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Dantrolene

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Spasticity (and dystonia) from Neurology perspective Dr Ram Kumar Consultant Paediatric Neurologist Alder Hey June 2010 Reduce spasticity-related pain Improve sleep ... – PowerPoint PPT presentation

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Title: Dantrolene


1
Spasticity (and dystonia) from Neurology
perspective Dr Ram Kumar Consultant Paediatric
Neurologist Alder Hey June 2010
2
Summary
  • Spasticity (and dystonia) what is it?
  • Overview of treatment strategy
  • Medications
  • Botulinum toxin

3
Spasticity and dystonia management Overview of
treatment strategy First confirm it is
spasticity (or dystonia)
Consensus on the appropriate use of ITB in
paediatric spasticity. Eur J Paed Neurol 2009
4
Legs feel stiff - causes
  • Is it a muscle or joint problem?
  • Is it mainly a muscle pain/fatigue problem?
  • Spasticity or dystonia hypertonia aka increased
    muscle tone
  • Neuromuscular conditions with increased tone e.g.
    myotonia
  • Inflammatory conditions of joints skin gt
    muscles e.g. rheumatoid arthritis, scleroderma
  • Joint and muscle contractures (due to any of the
    above, disuse)

5
What is spasticity?
  • One cause of increased muscle tone
  • Resistance to passive muscle stretch at a joint
  • Velocity and joint-angle dependent
  • Has to be palpated ie you need to lay on hands
  • Other features clonus, increased reflexes,
    upgoing plantars

6
Spasticity classic muscles
  • Classic lower limb muscle groups affected - the
    pyramidal pattern
  • Ankle plantarflexors and invertors
  • Knee extensors
  • Hamstrings
  • Hip flexors and adductors

7
Spasticity classic muscles
  • Classic upper limb muscle groups affected
  • Elbow flexors biceps, brachialis,
    brachioradialis
  • Forearm pronators pronator teres
  • Wrist flexors Flexor carpi radialis, ulnaris
  • Finger flexors (long) Flexor Digitorum
    Superficialis and Profundus
  • Thumb adductors thenar group and adductor
    pollicis

8
Upper limb spasticity pattern
9
Mechanisms of spasticity
Additional aspects when spasticity arises in the
developing brain and spinal cord Loss of
descending fibres from the brain increases reflex
fibres coming in at the spinal level
10
Co-existent muscle, tendon, joint, skin issues
  • Muscle weakness i.e. -paresis and -plegia
  • Lack of selective motor control
  • Dystonia sustained postures, active movements
  • Fixed contractures
  • Bone and joint deformities
  • Skin problems abrasions, Raynaud's
  • Treating spasticity can improve, worsen or not
    change the above.
  • And vice versa.

11
What is dystonia?
  • Sustained postures
  • Involuntary movements
  • Incorrect timing of muscle activations
  • Suggests active rather than passive movements
  • Not usually velocity-dependent
  • Very dependent on mental state alertness, emotion

12
Types of dystonia
  • Excessive movements chorea, athetosis, dystonic
    tremor, myoclonus, spasms
  • Decreased movements extrapyramidal rigidity,
    hypokinesia

13
Muscle groups affected
  • Oropharyngeal mouth, tongue, pharynx, larynx
  • Axial muscles cervical, erector spinae
    (opisthotonus)
  • Upper Limbs Elbow extensor rigidity, fisting
  • Lower limbs Ankle evertors as well as invertors

14
Where dystonia comes from
The basal ganglia controls aspects of voluntary,
semi-voluntary and involuntary muscle activation
and co-contraction
And not to forget the cerebellum
15
Why bother treating spasticity - outcomes
16
Assessing impact of spasticity
  • Sitting
  • Walking,
  • Splints - tolerability
  • Posture control equipment - tolerability
  • Other orthopaedic interventions
  • Upper limb ADL
  • Ease of cares
  • Pain e.g. cramps, or agitation
  • Sleep e.g. nocturnal cramps, need for
    repositioning
  • Long term consequences - controversial

17
Check non-medication treatments in place
18
Focal and generalised spasticity
19
Intramuscular Botulinum toxin injection
  • Treatment for focal and multi-focal hypertonia
  • Reduces neuromuscular junction transmission
  • Need to identify which muscles to inject and why
  • Transient effect good and bad features
  • Good for localised therapy
  • Relatively safe
  • Different formulations and doses

20
Botulinum toxin upper limb
  • Goals of treatment cares, function, splint
    tolerance, cosmetic
  • Adjunctive therapies splint, casting, OT,
    physio
  • Assessment tools AHA (bimanual), Melbourne
    Upper limb (unilateral), COPM, VAS with
    patient/parent defined goals (simpler)
  • Good evidence of benefit with repeated injections
  • May only need to repeat at 9 months or gt1 year

21
Botulinum toxin lower limb
  • Goals of treatment pain relief, cares,
    walking,sitting, splint and other equipment
    tolerance
  • Adjunctive therapies splints, casts, physio,
    surgery
  • Assessment tools gait analysis, GMFM, VAS and
    parent/patient-defined goals
  • Botulinum toxin does not prevent or treat
    musculoskeletal deformities need surgery

22
Other focal and multi-focal therapy
  • Intramuscular phenol injections
  • Selective peripheral neurotomy
  • Selective dorsal rhizotomy (more for generalised
    lower limb )

23
Focal and generalised spasticity
24
Spasticity Medication trials
  • In cerebral palsy
  • Baclofen vs Placebo
  • Dantrolene vs Placebo
  • Other spasticity groups
  • Tizanidine vs Placebo
  • Diazepam vs Amobarbital vs Placebo
  • Gabapentin vs Placebo
  • Diazepam vs Tizanidine
  • Baclofen vs Tizanidine
  • Dantrolene vs Placebo
  • Baclofen vs Placebo

25
Baclofen
  • Typical first-line medication
  • GABA-B agonist
  • Needs at lleast three times a day dose
  • Use up to 2.5mg/kg/day
  • Additional sleep inducing effects
  • Main adverse effects sleepiness, decreased trunk
    tone, ?seizures increased

26
Diazepam and similar
  • Used to be first-line before baclofen
  • GABA-A agonist
  • Multiple effects e.g. anxiolytic, anticonvulsant
  • Significant adverse effects e.g. respiratory
    depression
  • Tolerance
  • Start at low doses e.g. 0.1mg/kg/day

27
Dantrolene
  • Works on muscle calcium-contraction coupling
  • Not sedative effect of baclofen and diazepam
  • Main adverse effect liver failure or
    asymptomatic hepatic enzyme rises
  • Problems not reported at 12mg/kg/day

28
Trihexyphenidyl
  • Treatment for dystonic posturing (hypokinetic)
  • Possibly for excessive movements as well
  • Anticholinergic (muscarinic)
  • Side effects of most anticholinergics dry mouth
    (can be useful) behaviour change
  • Start at 1mg bd increase weekly by 0.1mg/kg/day
    to 1mg/kg/day as tds

29
Others
  • L-DOPA preparations e.g. Sinemet
  • Tetrabenazine
  • Tizanidine
  • Gabapentin
  • Pregabalin
  • Azumolene
  • Clonidine
  • Fampridine-SR

30
Spasticity and dystonia management
31
The updated European Consensus 2009 on the use of
Botulinum toxin for children with cerebral palsy.
Eur J Paed Neurol 2009
32
Spasticity and dystonia management role of ITB
33
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34
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35
Goals of treatment
  • Reduce spasticity-related pain
  • Improve sleep
  • Aid posture management
  • Reduce carer requirements
  • Improve function eg upper limb
  • Relief from adverse effects of oral medication
  • Possibly improve age-dependent changes
    contractures, joint deformities, respiratory
    problems

36
Evaluation
  • Multidisciplinary including orthopaedic, physio,
    neurology, neurosurgery
  • Co-morbidities
  • Social factors
  • Local factors (geography, adaptations)
  • Physical impairment measures
  • Care and comfort hypertonicity questionnaire
    (CCHQ)
  • Paediatric Pain Profile (PPP)

37
Case Study SK
14 year old boy CP due to neonatal
meningitis Asymmetric 4 limb spasticity, left
worse Severe intellectual disability,
blind Previous bilateral hip surgery
03 Increasing pain 2 years focal and general
38
Case Study SK
Baseline Paediatric Pain Profile scores
(pre-ITB) Good day 14 Hip pain 50 Back
pain 26
39
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40
Spasticity and dystonia management Overview of
treatment strategy
Consensus on the appropriate use of ITB in
paediatric spasticity. Eur J Paed Neurol 2009
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