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									Intrathecal Baclofen for Spasticity

              George Jallo MD,
     Division of Pediatric Neurosurgery
          Johns Hopkins University
Spasticity
Spastikos - “to draw or tug”
   Motor disorder
   Velocity-dependent increased resistance
    to passive stretch
   Exaggerated tendon jerks
   Hyperexcitability of the stretch reflex
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
Pathophysiology of
Cerebral Origin Spasticity
           Normal brain          Damaged brain
         delivers inhibitory   fails to generate or
         neural signals to      sends inadequate
          the spinal cord       inhibitory signals




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




          Inhibitory signals
                                  Lack of neural
           modulate reflex
                                inhibition leads to
             signals–tone
                                    spasticity
           remains normal
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
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
Measuring Spasticity
   Ashworth and Modified Ashworth scales
   Spasm and reflex scales
   Passive quantitative tests
   Active tests of movement
Factors That May Increase Spasticity
Uncontrollable                Controllable
   Urinary tract infection      Stress
   Kidney stones                Ingrown nails
   Menses                       Restrictive clothing
   Bowel impaction or gas       Fatigue
   Deep vein thrombosis         Psychological factors
   Pneumonia                    Change in temperature
   Wounds or infections          or humidity
   Progression of disease
Spasticity Associated with
Cerebral Palsy (CP)
   Disorders affecting
       movement
       posture
       balance
   Injury to the developing brain
   Permanent and non-progressive
   Developmental disability
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
Conditions Associated with
Cerebral Palsy
   Mental retardation, learning disabilities
   Seizures
   Gastrointestinal difficulties
   Urinary infections
   Respiratory problems
   Hearing/vision impairment
   Orthopedic problems
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
Spectrum of Care for
Management of Spasticity
                             Intrathecal
                Prevent       Baclofen
              Nociception      (ITB™)
                               Therapy


   Rehabilitation                           Oral
     Therapy                               Drugs
                       Patient



        Orthopedic                  Injection
        Treatments                  Therapy

                     Neurosurgery
Traditional Step-Ladder Approach
 to Management of Spasticity


                   Neurosurgical
                 Orthopedic
             Neurolysis
          Oral medications
      Rehabilitation Therapy
  Remove noxious stimuli
Rehabilitation Therapy
   Stretching              Pool therapy
   Weight bearing          EMG biofeedback
   Inhibitory casting      Electrical stimulation
   Vibration of the        Positioning and
    antagonist               rotary movements
Oral Medications
   Baclofen
   Diazepam
   Dantrolene Sodium
   Tizanidine
    Site of Action for Oral Drugs
Drug                 Site of action
Baclofen:            GABAb receptors in spinal
                     cord
Diazepam:            Central nervous system
Dantrolene Sodium:   Skeletal muscles beyond the
                     myoneural junction
                     Central acting (spinal and
Tizanidine:          supraspinal) at alpha2 –
                     adrenergic receptor sites
Neurosurgery
Surgical Treatments

Neurodestructive Procedures
   Neurectomy
   Myelotomy
   Rhizotomy
   Cordectomy
   Selective Dorsal Rhizotomy
  Selective Dorsal Rhizotomy
Surgical procedure where the dorsal
(sensory) nerve roots are severed
     Two primary goals:
         facilitate patient care
              sitting, dressing, transfers
         improve function
              walking
Orthopedic Surgeries
Soft Tissue Procedures
   Tenotomy
   Tendon lengthening
   Myotomy
   Tendon transfers
Why Intrathecal vs. Oral?
Baclofen Injection            Oral Baclofen
   Baclofen injection is        Low blood/brain barrier
    delivered to the CSF          penetration, with high
    and thought to act at         systemic absorption
                                  and low CNS absorption
    GABAb receptor sites at
    the spinal cord              Lack of preferential
                                  spinal cord distribution
   Lower doses than those       Some patients
    required orally               experience
   Potential for fewer           unacceptable side
    systemic side effects         effects at effective
                                  doses
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
      ITB™ Therapy Process

   Stage   1:   Patient Selection
   Stage   2:   Screening Test
   Stage   3:   Implant
   Stage   4:   Maintenance
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.
        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.
       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.
How Does Baclofen Injection Work?
                                               Spinal cord
                                                                                         To brain
                                                                                        Epidural
                                                                                        space

      Drug                                                                           Dura-arachnoid
                                                                                     membranes
      • Spinal level                     Capillary
                                        absorption                                      Intrathecal
      • Excitatory                                                                      space
        neurotransmitters
                                      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
   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
   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
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
Interdisciplinary Team Assessment

     Considers all facets of patient’s needs
      and resources
     Considers the “whole” person
     Provides optimal care for the patient
Contraindications of ITB™ Therapy

     Patient has a history of allergy
      (hypersensitivity) to oral baclofen
     Infection is present at time of screening
      or implant
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
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
                Screening Test Flow Chart
                                Bolus: 50 mcg


                               +                     -
                                                          24 hrs after
                                                         Bolus: 75 mcg

                                                          +                    -
  +       = Positive Response                                                       24 hrs after
            “Implant”                                                              Bolus: 100 mcg

   -      = Negative Response
                                                                                    +              -
            “No Implant”

Intrathecal Baclofen Therapy Clinical Reference Guide for Spasticity Management, Medtronic, Inc.
                                                                                                       Not a Candidate
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
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
InDura® Intraspinal
Two-Piece Catheter
   Two-piece catheter
    design
   Pre-attached pump
    connector
   Tapered, open tip
Catheter Implant
   Insert the catheter
    through the
    introducer needle to
    the desired level
    (T10-T12)
   Verify catheter tip    Advancing catheter under
    position through use        fluoroscopy

    of fluoroscopy and
    CSF backflow
Pump Implant
   Abdominal incision
       make a pocket for the pump no deeper
        than 2.5 cm or 1 inch
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
              Comparison of Techniques
  Method           Age          Candidate                  Outcome              Follow-up Care             Risks                Cost
                 (Years)
Oral             Any age   Spastic quadriplegia     Mild decrease in          PT, OT as needed      Drowsiness         Medications: $40-
Medications                Diffuse spasticity       spasticity; often need                                             50/month
                                                    SDR or ITB later
Botulinum        Any age   Spastic diplegia or      Decrease in spasticity    PT, OT to increase    None               Injection: $250-400
Toxin                      quadriplegia             of injected muscles for   range of motion                          Medication: $400-800
Injections                 Isolated spasticity      2-4 months                                                         (every 3-4 months)
Baclofen (ITB)   Age> 35   Spastic quadriplegia;    Decrease in spasticity;   Frequency of PT, OT   Infection: 5-10%   Hospitilization and
                 lbs       spasticity in legs>arms; improved speech,          depends on goals      Wound: 5-10%       implant: $25,000-30,000
                           Spasticity interferes    ADLs; decrease                                  CSF leak: 5-10%    Initial medication: $400
                           with comfort, care,      orthopedic operations;                                             Refills: $200-250 (3-
                           ADLS                     reversible                                                         5/year)
                                                                                                                       Pump replacement: 5-7
                                                                                                                       years
Rhizotomy        4-7       Spastic quadriplegia or    Marked, non-adjustable PT, OT                 Infection: 2%      Hospitlization and
(SDR)                      diplegia; good leg         decrease in spasticity,                       Wound: 2%          surgery: $20,000-25,000
                           strength; no severe        improved gait, ADLs,                          CSF leak: 3-5%     PT following surgery:
                           contractures; severe leg   permanent                                                        $15,000-25,000
                           spasticity
Conclusions
   Intrathecal delivery is an alternative to
    rhizotomy procedures in children
   Advantages: simple, adjustable,
    reversible
   Disadvantages: cost, infection, toxicity

								
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