Transcript Document

Intrathecal Baclofen for Spasticity
George Jallo MD,
Division of Pediatric Neurosurgery
Johns Hopkins University
Spasticity
Spastikos - “to draw or tug”
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Motor disorder
Velocity-dependent increased resistance
to passive stretch
Exaggerated tendon jerks
Hyperexcitability of the stretch reflex
Pathophysiology of Spasticity
Theory
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Imbalance between excitatory and
inhibitory impulses to the alpha motor
neuron
Due to a lack of descending inhibitory
input to the alpha motor neuron
Descending
Inhibition
Sensory
Excitation
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
signals–tone
remains normal
Lack of neural
inhibition leads to
spasticity
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
signals–tone
remains normal
Lack of neural
inhibition leads to
spasticity
Possible Advantages of Spasticity
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Maintains muscle tone
Helps support circulatory function
May prevent formation of deep vein
thrombosis
May assist in activities of daily living
Consequences of Spasticity
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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
Measuring Spasticity
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Ashworth and Modified Ashworth scales
Spasm and reflex scales
Passive quantitative tests
Active tests of movement
Factors That May Increase Spasticity
Uncontrollable
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Urinary tract infection
Kidney stones
Menses
Bowel impaction or gas
Deep vein thrombosis
Pneumonia
Wounds or infections
Progression of disease
Controllable
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Stress
Ingrown nails
Restrictive clothing
Fatigue
Psychological factors
Change in temperature
or humidity
Spasticity Associated with
Cerebral Palsy (CP)
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Disorders affecting
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movement
posture
balance
Injury to the developing brain
Permanent and non-progressive
Developmental disability
Classifications of Cerebral
Palsy
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Location of brain lesion
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Type of movement disorder
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pyramidal, extrapyramidal, mixed
spastic, dystonic, athetoid, ataxia, mixed
Extent and location of limb involvement
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monoplegia, diplegia, hemiplegia,
paraplegia, tetraplegia
Conditions Associated with
Cerebral Palsy
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Mental retardation, learning disabilities
Seizures
Gastrointestinal difficulties
Urinary infections
Respiratory problems
Hearing/vision impairment
Orthopedic problems
Goals of Spasticity: Management
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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
Spectrum of Care for
Management of Spasticity
Prevent
Nociception
Intrathecal
Baclofen
(ITB™)
Therapy
Rehabilitation
Therapy
Oral
Drugs
Patient
Orthopedic
Treatments
Injection
Therapy
Neurosurgery
Traditional Step-Ladder Approach
to Management of Spasticity
Neurosurgical
Orthopedic
Neurolysis
Oral medications
Rehabilitation Therapy
Remove noxious stimuli
Rehabilitation Therapy
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Stretching
Weight bearing
Inhibitory casting
Vibration of the
antagonist
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Pool therapy
EMG biofeedback
Electrical stimulation
Positioning and
rotary movements
Oral Medications
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Baclofen
Diazepam
Dantrolene Sodium
Tizanidine
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
Neurosurgery
Surgical Treatments
Neurodestructive Procedures
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Neurectomy
Myelotomy
Rhizotomy
Cordectomy
Selective Dorsal Rhizotomy
Selective Dorsal Rhizotomy
Surgical procedure where the dorsal
(sensory) nerve roots are severed
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Two primary goals:
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facilitate patient care
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sitting, dressing, transfers
improve function
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walking
Orthopedic Surgeries
Soft Tissue Procedures
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Tenotomy
Tendon lengthening
Myotomy
Tendon transfers
Why Intrathecal vs. Oral?
Baclofen Injection
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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
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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
Advantages of ITB™ Therapy
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Reversible
Potentially fewer systemic side effects
Programmable
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allows dose titration to give optimal benefit
Effective in reducing spasticity
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upper and lower extremities1
cerebral and spinal origin
ITB™ Therapy Process
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Stage
Stage
Stage
Stage
1:
2:
3:
4:
Patient Selection
Screening Test
Implant
Maintenance
Efficacy in Adults and Children
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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; 11:77-83.
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.
Reported Outcomes in Patients
with Spasticity of Cerebral Origin
Method
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37 patients
Spastic quadriplegia
ITB Therapy received over a range of 3 - 48 months
Results
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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.
Reported Outcomes in Patients with
Spasticity of Spinal Origin
Method
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20 patients
Diagnosed with spinal cord injury or multiple sclerosis
ITB Therapy received over a range of 10-33 months
Results
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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
70:30-32,1989.
Penn RD, Savoy SM, Corcos D, et al. Intrathecal Baclofen for Severe Spinal Spasticity N Engl J Med 329:1517-21,1989.
How Does Baclofen Injection Work?
Spinal cord
To brain
Epidural
space
Drug
• Spinal level
• Excitatory
neurotransmitters
Capillary
absorption
Dura-arachnoid
membranes
Intrathecal
space
Catheter
CSF
Drug
Vertebra
Anatomic figure adapted from Kroin, JS. Intrathecal drug administration: present use and future trends.
Clin Pharmacokinet 1992, 22:319-326.
GABA
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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
Pharmacokinetics of Baclofen
Oral
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60 mg dose: 0.024 mcg/mL IT lumbar
concentration
Half-life 3-4 hours
Intrathecal
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600 mcg/day dose: 1.24 mcg/mL IT lumbar
concentration
Lumbar to cervical concentration is 4:1
Half-life 4-5 hours
Pharmacodynamics of
Baclofen Injection
Bolus
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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
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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
Interdisciplinary Team Assessment
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Considers all facets of patient’s needs
and resources
Considers the “whole” person
Provides optimal care for the patient
Contraindications of ITB™ Therapy
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Patient has a history of allergy
(hypersensitivity) to oral baclofen
Infection is present at time of screening
or implant
Potential Risks of ITB™ Therapy
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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
Causes of Overdose
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Dosing error
Pump malfunction
Programming error
Injecting catheter access port during
refill
Filling catheter with syringe during
surgery
Use of concomitant drugs
Screening Test Flow Chart
Bolus: 50 mcg
+
24 hrs after
Bolus: 75 mcg
+
+
= Positive Response
“Implant”
-
= Negative Response
“No Implant”
24 hrs after
Bolus: 100 mcg
+
Intrathecal Baclofen Therapy Clinical Reference Guide for Spasticity Management, Medtronic, Inc.
Not a Candidate
SynchroMed® System
Components
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Pump
 infuses drug
Catheter
 delivers drug to the
intrathecal (subarachnoid)
space of the spinal cord
Programmer
 allows for precise dosing
 easily adjustable dosing
SynchroMed® EL Pump
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Battery life of
approximately 7 years
Flow rates down to
48 microliters/day
Four suture loops
Matte finish
No changes in
clinical procedure or
pump programming
InDura® Intraspinal
Two-Piece Catheter
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Two-piece catheter
design
Pre-attached pump
connector
Tapered, open tip
Catheter Implant
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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
Pump Implant
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Abdominal incision
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make a pocket for the pump no deeper
than 2.5 cm or 1 inch
Titration Period
After First 24-Hour Period
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Increase dose slowly
Increase only once every 24 hours until
desired clinical effect achieved
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Adults with spasticity of spinal origin
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Adults with spasticity of cerebral origin
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10-30% increments
5-15% increments
Pediatrics
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5-15% increments
Comparison of Techniques
Method
Age
(Years)
Oral
Medications
Any age
Botulinum
Toxin
Injections
Baclofen (ITB)
Any age
Rhizotomy
(SDR)
4-7
Age> 35
lbs
Candidate
Spastic quadriplegia
Diffuse spasticity
Outcome
Mild decrease in
spasticity; often need
SDR or ITB later
Spastic diplegia or
Decrease in spasticity
quadriplegia
of injected muscles for
Isolated spasticity
2-4 months
Spastic quadriplegia;
Decrease in spasticity;
spasticity in legs>arms; improved speech,
Spasticity interferes
ADLs; decrease
with comfort, care,
orthopedic operations;
ADLS
reversible
Spastic quadriplegia or
diplegia; good leg
strength; no severe
contractures; severe leg
spasticity
Follow-up Care
Risks
Cost
PT, OT as needed
Drowsiness
Medications: $4050/month
PT, OT to increase
range of motion
None
Frequency of PT, OT
depends on goals
Infection: 5-10%
Wound: 5-10%
CSF leak: 5-10%
Injection: $250-400
Medication: $400-800
(every 3-4 months)
Hospitilization and
implant: $25,000-30,000
Initial medication: $400
Refills: $200-250 (35/year)
Pump replacement: 5-7
years
Hospitlization and
surgery: $20,000-25,000
PT following surgery:
$15,000-25,000
Marked, non-adjustable PT, OT
decrease in spasticity,
improved gait, ADLs,
permanent
Infection: 2%
Wound: 2%
CSF leak: 3-5%
Conclusions
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Intrathecal delivery is an alternative to
rhizotomy procedures in children
Advantages: simple, adjustable,
reversible
Disadvantages: cost, infection, toxicity