Original Paper Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
Received: August 22, 2013 Accepted after revision: January 2, 2014 Published online: February 21, 2014
Complications of Intrathecal Baclofen Pumps in Children: Experience from a Tertiary Care Center Debabrata Ghosh Gayatra Mainali Jena Khera Mark Luciano Pediatric Neurology Center, Children’s Hospital, Cleveland Clinic, Cleveland, Ohio, USA
Abstract Background/Aims: Intrathecal baclofen (ITB) therapy is useful in treating spasticity and dystonia but it has many complications, more so in children. The main aim of the study was to look at the complications of ITB pumps in children with the goal of future prevention. Methods: Charts of all patients ≤21 years with an ITB pump, implanted by a single pediatric neurosurgeon, at a single center, between 1996 and 2011 were reviewed retrospectively. Data regarding an ITB test trial were also recorded. Results: During 1996–2011, 119 children (mean age 13.2 years) underwent ITB pump placement; 84% had spastic quadriplegic cerebral palsy. The gross motor function classification system level was ≥4 for most. The pump was removed in 5 (4.2%) patients due to inefficacy. The mean follow-up was 38 months. Mechanical complications requiring pump and/or catheter revision occurred in 19.3% and infections in an additional 21.8%. Seven patients (6%) had meningitis. No complication was noted after 72 months of initial pump insertion, even after pump reinsertion. Conclusion: There is a need for better infection control as well as better pump, catheter and surgical technology to lower the complications of ITB pumps in children. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 1016–2291/14/0493–0138$39.50/0 E-Mail [email protected] www.karger.com/pne
Introduction
Baclofen, structurally similar to γ-amino butyric acid, has γ-amino butyric acid mimetic action. It acts through stimulation of chloride channels inhibiting the release of excitatory neurotransmitter/s. Spasticity can be conceptualized as hyperactivity of the lower motor neuron, no more under inhibitory control of the upper motor neuron, either as part of brain (cerebral spasticity) or spinal cord (spinal spasticity) pathology. Baclofen controls spasticity by the reduction of the hyperactivity in this monosynaptic reflex arc at the level of the spinal cord. Dystonia can also improve through the same mechanism. The problem with systemic baclofen use is its wide spread effect in the central nervous system, in addition to the effect at the spinal cord. Delivering baclofen directly near its site of action around the spinal cord at the subarachnoid cerebrospinal fluid space may avoid many untoward central side effects. Hence came up the idea of the intrathecal baclofen (ITB) pump. In 1984, Penn and Kroin [1] were the first to use a baclofen pump to treat spasticity of spinal origin, and in 1985 Dralle et al. [2] for spasticity of cerebral origin. The Food and Drug Administration approved the ITB pump for spasticity of spinal origin in 1992 and of cerebral origin in 1996. The efficacy of ITB pumps for spasticity management has been proven by many studies, both in children and in adults [3–6]. This procedure is also helpful in the management of medically refractory secondary dystonias [7, Debabrata Ghosh, MD Pediatric Neurology Center, Desk S60 Cleveland Clinic 9500 Euclid Avenue, Cleveland, OH 44195 (USA) E-Mail ghoshd10 @ gmail.com
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Key Words Spastic quadriplegia · Dystonia · Cerebral palsy · Intrathecal baclofen pump · Complications
8]. The cost-effectiveness of this procedure in the treatment of spastic cerebral palsy has been proven in 2007 by the elegant study by De Lissovoy et al. [9]. With increasing experience and more stringent follow-up, the adverse effects of the ITB pump due to an accidental baclofen overdose (drowsiness, hypotension, respiratory depression, profound hypotonia and weakness), underdose or withdrawal (increasing muscle tone, pain, spasm, fasciculation, hyperpyrexia and muscle breakdown) have been minimized. However, the complications still remain high [5, 10–17]. The complications of ITB pumps may be categorized as: (a) mechanical and (b) infection-related. Mechanical complications are observed in 4–24% either due to pump or catheter problems. The common mechanical complications are erosion of the skin over the pump, disconnection of the catheter at the connector site, kinks or breaks in the catheter, cerebrospinal fluid leak at the catheter insertion site, cystic collection around the pump or spinal entry point of the catheter. Infections occur in 5–26% of cases in various series. They may occur as superficial or deep wound infection, pump or catheter infection, or meningitis. The overall complications due to an ITB pump vary from 20 to 50% depending on various factors like patient age, weight and severity of the disease process. The complication rates are higher in children when compared to those in adults [15, 16]. The study by Vender et al. [15] in 2006 had a total of 218 ITB pumps done over a 5-year period: 72 in adults and 146 in children. Pump revisions were needed in 3.4% of all children compared with 2.7% in adults, catheter revision in 24% of children versus 14% of adults. Wound infections were noted in 25% of children versus 5% of adults. In 2009, Fjelstad et al. [10] looked into the infection rate following ITB pump insertion in 91 children and compared it with that in 72 adults. The infection rate was significantly higher in children. There was some initial concern about rapid progression of scoliosis in children after the ITB pump based on some case reports, but later larger controlled studies disproved that notion [17–21]. With the undoubtedly proven efficacy of the ITB pump in managing spasticity and/or dystonia, the next step in improving the outcome from ITB pumps will be through reduction of the complication rate, more so in children. The experience of various centers dealing with ITB pumps in children may help in finding common factors contributing to the complications. Thus, we thought of sharing our experience of ITB pumps in children mainly in regard to the complications of the procedure in our setting so that more effective strategies in preventing the complications can be implemented.
Table 1. Primary diagnoses and GMFCS of the children with ITB
Intrathecal Baclofen Pump Complications
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
pumps Parameters Primary diagnoses Spastic quadriplegia Spastic diplegia Spastic hemiplegia Generalized dystonia GMFCS Level II Level III Level IV Level V
Number of patients (n = 119) 100 12 1 6 7 32 64 16
Methods All consecutive patients aged ≤21 years who underwent ITB pump surgery for spasticity and/or dystonia, inserted by a single pediatric neurosurgeon (M.L.) in a single center (the Cleveland Clinic) between the years 1996 and 2011 were included in this study. After obtaining permission from the Institutional Review Board, charts of all consecutive patients as mentioned above were obtained from the hospital record section. Those charts were extensively reviewed to extract the following data: age of the patient, age at pump insertion, diagnosis/indication, history, relevant examination findings including mental/cognitive status and associated dystonia, modified Ashworth tone scales for spasticity [22], ITB trial results, perioperative asepsis, location of the pump in the abdominal wall (subcutaneous or subfascial), site of the catheter tip, maximum dose of ITB, adverse effects, complications, change in degree of scoliosis, and follow-up. Those data were entered in an Excel spread sheet, and statistics were applied. The contribution of various factors like age, sex, weight, the site of the catheter tip, severity of spasticity and/or dystonia, Gross Motor Functional Classification Scale (GMFCS) in the production of the complications were looked into. KaplanMeyer survival curves were obtained for the development of total (all complications), mechanical and infectious complications over time.
A total of 119 children had ITB pumps in our center during the 16-year period (1996–2011). Males (n = 67) outnumbered females (n = 52). The mean age at pump insertion was 13.2 ± 5.5 years (range 3–21 years). Table 1 shows the primary diagnoses and GMFCS scores of the patients. The patients with significant spasticity involving more than one limb, not tolerating oral baclofen or other antispasticity medications due to sedation or other side 139
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Results
ITB Pump Data A single surgeon (M.L.) did all the pump insertions. Alcohol was used as prep solution which was replaced by betadine for the last 2 years of the study period. No routine perioperative antibiotic was used. In most patients the baclofen pump was placed subcutaneously, only 10 had subfascial placement. The catheter entered the spinal canal at the L3–L4 level, and the catheter tip was advanced to the C6–T4 level in 7 patients, the T5–T8 level in 55 cases, the T9 level in 42 cases and the T10–L5 level in 15 cases. The distribution of spasticity determined the catheter tip position; the lumbar area was chosen if spasticity involved primarily the lower limbs, the midthoracic region was chosen if the lower limbs were more affected than the upper, the lower cervical or upper thoracic region was chosen if the upper limbs were more severely affected than the lower limbs. The average dose of ITB was 334 ± 234 μg/day (range 25–1,099 μg/day). The dose requirement was not dependent on the level of the catheter tip. Improvement was noted in all except 5 cases who later decided to take the pump out. Only 1 patient had a serious adverse effect due to a programming error leading to accidental baclofen overdose during the refill and reprogramming process. The patient developed drowsiness, hypotension and respiratory depression requiring shortterm intubation in the intensive care unit. He had the catheter tip at the T5 level. Lowering the baclofen dose and bringing down the catheter tip to the T9 level helped managing his spasticity without any further adverse event. 140
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
0.8
0.6
0.4
0.2
0 0
20
40
60
80
100
120
Time (months)
Fig. 1. Kaplan-Meyer curve showing complication-free patient
survival of all patients with an ITB pump. The continuous line indicates total complications, the dashed line mechanical and the dotted line infectious complications.
Table 2. Major complications following ITB pump implantation
Total complications
Number of patients (n = 49)
Infection of incision site Meningitis without infection at incision site Meningitis with infection at incision site Catheter displacement/disconnection Skin erosion over pump Catheter fracture Cerebrospinal fluid leak
19 4 3 10 8 4 1
Complications Complications were noted in 49 patients when followed over a mean period of 38 months (range 0.5– 120 months). The overall complication-free survival at 72 months was 40% (fig. 1). Table 2 shows the major complications. Mechanical complications occurred in 23, and 26 had infections. The whole of the baclofen pump system (pump and catheter) was removed if there was meningitis or deep infection, to be replaced only after the infection had cleared. Only the pump was repositioned when skin erosion over the pump was noted without any infection. For catheter malfunction/kink/ fracture, only the catheter was revised keeping the pump in situ. A persistent cerebrospinal fluid leak in 1 patient Ghosh/Mainali/Khera/Luciano
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ITB Test Trial A test trial with a 50-μg bolus of ITB was performed in all. Pre-ITB and 4-hour post-ITB modified Ashworth scores (average) were calculated. The average decrease in Ashworth scores was 3.1 ± 2.42 (range 0.05–10.75). Postspinal tap headache was noted in 3 of 119 patients but was mild and managed with adequate hydration and supine posture.
1.0
Survival function
effects on the central nervous system were evaluated in a multidisciplinary spasticity clinic attended by a pediatric neurologist, neurosurgeon, orthopedic surgeon and the experienced therapists (both physical and occupational). The decision to subject the patient to an ITB trial was based on the consensus among the members of the spasticity clinic. The final decision to insert the pump was based on the objective documentation of improvement of spasticity after the ITB trial without any worsening of other clinical condition/s.
Table 3. Details of cases with meningitis without infection at the incision site Age, Sex years
Diagnosis
Level of catheter
Year of Timing of Sequelae pump meningitis placement
Organism
6 18 16 17
Spastic quadriplegia with VPS TBI, SAH, VPS Obstructive hydrocephalus with VPS Spastic CP
T10–T11 T10 T8–T9 T6
2001 2001 2001 2001
MSSA MSSA CONS Pseudomonas
Male Male Female Male
2 weeks 10 days 3 years 1 month
None, treated with IV antibiotics None, treated with IV antibiotics None, treated with IV antibiotics None, treated with IV antibiotics
was managed with repair of the hole around the spinal catheter entry site. Most infections (50%) occurred within the first month after surgery. Meningitis, the most serious infectious complication, can occur with or without local incision site infection. Details of cases with meningitis without associated incision site infection are presented separately in table 3. Catheter-related complications were spread throughout the postpump period, though they were clustered more (10 out of 23 occurrences) around 3–6 months after pump insertion. Age, sex, weight, pump or catheter tip location, severity of spasticity or GMFCS score did not predict the occurrence of the complications. We observed 35 documented scolioses before pump placement; 7 of them progressed further to require corrective scoliosis surgery after baclofen pump placement. The cumulative complication-free pump survival (Kaplan-Meyer) for all patients is shown in figure 1. The Kaplan-Meyer plot in figure 1 shows 3 graphs showing total, mechanical and infectious complications over time. The slopes of the curves again demonstrate the fact that infections happen more in the early postpump period, whereas mechanical complications can happen any time after the surgery. Importantly, the complication rate was negligible after a period of 72 months even after routine pump revision.
Discussion
A total of 119 children with ITB pumps make this series one of the larger ones in the literature. The facts that it is a single-center study and that all the surgeries are done by the same surgeon have both merits and demerits. The demerit is the smaller sample size. The possible merits are: (a) the data may be more meaningful due to reIntrathecal Baclofen Pump Complications
striction of the number of variables affecting the results; (b) interventions based on the observation may be easier. The spectrum of cases in our series conforms to other series in children [14, 16, 23–25]. Most had cerebral palsy, the commonest type being spastic quadriplegia (84%). As per the existing literature, also supported by our study, the ITB pump is effective in the management of spasticity and/or dystonia in children [3, 5, 6, 8, 9, 16, 26–29]. Of 119 cases in our series, only 5 (4.2%) patients’ parents were not happy with the response in spite of the therapeutic ITB dose. Those pumps were taken out with the insistence of the parents as efficacy declined over time. Each patient had a 50-μg bolus trial of ITB before the final decision of implanting the pump. All had positive responses to the bolus trial with a significant decrease in tone. None required a prolonged intrathecal catheter infusion trial. The catheter trial consists of slow continuous infusion of ITB with the help of an intrathecal catheter over 2–3 days. A catheter trial is rarely undertaken at some centers when there is a doubtful response to the bolus trial, in spite of clinically detectable prominent spasticity and/or dystonia. Except a self-limiting mild postlumbar puncture headache in 3, no other complication was observed in any case during or after the trial. In all cases the catheter entered the spinal canal through the lumbar area; however, the catheter tip was placed at various levels depending on the distribution of spasticity. Catheter tip location did not influence the dose required, side effects or complications. This observation is consistent with the existing literature [3, 13, 30]. The average daily amount needed to achieve an optimal response in our series was 334 μg/day, which is in accordance with other studies in children [3, 14, 17, 25, 31]. Regarding adverse effects, we encountered only one serious dose-related adverse effect in a patient where an Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
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VPS = Ventriculoperitoneal shunt; IV = intravenous; MSSA = methicillin-sensitive Staphylococcus aureus; TBI = traumatic brain injury; SAH = subarachnoid hemorrhage; CONS = coagulase-negative Staphylococcus; CP = cerebral palsy.
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are too limited to conclude that scoliosis progressed more rapidly after ITB pump insertion. This is more so in the context of the average age of the patients when pumps were placed. Rapid progression of scoliosis in children with cerebral palsy frequently occurs at around the same age when the ITB pump was inserted in our patients. Due to the small number, this study does not definitely answer the question but we agree with the recent literature disproving the older notion that scoliosis progresses more rapidly after the insertion of the ITB pump [18, 32]. It is very interesting to note that all the complications, both mechanical and infections, in this series are extremely uncommon after a period of 6 years even after routine revision of the pump. The most likely reason may be a better tolerance of the foreign body producing little reaction after years. Increase in weight, body surface area, ease of surgery or improvement in immunity with age may be some other reasons to explain this finding. The fact that adults have fewer complications lends support to the above theory. The main limitation of the study is its retrospective nature. The pros and cons of this study being a singlecenter study and patients being operated by a single surgeon have been highlighted earlier in the discussion. Another deficiency of the study is the lack of objective scales or parameters to document functional improvement. However, the primary goal of this study was not to demonstrate objective improvement or efficacy of the ITB pump which is already proven by many other studies. This study primarily focused on the complications. Due to the small number of cases, no specific conclusion was possible from our study regarding scoliosis progression after ITB pump placement in children.
Conclusions
The ITB pump is an effective method to manage spasticity and/or dystonia in children. Only 1 patient in our series had a clinically significant dose-related adverse event. Significant dose-related adverse effects following ITB pump insertion are very few and are easily treatable with increasing awareness and sensitivity among the caregivers with prompt action, if needed. In spite of good efficacy, even after 2 decades of its use in humans, the complication rates of the ITB pump remain high in children, both mechanical (catheter-related) and infection-related ones. Infections happen most commonly within the first month after surgery, suggestGhosh/Mainali/Khera/Luciano
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accidental overdose was mistakenly programmed after a routine refill of the pump; the catheter tip was at the T5 level. The problem was picked up quickly, and the patient was managed in the intensive care unit with short-term intubation and pressure support. The complication rate in our series was high which is however in conformity with the existing literature in children with ITB pumps [11, 14–17, 25, 31]. Infections occurred in 22% in our series compared with about 25% in other childhood series [15]. The infection rate is however much lower in adults, about 5% [10, 15]. Most (50%) of the infections in this series occurred within the first month after the surgery, most likely related to perioperative or immediate postoperative sepsis. This fact is important from the standpoint of prevention of infection. It is possible that impaired innate immunity in children may make them more vulnerable to infections when compared to adults. There is a need for a multicenter study to find out the management strategy to reduce the infection risk. While it is easy to suspect the diagnosis of meningitis in the presence of local incision site infection, the occurrence of meningitis without local infection may pose a problem in diagnosis. Four children in our series had meningitis without any local incision site infection (table 3). A high index of suspicion is essential to suspect and confirm the diagnosis of meningitis in the above situation. Mechanical complications, noted in 19.3% in our series, are also similar to those described in the literature. Mechanical complications were more evenly distributed over time after surgery though they show some clustering (10 out of 23 occurrences) during 3–6 months after baclofen pump insertion. To prevent mechanical complications, there is a need for better technology to develop finer, tougher, nonirritant catheter material. A better surgical way to fix the catheter at the entry point at the spinal canal may also help prevent dislodgement or kinking in the catheter system. Proper fixation of the pump itself not allowing much mobility, preferably insertion into the subfascial pocket, may prevent kinking or breaking of the catheter. One study demonstrated that the mechanical catheter-related complications are more frequent when a catheter with a port was used compared with the one without a port [11]. A catheter port may however be useful for a dye study (pumpogram) to investigate catheter malfunction. In our study we used only catheters with a port. Significant progression of scoliosis requiring corrective surgery was seen in 7 cases out of 35 documented to have scoliosis prior to pump insertion; however, our data
ing that improving asepsis during surgery and the immediate postoperative period may potentially prevent or decrease this complication. Catheter-related complications were dispersed more evenly throughout the follow-up period after surgery except some clustering 3–6 months after pump surgery.
That there has not been a significant change in the rate of mechanical complications over time suggests that improvements in pump/catheter design and performance are still necessary.
Acknowledgments
Future Directions There is a need for a large, multicentered, prospective study of children with ITB pumps for the following purposes: – to determine complication types and rates across centers; – to determine if there are statistically significant variabilities in types or rates of complications across centers; – if there is type or rate variability, to test hypotheses that might explain them, such as differences in aseptic precautions, use of prophylactic antibiotics, detection and treatment of skin fold pathogens or surgical technique.
We thank Stephen Dombrowski, PhD, for his valuable help in statistics and preparation of the graphs.
Disclosure Statement The authors received no financial support for the research and/ or the authorship of this article. Dr. Debabrata Ghosh received honoraria from serving as a consultant for Merz Inc., administers botulinum toxin in his clinical practice (20% effort) and bills for this procedure. Dr. Mark Luciano received grants from Medtronic, Johnson & Johnson and Aesculapia, and serves as a consultant for Johnson & Johnson. Dr. Gayatra Mainali and Dr. Jena Khera report no disclosures.
References
Intrathecal Baclofen Pump Complications
9 De Lissovoy G, Matza LS, Green H, Werner M, Edgar T: Cost-effectiveness of intrathecal baclofen therapy for the treatment of severe spasticity associated with cerebral palsy. J Child Neurol 2007;22:49–59. 10 Fjelstad AB, Hommelstad J, Sorteberg A: Infections related to intrathecal baclofen therapy in children and adults: frequency and risk factors. J Neurosurg Pediatr 2009; 4: 487–493. 11 Gooch JL, Oberg WA, Grams B, Ward LA, Walker ML: Complications of intrathecal baclofen pumps in children. Pediatr Neurosurg 2003;39:1–6. 12 Hoving MA, van Raak EP, Spincemaille GH, van Kranen-Mastenbroek VH, van Kleef M, Gorter JW, et al: Safety and one-year efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy. Eur J Paediatr Neurol 2009;13:247–256. 13 Liu JK, Walker ML: Posterior cervical approach for intrathecal baclofen pump insertion in children with previous spinal fusions: technical note. J Neurosurg 2005;102(suppl 1): 119–122. 14 Motta F, Buonaguro V, Stignani C: The use of intrathecal baclofen pump implants in children and adolescents: safety and complications in 200 consecutive cases. J Neurosurg 2007;107(suppl 1):32–35. 15 Vender JR, Hester S, Waller JL, Rekito A, Lee MR: Identification and management of intrathecal baclofen pump complications: a com-
16
17
18
19
20
21
22
parison of pediatric and adult patients. J Neurosurg 2006;104(suppl 1):9–15. Ward A, Hayden S, Dexter M, Scheinberg A: Continuous intrathecal baclofen for children with spasticity and/or dystonia: goal attainment and complications associated with treatment. J Paediatr Child Health 2009; 45: 720–726. Borowski A, Littleton AG, Borkhuu B, Presedo A, Shah S, Dabney KW, et al: Complications of intrathecal baclofen pump therapy in pediatric patients. J Pediatr Orthop 2010; 30: 76–81. Burn SC, Zeller R, Drake JM: Do baclofen pumps influence the development of scoliosis in children? J Neurosurg Pediatr 2010;5:195– 199. Hart AR, Tripathi C, Rowland DJ, Broadley P, Mordekar SR: Rapid progression of scoliosis complicating intrathecal baclofen pump insertion. Dev Med Child Neurol 2007;49:717. Shilt JS, Lai LP, Cabrera MN, Frino J, Smith BP: The impact of intrathecal baclofen on the natural history of scoliosis in cerebral palsy. J Pediatr Orthop 2008;28:684–687. Sansone JM, Mann D, Noonan K, Mcleish D, Ward M, Iskandar BJ: Rapid progression of scoliosis following insertion of intrathecal baclofen pump. J Pediatr Orthop 2006; 26: 125– 128. Bohannon RW, Smith MB: Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987;67:206–207.
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
143
Downloaded by: University of Tokyo 157.82.153.40 - 5/16/2015 11:08:33 AM
1 Penn RD, Kroin JS: Intrathecal baclofen alleviates spinal cord spasticity. Lancet 1984; i: 1078. 2 Dralle D, Muller H, Zierski J, Klug N: Intrathecal baclofen for spasticity. Lancet 1985; ii: 1003. 3 Albright AL, Gilmartin R, Swift D, Krach LE, Ivanhoe CB, McLaughlin JF: Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg 2003; 98: 291–295. 4 Brochard S, Remy-Neris O, Filipetti P, Bussel B: Intrathecal baclofen infusion for ambulant children with cerebral palsy. Pediatr Neurol 2009;40:265–270. 5 Campbell WM, Ferrel A, McLaughlin JF, Grant GA, Loeser JD, Graubert C, et al: Longterm safety and efficacy of continuous intrathecal baclofen. Dev Med Child Neurol 2002; 44:660–665. 6 Hoving MA, van Raak EP, Spincemaille GH, Palmans LJ, Becher JG, Vles JS, et al: Efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a randomised controlled trial. Eur J Paediatr Neurol 2009;13:240–246. 7 Albright AL, Barry MJ, Fasick P, Barron W, Shultz B: Continuous intrathecal baclofen infusion for symptomatic generalized dystonia. Neurosurgery 1996;38:934–938. 8 Albright AL, Barry MJ, Shafton DH, Ferson SS: Intrathecal baclofen for generalized dystonia. Dev Med Child Neurol 2001;43:652–657.
144
27 Guillaume D, Van Havenbergh A, Vloeberghs M, Vidal J, Roeste G: A clinical study of intrathecal baclofen using a programmable pump for intractable spasticity. Arch Phys Med Rehabil 2005;86:2165–2171. 28 Krach LE, Kriel RL, Gilmartin RC, Swift DM, Storrs BB, Abbott R, et al: GMFM 1 year after continuous intrathecal baclofen infusion. Pediatr Rehabil 2005;8:207–213. 29 Krach LE, Nettleton A, Klempka B: Satisfaction of individuals treated long term with continuous infusion of intrathecal baclofen by implanted programmable pump. Pediatr Rehabil 2006;9:210–218.
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
30 Grabb PA, Guin-Renfroe S, Meythaler JM: Midthoracic catheter tip placement for intrathecal baclofen administration in children with quadriparetic spasticity. Neurosurgery 1999;45:833–836; discussion 836–837. 31 Brennan PM, Whittle IR: Intrathecal baclofen therapy for neurological disorders: a sound knowledge base but many challenges remain. Br J Neurosurg 2008;22:508–519. 32 Senaran H, Shah SA, Presedo A, Dabney KW, Glutting JW, Miller F: The risk of progression of scoliosis in cerebral palsy patients after intrathecal baclofen therapy. Spine 2007; 32: 2348–2354.
Ghosh/Mainali/Khera/Luciano
Downloaded by: University of Tokyo 157.82.153.40 - 5/16/2015 11:08:33 AM
23 Kan P, Gooch J, Amini A, Ploeger D, Grams B, Oberg W, et al: Surgical treatment of spasticity in children: comparison of selective dorsal rhizotomy and intrathecal baclofen pump implantation. Childs Nerv Syst 2008; 24: 239– 243. 24 Sgouros S: Surgical management of spasticity of cerebral origin in children. Acta Neurochir 2007;97(suppl):193–203. 25 Rawlins PK: Intrathecal baclofen therapy over 10 years. J Neurosci Nurs 2004;36:322–327. 26 Albright AL, Awaad Y, Muhonen M, Boydston WR, Gilmartin R, Krach LE, et al: Performance and complications associated with the Synchromed 10-ml infusion pump for intrathecal baclofen administration in children. J Neurosurg 2004; 101(suppl 1):64– 68.
Received: August 22, 2013 Accepted after revision: January 2, 2014 Published online: February 21, 2014
Complications of Intrathecal Baclofen Pumps in Children: Experience from a Tertiary Care Center Debabrata Ghosh Gayatra Mainali Jena Khera Mark Luciano Pediatric Neurology Center, Children’s Hospital, Cleveland Clinic, Cleveland, Ohio, USA
Abstract Background/Aims: Intrathecal baclofen (ITB) therapy is useful in treating spasticity and dystonia but it has many complications, more so in children. The main aim of the study was to look at the complications of ITB pumps in children with the goal of future prevention. Methods: Charts of all patients ≤21 years with an ITB pump, implanted by a single pediatric neurosurgeon, at a single center, between 1996 and 2011 were reviewed retrospectively. Data regarding an ITB test trial were also recorded. Results: During 1996–2011, 119 children (mean age 13.2 years) underwent ITB pump placement; 84% had spastic quadriplegic cerebral palsy. The gross motor function classification system level was ≥4 for most. The pump was removed in 5 (4.2%) patients due to inefficacy. The mean follow-up was 38 months. Mechanical complications requiring pump and/or catheter revision occurred in 19.3% and infections in an additional 21.8%. Seven patients (6%) had meningitis. No complication was noted after 72 months of initial pump insertion, even after pump reinsertion. Conclusion: There is a need for better infection control as well as better pump, catheter and surgical technology to lower the complications of ITB pumps in children. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 1016–2291/14/0493–0138$39.50/0 E-Mail [email protected] www.karger.com/pne
Introduction
Baclofen, structurally similar to γ-amino butyric acid, has γ-amino butyric acid mimetic action. It acts through stimulation of chloride channels inhibiting the release of excitatory neurotransmitter/s. Spasticity can be conceptualized as hyperactivity of the lower motor neuron, no more under inhibitory control of the upper motor neuron, either as part of brain (cerebral spasticity) or spinal cord (spinal spasticity) pathology. Baclofen controls spasticity by the reduction of the hyperactivity in this monosynaptic reflex arc at the level of the spinal cord. Dystonia can also improve through the same mechanism. The problem with systemic baclofen use is its wide spread effect in the central nervous system, in addition to the effect at the spinal cord. Delivering baclofen directly near its site of action around the spinal cord at the subarachnoid cerebrospinal fluid space may avoid many untoward central side effects. Hence came up the idea of the intrathecal baclofen (ITB) pump. In 1984, Penn and Kroin [1] were the first to use a baclofen pump to treat spasticity of spinal origin, and in 1985 Dralle et al. [2] for spasticity of cerebral origin. The Food and Drug Administration approved the ITB pump for spasticity of spinal origin in 1992 and of cerebral origin in 1996. The efficacy of ITB pumps for spasticity management has been proven by many studies, both in children and in adults [3–6]. This procedure is also helpful in the management of medically refractory secondary dystonias [7, Debabrata Ghosh, MD Pediatric Neurology Center, Desk S60 Cleveland Clinic 9500 Euclid Avenue, Cleveland, OH 44195 (USA) E-Mail ghoshd10 @ gmail.com
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Key Words Spastic quadriplegia · Dystonia · Cerebral palsy · Intrathecal baclofen pump · Complications
8]. The cost-effectiveness of this procedure in the treatment of spastic cerebral palsy has been proven in 2007 by the elegant study by De Lissovoy et al. [9]. With increasing experience and more stringent follow-up, the adverse effects of the ITB pump due to an accidental baclofen overdose (drowsiness, hypotension, respiratory depression, profound hypotonia and weakness), underdose or withdrawal (increasing muscle tone, pain, spasm, fasciculation, hyperpyrexia and muscle breakdown) have been minimized. However, the complications still remain high [5, 10–17]. The complications of ITB pumps may be categorized as: (a) mechanical and (b) infection-related. Mechanical complications are observed in 4–24% either due to pump or catheter problems. The common mechanical complications are erosion of the skin over the pump, disconnection of the catheter at the connector site, kinks or breaks in the catheter, cerebrospinal fluid leak at the catheter insertion site, cystic collection around the pump or spinal entry point of the catheter. Infections occur in 5–26% of cases in various series. They may occur as superficial or deep wound infection, pump or catheter infection, or meningitis. The overall complications due to an ITB pump vary from 20 to 50% depending on various factors like patient age, weight and severity of the disease process. The complication rates are higher in children when compared to those in adults [15, 16]. The study by Vender et al. [15] in 2006 had a total of 218 ITB pumps done over a 5-year period: 72 in adults and 146 in children. Pump revisions were needed in 3.4% of all children compared with 2.7% in adults, catheter revision in 24% of children versus 14% of adults. Wound infections were noted in 25% of children versus 5% of adults. In 2009, Fjelstad et al. [10] looked into the infection rate following ITB pump insertion in 91 children and compared it with that in 72 adults. The infection rate was significantly higher in children. There was some initial concern about rapid progression of scoliosis in children after the ITB pump based on some case reports, but later larger controlled studies disproved that notion [17–21]. With the undoubtedly proven efficacy of the ITB pump in managing spasticity and/or dystonia, the next step in improving the outcome from ITB pumps will be through reduction of the complication rate, more so in children. The experience of various centers dealing with ITB pumps in children may help in finding common factors contributing to the complications. Thus, we thought of sharing our experience of ITB pumps in children mainly in regard to the complications of the procedure in our setting so that more effective strategies in preventing the complications can be implemented.
Table 1. Primary diagnoses and GMFCS of the children with ITB
Intrathecal Baclofen Pump Complications
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
pumps Parameters Primary diagnoses Spastic quadriplegia Spastic diplegia Spastic hemiplegia Generalized dystonia GMFCS Level II Level III Level IV Level V
Number of patients (n = 119) 100 12 1 6 7 32 64 16
Methods All consecutive patients aged ≤21 years who underwent ITB pump surgery for spasticity and/or dystonia, inserted by a single pediatric neurosurgeon (M.L.) in a single center (the Cleveland Clinic) between the years 1996 and 2011 were included in this study. After obtaining permission from the Institutional Review Board, charts of all consecutive patients as mentioned above were obtained from the hospital record section. Those charts were extensively reviewed to extract the following data: age of the patient, age at pump insertion, diagnosis/indication, history, relevant examination findings including mental/cognitive status and associated dystonia, modified Ashworth tone scales for spasticity [22], ITB trial results, perioperative asepsis, location of the pump in the abdominal wall (subcutaneous or subfascial), site of the catheter tip, maximum dose of ITB, adverse effects, complications, change in degree of scoliosis, and follow-up. Those data were entered in an Excel spread sheet, and statistics were applied. The contribution of various factors like age, sex, weight, the site of the catheter tip, severity of spasticity and/or dystonia, Gross Motor Functional Classification Scale (GMFCS) in the production of the complications were looked into. KaplanMeyer survival curves were obtained for the development of total (all complications), mechanical and infectious complications over time.
A total of 119 children had ITB pumps in our center during the 16-year period (1996–2011). Males (n = 67) outnumbered females (n = 52). The mean age at pump insertion was 13.2 ± 5.5 years (range 3–21 years). Table 1 shows the primary diagnoses and GMFCS scores of the patients. The patients with significant spasticity involving more than one limb, not tolerating oral baclofen or other antispasticity medications due to sedation or other side 139
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Results
ITB Pump Data A single surgeon (M.L.) did all the pump insertions. Alcohol was used as prep solution which was replaced by betadine for the last 2 years of the study period. No routine perioperative antibiotic was used. In most patients the baclofen pump was placed subcutaneously, only 10 had subfascial placement. The catheter entered the spinal canal at the L3–L4 level, and the catheter tip was advanced to the C6–T4 level in 7 patients, the T5–T8 level in 55 cases, the T9 level in 42 cases and the T10–L5 level in 15 cases. The distribution of spasticity determined the catheter tip position; the lumbar area was chosen if spasticity involved primarily the lower limbs, the midthoracic region was chosen if the lower limbs were more affected than the upper, the lower cervical or upper thoracic region was chosen if the upper limbs were more severely affected than the lower limbs. The average dose of ITB was 334 ± 234 μg/day (range 25–1,099 μg/day). The dose requirement was not dependent on the level of the catheter tip. Improvement was noted in all except 5 cases who later decided to take the pump out. Only 1 patient had a serious adverse effect due to a programming error leading to accidental baclofen overdose during the refill and reprogramming process. The patient developed drowsiness, hypotension and respiratory depression requiring shortterm intubation in the intensive care unit. He had the catheter tip at the T5 level. Lowering the baclofen dose and bringing down the catheter tip to the T9 level helped managing his spasticity without any further adverse event. 140
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
0.8
0.6
0.4
0.2
0 0
20
40
60
80
100
120
Time (months)
Fig. 1. Kaplan-Meyer curve showing complication-free patient
survival of all patients with an ITB pump. The continuous line indicates total complications, the dashed line mechanical and the dotted line infectious complications.
Table 2. Major complications following ITB pump implantation
Total complications
Number of patients (n = 49)
Infection of incision site Meningitis without infection at incision site Meningitis with infection at incision site Catheter displacement/disconnection Skin erosion over pump Catheter fracture Cerebrospinal fluid leak
19 4 3 10 8 4 1
Complications Complications were noted in 49 patients when followed over a mean period of 38 months (range 0.5– 120 months). The overall complication-free survival at 72 months was 40% (fig. 1). Table 2 shows the major complications. Mechanical complications occurred in 23, and 26 had infections. The whole of the baclofen pump system (pump and catheter) was removed if there was meningitis or deep infection, to be replaced only after the infection had cleared. Only the pump was repositioned when skin erosion over the pump was noted without any infection. For catheter malfunction/kink/ fracture, only the catheter was revised keeping the pump in situ. A persistent cerebrospinal fluid leak in 1 patient Ghosh/Mainali/Khera/Luciano
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ITB Test Trial A test trial with a 50-μg bolus of ITB was performed in all. Pre-ITB and 4-hour post-ITB modified Ashworth scores (average) were calculated. The average decrease in Ashworth scores was 3.1 ± 2.42 (range 0.05–10.75). Postspinal tap headache was noted in 3 of 119 patients but was mild and managed with adequate hydration and supine posture.
1.0
Survival function
effects on the central nervous system were evaluated in a multidisciplinary spasticity clinic attended by a pediatric neurologist, neurosurgeon, orthopedic surgeon and the experienced therapists (both physical and occupational). The decision to subject the patient to an ITB trial was based on the consensus among the members of the spasticity clinic. The final decision to insert the pump was based on the objective documentation of improvement of spasticity after the ITB trial without any worsening of other clinical condition/s.
Table 3. Details of cases with meningitis without infection at the incision site Age, Sex years
Diagnosis
Level of catheter
Year of Timing of Sequelae pump meningitis placement
Organism
6 18 16 17
Spastic quadriplegia with VPS TBI, SAH, VPS Obstructive hydrocephalus with VPS Spastic CP
T10–T11 T10 T8–T9 T6
2001 2001 2001 2001
MSSA MSSA CONS Pseudomonas
Male Male Female Male
2 weeks 10 days 3 years 1 month
None, treated with IV antibiotics None, treated with IV antibiotics None, treated with IV antibiotics None, treated with IV antibiotics
was managed with repair of the hole around the spinal catheter entry site. Most infections (50%) occurred within the first month after surgery. Meningitis, the most serious infectious complication, can occur with or without local incision site infection. Details of cases with meningitis without associated incision site infection are presented separately in table 3. Catheter-related complications were spread throughout the postpump period, though they were clustered more (10 out of 23 occurrences) around 3–6 months after pump insertion. Age, sex, weight, pump or catheter tip location, severity of spasticity or GMFCS score did not predict the occurrence of the complications. We observed 35 documented scolioses before pump placement; 7 of them progressed further to require corrective scoliosis surgery after baclofen pump placement. The cumulative complication-free pump survival (Kaplan-Meyer) for all patients is shown in figure 1. The Kaplan-Meyer plot in figure 1 shows 3 graphs showing total, mechanical and infectious complications over time. The slopes of the curves again demonstrate the fact that infections happen more in the early postpump period, whereas mechanical complications can happen any time after the surgery. Importantly, the complication rate was negligible after a period of 72 months even after routine pump revision.
Discussion
A total of 119 children with ITB pumps make this series one of the larger ones in the literature. The facts that it is a single-center study and that all the surgeries are done by the same surgeon have both merits and demerits. The demerit is the smaller sample size. The possible merits are: (a) the data may be more meaningful due to reIntrathecal Baclofen Pump Complications
striction of the number of variables affecting the results; (b) interventions based on the observation may be easier. The spectrum of cases in our series conforms to other series in children [14, 16, 23–25]. Most had cerebral palsy, the commonest type being spastic quadriplegia (84%). As per the existing literature, also supported by our study, the ITB pump is effective in the management of spasticity and/or dystonia in children [3, 5, 6, 8, 9, 16, 26–29]. Of 119 cases in our series, only 5 (4.2%) patients’ parents were not happy with the response in spite of the therapeutic ITB dose. Those pumps were taken out with the insistence of the parents as efficacy declined over time. Each patient had a 50-μg bolus trial of ITB before the final decision of implanting the pump. All had positive responses to the bolus trial with a significant decrease in tone. None required a prolonged intrathecal catheter infusion trial. The catheter trial consists of slow continuous infusion of ITB with the help of an intrathecal catheter over 2–3 days. A catheter trial is rarely undertaken at some centers when there is a doubtful response to the bolus trial, in spite of clinically detectable prominent spasticity and/or dystonia. Except a self-limiting mild postlumbar puncture headache in 3, no other complication was observed in any case during or after the trial. In all cases the catheter entered the spinal canal through the lumbar area; however, the catheter tip was placed at various levels depending on the distribution of spasticity. Catheter tip location did not influence the dose required, side effects or complications. This observation is consistent with the existing literature [3, 13, 30]. The average daily amount needed to achieve an optimal response in our series was 334 μg/day, which is in accordance with other studies in children [3, 14, 17, 25, 31]. Regarding adverse effects, we encountered only one serious dose-related adverse effect in a patient where an Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
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VPS = Ventriculoperitoneal shunt; IV = intravenous; MSSA = methicillin-sensitive Staphylococcus aureus; TBI = traumatic brain injury; SAH = subarachnoid hemorrhage; CONS = coagulase-negative Staphylococcus; CP = cerebral palsy.
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are too limited to conclude that scoliosis progressed more rapidly after ITB pump insertion. This is more so in the context of the average age of the patients when pumps were placed. Rapid progression of scoliosis in children with cerebral palsy frequently occurs at around the same age when the ITB pump was inserted in our patients. Due to the small number, this study does not definitely answer the question but we agree with the recent literature disproving the older notion that scoliosis progresses more rapidly after the insertion of the ITB pump [18, 32]. It is very interesting to note that all the complications, both mechanical and infections, in this series are extremely uncommon after a period of 6 years even after routine revision of the pump. The most likely reason may be a better tolerance of the foreign body producing little reaction after years. Increase in weight, body surface area, ease of surgery or improvement in immunity with age may be some other reasons to explain this finding. The fact that adults have fewer complications lends support to the above theory. The main limitation of the study is its retrospective nature. The pros and cons of this study being a singlecenter study and patients being operated by a single surgeon have been highlighted earlier in the discussion. Another deficiency of the study is the lack of objective scales or parameters to document functional improvement. However, the primary goal of this study was not to demonstrate objective improvement or efficacy of the ITB pump which is already proven by many other studies. This study primarily focused on the complications. Due to the small number of cases, no specific conclusion was possible from our study regarding scoliosis progression after ITB pump placement in children.
Conclusions
The ITB pump is an effective method to manage spasticity and/or dystonia in children. Only 1 patient in our series had a clinically significant dose-related adverse event. Significant dose-related adverse effects following ITB pump insertion are very few and are easily treatable with increasing awareness and sensitivity among the caregivers with prompt action, if needed. In spite of good efficacy, even after 2 decades of its use in humans, the complication rates of the ITB pump remain high in children, both mechanical (catheter-related) and infection-related ones. Infections happen most commonly within the first month after surgery, suggestGhosh/Mainali/Khera/Luciano
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accidental overdose was mistakenly programmed after a routine refill of the pump; the catheter tip was at the T5 level. The problem was picked up quickly, and the patient was managed in the intensive care unit with short-term intubation and pressure support. The complication rate in our series was high which is however in conformity with the existing literature in children with ITB pumps [11, 14–17, 25, 31]. Infections occurred in 22% in our series compared with about 25% in other childhood series [15]. The infection rate is however much lower in adults, about 5% [10, 15]. Most (50%) of the infections in this series occurred within the first month after the surgery, most likely related to perioperative or immediate postoperative sepsis. This fact is important from the standpoint of prevention of infection. It is possible that impaired innate immunity in children may make them more vulnerable to infections when compared to adults. There is a need for a multicenter study to find out the management strategy to reduce the infection risk. While it is easy to suspect the diagnosis of meningitis in the presence of local incision site infection, the occurrence of meningitis without local infection may pose a problem in diagnosis. Four children in our series had meningitis without any local incision site infection (table 3). A high index of suspicion is essential to suspect and confirm the diagnosis of meningitis in the above situation. Mechanical complications, noted in 19.3% in our series, are also similar to those described in the literature. Mechanical complications were more evenly distributed over time after surgery though they show some clustering (10 out of 23 occurrences) during 3–6 months after baclofen pump insertion. To prevent mechanical complications, there is a need for better technology to develop finer, tougher, nonirritant catheter material. A better surgical way to fix the catheter at the entry point at the spinal canal may also help prevent dislodgement or kinking in the catheter system. Proper fixation of the pump itself not allowing much mobility, preferably insertion into the subfascial pocket, may prevent kinking or breaking of the catheter. One study demonstrated that the mechanical catheter-related complications are more frequent when a catheter with a port was used compared with the one without a port [11]. A catheter port may however be useful for a dye study (pumpogram) to investigate catheter malfunction. In our study we used only catheters with a port. Significant progression of scoliosis requiring corrective surgery was seen in 7 cases out of 35 documented to have scoliosis prior to pump insertion; however, our data
ing that improving asepsis during surgery and the immediate postoperative period may potentially prevent or decrease this complication. Catheter-related complications were dispersed more evenly throughout the follow-up period after surgery except some clustering 3–6 months after pump surgery.
That there has not been a significant change in the rate of mechanical complications over time suggests that improvements in pump/catheter design and performance are still necessary.
Acknowledgments
Future Directions There is a need for a large, multicentered, prospective study of children with ITB pumps for the following purposes: – to determine complication types and rates across centers; – to determine if there are statistically significant variabilities in types or rates of complications across centers; – if there is type or rate variability, to test hypotheses that might explain them, such as differences in aseptic precautions, use of prophylactic antibiotics, detection and treatment of skin fold pathogens or surgical technique.
We thank Stephen Dombrowski, PhD, for his valuable help in statistics and preparation of the graphs.
Disclosure Statement The authors received no financial support for the research and/ or the authorship of this article. Dr. Debabrata Ghosh received honoraria from serving as a consultant for Merz Inc., administers botulinum toxin in his clinical practice (20% effort) and bills for this procedure. Dr. Mark Luciano received grants from Medtronic, Johnson & Johnson and Aesculapia, and serves as a consultant for Johnson & Johnson. Dr. Gayatra Mainali and Dr. Jena Khera report no disclosures.
References
Intrathecal Baclofen Pump Complications
9 De Lissovoy G, Matza LS, Green H, Werner M, Edgar T: Cost-effectiveness of intrathecal baclofen therapy for the treatment of severe spasticity associated with cerebral palsy. J Child Neurol 2007;22:49–59. 10 Fjelstad AB, Hommelstad J, Sorteberg A: Infections related to intrathecal baclofen therapy in children and adults: frequency and risk factors. J Neurosurg Pediatr 2009; 4: 487–493. 11 Gooch JL, Oberg WA, Grams B, Ward LA, Walker ML: Complications of intrathecal baclofen pumps in children. Pediatr Neurosurg 2003;39:1–6. 12 Hoving MA, van Raak EP, Spincemaille GH, van Kranen-Mastenbroek VH, van Kleef M, Gorter JW, et al: Safety and one-year efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy. Eur J Paediatr Neurol 2009;13:247–256. 13 Liu JK, Walker ML: Posterior cervical approach for intrathecal baclofen pump insertion in children with previous spinal fusions: technical note. J Neurosurg 2005;102(suppl 1): 119–122. 14 Motta F, Buonaguro V, Stignani C: The use of intrathecal baclofen pump implants in children and adolescents: safety and complications in 200 consecutive cases. J Neurosurg 2007;107(suppl 1):32–35. 15 Vender JR, Hester S, Waller JL, Rekito A, Lee MR: Identification and management of intrathecal baclofen pump complications: a com-
16
17
18
19
20
21
22
parison of pediatric and adult patients. J Neurosurg 2006;104(suppl 1):9–15. Ward A, Hayden S, Dexter M, Scheinberg A: Continuous intrathecal baclofen for children with spasticity and/or dystonia: goal attainment and complications associated with treatment. J Paediatr Child Health 2009; 45: 720–726. Borowski A, Littleton AG, Borkhuu B, Presedo A, Shah S, Dabney KW, et al: Complications of intrathecal baclofen pump therapy in pediatric patients. J Pediatr Orthop 2010; 30: 76–81. Burn SC, Zeller R, Drake JM: Do baclofen pumps influence the development of scoliosis in children? J Neurosurg Pediatr 2010;5:195– 199. Hart AR, Tripathi C, Rowland DJ, Broadley P, Mordekar SR: Rapid progression of scoliosis complicating intrathecal baclofen pump insertion. Dev Med Child Neurol 2007;49:717. Shilt JS, Lai LP, Cabrera MN, Frino J, Smith BP: The impact of intrathecal baclofen on the natural history of scoliosis in cerebral palsy. J Pediatr Orthop 2008;28:684–687. Sansone JM, Mann D, Noonan K, Mcleish D, Ward M, Iskandar BJ: Rapid progression of scoliosis following insertion of intrathecal baclofen pump. J Pediatr Orthop 2006; 26: 125– 128. Bohannon RW, Smith MB: Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987;67:206–207.
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
143
Downloaded by: University of Tokyo 157.82.153.40 - 5/16/2015 11:08:33 AM
1 Penn RD, Kroin JS: Intrathecal baclofen alleviates spinal cord spasticity. Lancet 1984; i: 1078. 2 Dralle D, Muller H, Zierski J, Klug N: Intrathecal baclofen for spasticity. Lancet 1985; ii: 1003. 3 Albright AL, Gilmartin R, Swift D, Krach LE, Ivanhoe CB, McLaughlin JF: Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg 2003; 98: 291–295. 4 Brochard S, Remy-Neris O, Filipetti P, Bussel B: Intrathecal baclofen infusion for ambulant children with cerebral palsy. Pediatr Neurol 2009;40:265–270. 5 Campbell WM, Ferrel A, McLaughlin JF, Grant GA, Loeser JD, Graubert C, et al: Longterm safety and efficacy of continuous intrathecal baclofen. Dev Med Child Neurol 2002; 44:660–665. 6 Hoving MA, van Raak EP, Spincemaille GH, Palmans LJ, Becher JG, Vles JS, et al: Efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a randomised controlled trial. Eur J Paediatr Neurol 2009;13:240–246. 7 Albright AL, Barry MJ, Fasick P, Barron W, Shultz B: Continuous intrathecal baclofen infusion for symptomatic generalized dystonia. Neurosurgery 1996;38:934–938. 8 Albright AL, Barry MJ, Shafton DH, Ferson SS: Intrathecal baclofen for generalized dystonia. Dev Med Child Neurol 2001;43:652–657.
144
27 Guillaume D, Van Havenbergh A, Vloeberghs M, Vidal J, Roeste G: A clinical study of intrathecal baclofen using a programmable pump for intractable spasticity. Arch Phys Med Rehabil 2005;86:2165–2171. 28 Krach LE, Kriel RL, Gilmartin RC, Swift DM, Storrs BB, Abbott R, et al: GMFM 1 year after continuous intrathecal baclofen infusion. Pediatr Rehabil 2005;8:207–213. 29 Krach LE, Nettleton A, Klempka B: Satisfaction of individuals treated long term with continuous infusion of intrathecal baclofen by implanted programmable pump. Pediatr Rehabil 2006;9:210–218.
Pediatr Neurosurg 2013;49:138–144 DOI: 10.1159/000358307
30 Grabb PA, Guin-Renfroe S, Meythaler JM: Midthoracic catheter tip placement for intrathecal baclofen administration in children with quadriparetic spasticity. Neurosurgery 1999;45:833–836; discussion 836–837. 31 Brennan PM, Whittle IR: Intrathecal baclofen therapy for neurological disorders: a sound knowledge base but many challenges remain. Br J Neurosurg 2008;22:508–519. 32 Senaran H, Shah SA, Presedo A, Dabney KW, Glutting JW, Miller F: The risk of progression of scoliosis in cerebral palsy patients after intrathecal baclofen therapy. Spine 2007; 32: 2348–2354.
Ghosh/Mainali/Khera/Luciano
Downloaded by: University of Tokyo 157.82.153.40 - 5/16/2015 11:08:33 AM
23 Kan P, Gooch J, Amini A, Ploeger D, Grams B, Oberg W, et al: Surgical treatment of spasticity in children: comparison of selective dorsal rhizotomy and intrathecal baclofen pump implantation. Childs Nerv Syst 2008; 24: 239– 243. 24 Sgouros S: Surgical management of spasticity of cerebral origin in children. Acta Neurochir 2007;97(suppl):193–203. 25 Rawlins PK: Intrathecal baclofen therapy over 10 years. J Neurosci Nurs 2004;36:322–327. 26 Albright AL, Awaad Y, Muhonen M, Boydston WR, Gilmartin R, Krach LE, et al: Performance and complications associated with the Synchromed 10-ml infusion pump for intrathecal baclofen administration in children. J Neurosurg 2004; 101(suppl 1):64– 68.
