THE UPPER MOTOR NEURON SYNDROME AND SPASTICITY:

PATHOPHYSIOLOGY AND MANAGEMENT

ROBERT J. CONI, DO

NEUROLOGY – GRAND STRAND REGIONAL MEDICAL CENTER

LEARNING OBJECTIVESAfter this discussion, the participant should be able to:

• Define and differentiate spasticity from other neurological conditions associated with increased tone and be able to articulate the intricacies of various treatment options available.

• Relate the various presentations and be able to outline appropriate treatment measures depending on the presentation.

• Define and appreciate the full range of treatment options available.

• Appreciate the natural history and progression of spasticity including the causes, consequences of the insult and the added effects of disuse of the affected region.

• Understand the various modalities of chemodenervation and where, when they are applied.

• Appreciate the pharmacology of applicable oral agents including; indications, side effects and use of these agents.

EPIDEMIOLOGY AND PREVALENCE OF SPASTICITY

• Spasticity affects > 12 Million people worldwide.

• Prevalence estimates vary and are specific to the associated conditions and/or etiology.• 19% of persons 3 months after a stroke.

• 17% of persons 1 year after a stroke.• 4% with disabling spasticity.

• 38% of persons 1 year after a stroke.• Arms and legs affected.

• 42% of persons 1 year after a stroke.

• Usually multiple joints affected.

PATHOPHYSIOLOGY OF SPASTICITY

• One of several components of the Upper Motor Syndrome.

• Causes:

• Stroke

• Brain or Spinal Cord Injury

• Cerebral Palsy

• Multiple Sclerosis

FEATURES OF SPASTICITY AND SPASTIC PARESIS

• Spasticity is one type of “muscle overactivity” which needs to be distinguished from other components of the syndrome including dystonia and rigidity.

• Muscle overactivity, soft tissue shortening and paresis are the 3 major disabling factors in spastic paresis of the UMN syndrome.

• Spasticity and muscle overactivity cause disability, interfere with ADLs and may cause pain and immobility.

NATURAL HISTORY OF SPASTIC PARESIS

ACUTE

DELAYED

CNS Damage

Paralysis

Immobilized and

shortened

T

FACTORS IN THE PATHOPHYSIOLOGY OF SPASTIC OVERACTIVITY

• SPINAL

• Enhanced excitability of monosynaptic pathways caused by multiple changes in reflex activity. Increased muscle spindle stimulation in stiffer muscles; α motor neuron excitability; presynaptic inhibition on group Ia afferents, group Ib inhibition, group II pathways, Renshaw cells and reciprocal group Ia inhibition.

• SUPRASPINAL

• Release of activity in excitatory brainstem descending pathways

causing dystonic posturing.

• A hemiplegic posture develops, where antigravity muscles

in particular are stimulated by motor neurons which develop

overactivity.

POST IMMOBILIZATION JOINT ROM LIMITATION

• Immobilization in the shortened position results in less longitudinal tension (unopposed) producing contracture.

• Muscle contracture – results in• Atrophy

• Loss of sarcomeres (shortening)

• Accumulation of connective tissue

• Increase in spindle responsiveness

NATURAL HISTORY OF SPASTIC PARESIS

ACUTE

DELAYED

CNS Damage

Paralysis

Immobilized and shortened

T

Soft Tissue Plastic

RearrangementsCONTRACTURE

Disuse

CNS Plastic Rearrangeme

nts *Spinal *Supraspinal

Muscle OveractivitySpasticitySpastic contractionDystoniaOthers

COMMON TYPES OF MUSCLE OVERACTIVITY IN UMN SYNDROME

• SPASTICITY• Velocity dependent increase in response to phasic stretch in absence of

volitional command (ie., at rest).

• Clasped knife response

• SPASTIC DYSTONIA• Stretch sensitive tonic muscle contraction in absence of volitional command

(ie., at rest), including command to neighboring or distant muscles, and in the absence of phasic stretch of that affected muscle.

• SPASTIC CO-CONTRACTION• Inappropriate antagonist recruitment triggered by volitional command

during effort of an agonist in absence of phasic stretch.

MUSCLE STRETCH REFLEX

MUSCLE PHYSIOLOGY CHARACTERISTICS

SIGNS OF THE UMN SYNDROME

• SPASTICITY (Increased muscle stretch reflexes)

• SPASTIC DYSTONIA

• SPASTIC CO-CONTRACTION

• RELEASED FLEXOR REFLEXES

• ASSOCIATED REACTIONS (SYNKINESIS)

• RHEOLOGIC CHANGES: INCREASED MUSCLE STIFFNESS AND CONTRACTURE

• MOTOR WEAKNESS

• MUSCLE FATIGUE

• LOSS OF SELECTIVE CONTROL OF SPECIFIC MUSCLES

Positive Signs

Negative Signs

FORCES THAT GENERATE UMN SYNDROME PATTERNS

A combination of positive and negative

signs and rheologic changes in muscle

produce the common patterns of

UMN dysfunction

Extensors Flexors

Extensors Spastic and/orContracted Flexors

UMN PATTERNS GENERATED BY DYNAMIC AND STATIC FORCES

UPPER LIMB• Adducted, internally rotated

at shoulder

• Flexed elbow

• Pronated forearm

• Flexed wrist

• Clenched fist

• Thumb-in-palm

LOWER LIMB• Flexed hip

• Adducted thighs

• Flexed knee

• Stiff knee

• Equinovarus or equinus foot

• Hyperextened hallus

• Flexed toes

ADVERSE EFFECTS OF MUSCLE OVERACTIVITY

• SLOW VOLUNTARY MOVEMENTS DUE TO SPASTICITY

• IMPAIRED COORDINATION

• SKIN SHEER AND BREAKDOWN

• RISK OF CONTRACTURES

• POOR BED AND WHEELCHAIR POSTURES

• IMPAIRED STANDING BALANCE

• IMPAIRED GAIT

• IMPAIRED SLEEP

• IMPAIRED PERINEAL HYGIENE AND SEXUAL FUNCTION

• DIFFICULTY DRESSING

• PAIN

CLINICAL MANIFESTATIONS OF THE UMN SYNDROME

• SYMPTOMATIC COMPLAINTS

• PROBLEMS OF PASSIVE FUNCTION

• Personal care

• Positioning

• PROBLEMS OF ACTIVE FUNCTION

• Limb use

• Mobility

CONSEQUENCES OF SPASTICITY

• POSSIBLE MEDICAL COMPLICATIONS

• Contracture, Fibrosis, Muscle atrophy

• NEGATIVE IMPACT ON PATIENTS AND CAREGIVERS

• Reduces mobility and impedes activities of daily living

• OFTEN POORLY TREATED AND MISMANAGED

• Inadequate assessment guidelines

• Lack of specialized spasticity management

• Treatment not individualized

• Inappropriate treatment selection

• Insufficient follow-up

ASSESSMENT ALGORITHM FOR MUSCLE OVERACTIVITY

Patient presents with muscle overactivity

EVALUATE PATIENTDoes the muscle overactivity

significantly interfere with function or will it lead to musculoskeletal

deformities

NO

YES

Patient and Caregiver objectives

Functional objectives

Technical objectives

Initiate comprehensive treatment program

ASSESSMENT OF SPASTICITY

INSTRUMENT MEASURED

• 3D Gait analysis

• Goniometric ROM

• Functional measures

• FIM

• Barthel index

• Disability scales

CLINICIAN REPORTED

• Muscle tone (modified Ashworth scale and Tardieu)

• Physician gait ratings

• ROM of joints

PATIENT/CAREGIVER REPORTED

• QOL

• Global outcome measures

• Satisfaction/preference

• Participation/impairments

• Dependence

• Functional status

CLEAR OUTCOMES MEASURES NEEDED

• NO GENERAL CONSENSUS

• Systematic review of botulinum toxin use in patients with cerebral palsy demonstrated that outcomes tend to focus on spasticity or ROM and not activity or function.

• There have been conflicting reports of use of the modified Ashworth scale to assess lower limb spasticity.

• Inter rater reliability and longitudinal rating reliability are poor.

• Thus, Ashworth scale lacks validity and reliability to measure spasticity.

IMPORTANCE OF SPASTICITY TREATMENT

• WHEN UNTREATED OR INADEQUATELY TREATED, THERE CAN BE LONG TERM HEALTH CONSEQUENCES

• Pain

• Bladder and bowel dysfunction

• Deformity

• Contracture

• Compromised cognitive function due to fatigue

• NONPHARMACOLOGIC OPTIONS TO TREAT MUSCLE OVERACTIVITY

• Physical and Occupational therapy

• Surgical interventions

OBJECTIVES IN TREATING MUSCLE OVERACTIVITY IN UMN SYNDROME

IMPROVE QUALITY OF LIFE

• Relieve symptoms and reduce disfigurement

• Ease personal care and positioning (passive function)

• Improve limb function and mobility (active function)

• Enable activities of daily living

• Reduce burden of care

MANAGEMENT INTERVENTIONS FOR MUSCLE OVERACTIVITY

GoalsReevalua

tion

Physical Therapy Occupational

TherapyEvaluation

ORAL MEDICATIO

NS• Baclofen• Dantrole

ne• Diazepa

m• Tizanidin

e

NEUROLYSIS• Phenol

injections• Alcohol

injections

CHEMODENERVATION

• Botulinum toxin

Intrathecal Medication (Baclofen)

Orthopedic surgery

Neurosurgery

NONPHARMACOLOGIC TREATMENT OPTIONS FOR SPASTICITY

PHYSICAL OR OCCUPATIONAL THERAPY

• Stretching

• Orthotics

• Casting, splinting, positioning

• Thermal or electrical modalities

• Biofeedback

SURGICAL OPTIONS

• Selective dorsal rhizotomy

• Tendon Lengthening or transfers

• Spinal cord stimulator

COMMONLY USED ORAL MEDICATIONS FOR SPASTICITY TREATMENT

ORAL MEDICATION

• BACLOFEN

• DANTROLENE

• DIAZEPAM

• TIZANIDINE

ADVANTAGES• Decreases frequency and

severity of painful spasms

• Improves ROM

• Decrease clonus, hyperreflexia, muscle stiffness and cramping

• Reduces muscle tone

• Reduces frequency of spasms

• Reduces muscle spasms

• Reduces spasticity without altering muscle power

DISADVANTAGES• Sedation, weakness, nausea,

dizziness

• Hallucinations due to sudden withdrawal

• Drowsiness, diarrhea, malaise, weakness

• Hepatotoxic

• Weakness, sedation

• Dependence with long use

• Weakness, sedation, drowsiness, dry mouth, dizziness

INTRATHECAL AGENTS: ADVANTAGES AND DISADVANTAGES

MEDICATIONIntrathecal baclofen (pump implantation)

Other drugs (eg. Morphine)

ADVANTAGESDirect administration of baclofen into spinal canal allows continuous supply of baclofen to site of action.

Useful for severe or generalized cases of spasticity that do not respond to other less invasive treatments.

Less CNS affects compared with oral baclofen because of the reduced dose required.

Reduced painful spasms

Reduces muscle tone and frequency of spasms while increasing ROM

DISADVANTAGESSurgical technique to implant reservoir and catheter to thecal sca.

Risk of complications due to catheter or pump failure and infection.

Drowsiness

Headache

Weakness

Risk of drug withdrawal

High upfront cost

COMMONLY USED NERVE AND MUSCLE INJECTABLE MEDICATIONS FOR SPASTICITY

MANAGEMENT

MEDICATIONAlcohol

Phenol

Botulinum toxin

ADVANTAGESQuick onset of action

Reduces tone, increased passive ROM

Reduces temporary nerve block lasting up to several months

Helps control muscle spasticity

Causes localized decrease in symptoms

Reduces spasticity related pain

Reversible

DISADVANTAGESAssociated pain, skin irritation, muscle discomfort

Highly variable duration of action, pain, muscle necrosis, dysesthesia

Transient muscle weakness

Tolerance can develop

NEUROLYTIC AGENTS: MECHANISM OF ACTION

MEDICATIONAlcohol, phenol

MECHANISM OF ACTIONPrimary mechanism involves denaturing proteins and tissue destruction.

Lower concentrations result in decreased conductance of potassium and sodium while high concentrations result in effects on proteins.

Behaves as a local anesthetic

Onset of actions < 1hr duration approximately 2-12 wks

Provides focal neuromuscular blockade

Complications include transient pain

Perineural blocks can be used for proximal muscles or when multiple muscles need to be injected (risk of long lasting dysesthesia)

CHEMODENERVATION AGENTS: MECHANISM OF ACTION

MEDICATIONBotulinum toxin

MECHANISM OF ACTIONSInhibition of acetylcholine in neuromuscular junction that leads to reduction in muscle activity.

Onset of action, within 7 days; duration, approximately several months.

Provides improvement in pain symptoms

Can result in weakness in non-target muscles

SURGICAL OPTIONS

• May reduce spasticity for some patients

• Combining orthopedic surgery and neurosurgery, with subsequent rehabilitation, helps normalize biomechanics of the spine and extremities and manage tone.

• Selective dorsal rhizotomy, in combination with physiotherapy, has been shown to be safe and effective for reducing spasticity.

BOTULINUM TOXIN SEROTYPES

• Serotypes and preparations

• A, B, C1, D, E, F, G

• Differ in complex size and compositionexcipients, serotype manufacture processes and testing methods.

• Dosing and pharmacology cannot be generalized across serotypes and brands/products.

• Duration of effect will vary widely among serotypes.

• Mechanism of actions will vary by serotype.

BOTULINUM TOXIN TARGET PROTEINS

ACTION/TARGET PROTEIN

• SELECTIVE CLEAVAGE OF SNAP-25

• Leads to inhibition of acetylcholine release

• CLEAVAGE OF VAMP, OTHERWISE KNOWN AS SYNAPTOBREVIN

• INHIBITION OF SUBSTANCE P, CGRP, AND GLUTAMATE RELEASE

SEROTYPE

A, C1, E

B, D, F, G

A

BOTULINUM TOXIN – MECHANISM OF ACTION

BOTULINUM TOXIN: PROPERTIES AND ACTIONS

• Focal intramuscular injection therapy

• Physiologic action

• Reversible

• Titratable to the patient’s needs

• Reduces muscle overactivity

• Improves passive /active function

• Facilitates ease of care

• Increases comfort

• Prevents or delays musculoskeletal complications

• Lessens disfigurement

PROPRIETARY BOTULINUM TOXINS AVAILABLE

• Abobotulinumtoxin A Serotype ADysport

• Incobotulinumtoxin A Serotype AXeomin

• Onabotulinumtoxin A Serotype A Botox

• Rimabotulinumtoxin B Serotype B Myobloc

INDICATIONS FOR THE DIFFERENT BOTULINUM TOXINS

Many of these have been tested for the other indications listed above with literature reports available

Indication Dysport Xeomin Botox Myobloc

Blepherospasm and strabismus

√ √

Cervical dystonia

√ √ √ √

Glabellar lines √ √

Axillary hyperhydrosis

√

Upper limb spasticity

√

BLACK BOX WARNING

• The effects of all botulinum toxin treatments may spread from the injection site to other areas, causing symptoms similar to botulinum toxin effects.

• Unexpected muscle weakness or loss of strength, hoarseness or trouble speaking, difficulty saying words clearly, loss of bladder control, double vision, blurred vision, drooping eyelids, and difficulty breathing or swallowing which can be life threatening. There have been deaths reported.

• Symptoms reported hours to weeks after injection

ONABOTULINUMTOXIN A - BOTOX• Serotype A

• Indications and usage:

• Cervical dystonia, primary axillary hyperhidrosis, blepherospasm, strabismus and chronic migraine.

• Also approved for upper extremity spasticity in adults.

• Decreases severity of increased muscle tome in elbow flexors (biceps). Wrist flexors (FCR and FCU), and finger flexors (FDP and FDS).

• Important limitations

• Safety and efficacy not established of other upper ext muscle groups or lower limb spasticity.

• Not demonstrated to improve function or ROM when joint is affected by fixed contracture.

• Does not replace usual standard of care rehabilitation therapies.

DOSING CONSIDERATIONS• The Pharmacology of the botulinum toxin preparations cannot

be compared to each other or exchanged.

• Variability exists with toxin preparation, injection techniques, injection site, severity of spasticity and other confounding dosing issues which must be considered.

• Awareness of the wide range of dosing schedules and understanding of how to incorporate this expertise into clinical setting are important to achieving optimal treatment results.

• Duration of effect will vary with different preparations.• In addition, even the dose units of different serotype A toxins are not

interchangeable and there are no dose conversion factors that are reliable.

BOTULINUM TOXIN INJECTION TECHNIQUE• Generally, the dose is based on the size of the muscle and motor unit.

• The smallest dose is generally used to start but may be based on the degree of spasticity.

• Distribution of the injection dose

• Smaller muscles may only require one injection site., usually mid-belly.

• Larger or wider muscles may require injections in more than one site.

• The needle is Teflon coated and will allow EMG to be performed or electrical stimulation in only a small number of motor units.

• Both techniques can be used to localize.

• Deeper muscles require longer needles.

• Ultrasound guidance can be used to direct the needle into the muscle for added specificity and accuracy.

• To evaluate for fixed contracture, a diagnostic nerve block can be performed with lidocaine or bupivacaine.

INCREASING EFFECTIVENESS OF BOTULINUM TOXIN INJECTIONS

• Target the motor end plate region.

• Perform active and passive stretching of injected muscles (with or without electrical stimulation).

• Nerve stimulation may boost botulinum toxin action.

• Studied in Gastroc/Soleus/Tib posterior.

• Botulinum toxin plus E-stim gave a better response to control group.

• Felt to help target muscle fascicules with a high density of NMJ.

• Increase the dilution of the toxin to allow greater spread.• Theoretical concerns include spread out of the injected muscle and systemically.

EXAMPLE: TREATMENT OF ADDUCTED, INTERNALLY ROTATED SHOULDER WITH

BOTULINUM TOXIN• Inject pectoralis major and minor

• Palpate the muscles to minimize the risk of pneumothorax.

• Distribute dose among several sites

• Lat dorsi and teres major may cause

shoulder adduction and are accessible

below the post axillary fold.

Increase accuracy with EMG,

Ultrasound and or E-Stim.

EXAMPLE: TREATMENT OF WRIST FLEXION WITH BOTULINUM TOXIN

• Inject flexor carpi ulnaris and flexor carpi radialis.

• May need to inject finger flexors too

• FDS for proximal interphalangeal joint flexion.

• FDP for distal interphalangeal joint flexion.

• Inject 2 sites per muscle

CONCLUSIONS• Spasticity is one type of “muscle overactivity.” Other visible components include spastic

dystonia and spastic co-contraction.

• These can be managed effectively with a combination of modalities, including but not limited to: PT/OT physical interventions, and medications given orally, intrathecally or directly into tissues in the form of neurolysis.

• Injury to the CNS leads to muscle over activity which leads to immobilization, shortening of tissues, contracture, disuse and then poor function, hygiene and discomfort.

• Management is dependent on the presentation but also on the desired effect and function and usually requires a comprehensive approach with good follow-up.

• Both medication management and neurolytic injections have advantages and disadvantages and often are used in combination depending on the outcome desired.

• More research is needed to define criteria for therapies, follow the effects of treatments in order to make definitive recommendations.