botulinum toxin in post stroke spasticity l.
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Botulinum Toxin in Post-Stroke Spasticity. 19/05/03 Craig Douglas. Spasticity. Overactivity in the muscles following damage to the brain or spinal cord Causes pain and deformity Decreases independence Increases post stroke complications

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Presentation Transcript
  • Overactivity in the muscles following damage to the brain or spinal cord
  • Causes pain and deformity
  • Decreases independence
  • Increases post stroke complications
  • Treatment may involve a combination of physio, antispasmodic drugs, BT and surgery
botulinum toxin
Botulinum Toxin
  • BT neurotoxin binds with H chain to the BT receptor at the cholinergic nerve ending
  • L chain then transported into the nerve ending, where it blocks the transport of molecules mediating the transport of Ach to the synapse
  • L chains also cleave SNARE proteins, preventing membrane formation for Ach transport
  • Action is terminated by axonal sprouting of the peripheral nerve (takes 12 weeks)
botulinum toxin6
Botulinum Toxin
  • Objective of therapy is to decrease dystonic strength as much as possible
  • However, BT has same effects on voluntary strength
  • Voluntary Strength = FS + RS
  • For BT to be effective, FS must be preserved
bt therapeutic goals
BT – Therapeutic Goals
  • Patient Care Indications

-Goals are expected decreases in staffing requirements, caring time and resource consumption

  • Therapeutic Indications

-Goals are increasing patient’s independency and decreasing pain

bt favourable prognosis
BT – Favourable Prognosis
  • Focal spasticity
  • No connective tissue involvement
  • Realistic goals
  • Relatively good power (BMRC >2)
  • Voluntary activity
  • Absence of psychological or mental impairment
  • Good motivation
bt available preparations
BT – Available Preparations
  • BOTOX and Dysport

-Neurotoxin per vial:

BOTOX = 4.8 ng

Dysport = 12.5 ng

-Adverse Reactions:

BOTOX = 15%

Dysport = 26%

bt clinical info
BT – Clinical Info
  • Clinical improvement after 2 weeks
  • Peak effects after 4-6 weeks
  • Contraindications:

-MG, aminoglycosides, bleeding disorders, pregnancy and lactation

  • Adverse Reactions:

-Purpura, arm pain, muscle weakness, hypertonia

  • No known transmission of HIV or Hep.
bt clinical info11
BT – Clinical Info
  • BOTOX – max. dose 400-500 units
  • 1 injection site for strap-like muscles
  • Multiple injection sites for flat/pennate muscles
  • May use EMG to help locate injection site
  • Therapeutic doses – too low to produce immune response
  • Macromolecule, mol wt 150 kDa, blood-brain barrier is not crossed
local treatments

Local Treatments

Local anaesthetics

Ethyl alcohol


local anaesthetics
Local Anaesthetics
  • Lidocaine, etidocaine or bupivocaine
  • Decrease/prevent the large transient increase in membrane permeability to Na ions
  • Reversible
  • Act within minutes, but effects only last hours!
local anaesthetics risks
Local Anaesthetics – Risks!
  • If drug enters systemic circulation, it interferes with the function of all organs where impulse conduction occurs
  • CNS effects- tremor, convulsions
  • May cause hypotension and inhibit cardiovascular reflexes
  • Allergic responses
  • Never use in hepatic dysfunction!
ethyl alcohol
Ethyl Alcohol
  • At low conc. (5-10%), it acts as a local anaesthetic by decreasing Na and K conductance
  • At higher conc. (30-50%), it acts as a hypobaric compound that denatures proteins and damages cells
ethyl alcohol risks
Ethyl Alcohol – Risks!
  • Burning pain at site of injections
  • Local Hyperaemia (Carpenter et al)
  • Phlebitis (O’Hanlon et al)
  • Temporary sensory defecit
  • Phenol is a derivative of benzene
  • It works by non-selectively denaturing proteins and causing tissue necrosis
  • May cause occlusion of small blood vessels and fibrosis in the injected area
phenol risks
Phenol – Risks!
  • Tendency to cause pain
  • Chronic dysaesthesiae (2-32%)
  • Peripheral oedema
  • DVT
  • Local infection due to bacteriocidal properties
  • Tremor and convulsions
alcohol and phenol

early onset action

low cost

better stability


lack of selectivity

tissue destruction

propensity to pain

lots of SE’s

Alcohol and Phenol
general treatments

General Treatments




  • Structural analogue of GABA
  • Rapid absorption, and half life of two to six hours
  • Binds to GABAb receptors pre and post synaptically, causing membrane hyperpolarisation and a decrease in endogenous transmitter release
  • Excreted by kidneys (unchanged)
baclofen side effects
Baclofen – Side Effects!
  • Sedation and fatigue
  • Confusion, N&V in brain injury!!!

-Hulme et al, Eur Journal of Clin Pharm, 1985

Trial stopped due to unacceptable levels of the above side effects in elderly stroke patients

  • Increase bronchoconstriction
  • May cause ataxia and paraesthesiae
  • May cause memory loss (animal stu)
  • These drugs work at the GABAa receptor
  • Increase presynaptic inhibition
  • Duration of action is related to metabolism of parent compound
  • Side Effects:

-Depression of CNS, synergistic with alcohol

A decrease in alertness, memory, co-ordination

Deterioration of ability to walk and grip strength

  • Unique
  • Acts at muscle fibre rather than at the neural level
  • Decreases muscle AP induced release of Ca from the SR, THEREFORE, partial uncoupling of motor nerve excitation and muscle contraction develops
dantrolene sde effects
Dantrolene – Sde Effects!
  • Sedating
  • Nausea and vomiting
  • Slurred speech, dizziness, diarrhoea and paraesthesiae
  • Hepatotoxicity – 2% of patients