Download Pharmacologic Treatment of Spasticity in Children and Adolescents

Pharmacological Treatment of
Spasticity in Children and
Adolescents with Cerebral Palsy
Report of the Quality Standards Subcommittee of
the American Academy of Neurology and Practice
Committee of the Child Neurology Society
Mauricio R. Delgado, MD, FRCPC, FAAN; Deborah Hirtz, MD, FAAN;
Mindy A. L. Aisen, MD, FAAN; Stephen Ashwal, MD, FAAN; Darcy
L. Fehlings, MD, MSc, FRCPC; J. McLaughlin, MD; Leslie A.
Morrison, MD; M. W. Shrader, MD; Ann H. Tilton, MD, FAAN; Jilda
Vargus-Adams, MD, MS
© 2010 AMERICAN ACADEMY OF NEUROLOGY
The AAN develops these presentation slides as
educational tools for neurologists and other
health care practitioners. You may download
and retain a single copy for your personal use.
Please contact [email protected] to learn
about options for sharing this content beyond
your personal use.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Presentation Objectives
• To review the evidence for the efficacy and
safety of pharmacological treatments for
childhood spasticity due to cerebral palsy
(CP)
− Treatment of localized or segmental spasticity
− Treatment of generalized spasticity
• To present evidence-based
recommendations
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Overview
•
•
•
•
Background
Gaps in care
AAN guideline process
Analysis of evidence, conclusions,
recommendations
• Recommendations for future research
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Background
• CP prevalence was recently reported to be 3.6 cases per 1000 in 8year-old children,1 with very little variation among Western nations.2
• CP is the most common cause of spasticity in children, and the
majority of children with CP are affected by spasticity.3
• The Taskforce on Childhood Motor Disorders defines spasticity as
“hypertonia in which one or both of the following signs are present:
− resistance to externally imposed movement increases with
increasing speed of stretch and varies with the direction of joint
movement
− resistance to externally imposed movement rises rapidly above
a threshold speed of joint angle”4
• Alleviation of spasticity may not always be desirable; some patients
may experience a decline in function with spasticity reduction.5
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Background, cont.
• The decision to use antispasticity medications requires careful
assessment of the patient’s other impairments (e.g., weakness,
movement disorders) and proper selection and use of the treatment.
• Reasons to treat spasticity include reducing pain and muscle
spasms, facilitating brace use, improving posture, minimizing
contractures and deformity, facilitating mobility and dexterity, and
improving patient ease of care as well as hygiene/self-care.6
• Several tools such as the Ashworth scale (AS)7 and the “Modified”
Ashworth scale8 have been used in clinical trials, with the
assumption that they measure spasticity. These scales measure a
broader set of neural and musculoskeletal factors of non-velocitydependent hypertonia in addition to spasticity itself.9
• The Tardieu scale accounts for the joint angle measure of the
spastic phenomenon at different velocities of joint movement.10
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Background, cont.
• Over the last 20 years, several pharmacological antispasticity
treatments (benzodiazepines, dantrolene, baclofen, and tizanidine;
neuromuscular blocking agents such as botulinum toxins A and B
[BoNT-A and BoNT-B, respectively]; chemical denervation using
phenol and alcohol; intrathecal baclofen [ITB]11) have been adapted
for use in patients with CP.
• Oral medications and ITB are used when a generalized
antispasticity effect is desired. Chemical denervation agents are
used to treat localized (one extremity) or segmental (lower body,
hemibody) spasticity. The mechanisms of action and pharmacology
of these drugs are described in other publications.12,13
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Gaps in Care
• There is a paucity of research on treatment of spasticity
in CP.
• Physicians often focus on treating impairment (spasticity)
but not activity/participation.
• There is strong evidence for efficacy of BoNT-A use in
spasticity but no evidence for efficacy of other
medication use in spasticity.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
AAN Guideline Process
Clinical Question
Evidence
Conclusions
Recommendations
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Questions
• The first step in developing guidelines is to
clearly formulate questions to be answered.
• Questions address areas of controversy,
confusion, or variation in practice.
• Questions must be answerable with data
from the literature.
• Answering the question must have the
potential to improve care/patient outcomes.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Literature Search/Review
Rigorous, Comprehensive, Transparent
Complete
Search
Review abstracts
Review full text
Select articles
Relevant
© 2010 AMERICAN ACADEMY OF NEUROLOGY
AAN Classification of
Evidence
• All studies rated Class I, II, III, or IV
• Five different classification systems:
– Therapeutic
• Randomization, control, blinding
– Diagnostic
• Comparison to gold standard
– Prognostic
– Screening
– Causation
© 2010 AMERICAN ACADEMY OF NEUROLOGY
AAN Level of
Recommendations
• A = Established as effective, ineffective or harmful (or
established as useful/predictive or not useful/predictive)
for the given condition in the specified population.
• B = Probably effective, ineffective or harmful (or
probably useful/predictive or not useful/predictive) for the
given condition in the specified population.
• C = Possibly effective, ineffective or harmful (or possibly
useful/predictive or not useful/predictive) for the given
condition in the specified population.
• U = Data inadequate or conflicting; given current
knowledge, treatment (test, predictor) is unproven.
Note that recommendations can be positive or negative.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Translating Class to Recommendations
• A = Requires at least two consistent Class I
studies.*
• B = Requires at least one Class I study or two
consistent Class II studies.
• C = Requires at least one Class II study or two
consistent Class III studies.
• U = Studies not meeting criteria for Class I
through Class III.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Translating Class to Recommendations,
cont.
*In exceptional cases, one convincing Class I
study may suffice for an “A” recommendation if
1) all criteria are met, 2) the magnitude of
effect is large (relative rate improved outcome
>5 and the lower limit of the confidence interval
is >2).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Applying This Process
to the Issue
We will now turn our attention to the guidelines.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Questions
1.
2.
3.
4.
5.
6.
What is the efficacy and safety of BoNT-A, BoNT-B, phenol,
or alcohol injection for treating spasticity in children with CP?
What is the efficacy and safety of diazepam for treating
spasticity in children with CP?
What is the efficacy and safety of dantrolene for treating
spasticity in children with CP?
What is the efficacy and safety of oral baclofen for treating
spasticity in children with CP?
What is the efficacy and safety of tizanidine for treating
spasticity in children with CP?
What is the efficacy and safety of ITB for treating spasticity
in children with CP?
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Methods
• MEDLINE and EMBASE
 1966 through July 2008
 Relevant, fully published, peer-reviewed articles
 Search terms were as follows:
–cerebral palsy, static encephalopathy, spasticity, hypertonia,
children, and infantile
–diazepam, Valium, tizanidine, Zanaflex, dantrolene, Dantrium,
baclofen, Lioresal, intrathecal baclofen, phenol, alcohol, botulinum
toxin A, Botox, Dysport, BTX-A, BoNT-A, botulinum toxin B, BoNTB, BTX-B, Myobloc, and Neurobloc
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Methods, cont.
• At least two authors reviewed each article for
inclusion.
• Risk of bias was determined using the
classification of evidence for each study (Classes
I–IV).
• Strength of practice recommendations were linked
directly to levels of evidence (Levels A, B, C, and
U).
• Conflicts of interest were disclosed.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Literature Review
Inclusion criteria:
978 abstracts
- Studies of CP, static
encephalopathy, spasticity,
hemiplegia, tetraplegia,
quadriplegia, diplegia
- Studies of oral antispasticity
medications; intrathecal
baclofen; BoNT, phenol, and
alcohol injections
- Limited to human subjects
- All foreign languages with
English abstracts
Exclusion criteria:
218 articles
© 2010 AMERICAN ACADEMY OF NEUROLOGY
- Articles not peer-reviewed
- Articles on patients over 19
years of age with CP
- Articles with fewer than nine
patients studied
AAN Classification of Evidence
for Therapeutic Intervention
• Class I: A randomized, controlled clinical trial of the intervention of
interest with masked or objective outcome assessment, in a
representative population. Relevant baseline characteristics are
presented and substantially equivalent among treatment groups or
there is appropriate statistical adjustment for differences. The following
are also required:
 a. concealed allocation
 b. primary outcome(s) clearly defined
 c. exclusion/inclusion criteria clearly defined
 d. adequate accounting for drop-outs (with at least 80% of enrolled subjects
completing the study) and cross-overs with numbers sufficiently low to have
minimal potential for bias.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
AAN Classification of Evidence
for Therapeutic Intervention
 e. For noninferiority or equivalence trials claiming to prove efficacy for one
or both drugs, the following are also required*
1. The authors explicitly state the clinically meaningful difference to be excluded by
defining the threshold for equivalence or non-inferiority.
2. The standard treatment used in the study is substantially similar to that used in
previous studies establishing efficacy of the standard treatment. (e.g. for a drug,
the mode of administration, dose and dosage adjustments are similar to those
previously shown to be effective).
3. The inclusion and exclusion criteria for patient selection and the outcomes of
patients on the standard treatment are comparable to those of previous studies
establishing efficacy of the standard treatment.
4. The interpretation of the results of the study is based upon a per protocol
analysis that takes into account dropouts or crossovers.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
AAN Classification of Evidence
for Therapeutic Intervention, cont.
• Class II: A randomized controlled clinical trial of the intervention of
interest in a representative population with masked or objective
outcome assessment that lacks one criteria a-e above or a prospective
matched cohort study with masked or objective outcome assessment
in a representative population that meets b-e above. Relevant baseline
characteristics are presented and substantially equivalent among
treatment groups or there is appropriate statistical adjustment for
differences.
• Class III: All other controlled trials (including well-defined natural
history controls or patients serving as own controls) in a representative
population, where outcome is independently assessed, or
independently derived by objective outcome measurement.***
© 2010 AMERICAN ACADEMY OF NEUROLOGY
AAN Classification of Evidence
for Therapeutic Intervention, cont.
• Class IV: Studies not meeting Class I, II or III criteria including
consensus or expert opinion.
**Note that numbers 1-3 in Class Ie are required for Class II in equivalence
trials. If any one of the three are missing, the class is automatically
downgraded to Class III.
***Objective outcome measurement: an outcome measure that is unlikely to be
affected by an observer’s (patient, treating physician, investigator) expectation
or bias (e.g., blood tests, administrative outcome data).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Analysis of Evidence
Question 1: What is the efficacy and safety
of BoNT-A, BoNT-B, phenol, or alcohol
injection for treating spasticity in children
with CP?
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Conclusion
Conclusion:
 For children with CP, BoNT-A is established as an
effective treatment to reduce spasticity in the upper and
lower extremities (Class I and II evidence), but there is
conflicting evidence regarding functional improvement.
The available evidence suggests that BoNT-A is
generally safe in children with CP. However, severe
generalized weakness may occur.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Recommendations
Recommendations:
 For localized/segmental spasticity in the upper and lower
extremities of children with CP that warrants treatment,
BoNT-A should be offered as an effective and generally
safe treatment (Level A).
 There is insufficient evidence to support or refute the use
of BoNT-A to improve motor function in this population
(Level U).
 There is insufficient evidence to support or refute the use
of BoNT-B, phenol, and alcohol injections as a treatment
for spasticity in children with spastic CP (Level U).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
 At the time of this writing, the US Food and Drug
Administration (FDA) has not approved BoNT-A for the
treatment of spasticity in children. BoNT-A is approved
for the treatment of spasticity in children and adults in
Canada and several other countries. Different
formulations are not bioequivalent and may have
different therapeutic efficacy and safety profiles.14,15
 The AAN recently published an evidence-based review
on the safety and efficacy of BoNT for the treatment of
adult and childhood spasticity.16
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
A Level A recommendation was given for the use of
BoNT-A as a treatment of spasticity in the lower
extremities (equinus and hip adductor spasticity) and a
Level B recommendation was given for the treatment of
spasticity in the upper extremities of children with CP.
 It is common practice to use BoNT-A in combination with
serial casting, orthoses, and physical therapy and
occupational therapy.17 Typically, there is a 3- to 4-month
clinical response requiring repeated injections. Some
experts recommend using the smallest dose of BoNT-A
and avoiding injecting more frequently than every 3
months to minimize the risk of antibody resistance.18
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context, cont.
 On the basis of postmarketing reports from its Adverse
Event Reporting System, the FDA released on February
8, 2008, an “early communication” describing a “relative
handful of systemic reactions” after BoNT injection (A or
B) for limb spasticity associated with CP. At the time of
this writing, the FDA has not completed the review of
reported serious adverse events (Aes) related to BoNT,
and has made the following recommendations:
–Understand that potency determinations expressed in “Units” or
“U” differ among the BoNT products; clinical doses expressed in
units are not comparable from one botulinum product to the next.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context, cont.
–Be alert to the potential for systemic effects following
administration of BoNT such as dysphagia, dysphonia, weakness,
dyspnea, or respiratory distress.
–Understand that these effects have been reported as early as 1
day and as late as several weeks after treatment.
–Provide patients and caregivers with the information they need to
be able to identify the signs and symptoms of systemic effects
after receiving an injection of BoNT.
–Tell patients they should receive immediate medical attention if
they have worsening or unexpected difficulty swallowing or
talking, trouble breathing, or muscle weakness.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Analysis of Evidence
Question 2: What is the efficacy and safety
of diazepam for treating spasticity in
children with CP?
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Conclusion
Conclusion:
 Diazepam is probably effective for the short-term
treatment of spasticity in children with CP (one Class I
study and one Class II study). None of the studies
formally addressed whether diazepam improved motor
function. Ataxia and drowsiness were identified in the
side-effect profile of most studies.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Recommendations
Recommendations:
 Diazepam should be considered as a short-term
antispasticity treatment in children with CP (Level B).
 There is insufficient evidence to support or refute the use
of diazepam to improve motor function in this population
(Level U).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
 The incidence of AEs associated with diazepam,
such as drowsiness, sedation, hypersalivation, and
weakness, are important limiting factors for longterm use.
 Experts caution that the prolonged use of this
medication can produce physical dependence and
recommend against abrupt discontinuation.11
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Analysis of Evidence
Question 3: What is the efficacy and safety
of dantrolene for treating spasticity in
children with CP?
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Conclusion/Recommendation
Conclusion:
 There is conflicting evidence regarding the effectiveness
of dantrolene in reducing spasticity in children with CP.
Dantrolene frequently causes side effects in children
with spastic CP, such as weakness, drowsiness, and
irritability.
Recommendation:
 There is insufficient evidence to support or refute the use
of dantrolene for the treatment of spasticity in children
with CP (Level U).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
 On the basis of the author panel’s experience,
dantrolene is rarely used in clinical practice to reduce
spasticity in children with CP. This may be due to the
lack of evidence in the literature to support its efficacy
and the general concern regarding its potential frequent
and/or serious AEs.
 Although dantrolene has been associated with
hepatotoxicity,19 none of the studies reviewed reported
this AE in children, perhaps due to the small number of
subjects included in these investigations.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Analysis of Evidence
Question 4: What is the efficacy and safety
of oral baclofen for treating spasticity in
children with CP?
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Conclusion/Recommendation
Conclusion:
 There is conflicting Class II evidence regarding the
effectiveness of oral baclofen in reducing spasticity and
improving function in children with CP. Systemic toxicity
was found in some patients.
Recommendation:
 There is insufficient evidence to support or refute the use
of oral baclofen for the treatment of spasticity or to
improve motor function in children with CP (Level U).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
 Baclofen is widely used in clinical practice to treat
spasticity in children with CP. Experts recommend
starting baclofen at the lowest possible dose (5-10
mg/day divided into three doses a day)5 to minimize AEs
like drowsiness and sedation.
 The dose is gradually tapered until discontinuing
because abrupt discontinuation may cause withdrawal
symptoms, including increased spasticity, hallucinations,
confusion, hyperthermia, and seizures.11
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Analysis of Evidence
Question 5: What is the efficacy and safety
of tizanidine for treating spasticity in
children with CP?
Note: One small Class II placebo-controlled parallel study
treated 10 children with a mean age of 4.1 years (range 2–
15) with tizanidine 0.05 mg/kg/day and 30 children with
placebo for 6 months.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Conclusion/Recommendations
Conclusion:
 Tizanidine is possibly effective to treat spasticity in
children with CP. No toxicity was found in this small
study.
Recommendations:
 Tizanidine may be considered for the treatment of
spasticity in children with CP (Level C).
 There is insufficient evidence to support or refute the use
of tizanidine to improve motor function in this population
(Level U).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
 Tizanidine’s antispasticity effect has been demonstrated
in adults with multiple sclerosis and spinal cord injury.20
Little information is available to assist practitioners with
the effective use of this drug to treat spasticity in
children.
 Because tizanidine is extensively metabolized by the
liver, hepatic impairment may have a significant effect on
its pharmacokinetics.
 AEs related to tizanidine use in adults include
hypotension, sedation, asthenia, dry mouth, dizziness,
hallucinations, and hepatotoxicity. Their incidence in
pediatric patients has not been studied.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Analysis of Evidence
Question 6: What is the efficacy and safety
of ITB for treating spasticity in children with
CP?
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Conclusion/Recommendation
Conclusion:
 Data are inadequate concerning the use of continuous
ITB as an antispasticity treatment in children with CP.
CSF leaks, seromas, catheter-related complications, and
wound infection occur frequently, and other, milder
complications occur less frequently.
Recommendation:
 There is insufficient evidence to support or refute the use
of continuous ITB for the treatment of spasticity in
children with CP (Level U).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Clinical Context
 In 1996, ITB received FDA approval to treat spasticity of
cerebral origin. A major factor in the lack of Class I and II
evidence may be the difficulty of performing a
randomized control trial or crossover trial in subjects with
ITB pumps.
 Catheter-related complications, pump pocket collections,
and wound infections remain a concern, and ongoing
efforts aim to reduce their incidence.
 One retrospective study of the safety of ITB in children
(N=200) found that 11% had CSF leakage, 7% had
catheter-related problems, and 5.5% developed
infections.21
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Future Research
• The AS has been used by most spasticity studies. It
measures muscle resistance to passive movement but
fails to describe the velocity of the stretching movement
and therefore is inadequate to measure spasticity and
distinguish it from other types of hypertonia (e.g.,
dystonia).
• Standardized and validated spasticity scales and
clinically relevant measures sensitive enough to detect
change should be used to qualify and quantify spasticity
according to its current definition (e.g., Tardieu Spasticity
Scale).
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Future Research, cont.
• None of the oral medications used to treat spasticity in
children has been adequately tested for safety and
efficacy. There are minimal or no data regarding the
pharmacokinetics or appropriate dosing parameters to
treat children. These critical questions deserve serious
research efforts.
• The effects of both spasticity and the treatment of
spasticity on activity and participation as defined by the
International Classification of Function, Disability and
Health of the World Health Organization need to be
studied in children with CP.22
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Future Research, cont.
• Although there is sufficient evidence to recommend
BoNT-A as an effective antispasticity treatment in
children with CP, its beneficial effects on function, ease
of caregiving, activity, and participation need to be
established. More data about safety and long-term
effects are also needed.
• The efficacy and safety of BoNT-B, phenol, and alcohol
chemodenervation as treatments for spasticity in
children with CP need to be determined.
• The efficacy and safety of oral baclofen and the longterm continuous intrathecal pump administration of this
medication need to be determined in children with CP.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Future Research, cont.
• The few available treatments to reduce generalized
spasticity are associated with a high incidence of AEs
and complications.
• There is an urgent need to find safer and more effective
treatments to help children affected by generalized
spasticity due to CP. A first step could be to investigate
medications that have shown antispasticity effect in adult
patients (e.g., gabapentin).23
© 2010 AMERICAN ACADEMY OF NEUROLOGY
References
1.
2.
3.
4.
5.
6.
7.
8.
Yeargin-Allsopp M, Van Naarden Braun K, Doernberg BA, Benedict RE, Kirby RS,
Durkin MS. Prevalence of cerebral palsy in 8-year-old children in three areas of the
United States in 2002: A multisite collaboration. Pediatrics 2008;121:547-554.
Paneth N, Hong T, Korzeniewski S. The Descriptive Epidemiology of Cerebral Palsy.
Clin Perinatol 2006;33:251-267.
Ronan S, Gold JT. Nonoperative management of spasticity in children. Childs Nerv
Syst 2007;23:943-956.
Sanger TD, Delgado MR, Gaebler-Spira D, Hallett M, Mink JW. Classification and
definition of disorders causing hypertonia in childhood. Pediatrics 2003; 111:e89-e97.
Milla PJ, Jackson AD. A controlled trial of baclofen in children with cerebral palsy. J
Int Med Res 1977;5:398-404.
Ward A. Long-Term modification of spasticity. J Rehabil Med 2003;35:60-65.
Ashworth B. Preliminary trial of carisoprodol in multiple sclerosis. Practitioner
1964;192:540-542.
Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle
spasticity. Phys Ther 1987;67:206-207.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
References, cont.
9.
10.
11.
12.
13.
14.
15.
Nielsen JF, Sinkjaer T. A comparison of clinical and laboratory measures of spasticity.
Mult Scler 1996;1:296-301.
Haugh AB, Pandyan AD, Johnson GR. A systematic review of the Tardieu Scale for
the measurement of spasticity. Disabil Rehabil 2006; 28(15):899-907.
Verrotti A, Greco R, Spalice A, Chiarelli F, Iannetti P. Pharmacotherapy of Spasticity
in Children with Cerebral Palsy. Pediatr Neurol 2006;34:1-6.
Gracies JM, Elovic E, McGuire J, Simpson D. Traditional pharmacological treatments
for spasticity. Part I: Local treatments. Muscle Nerve [Suppl] 1997;6:S61-S91.
Gracies JM, Nance P, Elovic E, McGuire J, Simpson DM. Traditional pharmacological
treatments for spasticity. Part II: General and regional treatments. Muscle Nerve
[Suppl] 1997;6:S92-S120.
Wenzel R, Jones D, Borrego JA. Comparing two botulinum toxin type A formulations
using manufacturers' product summaries. J Clin Pharm Ther 2007;32:387-402.
Simonetta Moreau M, Cauhepe C, Magues JP, Senard JM. A double-blind,
randomized, comparative study of Dysport vs. Botox in primary palmar hyperhidrosis.
Br J Dermatol 2003;149:1041-1045.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
References, cont.
16. Simpson DM, Gracies JM, Graham HK, et al. Assessment: Botulinum neurotoxin for
the treatment of spasticity (an evidence-based review): report of the Therapeutics
and Technology Assessment Subcommittee of the American Academy of Neurology.
Neurology 2008;70:1691-1698.
17. Wallen M, O'Flaherty SJ, Waugh MC. Functional outcomes of intramuscular
botulinum toxin type a and occupational therapy in the upper limbs of children with
cerebral palsy: a randomized controlled trial. Arch Phys Med Rehabil 2007;88:1-10.
18. Tilton AH. Management of spasticity in children with cerebral palsy. Semin Pediatr
Neurol 2004;11:58-65.
19. Ward A, Chaffman MO, Sorkin EM. Dantrolene. A review of its pharmacodynamic and
pharmacokinetic properties and therapeutic use in malignant hyperthermia, the
neuroleptic malignant syndrome and an update of its use in muscle spasticity. Drugs
1986;32:130-168.
20. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle
relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain
Symptom Manage 2004;28:140-175.
© 2010 AMERICAN ACADEMY OF NEUROLOGY
References, cont.
21. 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;107:32-35.
22. International Classification of Functioning, Disability and Health. Geneva: World
Health Organization: World Health Organization, 2001.
23. Formica A, Verger K, Sol JM, Morralla C. [Gabapentin for spasticity: a randomized,
double-blind, placebo-controlled trial]. Med Clin (Barc) 2005;124:81-85.
For a complete list of references, please access the full
guidelines at www.aan.com/guidelines
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Questions/Comments
© 2010 AMERICAN ACADEMY OF NEUROLOGY
Thank you for your participation!
© 2010 AMERICAN ACADEMY OF NEUROLOGY