1. Intrathecal baclofen Best practices project Troubleshooting Michael Saulino, MD PhD Physiatrist MossRehab Elkins Park

2. My Disclosures Speaker’s bureau and clinical investigator for Jazz Pharmaceuticals Speaker’s bureau and clinical investigator for Medtronic, Inc Clinical investigator for Mallinckrodt Consultant for SPR therapeutics NANS Board of Directors

3. Objectives / Outline Review the techniques for evaluation and management of optimal intrathecal baclofen therapy Under-dosing Over-dosing

4. Important Caveat While this presentation (and related manuscript) focus on device related issues, it is important to recognize non-device related issues that can present in a similar fashion Noxious stimuli can drive increased tone Disease progression or exacerbation can mimic over or under dosing

5. Diagnostic evaluation process Targeted medical history –onset, course, duration, exacerbating / relieving factors of current presentation, associated symptoms –Recent intrathecal history – last refill, last dosing adjustment, last surgery, etc. Focused physical examination –Vitals –Neuromuscular exam –Item relevant for potential noxious stimuli

6. Diagnostic evaluation process Judicious use of radiologic/laboratory testing –Noxious stimuli search –CK levels –Newer Medtronic catheter is radiolucent Obtain current telemetry –Compare to prior history –Consider a bolus as a combined diagnostic / therapeutic maneuver Check reservoir volume and compared to predicted volume

7. Diagnostic evaluation process Catheter access port (CAP) aspiration Catheter dye study vs. CT myelogram with dye injection through CAP Nuclear medicine cisternogram MRI of thoracic spine

8. Differential diagnosis: under dosing Other medications Sepsis Meningitis Neuroleptic malignant syndrome Autonomic dysreflexia Serotonin syndrome Malignant hyperthermia Seizure disorder

9. Differential diagnosis: overdose Other medications Sepsis Intracranial hemorrhage Hypoglycemia Increased intracranial pressure (Cushing’s triad) Electrolyte imbalance Seizure disorder

10. Under dose/withdrawal management Treatment occurs prior to or in parallel with diagnostic workup Patient require monitoring (local resources) Tossup – triage/stabilize remotely vs. immediate transport First line therapy: restoration of intrathecal baclofen delivery –Single vs multiple boluses –LP, external catheter, new implanted system

11. Under dose/withdrawal management Restart dosing based on intensity and duration of symptoms It intrathecal delivery cannot be achieved promptly, oral medication can be used as temporizing measure Oral baclofen is agent of choice but should not be relied on to halt progressive withdrawal No uniform oral to intrathecal conversion Additional options include benzodiazepines (IV) and cyproheptadine

12. Overdose management Support airway, respiration and circulation Reduce or stop ITB delivery Option: CSF drainage Advise against physiostigmine Watch for rebound withdrawal Determine underlying cause

13. Emergency preparedness Structured, consistent on-call system including off hours coverage Direct communication between the managing clinician, implanting surgeon, emergency department, and critical-care team Patients should be educated on the signs and symptoms of over- and under dosing Patients in distress should call their managing physician AND go directly to the ED

14. Summary Patients demonstrating suboptimal effects of ITB therapy should be evaluated promptly with a focused medical history, targeted physical examination, system interrogation, and radiologic testing. Patients can demonstrate adverse effects from both over- and underdo sing. Clinicians managing these patients should be familiar with the evaluation and management of these syndromes.

15. Summary Providers of ITB therapy should create on-call and triage protocols for management of adverse effects. Patients should be educated on how to engage these protocols.