Spasticity Mechanisms and Management

SPASTICITYMECHANISMS AND MANAGEMENT

Allison Oki, MDOctober 11, 2014

Objectives

Video – Development/Basic Mechanics of Gait

Overview Motor Disorders, Hypertonia, Spasticity

Pathophysiology Cerebral Palsy UMN syndrome - Consequences of Spasticity Medical Management Neurosurgical Interventions: ITB and SDR

Development

Bipeds center of mass (COM) level of S2

Inherently unstable

Continual postural adjustment to maintain COM within base of support

Sit 6 mo Crawl 9 mo Independent

walking 12 mo Gait maturation

at 6.5 years

Motor System

Motor system hierarchical

chain of command

extends from the cortical centers down to the nerves that innervate the muscles

Components of Motor System Supplementary

motor cortex Cortical motor

control centers Basal Ganglia Cerebellum Brainstem Motor

nuclei Central pattern

Generators

Motor Pyramid

Pyramidal and Extrapyramidal Upper Motor NeuronsPyramidal

direct corticospinal tractFine coordination motion

Extrapyramidalindirect cortco-bulbo-spinal tracts (vestibular/ reticular tracts)Balance, posture, coordination

Central Pattern Generators

Located in the SC generate a consistent specific movement pattern

Analogy – piano key and note, central pattern generator when stimulated produces the same movement pattern

Anterior horn of SC Pyramidal – lateral Extrapyramidal - medial

Motor Disorders

Disorders of multiple neural components basal ganglia cerebellum cerebral cortex brainstem descending spinal tracts

Hypertonia is a component of many motor disorders Spasticity, dystonia and rigidity

Motor Disorders

Pyramidal cortical projections to

the brainstem (corticobulbar)

SC (corticospinal)

clinically: weakness and increased stretch reflexes

“pyramidal”“upper motor neuron”

weakness

Extra-pyramidal Injury to BG,

cerebellum or non-primary motor cortical areas

clinically: abnormal motor control without weakness or changes in spinal reflexes

What is spasticity?

“Spasticity is a motor disorder characterized by a velocity dependent increase in tonic stretch reflexes, with exaggerated tendon jerks resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome” Lance 1980

Resistance to stretch increases with increasing speed and varies with the direction of the joint movement

Rapid rise in resistance to stretch above a threshold speed or joint angle

Sanger et al, Classification and Definition of Disorders Causing Hypertonia in Childhood, Pediatrics 2003

Hypothetical Mechanism

Pathophysiology of SpasticityTheories

Imbalance between excitatory and inhibitory impulses to the alpha motor neuron in the spinal cord

Due to a loss of descending inhibitory input to the alpha motor neuron due to injury to the cortical spinal tracts

DescendingInhibition

SensoryExcitation

Cerebral Palsy: Definition

Primary abnormality of movement and posture secondary to a nonprogressive lesion of a developing brain

Represents a group of disorders rather than a single entity

Abnormal motor control and tone in the absence of underlying progressive disease

Epidemiology CP Most common motor

disorder of childhood 3.6/1000 school age

children Higher survival rate

of premature infants

Etiology – majority of term infants do not have an identifiable cause

Causative factors Prematurity Infection Inflammation Coagulopathy

Greatest RF prematurity <37wks Incidence highest in

the very premature

Pathology CP >80% abnormal

neuroimaging PVL – white matter

near the lateral ventricles

Premature 90% vs term 20%

IVH Corticospinal tract

fibers to LE are medial to UE → spastic diparesis

Common Gait Deviations CP

Location Impairment Potential Effects

Hip ↑ adductor tone Scissoring, difficulty advancing leg in swing

↑ iliopsoas tone Anterior pelvic tilt, lumbar lordosis, crouched gait

↑ femoral anteversion Intoeing, false genuvalgus, compensatory external tibial torsion

Abductor weakness Trendelenberg gait

Knee ↓ hamstring ROM Crouched gait

Hamstring/Quad co-contraction Stiff-kneed gait

Ankle ↑ gastroc tone/contracture Toe walking, genu recurvatum, difficulty clearing foot during swing

Internal tibial torsion Intoeing, ineffective toe-off

External tibial torsion Out-toeing, ineffective toe-off

Varus ↑ supination in stance or swing

Valgus ↑ pronation in stance or swing, midfoot breakdown

Upper Motor Neuron Syndrome UMNS

Positive

Spasticity Spastic Dystonia Clonus/ hyper-reflexia Reflex flexor and

extensor spasms Associated reactions

Negative

Weakness Fatigue Loss of selective

motor control Sensory deficits Incoordination Poor balance

Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron Syndrome, Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron Syndrome, 2008

David Scrutton et al, Management of the Motor Disorders of Children with Cerebral Palsy, H. Kerr Graham, Ch.8 Mechanisms of Deformity

UMNS

UMNS disability = positive + negative + rheologic properties

Rheologic properties: viscoelastic properties of the muscle and other soft tissues

Structural changes occur in the muscle cells causing intrinsic muscle stiffness (Olsen et al. 2006)

Combined effects of all signs → chronic unidirectional postures and movements that are generated by a net balance of muscle torques exerted across the involved joints


UMNS

Torque – force generated by muscle acting through a bony lever arm →rotational movement

Normal movement is bi- or multi-directional, agonist and antagonist torques create motion

UMNS → net unidirectional movements (positive signs) often persist as postures because voluntary bi- or multi-directional movement is impaired (negative signs) → chronic effects on soft tissue, joint structures and bone


Why is spasticity important?

Clinically diagnosed and treated

Musculoskeletal and neurologic exam Tone, reflexes, strength,

coordination

Spasticity →

significant disability

ADLs Seating Comfort Contracture Loss of ROM Negative impact on

function Bone deformity Pain Skin Hygiene Ability to provide cares

Allison Brashear, Elie Elovic, Spasticity Diagnosis and Management, 2010, Ch 1.1 Why is spasticity important?

Secondary effects of SpasticityMay effect function and long-term outcome Persistent muscle imbalance → muscle/tendon

contractures → joint or bone deformities weak antagonists muscles → require passive

stretch for a minimum of 6 out of 24 hrs to maintain muscle length (Tardieu 1988) and to avoid development of a fixed contracture (Eames 1999)

Abnormal forces across joints → prolonged abnormal posture, increase energy expenditure, impair function, and negatively affect both the caregiver’s and patient’s QOLL. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press, p.40

Abnormal Forces across Joints Ankle and subtalar → fixed equinus, equinovarus

or equinovalgus hindfoot deformities Adductor and iliospoas spasticity → hip

subluxation and dislocation Once a critical degree (50%) of hip subluxation is

present, dislocation is inevitable unless intervention occurs (Reimers 1987)

The resultant pelvic obliquity compromises sitting balance → chronic pain

L. Andrew Koman, et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press

Bone Deformity

Abnormal muscle forces act on a growing skeleton

Hips and spine → essential in weight bearing and positioning

Femur → muscle and gravity loading forces during growth

Muscle forces in CP → increased anteversion of femoral neck

hip flexion, adduction and internal rotation of the femur → femoral head in a superoposterolateral direction, out of the acetabulum → coxa valgus: deformation of the femoral head and shallow acetabulum

Randall L. Braddom, Physical Medicine and Rehabilitation, 3rd Edition, Chapter 54: Cerebral Palsy, p.1249

Hip Dysplasia

Hip Subluxation

James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009, Kevin Walker, Chapter 3.4 Radiographic Evaluation of the Patient with Cerebral Palsy

Bone Deformity

Asymmetric muscle pull → deformity of the spine Kyphosis, scoliosis, rotational deformities

Comfort Tone Sitting Standing alignment Balance

Severe → respiratory function compromise


Goals of Spasticity Management Decrease spasticity Improve functional ability and independence Decrease pain associated with spasticity Prevent or decrease incidence of contractures Prevent bony deformity Improve ambulation, mobility, function Facilitate hygiene Ease rehabilitation procedures Improve ease of caregiving

Traditional Step-Ladder Approach to Management of Spasticity

Neurosurgical procedures

Orthopedic procedures

Neurolysis

Oral medications

Rehabilitation Therapy

Remove noxious stimuli

Interdisciplinary team

Patient and family Neurologist Neurosurgeon Occupational therapist Physical Therapist Physiatrist Orthopedic Surgeon Primary care physician

Rehabilitation Therapy

Stretching Weight bearing Inhibitory casting Bracing Strengthening

EMG biofeedback Electrical

stimulation Positioning

Oral Pharmacologic Management

Baclofen Diazepam Clonidine Tizanidine Dantrolene

Sodium

Allison Brashear, Elie Elovic, Spasticity Diagnosis and Treatment, 2010, Ch.15 Pharmacologic Management of Spasticity: Oral Medications

Systemic medications: limitations

Sedation Hypotension Confusion Weakness Nausea For generalized rather than focal

spasticity

Baclofen – GABA analog

Binds to presynaptic GABA-B receptors in the brainstem, dorsal horn of SC and other CNS sites

Depresses both monosynaptic and polysynaptic reflexes by blocking the release of NTS

Inhibition of gamma motor neuron activity to the muscle spindle

Because these reflexes facilitate spastic hypertonia, inhibition reduces the overactive reflex response to muscle stretching or cutaneous stimulation

Baclofen

Dystonia Baclofen some

supraspinal activity that may contribute to clinical side effects

Orally – relatively low concentrations in CSF

Side Effects Central SE – drowsiness,

confusion, attentional disturbances

Others – hallucinations, ataxia, lethargy, sedation and memory impairment

Lower seizure threshold Sudden withdrawal →

seizures, hallucinations

Baclofen

Pharmokinetics Relatively well

absorbed, peak effect 2 hrs, t ½ 2.5-4 hours

Excreted unchanged by kidney, 6-15% metabolized in the liver

Schedule 3x a day due to short half life

Considerations: Cerebral lesions more

prone to SE DOC for spinal causes

Diazepam - Benzodiazepine

MOA: does not directly bind to GABA receptors

Promotes the release of GABA from GABA-A neurons

Enhanced pre-synaptic inhibition, likely why useful in epilepsy

All CNS depressants Anti-anxiety, hypnotic,

anti-spasticity and anti-epileptic

Side Effects: Sedation and lethargy Impair coordination and

prolonged use can lead to physical/psych dependence

Effective doses vary considerably, upper doses primarily limited by SE

Rapid withdrawal → irritability, tremors, nausea and seizures

Neuromuscular Blockade

Goal: Restore balance between agonist and antagonist muscles

Why is this important? Shortened over contracted muscles → decreased muscle

growth despite linear bone growth → antagonist muscles become over-lengthened → weakness and imbalance

Contractures → bone and joint deformity → impaired function Early intervention – life long patterns of mobility Blockade of agonist muscles → improved stretch, ROM,

increased resting length, antagonist muscles can continue activity and strengthening

Ann H. Tilton, Injectable Neuromuscular blockade in the treatment of Spasticity and Movement disorders, Journal of Child Neurology, 2003:18:S50-66

Botulinum Toxin A in the management of spasticity related to CPBTX-A is currently used for children of all

ages with CP for spasticity management as determined by the practitioner

This use is off-label in the US Dysport (British formulation), approved in

UK and EU for “treatment of dynamic equinus foot deformity due to spasticity in ambulant pediatric CP patients, two years of age or older…UE spasticity post-stroke, spasmodic torticollis, blepharospasm, and hemifacial spasm”L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press

Neuromuscular Junction

NMJ – connection between the peripheral nerve and muscle fibers

Signals from the motor neuron are transmitted by the release of Ach from presynaptic vesicles

Ach crosses the synaptic cleft and attaches to post-synaptic receptors → muscle contraction

L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press

Neuromuscular Junction

Chemodenervation, The Role of Chemodenervation in the Management of Hyperkinetic Movement Disorders, We Move 2007

Selected Literature Review

1990 several studies supported the safety and efficacy of therapeutic BTX in children with CP

Goals: decreasing spastic equinus, improving crouch knee gait, decreasing hip flexion, improving hand use

Studies demonstrated changes in muscle tone (reduction in spasticity scores), improvements in ROM, and kinematic changes in gait analysis

However, functional benefit was not demonstrated in blind, randomized controlled trials

2013 Systematic review of interventions for children with CP: state of the evidence – BTX was recommended for spasticity reduction and improved walking

Iona Novak et Al, A systematic Review of interventions for children with cerebral palsy: state of the evidence, Developmental Medicine & Child Neurology, 2013

Selected Literature Review

Why is it so difficult to show functional benefit? Weakness and poor coordination co-exist in

persons with spasticity, perhaps reducing muscle overactivity is not sufficient to see a functional change in the absence of a robust post-treatment program

Variability in injection protocols patient selection Insensitive outcome measures Individualized treatment

Geoffrey L. Sheean, Botulinum treatment of Spasticity: Why is it so difficult to show a functional benefit?, Current Opinion in Neurology, 2001, 14: 771-776

BoNT

IndicationsDynamic deformity –function, pain, progressive deformityEquinus, crouch gait, pelvic obliquityUE Focal dystoniaMuscle imbalanceSialhorrhea

ContraindicationsAllergic rxn to toxin or vehicleResistance to toxin effectsSignificant muscle weaknessFailure to respond to injectionsFixed contracture

Side Effects

Most common weakness

Hoarseness or trouble talking

Dysarthria Loss of bladder

control Trouble breathing Trouble swallowing

FDA warning label and risk mitigation strategy 2009

Advise patients to seek immediate medical attention if they develop any of these symptoms

Equinus

Gastrocnemius

Soleus

Posterior tibialis

Phenol Injections

Injections of phenol were used for several decades prior to the advent of BoNT-A

Chemical neurolysis – phenol injected onto a motor nerve denervating that particular muscle

EMG stimulus to localize the target nerve

Can be injected into:Motor points: Motor neurons within a muscleMotor nerves: before they innervate a muscle

Phenol Injections

Localization of the motor neuron needs to be precise. Time required depends on which and how many nerves are injected

Typically requires multiple needle placements and burns with injection – anesthesia in sensory aware/ cognitively aware child

Dosing guidelines not well established in peds

<30mg/kg considered safe

Phenol Injections

Adverse EffectsDysesthesias most commonTypically occur if phenol injected into a sensory nerve, can result in burning sensation or hypersensitivity to touch that can last for several weeksIbuprofen, gabapentin or carbamazapine

Phenol Injections

Duration of action3-12 months, can be longer than 1 yrIncreased duration typically occurs in muscles with more accessible nerves Obturator - hip adductors Musculocutaneous nerve - biceps motor points within the medial hamstrings are more difficult to find

Discussion

Both BoNT and phenol cause selective and temporary muscular denervationTreatment for focal spasticityDifferent mechanisms of actionPhenol has proven effectiveness, immediate onset, low cost and potentially longer duration of effects, but generally less popular than BoNTTechnical challenges with administration, concerns for safety and adverse effects

Summary

Intramuscular injection of BTX-A well tolerated and efficacious - balance muscle forces across joints

Pre-defining injection goals, appropriate patient selection, and monitoring are essential

equinus deformity, managing selected upper limb deformities, adjunct in the global management of spasticity

Decrease pain related to spasticity, care-giver burden and enhance health-related quality of life

treatment philosophy includes early use in appropriate patients, to avoid contracture, delay/prevent bone and joint abnormalities, and avoid corrective surgery.

Goals of ITB Therapy

Reduce spasticity

Decrease pain associated with spasticity

Improve function Facilitate care

Intrathecal Baclofen vs Oral

ITBCSF acts at GABAB

receptor sites at spinal cordLower doses than required dailyFewer side effects

Oral baclofenLow blood/brain barrier penetration, high systemic absorption and low CNS absorptionLack of preferential SC distributionUnacceptable SE at effective doses

Plasma CSF Plasma (est) CSF

Plasma vs CSF drug levels

Penn RD, Kroin JS. Intrathecal baclofen in the long-term management of severe spasticity. Neurosurg. 1989; 4(2): 325-332.

Intrathecal Delivery

AdvantagesHigher concentration of drug in CSFDecreased SETitrateable

DisadvantagesInvasiveRisk of infectionSurgical riskDevise riskMaintenanceCost

Intrathecal Baclofen Therapy

Baclofen directly to CSF target neurons in the SC

Externally programmable, surgically implanted pump, drug delivered at precise flow rates via catheter placed in the spinal canal

Decreases hypertonicity CP, SCI, MS, Strole trauma or hypoxia

Neurophysiologic effects

Dose dependent decrease in spinal reflex response

Disappearance of tendon taps and decrease in severity of spasms

Biomechanical and neurophysiologic studies – evidence of decreased resistance to imposed stretch, decrease in EMG response

At neuronal level – baclofen acts as potent GABA-B receptor agonist

GABA-B extensively distributed in SC

Baclofen directly administered to the subarachnoid space – enhanced access to receptors → greater reflex inhibition and tone reduction

Intrathecal Baclofen

Patient Selection Grid illustration to compare

various therapies for spasticity

ITB – reversible (neural structures are not surgically altered, dose rate adjustable) and global

Pts with global or multifocal spasticity, who may benefit from adjustable (vs permanent) clinical effects are generally considered as better candidates

Grahm HK, Aoki KR, et al, Gait and Posture, vol II, 2000:67-69

Components of ITB Therapy

Accessible drug reservoir Catheter that connects

drug reservoir to the CSF Programmable –

adjustable for independent patient needs and response

External programming device

Synergistic Therapeutic effects ITB combined with other

modalities for synergist therapeutic effect

Rehabilitative therapies, oral pharmacotherapy, neurolytic procedures and muscle tendon lengthening

Combining ITB with neurolytic procedure –focal dystonic features and global hypertonicity or residual UE hypertonia

Orthopedic procedures and ITB – correction of fixed deformities in the setting of ongoing spastic hypertonia

Concomitant use – in children with CP may reduce the need for subsequent orthopedic surgery

Gertzen et al, Intrathecal baclofen infusion and subsequent orthopedic surgery in patients with Cerebral Palsy. J Neurosurg 1998;88:1009-13

Pump Placement

Ambulatory Function

1. CNS injury or disease, will ITB administration permit ambulation or improve ambulation?

2. Pts able to walk with assistance, will ITB improve their walking ability or allow them to walk independently

3. For pts who are able to walk, will they experience decline of walking ability after ITB?

Isolated case reports of regained ability to walk

Prognosis for improving ambulatory function favors those with better baseline function

Most larger studies report mixed results, some pts improving, smaller percentage significantly worsening, with the largest subgroup non-significant changes overall

Withdrawal

Abrupt cessation → withdrawal, serious and potentially fatal

“itchy, twitchy, bitchy” Pruritus, seizures,

hallucinations, autonomic dysreflexia

Exaggerated rebound spasticity, fever, hemodynamic instability and AMS

Can progress over 24-72 hrs to rhabdomyolysis (CK and phosphokinase), elevated transaminase levels, hepatic and renal failure and rarely death

Treatment: Supportive care Observation and

replacement of baclofen either enteral, or preferably through restoration of intrathecal delivery

Oral baclofen 10 -20 mg PO Q 4-6 hrs prn,

Tranxene 3.75 1-2 tabs mg Q4

Alternating every 2 hrs

ITB Therapy

ITB therapy has become a mainstay of long term spasticity management

Benefits include more potent effects, fewer systemic side effects, titratable

Disadvantages – cost, maintenance, requires vigilance, risk of malfunction of catheter pump system, withdrawal and overdose, surgical risks

Appropriate patient selection and education are critical

SDR: The Basics

First performed in 1913, but did not become popular until 1970’s

Dorsal rhizotomy became selective and outcomes evaluated since 1987

SDR involves cutting sensory nerve roots that when stimulated, trigger exaggerated motor responses as measured by EMG intraoperatively

The Procedure

Multilevel laminectomy vs. minimally invasive approaches

L1 – S1 sensory roots are identified and divided into 3-5 rootlets

Each rootlet is stimulated and responses are measured via EMG

Rootlets with the most abnormal signal are cut

Surgery takes about 4 hours

Potential Complications

Paralysis of legs Neurogenic bladder Sensory loss or dysethesias Wound infection CSF leak

SDR: Outcomes of Metanalysis Children with diplegic CP (GMFCS II-III)

received SDR + PT, or PT w/o SDR. Concluded that SDR + PT is

efficacious in reducing spasticity and has a small effect on gross motor function

McLaughlin J et al. Dev Med Child Neuro 2002, 44: 17-25.

SDR versus ITB

1-year outcomes of 71 children who underwent SDR before 1997 versus 71 children with ITB, matched by GMFCS and age

Both interventions significantly decreased Ashworth scores, increased PROM, improved function and resulted in high parental satisfaction

Compared with ITB SDR provided greater improvements in muscle tone,

PROM, and gross motor function Fewer patients in the SDR group required subsequent

orthopedic procedures No difference between the degree of parents’

satisfaction

Kan P et al. Childs Nerv Syst. 2007 Sep 5.

Outcomes

Short and long term outcomes demonstrate:Decreased spasticityImproved or unchanged strengthImproved gait patternDecreased oxygen costImproved overall function including decreased use of walking aids

Candidacy Determinations

Pre-term birth Imaging consistent with PVL Primarily spastic tone Evidence of fair selective motor control Demonstrated ability to cooperate and

follow through with rehabilitation program

Patient selection

Candidacy Determinations

Red flags Hyperextension at the knee in gait Multiple orthopedic procedures Generalized lower extremity/trunk

weakness Poor incorporation of trunk in gait Poor isolated control of lower extremity

movement Poor rehab potential (behavior, sensory

issues, cognition, social)

Summary

Spasticity: Abnormal, velocity dependent increase in resistance to passive movement of peripheral joints due to increased muscle activity

Spasticity is a type of hypertonia that is a component of the UMNS

Due to a loss of presynaptic inhibition - modulation of the afferent stimulus by the descending tracts

Positive and negative signs of the UMNS collectively cause net unidirectional movements that often persist as postures → chronic effects on soft tissue, joint structures and bone

Spasticity contributes to significant disability

Summary

CP – spasticity is a common clinical feature associated with PVL

Traditional step ladder approach to management: therapies, oral medications, injection therapies, orthopedic procedures, ITB or SDR, patient/family goals

Thank you

References

Sanger et al, Classification and Definition of Disorders Causing Hypertonia in Childhood, Pediatrics 2003


James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009, Warwick J. Peacock, Chapter 2.2 Pathophysiology of Spasticity

David Scrutton et al, Management of the Motor Disorders of Children with Cerebral Palsy, H. Kerr Graham, Ch.8 Mechanisms of Deformity



James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009, Kevin Walker, Chapter 3.4 Radiographic Evaluation of the Patient with Cerebral Palsy

References Continued

MC Olsen et al, Fiber type-specific increase in passive muscle tension in spinal cord injured subjects with spasticity, Journal of Physiology, 577:339-52, 2006

Allison Brashear, Elie Elovic, Spasticity Diagnosis and Management, 2010, Ch 1.1 Why is spasticity important?

Allison Brashear, Elie Elovic, Spasticity Diagnosis and Treatment, 2010, Ch.15 Pharmacologic Management of Spasticity: Oral Medications

R. Zafonte et al, Acute care management of post-TBI spasticity, Journal of Head trauma Rehabilitation 19(2):89-100

Stretch Reflex Pathway

1. Muscle spindle stretch receptor detects changes in muscle length

2. Myelinated sensory afferent neuron

3. The synapse4. Homonymous motor

neuron5. Muscle innervated by the

motor neuron


Stretch Reflex Pathway

Stretch detected by the muscle spindle → CNS by Ia afferents through the dorsal root, connections in the SC:

Homonymouos motor neuron monsynaptic excitatory connection with alpha motor neuron

Heteronymous motor neuron monosynaptic excitatory connections to synergist

Ia inhibitory interneuron projects to alpha motor neurons of antagonist muscles


Stretch Reflexes

Reciprocal inhibition – normal pattern simultaneous excitation of agonist and inhibition of antagonist motor neuron

Co-contraction – inappropriate activation of antagonist muscles during voluntary contraction of agonist muscles, superimposed stretch reflex activity – stretching antagonists during movement

joint stability (ie eccentric contraction of the triceps during biceps activation to control flexion of the elbow)

Activated and deactivated at the cortical level

May represent an impairment of supraspinal control of reciprocal inhibition


Traditional Step-Ladder Approach to Management of Spasticity

Neurosurgical procedures

Orthopedic procedures Neurolysis/

Chemodenervation Oral medications Rehabilitation Therapy Remove noxious stimuli

Common Patterns of Motor Dysfunction in CP

Most common pattern of spasticity in CP:Upper Extremity Internal rotation of shoulder Elbow flexion Forearm pronation Wrist and finger flexion Thumb in palm

Lower Extremity Hip flexion and adduction Knee flexion Hindfoot valgus Forefoot pronation

Spasticity Associated with CP in Children, Guidelines for the use of Botulinum Toxin A, L. Andrew Koman et al, Pediatric Drugs, 2003, 5 (1) p.11-23

Windswept Deformity

Possible Advantages of Spasticity Maintains muscle tone Helps support circulatory function May prevent formation of deep vein

thrombosis May assist in function

Diazepam - Benzodiazepine

MOA: does not directly bind to GABA receptors

Promotes the release of GABA from GABA-A neurons

Enhanced pre-synaptic inhibition, likely why useful in epilepsy

All CNS depressants Anti-anxiety, hypnotic,

anti-spasticity and anti-epileptic

Side Effects: Sedation and lethargy Impair coordination and

prolonged use can lead to physical/psych dependence

Effective doses vary considerably, upper doses primarily limited by SE

Rapid withdrawal → irritability, tremors, nausea and seizures

Clonidine Central Alpha Adrenergic Agent

Monoamines are widely distributed in CNS

Important role as modulators of spinal neuron excitability

Modulate sensory inputs via presynaptic inhibition of spinal afferent inputs

Also direct inhibitory effect on interneurons

When descending pathways from the brainstem to SC are disrupted, there is a reduction in the NE → increased hypertonia

Clonidine Central Alpha Adrenergic Agent

Centrally acting apha-2 receptor agonist → antispasticity effects

Also alpha-1 receptor agonist → antihypertensive effects

profound nociceptive pain reliever

central sympatholytic effects on BP

Therefore little effect on the BP of persons with complete SCI, but can lower the BP for those with incomplete injuries

Side Effects BP Bradycardia, dry

mouth, ankle edema, depression

Tizanidine – Central Selective Alpha-2 adrenergic agonist

Structurally related to clonidine

1/10 to 1/15 the potency of clonidine in lowering BP or slowing HR

Preference for alpha-2 receptors

Active at both segmental spinal and supraspinal levels in both motor and sensory pathways

No effect on monosynaptic reflexes – standard DTR

No activity at NMJ, no direct effect on skeletal muscle fibers, does not cause any muscle weakness

Extensive first pass metabolism

Tizanidine – Central Selective Alpha-2 adrenergic agonist

Side Effects: Sedation, asthenia,

dizziness, dry mouth Very little hypotension or

bradycardia at clinically relevant doses, virtually none in the lower half of the dose range

Rebound HTN Hallucinations and

nightmares GI - constipation

Precautions Chronic use –

potential for hepatotoxicity

Liver enzymes should be periodically checked as dose is increased

Dantrolene Sodium Direct Acting Muscle Relaxant

No centrally acting SE Acts peripherally by

decreasing release of calcium from SR→ uncoupling electrical excitation from contraction and decreasing the force of contraction

Affects intrafusal and extrafusal fibers, reducing spindle sensitivity

Action is specific for skeletal muscle and affects reflex contractions or spasticity more than voluntary contraction

Weakness -twice the voluntary effort is required to maintain a desired muscle tension


Because of propensity to cause weakness several reports advocate limiting use in CP, spasticity of spinal origin and MS pts

1980 AMA “Dantrolene should be used primarily in non-ambulatory pts and only if the resultant decrease in spasticity will not prevent the patient from functioning”

Recent report has recommended as a first line agent in the treatment of spasticity after TBI, especially in the acute setting, as it exhibits minimal cognitive effects and may not interfere with neural recovery

R. Zafonte et al, Acute care management of post-TBI spasticity, Journal of Head trauma Rehabilitation 19(2):89-100


Risks: Significant increased risk of

hepatotoxicity, 1% overall, especially with doses over 400mg

Active hepatic diagnosis contraindication RF: female, >35, polypharmacy LFTs need to be monitored, lowest

optimally effective dose should be prescribed

History of Botulinum Toxin A

1875 – Claude Bernard – “poisons can be employed as means for the destruction of life or as agents for the treatment of the sick”

This concept was first used regarding CP in the 20th century

Tardieu – Alcohol as a muscular neurolytic agent, 1970s

Carpenter (Richmond CP Hospital) – 45% alcohol and bupivicaine

1897 van Ermengem (Belgium) identifies Clostridium botulinum, obligate anaerobe bacillus

WWII - Schantz – extensive research identifies the toxins produced by C. botulinum

7 serotypes purified and identified (A-G)

Emphasis on type A, the most potent biologic toxin known

Techniques developed by Schantz and Lammana → commercial preparations available today

Lamanna – produced crystalline BTX-A, forerunner of Oculinum

British military → British formulation BTX-A, DysportL. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of

Cerebral Palsy, 2002, Wake Forest University Press


1960s – Alan B. Scott, Opthalmologist in SF, toxin as therapeutic agent for strabismus

1981 – BTX-A in humans dystonia and other movement

disorders Schantz type A toxin, Oculinum used in

these protocols under the oversight of the FDA

1988 – Koman et al, first clinical trial for treatment of spasticity in CP

Oculinum, preliminary results 1993 Subsequent trials, including large

multi-center placebo controlled trials → efficacy of BTX-A for managing equinus foot deformity (Koman 2000)

Since then – BoNT → safe and effective for a large number of neurologic and non-neurologic diseases

regarding CP, additional studies confirmed indication for:

UE CP (Corry 1997, Fehlings 2000)

Analgesia after hip surgery (Barwood 2000)

Crouched gait (Molanaers 1999) Alternative to serial casting

(Corry 1998) Hamstring spasticity (Corry

1999)



1989 – Allergan purchases the Oculinum in stock and the process to produce new bulk source of toxin from Dr. Scott

FDA approves BTX-A for strabismus, blepharospasm, and hemi-facial spasm (>12)

1992 – registers tradename BOTOX

2000 – BTX-A and B (Myobloc/Neurobloc, Solstice) FDA approval for dystonia

2002 – FDA approval for cosmetic use

2004 – FDA approval for hyperhidrosis

2010 – approval for UE spasticity in Adults

Acceptance for treatment of spasticity is growing, with approvals in many European countries

Continued clinical trials for expanding indications


Summary

Intramuscular injection of BTX-A is well tolerated and efficacious if used to balance muscle forces across joints in the absence of fixed contractures

Pre-defining injection goals, appropriate patient selection, and monitoring are essential

It is well documented as a treatment option for equinus deformity, managing selected upper limb deformities, and is valuable as an adjunct in the global management of spasticity

It can diminish pain related to spasticity, decrease care-giver burden and enhance health-related quality of life

treatment philosophy includes early use in appropriate patients, to avoid contracture, delay/prevent bone and joint abnormalities, and avoid corrective surgery.

Spasticity Mechanisms and Management

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Transcript of Spasticity Mechanisms and Management