THE UPPER MOTOR NEURON
SYNDROME AND SPASTICITY:
PATHOPHYSIOLOGY AND
MANAGEMENT
ROBERT J. CONI, DO
NEUROLOGY – GRAND STRAND REGIONAL MEDICAL CENTER
LEARNING OBJECTIVES
After 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
CNS Damage
Paralysis
Immobilized and
shortened
DELAYED
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
DELAYED
ACUTE
CNS Plastic
Rearrangements
*Spinal
*Supraspinal
CNS Damage
Paralysis
Disuse
Immobilized and
shortened
Soft Tissue Plastic
Rearrangements
Muscle Overactivity
Spasticity
Spastic contraction
Dystonia
Others
T
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
Positive Signs
Negative Signs
• SPASTICITY (Increased muscle stretch reflexes)
• MOTOR WEAKNESS
• SPASTIC DYSTONIA
• MUSCLE FATIGUE
• SPASTIC CO-CONTRACTION
• LOSS OF SELECTIVE CONTROL OF SPECIFIC
MUSCLES
• RELEASED FLEXOR REFLEXES
• ASSOCIATED REACTIONS (SYNKINESIS)
• RHEOLOGIC CHANGES: INCREASED MUSCLE
STIFFNESS AND CONTRACTURE
FORCES THAT GENERATE UMN SYNDROME PATTERNS
Extensors
Flexors
A combination of positive and negative
signs and rheologic changes in muscle
produce the common patterns of
UMN dysfunction
UMN PATTERNS GENERATED BY DYNAMIC AND STATIC
FORCES
UPPER LIMB
LOWER LIMB
• Adducted, internally rotated at
shoulder
• Flexed hip
• Flexed elbow
• Flexed knee
• Pronated forearm
• Stiff knee
• Flexed wrist
• Equinovarus or equinus foot
• Clenched fist
• Hyperextened hallus
• Thumb-in-palm
• Flexed toes
• Adducted thighs
ADVERSE EFFECTS OF MUSCLE OVERACTIVITY
• SLOW VOLUNTARY MOVEMENTS DUE TO
SPASTICITY
• IMPAIRED STANDING BALANCE
• IMPAIRED COORDINATION
• IMPAIRED SLEEP
• SKIN SHEER AND BREAKDOWN
• RISK OF CONTRACTURES
• IMPAIRED PERINEAL HYGIENE AND SEXUAL
FUNCTION
• POOR BED AND WHEELCHAIR POSTURES
• DIFFICULTY DRESSING
• IMPAIRED GAIT
• 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 PATIENT
Does the muscle overactivity significantly
interfere with function or will it lead to
musculoskeletal deformities
NO
YES
Patient and
Caregiver
objectives
Functional
objectives
Initiate comprehensive treatment program
Technical
objectives
ASSESSMENT OF SPASTICITY
INSTRUMENT MEASURED
• 3D Gait analysis
• Goniometric ROM
• Functional measures
CLINICIAN REPORTED
PATIENT/CAREGIVER
REPORTED
• Muscle tone (modified
Ashworth scale and Tardieu)
• QOL
• Physician gait ratings
• Satisfaction/preference
• ROM of joints
• Participation/impairments
• Global outcome measures
•
FIM
•
Barthel index
• Dependence
•
Disability scales
• 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
Evaluation
Physical Therapy
Occupational Therapy
Goals
Reevaluation
Intrathecal
Medication
(Baclofen)
Orthopedic surgery
Neurosurgery
NEUROLYSIS
• Phenol injections
• Alcohol injections
CHEMODENERVATION
• Botulinum toxin
ORAL
MEDICATIONS
• Baclofen
• Dantrolene
• Diazepam
• Tizanidine
NONPHARMACOLOGIC TREATMENT OPTIONS FOR
SPASTICITY
PHYSICAL OR OCCUPATIONAL
THERAPY
SURGICAL OPTIONS
• Stretching
• Selective dorsal rhizotomy
• Orthotics
• Tendon Lengthening or transfers
• Casting, splinting, positioning
• Spinal cord stimulator
• Thermal or electrical modalities
• Biofeedback
COMMONLY USED ORAL MEDICATIONS FOR
SPASTICITY TREATMENT
ORAL MEDICATION
•
•
•
•
BACLOFEN
DANTROLENE
DIAZEPAM
TIZANIDINE
ADVANTAGES
•
Decreases frequency and severity of
painful spasms
•
Improves ROM
•
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
Decrease clonus, hyperreflexia, muscle
stiffness and cramping
•
Reduces muscle tone
•
Reduces frequency of spasms
•
Reduces muscle spasms
•
Reduces spasticity without altering
muscle power
INTRATHECAL AGENTS: ADVANTAGES AND
DISADVANTAGES
MEDICATION
Intrathecal baclofen (pump implantation)
Other drugs (eg. Morphine)
ADVANTAGES
Direct 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.
DISADVANTAGES
Surgical technique to implant reservoir and
catheter to thecal sca.
Risk of complications due to catheter or
pump failure and infection.
Drowsiness
Headache
Weakness
Reduced painful spasms
Risk of drug withdrawal
Reduces muscle tone and frequency of spasms
while increasing ROM
High upfront cost
COMMONLY USED NERVE AND MUSCLE INJECTABLE
MEDICATIONS FOR SPASTICITY MANAGEMENT
MEDICATION
Alcohol
Phenol
ADVANTAGES
Quick onset of action
DISADVANTAGES
Reduces tone, increased passive ROM
Associated pain, skin irritation, muscle
discomfort
Reduces temporary nerve block lasting up to
several months
Highly variable duration of action, pain,
muscle necrosis, dysesthesia
Helps control muscle spasticity
Botulinum toxin
Causes localized decrease in symptoms
Transient muscle weakness
Reduces spasticity related pain
Reversible
Tolerance can develop
NEUROLYTIC AGENTS: MECHANISM OF ACTION
MEDICATION
Alcohol, phenol
MECHANISM OF ACTION
Primary 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
MEDICATION
Botulinum toxin
MECHANISM OF ACTIONS
Inhibition 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
SEROTYPE
• SELECTIVE CLEAVAGE OF SNAP-25
A, C1, E
• Leads to inhibition of acetylcholine release
• CLEAVAGE OF VAMP, OTHERWISE KNOWN
AS SYNAPTOBREVIN
• INHIBITION OF SUBSTANCE P, CGRP, AND
GLUTAMATE RELEASE
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 A
Dysport
• Incobotulinumtoxin A
Serotype A
Xeomin
• Onabotulinumtoxin A
Serotype A
Botox
• Rimabotulinumtoxin B
Serotype B
Myobloc
INDICATIONS FOR THE DIFFERENT BOTULINUM TOXINS
Indication
Dysport
Blepherospasm and
strabismus
Cervical dystonia
√
Glabellar lines
√
Xeomin
Botox
√
√
√
√
Myobloc
√
√
Axillary
hyperhydrosis
√
Upper limb
spasticity
√
Many of these have been tested for the other indications listed above with literature reports available
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.