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SPASTICITYSPASTICITY POSTPOSTSTROKESTROKE

Sepideh Pooyania MD. FRCPCSepideh Pooyania MD. FRCPC

April 13, 2010April 13, 2010

ObjectivesObjectivesSpasticitySpasticityPost strokePost stroke

Case presentationCase presentation

DefinitionDefinition

PathophysiologyPathophysiology

Clinical presentationClinical presentation

EvaluationEvaluation

Management: NonManagement: Non--pharmacological,pharmacological,Pharmacological, SurgicalPharmacological, Surgical

Back to the caseBack to the case

Case 1Case 1 Mrs. A is a 67Mrs. A is a 67--yearyear--old woman who had a strokeold woman who had a stroke

18 months ago that resulted in spastic left18 months ago that resulted in spastic left

hemiplegiahemiplegia. She has no useful function in her left. She has no useful function in her left

upper extremity but is able to walk with a caneupper extremity but is able to walk with a cane

and ankle brace.and ankle brace.Over the last 6 months she has noticed aOver the last 6 months she has noticed a

gradually increasing tightness in her left leg, andgradually increasing tightness in her left leg, and

on several occasions she has tripped over theon several occasions she has tripped over the

left toes, which has resulted in minor falls. Herleft toes, which has resulted in minor falls. Her

husband is concerned that she may have ahusband is concerned that she may have a

serious fall, leading to bone injury.serious fall, leading to bone injury.


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STROKESTROKE

Within our aging population, stroke is anWithin our aging population, stroke is an

increasingly common and often disablingincreasingly common and often disablingcondition.condition.

It is the leading cause of adult neurologicdisability in Canada, with over 300,000 people(1% of the population) living with its effects.

Incidence doubles every 10 years after theage of 55

40% of stroke patients have moderate tosevere impairment.

Stroke survival has increased.Stroke survival has increased.

Stroke mortality fell an average of 7%Stroke mortality fell an average of 7%

(from 1990 to 1997)(from 1990 to 1997) and fell an average of 5.4% per year inand fell an average of 5.4% per year in

1998 to 20021998 to 2002

Yang Q,Yang Q, BottoBotto LD, Erickson JD,LD, Erickson JD, et alet al.. Improvement in strokeImprovement in strokemortality in Canada and the United States, 1990 to 2002.mortality in Canada and the United States, 1990 to 2002. CirculationCirculation2006 Mar 14;113(10):13352006 Mar 14;113(10):1335--4343..


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Stroke Related SpasticityStroke Related Spasticity

is a Large & Growingis a Large & Growing

ProblemProblem

The prevalence of spasticity amongThe prevalence of spasticity among

initially hospitalized stroke patients wasinitially hospitalized stroke patients was

%19 at 3 months and %38 at one year.%19 at 3 months and %38 at one year.

Watkins et al,Watkins et al, PrevelancePrevelance of spasticity post stroke, Clinical Rehab 2002, 16:of spasticity post stroke, Clinical Rehab 2002, 16:

515515--522522

SommerfeldSommerfeld et al,et al, SpasticitySpasticity after stroke. Its occurrence and associationafter stroke. Its occurrence and association

with motor impairment and activity.with motor impairment and activity.


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SpasticitySpasticity was associated with worse function.was associated with worse function.

To obtain an accurate picture of prevalence ofTo obtain an accurate picture of prevalence of

spasticityspasticity post stroke, one must assess armspost stroke, one must assess arms

and legs.and legs.

Watkins et al,Watkins et al, PrevelancePrevelance ofof spasticityspasticity post stroke, Clinical Rehabpost stroke, Clinical Rehab

2002, 16: 5152002, 16: 515--522522

SommerfeldSommerfeld et al,et al, SpasticitySpasticity after stroke. Its occurrence andafter stroke. Its occurrence and

association with motor impairment and activity.association with motor impairment and activity.

SpasticitySpasticity

A motor disorder characterized by aA motor disorder characterized by a velocityvelocity--dependentdependentincrease in the tonic stretchincrease in the tonic stretchreflexes (muscle tone) with exaggeratedreflexes (muscle tone) with exaggeratedphasicphasic stretch reflexes (tendon jerks, clonus)stretch reflexes (tendon jerks, clonus)resulting fromresulting from hyperexcitabilityhyperexcitability of the stretchof the stretchreflex and is one of the component of thereflex and is one of the component of theupper motor neuron syndrome.upper motor neuron syndrome.

Lance JW. Symposium synopsis. In: Feldman RG et al, eds. Spasticity: Disordered Motor Control.Chicago, Ill: Year Book Medical Publishers; 1980:487-489.

Copyright2003 Canadian Medical Association or its licensors

Satkunam, L. E. CMAJ 2003;169:1173-1179

Fig. 1: The stretch reflex arc


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HyperexcitabilityHyperexcitability of the stretch reflex canof the stretch reflex can

occur as a result of :occur as a result of :1) Alpha Motor neuron being1) Alpha Motor neuron being hyperexcitablehyperexcitable at the level ofat the level of

spinal cord segment.spinal cord segment.

2) Excessive afferent input from muscle spindle.2) Excessive afferent input from muscle spindle.


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Clinical presentations ?Clinical presentations ?

Clinical presentationsClinical presentations Signs and symptomsSigns and symptoms

StiffnessStiffness

ClonusClonus

PainPain

Flexor and extensor spasmsFlexor and extensor spasms DisfigurementDisfigurement

Impaired active functionImpaired active function Reach, graspReach, grasp

Gait, transfersGait, transfers

Impaired passive functionImpaired passive function Personal carePersonal care

PositioningPositioning


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Evaluation ofEvaluation ofSpasticitySpasticity

EvaluationEvaluation

Some of the factors to consider:Some of the factors to consider:

ChronicityChronicity: It may influence the goals and: It may influence the goals andtype of treatment to be administrated.type of treatment to be administrated.ChronicChronic sapsticitysapsticity may be more resistantmay be more resistantto treatment, specially if contractures haveto treatment, specially if contractures havedeveloped.developed.

SeveritySeverity: Mild: Mild SpasticitySpasticity may need lessmay need lessaggressive conservative measures.aggressive conservative measures.

Scope ofScope of SpasticitySpasticityMild

SpasticityChronic

SpasticitySevere

Spasticity

Courtesy of Nathaniel H. Mayer, MD, and Alberto Esquenazi, MD.


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DistributionDistribution: Focal versus global.: Focal versus global.

DistributionDistribution

Focal

Courtesy of Nathaniel H. Mayer, MD, and Alberto Esquenazi, MD.

Multifocal Regional

Spinal versus CerebralSpinal versus Cerebral::

OralOral antispasticityantispasticity meds tend to respondmeds tend to respond

better with spinalbetter with spinal spasticityspasticity..

CoCo--morbiditiesmorbidities: Poor motor control,: Poor motor control,

cognitive deficits may influence thecognitive deficits may influence the

decision to treat.decision to treat.

Availability of care and ongoingAvailability of care and ongoing

support.support.


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Clinical Scales for ratingClinical Scales for rating SpasticitySpasticity

Ashworth ScaleAshworth Scale Ordinal scale for measuring muscle tone; range 0 to 4Ordinal scale for measuring muscle tone; range 0 to 4

Modified Ashworth ScaleModified Ashworth Scale Defines the lower end of the scale by adding theDefines the lower end of the scale by adding the 1+1+ gradegrade

Tardieu ScaleTardieu Scale Interval scale for measuring stretch response reactions atInterval scale for measuring stretch response reactions at

specific velocitiesspecific velocities

Other ScalesOther Scales Spasm Frequency ScoreSpasm Frequency Score

Ordinal scale for measuring spasm frequency; ratesOrdinal scale for measuring spasm frequency; ratesfrequency of leg spasms/dayfrequency of leg spasms/day

Degree of Adductor Muscle ToneDegree of Adductor Muscle Tone Ordinal scale for measuring muscle tone in a specific muscleOrdinal scale for measuring muscle tone in a specific muscle

group;group; egeg, hip adductors for patients being treated for, hip adductors for patients being treated forreduction in the adducted leg positionreduction in the adducted leg position

The clinical assessment of spasticityThe clinical assessment of spasticity

incorporates descriptive scales ofincorporates descriptive scales of

resistance to passive movement, but theresistance to passive movement, but the

use of ause of a neurophysiologicalneurophysiological measure ofmeasure of

muscle activity levels has been advocated.muscle activity levels has been advocated.

Quantitative measures of spasticityQuantitative measures of spasticity

in postin post--stroke patientsstroke patients

Mechanical stretches of the wrist flexor musclesMechanical stretches of the wrist flexor muscles

of 53 postof 53 post--stroke patients were imposed bystroke patients were imposed by

means of a torque motor at constant speed.means of a torque motor at constant speed.

Patients were clinically studied using thePatients were clinically studied using theAshworth scale for spasticity and the MedicalAshworth scale for spasticity and the Medical

Research Council score for residual muscleResearch Council score for residual muscle

strength.strength.

PisanoPisano F, Quantitative measures of spasticity in postF, Quantitative measures of spasticity in post--strokestroke

patients.patients. ClinicClinic NeurophysiolNeurophysiol.. 2000 Jun;111(6):10152000 Jun;111(6):1015--22.22.


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TheThe neurophysiologicalneurophysiological measures weremeasures were

Hoffmann reflex latency,Hoffmann reflex latency, Hmax/MmaxHmax/Mmaxratio, stretch reflex threshold speedratio, stretch reflex threshold speed

(SRTS), stretch reflex (SR) latency and(SRTS), stretch reflex (SR) latency and

area, passive and total stiffness indices.area, passive and total stiffness indices.

PisanoPisano F, Quantitative measures ofF, Quantitative measures of spasticityspasticity in postin post--strokestroke


This EMGThis EMG--biomechanical technique allows anbiomechanical technique allows an

objective evaluation of changes in muscle toneobjective evaluation of changes in muscle tone

in postin post--stroke patients, providing easilystroke patients, providing easily

measurable, quantitative indices of musclemeasurable, quantitative indices of muscle

stiffness.stiffness.



The linear distribution of these measures isThe linear distribution of these measures is

particularly indicated for monitoring changesparticularly indicated for monitoring changes

induced by treatment. The apparatus seemsinduced by treatment. The apparatus seems

suitable to characterize neural stiffness, whilesuitable to characterize neural stiffness, whiledifficulties were found in isolating the passivedifficulties were found in isolating the passive

components, because of the occurrence of toniccomponents, because of the occurrence of tonic

EMG activity in most spastic patients.EMG activity in most spastic patients.




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Quantitative measurement ofQuantitative measurement of

post stroke spasticitypost stroke spasticity

Raw EMG data were notch filtered ( 50 HZ) andRaw EMG data were notch filtered ( 50 HZ) andthen smoothed with root mean square methods (then smoothed with root mean square methods (50 millisecond window width). For the analysis of50 millisecond window width). For the analysis ofspasticityspasticity, the average integrated EMG activity (, the average integrated EMG activity (referred to angular displacement) was calculatedreferred to angular displacement) was calculatedduring both lowduring both low--velocity and highvelocity and high--velocityvelocitypassive stretches by use ofpassive stretches by use of MathcadMathcad..

Cousins et al Quantitative Measurement ofCousins et al Quantitative Measurement of PoststrokePoststroke Spasticity andSpasticity andResponse to Treatment WithResponse to Treatment With BotulinumBotulinum Toxin: A 2Toxin: A 2--Patient Case Report.Patient Case Report.Physical therapy Volume 8, Number 7, June 2009.Physical therapy Volume 8, Number 7, June 2009.

TheThe neurophysiologicalneurophysiological measure was able tomeasure was able to

identify when muscle activity levels had beenidentify when muscle activity levels had been

reduced, but a reduction in muscle activity levelsreduced, but a reduction in muscle activity levels

did not always correspond with a reduction indid not always correspond with a reduction in

Modified Ashworth Scale scores.Modified Ashworth Scale scores.

Cousins et al Quantitative Measurement ofCousins et al Quantitative Measurement of PoststrokePoststroke SpasticitySpasticity and Responseand Response

to Treatment Withto Treatment With BotulinumBotulinum Toxin: A 2Toxin: A 2--Patient Case Report. PhysicalPatient Case Report. Physical

therapy Volume 8, Number 7, June 2009.therapy Volume 8, Number 7, June 2009.

Management ofManagement of



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Satkunam, L. E. CMAJ 2003;169:1173-1179

Elimination of noxious stimulationElimination of noxious stimulation

Urinary tract infectionsUrinary tract infections ConstipationConstipation Ingrown toe nailsIngrown toe nails Pressure ulcersPressure ulcers Poor fit in a brace or wheelchairPoor fit in a brace or wheelchair Tight clothingTight clothing Infections (e.g. pneumonia)Infections (e.g. pneumonia) Neuroleptic agentsNeuroleptic agents Fractures/dislocationsFractures/dislocations Heterotropic ossificationHeterotropic ossification Renal stonesRenal stones

SyrinxSyrinx in a SCIin a SCI Poor posture in bed/wheel chairPoor posture in bed/wheel chair


Satkunam, L. E. CMAJ 2003;169:1173-1179

Fig. 3: Treatment planning for patients with spasticity


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In post strokeIn post stroke spasticityspasticity, general, generalpharmacological treatments are limited bypharmacological treatments are limited byadverse events and lack of evidence ofadverse events and lack of evidence of

functional benefit.functional benefit.

The place of chemicalThe place of chemical neurolysisneurolysis with use ofwith use ofalcohol or phenol should be evaluated withalcohol or phenol should be evaluated withsurgicalsurgical neurotomyneurotomy andand botulinumbotulinum toxin therapy.toxin therapy.

YelnikYelnik , Pharmacology and upper limb post stroke, Pharmacology and upper limb post stroke spasticityspasticity ..

AnnalesAnnales dede readaptationareadaptationa et de medicine physique 47(2004)et de medicine physique 47(2004)

Drug treatments forDrug treatments for spasticityspasticity

A.P.A.P. YelnikYelnik et al,et al, Ann PhysAnn Phys RehabilRehabil Med.Med. 2009 Nov 32009 Nov 3

Drug treatments forDrug treatments for spasticityspasticity

A.P.A.P. YelnikYelnik et al,et al, Ann PhysAnn Phys RehabilRehabil Med.Med. 2009 Nov 32009 Nov 3


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NonNon--pharmacologicalpharmacological

The role of Physical andThe role of Physical and

occupational therapyoccupational therapy The choice of treatment is individualized to meet theThe choice of treatment is individualized to meet the

needs of the person withneeds of the person with spasticityspasticity..

StretchingStretching::It helps to maintain the full range of motion of the joint.It helps to maintain the full range of motion of the joint.

Prevents contractures.Prevents contractures.

To be effective, should be done regularly, usually once orTo be effective, should be done regularly, usually once or twice atwice aday.day.

StrengtheningStrengthening::

To restore the proper level of strength to affected muscles, soTo restore the proper level of strength to affected muscles, so as theas thetone is decreased through other treatments, the affected limb catone is decreased through other treatments, the affected limb ca n ben beused to its fullest potential.used to its fullest potential.

OrthosesOrthoses and castsand casts::

To allow the spastic limb to be maintained in aTo allow the spastic limb to be maintained in amore normal position and reduce contracture.more normal position and reduce contracture.

A cast is a temporary brace. Serial castingA cast is a temporary brace. Serial castinggradually stretches out a contracted limbgradually stretches out a contracted limb..

PositioningPositioning::

Improves comfort and reducesImproves comfort and reduces spasticityspasticity..

ColdCold ::It affects the firing rate of muscle spindle.It affects the firing rate of muscle spindle.


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Electrical stimulation:Electrical stimulation:

Used to stimulate a weak muscle to oppose the activityUsed to stimulate a weak muscle to oppose the activityof a stronger spastic ones.of a stronger spastic ones.

Biofeedback:Biofeedback:Using biofeedback the person withUsing biofeedback the person with spasticityspasticity may be ablemay be able

to train himself to reduce muscle tone consciously.to train himself to reduce muscle tone consciously.

Pharmacotherapy inPharmacotherapy in SpasticitySpasticity

AntispasticAntispastic agentsagents

Muscle weakness,Muscle weakness,

rarerare hapatotoxicityhapatotoxicity

dizzinessdizziness

100 mg100 mg

QIDQID

25 mg25 mg

/day/day

reduces calciumreduces calcium

flux across theflux across the

sarcoplasmicsarcoplasmic

reticulum of skeletalreticulum of skeletal

musclemuscle

DantroleneDantrolene

SodiumSodium

Dizziness,Dizziness,

DrowsinessDrowsiness

Liver dysfunctionLiver dysfunction

36 mg36 mg

/ day/ day

22--4 mg4 mg

QhsQhs

Central alpha 2Central alpha 2

agonist,agonist,

imadazolineimadazoline

receptor inhibitorreceptor inhibitor

TizanidineTizanidine

Sedation,Sedation,

CognitiveCognitive

dysfunctiondysfunction

50 mg50 mg

/ day/ day

5 mg5 mg

QhsQhs

GABA A receptorGABA A receptor

blockerblocker

BenzodiazepinsBenzodiazepins

Sedation, seizures,Sedation, seizures,

confusion, fatigue,confusion, fatigue,

ataxia,hallucinationsataxia,hallucinations

80mg80mg

/day/day

5mg5mg

TIDTID

GABA B agonistGABA B agonist

Pre and PostPre and Post

synapticsynaptic

BaclofenBaclofen

Side effectsSide effectsMax.Max.

dosedose

StartingStarting

dosedoseMechanismMechanism

of actionof action


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othersothers

GabapentinGabapentinis emerging as a useful alternativeis emerging as a useful alternative

inin spasticityspasticity management. Patients may requiremanagement. Patients may requirehigher doses of this drug (2700higher doses of this drug (27003200 mg/d).3200 mg/d).

It reducesIt reduces spasticityspasticity in MS without the sidein MS without the side

effects of worsening concentration and fatigue.effects of worsening concentration and fatigue.

Cutter et al,Cutter et al, GabapentinGabapentin effect oneffect on spaspticityspaspticity in Multiple sclerosis .in Multiple sclerosis .

Arch Phys MedArch Phys Med RehabilRehabil ,2000 Feb; 81(2) 164,2000 Feb; 81(2) 164--99

FampridineFampridine--SRSR(sustained(sustained--release 4release 4--aminopyridine) is a potassiumaminopyridine) is a potassium--channelchannelblocker. Some studies has shown it helpfulblocker. Some studies has shown it helpfulin managingin managing spasticityspasticity in patients within patients withspinal cord injuries.spinal cord injuries.

Potter PJ, et al. Randomized doublePotter PJ, et al. Randomized double--blind crossover trial ofblind crossover trial of fampridinefampridine--SR (sustainedSR (sustainedrelease 4release 4--aminopyridine) in patients with incomplete spinal cord injury.aminopyridine) in patients with incomplete spinal cord injury. JJ

NeurotraumaNeurotrauma1998;15(10):8371998;15(10):837--4949

CannabinoidsCannabinoids

DeltaDelta--99--tetrahydrocannabinol, the activetetrahydrocannabinol, the active

ingredient in cannabis, has also beeningredient in cannabis, has also been

shown to be useful inshown to be useful in spasticityspasticity; however,; however,

evidence of its efficacy compared withevidence of its efficacy compared withother medications requires evaluation.other medications requires evaluation.

PetroPetro DJ. Treatment of humanDJ. Treatment of human spasticityspasticity with delta 9with delta 9--tetrahydrocannabinol.tetrahydrocannabinol.JJ

ClinClinPharmacolPharmacol1981;21(81981;21(8--9 Suppl):413S9 Suppl):413S--416S416S..


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Chronic infusion of medications into theChronic infusion of medications into the

intrathecalintrathecal spacespace

InjectableInjectable pharmacologic therapypharmacologic therapy

IntratechalIntratechal BaclofenBaclofen::administration results in a 100administration results in a 100--fold increase in potencyfold increase in potencycompared with the oral treatment.compared with the oral treatment.

Although this form ofAlthough this form of antispasticityantispasticity therapy is highlytherapy is highlyeffective, its use is limited by the invasive nature of theeffective, its use is limited by the invasive nature of the

treatment and the cost of the implantable devices.treatment and the cost of the implantable devices.

IntrathecalIntrathecal morphine (morphine (InfumorphInfumorph) and) and midazolammidazolam(Versed) :(Versed) :effectiveeffective antispasticityantispasticity as well as analgesic treatmentas well as analgesic treatment

tolerance,tolerance, pruritispruritis, nausea, hypotension, urinary, nausea, hypotension, urinaryretention, and respiratory depression can occur with anretention, and respiratory depression can occur with an

intrathecalintrathecal morphine bolus dose as low as 0.4 mgmorphine bolus dose as low as 0.4 mg

Initially, ITB was considered only in conditionsInitially, ITB was considered only in conditionscharacterized by severe multicharacterized by severe multi--limb spasticlimb spastichypertoniahypertonia in nonin non--ambulatory individuals. Lately,ambulatory individuals. Lately,ITB is used in persons with stroke who canITB is used in persons with stroke who canambulate, with the intent of further improvingambulate, with the intent of further improvingwalking ability. Early clinical experience andwalking ability. Early clinical experience and

evidence suggest that when used in theevidence suggest that when used in theappropriate patient, ITB is efficient and safe inappropriate patient, ITB is efficient and safe inmanaging postmanaging post--strokestroke hypertoniahypertonia in individualsin individualsof various functional levels.of various functional levels.

Francisco GFrancisco GEE.. IntrathecalIntrathecal baclofenbaclofen in the management of postin the management of post--strokestroke hypertoniahypertonia: current applications and future directions: current applications and future directionsstrokestroke RehabilRehabil 2006.2006.


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Clinical issues unique to strokeClinical issues unique to stroke

patients in relation to ITBpatients in relation to ITB 1) Anticoagulation1) Anticoagulation

2) Screening: Should be performed based on2) Screening: Should be performed based onfunction difference ( gait change) or evaluationfunction difference ( gait change) or evaluationby caregiver for hygiene and other passiveby caregiver for hygiene and other passivefunctions rather than Ashworth scale.functions rather than Ashworth scale.

3) Seizure:3) Seizure: SzSz are known to occur during ITBare known to occur during ITBscreening and after pump implantation. This riskscreening and after pump implantation. This riskshould be discussed with the patient.should be discussed with the patient.

Francisco GFrancisco GEE.. IntrathecalIntrathecal baclofenbaclofen in the management of postin the management of post--strokestroke hypertoniahypertonia: current applications and future directions.: current applications and future directions.strokestroke RehabilRehabil 20062006

4) Bowel and bladder: Some studies have4) Bowel and bladder: Some studies haveshown changes in GI motility following ITBshown changes in GI motility following ITBimplantation.implantation. PremorbidPremorbid bowel or bladderbowel or bladderdysfunction may be aggravated by ITB.dysfunction may be aggravated by ITB.

5) MRI scans: may be an issue in5) MRI scans: may be an issue in SynchoMedSynchoMed IIIIpump model .pump model .


Guidelines for ITB in Post strokeGuidelines for ITB in Post stroke


1) Preferred candidates are the patients who did1) Preferred candidates are the patients who didnot respond adequately to the other treatment ornot respond adequately to the other treatment ordid not tolerate adverse effects of otherdid not tolerate adverse effects of othertherapies and are motivated to participate intherapies and are motivated to participate inlong term ITB management.long term ITB management.

2) The optimal dose can be defined as the dose2) The optimal dose can be defined as the dosethat helps achieve the treatment goals.that helps achieve the treatment goals.



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Local Anesthetics andLocal Anesthetics and

ChemodenervatingChemodenervating AgentsAgents Local anestheticsLocal anesthetics

LidocaineLidocaine BupivacaineBupivacaine

EtidocaineEtidocaine

ShortShort--durationduration

diagnostic blockdiagnostic block(2 to 8 hours)(2 to 8 hours)

NeurolysisNeurolysis

PhenolPhenol

AlcoholAlcohol

NeuromuscularNeuromuscularjunction blockadejunction blockade

BotulinumBotulinum NeurotoxinNeurotoxinType AType A

BotulinumBotulinum NeurotoxinNeurotoxinType BType B

LongLong--duration effectduration effect(3 to 6 months)(3 to 6 months)

GraciesJ-M et al.Muscle Nerve. 1997;20(suppl 6):S61-S91.Goodman LS et al. Goodman & Gilmans The Pharmacological Basis of Therapeutics. 9th ed.

New York, NY: McGraw-Hill; 1996;331-347.

ReinjectionReinjection more difficultmore difficultyesyesRepeated use,Repeated use,

long term safetylong term safety

recordrecord

22--8 months, 36 months in some8 months, 36 months in some

referencesreferences33--6 months6 monthsDuration of benefitDuration of benefit

NeededNeededNot neededNot neededMotor pointMotor point

injection techniqueinjection technique

Volume dependentVolume dependentNeedle onlyNeedle onlyPain duringPain during

injectioninjection

NonselectiveNonselective neurolysisneurolysisReversible muscleReversible muscle

relaxationrelaxation

Effects on tissuesEffects on tissues

nonoyesyesAdjustable dilution toAdjustable dilution tomaximize diffusionmaximize diffusion

Potential edema , necrosisPotential edema , necrosisNo irritationNo irritationLocal toxicityLocal toxicity

Immediate anesthetic effect,Immediate anesthetic effect,

NeurolysisNeurolysis at 48at 48--72 hours72 hours11--5 days, peak at days5 days, peak at days

2121--2828OnsetOnset

Depends on number of motor branchesDepends on number of motor branchesDose dependentDose dependentTitration effectTitration effect

PhenolPhenolBoNTBoNT--AA


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BotulinumBotulinum toxin type A injections havetoxin type A injections have

been used to block the final commonbeen used to block the final commonpathway at the neuromuscular junction.pathway at the neuromuscular junction.

It affects the neuromuscular junction throughIt affects the neuromuscular junction throughbinding, internalization and inhibition of ACHbinding, internalization and inhibition of ACHrelease.release.

SimpsonSimpson DMetDMet al.al. BotulinumBotulinum toxin type A in the treatment of upper extremitytoxin type A in the treatment of upper extremityspasticityspasticity: a randomized, double: a randomized, double--blind, placeboblind, placebo--controlled trial.controlled trial. NeurologyNeurology1996;46(5):13061996;46(5):1306--10.10.

Simpson DM. Clinical trials ofSimpson DM. Clinical trials of botulinumbotulinum toxin in the treatment oftoxin in the treatment of spasticityspasticity..Muscle NerveMuscle NerveSupplSuppl1997;6:S1691997;6:S169--7575

Some studies showed central effects ofSome studies showed central effects of

botulinumbotulinum toxin in human.toxin in human.

These effects may include decreasedThese effects may include decreased RenshawRenshaw

inhibition and increased preinhibition and increased pre--synaptic inhibitionsynaptic inhibition

exerted on theexerted on the motoneuronsmotoneurons supplying thesupplying the

injected muscle and reduction of their overallinjected muscle and reduction of their overall

excitability.excitability.

GracisGracis et al, The role ofet al, The role of botulinumbotulinum toxin injection in the management oftoxin injection in the management of

musclemuscle overactivityoveractivity of the lower limb.of the lower limb. DisabDisab and Rehab ,Dec 2007,and Rehab ,Dec 2007,

After about 3 months theAfter about 3 months the presynapticpresynaptic

terminal sprouts and reterminal sprouts and re--establishes itsestablishes its

communication with the muscle fibercommunication with the muscle fiber

(muscle tone returns). Thus,(muscle tone returns). Thus, botulinumbotulinumtoxin type A takes effect about 1 weektoxin type A takes effect about 1 week

after injection and lasts about 3 months,after injection and lasts about 3 months,

after which muscle tone returns toafter which muscle tone returns to

baseline levelsbaseline levels


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Side effects are minimal.Side effects are minimal.

Injection related: Local discomfort, Bruising,Injection related: Local discomfort, Bruising,infection.infection.

Skin reactionSkin reaction

Hypersensitivity to BTXHypersensitivity to BTX--A, rarely reportedA, rarely reportedanaphylaxis,anaphylaxis, urticariaurticaria, soft tissue edema, and, soft tissue edema, anddyspneadyspnea..

EMG changesEMG changes

Diminished type II fiber size in muscles distal toDiminished type II fiber size in muscles distal toinjection siteinjection site

Isolated reports of :Isolated reports of :

precipitated gall bladder attack( likely due toprecipitated gall bladder attack( likely due toautonomic effect of toxin)autonomic effect of toxin)

urinary incontinenceurinary incontinence

necrotizingnecrotizing fascitisfascitis

botulism like syndromebotulism like syndrome

brachialbrachial plexopathyplexopathy

hospitalization and death ( under investigationhospitalization and death ( under investigationby FDA and health Canada)by FDA and health Canada)

Mild long term effects: Change in fiber sizeMild long term effects: Change in fiber size

and EMG abnormalitiesand EMG abnormalities

Caution to use in persons with motorCaution to use in persons with motor

neuropathies, ALS, neuromuscularneuropathies, ALS, neuromuscular

junction disorders.junction disorders.


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BotuliniumBotulinium toxin in the spastic lowertoxin in the spastic lower

extremity has been shown to reduceextremity has been shown to reducespasticity but not necessarily function.spasticity but not necessarily function.

Teasell et al, 2008, SREBR( 11Teasell et al, 2008, SREBR( 11 thth edition)edition)

There is strong evidence that treatment withThere is strong evidence that treatment with

botulinumbotulinum toxin either alone or in combinationtoxin either alone or in combination

with therapy significantly decreases spasticity inwith therapy significantly decreases spasticity in

the upper extremity.the upper extremity.

In stroke survivors. However it is not clear if theIn stroke survivors. However it is not clear if the

improvement is sustained, nor is there strongimprovement is sustained, nor is there strong

evidence that they are associated with improvedevidence that they are associated with improved

function and quality of life.function and quality of life.

Teasell et al, 2008, SREBR( 11Teasell et al, 2008, SREBR( 11 thth edition)edition)

Some of the common indications for use ofSome of the common indications for use of

botulinumbotulinum toxin in spastic UEtoxin in spastic UE

Impairs ability toImpairs ability to

orient handorient handPr. quadratesPr. quadrates

PrPr teresteres

PronatedPronated ForearmForearm

Dressing difficultyDressing difficulty

Skin breakdownSkin breakdown

BrachioradialisBrachioradialis

BicepsBiceps

BrachialisBrachialis

Flexed elbowFlexed elbow

RestrictedRestricted

reaching targetsreaching targets

Frozen shoulderFrozen shoulderDressing problemDressing problem

PecPec MajorMajor

LatsLats.. DorsiDorsi

TeresTeres MajorMajorSubscapularisSubscapularis

Adducted/Adducted/

internally rotatedinternally rotated

ShoulderShoulder

Functional impactFunctional impactMuscles involvedMuscles involved


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Thumb unable toThumb unable to

function duringfunction during

key graspkey grasp

AddAdd PollicisPollicis

Flex Poll LongFlex Poll Long

ThenarThenar groupgroup

Thumb inThumb in

palmpalm

deformitydeformity

Unable to washUnable to wash

palm,palm,

Skin macerationSkin maceration

FDPFDP

FDSFDS

ClenchedClenched

FistFist

Difficulty inDifficulty in

dressing,dressing,

CTS may occurCTS may occur

FCR,FCUFCR,FCUFlexed WristFlexed Wrist

Some of the common indications for use ofSome of the common indications for use of

botulinumbotulinum toxin in spastic LEtoxin in spastic LE

Limited limbLimited limb

advancementadvancement

Short step lengthShort step length

HamstringsHamstrings

GastrocnemiusGastrocnemius

Flexed kneeFlexed knee

IliopsoasIliopsoas

HamstringsHamstrings

Flexed hipFlexed hip

Scissoring,Scissoring,

Difficulty inDifficulty in

hygiene,cathhygiene,cath,,

dressing, mobilitydressing, mobility

Add Long/Add Long/Brv/magBrv/mag

GracillicGracillic

PectineusPectineus

Add thighsAdd thighs

Functional impactFunctional impactMuscle involvedMuscle involved

Long or short toeLong or short toe

flexorsflexorsToe clawing orToe clawing or

curlingcurling

Inability to wearInability to wear

shoe, painshoe, painEHLEHLStriated toeStriated toe

Forefoot contact inForefoot contact instance gait,stance gait,

Weight on lat footWeight on lat foot

GastrocGastroc//SoleusSoleusTibTib Post, EHL,Post, EHL,

PerPer LngLng, Long toe flex, Long toe flex

EquinovarusEquinovarusfootfoot

Toe drag,Toe drag,

Trip and fallTrip and fall

GluGlu Max.Max.

QuadricepsQuadriceps

IlipsoasIlipsoas

Extended kneeExtended knee


24/282

Efficacy and Safety ofEfficacy and Safety of BotulinumBotulinum

Neurotoxin NT 201 inNeurotoxin NT 201 in PoststrokePoststroke UpperUpper

LimbLimb SpasticitySpasticity

KanovskKanovsk et al,et al, ClinClin NeuropharmacolNeuropharmacol.. 20092009

SepSep--Oct;32(5):259Oct;32(5):259--6565

Methods: One 148 patients with anMethods: One 148 patients with anAshworth Scale score of 2 or higher forAshworth Scale score of 2 or higher forwrist and finger flexors and at leastwrist and finger flexors and at leastmoderate disability in their principalmoderate disability in their principaltherapeutic target of the Disabilitytherapeutic target of the DisabilityAssessment Scale were treated either withAssessment Scale were treated either withNT 201 (median, 320 U) or placebo andNT 201 (median, 320 U) or placebo andfollowed up for up to 20 weeks.followed up for up to 20 weeks.

..


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Results: A significantly higher proportion ofResults: A significantly higher proportion of

patients treated with NT 201 werepatients treated with NT 201 wereresponders (improvement of >=1 point inresponders (improvement of >=1 point in

the Ashworth Scale score), as observed inthe Ashworth Scale score), as observed in

comparison to placebo 4 weeks aftercomparison to placebo 4 weeks after

treatment in wrist flexors (odds ratio, 3.97;treatment in wrist flexors (odds ratio, 3.97;

95% confidence interval, 1.995% confidence interval, 1.9--8.3; P


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Muscle Nerve.Muscle Nerve. 2009 Sep;40(3):3742009 Sep;40(3):374--80.80.

Assay of diffusion of differentAssay of diffusion of differentbotulinumbotulinum neurotoxin type aneurotoxin type a

formulations injected in the mouse leg.formulations injected in the mouse leg.

CarliCarli LL,, MontecuccoMontecucco CC,, RossettoRossetto OO

They assessed the extent of diffusion ofThey assessed the extent of diffusion of

three commercial preparations ofthree commercial preparations of BoNTBoNT/A:/A:

BotoxBotox ((AllerganAllergan),), DysportDysport ((IpsenIpsen), and), and

XeominXeomin ((MerzMerz Pharmaceuticals) using aPharmaceuticals) using a

sensitive test based on neural cellsensitive test based on neural cell

adhesion molecule (Nadhesion molecule (N--CAM) expression inCAM) expression in

muscle.muscle.

This allows fine monitoring of theThis allows fine monitoring of the

functional diffusion of this toxin. Thefunctional diffusion of this toxin. The

results indicate that there is no significantresults indicate that there is no significant

difference betweendifference between BotoxBotox,, DysportDysport, and, andXeominXeomin with respect to diffusion intowith respect to diffusion into

adjacent muscles in the mouse leg.adjacent muscles in the mouse leg.


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SURGICAL INTERVENTIONSSURGICAL INTERVENTIONS

Common goals of surgery are usually toCommon goals of surgery are usually to

increase mobility,increase mobility,

decrease the use of external aids,decrease the use of external aids,

correct or prevent deformity,correct or prevent deformity,

and ultimately maximize function.and ultimately maximize function.

Musculoskeletal compensatory techniquesMusculoskeletal compensatory techniques

used by the orthopedic surgeons includeused by the orthopedic surgeons include

tendon lengthening, muscletendon lengthening, muscle--tendontendon

transfer (e.g. the split anteriortransfer (e.g. the split anterior tibialtibial

transfer), contracture release,transfer), contracture release,

capsulotomycapsulotomy,, osteotomyosteotomy, resection, resection

arthroplastyarthroplasty,, arthrodesisarthrodesis,, epiphyseodesisepiphyseodesis,,

ankle fusion, and spine fusionankle fusion, and spine fusion

TheThe neuroablativeneuroablative techniques used by thetechniques used by the

neurosurgeons involve the interruption ofneurosurgeons involve the interruption of

the spinal reflex arc bythe spinal reflex arc by neurectomyneurectomy,,

neurotomyneurotomy,, rhizotomyrhizotomy, dorsal root entry, dorsal root entryzone lesion, andzone lesion, and myelotomymyelotomy..

Other procedures includeOther procedures include cordotomycordotomy,,

cordectomycordectomy, implantation of stimulators, or, implantation of stimulators, or

drug infusion devicesdrug infusion devices


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CASE 1CASE 1

Mrs. A is experiencing a gradual increaseMrs. A is experiencing a gradual increase

in spasticity, confined to her left lowerin spasticity, confined to her left lowerextremity. The patient's main functionalextremity. The patient's main functional

problem is increased plantar flexion, whichproblem is increased plantar flexion, which

is causing her toes to drag and resulting inis causing her toes to drag and resulting in

falls. Oral medication therapy is not thefalls. Oral medication therapy is not the

first choice, as it tends to be less effectivefirst choice, as it tends to be less effective

in treating cerebral causes of spasticity.in treating cerebral causes of spasticity.

Mrs. A is a good candidate for focalMrs. A is a good candidate for focal

treatment of spasticity withtreatment of spasticity with botulinumbotulinum toxintoxin

type A injections into her plantar flexors. Iftype A injections into her plantar flexors. If

she responds well to the first set ofshe responds well to the first set of

injections, she will require repeat injectionsinjections, she will require repeat injections

every 3every 34 months to maintain safe4 months to maintain safe

ambulation. Referral to a physiatrist for theambulation. Referral to a physiatrist for the

injections would be most appropriate.injections would be most appropriate.

THANK YOUTHANK YOU

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