Interview Bill Cosby, NavistarCM Describe your current p

Interview: Bill Cosby, Navistar
CM: Describe your current position?
BC:I am a product support specialist, serving 24 dealers in 5
U.S. states. My goal is to assist my service departments in
creating lean and profitable businesses that serve our
customers’ needs quickly and efficiently.
CM: What was your experience prior to your current
assignment?
BC:I was a service manager in a large dealer location for 7
years prior to this role, having worked my way up from
Foremen and technician.
CM: How long have you been in this industry?
BC:I have been in the heavy diesel repair industry for 30 years
CM: Describe the business you are in.
BC:Heavy Diesel transports everything you touch every day.
Navistar builds International trucks and IC buses which are sold
and serviced through a large dealer network in North and South
America as well as Russia, S. Korea and several African
nations.
CM: What are your company’s current strategic goals?
BC:Drive operational Excellence by reducing manufacturing
costs, grow our core business through increased channel
effectiveness and build new sources of revenue through our
product expansions and connected services.
CM: 3 year goals?
BC:A 5% increase in overall market share of truck and bus sales

CM: What is your company’s “global footprint? In other words,
with what countries does your company conduct business?
BC:Navistar has manufacturing facilities in the U.S., Canada,
Mexico and Brazil. We sell our products in those regions as
well as Asia, Europe, Africa and Australia.
CM: Is the current state of global woes impacting your
company?
BC:Currently, we are doing better globally than previous years.
CM: How so?
BC:Our productshave been well received overseas recently as
we can build to their required emissions standards where as
other OEM’s are challenged to build multiple emissions
platforms.
CM: In your opinion, is the current state of global woes likely
to trigger demand for a new style of corporate leadership? If so,
what would this new leadership style look like? If not, then how
does the exciting leadership style support your company’s
future goals?
BC:Corporate leadership is always evolving. Leaders are
constantly adapting to changes in culture, economies and
regulations. The current evolution has leaders more focused on
environmental impacts as well as new technologies that will aid
both their core businesses as well as help our customer base
with their needs and desires.
CM: With the current rate of change in the various business
environments outpacing established abilities for US to meet
demand for human resources, physical resources’, financial
resources, how is your company meeting these demands?
BC:In reality, we’re not. Our industry is service based manual

labor. With the ever increasing perception from our public
school system to college or failure, the youth today do not feel
that a skilled profession a viable sustainable living. Yet, most
technicians today with 2 years of experience are making $50k a
year and that doubles at 5 years of experience. Our company has
created our own training program within a technical college in
an effort to recruit and train those interested in our field.
CM: What are your company’s opportunities for import/export
expansion?
BC:Navistar has been increasing our export sales year over year
for several years now and we will continue that trend into the
foreseeable future.
CM: What are some of the significant changes in workforce
demographics and how are they affecting your organization?
BC:As our long term employees retire, we are faced with the
challenges of a younger more mobile work force. Retention
among today’s younger workforce has been a significant
challenge.
CM: What is your company’s mission statement?
BC:It takes more than just a mission to succeed. It takes
perseverance. It takes courage. And it takes drive. At Navistar
we believe the world is propelled forward by new ideas, brave
inventors and bold thinkers. That's why we're committed to
giving our customers our best every day. We find new ways to
help America's workers go that extra mile. We pioneer
technologies that burn cleaner fuel. And we use the latest
innovations to protect our troops, so they ride more safely into
conflict - and back home. Pushing our industry forward is more
than just our passion. It's our drive to deliver.
CM: What is your advice to professionals who desire to advance

in a global business environment? Give three specific
recommendations.
BC:Invest in people.How you treat someone is the only true
aspect you have control of.
Add value. Don’t wait for someone to tell you what to do.
Anticipate what needs to be done and do it.
Go the extra mile. It’s never crowed there.
CM: What is the key to your success?
BC:Understanding the products and services I have to offer and
how those can become solutions for my customer base.
Being innovative. Looking at a problem from a 360 degree
perspective and taking an outside the box approach to solving it.
Working hard. There is no substitute for putting in the
work.
Literature Review (Oral)
· Points 100
Objective: Students will provide an oral presentation of a
literature review.
General Instructions: Prepare a PowerPoint to convey
information included in the written literature review. Use Tips
for Effective Visual Presentation guide which is included below
as you prepare the PowerPoint.
Specific Instructions:
1. All studies reviewed should be included in the presentation.
2. Include speaking notes* in PowerPoint.
*Speaking notes should capture much of what will be said, but
complete sentences are not required.

Rubric
Literature Review Oral Presentation
Literature Review Oral Presentation
Criteria
Ratings
Pts
This criterion is linked to a Learning OutcomeAll studies
included in the presentation
5.0 pts
Full Marks
0.0 pts
No Marks
5.0 pts
This criterion is linked to a Learning OutcomeSpeaking notes
included in the submitted presentation.
10.0 pts
Full Marks
0.0 pts
No Marks
10.0 pts
This criterion is linked to a Learning OutcomeReferences
included in final slides and are formatted as per the Publication
Manual of the American Psychological Association, but may be
single-spaced.
10.0 pts
Full Marks
0.0 pts
No Marks
10.0 pts
This criterion is linked to a Learning OutcomeAdherence to
Guidelines for Effective Visual Presentation
70.0 pts
Full Marks

0.0 pts
No Marks
70.0 pts
This criterion is linked to a Learning OutcomeAll students
presented and are able to speak without reading continuously
from notes.
view longer description
5.0 pts
Full Marks
0.0 pts
No Marks
5.0 pts
Total Points: 100.0
TIPS FOR EFFECTIVE VISUAL PRESENTATION
Color
· Choose complementary colors yet contrasting colors.
· Use dark on light and light on dark.
· For hints on use of color:
http://owl.english.purdue.edu/owl/resource/715/01/
Background
Textured backgrounds may look beautiful, but they do not
translate well when projected. When too many colors are used
in the background the text may vary with respect to contrast.
Strong contrast is preferable.
Motion
Motion is useful for capturing attention, but is easily overused

and often distracting. Use motion when it makes sense to do so.
Most problematic is motion that occurs too quickly to be
meaningful or too slowly (causing boredom).
Font Style
· Use sans serif font especially for the body text. Serif font is
acceptable for titles and larger font size.
· Font size minimums: 36- 44 point for titles, 24 - 32 point for
body. No more than 3 font sizes on one slide.
· Font selection should be complimentary to the presentation.
Cute or highly decorative fonts do not belong in a professional
presentation.
· Strive to keep titles of slides consistent with respect to font
size.
· Start all sentences and bulleted items with upper case letters.
· Use combinations of upper- and lower-case letters.
· If using all upper-case letters, consider using caps and small
caps.
· Maintain font style as much as possible.
Layout
· Maintain an imaginary frame around a slide. Avoid screen
“fall off”. There are occasions when you may purposely ignore
this rule, but you should have an aesthetic purpose in mind.
Screen “fall off” usually occurs because the presenter is
attempting to force too many words onto the screen and as a
result the words tend to be pushed beyond the frame of the
slide. When this occurs, words get cut off or the slide is
otherwise not aesthetically pleasing. Sometimes this occurs
because the presenter wants to follow the “don’t change the font
size rule” and as a result crams the words onto the screen.
· Strive for achieving the “rule of six”: No more than six words
per line. No more than six lines per slide.
· If using bullets be sure that you have more than one item in

the series. Bullets are NOT needed if you have a list of one
item.
Content
· Avoid full sentences.
· Select key words (no filler words).
Graphics
· Use graphics when it makes sense to do so and select graphics
that give meaning or add to the audiences’ understanding of the
content. Avoid adding graphics just because you can.
· Use graphics of high resolution.
· Do not use graphics with watermarks!
331
cause of the high prevalence of CP (1-
2 in 1000 in developed countries)4,5
and conservative nature of the treat-
ment. It is postulated that by decreas-
ing spasticity, there will be improved
control of movement patterns, stretch-
ing and increased excursion of short-
ened muscles, improved posture, and
secondary strengthening of antagonis-
tic muscles. By implication, these
changes should be associated with im-
proved motor function. Most studies to
date have focused on the use of BTA

injections into the lower extremity gas-
trocnemius muscle and have demon-
strated a temporary reduction in spas-
ticity, temporary improvement in gait,
and improved range of motion.6-9 Min-
imal information is available on the
impact on function of upper extremity
injections in children with CP. Wall et
al10 report positive gains in function
and cosmetic appearance in a prospec-
tive case series of 5 children with a
“thumb in palm” deformity associated
with CP treated with BTA injected into
the adductor pollicis muscle and rigid
splinting of the thumb.10 Denislic and
Meh11 injected BTA into the upper
limbs of 10 children with CP and
Intramuscular injections of Clostridium
botulinum-A toxin into spastic muscles
cause a local temporary muscle paraly-
sis associated with decreased spastici-
ty. The biologic effects of BTA are well
understood.1 Botulinum toxin has
An evaluation of botulinum-A toxin injections
to improve upper extremity function in children
with hemiplegic cerebral palsy
Darcy Fehlings, MD, MSc, Mercer Rang, MB, BS, Janet
Glazier, BSc(OT), and Catherine Steele, PhD
been used therapeutically in adults
over the last 25 years in neuromuscu-
lar conditions associated with focal
dystonia (strabismus, torticollis).2

The use of BTA in cerebral palsy3
has received much interest recently be-
From the Division of Neurology and General Pediatrics,
Department of Pediatrics and the Division of Orthopedics,
Department of Surgery, Bloorview MacMillan Centre and The
Hospital for Sick Children, Toronto, Ontario, Cana-
da.
Supported by the Easter Seal Research Institute (Kids Action
Research).
Submitted for publication Oct 13, 1999; revision received Feb
23, 2000; accepted Apr 28, 2000.
Reprint requests: Darcy Fehlings, MD, MSc, Bloorview
MacMillan Centre, 350 Rumsey Rd,
Toronto, Ontario, M4G 1R8, Canada.
Copyright © 2000 by Mosby, Inc.
0022-3476/2000/$12.00 + 0 9/21/108393
doi:10.1067/mpd.2000.108393
ANOVA Analysis of variance
BTA Botulinum-A toxin
CP Cerebral palsy
PEDI Pediatric Evaluation of Disability
Inventory
QUEST Quality of Upper Extremities Test
Objective: In a randomized, controlled, single-blind trial, to test
the hy-

pothesis that botulinum-A toxin (BTA) injections into the upper
extremity
of children with spastic hemiplegia improve upper extremity
function.
Study design: Thirty children with hemiplegia, aged 2.5 to 10
years, were
randomly assigned to receive: (1) a BTA injection into 1 or
more of 3 mus-
cle groups (biceps, volar forearm muscles, adductor pollicis)
plus occupa-
tional therapy or (2) occupational therapy alone. Blinded
outcomes ob-
tained at baseline and at 1, 3, and 6 months included the Quality
of Upper
Extremity Skills Test (QUEST), goniometry measurements, grip
strength,
and Ashworth scores. The caregiver completed the self-care
domain of the
Pediatric Evaluation of Disability Inventory.
Results: Twenty-nine subjects completed the study. The QUEST
demon-
strated a significant improvement favoring the treatment group
on a 2-way
analysis of variance (F = 4.69, df = 1,83; P = .039). BTA
treatment was also
associated with an improvement in score on the self-care
domain of the Pe-
diatric Evaluation of Disability Inventory (F = 4.68, df = 1,82;
P = .04).
Conclusions: This study supports the effectiveness of BTA
injections to im-
prove upper extremity function of children with hemiplegia who
have at

least moderate spasticity. (J Pediatr 2000;137:331-7)
See editorial, p. 300.
FEHLINGS ET AL THE JOURNAL OF PEDIATRICS
SEPTEMBER 2000
found an improvement in upper limb
function in 9. A double-blind controlled
study by Corry et al12 reports mixed re-
sults on the impact on function in hemi-
plegic CP. Functional improvements
were not found 2 weeks after injection.
A small improvement was found at 12
weeks, favoring the BTA group in a
grasp-and-release activity, but was not
found in another grasp activity (the
ability to pick up coins).
We report the results of a random-
ized, controlled, single-blind trial of
BTA injections into the involved hand
or arm of 30 children with hemiplegic
CP using the Quality of Upper Ex-
tremity Skills Test, a standardized mea-
sure of quality of function of the upper
extremity, as our principal outcome.
METHODS
Participants
Eligible children met the following
criteria: 2.5 to 10 years of age; a diag-
nosis of hemiplegic CP; moderate spas-

ticity at the elbow, wrist, or thumb
with a modified Ashworth score ≥213;
full passive range (defined in this study
as elbow extension to neutral, wrist ex-
tension to 30 degrees past neutral with
the fingers extended, forearm supina-
tion to 30 degrees past neutral, and
thumb extension to neutral); and the
ability to initiate voluntary movement
of the digits. Children were excluded if
they were using a rigid splint to maxi-
mize homogeneity and allow active
movement in the hand.
Study Design
The study was approved by the
Bloorview MacMillan Centre Re-
search Ethics Review Board. The
ethics board, guided by Canadian ethi-
cal standards, did not grant approval
for a double-blind BTA study in which
the control group would receive an in-
tramuscular injection of saline solution
because this was judged to be too
painful and invasive for a placebo.14
When the eligibility criteria were met
and written informed consent was ob-
tained, children were randomly as-
signed, by using a uniform random
number generator, to a treatment or
control group. The treatment group re-
ceived an intramuscular injection of
BTA (Botox, Allergan, USA), at a

dosage of 2 to 6 U/kg body weight, into
at least 1 of 3 muscle groups (biceps,
volar forearm muscles, or adductor
pollicis muscle). Two investigators
(D.F. and M.R.) determined jointly
which muscle groups to inject during
reach-and-grasp activities of the in-
volved hand or arm. If the child
demonstrated persistent elbow flexion,
the biceps was injected; for thumb ad-
duction, the adductor pollicis muscle
was injected. In the volar forearm mus-
cles, for pronation, the pronator teres
muscle was injected; wrist flexion was
an indication for flexor carpi ulnaris
muscle injections; and finger flexion
was an indication for injection of the
finger flexors. The location of the in-
jection was determined by anatomic
knowledge and muscle palpation.15-17
The biceps was injected in the top
third of the muscle at 2 sites, the volar
flexor muscle was injected at 2 sites, 2
to 3 cm below the medial epicondyle.
The pronator teres was injected at one
site in the upper third of the muscle,
and the adductor pollicis was injected
in one site in the belly of the muscle.
Children in both groups were asked
to continue with community-based oc-
cupational therapy at a minimum fre-
quency of one session every 2 weeks.
Research funding was not available

to provide occupational therapy by
research personnel. An occupational
therapy manual with guidelines was de-
veloped for the study and sent to each
of the participating occupational thera-
pists. The guidelines were based on
standard practice for therapy manage-
ment of spastic hemiplegia and incor-
porated activities for upper extremity
strengthening and the development of
skills for activities of daily living.18,19
Children were seen at baseline and at
1, 3, and 6 months. A single investigator
(J.G.), blinded to the subject group
assignment, obtained all objective out-
come measurements. The primary out-
come measure was the QUEST.20-22
This is an objective standardized mea-
sure evaluating the quality of upper
extremity function in 4 domains: disso-
ciated movement (an isolated joint
movement of the upper extremity that
counters a pattern of spastic synergy),
grasp, protective extension, and weight
bearing. Scores for the QUEST are cal-
culated as percentages with a maximum
score of 100. The QUEST was de-
signed with minimal developmental se-
quencing so that scoring reflects the
severity of the disability rather than age.
A caregiver completed the self-care
domain of the Pediatric Evaluation of
Disability Inventory to assess the

child’s activities of daily living.23 The
self-care domain has 73 items in 15
332
Treatment group Control group
Characteristic (n = 14) (n = 15) P value
Age (mo) 68 ± 31 64 ± 28 .71
Gender (M/F) 10/5 10/5 1.00
Involved side (right/left) 10/4 7/8 .17
Modified Ashworth score* 2.3 ± 0.75 2.2 ± 0.59 .89
QUEST baseline 19.2 ± 15.1 27.6 ± 19.0 .41
PEDI baseline 50.2 ± 11.1 52.2 ± 15.4 .25
Grip strength (mm Hg) 56.40 ± 16.59 53.38 ± 21.33 .46
Values are expressed as means ± SD.
*Represents the mean of Ashworth measurements for elbow and
wrist extension, forearm
supination, and thumb extension.
Table I. Baseline comparability of the treatment and control
groups*
THE JOURNAL OF PEDIATRICS FEHLINGS ET AL
VOLUME 137, NUMBER 3
skill areas, such as hand washing. Raw
scores can be converted to a scaled
score with a 0 to 100 distribution based
on Rasch scale modeling. The PEDI
has been designed to measure function
in children with physical disabilities

and has established reliability, validity,
and responsiveness.23-26
Secondary outcome measures in-
cluded manual goniometric measure-
ments of passive range of motion27;
modified sphygmomanometer mea-
surements of grip strength28; and the
modified Ashworth score of spasticity
at elbow extension, wrist extension,
forearm supination, and thumb exten-
sion.13 Test-retest reliability for passive
goniometry measurements and grip
strength was evaluated before the
study in children with upper extremity
spasticity and was found to be high,
with correlation coefficients ranging
from 0.58 to 0.97.29
Statistical Analyses
The analyses were conducted by using
the SAS microcomputer-based pack-
age.30 The following tests were used.
1. A preliminary analysis included a
thorough check of the data (re-
view of outliers and missing data),
a descriptive summary, and plots
of each variable.
2. Chi-square and unpaired t tests
were used to check the compara-
bility of the BTA treatment and
control groups at baseline for age,

sex, involved side, and baseline
Ashworth, QUEST, and PEDI
scores.
3. A 2-way analysis of variance was
computed to detect differences
between the BTA treatment and
control groups during the study
period in the QUEST, the PEDI,
grip strength, Ashworth scores,
and passive goniometry measure-
ments. To account for baseline ef-
fects, the differences between
baseline and 1 month, baseline
and 3 months, and baseline and 6
months were used. Statistical sig-
nificance was set a priori at P < .05
for the 2 functional outcomes, the
QUEST and the PEDI, and set at
P < .01 for the secondary out-
comes to account for the multiple
testing.
4. A post hoc Wilcoxon rank sums
test was performed to examine the
significance of group differences
at 1, 3, and 6 months for variables
that demonstrated statistical sig-
nificance on the ANOVA.
RESULTS
Participant Characteristics
Fifty children were screened; 20 did
not meet the eligibility criteria (13 had

an Ashworth score <2, 6 had an inabil-
ity to initiate voluntary movement in
the involved hand, and 2 had fixed
contractures). Thirty children were re-
cruited into the study and randomly
assigned to the treatment (n = 15) and
control (n = 15) groups. Thus 29 chil-
dren completed the study, with one
child in the treatment group dropping
out before the 1-month assessment.
Table I outlines the comparability of
the 2 groups at baseline. No significant
differences were found.
Table II outlines the BTA treatment
for each child with respect to dosage
and location. Both groups received oc-
cupational therapy in the community
at a recommended frequency of once
every 2 weeks. The treatment group
received a mean of 11.93 (SD 6.89)
333
QUEST
Muscle injected (U/kg)
change Volar Pronator Adductor
Subject No. BTA (U/kg) (to 1 mo) Biceps flexors teres muscle
pollicis muscle
1 4 36.67 — 4.0 — —
2 4 4.48 — 4.0 — —
3 2 19.36 2.0 — — —
4 4 12.19 — 4.0 — —
5 4 8.53 — 4.0 — —

6 4 23.90 — 1.3 1.3 1.3
7 5.2 –1.97 — 3.6 1.6 —
8 3.8 21.37 — 2.9 — 1.0
9 4.3 2.21 3.2 1.1 — —
10 2.7 0.78 — 1.8 — 0.9
11 3.3 –9.71 — 2.2 — 1.1
12 3.6 30.18 1.8 — — 1.8
13 6.6 14.29 — 4.9 — 1.6
14 3.4 Dropout — 1.1 1.1 1.1
15 6.3 12.79 1.6 3.2 — 1.6
Table II. Dosage and location of injection for each participant
in the BTA treatment group
SEPTEMBER 2000
treatment sessions, and the control
group received a mean of 16.07 (SD
7.60) treatment sessions over the 6-
month period of the study. This differ-
ence favored the control group but was
not statistically significant (P = .74).
Main Results
The total score for the involved side
on the QUEST, the primary outcome
measure, demonstrated a statistically
significant improvement favoring the
BTA treatment group on the ANOVA
(F = 4.69, df = 1,83; P = .039). The time-
group interaction was not significant (P

= .50). Post hoc testing with the
Wilcoxon rank sum test showed signifi-
cant differences between the treatment
and control groups at 1 month (P = .01)
but not at 3 (P = .13) or 6 months (P =
.14). These results are outlined in the
Figure. On the 4 subtests of the
QUEST, the subtest “weight bearing”
(P = .009) showed a significant im-
provement favoring the treatment
group. On the other 3 subtests, results
favored the treatment group but were
not statistically significant: “dissociated
movement” (P = .63), “grasp” (P = .33),
and “protective extension” (P = .55).
The results of the PEDI and sec-
ondary outcomes are listed in Table
III. A statistical difference was found
in the raw scores of the parent-com-
pleted self-care domain of the PEDI (F
= 4.68, df = 1; P = .04). The time-group
interaction was not significant (P =
.84). Post hoc testing with the Wilcox-
on rank sums test approached signifi-
cance at 1 month (P = .08) and 6
months (P = .06). The corresponding
ANOVA evaluating the PEDI scaled
scores approached significance (F =
3.22, df = 1; P = .08). No significant dif-
ferences between the treatment and
control groups were found in grip
strength, Ashworth scores, or passive
goniometry measurements.

The injections in the treatment group
were well tolerated. Aside from the dis-
comfort of the injection, only one child
(Table II, subject 1) reported temporary
decreased grip strength lasting 2 weeks.
No other side effects were noted.
DISCUSSION
This controlled clinical trial provides
evidence to support the use of intra-
muscular BTA injections to improve
both quality of functional movement of
the upper extremity and functional ca-
pability in children with hemiplegic
CP. A clinical and statistically signifi-
cant improvement in quality of func-
tion was found at 1 month. Children in
the BTA group improved from 19.2%
on the QUEST at baseline to 32.5% at
1 month compared with a 1.7% change
in the control group. Moderate im-
provements were maintained up to 6
months after injection. This is clinical-
ly important because the effect of the
BTA injection on function lasts longer
than the neuromuscular blockade,
which disappears, on average, at 3
months.1 In the control group a
gradual improvement in quality of
function was found over the 6-month
period of the study. The positive
change in function in the control
group may reflect both the impact of
the occupational therapy intervention
and developmental improvements

with time; and this highlights the im-
portance of including a control group
when studying changes in child devel-
opment. The improvement in the con-
trol group and low statistical power
(16%) may explain the lack of statisti-
cal significance at the 6-month testing.
Within the subtests of the QUEST,
weight-bearing activities demonstrat-
ed the most change.
For children receiving the BTA in-
jections, the parents also reported
small positive functional change in the
children’s self-care skills (eg, dressing,
eating). This supports carry-over of
functional change into the children’s reg-
ular environments and daily activities.
Grip strength declined at 1 and 3
months in the BTA group but normal-
ized by 6 months after injection. This
finding was expected because BTA
blocks conduction at the neuromuscu-
lar junction, which reduces spasticity
but also causes muscle weakness.
334
Figure. Mean change from baseline in the QUEST total scores.
Changes in scores were analyzed
with 2-way ANOVA. Post hoc Wilcoxon rank sums test was
done at 1, 3, and 6 months. Asterisk
indicates P < .05 on post hoc testing.

Though the grip was weaker after
BTA, function improved.
Differences in the modified Ash-
worth score of spasticity favored the
BTA group but were not significantly
different. Both groups showed a de-
cline in spasticity throughout the peri-
od of the study. It is interesting to spec-
ulate on the reason for the decline in
spasticity within the control group.
This may be secondary to developmen-
tal improvements in spasticity with
time, familiarity with the test, the im-
pact of the occupational therapy, or
measurement variation.
The ideal dosage of BTA for upper
extremity spasticity requires further
research. It is hard to predict the func-
tional impact of higher dosing. Increas-
ing the dosage will result in a greater
decline in spasticity but will also lead
to greater reductions in grip strength,
which in turn may have a negative im-
pact on functional outcome.
Passive range of motion also did not
show a significant change between the
BTA and control groups. This reflects

the excellent baseline flexibility of the se-
lected subjects who had full range in the
majority of joint measurements assessed.
335
Change from baseline
One month Three months Six months P value*
PEDI (raw score)
BTA group 2.00 ± 5.99 3.85 ± 5.11 6.77 ± 5.82 .04
Control group –1.93 ± 5.78 1.13 ± 5.19 2.64 ± 5.75
PEDI (scaled score)
BTA group 2.57 ± 6.91 2.78 ± 3.72 5.50 ± 4.54 .08
Control group –1.51 ± 4.07 1.09 ± 4.07 3.30 ± 6.05
Grip strength (mm Hg)
BTA group –7.60 ± 14.57 –6.86 ± 13.06 2.00 ± 12.74 .34
Control group 1.50 ± 18.76 3.83 ± 22.81 –0.27 ± 20.77
Ashworth/elbow
BTA group –0.29 ± 0.47 –0.23 ± 0.48 –0.38 ± 0.46 .89
Control group –0.20 ± 0.62 –0.37 ± 0.44 –0.29 ± 0.51
Ashworth/wrist
BTA group –0.43 ± 0.43 –0.31 ± 0.38 –0.35 ± 0.43 .81
Control group –0.36 ± 0.44 –0.33 ± 0.45 –0.25 ± 0.55
Ashworth/forearm
BTA group –0.32 ± 0.42 –0.35 ± 0.38 –0.27 ± 0.60 .51
Control group –0.20 ± 0.49 –0.20 ± 0.53 –0.18 ± 0.58
Ashworth/thumb
BTA group –0.31 ± 0.48 –0.25 ± 0.40 –0.33 ± 0.39 .90

Control group –0.28 ± 0.57 –0.29 ± 0.54 –0.27 ± 0.48
Elbow extension†
BTA group 0.07 ± 6.62 5.46 ± 11.74 2.84 ± 6.69 .11
Control group –0.80 ± 6.62 3.00 ± 12.83 0.79 ± 9.32
Forearm supination†
BTA group 3.43 ± 9.00 5.15 ± 8.10 3.00 ± 12.08 .34
Control group 1.67 ± 5.63 1.67 ± 6.28 0.64 ± 6.62
Wrist extension†
BTA group 4.08 ± 7.35 4.58 ± 11.92 2.00 ± 15.02 .55
Control group 0.67 ± 8.78 1.27 ± 9.91 2.07 ± 11.49
Palmar thumb abduction†
BTA group 2.14 ± 5.91 1.46 ± 8.52 2.77 ± 8.12 .48
Control group 1.00 ± 7.97 –0.60 ± 10.01 1.21 ± 6.96
Values are expressed as means ± SD.
*P value refers to the significance of overall differences
between the BTA group and control group on the ANOVA.
†Goniometry measurements.
Table III. Results of the 2-way ANOVA for the secondary
outcome measures
SEPTEMBER 2000
It is important to note that the posi-

tive effects on upper-extremity func-
tion observed after BTA injection are
generalizable to children who are clini-
cally similar to the subjects selected for
the study. Many children with a clini-
cal diagnosis of spastic hemiplegic CP
have Ashworth spasticity scores <2 or
poor distal voluntary muscle control.
This clinical trial excluded both of
these groups of children. Further re-
search is required before results are
generalized to these subgroups.
A limitation of the study is the sin-
gle-blind design. Both the children
and their parents knew whether they
were in the treatment or the control
group. This could have an impact on
the parent-completed PEDI. A single
objective evaluator who was blinded
to the group assignment completed all
other outcome measurements, includ-
ing the QUEST. The large number of
subjects assessed and the similarity of
changes in Ashworth score between
the 2 groups prevented the uninten-
tional unblinding of this evaluator,
minimizing the impact of the single-
blind design on the primary results of
this study.
Botulinum toxin injections were
given without electromyographic guid-
ance. This has the advantage that con-
scious sedation is not required, which
has fewer side effects and allows the

use of BTA in ambulatory and rehabil-
itation settings. Evaluation of the indi-
vidual responses of subjects showed
that the BTA injection was successful
(positive change >5% on the QUEST)
in 9 of 14 subjects. However, 5 subjects
(33%) received a BTA injection but
did not show improvement in function.
One potential explanation for this is
that the intended muscle groups were
not targeted accurately. There is some
support for improved accuracy of BTA
injections with electromyographic
guidance in the literature.31
Continued research is required to
evaluate the dose response and the im-
pact on function of repeated BTA
upper-extremity injections.
We thank the children and families who par-
ticipated in the study. We also thank Allergan
for providing the botulinum-A toxin for the
study.
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337
Low-dose/high-
concentration localized
botulinum toxin A
improves upper limb
movement and
function in children
with hemiplegic
cerebral palsy
Kevin Lowe* MBBS FRACP FAFRM, Department of Paediatric
Rehabilitation, Sydney Children’s Hospital and University of
New South Wales, Randwick;
Iona Novak MSc BAppSc, Manager Research and Education,
Cerebral Palsy Institute, Sydney;
Anne Cusick BAppSc GradDipBehSc MA (Psych) MA
(Interdisc Stud) PhD, Professor, Associate Dean, College of
Science and Health, University of Western Sydney (UWS),
Australia.
*Correspondence to first author at Department of
Paediatric Rehabilitation, Sydney Children’s Hospital, High
Street, Randwick, Australia.
E-mail: [email protected]
The objective was to determine the effects of low -dose, high-

concentration, dual localized botulinum toxin A (BTX-A)
injections on upper limb movement quality and function. Study
design was an evaluator-blinded, randomized, controlled trial.
Forty-two children (31 males, 11 females; range 2–8y, mean 4y
[SD 1.6]) with hemiplegic cerebral palsy (Gross Motor Function
Classification System level I) participated. All received
occupational therapy. The treatment group (n=21) received one
injection series (mean muscles injected 6 [SD 1.05]; total dose
82–220 units, mean 139 [SD 37.48]; dilution 100 units/0.5ml).
Primary outcome of Quality of Upper Extremity Skills Test
(QUEST) at 6 months was not significant (p=0.318). Secondary
outcomes were average treatment effects at 1, 3, and 6 months,
which favoured the treatment group: QUEST (p<0.001);
Canadian Occupational Performance Measure (performance,
p=0.002; satisfaction p=0.007); parent Goal Attainment Scaling
(GAS; p=0.001), therapist GAS (p<0.001); Pediatric
Evaluation of Disability Inventory (PEDI) functional skills
(p=0.030); Ashworth (p<0.001). PEDI caregiver assistance
was not significant (p=0.140). Therapy alone is effective, but at
1 and 3 months movement quality is better where BTX-A is
also used. Moreover, function is better at 1, 3, and 6 months,
suggesting BTX-A enhances therapy outcomes beyond the
pharmacological effect. One- and 3-month Ashworth and
QUEST scores suggest precise needle placement accuracy.
Children with cerebral palsy (CP) experience many daily chal -
lenges as a result of the upper motor neurone syndrome.
Symptoms include the following: spasticity, weakness, loss of
dexterity, poor motor control, and sensory impairment. Bot-
ulinum toxin A (BTX-A) reduces spasticity (Corry et al. 1997,
Love et al. 2001, Delgardo 2002, Boyd et al. 2003, Chin and
Graham 2003, Yang et al. 2003, Hoare and Imms 2004) and is
usually used with interventions such as physical and occupa-
tional therapy to help children attain functional goals. Red-
uction of spasticity in children with CP is clinically important
because the following outcomes can occur: muscle length imp-

rovement leading to a slowing of contracture development
rates (Corry et al. 1997); improved tolerance of splinting and
casting interventions, which increase range and function (Del -
gardo 2002); enhanced function (Russman et al. 1997, Love et
al. 2001, Delgardo 2002, Boyd et al. 2003); more opportun-
ity for therapy interventions to be introduced (Russman et al.
1997); and reduction in pain (Delgardo 2002). As recently as
2002 the use of BTX-A in the upper limb in CP was regarded as
experimental (Wasiak et al. 2002); however, expert clinical op-
inion about its potential (Russman et al. 1997) is rapidly being
complemented by positive findings of effect (Fehlings et al.
2000, Boyd and Hays 2001, Boyd et al. 2002, Wallen et al.
2004).
Accurate needle placement in BTX-A injection is important
because this avoids severe side effects and helps to determine
whether an observed lack of response to the drug is related to
the region of injection. The use of localization techniques is
known to improve needle placement accuracy (Chin et al.
2003). Manual localization techniques provide promising fun-
ctional results (Corry et al. 1997, Fehlings et al. 2000). More
recently, localization with the use of electrical stimulation has
demonstrated good functional lower limb outcomes (Love et
al. 2001) and sustained improvement in the upper limb (Boyd
et al. 2003, Wallen et al. 2004). Ultrasound is an emerging
local-
ization technique (Westhoff et al. 2003), and electrical stimula -
tion has been shown to be more accurate in needle placement
than manual techniques (Chin et al. 2005). So far there have
been no studies specifically examining BTX-A injected into
upper limbs of children with CP with the use of both elec-
tromyography and stimulation. The use of electromyography
should enable spastic muscles to be identified (O’Brien 2002)
so that muscles with contracture can be excluded as injection
sites. Enhanced accuracy in needle placement should also
increase efficacy because lower total doses can be used in high-

er concentrations within muscles related to functional goals.
This study investigated whether or not there was a differ-
ence in clinical outcomes for young children with spastic hemi -
plegic CP receiving occupational therapy, if they received one
session of low-dose, high-concentration BTX-A injected using
dual-mode localization. The primary clinical outcome measure
was quality of movement at 6 months. Secondary outcomes of
interest were the weighted average of treatment effects at 1, 3,
and 6 months in the following: (1) quality of upper limb move-
ment (1 and 3 months, and percentage of participants with
more than 20% improvement); (2) function; and (3) spasticity.
Methods
DESIGN
This study was a randomized, controlled, evaluator-blinded,
prospective parallel-group trial based on Consolidated Stan-
dards of Reporting Trials (CONSORT) guidelines. Following
170 Developmental Medicine & Child Neurology 2006, 48:
170–175
Localized Injections of Botulinum Toxin A Kevin Lowe et al.
171
subject screening, informed consent was obtained from chil -
dren’s parents using Ethics Committee approved participant
information sheets and consent forms. All outcome measures
were administered at baseline and at 1, 3, and 6 months. The
study was conducted through The Spastic Centre and the
Sydney Children’s Hospital and was approved by the Research
Ethics Committees of South Eastern Sydney Area Health Ser-
vice, the Spastic Centre, and the University of Western Sydney

Macarthur, Australia. All analyses were determined prospec-
tively with an intention-to-treat approach.
SAMPLE
To estimate sample size, an improvement of more than 20% in
Quality of Upper Extremity Skills Test (QUEST) scores from
baseline was used in power calculations. This degree of change
was selected on the basis of a pre-study pilot and evidence of
change likely from the control intervention alone (Hickey and
Ziviani 1998). Twenty participants per group were estimated to
have at least 80% power to detect a 10-unit difference in
QUEST
score between groups (two-sided test at 0.05 significance),
assuming that the SD of change in total QUEST score was 8.98
units. A convenience sample was used with participation invit-
ed through statewide recruitment advertisements and a
mailout to all paediatricians.
The inclusion criteria were as follows: age 2 to 8 years;
diagnosis of hemiplegic CP; presence of spasticity scoring at
least 2 on the Ashworth Scale interfering with functional
movement; at least 10˚ active range of movement in antago-
nistic muscle during use; volitional limb use observed by
both parent and investigator when instructed to play bilater-
ally; access to occupational therapy after baseline assessment;
and parental agreement to participate in a home programme.
The exclusion criteria were as follows: lower limb BTX-A
in the past 6 months; upper limb BTX-A in the past 12
months; upper limb fixed contracture greater than 40˚; lack
of sensory response to light touch or pain in the affected
limb; child refused or was unable on 100% of occasions to
demonstrate volitional upper limb movement in response
to parent or investigator instructions and parent confirmed

that this was consistent with their upper limb use at home.
During 16 months of recruitment, 57 children were screen-
ed and 43 were enrolled. One child withdrew in the control
group after 1 month because of travel difficulties. A total of 42
patients were analyzed at each follow-up: 21 in the treatment
group and 21 in the control group; all were at GMFCS level I;
age range 2 to 8 years (mean 4y [SD 1.6] for both groups); there
were 31 males and 11 females.
RANDOMIZATION
An independent officer used computer-generated random
allocation sequences in numbered sealed envelopes to achieve
randomization. Participants volunteered from rural and met-
ropolitan locations. To plan for travel and accommodation,
parents were informed of their group allocation before base-
line measures. The study managed allocation awareness by
requesting families not to tell raters their allocation and
explain-
ing why, by using standardized observational assessments in
which performance could not reasonably be manipulated in
the light of known allocation, and by conducting between-
group baseline analyses.
INTERVENTION
Both groups received occupational therapy from the same
occupational therapist, and the treatment group received
intramuscular injections of BTX-A. The therapy provided was
based on best available evidence including the use of individ-
ualized family goals (e.g. independent dressing or sports par -
ticipation) with mutually agreed levels of attainment dev-
eloped through two collaborative interviews. Individualized
home programmes were developed with the family to imple-
ment in goal-relevant contexts of home or school/pre-school.

Programmes drew on a suite of interventions offered by the
therapist but driven by the family, including functional training,
strengthening, splinting, casting, and motor learning (Cop-
ley and Kuipers 1999, Wilton 2003, Steultjens et al. 2004).
Standard indicators were used to verify the need for and to
prescribe splinting and casting (Copley and Kuipers 1999).
BTX-A intervention
Electromyography was used to exclude muscle contracture, to
Table I: Botulinum toxin A (BTX-A) exposure by muscle group
Muscle group Total number of units/kg/muscle group
BTX-A-injected
Elbow flexors
n 4
Mean 3.5
SD 0.32
Range 3.1–3.9
Pronators
n 18
Mean 3.3
SD 0.95
Range 1.1–4.3
Wrist flexors
n 14
Mean 2.1
SD 0.75
Range 1.1–3.2
Wrist extensors

n 1
Mean 1.0
SD –
Range 1.0–1.0
Finger flexors
n 12
Mean 2.2
SD 0.70
Range 1.0–3.2
Thumb adductor
n 9
Mean 0.6
SD 0.15
Range 0.5–0.9
Thumb opponens
n 20
Mean 0.7
SD 0.18
Range 0.5–1.1
Thumb flexors
n 4
Mean 0.8
SD 0.31
Range 0.5–1.2
assist in identifying the most spastic muscles and to identify
muscle penetration to minimize trauma to other tissues. In all
cases, electromyography guidelines (Perotto 1994) were used
to assist in identifying injection sites. To refine the identifica -
tion of the correct muscle point for injection, stimulation was

used at threshold levels by observation of movement respons-
es to stimulus. Injection muscle choice was based on the
degree of spasticity (baseline Ashworth score of at least 2),
esti-
mated effect on functional abilities, and parental preference of
likely arm posture if BTX-A was effective. The number of
partic-
ipants with affected muscles in treatment versus control were
as follows: elbow flexor, 16:15; pronators, 20:21; wrist flexor,
17:16; wrist extensor, 1:2; finger flexor, 14:10; thumb adduc-
tor, 13:18; thumb opponens, 21:21; and thumb flexor, 6:4.
The total dose of BTX-A injected did not exceed 8 units/kg
body weight, which is lower than the expert consensus maxi-
mum dose of 12 units/kg per session (Delgardo 2002). A clini -
cal estimate of likely muscle size was used to guide the app-
ropriate dose calculation per muscle from the total of 8 units
(Table I, range 0.5–2.0 units/kg/muscle). Dilution of 100 units
of BTX-A was with 0.5ml of normal saline, which is more con-
centrated than usual. Volume of injection to muscle was deter -
mined by dose per individual muscle; number of muscles
injected, mean 6 (SD 1.05); total dose 82 to 220 units, mean
139 (SD 37.48). Participants who received injections received
nil by mouth and were admitted to a day-stay ward at the
Sydney Children’s Hospital. A eutectic mixture of local anaes-
thetics cream, chloral hydrate, pethidine, droperidol, and
midazolam were used in various combinations to achieve ade-
quate sedation and analgesia.
DATA COLLECTION AND INSTRUMENTS
Data were collected at baseline and at 1, 3, and 6 months. The
baseline data were a therapy history survey and a physical
examination (height, weight, pulse rate, and blood pressure).
All other instruments were used on all four occasions.

Adverse events form
Safety was assessed by recording and reporting to the South
Eastern Sydney Area Health Service Committee any adverse
events (start and stop dates, relationship to the study med-
ication, severity, frequency, action taken, and outcome).
Quality of Upper Extremity Skills Test (QUEST)
The primary outcome measure was two domains of the QUEST
(dissociated movement and grasp) scored blind by one trained
assessor from video footage of the QUEST (DeMatteo et al.
1992). Test authors report that the use of less than the total
four domains is psychometrically sound. QUEST at 6 months
was chosen because there was known sensitivity to capture
change in CP, investigators were interested in whether BTX-
A injection effect plus therapy outlasted known pharmaco-
logical effect timelines, there was a precedent for its use with
young children (Fehlings et al. 2000), and psychometric
properties were good (Hickey and Ziviani 1998). The total
possible standard score across the two domains is 100.
Canadian Occupational Performance Measure (COPM)
Two trained, blinded occupational therapists administered and
scored the COPM (Law et al. 1994), which had been adapted
for use with children. COPM had been used to measure effec-
tiveness of upper limb BTX-A intervention for children with
CP (Boyd et al. 2003). Psychometric properties of the adapt-
ed instrument were generally good (Cusick et al. forthcom-
ing). The total possible score was 20 (10 for performance
and 10 for satisfaction).
Pediatric Evaluation of Disability Inventory (PEDI)
The PEDI (Haley et al. 1992) was scored from parental r eport

interviews. The PEDI has robust psychometric properties
(Feldman et al. 1990, Nichols and Case-Smith 1996) and has
been used with children with spastic hemiplegic CP (Fehlings
et al. 2000). The total possible score for self-care/ functional
170–175
Table II: Efficacy analysis
Measure Baseline 1 mo 3 mo
Control score BTX-A score Control score BTX-A score Control
score BTX-A score
QUEST total 33.3 (2.6) 32.1 (2.4) 36.0 (2.7) 43.9 (3.3) 37.1
(2.6) 46.2 (3.5)
Family GAS 23.1 (0.6) 21.6 (0.9) 27.1 (1.4) 36.1 (2.8) 34.1
(2.0) 42.0 (2.2)
Therapist GAS 30.5 (1.8) 27.5 (1.3) 40.5 (2.6) 57.8 (3.0) 46.8
(2.7) 61.0 (3.8)
COPM performance 3.3 (0.3) 3.3 (0.3) 3.8 (0.3) 4.5 (0.2) 4.5
(0.3) 5.3 (0.3)
COPM satisfaction 3.5 (0.4) 3.8 (0.3) 4.1 (0.4) 5.1 (0.3) 4.7
(0.4) 5.8 (0.3)
PEDI functional skills 43.4 (3.1) 50.7 (3.0) 44.2 (2.9) 53.1 (2.5)
48.3 (2.4) 55.8 (2.5)
PEDI caregiver assistance 21.5 (2.7) 26.2 (2.3) 23.6 (2.4) 28.2
(1.8) 26.0 (2.0) 29.8 (1.7)
Ashworth
Elbow flexors 2.3 (0.1) 2.2 (0.1) 2.3 (0.1) 1.4 (0.1) 2.1 (0.1) 1.4
(0.1)
Pronators 2.5 (0.1) 2.6 (0.1) 2.4 (0.1) 1.5 (0.1) 2.4 (0.1) 1.5
(0.1)
Wrist flexors 2.3 (0.1) 2.2 (0.1) 2.2 (0.1) 1.1 (0.1) 2.1 (0.1) 1.5

(0.1)
Wrist extensors 2.0 (0.0) 3.0 (0.0) 2.0 (0.0) 2.0 (0.0) 1.5 (0.5)
2.0 (0.0)
Finger flexors 2.2 (0.1) 2.4 (0.1) 2.2 (0.1) 1.4 (0.1) 2.2 (0.1) 1.6
(0.2)
Thumb adductor 2.2 (0.1) 2.2 (0.1) 2.2 (0.1) 1.1 (0.1) 2.2 (0.1)
1.6 (0.2)
Thumb opponens 2.1 (0.1) 2.2 (0.1) 2.1 (0.1) 1.0 (0.0) 2.1 (0.1)
1.4 (0.1)
Thumb flexors 2.0 (0.0) 2.3 (0.2) 2.0 (0.0) 1.2 (0.2) 1.8 (0.3)
2.0 (0.4)
aTreatment effect is reported in terms of unit of measurement
for each instrument. bThere were insufficient numbers for
calculation.
The p value given is that of repeat-measures analysis. Scores
and effects are shown in brackets as mean. BTX-A, botulinum
toxin A;
QUEST, Quality of Upper Extremity Skills Test (DeMatteo et
al.1992); GAS, Goal Attainment Scaling (Kiresuk et al. 1994);
COPM, Canadian
Occupational Performance Measure (Law et al. 1994); PEDI,
Pediatric Evaluation of Disability Inventory (Haley et al. 1992).
skills is 73, and for self-care caregiver assistance the maximum
score is 40.
Goal Attainment Scaling (GAS)
Goal Attainment Scaling (Kiresuk et al. 1994) is recommended
to identify clinically significant functional change after BTX-A
injections (Russman et al. 1997) and has been used in other
BTX-A upper limb trials (Boyd et al. 2003, Wallen et al. 2004).
The family developed their own ‘family GAS’ of three to five

goals before the administration of COPM. The goals and attain-
ment levels were of their selection, design and priority,
facilitat-
ed and later scored by two trained blinded occupational
therapists. Another ‘therapist GAS’ was developed by an inves-
tigator; it identified functional tasks and levels of performance
not covered elsewhere in other measures. Performance of
‘therapy GAS’ tasks was videoed and scored by a blind evalua-
tor (dressing and toileting were not videoed because of child
protection standards; parental report was used instead). There
is no standardized total possible score; however, goal attain-
ment across all goals is indicated by the ‘T’ score. A goal
attain-
ment T score of 50 (SD 10) equates to expected gains.
Ashworth Scale
The Ashworth Scale (Ashworth 1964) is sensitive to change
from spasticity pharmacological management including
BTX-A (Love et al. 2001). It was, therefore, used as a measure
of the technical effect of the BTX-A. Reliability of the Ash-
worth Scale in elbow flexors is good (Bohannon and Smith
1987). Individual muscles are rated on a scale between 0 (nor -
mal) and 5 (most severe), with no total possible score.
Analysis of primary outcome measure
QUEST total score at 6 months was modelled by using linear
regression; baseline QUEST score, age, and intervention
assignment were covariates.
Analysis of secondary outcome measures
Secondary outcomes were changes in QUEST, Ashworth, fami-
ly GAS, therapy GAS, COPM, and PEDI scores from baseline to
1, 3, and 6 months. Treatment effect sizes and standard errors

were calculated with repeated-measures analyses (PROC GEN-
MOD) adjusting for corresponding score baseline values, visit
(as a categorical variable used because of the expectation of
participant improvement over time) and age at baseline, and at
1, 3, and 6 months (with the exception of Ashworth scores).
The estimated treatment effect was interpreted as the average
treatment effect measured across the three post-baseline visits
with a 95% confidence interval (CI). All tests were performed
as
two-tailed tests (p≤0.01). Another secondary outcome was the
percentage of participants with at least 20% improvement in
total QUEST scores over baseline at 1, 3, and 6 months. Two-
sided Fisher’s exact tests were used to assess significance.
Results
BETWEEN GROUP BASELINE ANALYSIS
There were no significant differences between groups in base-
line QUEST, COPM, GAS (therapist or family), Ashworth mea-
sures, or self-reported history of involvement in therapy (phys-
ical or occupational; Table II). Baseline PEDI scores for
caregiv-
er assistance were significantly different, favouring intervent-
ion, which might possibly reflect their group allocation aware-
ness, because BTX-A could reasonably be considered a ‘high
promise intervention’ (Russman et al. 1997) and parent inter -
views might have permitted an expression of high hopes rather
than a functional difference as other measures were not signifi -
cantly different. During intervention, there was no difference
in use of splinting (100% for each group) or contracture casting
(n=3 in each group).
BETWEEN-GROUP OUTCOME ANALYSES
Table II summarizes study results in mean scores over time,
and 6-month treatment effects and CIs for primary and sec-
ondary outcomes.

Safety
There were 31 adverse events reported by 15 participants and
no between-group difference. No events were considered
related to BTX-A by the South Eastern Sydney Area Health
Service review panel.
QUEST
After adjusting for baseline score and age, differences in mean
QUEST total scores between the treatment and control groups
were significant at 1 month (9.7 points; 95% CI 5.5 to 13.8;
p<0.001) and 3 months (10.8 points; 95% CI 6.0 to 15.7;
p<0.001), but not at 6 months (2.7 points; SE 2.4; 95% CI –2.1
to 7.4; p=0.318; Fig. 1). A significantly larger proportion of
treatment group participants showed more than 20% change
above baseline QUEST scores compared with the control
group at 1 month (67 vs 19%; p=0.004) and 3 months (71 vs
33%; p=0.03), but not at 6 months (52 vs 48%; p=1.0).
Children in the treatment group had better quality of upper
limb movement sooner, even though all children improved
with occupational therapy at higher levels than previously
reported and all children sustained improvement at 6 months.
ASHWORTH
Greatest differences were seen at 1 and 3 months (Table II),
173
Table II: continued
6 mo

Control score BTX-A score Treatment effecta 95% CI p
39.6 (2.8) 40.7 (3.2) 7.7 (1.9) 4.0 to 11.5 <0.001
40.1 (2.9) 46.8 (2.3) 7.5 (2.3) 2.9 to 12.1 0.001
49.9 (2.7) 58.7 (3.4) 14 (3.5) 7.1 to 21.0 <0.001
5.1 (0.4) 5.9 (0.3) 0.8 (0.3) 0.3 to 1.3 0.002
5.4 (0.5) 6.2 (0.3) 0.8 (0.3) 0.2 to 1.4 0.007
51.1 (2.6) 57.9 (2.2) 3.1 (1.4) 0.3 to 6.0 0.03
26.7 (2.1) 32.0 (1.7) 1.9 (1.3) –0.6 to 4.4 0.140
2.0 (0.2) 1.9 (0.1) –0.5 (0.1) –0.7 to –0.4 <0.001
2.4 (0.1) 2.2 (0.1) –0.8 (0.1) –1.0 to –0.6 <0.001
2.3 (0.1) 1.9 (0.1) –0.7 (0.1) –0.9 to –0.5 <0.001
1.5 (0.5) 2.0 ( . ) 0.3 (0.0) 0.3 to 0.3 b
2.2 (0.2) 2.1 (0.2) –0.8 (0.1) –0.9 to –0.6 <0.001
2.1 (0.1) 2.0 (0.2) –0.6 (0.1) –0.8 to –0.4 <0.001
2.1 (0.1) 2.1 (0.1) –0.6 (0.1) –0.8 to –0.5 <0.001
1.3 (0.3) 2.2 (0.3) –0.3 (0.1) –0.4 to –0.1 0.001
which suggests that the BTX-A was accurately localized.
FAMILY GAS
Table II illustrates that both the treatment and control
groups increased average ‘family’ T scores over study dura-
tion. Results of the repeated-measures analysis showed a treat-
ment effect size of 7.5 points (95% CI 2.9–12.1; p=0.001).
This result shows the weighted average of treatment effects.
It shows that all children made progress towards attaining
goals developed by the family but the treatment group had

consistently greater improvement that was sustained beyond
the pharmacologically active period of BTX-A.
THERAPY GAS
Table II illustrates that both groups increased average ‘thera -
pist’ T scores over the study duration. Results of repeated-
measures analysis showed a treatment effect size of 14 points
(95% CI 7.1–21.0; p<0.001). These results indicate that
although all children made progress towards attaining goals
developed by the therapist, the treatment group had the
greatest improvement.
COPM
Both groups showed consistent improvement in performance
and satisfaction scores (Table II). Results of repeated-measures
analysis showed a treatment effect size for performance of
0.8 points (95% CI 0.3–1.3; p=0.002) and for satisfaction of
0.8 points (95% CI 0.2–1.4; p=0.007). These results indicate
that although all children made consistent gains in function
and their parents’ level of satisfaction with their performance,
the treatment group had consistently greater improvement.
PEDI
Both groups showed consistent improvement in functional
skills and caregiver assistance (Table II). Results of the repeat-
ed-measures analysis showed a treatment effect size for func-
tional skills of 3.1 points (95% CI 0.3–6.0; p=0.03) and for
caregiver assistance of 1.9 points (95% CI –0.6– 4.4; p=0.140).
These results indicate that although all children made con-
sistent gains in functional skills, the treatment group had
greater improvement; they also show that although all chil -
dren made gains in caregiver assistance scores, with scores
being higher in the treatment group, they were not signifi-

cantly different for the treatment group.
Discussion
BTX-A has already been shown to decrease spasticity in the
hemiplegic upper limb and to enhance functional outcomes
in children with spastic hemiplegic CP. This study comple-
ments previous study findings on BTX-A effects on upper
limbs for children with CP. Our study was adequately pow -
ered, used measures directly targeting domains of interest,
used blinded evaluation in most measures, and had therapy
interventions that were consistently delivered and were
based on best available evidence. The new finding is that
although occupational therapy on its own is effective, clinical
outcomes for children receiving occupational therapy are
markedly enhanced by a single session of dual-mode local-
ized BTX-A injection because it produces greater 1-month
and 3-month gains in upper limb quality of movement, func-
tion, and spasticity, and greater 6-month gains in function.
Children who receive BTX-A in addition to therapy, there-
fore, have greater clinical gain faster and this gain is sus-
tained at 6 months. These short-term and long-term gains
were made with lower doses and higher concentrations
than previously reported, and with higher thresholds for
clinical change required in QUEST scores (20% from base-
line). Apart from this key result, findings related to adminis-
tration technique, therapy programme, and injection cand-
idate characteristics are worth comment.
The dual-mode localized administration technique seems
to be an effective method for precise needle placement because
low-dose, high-concentration injections had a marked clini-
cal and ‘technical’ effect at 1 and 3 months. Because other
non-invasive techniques such as manual or ultrasound local -
ization are usually paired with a higher dose and lower con-
centrations, there may be merit in future research to compare

invasive versus non-invasive localization techniques and dif-
ferent dose regimes. For now, it is clear that stimulation with
electromyography provides enhanced precision in adminis-
tration, offering the possibility of lower doses.
Therapy intervention was based on best available evidence
and was delivered by one experienced therapist. This might
explain the high level of improvement in quality of move-
ment and function by all children in the study, including those
who did not receive BTX-A injection. Improvement was
greater than that previously reported in similar studies of
younger children (Fehlings et al. 2000, Boyd et al. 2003,
Wallen et al. 2004), and higher than the 4.5% change estimat-
ed to occur as a result of therapy intervention by QUEST test
developers (DeMatteo et al. 1992). Although the effective-
ness of therapy alone is a good result, the marked clinical
benefit provided by BTX-A is important. It means that faster
and greater functional gains can be made by children who
have therapy if they receive BTX-A.
Injection candidate characteristics can also be considered
in the light of this study. Exclusion and inclusion criteria
were based on previous study findings (Corry et al. 1997,
Fehlings et al. 2000) and they proved to be both practical and
useful in sample selection because a uniform and positive
170–175
Figure 1: QUEST change over 6 months. QUEST, Quality of
Upper Extremity Skills Test; BTX-A, botulinum toxin A; OT,
occupational therapy.
50

45
40
35
30
25
Baseline 1 mo 3 mo 6 mo
BTX-A & OT Control
QUEST total score
175
response to BTX-A was demonstrated. These characteristics
might, therefore, provide useful clinical guides for the selec-
tion of very young children with CP for BTX-A intervention,
particularly when high efficacy is required, spasticity is not
severe, therapy is received, and upper limb quality of move-
ment and function are intervention goals.
LIMITATIONS AND RECOMMENDATIONS
Our study was limited by single evaluator blinding: both par-
ent and child knew whether or not they were in the treat-
ment group because placebo injections were not used. The
study investigated only one injection administration technique.
In practice the CP population of young children is quite
diverse and the study inclusion and exclusion criteria were

restrictive. This study used one injection, monitored for
only 6 months, with occupational therapy intervention
begun after baseline. The effect of repeat injections, previous
occupational therapy, and longer-term outcomes of the sin-
gle injection needs investigation.
Conclusion
Low-dose, high-concentration BTX-A injections localized with
the use of both electromyography and stimulation seem clini -
cally worthwhile for young children with CP, because they pro-
vide short-term quality of movement gains that are faster and
greater than those generated by therapy alone, and better
short-term and long-term functional gains are achieved.
DOI: 10.1017/S0012162206000387
Accepted for publication 12th April 2005.
Acknowledgements
Dr Terry Neeman, Principal Statistician, Covance Pty Ltd,
provided
statistical support.
Competing interests
Allergan gave partial support by providing the BTX-A used in
the
study, by payment of a blind rater for the QUEST, data entry,
and
some analysis done by an independent data management firm.
The
authors have no pecuniary interest in Allergan. Investigator and
research assistant labour apart from that already identified were
supported by the Spastic Centre, University of Western Sydney,
and
Sydney Children’s Hospital.

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