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
spasticity
Spasticity
  • 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

Phenol

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
Phenol
  • 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
Advantages:

early onset action

low cost

better stability

Disadvantages:

lack of selectivity

tissue destruction

propensity to pain

lots of SE’s

Alcohol and Phenol
general treatments

General Treatments

Baclofen

Benzodiazepines

Dantrolene

baclofen
Baclofen
  • 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)
benzodiazepines
Benzodiazepines
  • 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

dantrolene
Dantrolene
  • 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