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Practice Parameter: Pharmacologic treatment of spasticity in children and
adolescents with cerebral palsy (an evidence-based review): Report of the Quality
Standards Subcommittee of the American Academy of Neurology and the Practice
Committee of the Child Neurology Society
M. R. Delgado, D. Hirtz, M. Aisen, S. Ashwal, D. L. Fehlings, J. McLaughlin, L. A.
Morrison, M. W. Shrader, A. Tilton and J. Vargus-Adams This information is current as of April 28, 2010
The online version of this article, along with updated information and services, is http://www.neurology.org/cgi/content/full/74/4/336 ® is the official journal of the American Academy of Neurology. Published continuously Neurologysince 1951, it is now a weekly with 48 issues per year. Copyright 2010 by AAN Enterprises, Inc. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X. SPECIAL ARTICLE
Practice Parameter: Pharmacologic treatment ofspasticity in children and adolescents withcerebral palsy (an evidence-based review)Report of the Quality Standards Subcommittee of the American Academy ofNeurology and the Practice Committee of the Child Neurology Society ABSTRACT
Objective: To evaluate published evidence of efficacy and safety of pharmacologic treatments for
childhood spasticity due to cerebral palsy.
Methods: A multidisciplinary panel systematically reviewed relevant literature from 1966 to July
Results: For localized/segmental spasticity, botulinum toxin type A is established as an effective
treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in chil- dren with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B injections. For generalized spasticity, diazepam is probably effective in reducing spasticity, but there are insufficient data on its effect on motor function and its side-effect profile. Tizanidine is possibly effective, but there are insufficient data on its effect on function and its side-effect profile. There were insufficient data on the use of dantrolene, oral baclofen, and intrathecal baclofen, and toxicity was frequently Academy of Neurology, 1080Montreal Avenue, St. Paul, MN Recommendations: For localized/segmental spasticity that warrants treatment, botulinum toxin
type A should be offered as an effective and generally safe treatment (Level A). There are insuffi- cient data to support or refute the use of phenol, alcohol, or botulinum toxin type B (Level U). For generalized spasticity that warrants treatment, diazepam should be considered for short-term treatment (Level B), and tizanidine may be considered (Level C). There are insufficient data to support or refute use of dantrolene, oral baclofen, or continuous intrathecal baclofen (Level U).
Neurology® 2010;74:336 –343
GLOSSARY
AAN ϭ American Academy of Neurology; AE ϭ adverse event; AS ϭ Ashworth scale; BoNT-A ϭ botulinum toxin type A;
BoNT-B ϭ botulinum toxin type B; CP ϭ cerebral palsy; FDA ϭ Food and Drug Administration; GAS ϭ Goal Attainment Scale;
GMFM ϭ Gross Motor Function Measure; ITB ϭ intrathecal baclofen; MAS ϭ Modified Ashworth scale; OT ϭ occupational
therapy; PT ϭ physiotherapy; QUEST ϭ Quality of Upper Extremity Skills Test; TS ϭ Tardieu scale.
The prevalence of cerebral palsy (CP) was recently The Taskforce on Childhood Motor Disorders defines reported to be 3.6 cases per 1,000 in 8-year-old chil- spasticity as “hypertonia in which one or both of the dren,1 with very little variation among Western na- following signs are present: 1) resistance to externally tions.2 More than 10,000 babies born in the United imposed movement increases with increasing speed of States each year will be affected by CP.3 CP is the stretch and varies with the direction of joint movement; most common cause of spasticity in children, and the 2) resistance to externally imposed movement rises rap- majority of children with CP are affected by spasticity.4 idly above a threshold speed of joint angle.”5 Supplemental data at
www.neurology.org
From the University of Texas Southwestern Medical Center (M.R.D.), Dallas; National Institute of Neurological Disorders and Stroke (D.H.),Bethesda, MD; United Cerebral Palsy Research Foundation (M.A.); Loma Linda University (S.A.), Loma Linda, CA; Bloorview Kids Rehab (D.L.F.),Toronto, Canada; University of Washington (J.M.), Seattle; University of New Mexico (L.A.M.), Albuquerque; The Core Institute (M.W.S.), SunCity West, AZ; Louisiana State University (A.T.), New Orleans; and Cincinnati Children’s Hospital (J.V.-A.), Cincinnati, OH.
Appendices e-1 through e-4, tables e-1 through e-3, and references e1 through e19 are available on the Neurology® Web site at www.neurology.org.
Approved by the Quality Standards Subcommittee on February 7, 2009; by the AAN Practice Committee on April 10, 2009; by the CNS PracticeCommittee on December 7, 2009; by the AAN Board of Directors on October 19, 2009; and by the CNS Board of Directors on December 11, 2009.
Disclosure: Author disclosures are provided at the end of the article.
Copyright 2010 by AAN Enterprises, Inc.
Spasticity is one component of the multifaceted infantile. Key text and index words for the intervention motor disability of CP and may not be the main included diazepam, Valium, tizanidine, Zanaflex, dan- factor interfering with function, participation, or ac- trolene, Dantrium, baclofen, Lioresal, intrathecal ba- tivity.6 Alleviation of spasticity may not always be clofen, phenol, alcohol, botulinum toxin A, Botox, desirable; some patients may experience a decline in Dysport, BTX-A, BoNT-A, botulinum toxin B, function with spasticity reduction.7 The decision to BoNT-B, BTX-B, Myobloc, and Neurobloc.
use antispasticity medications requires careful assess- The inclusion criteria were all foreign languages ment of the patient’s other impairments (e.g., weak- with English abstracts, human subjects, peer re- ness, movement disorders) and proper selection and viewed, patients 19 years of age or younger with CP, use of the treatment. Reasons to treat spasticity in- and more than 9 patients studied. Citations of review clude reducing pain and muscle spasms, facilitating articles from 2000 to 2008 were checked for addi- brace use, improving posture, minimizing contrac- tures and deformity, facilitating mobility and dexter- A total of 978 abstracts were initially found. From ity, and improving patient ease of care as well as these, 528 were identified as potentially pertinent and reviewed in full. Finally, 218 articles were se- Several tools such as the Ashworth scale (AS)9 and lected that fulfilled the inclusion/exclusion criteria.
the Modified Ashworth scale (MAS)10 have been Each article was reviewed, abstracted, and classi- used in clinical trials, with the assumption that they fied by at least 2 authors. Disagreements were re- measure spasticity. These scales measure a broader set solved by reaching consensus among the reviewers, of neural and musculoskeletal factors of non- the first author, and at least 2 other authors. The velocity-dependent hypertonia in addition to spastic- AANЈs 4-tiered classification scheme for therapeutic ity itself.11 A tool that is more consistent with the evidence was used to classify articles (appendix e-3 on proposed definition of spasticity above is the Tardieu the Neurology® Web site at www.neurology.org), and scale (TS).12 The TS accounts for the joint angle the strength of the recommendation was linked measure of the spastic phenomenon at different ve- Over the last 20 years, several pharmacologic an- ANALYSIS OF EVIDENCE Treatment of localized
tispasticity treatments have been adapted for use in or segmental spasticity. There were no publications
patients with CP. These include oral medications on phenol, alcohol, or BoNT-B that met criteria for like benzodiazepines, dantrolene, baclofen, and tiza- nidine; neuromuscular blocking agents such as botu- A total of 148 studies using BoNT-A to reduce linum toxins A and B (BoNT-A and BoNT-B); spasticity in children with CP met eligibility criteria.
chemical denervation using phenol and alcohol; and Fifteen studies were Class I and 5 were Class II (table intrathecal baclofen (ITB).13 Oral medications and e-1). Five of these studies assessed the effect of ITB are used when a generalized antispasticity effect BoNT-A in the upper extremity16–20; the rest assessed is desired. Chemical denervation agents are used to only the lower extremity. A total of 573 children re- treat localized (one extremity) or segmental (lower ceived BoNT-A in the Class I and II studies. The body, hemibody) spasticity. The mechanisms of ac- majority of the studies included children as young as tion and pharmacology of these drugs are described 2 years of age. Spasticity was measured using the AS or the MAS in 13 of the 20 studies. The BoNT-A This article reviews and evaluates published evi- doses used are indicated in table e-1.
dence of the efficacy and safety of these medications Spasticity reduction. Spasticity reduction was re-
in children and adolescents affected by spasticity due ported in all but 3 studies.20–22 In one study, spastic- ity was significantly reduced by electromechanicalmeasure but not by AS.23 Spasticity was reduced at 2 DESCRIPTION OF THE ANALYTIC PROCESS
weeks ( p ϭ 0.0001),24 4 weeks (p Ͻ 0.001),25 and 3 The American Academy of Neurology (AAN) con- months ( p ϭ 0.01)16 after treatment.
vened a multidisciplinary author panel consisting of One Class I study provided information regard- 5 pediatric neurologists, 2 developmental pediatricians, ing the degree of spasticity improvement. This study 1 pediatric physiatrist, 1 pediatric orthopedist, and 1 compared the effect of BoNT-A lower extremity adult neurologist. Literature searches of MEDLINE treatment combined with physiotherapy (PT) vs PT and EMBASE were conducted for relevant articles alone and reported a mean increase in score on the published from 1966 to July 2008 using the follow- MAS (increased tone) after 6 months (approximately ing key text and index words: cerebral palsy, static half of an MAS point) in the control group, whereas encephalopathy, spasticity, hypertonia, children, and the BoNT-A group showed a mean decrease in MAS score (decreased tone) 6 months after injection (ap- trical stimulation. In another Class I study (n ϭ proximately 1 MAS point) ( p Ͻ 0.05).26 29),17 BoNT-A was injected into upper extremity Lower extremity functional improvement. A Class I
muscles using anatomic knowledge only to guide in- dose-comparison parallel study found a significant jection location. The study used the same BoNT-A dose-effect correlation in gait kinetics and kinematics formulation and similar doses, demonstrating an im- using 3-dimensional gait analysis.27 The high-dose provement in QUEST scores at 1 month ( p Ͻ 0.05) group showed greater ankle dorsiflexion in stance but not at 3 or 6 months after treatment. In a small ( p Ͻ 0.001) and swing (p Ͻ 0.05) at 4 weeks than at Class II study (n ϭ 14)16 in which BoNT-A was in- baseline; these differences were not seen in the low- jected using anatomic knowledge only to guide injec- dose group. The high-dose group also showed a tion location, despite an increase in maximum active longer effect than the low-dose group, demonstrating elbow and thumb extension ( p ϭ 0.02 and p ϭ 0.03) increased ankle dorsiflexion during stance at 12 and a reduction of tone in the wrist and elbow ( p ϭ weeks compared to baseline ( p Ͻ 0.01). A Class I 0.003 and p ϭ 0.01) 2 weeks after BoNT-A treat- study28 (n ϭ 40; spastic diparesis and hemiparesis) ment, only a modest improvement in hand function reported significant functional lower extremity im- was reported by the grasp-and-release score measure provement by the Gross Motor Function Measure at 12 weeks ( p ϭ 0.01). However, no improvement was noted in fine motor function, assessed by the BoNT-A treatment in the lower extremities. Of pa- ability to pick up coins, and in some cases this ability tients treated with BoNT-A, 37% (7/19) (mean im- deteriorated temporarily. A Class I study (n ϭ 80) provement 9.7%) showed improvement compared demonstrated a much higher functional benefit when with 7% (1/15) in the placebo group ( p ϭ 0.04). A BoNT-A was used in combination with OT than Class II study that measured functional improve- ment by the Goal Attainment Scale (GAS) reported Adverse events. Specific adverse events (AEs) were
that 11 of 33 (33%) functional ability goals were reported in 17 studies (table e-1). All were transient achieved by 7 of 11 children with CP after BoNT-A and did not require hospitalization. The most com- treatment in the lower extremities ( p ϭ 0.001).29 mon AEs were localized pain, excessive weakness, un- Gait improvement was reported by using the Physi- steadiness and increased falls, and fatigue. Urinary cian Rating Scale in a Class I study.28 The mean im- incontinence was reported in 5 patients and dyspha- provement change was twice as great in the treated gia in 2 patients. No deaths were reported.
group as in the placebo group 12 weeks after treat- Conclusions. For children with CP, BoNT-A is es- tablished as an effective treatment to reduce spastic- In contrast, 3 Class I placebo-controlled studies— ity in the upper and lower extremities (Class I and II (n ϭ 64),22 (n ϭ 125),30 and (n ϭ 52)31— using the evidence), but there is conflicting evidence regarding same BoNT-A preparation at slightly higher dose (30 functional improvement. The available evidence sug- U/kg vs 25 U/kg) and the same outcome measure gests that BoNT-A is generally safe in children with (GMFM) failed to demonstrate a significant func- CP. However, severe generalized weakness may occur.
tional improvement, despite significant improve- ments in ankle dorsiflexion30 4 weeks after injections 1. For localized/segmental spasticity in the upper and initial foot contact31 16 weeks after injections.
and lower extremities of children with CP that Upper extremity functional improvement. The effect of
warrants treatment, BoNT-A should be offered as BoNT-A treatment on upper extremity function in an effective and generally safe treatment (Level children with hemiplegic CP was measured using the A). There is insufficient evidence to support or Quality of Upper Extremity Skills Test (QUEST) in refute the use of BoNT-A to improve motor func- 4 Class I studies.17–20 One study (n ϭ 42),18 which compared the effect of a single low-dose, high- 2. There is insufficient evidence to support or refute concentration BoNT-A treatment plus occupational the use of BoNT-B, phenol, and alcohol injec- therapy (OT) to OT alone, found upper extremity tions as a treatment for spasticity in children with functional improvement at 1 month ( p Ͻ 0.001) and 3 months ( p Ͻ 0.001) but not at 6 months aftertreatment. A larger proportion of treatment group Clinical context. At the time of this writing, the Food subjects showed more than 20% change above base- and Drug Administration (FDA) has not approved line QUEST scores compared with the control group BoNT-A for the treatment of spasticity in children.
at 1 month (67% vs 19%; p ϭ 0.004) and 3 months BoNT-A is approved for the treatment of spasticity (71% vs 33%; p ϭ 0.03) but not at 6 months. Appli- in children and adults in Canada and several other cation of BoNT-A in this study was guided by elec- countries. Different formulations are not bioequiva- lent and may have different therapeutic efficacy and weeks after treatment included a dose-dependent re- duction of tone ( p Ͻ 0.001 as measured by the The AAN recently published an evidence-based MAS), increased passive range-of-motion angles review on the safety and efficacy of BoNT for the ( p Ͻ 0.001), and an increase in spontaneous move- treatment of adult and childhood spasticity.34 A Level A ments ( p Ͻ 0.001); no functional outcome measures recommendation was given for the use of BoNT-A as a were reported. No daytime drowsiness was noted.
treatment of spasticity in the lower extremities (equinus One Class II studye5 compared the antispastic effect and hip adductor spasticity) and a Level B recommen- of diazepam at a dose as high as 12 mg a day vs dation was given for the treatment of spasticity in the dantrolene and placebo and found a subjective re- upper extremities of children with CP.
duction of spasticity, which was even more notice- It is common practice to use BoNT-A in combi- able when diazepam and dantrolene were combined.
nation with serial casting, orthoses, and PT and Although teachers and parents reported a subjective OT.19 Typically, there is a 3- to 4-month clinical improvement in activities of daily living, no stan- response requiring repeated injections. Some experts dardized outcome measures were used. The other recommend using the smallest dose of BoNT-A and Class II study37 did not evaluate the antispasticity avoiding injecting more frequently than every 3 effects of diazepam but mentioned improved behav- months to minimize the risk of antibody resistance.35 ior and coordination (12/16 subjects improved on On the basis of postmarketing reports from its Adverse Event Reporting System, the FDA released Conclusions. Diazepam is probably effective for the on February 8, 2008, an “early communication” de- short-term treatment of spasticity in children with scribing a “relative handful of systemic reactions” af- CP (1 Class I study and 1 Class II study). None of ter BoNT injection (A or B) for limb spasticity the studies formally addressed whether diazepam im- associated with CP. At the time of this writing, the proved motor function. Ataxia and drowsiness were FDA has not completed the review of reported seri-ous AEs related to BoNT, and has made the follow- identified in the side-effect profile of most studies.
ing recommendations: 1) understand that potency Recommendations. Diazepam should be considered as determinations expressed in “Units” or “U” differ a short-term antispasticity treatment in children with among the BoNT products; clinical doses expressed CP (Level B). There is insufficient evidence to sup- in units are not comparable from one botulinum port or refute the use of diazepam to improve motor product to the next; 2) be alert to the potential for function in this population (Level U).
systemic effects following administration of BoNT Clinical context. The incidence of AEs associated with such as dysphagia, dysphonia, weakness, dyspnea, or diazepam, such as drowsiness, sedation, hypersalivation, respiratory distress; 3) understand that these effects and weakness, are important limiting factors for long- have been reported as early as 1 day and as late as term use. Experts caution that the prolonged use of this several weeks after treatment; 4) provide patients and medication can produce physical dependence and rec- caregivers with the information they need to be able to identify the signs and symptoms of systemic effects Dantrolene. One Class I,40 2 Class II,e1,e2 and 2
after receiving an injection of BoNT; 5) tell patients Class IVe3,e4 studies met the selection criteria (table they should receive immediate medical attention if they e-2). The Class I study and 1 of the Class IIe1 studies have worsening or unexpected difficulty swallowing or found conflicting results using a similar dose of 4 –12 talking, trouble breathing, or muscle weakness.
mg/kg/day. The Class I study found no spasticityimprovement, no functional gain, and strength re- Treatment of generalized spasticity. Seventy studies
using oral antispasticity medications and ITB were
duction ( p ϭ 0.013). The Class II study,e1 which identified, and 20 met selection criteria: 4 used diaz- used a within-subject crossover design, found spastic- epam,36–39 5 used dantrolene,40,e1-e4 1 used both,e5 3 ity improvement (not graded) with changes in the used oral baclofen,7,e6,e7 1 used tizanidine,e8 and 6 neurologic examination (tone, tendon reflexes, clo- nus) ( p Ͻ 0.01). Although there was no change in Diazepam. Regarding diazepam treatment, we
gross motor function, activities of daily living (in- identified 1 Class I study,36 2 Class II studies,37,e5 1 cluding coordination in dressing and eating, control Class III study,38 and 1 Class IV study39 (table e-2).
of limbs in spontaneous play, stamina, freedom of The doses and regimens used varied from 0.5 mg a movement, and facilitation of therapy) improved day to 5 mg TID. The Class I study (n ϭ 180) ran- during the treatment period compared to baseline domized children with spastic CP weighing less than ( p Ͻ 0.02). Improvement in reflexes (p Ͻ 0.005) 15 kg to receive 1 of 2 doses of diazepam (0.5–1 mg and reduced scissoring ( p Ͻ 0.05) were reported in vs 1–2 mg) or placebo at bedtime. Improvements 3 the other Class II study.e2 AEs were found in 30% to 60% of the patients and included fatigue, irritability, dren with CP. Systemic toxicity was found in drowsiness, anorexia, and gastrointestinal symptoms (e.g., vomiting and diarrhea). Four of 9 children who Recommendation. There is insufficient evidence to continued taking dantrolene after the study was com- support or refute the use of oral baclofen for the pleted developed or had exacerbations of seizures.e1 treatment of spasticity or to improve motor function Conclusions. There is conflicting evidence regarding the effectiveness of dantrolene in reducing spasticity Clinical context. Baclofen is widely used in clinical in children with CP. Dantrolene frequently causes practice to treat spasticity in children with CP. Ex- side effects such as weakness, drowsiness, and irrita- perts recommend starting baclofen at the lowest pos- sible dose (5–10 mg/day divided into 3 doses a day)7 Recommendation. There is insufficient evidence to to minimize AEs like drowsiness and sedation. The support or refute the use of dantrolene for the treat- dose is gradually tapered until discontinuing because ment of spasticity in children with CP (Level U).
abrupt discontinuation may cause withdrawal symp- Clinical context. On the basis of the author panel’s toms, including increased spasticity, hallucinations, experience, dantrolene is rarely used in clinical practice to reduce spasticity in children with CP. This may be Tizanidine.
due to the lack of evidence in the literature to support controlled parallel study treated 10 children with a its efficacy and the general concern regarding its poten- mean age of 4.1 years (range 2–15) with tizanidine tial frequent and/or serious AEs. Although dantrolene 0.05 mg/kg/day and 30 children with placebo for 6 has been associated with hepatotoxicity,e15 none of months (table e-2). A reduction in spasticity ( p ϭ the studies reviewed reported this AE in children, 0.0001) was found beginning 2 weeks after initiating perhaps due to the small number of subjects included treatment and was sustained throughout the trial.
Postural and reflex improvement was also reported Baclofen (oral). Two Class II studies 7,e7 and 1 Class
( p ϭ 0.0001). No functional assessments were done.
IV studye6 met selection criteria (table e-2). The Class II No side effects were found, and liver enzymes remained studies showed conflicting results. A double-blind cross- normal throughout the duration of the study.
over trial in 20 children 2–16 years old receiving a dose Conclusions. Tizanidine is possibly effective to treat of 10 – 60 mg/day found a reduction in spasticity by spasticity in children with CP. No toxicity was found means of the AS (p Ͻ 0.001).7 After 28 days of treat- ment, 14 patients improved at least 1 level and 5 im- Recommendations. Tizanidine may be considered for proved more than 1 level. Only 2 patients improved the treatment of spasticity in children with CP (Level while taking placebo. Spasticity improvement was dem- C). There is insufficient evidence to support or refute onstrated by increased passive range of motion, seen in the use of tizanidine to improve motor function in 11 patients (p Ͻ 0.001). Ten patients who were able towalk without assistance prior to treatment showed no significant functional improvement. Furthermore, one Clinical context. Tizanidine’s antispasticity effect has patient who relied on the spastic “crutch” to ambulate been demonstrated in adults with multiple sclerosis showed walking impairment after treatment as the un- and spinal cord injury.e16 Little information is avail- derlying weakness was manifested. The other Class II able to assist practitioners with the effective use of study,e7 a double-blind placebo crossover trial (n ϭ 15) this drug to treat spasticity in children. Because tiza- using a similar dose and age group, was powered to de- nidine is extensively metabolized by the liver, hepatic tect a difference as measured by the GAS but not for impairment may have a significant effect on its other measures. Although improvement on the GAS pharmacokinetics. AEs related to tizanidine use in was reported (p ϭ 0.05), there was no improvement in adults include hypotension, sedation, asthenia, dry spasticity (modified TS) or functional benefit measured mouth, dizziness, hallucinations, and hepatotoxic- using the Pediatric Evaluation of Disability Inventory at ity. Their incidence in pediatric patients has not 12 weeks. The first study found AEs in 25% of patients taking the medication, and no AEs were noticed in Intrathecal baclofen pump. One Class III studye9 and
those taking placebo. Side effects included somnolence 5 Class IV studiese10-e14 assessing ITB met inclusion or sedation (20%) and hypotonia (15%) that resolved criteria (table e-3). All studies reported reduced spas- after drug discontinuation. The second study did not find a significant difference in AEs between groups.
Occasional headache, vomiting, lethargy, disori- Conclusions. There is conflicting Class II evidence entation, agitation, irritability, and meningitis were regarding the effectiveness of oral baclofen in re- reported in 2 of the Class IV studies.e10,e14 CSF leaks ducing spasticity and improving function in chil- (17%), seromas (29%), catheter malfunction (43%), and wound infection (39%) were reported more 5. The efficacy and safety of BoNT-B, phenol, and alcohol chemodenervation as treatments for spas- Conclusions. Data are inadequate concerning the use ticity in children with CP need to be determined.
of continuous ITB as an antispasticity treatment in 6. The efficacy and safety of oral baclofen and the children with CP. CSF leaks, seromas, catheter- long-term continuous intrathecal pump adminis- related complications, and wound infection occur tration of this medication need to be determined frequently, and other, milder complications occur 7. The few available treatments to reduce general- Recommendation. There is insufficient evidence to ized spasticity are associated with a high incidence support or refute the use of continuous ITB for of AEs and complications. There is an urgent the treatment of spasticity in children with CP need for studies to establish the efficacy of the current therapies and find additional safe and Clinical context. In 1996, ITB received FDA ap- effective treatments to help children affected by proval to treat spasticity of cerebral origin. A major generalized spasticity due to CP. A first step factor in the lack of Class I and II evidence may be could be to investigate medications that have the difficulty of performing a randomized control shown antispasticity effect in adult patients (e.g., trial or crossover trial in subjects with ITB pumps.
Catheter-related complications, pump pocket collec-tions, and wound infections remain a concern, andongoing efforts aim to reduce their incidence. One DISCLOSURE
retrospective study of the safety of ITB in children Dr. Delgado serves on the editorial board of Developmental Medicine andChild Neurology; has received research support from Abbott, Sciele (n ϭ 200) found that 11% had CSF leakage, 7% had Pharma, Inc., UCB, Allergan, Inc., the Hurst Foundation, the United catheter-related problems, and 5.5% developed Cerebral Palsy Research & Educational Foundation, the Linda and Don Carter Foundation, and the Crowley Carter Foundation; and estimatesthat 50% of his clinical effort is spent on assessment and management ofmotor disorders of childhood, which includes treating children with cere- RECOMMENDATIONS FOR FUTURE RESEARCH
bral palsy with oral antispasticity medications, ITB, and botulinum toxin 1. The AS has been used by most spasticity studies.
injections. Dr. Hirtz reports no disclosures. Dr. Aisen serves as MedicalDirector of Cerebral Palsy International Research Foundation. Dr. Ash- It measures muscle resistance to passive move- wal serves on the editorial board of Pediatric Neurology; receives royalties ment but fails to describe the velocity of the from publishing Pediatric Neurology: Principles and Practice (Elsevier, stretching movement and therefore is inadequate 2006); and receives research support from the NIH [R01 NS054001-01 to measure spasticity and distinguish it from (PI); 1R01NS059770-01A2 (PI)]. Dr. Fehlings has received speaker hon-oraria and funding for travel from RX Media; receives research support other types of hypertonia (e.g., dystonia). Stan- from Allergan, Inc., the Canadian Institutes of Health Research (CIHR), dardized and validated spasticity scales and clini- Social Sciences and Humanities Research Services (SSHRS), the Bloor- cally relevant measures sensitive enough to detect view Research Institute, and Physician Services Inc.; and estimates 50% of change should be used to qualify and quantify her clinical effort is spent on spasticity intervention including botulinumtoxin injections and ITB. Dr. McLaughlin has received research support spasticity according to its current definition (e.g., from Medtronic, Inc., the NIH [NINDS NO1-HD-3–3351 (site PI), 1 U01 AR52171-01 (site PI), 1RC 1HD063838-01 (site PI)], and United 2. None of the oral medications used to treat spas- Cerebral Palsy Research & Education Foundation; and spends 10% of his ticity in children has been adequately tested for time evaluating and managing children with oral medications, baclofenpumps, and botulinum toxin. Dr. Morrison serves on the editorial boards safety and efficacy. There are minimal or no data of the Journal of Child Neurology and Pediatric Neurology; and estimates regarding the pharmacokinetics or appropriate that Ͻ1% of her clinical effort is spent on skin biopsy and Ͻ1% on dosing parameters to treat children. These critical lumbar puncture. Dr. Shrader has received funding for travel from questions deserve serious research efforts.
Stryker; and has received research support from Stryker, Smith and 3. The effects of both spasticity and the treatment Nephew, Biomet, and VQ Orthocare. Dr. Tilton has served on a speakers’bureau for and received speaker honoraria and funding for travel from of spasticity on activity and participation as de- Medtronic, Inc.; has received research support from Allergan, Inc.; holds fined by the International Classification of patent rights on a non-neurologic application of botulinum toxin (under Function, Disability and Health of the World consideration for licensure to her institution); and estimates 8%–10% of Health Organization need to be studied in chil- her clinical effort is spent on botulinum toxin injections and 10%–15%on intrathecal baclofen pumps. Dr. Vargus-Adams receives research sup- port from the NIH [K23 HD049552 (PI), NICHD-2005-13-2 (Co-I), 4. Although there is sufficient evidence to recom- U01 AR057940-01 (Co-I)] and the Ohio Division of Emergency Medical mend BoNT-A as an effective antispasticity treat- Systems; her immediate family member holds financial interest in Novar- ment in children with CP, its beneficial effects on tis, Dermik Laboratories, Inc., and Proctor & Gamble and holds equityinterest in Proctor & Gamble, Ligand, and GlucoWatch; and estimates function, ease of caregiving, activity, and partici- 3% of her clinical effort is spent on intrathecal baclofen test dose and pation need to be established. More data about management, 15% on botulinum toxin injections, and 2% on phenol safety and long-term effects are also needed.
DISCLAIMER
Bohannon RW, Smith MB. Interrater reliability of a mod- This statement is provided as an educational service of the American ified Ashworth scale of muscle spasticity. Phys Ther 1987; Academy of Neurology. It is based on an assessment of current scientific and clinical information. It is not intended to include all possible proper Nielsen JF, Sinkjaer T. A comparison of clinical and labo- methods of care for a particular neurologic problem or all legitimate crite- ratory measures of spasticity. Mult Scler 1996;1:296 –301.
ria for choosing to use a specific procedure. Neither is it intended to Haugh AB, Pandyan AD, Johnson GR. A systematic re- exclude any reasonable alternative methodologies. The AAN recognizes view of the Tardieu Scale for the measurement of spastic- that specific patient care decisions are the prerogative of the patient and ity. Disabil Rehabil 2006;28:899 –907.
the physician caring for the patient, based on all of the circumstances Verrotti A, Greco R, Spalice A, Chiarelli F, Iannetti P.
involved. The clinical context section is made available in order to place Pharmacotherapy of spasticity in children with cerebral the evidence-based guideline(s) into perspective with current practicehabits and challenges. No formal practice recommendations should be palsy. Pediatr Neurol 2006;34:1– 6.
Gracies JM, Elovic E, McGuire J, Simpson D. Traditionalpharmacological treatments for spasticity: part I: localtreatments. Muscle Nerve 1997;6 (suppl):S61–S91.
CONFLICT OF INTEREST
Gracies JM, Nance P, Elovic E, McGuire J, Simpson DM.
The American Academy of Neurology is committed to producing inde- Traditional pharmacological treatments for spasticity: part pendent, critical and truthful clinical practice guidelines (CPGs). Signifi- II: general and regional treatments. Muscle Nerve 1997;6 cant efforts are made to minimize the potential for conflicts of interest to influence the recommendations of this CPG. To the extent possible, the Corry IS, Cosgrove AP, Walsh EG, McClean D, Graham AAN keeps separate those who have a financial stake in the success or HK. Botulinum toxin A in the hemiplegic upper limb: a failure of the products appraised in the CPGs and the developers of the double-blind trial. Dev Med Child Neurol 1997;39:185– guidelines. Conflict of interest forms were obtained from all authors and reviewed by an oversight committee prior to project initiation. AAN lim- Fehlings D, Rang M, Glazier J, Steele C. An evaluation of its the participation of authors with substantial conflicts of interest. TheAAN forbids commercial participation in, or funding of, guideline botulinum-A toxin injections to improve upper extremity projects. Drafts of the guideline have been reviewed by at least three AAN function in children with hemiplegic cerebral palsy. J Pedi- committees, a network of neurologists, Neurology® peer reviewers, and representatives from related fields. The AAN Guideline Author Conflict Lowe K, Novak I, Cusick A. Low-dose/high-concentration of Interest Policy can be viewed at www.aan.com.
localized botulinum toxin A improves upper limb move-ment and function in children with hemiplegic cerebral Received April 23, 2009. Accepted in final form October 9, 2009. palsy. Dev Med Child Neurol 2006;48:170 –175.
Wallen M, O’Flaherty SJ, Waugh MC. Functional out-comes of intramuscular botulinum toxin type a and occu- REFERENCES
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Committee of the Child Neurology Society
M. R. Delgado, D. Hirtz, M. Aisen, S. Ashwal, D. L. Fehlings, J. McLaughlin, L. A.
Morrison, M. W. Shrader, A. Tilton and J. Vargus-Adams This information is current as of April 28, 2010
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