1. Intrathecal Baclofen Pump & other management strategies for Spasticity William O McKinley MD Director, SCI Rehabilitation Medicine Dept. PM&R VCU / 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. Symptoms of Spasticity NEGATIVE SX’s Weakness Function Sleep Pain Skin, hygiene Social, Sexuality contractures USEFUL SX’s Stability Function Circulation Muscle “bulk”

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. Spasticity Scales “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

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