference between rabbit (motor branches) and rat (whole sciatic)sciatic)

    Could be species or procedural differenceCould be species or procedural difference

    Intact muscles maintain vascular pumping, may avoid damage due tIntact muscles maintain vascular pumping, may avoid damage due to venouso venous

    congestioncongestion

    ConclusionsConclusions Stimulation does not improve endurance; may make it worseStimulation does not improve endurance; may make it worse

    Rabbit is a GOOD model of human muscle at 1Rabbit is a GOOD model of human muscle at 1--2 years post2 years post--injuryinjury

    Rat may be a good model of degenerative changes at longer periodRat may be a good model of degenerative changes at longer periodss

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    Transformation of results from the rabbit studyTransformation of results from the rabbit study

    Testing of patient equipmentTesting of patient equipment

    Pig Study

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    surgicalsurgical modelmodel forfor chronicchronic denervationdenervation::isolatedisolated transsectiontranssection andand resectionresectionof TA and EDLof TA and EDL motormotor branchbranch

    PIG MODEL

    Winfried Mayr Vienna Medical University - Center of Biomedical Engineering& Physics

    80

    0

    1

    2

    3

    4

    5

    6

    7

    8

    9

    0 10 20 30 40 50 60 70 80 90 100 110weeks

    pigs

    81

    TechnicalTechnical setupsetupforfor invasiveinvasive investigationinvestigation::

    SurgicalSurgical exposureexposure of TA and EDLof TA and EDL

    DirectDirect needleneedle EMGEMGIntramuscularIntramuscular stimulationstimulationtoto evaluateevaluateELECTROPHYSIOLOGICAL PARAMETERSELECTROPHYSIOLOGICAL PARAMETERS

    BIOPSIESBIOPSIES forfor histochemicalhistochemical investigationinvestigation

    PIG EXPERIMENTS

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    Weight & Handling Problems

    Bodyweight:time of denervation mean 29 kgnowR 1 - 5 mean age 103 weeks 105kgR 6 - 9 mean age 76 weeks 98kg

    83

    PIG EXPERIMENTS

    FESR2 since 29.08.05R5 since 05.12.05

    84

    R1 44 weeks denervated EDL

    muscle 73%

    fat, connective tissue 27%

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    R1 67 weeks denervated EDL

    muscle 25%

    fat, connective tissue 75%

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    Electrode arrangement

    A... monopolar stimulation needleB... stimulation reference

    C... concentric EMG-needle

    A

    B

    C

    Measurementsetup:

    BenchstimulatorDAQ PC-Card with preamplifieroszilloscope

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    R1 EDL den

    0

    10

    20

    30

    40

    50

    60

    70

    80

    90

    100

    0 10 20 30 40 50

    Pulsbreite/ms

    Amplitude/V

    l i ED L 15 12 04 _4 4w l i ED L 23 02 05 _5 1w l i ED L 20 04 05 _6 7w l i ED L 08 08 05 _8 3w

    83w

    67w

    49w51w

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    49w 51w

    3V/0.1ms; D:22mmLatency: 3,6msspeed:6,1m/s

    3V/0.1ms; D:22mmLatency: 3.7msspeed:5,9m/s

    1-2ms 1-2ms

    89w

    EMG-signanot found

    R1_EDL li

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    TechnicalTechnical WPsWPs WP 3: Equipment for homeWP 3: Equipment for home--based trainingbased training

    WP 4: TestWP 4: Test-- and measurement equipmentand measurement equipment

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    Patient Study / Technical WP3

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    Required pulse width

    initially 120 - 150 ms

    after appr. 1 year 30 - 40 ms

    shortest pulse width 25 - 35 ms

    t

    (Nerve stimulation: 0.2 2ms)

    Peak amplitude

    +/- 80 V +/- 250 mA

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    Technical WP 3Technical WP 3

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    Agonist

    Antagonist

    FES

    ForceDisplacement

    Tendometry

    t

    50 100 150 200 250 300 350 400

    -0.05

    0

    0.05

    0.1

    0.15

    0.2

    t

    F

    MucleStiffness& Viscosity

    no stimulatin

    Withstimulation

    Transversal muscle stiffness

    Oscillation Tonometry

    Problem ofCo-contraction

    0 2 4 6 8 1 0 12 1 4 160

    0.5

    1

    1.5

    2

    2.5

    3

    3.5

    4

    Force

    Kontraction

    Displacement

    Patient Study / Technical Workpackage 4

    96

    a mobile and a stationary system

    Oscillation Tonometry

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    no stimulation weak stimulationOscillation TonometryPiendl

    0,0

    0,2

    0,4

    0,6

    0,8

    1,0

    1,2

    1,4

    1,6

    1,8

    2,0

    0 50 60 70 80 90 99

    Stimulationin %of 80V

    Frequenz

    Daempfung

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    LegLeg responsesresponses whilewhile FESFES amplitudeamplitude waswas increasedincreased

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    Pendulum testModeling and estimated parameters

    pendulumtestdata

    model

    forpendular

    legmotion

    T... joint torque

    limb

    geometricaldata

    C...joint stiffness

    D...viscous moment

    J...moment of inertiaCG... gravity spring

    sin( ) 0J D mgL C + + + =&& & sin( ) GmgL C =with

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    100

    110 Skul

    116 Ness

    111 Pien

    117 Lan

    205 Br

    206 Bt

    119 Th

    Oscillation TonometryFES-induced elastic moment [%]

    -100

    0

    100

    200

    300

    400

    500

    600

    700

    0 8 16 24 32 40 48 56 64 72 80

    stimulation [V]

    FES-inducedelasticmoment[%]

    109-7.7y

    105-7.5y

    301-6.5 y

    112-6.2y

    117-6.2y

    206-5.5y

    104-4.1y

    106-3.5y

    108-3.3y

    119-3.3y

    111-1.8y

    113-1.7y

    207-15m

    118-13m

    110-11m

    116-10m

    114-10m

    120-10m

    115-10m

    205-9m

    201-9m

    mean

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    Vergleich:Vergleich:nderung des Parameters Dnderung des Parameters D

    Beispiel: Patient 7,3 Jahre denerviert

    0,00

    0,02

    0,04

    0,06

    0,08

    0,10

    0,12

    0,14

    0 8 16 24 32 40 48 56 64 72 80

    Stimulationsamplitude in V

    nderungvonDinNms

    vor demTraining

    nach 1 Jahr Training

    Beispiel: Patient 1,5 Jahre denerviert

    0,00

    0,50

    1,00

    1,50

    2,00

    2,50

    0 8 16 24 32 40 48 56 64 72 80

    Stimulationsamplitude in V

    nderu

    ngvonD

    inNms

    vor dem Training

    nach 1 Jahr Training

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    Rot:preFES

    Blau:1 Jahr FES

    50 100 150 200 250 300 350 400

    -0.05

    0

    0.05

    0.1

    0.15

    0.2

    t

    F

    TTP, HRT und El.Mech.Delay bei verschiedenen Pulsbreiten(1, 5, 10, 20, 40, 80, 120, 160ms)

    Kein Balken bedeutet: kein Twitch detektierbarMit FES ist die Detektionsschwelle von 40ms auf 20ms gesunken.

    Time to peak(TTP) Half relaxationtime (HRT) El.mech. delay

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    SingleSingle fiberfiber recordings / measurement setuprecordings / measurement setup

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    Analysis of muscle fibre conduction velocityAnalysis of muscle fibre conduction velocity(MFCV)(MFCV)

    first pos. spike > 50Vfirst pos. spike > 50V

    (5.76 ms)(5.76 ms)

    last pos. spike (8.22 ms)last pos. spike (8.22 ms)

    mean latency of all recordedmean latency of all recorded

    spikes > 50V (7.10 ms)spikes > 50V (7.10 ms)

    distancedistance betwbetw. electrodes. electrodes

    32 mm32 mm

    max. MFCVmax. MFCV = 5.6 ms= 5.6 ms--11

    min. MFCVmin. MFCV = 3.9 ms= 3.9 ms--11

    mean MFCV = 4.5 msmean MFCV = 4.5 ms--11

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    Double pulse stimulation ofDouble pulse stimulation of

    denervateddenervated musclemuscle

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    RISE Pat. 108RISE Pat. 108 afterafter 11stst and 2and 2ndnd yearyear of FESof FES

    ISI = 6 ms; MFCV = 1.85 m/s ISI = 3 ms; MFCV = 4.12 m/s

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    RISE Pat. 119RISE Pat. 119 beforebefore andand afterafter 11 yearyear of FESof FES

    MFCV = 0.98 m/s; ISI = 8 ms MFCV = 1.83 m/s; ISI = 3 ms

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    CTCTscansscans everyevery 10 cm10 cm

    trochanter

    20 cm

    10 cm

    30 cm

    40 cm

    0 cm

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    8.7a denervatedcross sectional area = ???

    1.7a dendervatedcross sectional area = 50.17 cmmean density= 30 HU

    PlanimetryPlanimetry

    Cross Sectional Area (cm) andDensity (HU)

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    A.B. #18 ( 205 )

    0.8y denervated

    20cm

    30cm

    CrossCross sectionsection rightrightthighthighat 20 &at 20 &

    30cm30cm

    0y 1y 2.5y0y 1y 2.5y stimulationstimulation

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    H.T. #36 ( 119 )

    3.2y denervated

    20cm

    30cm

    CrossCross sectionsection rightrightthighthighat 20 &at 20 &

    30cm30cm

    0y 1.1y 1.6y0y 1.1y 1.6y stimulationstimulation

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    K.L. #24 ( 109 )

    7.7y denervated

    20cm

    30cm

    CrossCross sectionsection rightrightthighthighat 20 &at 20 &

    30cm30cm

    0y 1.3y 2.5y0y 1.3y 2.5y stimulationstimulation

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    116

    Biopsies

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    Prof. Ugo Carraro - Applied Myology Lab -Padova [email protected]

    0.9-y [110 (26-5)]

    1.9-y [111 (28-5)]

    4.0-y [104 (20-5)]

    8.7-y [103 (14-1)]

    Long-term Denervated Human Muscle

    Lower Motor Neuron Lesion

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    From: Kern H et al J Rehabil

    Res Dev 2005

    Prof. Ugo Carraro -Applied

    Myology Lab -Padova

    [email protected]

    Long-term Lower Motor Neuron Lesion

    FES Training of Denervated Human Muscle

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    Myofiber

    Regeneration

    in Long-term

    Denervated

    Human

    Muscle

    FES -

    Training

    Lower

    Motor

    Neuron

    Lesion

    MHC-emb+

    RegeneratingMyofibers

    From: Kern H et al J. Neuropathl Exp Neurol

    2004; 63: 919-931.

    Prof. Ugo Carraro -Applied Myology Lab -

    Padova [email protected]

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    Effect of FES Training on Myofiber Size of

    Long-term Denervated Human Muscle

    Prof. Ugo Carraro - Applied Myology Lab -Padova u [email protected] ECPRM - Wien, May 15, 2004

    0

    10

    20

    30

    40

    50

    60

    70

    0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

    Denervation (year)

    MinimumDiameter(m)

    FES Trained Normal Peripheral Denervation Central Lesion

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    MuscleMuscle excitabilityexcitability

    CaCa++++ releaserelease

    -- tttubulustubulus (1)(1)

    -- sarcoplasmaticsarcoplasmatic reticulumreticulum (2)(2)

    -- triadtriad (3)(3)

    1

    2

    3

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    A, Severe atrophic fiber. B, a triad in normally innervated muscle. C-D, following long-termdenervation the frequency of ECC units decreases and the morphology changes

    dramatically: Many junctions appear to be dyspedic (i.e. they lack RyRs).

    1515--monthmonth DenervatedDenervated Human Quadriceps MuscleHuman Quadriceps Muscle

    UgoCarraro, Applied MyologyLab, University of Padova

    N

    N

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    Conclusions

    1. Human skeletal muscle undergoes three phases during long-term

    denervation:

    i) Atrophy; ii) Lipodystrophy; iii) Fibrosis,

    2. Myofibers survive denervation much longer than generally accepted

    (years)

    3. After permanent lower-motoneuron lesion repeated cycles of myofiber

    death/regeneration contribute to long-term skeletal muscle tissue

    persistence

    4. Regenerated myofibers have higher excitability and strength than long-

    term denervated myofibers

    5. Long-term FES training reverts severe denervation atrophy and

    maintains trophism of regenerated myofibers

    Prof. Ugo Carraro - Applied Myology Lab -Padova [email protected]

    Long-term Denervated Human Muscle

    Lower Motor Neuron Lesion

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    Patient StudyPre- Clinical

    selection Evaluation September 03 May 04 End of study

    Wilhelminenspital 15 12 8 2 3 4

    Weier Hof 13 8 5 1 2 3

    Bad Hring 13 8 5 1 2 3

    Murnau 13 8 5 2 5 3

    Heidelberg 13 8 5 3 4 3

    Hamburg 13 8 5 0 2 3

    Tbingen 13 8 5 1 1 3

    Vicenza 1 2

    Island 2 3

    Piacenza/Lotta 1 1

    Patienten

    gesamt

    93 60 3 8 14 25 22

    Begin of

    study

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    PatientPatient StudyStudy

    55 womenwomen 43 a43 a 5.8 a denervated5.8 a denervated

    23 men

    36 a

    4.9 a denervated

    28 Patients with traumatic fracture betweenTh5 und L1

    (9 Th11, 13 Th12)

    0

    1

    2

    3

    4

    5

    6

    7

    8

    9

    10

    11

    up to 1,5 2 to 5 6 to 10 11 to 20 20 +

    yearsof denervation

    numberofpatients

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    A B

    x 40

    x 4500

    additional Rat Study

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    field distribution in the thigh

    AP-Excitation and Propagation

    Simulation of FESmuscle fiber

    tubular openings

    extra cellular

    intra cellular

    sarcomere

    myofibri l lssarkolemma

    transversal tubulus

    longitudinal tubulus

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    ColourColour--coded T2coded T2--maps of humanmaps of humanskeletal muscle before (left) andskeletal muscle before (left) and

    after (right) shortafter (right) short--term FES.term FES.

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    RISE Plenary Meeting - Iceland June 2005

    End of RISE - May 31, 2006

    132

    9th VIENNA INTERNATIONAL WORKSHOP on

    FUNCTIONAL ELECTRICAL STIMULATION

    Basics, Technology, Application

    19.Sept. - 22. Sept. 2007

    The conference location is in one the mostlovely regions of Austria named "Wachau",

    in the city of Krems/Danube

    http://2007.fesworkshop.org/

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