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
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

5. 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

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
Prevent Nociception
Intrathecal Baclofen (ITB™) Therapy
Rehabilitation Therapy
Oral Drugs
Patient
Orthopedic Treatments
Injection Therapy
Neurosurgery

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
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:
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:

26. Reported Outcomes in Patients with Spasticity of Cerebral Origin
Method
37 patients
Spastic quadriplegia
ITB Therapy received over a range of 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): , 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 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: ,1989.

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

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

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. Advancing catheter under fluoroscopy
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

43. Comparison of Techniques

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