pathophysiology of spasticity

SPASTICITY - PATHOPHYSIOLOGY AND MANAGEMENT

DR. SUMIT S. KAMBLESENIOR RESIDENTDEPT. OF NEUROLOGYGMC, KOTA

• Spasticity is frequent and often disabling feature of neurological disease.

• Spasticity is motor disorder that is characterized by velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper excitability of the stretch reflex, as one component of the upper motor neuron syndrome. J.W.Lance(1980)

CHARACTERISTIC FEATURES• Velocity dependence- increased tone of spasticity is velocity

dependent, that is, the faster the stretch, the greater the muscle resistance

• ‘Clasp-knife’ phenomenon- spastic limb initially resists movement and then suddenly gives way, like the resistance of a folding knife blade

• Distribution- differential distribution with antigravity muscles being more affected

ACCOMPANIMENTS OF SPASTICITYPositive features• Clonus- involuntary rhythmic contractions, response to sudden

sustained stretch, alternate loading and off-loading of muscle spindles

• Spasms- sudden involuntary movements involving multiple muscle groups and joints, repetitive and sustained, represent an exaggerated reflex withdrawal response to nociceptive stimuli

• Exaggerated tendon reflexes

• Babinski sign

Negative components

• Spastic co-contraction- inappropriate activation of antagonistic muscles during voluntary activity. It is due to loss of reciprocal inhibition during voluntary contraction

• Motor weakness

• Slowed movements

• Loss of dexterity

COMPLICATIONS Spasticity if left untreated or sub-optimally treated, may lead to

consequences, such as:• Muscle contractures (leading to abnormal body segment loading

and sensory change),• Limb deformity and altered body mechanics,• Pressure sores,• Difficulty in the management of pressure sores,• Pain from muscle spasms,• Degenerative joint disease,• Loss of function, and• Mood problems and inability to participate in rehabilitation.

VICIOUS CYCLE OF SPASTICITY

PATHOPHYSIOLOGYMuscle tone• Visco-elastic properties of muscle• Neural drive from spinal motor neurons

Control• Cortical- motor areas of the cortex facilitate ventromedial reticular

formation• Supraspinal descending pathwaysInhibitory pathway- dorsal reticulospinal tract, which arises in the

ventromedial reticular formationExcitatory pathways1) Medial reticulospinal tract- arising in the bulbopontine tegmentum,

major pathway2) Vestibulospinal tract

NORMAL PHYSIOLOGY• Function of muscle spindle1. It is receptor organ for stretch reflex 2. It is play important role in maintaining the muscle tone.

INNERVEATIONS OF SPINDLES

GOLGI TENDON ORGAN

RECIPROCAL INHIBITION

PATHOPHYSIOLOGY• Immediately after SCI, there are depressed spinal reflexes during

state of spinal shock, followed by development of hyperreflexia and spasticity over the following weeks to month.

• Pathophysiology of spasticity is not completely understood; however, it is believed to arise primarily from loss of the effect of numerous descending inhibitory pathways. These include reciprocal 1a interneuronal inhibition, presynaptic inhibition, renshaw-mediated recurrent inhibition, group II afferent inhibition, and Golgi tendon organs.

• Axonal collateral sprouting and denervation super sensitivity are change that may also play a role in the development of spasticity.

MECHANISM AT VARIOUS LEVELSCortical & Supraspinal descending pathways• Loss of cortical facilitation of the inhibitory pathway(dorsal

reticulospinal tract)• Partial spinal cord lesion, which destroys the inhibitory pathways

but preserves the excitatory fibres• Complete spinal cord lesion affecting both inhibitory and

excitatory pathways

Spinal Cord• Loss of recurrent inhibition- mediated by motor axon collaterals

and Renshaw cell• Loss of reciprocal inhibition- mediated by antagonistic muscle

spindle afferents

• Reduced inverse stretch reflex- mediated by Golgi tendon organs• Reduced presynaptic inhibition of muscle spindle afferents

Spinal motor neuron• Denervation supersensitivity• Collateral sprouting

Muscles and joints• Shortening of sarcomeres• Loss of elastic tissue• Fibro-fatty deposits in muscles and tendons

Upper extremity patterns

1. Adduction and internal rotation of the shoulder

2. Flexion of the elbow and wrist

3. Pronation of the forearm

4. Flexion of the fingers and adduction of the thumb

• PECTORALIS MAJOR • LATISSIMUS DORSI • TERES MAJOR • BICEPS • BRACHIORADIALIS • BRACHIALIS

• PRONATOR TERES AND QUADRATUS

• FLEXOR CARPI RADIALIS AND ULNARIS

• FLEXOR DIGITORUM PROFUNDUS AND SUPERFICIALIS

• ADDUCTOR POLLICIS

Lower extremity patterns1. HIP ADDUCTION AND

FLEXION

2. KNEE FLEXION

3. ANKLE PLANTAR FLEXION OR EQUINOVARUS POSITIONING

4. KNEE EXTENSION

5. EQUINUS AND/OR VALGUS ANKLE

6. GREAT TOE DORSIFLEXION

• ADDUCTOR MAGNUS • ILIOPSOAS

• HAMSTRINGS (MEDIAL MORE OFTEN THAN LATERAL)

• TIBIALIS POSTERIOR • SOLEUS • GASTROCNEMIUS

• QUADRICEPS FEMORIS

• PERONEUS LONGUS

• EXTENSOR HALLUCIS LONGUS

ADDUCTED/INTERNALLY ROTATED SHOULDER

FLEXED ELBOW PRONATED FOREARM FLEXED WRIST

CLINCHED FIST THUMB IN PALM DEFORMITY STRIATAL TOE EQUINOVARUS

STIFF KNEE FLEXED KNEE ADDUCTED THIGHS

ASSESSMENT

Modified Ashworth scale

• Most frequently used clinical methods for estimation of spasticity

Tardieu scale

Waternberg Pendulum Test

• Patient is seated or lying with lower leg hanging over end of couch.

• Examiner then extends the leg to the horizontal position, while patient is told to relax. Leg is then released and allowed to swing freely under the action of gravity.

• With the use of electrogoniometers, swing of the leg about knee joint may be evaluated

• In individuals with spasticity, reduction of swing is generally found.

MANAGEMENTWhen to treat• Not all spasticity requires treatment- inappropriate treatment of

spasticity may lead to loss of function, when spasticity is counterbalancing effects of paresis

• May need to be treated when it causesPainDifficulty performing ADLImpaired mobility, whether related to ambulation or transfersPoor joint positioningIncreased risk for development of contractureSkin breakdown

Aims to reduce the impact of spasticity to prevent secondary complications

Goals relief of discomfort improved sitting, standing and walking, facilitated activities of

daily living reduced burden of care improved body image and self-esteem prevention of complications

Identification and elimination of triggers

Non pharmacological interventions • Passive movements• Exercises• Posture & Standing• Physical modalities

Medications• Oral• Injectables

Surgical

Identification and elimination of triggers

Patient and carer education to recognise these triggers is important part of management

• Pressure ulcers• Ingrown toenails• Skin infections• Injuries• Constipation• Urinary tract infection• Deep vein thrombosis• Improper seating• Ill-fitting orthotics

Passive movements

Passive stretching decreases excitability of motor neurones and maintains visco-elastic properties of muscles and joints

Prolonged stretching can help to treat contractures

Stretching can be facilitated by using casts or splints, sometimes used together with botulinum toxin injections

No conclusive evidence whether therapy is effective but no evidence that it is harmful

Exercises Improve motor control and cardiovascular fitness in people with

UMN disorders

Posture and standing• Stretches spastic muscles and decrease sensitivity of stretch

reflex and brain stem reflexes that trigger spasticity• Weight bearing and standing also help to improve psychological

wellbeing, to improve bone mineral density, facilitate pulmonary drainage and helps bowel and bladder functions

• Proper positioning of limbs and trunk is essential to prevent aggravation spasticity and development of contractures

• Devices such as splints help to position limbs properly

Physical modalities• These physical modalities work through either modulating the

visco-elastic properties of muscles and tendons

UltrasoundCryotherapy Vibration Shockwave therapy Magnetic stimulationTranscutaneous electrical nerve stimulation (TENS)

• limited evidence base to support the use

Medications Principles of drug therapy• Weakness is a side effect of all antispasticity drugs, usually due

to unmasking of underlying UMN weakness

• A ‘start low and go slow’ policy limits these unwanted functional effects

• Reach maximal tolerated dose for a sufficiently long period before stopping a drug and labeling it as ineffective

• Patients not responding to one drug may respond to another

• Sudden stopping of even an apparently ‘ineffective’ drug may cause a rebound increase in spasticity. It is better to taper initial drug while simultaneously introducing the second drug.

• Combination of two drugs should be tried if the spasticity does not respond to a single agent

• It is important to time the doses according to the patient’s activity, care and therapy

Oral agentsGamma aminobutyric acid (GABA)ergic system• Baclofen• Gabapentin • Benzodiazepines

α-2 adrenergic system • Tizanidine

Block calcium release into the muscles• Dantrolene

Cannabinoids

Baclofen• Most widely used oral antispasticity drug• Mechanism GABA-B receptor agonistReduces calcium influx↓s release of excitatory neurotransmitters(glutamate & aspartate)Down-regulates activity of 1a sensory afferents, spinal interneurones

& motor neurones

Dosestarting - 5 mg thrice dailyMaintenance- ↑d by 5–10 mg weekly, until there is an optimal

effectMax- 90–120 mg per day

Adverse effects• Weakness, drowsiness and dizziness• Sexual dysfunction & urinary incontinence• Reduces seizure threshold• Sudden withdrawal may also cause seizures and hallucinations,

sometimes accompanied by extreme hyperthermia and increased spasticity (baclofen withdrawal syndrome)

• Caution pregnancy- animal studies show impaired sternal ossification and omphalocele

Benzodiazepines• Act on GABA-A receptors, enhances the presynaptic inhibitory

effect of GABA and decreases spasticity

• Absorbed faster than baclofen, acts faster, and has a longer lasting effect

• Drowsiness and behavioural side effects limit its use during the daytime

• Particularly useful to treat spasticity that interferes with sleep• Clonazepam is particularly useful to treat nocturnal spasmsUsual starting dose is 0.5 mg at nightMaximum dose of 1 mg

Tizanidine• Mechanismα-2 receptor agonist Inhibits excitatory spinal interneurones and tracts from locus

coeruleus• DoseStarting dosage is 2 mg at bedtime, increased by 2 mg weekly to a

maximum of 36 mg, divided into 3–4 daily doses• Adverse effectsDry mouth, gastrointestinal disturbance, hypotension and acute

hepatitisSudden stopping of tizanidine can lead to a hyperadrenergic

syndrome, characterised by anxiety, tremor, hypertension and tachycardia

Dantrolene• MechanismBlocks calcium release from sarcoplasmic reticulum and interferes

with excitation–contraction coupling of the skeletal muscleActs directly on the muscle and so is less sedative

• DoseStarting dose is 25 mg daily for the first week, increased in steps of

25 mg per week to a top dose of 100 mg 3–4 times daily

• Adverse effectsMuscle weakness, sedation, diarrhoeaMost important side effect is hepatotoxicity, and so liver function

must be monitored carefully

Cannabinoids• Cannabinoid receptors in dorsal spinal cord, basal ganglia,

hippocampus and cerebellum, and these modulate spasticity

• Cannabidiol & Nabiximols limited role in managing treatment-resistant spasticity

• May be worth trying in patients who are not responding to a combination of two drugs in adequate doses

• 30–40% of people show a response, treatment effect should be reviewed at 4–6 weeks and continued only if there is an objective improvement

• Concerns about its long-term effects on cognition, behaviour and mental health

Botulinum toxin• Prepared from the bacterium Clostridium botuliniumMechanismHeavy chain binds to and becomes internalised into presynaptic

nerve endingsDegrades synaptosomal-associated protein 25, a protein required

for fusion of acetylcholine vesicles to the presynaptic membrane.Inhibits release of acetylcholine, thereby blocking neuromuscular

transmissionAfferent effectAnalgesic effectReversal• Effect is reversed by nerve sprouting and reinnervation which

develops over 3-4 months

• UsageParticularly useful in treatment of focal spasticity. Electromyography, nerve stimulator or ultrasound can be used

to identify the target musclePostinjection interventions such as physiotherapy, splinting and

serial casting help to maximize benefitsPatient should be reassessed 4–6 weeks after the initial

injections to assess the efficacy of the injectionsIf required, further injections should be planned after 3–4

months

• Adverse effectsMuscle weakness, urinary incontinence, falls, fever and pain.

Phenol• Chemical neurolysis5% concentration Injected directly into peripheral nerves cause destruction of

neural tissue by protein coagulation• Usageeffective in treating spasticity that occurs in large, powerful

muscle groups close to the trunk- thigh adductorsblocks to the medial popliteal muscles to aid spastic foot drop,

or obturator nerve blocks either in patients with scissoring gait or to improve perineal hygiene and seating posture

A neurostimulator with a Teflon-coated needle electrode is used for guidance

Often has effects lasting many months(~6mths) and can be repeated if necessary

Nerve sprouting may lead to recurrence of spasticity

Adverse effectsNerve injury, causalgia or neuropathic pain because of sensory

fiber damage, Tissue edema, venous thrombosis, and compartment syndrome

resulting from large amounts of phenol in constrained space Skin sloughing and wound infection.

PhenolInjection of phenol guided by nerve stimulation forobturator nerve for treatment of adductor spasticity

Alcohol• Acts as a local anesthetic by decreasing sodium and potassium

conductance at the nerve membrane at low concentrations.

• It causes protein denaturation at higher concentration

Adverse effects• Causes pain during injection

Local anesthetics• Block nerve conduction by changing membrane permeability to

sodium ions• Effect is completely reversible• Effect starts within 3-15 minutes after the injection and lasts

from 45 minutes to 8-12 hours• Lidocaine, etidocaine and bupivacaine are used for nerve blocks• 3 mg/kg of 0.25 to 0.75% solution bupivacaine

Intrathecal baclofen• Indication-Significant lower-limb spasticity which persists despite

adequate treatment with at least two oral antispasticity drugs concomitantly

• Principle- Oral baclofen has only very low bioavailability to GABAergic

neurones in spinal cordAdministered intrathecally, arelatively small dose of baclofen

can give a high concentration of drug within the spinal cordPatients should initially be screened using a temporary catheter

with an initial test dose is 50 micrograms.

• Devicecomprises a subcutaneous pump which stores and delivers

programmable doses of baclofen through a catheter into the spinal subarchanoid space

can be adjusted to vary the doses delivered, depending on the level of patient activity and needs

• antispastic effects of intrathecal baclofen are obtained at 1% of daily oral dose

• ComplicationsProcedure related complications- infection, skin erosions, cerebrospinal

fluid leak.Abruptly stopping ITB can cause high fever, confusion, rebound

spasticity and muscle rigidity, similar to neuroleptic malignant syndrome• Signs of overdose are drowsiness, dizziness, somnolence, seizures,

respiratory depression and loss of consciousness progressing to coma.

Intrathecal baclofen

Neurosurgical management• For severe spasticity following the failure of noninvasive

management (adequate medical and physical therapy)

PERIPHERAL NEUROTOMYIndications

Procedure It involves microdissection guided by neuro-stimulation at low

intensity Extent of the nerve resection- must be limited to a maximum to

4/5 fibres, over a length of 5 mm, to prevent any regrowth Care must be taken with the sensory fibres, if too many cut in the

sensory peripheral nerve, may induce neurogenic pain

Results(Mertens et al., 180 pts) Reduction of spasticity in 82% of cases, with recurrence in only

8% Reduction in pain 85%, and a reduction in cutaneous lesions 78% 10% functional improvement, recovery of some ability to walk

Microsurgical DREZotomyPrinciple Modern dorsal rhizotomy is a hyper-selective rhizotomy

At the periphery, nerve fibres are mixed

Technique of Dorsal Root Entry Zone-otomy (DREZotomy) consists of selective cutting of fibres at the dorsal root zone, including a large area up to the superfcial layers of the posterior grey matter

• Technique was especially developed for treating neurogenic pain

Indication• Severe and regional spasticity, possibly associated with chronic

intractable pain

Procedure• Lesion, max depth 3mm is placed 45° in the ventromedial

direction at dorsal radicular spinal junction

Results (Mertens and Sindou (1998) ) n =151 patients with lower limb spasticity, follow-up 5.6 yrs Decreased hypertonia - 78% Ashworth < 2 Decreased spasms - 88% Increased voluntary mobility - 11% Decreased pain - 82%

Spinal cord stimulationPrinciple Selective stimulation of the larger fibres in order to inhibit the

activity of the smaller nociceptive fibres and so to decrease the nociceptive input at the level of the spinal cord

Level of stimulation dependent on the topography of the spasticity Electrode must be placed in the posterior epidural space in order to

stimulate the dorsal columns Various authors report improvement varying from 50% to 80%

over a period of 2 to 5 yrs, some report no significant improvement Currently considered as an alternative only if other conservative

and surgical treatments do not work

Stratified management approach

European Journal of Neurology 2002, 9 (suppl. 1): 48–52

THANK YOU

REFERECES

• Spasticity: pathophysiology, evaluation and management Practical Neurology 2012;12:289–298

• Sheean G. 2002. The pathophysiology of spasticity. European Journal of Neurology 9 (Suppl 1):3-9.

• Pathophysiology of spasticity Journal of Neurology, Neurosurgery, and Psychiatry 1994;57:773-777

• Pathophysiology of Spasticity: Implications for Neurorehabilitation BioMed Research InternationalVolume 2014 (2014), Article ID 354906,

• Dejong Neurology 7th edition • UPTODATE.COM