Good

1. Intrathecal Baclofen for Spasticity
George Jallo MD,
Division of Pediatric Neurosurgery
Johns Hopkins University

2. Spasticity
Spastikos - “to draw or tug”
 Motor disorder
 Velocity-dependent increased resistance
to passive stretch
 Exaggerated tendon jerks
 Hyperexcitability of the stretch reflex

3. 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
Descending
Inhibition
Sensory
Excitation

4. Pathophysiology of
Cerebral Origin Spasticity
Inhibitory signals
modulate reflex
signals–tone
remains normal
Lack of neural
inhibition leads to
spasticity
Normal brain
delivers inhibitory
neural signals to
the spinal cord
Damaged brain
fails to generate or
sends inadequate
inhibitory signals

5. Pathophysiology of
Spinal Origin Spasticity
Inhibitory signals
modulate reflex
signals–tone
remains normal
Lack of neural
inhibition leads to
spasticity
Inhibitory neural
signals sent to the
alpha motor
neuron
Damaged spinal
cord fails to relay
adequate inhibitory
signals
Normal Damaged

6. 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

7. 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

8. Measuring Spasticity
 Ashworth and Modified Ashworth scales
 Spasm and reflex scales
 Passive quantitative tests
 Active tests of movement

9. 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

10. Spasticity Associated with
Cerebral Palsy (CP)
 Disorders affecting
 movement
 posture
 balance
 Injury to the developing brain
 Permanent and non-progressive
 Developmental disability

11. 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

12. Conditions Associated with
Cerebral Palsy
 Mental retardation, learning disabilities
 Seizures
 Gastrointestinal difficulties
 Urinary infections
 Respiratory problems
 Hearing/vision impairment
 Orthopedic problems

13. 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

14. Spectrum of Care for
Management of Spasticity
Injection
Therapy
Neurosurgery
Orthopedic
Treatments
Rehabilitation
Therapy
Prevent
Nociception
Intrathecal
Baclofen
(ITB™)
Therapy
Oral
Drugs
Patient

15. Traditional Step-Ladder Approach
to Management of Spasticity
Neurosurgical
Orthopedic
Neurolysis
Oral medications
Rehabilitation Therapy
Remove noxious stimuli

16. Rehabilitation Therapy
 Stretching
 Weight bearing
 Inhibitory casting
 Vibration of the
antagonist
 Pool therapy
 EMG biofeedback
 Electrical stimulation
 Positioning and
rotary movements

17. Oral Medications
 Baclofen
 Diazepam
 Dantrolene Sodium
 Tizanidine

18. 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

19. Neurosurgery
Surgical Treatments
Neurodestructive Procedures
 Neurectomy
 Myelotomy
 Rhizotomy
 Cordectomy
 Selective Dorsal Rhizotomy

20. 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

21. Orthopedic Surgeries
Soft Tissue Procedures
 Tenotomy
 Tendon lengthening
 Myotomy
 Tendon transfers

22. 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

23. 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

24. ITB™ Therapy Process
 Stage 1: Patient Selection
 Stage 2: Screening Test
 Stage 3: Implant
 Stage 4: Maintenance

25. 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; 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.

26. 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.

27. 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
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.

28. Drug
• Spinal level
• Excitatory
neurotransmitters
Anatomic figure adapted from Kroin, JS. Intrathecal drug administration: present use and future trends.
Clin Pharmacokinet 1992, 22:319-326.
Intrathecal
space
Dura-arachnoid
membranes
Epidural
space
CSF
To brain
Capillary
absorption
Catheter
Drug
Vertebra
Spinal cord
How Does Baclofen Injection Work?

29. 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

30. 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 4:1
 Half-life 4-5 hours

31. Pharmacodynamics of
Baclofen 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

32. Interdisciplinary Team Assessment
 Considers all facets of patient’s needs
and resources
 Considers the “whole” person
 Provides optimal care for the patient

33. Contraindications of ITB™ Therapy
 Patient has a history of allergy
(hypersensitivity) to oral baclofen
 Infection is present at time of screening
or implant

34. 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

35. 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

36. Screening Test Flow Chart
Not a Candidate
Intrathecal Baclofen Therapy Clinical Reference Guide for Spasticity Management, Medtronic, Inc.
Bolus: 50 mcg
24 hrs after
Bolus: 75 mcg
24 hrs after
Bolus: 100 mcg
+ -
+ -
+ -
= Positive Response
“Implant”
= Negative Response
“No Implant”
+
-

37. 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

38. SynchroMed® EL Pump
 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

39. InDura® Intraspinal
Two-Piece Catheter
 Two-piece catheter
design
 Pre-attached pump
connector
 Tapered, open tip

40. 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

41. Pump Implant
 Abdominal incision
 make a pocket for the pump no deeper
than 2.5 cm or 1 inch

42. 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

43. Comparison of Techniques
Method Age
(Years)
Candidate Outcome Follow-up Care Risks Cost
Oral
Medications
Any age Spastic quadriplegia
Diffuse spasticity
Mild decrease in
spasticity; often need
SDR or ITB later
PT, OT as needed Drowsiness Medications: $40-
50/month
Botulinum
Toxin
Injections
Any age Spastic diplegia or
quadriplegia
Isolated spasticity
Decrease in spasticity
of injected muscles for
2-4 months
PT, OT to increase
range of motion
None Injection: $250-400
Medication: $400-800
(every 3-4 months)
Baclofen (ITB) Age> 35
lbs
Spastic quadriplegia;
spasticity in legs>arms;
Spasticity interferes
with comfort, care,
ADLS
Decrease in spasticity;
improved speech,
ADLs; decrease
orthopedic operations;
reversible
Frequency of PT, OT
depends on goals
Infection: 5-10%
Wound: 5-10%
CSF leak: 5-10%
Hospitilization and
implant: $25,000-30,000
Initial medication: $400
Refills: $200-250 (3-
5/year)
Pump replacement: 5-7
years
Rhizotomy
(SDR)
4-7 Spastic quadriplegia or
diplegia; good leg
strength; no severe
contractures; severe leg
spasticity
Marked, non-adjustable
decrease in spasticity,
improved gait, ADLs,
permanent
PT, OT Infection: 2%
Wound: 2%
CSF leak: 3-5%
Hospitlization and
surgery: $20,000-25,000
PT following surgery:
$15,000-25,000

44. Conclusions
 Intrathecal delivery is an alternative to
rhizotomy procedures in children
 Advantages: simple, adjustable,
reversible
 Disadvantages: cost, infection, toxicity