SPASTICITY Pathophysiology

and Treatment after a Brain Injury

Kenneth A. Mook, MD, PhD Gateway Rehabilitation Hospital

At Florence

DISCLOSURE STATEMENT

• I have nothing to disclose • I am the Medical Director at

Gateway Rehabilitation Hospital at Florence

Types of Brain Injury – Traumatic Brain Injury – brain injury from an external force to the

skull and brain. – Congenital - Genetic, Chromosomal, Multifactorial – Acquired Brain Injury - damage to the brain that occurs after birth

and is not related to a congenital disorder or a degenerative disease, and occurs between perinatal and geriatric.

• Excludes Cerebral Palsy, Alzheimer’s disease, Multiple Sclerosis, Parkinson’s Disease.

Objectives • Understand Basic Neuroanatomy to

Understand Spasticity • Understand Clinic Evaluation and Treatment

Options for Spasticity • Understand Medication Management of

Spasticity • Understand Invasive Options to inhibit

spasticity locally or at the CNS

Brain Functions

• Brain has millions of neurons and connections or synapses

• Different areas of the brain control specific body functions and other areas are “connectors” or “regulators” between brain function and information sent to the spinal cord to the lower motor neurons and back from sensory neurons.

How does Traumatic Brain Damage Occur? • Focal Damage - contusion or trauma to the location of a

particular area of impact: coup-countercoup effects resulting in Fronto-temporal contusions

• Diffuse axonal injury – shifting or rotation of brain inside the skull causing shearing and tearing injuries of neurons/axons

• These injuries result in hematoma, brain edema, and/or increased intracranial pressure.

Physical Effects of acquired brain injuries • Motor weakness or paralysis • Extrapyramidal effects on balance, ataxia,

uncoordinated movement patterns • Sensory impairments to vision, sensation, and

hearing • Seizures • Hearing, speech (dysarthria), taste, smell, and

swallow deficiencies • High fatigability • Sleep disturbances • Increased sensitivity to caffeine, alcohol and drugs

Physiology of Spasticity

• Spasticity = Motor disorder characterized by: – “velocity dependent increase in muscle tone”, – “involuntary muscle contractions” – “hyperexcitability of tonic stretch reflexes”

• Tone = resistance to passive movement. • Rigidity = hyperactivity from prolonged

discharge of alpha motor neurons.

Upper Motor Neuron vs.

Lower Motor Neuron Injuries

Upper Motor Neuron Lower Motor Neuron Cerebral Cortex Corticospinal tracts

Definition

Anterior Horn Cell Ventral root axon to striated muscle

Initial: Paresis or Paralysis Later: Hypertonicity Hyperactive reflexes, Babinski sign Atrophy

Injury Initial: Loss of tone Rapid atrophy Loss of myotactic reflexes Later: same, no significant changes

Segmental reflex arc intact

Neurology Reflex arc broken

CVA, Cerebral Injury, Spina Cord Injury

Examples Poliomyelitis, SMA, Root injury, Cauda equina

UMN Syndrome • Muscle “Softening” Initially

– Weakness – Fatigability – Slow initiation – Reduced motor unit

recruitment – Reduced dexterity

• Muscle “Tightening” Subsequently – Velocity-dependent tone increases – Abnormal relaxation phase – Clonus – Rigidity – Dystonia – Flexor/Extensor spasms – Stretch/cutaneous hyperreflexia – Autonomic hyperreflexia – Babinski reflex

Cerebral Cortex

NeuroScience Online – UTHealth & McGovern Medical School http://neuroscience.uth.tmc.edu/s3/chapter01.html

Cerebral Cortex

NeuroScience Online – UTHealth & McGovern Medical School http://neuroscience.uth.tmc.edu/s3/chapter01.html

Cerebral Cortex

Motor Unit and Motor Neuron Pools

Motor Unit: • Individual muscle fibers are innervated by an individual alpha motor neuron. Motor Neuron Pool: • Groups of muscle fibers are innervated by a series of motor neuron nuclei clustered in columns

in the anterior horn of the spinal cord which is called a motor neuron pool. Innervation Ratio: • Light force muscle have a small number of muscle fibers innervated by a each motor neuron

while gross, large force muscles have a large number of muscle fibers innervated by each motor neuron.

Muscle Force: • Muscle force production is determined by how fast a motor neuron fires (Rate code), as well as

how many motor neurons are recruited to fire their respective muscle fibers ( Size Principle)

Muscle Spindles and Golgi Tendon Organs

• Muscle Spindles – signal the LENGTH of a muscle and the

RATE OF CHANGE in length of a muscle.

– specialized muscle fibers within a skeletal muscle itself that consists of Intrafusal fibers and Extrafusal fibers.

• Golgi Tendon Organ – Signal the FORCE applied to a muscle

NeuroScience Online – UTHealth & McGovern Medical School http://neuroscience.uth.tmc.edu/s3/chapter02.html

Muscle Spindle Fibers

• Muscle Spindle Fibers – Dynamic Nuclear Bag Fibers –

bundled nuclei that signal information about the DYNAMIC rate of change (velocity) of muscle length

– Static Nuclear Bag Fibers – bundled nuclei that signal information about the STATIC length of a muscle

– Nuclear Chain Fibers – single row nuclei that signal information about the STATIC length of a muscle

Muscle Spindle Innervation • Ia, II = Sensory Innervation

– Group Ia afferents - form annulospiral endings around the intrafusal fibers and signal LENGTH and VELOCITY.

– Group II afferents – form flower spray endings that innervate the ends of nuclear chain and static nuclear bag fibers and signal only about LENGTH.

• Gamma = Motor innervation – Gamma Motor Neurons – innervate

Intrafusal fibers to keep muscle spindles taut and sensitive to further stretch.

Golgi Tendon Organ

– Located between the muscle fibers and tendon. – Signals information about the FORCE applied to

the muscle. – Group Ib fiber afferent innervation increases firing

rate as the force on the muscle increases.

Spinal Reflexes Myotatic Reflex (Monosynaptic) • Sudden stretch of muscle spindles stimulates

Ia afferent firing which has a monosynaptic innervation on the alpha motor neuron that results in muscle contraction to shorten the muscle.

• Role in maintaining POSTURE.

Reciprocal Inhibition • The myotatic reflex occurs as the Ia afferent

bifurcates and innervates the alpha motor neuron, but also innervates a Ia inhibitory interneuron on the alpha motor neuron of the opposing muscle group.

Spinal Reflexes • Autogenic Inhibition Reflex

– GOLGI TENDON ORGAN – Ib afferents fibers innervate a Renshaw inhibitory interneuron to inhibit the alpha motor neuron to the contracting muscle resulting in ceasing muscle fiber firing.

– Not a complete safety mechanism from a heavy weight.

– Helps to spread the work more evenly throughout a muscle via recruiting some fibers and allowing inhibition of other muscle fibers.

Spinal Reflexes

• Reciprocal Excitation in the Golgi tendon organ’s autogenic inhibition reflex – Ib afferent fibers innervate an

excitatory interneuron on the alpha motor neuron of the antagonist muscle, while via an inhibitory interneuron, inhibiting the alpha motor neuron of the agonist muscle, and allowing relaxation of the agonist muscle.

Descending Motor Pathways • Descending pathways from the brain

regions send nerve axons down the spinal cord to innervate alpha motor neurons, gamma motor neurons, and interneurons through several tracts.

• Flexor-Extensor rule: flexor muscle motor neurons are located posteriorly to the extensor muscle motor neurons.

• Proximal-Distal rule: distal muscle motor neurons are located lateral to proximal muscle motor neurons. NeuroScience Online – UTHealth & McGovern Medical

School http://neuroscience.uth.tmc.edu/s3/chapter03.html

Descending Motor Pathways

• Lateral Pathways – Control proximal and

distal muscles – Voluntary movement

of arms and legs – Tracts:

• Lateral corticospinal tract

• Rubrospinal tract

• Medial Pathways – Control muscles of posture,

balance, coarse control of axial and proximal muscles

– Tracts: • Vestibulospinal tracts • Reticulospinal tracts • Tectospinal tract • Anterior corticospinal tract

Descending Motor Pathways Lateral Pathway: Pyramidal System Corticospinal Tracts • Sensori/Premotor Cortex -> motor cortex -> internal

capsule -> cerebral peduncle in midbrain -> medullary pyramids (brainstem) -> splits into two branches

– 90% cross over to lateral corticospinal tract – 10% do not cross over and form the anterior

corticospinal tract but cross over at their respective spinal cord level of innervation)

– CONTROL VOLUNTARY MOVEMENT – Lateral corticospinal tract – distal muscle fine

motor control. – Anterior corticospinal tract – proximal muscle

gross motor control.

Descending Motor Pathways Lateral Pathway: ExtraPyramidal System Rubrospinal tract

– Red Nucleus (Midbrain) -> cross over -> lateral funiculus of spinal cord

– Minor pathway in humans – Purpose:

• Excitation of flexor muscles and inhibition of extensor muscles.

• Role in MOVEMENT VELOCITY (Cerebellum innervates the Red nucleus resulting in LEARNED MOTOR COMMANDS)

• Some innervation from the Motor Cortex (allows some recovery after corticospinal tract damage).

Descending Motor Pathways Medial Pathway: ExtraPyramidal System Vestibulospinal Tracts • Lateral Vestibulospinal tract – antigravity muscles

for balance during tilting. • Medial Vestibulospinal tract – stimulates neck

muscles to stabilize the head position and eyes movements

• Mediate: – POSTURAL ADJUSTMENTS – HEAD MOVEMENTS – BALANCE

Descending Motor Pathways

Medial Pathway: ExtraPyramidal System Reticulospinal tract

– Alternative to corticospinal tract where cortical input via the BRAINSTEM RETICULAR FORMATION can excite alpha motor neurons.

– Regulate flexor responses to only noxious stimuli

– Also control orientation, stretching, and maintaining complex postures.

– Integration of sensory input to guide motor output.

• Pontine Reticulospinal tract • Medullary Reticulospinal tract

Neurotransmitters • Nerves “talk” to each other through

NEUROTRANSMITTERS. • These chemicals are released from

one nerve terminal when an action potential arrives and they cross over a synaptic cleft to bind to RECEPTORS on the nerve or muscle or terminal organ to pass on “information”.

• Neurotransmitters are then taken back up by the nerve terminal and stored until another action potential wave comes and tells them to release again.

Neurotransmitters Cerebral Neurotransmitters • Glutamate

– excitatory to next neuron.

• GABA – inhibitory

• Dopamine – excitatory

• Serotonin – Excitatory/Inhibitory

Spinal Cord Neurotransmitters • Acetylcholine

– excitatory • Glycine

– inhibitory

So How Does All this

Relate to Spasticity?

Pathophysiology of Spasticity Imbalance between inhibitory

and excitatory

neural input

• Loss of Inhibitory influence on segmental reflexes from suprasegmental pathways

• Spinal reflex excitability from denervation or collateral sprouting

• Gamma motor neuron hyperexcitability

Clinical Evaluation of Spasticity Physical Evaluation

– Velocity-dependent – UE flexors, LE extensors – Occurs at early ROM and sudden release

with sustained tension – Clonus vs. spasms – Upper Motor Neuron signs (Babinski)

Modified Ashworth Scale

• Modified Ashworth 0 = no increased tone 1 = Light increase in tone, manifested by a catch and release, minimal resistance at end of range of motion 1+ = slight increase in tone, followed by a catch, with minimal resistance through the entire ROM 2 = more marked increase in tone but easily flexed 3 = considerable increase in tone, PROM difficult 4 = Affected part rigid in flexion and extension

Bohannon, R. and Smith, M. (1987). "Interrater reliability of a modified Ashworth scale of muscle spasticity." Physical Therapy 67(2): 206.

Clinical Evaluation of Spasticity

– ADLs – Transfers – Resting Position – ROM

– Balance – Endurance – Orthoses – Sleep patterns – Gait analysis

Functional Capacity Evaluation

Common Clinical Conditions with Spasticity

• Traumatic Brain Injury • Stroke • Cerebral Palsy • Multiple Sclerosis • Anoxic Encephalopathy • Spinal Cord Injury • Developmental Abnormalities

Initial Approach to Spasticity

• Functional impairment from spasticity?

• Gait disturbance? • Is hypertonicity needed for standing? • Flexor spasms? • Painful spasms?

• Basic Management – Proper bed positioning – Avoid noxious stimuli – Daily stretching program

• Physical Measures – Therapeutic facilitation – Topical Cold/anesthesia – Casting/Splinting

Care of Spasticity

• Initiate with Conservative measures and progress to more invasive procedures as needed

Step 1 • Prevention of noxious

stimuli – UTI – Bowel impaction – pressure ulcers – fractures – paronychia – acute abdomen

• Patient education – Use slow movements – Use foot protection – Skin inspection – Avoid stimulus for spasticity – Teach proper body

mechanics for lifting, pushing, pulling

Step 2

• Proper positioning – Check W/C, Bed, Chair for proper positioning to

prevent contractures and pressure ulcers • Daily ROM and Stretching Program

– Static stretch to prevent contractures, capsule tightness, reduce stretch reflex hyperactivity, and improve motor control

Step 3

• Physical Modalities – Muscle cooling – Heat – Therapeutic exercises – Biofeedback – Peripheral Electrical Stimulation

• Splinting/Orthotics

Spasticity: Modalities • Cold (Cryotherapy)

– decrease myotatic stretch reflex activity

– decreases Golgi Tendon Organ firing

– slows NCV – decreases sensitivity of cutaneous

afferents – 15 - 20 min, temp < 32C – duration of effect = hrs

• Heat – physiology less clear – increases Ia afferent

firing – decreases II afferent

firing – increase Golgi tendon

firing

Spasticity: Modalities • Electrical Stimulation

– increase Ia afferent firing and inhibitory neuron firing

– neurotransmitter modulation

– duration = few hrs

• Casting/Splinting – cutaneous stimuli to

extremity - decreases tone – elongates elastic

component – increases number of

muscle fiber sarcomeres – serial casting q 2-5 days

Step 4 • Antispasticity Medications

– Zanaflex (Tizanidine) – Catapres (Clonidine) – Valium (Diazepam) – Baclofen (Lioresal) – Dantrium (Dantrolene Sodium)

Tizanidine and Clonidine Alpha-2 adrenergic agonist

– Inhibit presynaptic release

of norepinephrine from the presynaptic terminal, as well as decreases postsynaptic adrenergic neuron.

– Start Tizanidine 2mg BID and increase as tolerated

– Start Clonidine 0.1mg daily and increase 0.1mg as tolerated

• Side Effects: – Hypotension – Hepatotoxicity – Toxicity if combined with

Cipro, Levaquin, Amiodarone

– Dizziness, drowsiness, weakness, nervousness, hallucinations, depression, vomiting, dry mouth, constipation, GERD, rash

Kamen, L.; Henney, HR.; Runyan, JD. (Feb 2008). "A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury.". Curr Med Res Opin. 24 (2): 425–39. Ahlquist RP (Jun 1948). "A study of the adrenotropic receptors". The American Journal of Physiology. 153 (3): 586–600

Valium and Baclofen Gamma-aminobutyric acid (GABA)

• Valium – GABA-A receptor – GABA receptor increases

Chloride influx to hyperpolarize neuron and inhibit firing.

– Unsuitable for TBI – SE: sedation, dependence,

depression, impotence, ataxia – Dose: 4-60 mg. – Start 2 mg bid, increase by

2mg qwk

• Baclofen – GABA-B receptor – Drug of choice for SCI, CP,

MS, not cerebral forms – Less sedating than Valium – Sudden withdrawal - seizures – SE: weakness, sedation,

respiratory depression, seizures, itching, bradycardia, hypertension, incontinence, hallucinations

– Dose:10-80 mg. Start 5 mg bid, increase by 5 mg qwk Kuffler SW, Edwards C (November 1958). "Mechanism of gamma

aminobutyric acid (GABA) action and its relation to synaptic inhibition". J. Neurophysiol. 21 (6): 589–61

Peripheral Acting Agents • Dantrolene Sodium: (Ca++ inhibition)

– Works at the muscle level – Reduces Ca release from sarcoplasmic reticulum – Reduces phasic > tonic stretch reflexes – Effects fast twitch > slow twitch muscle fibers – Preferred for cerebral source of spasticity – SE: liver toxicity (1%), weakness, sedation,

dizziness, paresthesias – Dose: 25 - 400 mg. Start 25 mg bid, increase 25-

50mg qwk Krause T, Gerbershagen MU, Fiege M, Weisshorn R, Wappler F (2004). "Dantrolene – a review of its pharmacology,

therapeutic use and new developments". Anaesthesia. 59 (4): 364–73

Invasive Treatments • Motor point blocks • Peripheral Nerve blocks • Intrathecal Baclofen Pump • Neurolysis/Neurectomy • Selective Dorsal Rhizotomy • Botox Injections

Step 5

Chemical Neurolysis

– Blocks the alpha motor neuron to muscle fibers

– Decreases clonus – Increase speed and dexterity of

movement – Improved positioning and ROM – Prevent joint contractures – Increase tolerance to splinting

Chemical Nerve Blocks

• Local Anesthetics • Neurolytic Agents

– Phenol – Ethyl Alcohol

• Neurotoxins – Botox A – Myobloc B

Chemical Nerve Blocks

• Peripheral Nerve Blocks – Lumbar Spinal Nerves – Obturator Nerve – Femoral Nerve – Perineal Nerve – Sciatic Nerve – Tibial Nerve – Musculocutaneous Nerve – Median Nerve

Botulinum Toxins • Produced by Clostridium botulinum bacteria

• Seven distinct serotypes (A, B, C1, D, E, F, G)

• Type A (Botox®, Allergan; Dysport, Ipsen Ltd.) is a vacuum-dried form of purified toxin

– Botox is FDA-approved for the treatment of cervical dystonia, strabismus, blepharospasm, severe glabellar lines, and severe primary axillary hyperhidrosis that is inadequately managed with topical agents

• Type B (Myobloc®/NeuroBloc®) is a sterile liquid formulation of purified neurotoxin

– Myobloc/NeuroBloc is approved in the United States, Canada, and Europe for the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia

Simpson LL, et al. J Pharmacol Exp Ther. 2004;308:857-864. Fernandez-Salas E, et al. Proc Natl Acad Sci U S A. 2004;101:3201-3213. Data on file, Allergan Pharmaceuticals: Prescribing Information, October 2004. Data on file, Solstice Neurosciences Inc.: Prescribing Information, July 2005.

Botulinum Toxin

• Effective in 4-7 days, peaks in 4-6 weeks and lasts 3-4 months

• Immunologic development with multiple injections (no earlier than 12 weeks)

Acetycholine Vesicle Fusion Complex

Development of Extrajunctional Acetylcholine Receptors

Step 6 Surgical Intervention

• Intrathecal Medications – Intrathecal Baclofen

• Rhizotomy – Selective Dorsal Rhizotomy

• Disrupts spinal reflex arcs, not supraspinal pathways

• Young children with spastic CP – Percutaneous radiofrequency rhizotomies

Step 6 Surgical Intervention

Orthopedic Surgery – tenotomy – tendon lengthening – tendon transfers – myotomy – arthrodesis – neurectomy

Step 6 Surgical Intervention

• Myelotomy - severing tracts of spinal cord • Cordectomy - excision of portions of the

spinal cord. – Leads to severe muscle atrophy, bowel and

bladder dysfunction, loss of erectile function

CONCLUSION

• Understand Basic Neuroanatomy to Understand Spasticity

• Understand Clinic Evaluation and Treatment Options for Spasticity

• Understand Medication Management of Spacticity • Understand Invasive Options to inhibit spasticity

locally or at the CNS

Thank You