Transcript neuropharmacology of spasticity

Improving life and end-of-life care in
advanced neurological conditions:
Spasticity Management
Rory O’Connor MD
Consultant Physician in Rehabilitation Medicine
Airedale General Hospital
Overview
What is spasticity?
Epidemiology
Current spasticity treatment
Pharmacotherapy
What is Spasticity?
Spasticity Diagnosis
Central nervous system lesion
– Motor and sensory loss
Increased muscle tone
– Especially rate dependent increase in tone
Provoked or unprovoked spasms
Consequences of Spasticity
Contractures
Skin breakdown
Pain and discomfort
Impairments
Restricted participation
Caregiver strain
Spasticity
What is Spasticity?
Supraspinal Input
Supraspinal or higher spinal lesion results
in a net loss of inhibition below lesion
– Dorsal Reticulospinal tract ( - )
– Medial Reticulospinal tract (+)
– Corticospinal tract (+)
– Vestibulospinal tract (+)
– Coerulospinal tract (+)
Spinal Input
1. Reflex disinhibition
– Nociceptive reflex: flexor withdrawal
– Propriospinal phasic reflex: tendon reflex
2. Primitive reflex release
– Cutaneous: extensor plantar response
– Proprioceptive: positive support reaction
3. Tonic stretch reflex
Tonic Stretch Reflex
No reflex activity in response to muscle
stretch in a relaxed normal person
Mediated via 1a afferents from muscle
spindle
Length dependent
– Reflex inversely related to muscle length
Loss of Supraspinal Input
Uncontrolled efferent drive
– Hemiplegic posture
Associated reaction
– Failure to inhibit spread of motor activity
Disordered muscle control
– Co-contraction
Neurotransmitters
Gamma amino butyric acid (GABA)
– Inhibition of motor neurons
Glutamate
– Excitation of motor neurons
Alpha-2 adrenergic
– Spinal interneuron inhibition
Soft Tissues in Spasticity
Muscle biochemical changes: thixotropy
–
–
–
–
Stiffness
Contracture
Fibrosis
Atrophy
Tendon changes
Joint changes
What is Spasticity?
An increased tonic stretch reflex resulting
in velocity- and length-dependent
hypertonia due to abnormal spinal
processing of proprioceptive input
Epidemiology of Spasticity
Epidemiology of Spasticity
Spinal
– Traumatic spinal cord injury
– Non-traumatic spinal cord injury
60%
Supraspinal
– Stroke
– Multiple Sclerosis
– Cerebral Palsy
– Traumatic Brain Injury
20%
30%
50%
19%*
Current Spasticity Treatment
Current Spasticity Treatment
Reduction of noxious stimuli
Multidisciplinary programme
Pharmacotherapy
– Generalised, regional, focal
Surgery
Spasticity Treatment
Cost may inhibit decision to treat
– Time-consuming and multidisciplinary
– Expensive equipment and seating systems
But untreated spasticity
– May mask voluntary movement
– Result in permanent contractures
– Window of opportunity may be small
Reduction of Noxious Stimuli
Reduction of Noxious Stimuli
Reduction of Noxious Stimuli
Reduction of Noxious Stimuli
Reduction of Noxious Stimuli
Reduction of Noxious Stimuli
Multidisciplinary Teamwork
Careful positioning throughout 24-hours
– Maintaining muscle length
– Reducing deformity
Regular stretching
Splinting and orthoses
All act to reduce the tonic stretch reflex
Seating
Pharmacotherapy
Pharmacotherapy Follow-up
No point in pharmacotherapy without
– Avoidance of precipitating factors
– Adequate therapy/splinting/orthosis
– Appropriate seating review
Pharmacotherapy
Generalised
– Oral baclofen, dantrolene, tizanidine
Regional
– Intrathecal baclofen or phenol
Focal
– Intramuscular botulinum, phenol neurolysis
Generalised
Generalised
Reduce excitatory neurotransmitters
– Tizanidine
Facilitate inhibitory neurotransmitters
– Baclofen
Inhibit skeletal muscle contraction
– Dantrolene
Regional
Intrathecal Baclofen
Test dose to screen for effectiveness
Non-destructive and reversible
Dose titratable
Reduction of side effects compared to
oral baclofen
– 1% of oral dose
Intrathecal Pump
Abdominal pocket for
pump
Intrathecal catheter
tunnelled
subcutaneously
Intrathecal Phenol
Severe lower limb spasticity affecting
care, positioning or causing pain
Generalised treatments ineffective or
causing side effects
Other regional and focal treatments
inappropriate
Bowel, bladder and sexual dysfunction
Modified Right Lateral Position
30o
Spinal fluid
Modified Right Lateral Position
Injection of Phenol
Injection of Phenol
Spinal fluid
Injection of Phenol
End Result
Spinal fluid
Unexpected Findings
Final Outcome
Focal
Phenol Nerve Blocks
Non-selective denervation
– Protein denaturation
– Destruction of nerve axons
Effect apparent immediately and
diminishes with time
Injection of mixed nerves will cause
anaesthesia as well as paralysis
Commonly Blocked Nerves
Musculocutaneous
– Biceps brachii, brachialis
Obturator
– Hip adductors
Sciatic
– Hamstrings
Posterior tibial
– Gastrocnemius, soleus
Botulinum
Botulinum exotoxin
– Types A and B available commercially
Intramuscular injection
– Endocytosed in pre-synaptic neuron
– Cleaves acetylcholine
– Neuromuscular junction function inhibited
Axon sprouting terminates effect 2-6
months
EMG Guidance
Botulinum - FDS
Botulinum - FDP
Botulinum - Hypersalivation
Botulinum - Hypersalivation
Take Home Message I
Spasticity limits activities in two ways
– Inhibiting muscle power and coordination
– “Masking” profound muscle weakness
But anti-spasticity agents produce muscle
weakness
Take Home Message II
Spasticity is the result of
– Neural
– Non-neural
} abnormalities
Take Home Message III
Multidisciplinary treatment must comprise
– Neural
– Non-neural
} modalities