Intrathecal Baclofen Pump & other management strategies for Spasticity William O McKinley MD Director, SCI Rehabilit

1. Intrathecal Baclofen Pump & other management strategies for SpasticityWilliam O McKinley MDDirector, SCI Rehabilitation Medicine Dept. PM&RVCU / MCV

2. What is Spasticity ? • Abnormal, velocity-dependent increase in resistance to passive movement of peripheral joints due to increased muscle activity.

3. Spasticity: Etiology (Diagnosis) • Spinal Cord Injury • Traumatic Brain Injury • Stroke • Multiple Sclerosis • Cerebral Palsy

4. Pathophysiology • Intrinsic hyperexcitability of alpha motor neurons within the spinal cord secondary to damage to descending pathways • cortico, vestibulo, reticulospinal • CNS modification • neuronal sprouting • denervation hypersensitivity

5. NEGATIVE SX’s Weakness Function Sleep Pain Skin, hygiene Social, Sexuality contractures USEFUL SX’s Stability Function Circulation Muscle “bulk” Symptoms of Spasticity

6. Spasticity: Treatment Decisions • Is Spasticity: • Preventing function?, Painful? • A result of underlying treatable stimulus • A set-up for further complications? • What Rx has been tried? • Limitations and SE’s of Rx… • Therapeutic goals

7. Goals of Therapy • Ease function (ambulation, ADL) • Decrease Pain, contracture • Facilitate ROM, hygiene

8. “Modified” Ashworth 0= no increased tone 1= slight “catch” in ROM 1+= minimal resistance 2= moderate tone, easy ROM 3= marked tone, difficult ROM 4= Rigid in flexion or extension Spasm Frequency Scale 0= none 1= mild 2= infrequent 3=> 1 per hour 4= > 10 per hour Spasticity Scales

9. Rehab Evaluation (con’t) • Gait patterns • Transfer abilities • Resting positioning • Balance • Endurance

10. Management Options • Physical interventions • systemic medications • chemical denervation • Intrathecal agents • orthopedic interventions • neurosurgical interventions

11. Rehabilitation Interventions • Positioning (bed, wheelchair) • Modalities • heat (relaxation) • cold (inhibition) • Therapeutic Exercise • inhibitory to spastic muscles • facilatory to opposing muscles • Orthotics

12. Non-Conservative Treatment Options • Oral Medications • Injections (Phenol , Botox) • ITB (Intra-Thecal Baclofen) • Surgical (nerve, root, SC) • Spinal Cord Stimulator

13. Oral Antispasticity Medications • Baclofen • Dantrium • Diazepam • Clonidine • Tizanidine • (limitations: non-selective, side effects)

14. Baclofen (Lioresal) • GABA-B analogue; binds to receptors • inhibits release of excitatory neurotransmitters (spasticity control) • Ca++ (pre-synaptic inhibition) • K+ (post-synaptic inhibition) • may also decrease release of substance P (pain control)

15. Dantrium • Inhibits Ca++ release at muscle level • Preferred : TBI, CVA, CP • SE’s - weakness, GI • Hepatotoxicity (<1%)

16. Diazepam • GABA “potentiation” • Usage : SCI, MS • SE’s - CNS depression, dependence,

17. Clonidine • Alpha-2 receptor blockage • Usage : SCI • Max dose - .4mg/d (oral & patch) • SE’s - OH, syncope, drowsiness

18. Tizanidine (Zanaflex) • 1996 - Approved for SCI, MS, CVA • Alpha-2 agonist (pre-synaptic inhibition) • 1/10 potency of Clonidine In lowering BP • Dose: T1/2: 2-5hr, begin 4 mg qhs (max 36 mg) • SE’s - Sedation, nausea, LFT’s

19. Chemical Neurolysis • Phenol 5-7%- Motor Point/Nerve block • Non-selective destruction of axons/myelin • Inds: Local (not general) spasticity • Duration: 3-6 months • SE’s - dysesthetic pain

20. Botulinum Toxin • 1989 FDA approved for strabismus & blepherospasm • Botox-A inhibits Ach Release at NMJ • Dose: 300-400u total (50-200/muscle) • Onset: 2-4 hours, Peak : 2-4 weeks • Duration: 3-6 months • ? Immunoresistance w/repeated inj’s

21. Spasticity: Surgical Management • Rhizotomy (posterior) • Cordotomy • Tendon Release • (limitations: invasive, bowel/bladder changes, irreversible, effectiveness varies)

22. Intrathecal Baclofen and Spasticity • Intrathecal delivery of baclofen via an inplantable pump is a safe and effective therapy for the management of spasticity !

23. Intrathecal Baclofen • Indicated for patients unresponsive to oral meds or with SE’s • Delivered directly to intrathecal space affording much higher drug concentration • Implantable system allows non-invasive monitoring & adjustments

24. ITB: Successful Outcomes • Study results since 1984 demonstrate reduction of Ashworth spasticity scores and spasm scales • Other results include improvements in: • pain • bladder function • chronic drug side effects • quality of life for patient & caregiver

25. ITB: Outcome Studies • “Intrathecal baclofen for spasticity of spinal origin: seven years of experience”…Penn* (J. neurosurg 77:236-40, 1992) • 66 patients with intractable spasticity • followed for 30 months • “It is suggested that long term control of spinal spasticity by intrathecal baclofen can be achieved in most patients”

26. ITB: Outcome Studies • “Intrathecal baclofen for intractable spasticity of Spinal of spinal origin: a long-term multicenter study”…..Coffe* (J. Neurosurg 78; 226-32, 1993) • 93 patients with intractable spasticity • followed 19 months • “Results indicate intrathecal baclofen can be safe and effective for long term management in SCI or MS”

27. Outcome Studies: Meta Analysis • *Dijkers- Meta analysis of 37 studies • 77% positive response to bolus dose • 91% of whom opted for implant • 84% of whom had benefit w/o SE’s • Avg Dec’d Ashworth: 3.95-1.53 (P<.0001) • negligible effect of LOI • * J.Spinal Cord Med:19(2), 138, 1996

28. ITB • 1992 - FDA Approved ITB for spinal Spasticity • 1996 - FDA Approved for Cerebral Etiologies (BI and CP)

29. ITB: Pharmacokinetics • Baclofen: GABA-b agonist; inhibits neuronal firing • ITB (Lioresal) • preservative-free; stable for 90 days • half-life 1.5 hours • typical dose: 1/100 of oral dose • average daily dose: 300-800ug • lumbar/cervical ratio 4:1

30. Decision to Treat w/ ITB • Have oral antispasticity meds truly failed? • Are their SE’s too great? • Can a single definitive surgical procedure accomplish similar goals? • Is precise control necessary for functional gains? • Does gain in function / comfort justify invasive procedure & maintenance?

31. Exclusion Criteria • Severely impaired renal function • Pregnancy / nursing mothers • Severe Aut. Dysreflexia • Hx of Hypersensitivity to baclofen • Hx of Noncompliance to regimens or follow-up

32. Trial Dose • Trial dose via intrathecal lumbar puncture • Begin with 50 ug (if no response, 75-100 ug) • Observe 2-8 hrs • Positive response = decrease in spasticity • also access functional abilities

33. ITB: Surgical Phase • Subcutaneous abdominal placement • Catheter tunneled to mid-lumbar region below L3 and advanced 10 cm • Intra-operative fluoroscopy confirms catheter placement without twisting • Total time: 1-2 hours

34. Post-Operative Phase • Pump programming via radio-telemetry and computer begins day one post-imp;ant • ITB concentration: 500mcg/ml • ITB rate: 2 X bolus response (less if patient had prolonged (>12 hrs) response) • Can increase 10-15% every 24 hrs • maintenance follow-up: 1-4 weeks

35. Post-Implant Clinical Care • Post-Operative Adjustments • Pump Dosing Adjustments • Taper Oral Meds • Pump Refills • Patient Education

36. ITB: Maintenance Phase • scheduled follow-ups for pump reassessment, refill and reprogramming • percutaneous refill into “port” (template) • dose adjustment: portable computer/telemetry • calculate next refill date • if sudden changes in spasticity occurs, assess for potential infection, bowel/bladder regimen, before increasing dosage • consider “drug holiday”

37. Pump Adjustments • Adjustment parameters include: • drug name and concentration • reservoir status ( __ ml) • alarms (low battery; low reservoir) • infusion rate • infusion pattern (continuous, intermittent, complex) • may increase by up to 15% per adjustment

38. Infusion Modes • Continuous: drug delivered at continuous specified rate • Continuous-complex: step-wise increases/decreases at specified times • Bolus-delay: drug delivered intermittently at specific intervals

39. ITB Side Effects • Drowsiness • Dizziness • Blurred Vision • Slurred Speech • Nausea • Orthostasis • Confusion

40. Potential Pump Complications • Drug over-infusion - somnolence, coma • no antidote • Physostigmine 1-2mg IV (.02 mg/kg) over 5-10 min • titrate ITB • Pump / Catheter malfunctions (kinking, disconnection, breaks)…often readily correctable under local anesthesia • Infections

41. Pump /System Complications & Trouble-shooting • r/o volume discrepancy • check pump setting • empty & compare fluid reservoir • r/o catheter kink, occlusion, disconnection • X-Ray catheter / CT intrathecal catheter • dye/ contrast study to check patency • bolus/infusion w/sereal scans over 12-24 hr • r/o pump underinfusion • X-Ray “roller” pre/post bolus

42. Pocket Complications • seroma, hematoma, infection • Causes • post-op swelling • inadequate fixation • infection • pocket too small • drug extravasation

43. Suspected CSF Leak • headache, dizziness, N/V, spinal swelling / redness • RX: • X-Ray / CT • culture of fluid • blood patch • surgical revision

44. Advantages of Programmable System • Consistent optimal dosage • can be programmed to decrease or increase spasticity at certain times during the day • reduces adverse drug effects