1. Nestor D. Tomycz M.D., Raj Nangunoori B.S., Joseph Hobbs M.D., Donald M. Whiting M.D., Michael Y. Oh M.D. Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA, U.S.A.

2.  Baclofen: an analogue of γ-aminobutyric acid (GABA)  Oral baclofen  In 1984, Penn and Kroin demonstrated the effectiveness of intrathecal baclofen  Intrathecal baclofen (ITB) has become routine in the management of spasticity and dystonia arising from either spinal or cerebral origin

3.  Dearth of literature which effectively characterizes complications related to ITB therapy  No coherent system for reporting ITB complications  To better characterize complications related to ITB therapy and to devise a simple, comprehensive, and more patient- centered scheme for complication reporting

4.  MEDLINE search: January 1985 to May 2010  N≥10 and if complications were reported  Articles were excluded if N<10 and if there were multiple articles by the same author with an overlap in patient populations  310 articles found, 28 met criteria  Reclassified complications into 4 categories: technique, device, drug, and infection

5.  Technique: due to the operative procedure itself ◦ CSF-related complications (CSF wound leaks, pseudomeningoceles), hematoma/seroma, and wound dehiscence  Drug: subjective complaints and symptoms related to baclofen ◦ Nausea, vomiting, somnolence, hypotonia, hypertonia, gastrointestinal disturbances, respiratory depression, and coma, overdose and withdrawal  Device: problems with the hardware itself ◦ pump (flipping, failure), catheter (kinks, breaks, tears, and migration)  Infections: related to the pump or catheter incision ◦ Wound infection/dehiscence was categorized here due the cause and effect relationship to the two, “wound dehiscence” was otherwise categorized as a complication of surgical technique.

6.  28 papers met criteria for systematic review and included prospective trials, retrospective studies, and case series  2,623 unique patients, 1,637 complications  Combined complication incidence: 62.4%  Range in total complication incidence: 10-570%  Device complications (n=587, 35.5%) were the most frequent followed by drug (n=544, 33.2%) followed by technique (n=293, 17.8%), and infection (n=213, 13.4%)

7.  Among technique complications, CSF-related complications (n = 113, 6.9%) were the most common followed by hematoma/seroma (n = 14, 0.9%)  Among drug complications, non-postural headache, nausea, vomiting, dizziness, and drowsiness were the most commonly reported (n = 212, 13.0%)  Baclofen overdose/withdrawal: n = 28, 1.7%  Among device complications, catheter-related problems were the most common (n = 193, 11.8%)  8/28 studies (28.6%) reported no drug complications

8. Table 1. Complications by Author Articles (Author)Year# of patientsTechnique (%)Drug (%)System (%)Infection (%)# of complic Albright et al.20036811.614.93.91.4141 Albright et al.200410014.70.01.02.354 Smail et al.2006640.30.01.51.413 Follett et al.20002091.70.24.87.049 Gilmartin et al.20005110.223.04.12.3184 Gooch et al.20041524.10.79.93.882 Guillaume et al.20051293.40.21.51.924 Ivanhoe et al.2006743.411.21.42.384 McCall et al.2006480.70.01.71.415 Murphy et al2002231.41.11.05.227 Nielsen et al.2002792.70.62.93.335 Plassat et al.2004400.06.15.33.872 Rawlins et al.2004505.12.66.00.565 Sadiq et al.2006361.00.03.90.026 Vender et al.20061955.81.59.411.3104 Wunderlinch et al.20065710.0 21.145 Zahavi et al.2004215.512.95.30.9119 Hoving et al2008178.59.40.5 80 Motta et al.200720011.60.03.69.475 Armstrong et. al.1997120.32.21.71.426 Borowski et. al.20101741.45.38.214.6112 Heetla et. al.2009370.02.91.90.929 Rawicki et. al.1999180.70.60.30.58 Ford et. al.1996121.01.70.20.013 Penn et. al.19951020.0 11.20.066 Coffey et. al.1993751.72.24.30.543 Teddy et. al.1992462.70.94.12.342 Penn et. al.1989200.30.000.510.004 2623 patients293 technique complications 544 drug complications 587 device complications 213 infections1637 total complications

9. Table 1. Technique Complications Defined Complication# of Total Events% of Total % of Surgical Complications CSF leak (and other CSF-related)1136.938.6 wound hematoma/seroma513.117.4 other231.47.8 non-serious221.37.5 pain/discomfort/swelling161.05.5 wound dehiscence140.94.8 spinal headache140.94.8 surgery related140.94.8 wound pruritus40.21.4 wound leakage40.21.4 moving pump30.21.0 skin necrosis/breakdown30.21.0 suture site inflammation20.10.7 incontinence20.10.7 pocket erosion20.10.7 catheter dislodgement during surgery10.10.3 debridement of granuloma10.10.3 incomplete operation10.10.3 pressure ulcer10.10.3 femoral vessel occlusion10.10.3 skin erosion req. pump removal10.10.3

10. Table 2. Drug Complications Defined Complication # of Total Events % of Total % of Drug Complications headache/nausea/vomiting/dizziness/d rowsiness 21213.039.0 hypotonia/hypertonia/muscle weakness/spasms 996.018.2 epileptic seizures/convulsions/psychiatric changes/alteration in consciousness 613.711.2 constipation/urinary or fecal incontinence/drooling or salivation 402.47.4 drug overdose/withdrawal and drug overinfusion/underinfusion § 281.75.1 cardiovascular/respiratory system related 201.23.7 dysarthria/dysphagia/appetite changes/difficulty swallowing 130.82.4 other140.92.6 accidental injury120.72.2 pain110.72.0 loss of efficacy/lack of response80.51.5 pressure sore40.20.7 sweating30.20.6 auditory hallucinations20.10.4 baclofen side effects when oral medication added 20.10.4 decubitus20.10.4 decreased trunk control20.10.4 significant side effect/drug adverse effect 20.10.4 dry mouth20.10.4 malignant hyperthermia/death*10.10.2 chemical meningitis10.10.2 hair loss10.10.2 paroxysmal paleness10.10.2 urticaria10.10.2 hypothermia10.10.2 coma after baclofen overdose10.10.2

11. Table 3. Device Complications Defined Complication # of Total Events # of Total % of Device Complications catheter kink/break/tear/hole/occlusion 19311.832.9 catheter disconnection/dislodgement/ migration* 1378.423.3 unspecified catheter problems/catheter dysfunction 1076.518.2 pump problems (flip/failure/others) 865.314.7 catheter problems (drawing out, disconnection, breakage) § 211.33.6 other140.92.4 catheter fibrosis110.71.9 catheter cut, break, or disconnection § 60.41.0 malfunction of unidentified cause 40.20.7 underinfusion30.20.5 back pain at catheter site20.10.3 inversion20.10.3 malfunction of side port10.10.2

12. Table 4. Infection Complications Defined Complication# of Total Events% of Total% of Infections Infection (unspecified)804.937.6 pump explantation due to infection503.123.5 pump/pump pocket infection462.821.6 wound infection/dehiscence100.64.7 septic/aseptic meningitis100.64.7 infection in the back70.43.3 urinary tract infection50.32.3 lumbar infection10.10.5 aspiration pneumonia10.10.5 infected hematoma10.10.5 infection w/pump salvage after antibiotic therapy 10.10.5 cystitis10.10.5

13.  Our primary objective: report the combined incidence of complications related to ITB therapy and to devise a classification scheme that is more patient-centered  We selected the 4 categories for classification for their simplicity and comprehensiveness  We found a combined complication incidence of 62.4%

14.  The incidence of complications related to ITB remains high  Much of the reporting on ITB complications has neglected patient- centered complaints (especially drug complications)  Although ITB has been touted as having a lower side effect profile than oral baclofen, drug complications from ITB are not rare  Improvements in ITB may be prompted by better complication reporting  The 4-tiered complication scheme for ITB will help patients better appreciate the risks of ITB