Intrathecal Baclofen for Spasticity

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Intrathecal Baclofen for Spasticity

• George Jallo MD,
• Division of Pediatric Neurosurgery
• Johns Hopkins University

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Spasticity

• Spastikos - to draw or tug
• Motor disorder
• Velocity-dependent increased resistance to
  passive stretch
• Exaggerated tendon jerks
• Hyperexcitability of the stretch reflex

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Pathophysiology of Spasticity

• Theory
• Imbalance between excitatory and inhibitory
  impulses to the alpha motor neuron
• Due to a lack of descending inhibitory input to
  the alpha motor neuron

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Pathophysiology of Cerebral Origin Spasticity
Normal brain delivers inhibitory neural signals
to the spinal cord
Damaged brain fails to generate or sends
inadequate inhibitory signals
Inhibitory signals modulate reflex signalstone
remains normal
Lack of neural inhibition leads to spasticity
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Pathophysiology of Spinal Origin Spasticity
Normal
Damaged
Inhibitory neural signals sent to the alpha motor
neuron
Damaged spinal cord fails to relay adequate
inhibitory signals
Inhibitory signals modulate reflex signalstone
remains normal
Lack of neural inhibition leads to spasticity
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Possible Advantages of Spasticity

• Maintains muscle tone
• Helps support circulatory function
• May prevent formation of deep vein thrombosis
• May assist in activities of daily living

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Consequences of Spasticity

• May interfere with mobility, exercise, joint
  range of motion
• May interfere with activities of daily living
• May cause pain and sleep disturbance
• Can make patient care more difficult

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Measuring Spasticity

• Ashworth and Modified Ashworth scales
• Spasm and reflex scales
• Passive quantitative tests
• Active tests of movement

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Factors That May Increase Spasticity

• Uncontrollable
• Urinary tract infection
• Kidney stones
• Menses
• Bowel impaction or gas
• Deep vein thrombosis
• Pneumonia
• Wounds or infections
• Progression of disease

• Controllable
• Stress
• Ingrown nails
• Restrictive clothing
• Fatigue
• Psychological factors
• Change in temperature or humidity

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Spasticity Associated with Cerebral Palsy (CP)

• Disorders affecting
• movement
• posture
• balance
• Injury to the developing brain
• Permanent and non-progressive
• Developmental disability

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Classifications of Cerebral Palsy

• Location of brain lesion
• pyramidal, extrapyramidal, mixed
• Type of movement disorder
• spastic, dystonic, athetoid, ataxia, mixed
• Extent and location of limb involvement
• monoplegia, diplegia, hemiplegia, paraplegia,
  tetraplegia

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Conditions Associated withCerebral Palsy

• Mental retardation, learning disabilities
• Seizures
• Gastrointestinal difficulties
• Urinary infections
• Respiratory problems
• Hearing/vision impairment
• Orthopedic problems

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Goals of Spasticity Management

• Decrease spasticity
• Improve functional ability and independence
• Decrease pain associated with spasticity
• Prevent or decrease incidence of contractures
• Improve ambulation
• Facilitate hygiene
• Ease rehabilitation procedures
• Save caregivers time

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Spectrum of Care forManagement of Spasticity

PreventNociception
IntrathecalBaclofen(ITB)Therapy
RehabilitationTherapy
OralDrugs
Patient
InjectionTherapy
OrthopedicTreatments
Neurosurgery
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Traditional Step-Ladder Approach to Management
of Spasticity

• Neurosurgical
  Orthopedic Neurolysis
• Oral medications
• Rehabilitation Therapy
• Remove noxious stimuli

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Rehabilitation Therapy

• Stretching
• Weight bearing
• Inhibitory casting
• Vibration of the antagonist

• Pool therapy
• EMG biofeedback
• Electrical stimulation
• Positioning and rotary movements

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Oral Medications

• Baclofen
• Diazepam
• Dantrolene Sodium
• Tizanidine

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Site of Action for Oral Drugs

• Drug
• Baclofen
• Diazepam
• Dantrolene Sodium
• Tizanidine

• Site of action
• GABAb receptors in spinal cord
• Central nervous system
• Skeletal muscles beyond the myoneural junction
• Central acting (spinal and supraspinal) at alpha2
  adrenergic receptor sites

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NeurosurgerySurgical Treatments

• Neurodestructive Procedures
• Neurectomy
• Myelotomy
• Rhizotomy
• Cordectomy
• Selective Dorsal Rhizotomy

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Selective Dorsal Rhizotomy

• Two primary goals
• facilitate patient care
• sitting, dressing, transfers
• improve function
• walking

Surgical procedure where the dorsal (sensory)
nerve roots are severed
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Orthopedic Surgeries

• Soft Tissue Procedures
• Tenotomy
• Tendon lengthening
• Myotomy
• Tendon transfers

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Why Intrathecal vs. Oral?

• Baclofen Injection
• Baclofen injection is delivered to the CSF and
  thought to act at GABAb receptor sites at the
  spinal cord
• Lower doses than those required orally
• Potential for fewer systemic side effects

• Oral Baclofen
• Low blood/brain barrier penetration, with high
  systemic absorption and low CNS absorption
• Lack of preferential spinal cord distribution
• Some patients experience unacceptable side
  effects at effective doses

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Advantages of ITB Therapy

• Reversible
• Potentially fewer systemic side effects
• Programmable
• allows dose titration to give optimal benefit
• Effective in reducing spasticity
• upper and lower extremities1
• cerebral and spinal origin

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ITB Therapy Process

• Stage 1 Patient Selection
• Stage 2 Screening Test
• Stage 3 Implant
• Stage 4 Maintenance

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Efficacy in Adults and Children

• 86 cerebral origin (screening test)
• 97 spinal cord origin (screening test)
• Upper and lower extremities
• Both patients with functional goals and patients
  with goals of improving comfort and ease of care
• Albright, A. Leland. Baclofen in the Treatment
  of Cerebral Palsy, J Child Neurol 1996 1177-83.
• Becker, R., Alberti, O., and Bauer, B.L.
  Continuous intrathecal baclofen infusion in
  severe spasticity after traumatic or hypoxic
  brain injury, J Neurol 1997 244 160-166.
• Campbell, Susan K., Almeida, Gil L., Penn,
  Richard D., and Corcos, Daniel M. The Effects of
  Intrathecally Administered Baclofen on Function
  in Patients with Spasticity, Phys Ther 1995 75
  352-362.

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Reported Outcomes in Patients with Spasticity of
Cerebral Origin

• Method
• 37 patients
• Spastic quadriplegia
• ITB Therapy received over a range of 3 - 48
  months
• Results
• 6 and 12 months post implant
• muscle tone significantly decreased in lower and
  upper extremities
• 25 children capable of self-care at start of
  study
• significant improvement in
• ADL
• upper extremity function
• hamstring extensibility

Albright AL, Barron WB, Fasick MP, et al.
Continuous Intrathecal Baclofen Infusion for
Spasticity of Cerebral Origin. JAMA
270(20)2475-77, Nov 24, 1993.
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Reported Outcomes in Patients with Spasticity of
Spinal Origin

• Method
• 20 patients
• Diagnosed with spinal cord injury or multiple
  sclerosis
• ITB Therapy received over a range of 10-33 months
• Results
• Statistically significant decreases in muscle
  tone of hip, knee, and ankle musculature
• based on Ashworth score
• Statistically significant decrease in frequency
  of spasms
• Functional status tracked in 8 patients (6 months
  duration)
• improved ADL
• improved bowel and bladder management programs

Parke B, Penn RD, Savoy SM, et al. Functional
Outcome after Delivery of Intrathecal Baclofen.
Arch Phys Med Rehabil 7030-32,1989. Penn RD,
Savoy SM, Corcos D, et al. Intrathecal Baclofen
for Severe Spinal Spasticity N Engl J Med
3291517-21,1989.
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How Does Baclofen Injection Work?
Spinal cord
To brain
Epiduralspace

• Drug
• Spinal level
• Excitatory neurotransmitters

Dura-arachnoidmembranes
Capillaryabsorption
Intrathecalspace
Catheter
CSF
Drug
Vertebra
Anatomic figure adapted from Kroin, JS.
Intrathecal drug administration present use and
future trends. Clin Pharmacokinet 1992,
22319-326.
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GABA

• Gamma-butyric acid (GABA)
• an inhibitory neurotransmitter
• Baclofen
• thought to act as a GABA agonist in the spinal
  cord, reducing positive input to the alpha motor
  neuron

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Pharmacokinetics of Baclofen

• Oral
• 60 mg dose 0.024 mcg/mL IT lumbar concentration
• Half-life 3-4 hours
• Intrathecal
• 600 mcg/day dose 1.24 mcg/mL IT lumbar
  concentration
• Lumbar to cervical concentration is 41
• Half-life 4-5 hours

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Pharmacodynamics ofBaclofen Injection

• Bolus
• Onset of action is one-half hour to 1 hour after
  intrathecal bolus
• Peak effect at 4 hours after dosing
• Effects may last from 4 to 8 hours
• Continuous
• Effects are first seen at 6 to 8 hours after
  initiation of continuous infusion
• Maximum effect observed in 24 to 48 hours
• Onset, peak response, and duration of action may
  vary

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Interdisciplinary Team Assessment

• Considers all facets of patients needs and
  resources
• Considers the whole person
• Provides optimal care for the patient

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Contraindications of ITB Therapy

• Patient has a history of allergy
  (hypersensitivity) to oral baclofen
• Infection is present at time of screening or
  implant

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Potential Risks of ITB Therapy

• Common side effects hypotonia, somnolence,
  nausea/vomiting, headache, dizziness
• Overdose, although rare, could lead to
  respiratory depression, loss of consciousness,
  reversible coma, and in extreme cases, may be
  life-threatening
• Catheter and procedural complications may occur

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Causes of Overdose

• Dosing error
• Pump malfunction
• Programming error
• Injecting catheter access port during refill
• Filling catheter with syringe during surgery
• Use of concomitant drugs

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Screening Test Flow Chart
Bolus 50 mcg

24 hrs after Bolus 75 mcg

24 hrs after Bolus 100 mcg
-

Not a Candidate
Intrathecal Baclofen Therapy Clinical Reference
Guide for Spasticity Management, Medtronic, Inc.
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SynchroMed System Components

• Pump
• infuses drug
• Catheter
• delivers drug to the intrathecal (subarachnoid)
  space of the spinal cord
• Programmer
• allows for precise dosing
• easily adjustable dosing

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SynchroMed EL Pump

• Battery life of approximately 7 years
• Flow rates down to48 microliters/day
• Four suture loops
• Matte finish
• No changes in clinical procedure or pump
  programming

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InDura IntraspinalTwo-Piece Catheter

• Two-piece catheter design
• Pre-attached pump connector
• Tapered, open tip

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Catheter Implant

• Insert the catheter through the introducer needle
  to the desired level (T10-T12)
• Verify catheter tip position through use of
  fluoroscopy and CSF backflow

Advancing catheter under fluoroscopy
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Pump Implant

• Abdominal incision
• make a pocket for the pump no deeper than 2.5 cm
  or 1 inch

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Titration Period

• After First 24-Hour Period
• Increase dose slowly
• Increase only once every 24 hours until desired
  clinical effect achieved
• Adults with spasticity of spinal origin
• 10-30 increments
• Adults with spasticity of cerebral origin
• 5-15 increments
• Pediatrics
• 5-15 increments

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Comparison of Techniques
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Conclusions

• Intrathecal delivery is an alternative to
  rhizotomy procedures in children
• Advantages simple, adjustable, reversible
• Disadvantages cost, infection, toxicity