982
SPECIAL SECTION: ORIGINAL ARTICLE
Comparative Impact of 2 Botulinum Toxin Injection
Techniques for Elbow Flexor Hypertonia
Nathaniel H. Mayer, MD, John Whyte, MD, PhD, Gunilla Wannstedt, MS, PT, Colin A. Ellis, ScB
ABSTRACT. Mayer NH, Whyte J, Wannstedt G, Ellis CA.
Comparative impact of 2 botulinum toxin injection techniques
for elbow flexor hypertonia. Arch Phys Med Rehabil 2008;89:
982-7.
Objective: To compare 2 techniques of botulinum toxin
injection for elbow flexor hypertonia.
Design: Parallel-group, randomized, controlled trial with
blinded outcome assessment.
Setting: Laboratory, tertiary rehabilitation hospital.
Participants: Adults (N⫽31) with acquired brain injury (21
with traumatic brain injury, 8 with stroke, 2 with hypoxic
encephalopathy) provided 36 sets of elbow flexors with Ash-
worth Scale scores equal to 3.
Intervention: Botulinum toxin type A (BTX-A) was injected
with a motor point or a multisite injection technique after obtain-
ing 2 baseline evaluations of the main outcome measures. Motor
point technique involved decremental electric stimulation with
delivery of 60U of BTX-A (Botox) in 2.4mL or 30U BTX-A in
1.2mL of preservative-free saline at single biceps and brachiora-
dialis motor points, respectively. Distributed injection was per-
formed using electromyographic feedback. Fifteen units in 0.6mL
were delivered to each of 4 biceps sites and 2 brachioradialis sites.
Total dose (90U) and total injection volume (3.6mL) were iden-
tical across groups. Only sites and injection techniques varied. The
brachialis was not injected in either group.
Main Outcome Measures: Ashworth Scale, Tardieu catch
angle, and root mean square surface electromyographic activity
of the biceps, brachialis, and brachioradialis.
Results: Postintervention testing at 3 weeks showed no signif-
icant differences between groups (P range, .31–.82 across 3 out-
come measures). However, within each group, significant treat-
ment effects were observed on all outcome measures (all P⬍.01).
For the uninjected brachialis muscle, electromyographic reduction
was greater for the distributed group.
Conclusions: In 31 adults with acquired brain injury, single
motor point and multisite distributed injections of low-dose, high-
volume BTX-A had similar impact. Findings suggest that low-
dose, high-volume strategies may have a potential role in reducing
drug cost and helping clinicians stay within accepted limits for
total body dose in patients with upper motoneuron syndrome
requiring many injections.
From the Department of Physical Medicine and Rehabilitation, Temple University
School of Medicine, Philadelphia, PA (Mayer); Moss Rehabilitation Research Institute,
Albert Einstein Healthcare Network, Philadelphia, PA (Mayer, Whyte, Ellis); Department
of Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, PA (Whyte); and
Motor Control Analysis Laboratory, MossRehab, Elkins Park, PA (Mayer, Wannstedt).
Supported in part by the National Institute on Disability and Rehabilitation Re-
search (grant no. H133A020505) and an educational grant from Allergan Inc.
No commercial party having a direct financial interest in the results of the research
supporting this article has or will confer a benefit upon the authors or upon any
organization with which the authors are associated.
Correspondence to Nathaniel H. Mayer, MD, MossRehab, 60 E Township Line Rd,
Elkins Park, PA 19027, e-mail: nmayer@einstein.edu. Reprints are not available from
the authors.
0003-9993/08/8905-00662$34.00/0
doi:10.1016/j.apmr.2007.10.022
Arch Phys Med Rehabil Vol 89, May 2008
Key Words: Botulinum toxins; Brain injuries; Injections;
Muscle hypertonia; Rehabilitation.
© 2008 by the American Congress of Rehabilitation Medi-
cine and the American Academy of Physical Medicine and
Rehabilitation
N RECENT YEARS, botulinum toxin type A (BTX-A) has
Imuscle
gained in usage as a treatment for the consequences of
overactivity in patients with an upper motoneuron
syndrome (UMNS).1-5 Because upper and lower limbs are
frequently involved, patients with UMNS often have many
target muscles to treat. One practical problem of treating many
muscles is keeping the total dose of BTX-A within current
guidelines for maximum body dose of toxin a visit.6 Therefore,
using elbow flexor hypertonia as our clinical model, our goal in
this study was to find a more efficient way to treat UMNS
patients with BTX-A. Ways of tackling this problem have
included winnowing muscle selection through better history
and physical examination, using gait laboratory and motion
analysis to aid muscle selection, injecting smaller amounts of
toxin in larger volumes, and finding better ways to inject. For
example, Childers et al,7 concerned with finding a better way to
inject large muscles, compared 2 different delivery techniques
of BTX-A in the large gastrocnemius muscle of spastic
hemiplegics. In this study, we also looked at large upper-limb
muscles using 2 different methods of injection: a motor point
technique and a distributed quadrants technique. Clinical ben-
efits of BTX-A injections depend primarily on preventing
release of acetylcholine at the neuromuscular junction, also
called the endplate.8 Dosing for UMNS hypertonia was initially
determined empirically and through shared clinical experi-
ences. Because differently sized muscles were involved, clini-
cians soon emphasized injecting many sites for larger muscles
and fewer sites for smaller ones.9 For the biceps, 4 distributed
sites have been recommended, using a dose range of 50 to
200U (Botox). Some injectors divided the biceps into 4 quad-
rants for injection, and others injected the estimated middle of
the muscle or its greatest palpable bulk. For the brachioradialis,
2 injections distributed along the long axis of the muscle were
recommended, using a dose range of 25 to 75U. Because
BTX-A diffuses after injection, perhaps as much as 5cm, even
crossing anatomic barriers such as fascia,10,11 the utility of
multisite injections depends on diffusion to cover as much
territory as possible for toxin to find its way to endplates.
The distributed method inefficiently encourages larger doses
of toxin because it does not target endplates. Endplate targeting
has been reported to potentiate effects of BTX-A in a canine
model.12 Animal models and clinical studies have indicated
that distance to endplates influences efficiency of treatment
with BTX-A. Shaari and Sanders13 observed that injections
5mm from the endplate resulted in a 50% decrease (compared
with endplate injections) in glycogen staining as a marker of
paralysis for rabbit longissimus dorsi. In humans, Gracies
et al14 injected a small volume of BTX-A close to endplates of
the biceps brachii using an endplate-targeting technique. The
result was more effective than injecting the same volume at a
 IMPACT OF 2 BOTULINUM TECHNIQUES, Mayer 983

greater distance from the endplate region. Injecting the same
dose in a larger volume at a greater distance from the endplate
was as effective as the smaller volume closer to the endplate.
What do we know about the location of endplates for the
biceps? Coërs and Woolf15,16 found that the innervation band
(zone of endplates) of human biceps underlies its motor point,
found on the skin by electric stimulation. Warfel’s map17 for
the motor point of the biceps diagrams it as half-way between
the proximal and distal tendons of the biceps. Aquilonius et al18
described biceps brachii endplates as a 5- to 10-mm–wide band
in a 4- to 6-cm–long region half-way between the proximal and
distal tendons of the biceps. Deshpande et al19 recently de-
scribed the endplates of the biceps as an inverted V-shaped
band just below the midpoint of the humerus.
Much less is known about the motor point of the brachiora-
dialis. Unlike the biceps, whose motor point overlies its end
plates, Coërs15 noted that the motor endplates of the brachi-
oradialis were deeply situated. The fasciculi of the brachiora-
dialis arise from a superficial layer of the fascia, running
toward a deeply situated musculotendinous junction. As a
consequence, nerve endings of the endplate, in relation to the
surface site of the motor point, lie at an uncertain distance. We
reasoned that careful electric stimulation with iteratively de-
creasing current intensity might help guide the needle tip closer
to the vicinity of the endplates, if indeed the endplates are
located close to the motor point of the brachioradialis. We also
reasoned that greater dilutions might also promote toxin diffu-
sion onto endplates of the brachioradialis.
Given the relationship between the anatomic location of
endplates and physiologically determined motor points de-
scribed by Coërs and others in the literature cited earlier, we
reasoned that toxin instilled with a motor point technique,
especially in larger fluid volumes, might disperse more effi-
ciently into the vicinity of the endplates of the biceps and
brachioradialis. Accordingly, we arrived at the following hy-
pothesis: given an injection of a constant dose of BTX-A
delivered in a constant volume per muscle to patients with
spastic hypertonia, a single-site motor point injection technique
will be superior in reducing hypertonia compared with the
more standard distributed technique of injecting the biceps in 4
sites and the brachioradialis in 2 sites, remote from their motor
points.9
METHODS
Participants
Participants were 31 adult patients with acquired brain injury
who were referred to the Motor Control Analysis Laboratory
for evaluation and treatment of severe elbow flexor hypertonia.
Five patients were bilaterally involved; therefore, 36 elbows
were studied. All limbs had an Ashworth Scale score of 3.
There were no contraindications to treatment with BTX-A such
as concurrent use of aminoglycosides, myasthenia gravis, or
treatment with BTX-A within 3 months. Patients were ex-
cluded if they had hypertonia elsewhere in the upper limb that
required additional medical intervention. An initial exclusion
criterion was flexion contracture greater than 60°; this was later
relaxed to 70°. Patients or their surrogates gave written in-
formed consent, and the project was approved by our institu-
tional review board. Characteristics of the participants can be
seen in table 1. Of the 10 patients with nontraumatic brain
injury, 8 patients had stroke and 2 patients had hypoxic en-
cephalopathy.
Outcome Measures and Instrumentation
Three clinicophysiologic variables were studied: the Tardieu
catch angle (part of the Modified Tardieu Scale20,21), the Ash-
worth Scale,22 and the root mean square (RMS) quantification
of surface electromyographic activity recorded during the Ash-
worth maneuver.

Table 1: Balance of Experimental Groups at Baseline

Distributed Quadrants Motor Point Effect
Characteristics (n⫽18) (n⫽18) Size t34 P

Age (y) 34.7⫾21.9 37.9⫾19.9 .16 0.47 0.64

Time postinjury (d) 481.9⫾890.1 256.7⫾418.7 .32 0.97 0.34
Maximum passive elbow extension (deg) 31.5⫾25.2 23.9⫾26.5 .30 0.89 0.38

␹12

Sex (n) 1.80 0.18*

Male 17 13
Female 1 5
Etiology (n) 0.50 0.73*
TBI 11 13
Non-TBI 7 5
Chronicity (n) 0.12 1.00*
Subacute (⬍6mo) 12 11
Chronic (⬎6mo) 6 7
Outcome Variables Mann-Whitney U

TCA (deg) 105.1⫾9.6 102.9⫾11.9 .21 178.5 0.60

RMS EMG values (mV)
Biceps 0.158⫾0.136 0.119⫾0.106 .32 195 0.30
Brachialis 0.091⫾0.068 0.070⫾0.054 .34 196 0.28
Brachioradialis 0.197⫾0.166 0.132⫾0.077 .50 185 0.47
3-muscle average 0.149⫾0.119 0.107⫾0.067 .43 190.5 0.37

NOTE. Values are mean ⫾ standard deviation (SD) or n or as indicated.

Abbreviations: EMG, electromyographic activity; TCA, Tardieu catch angle.
*Fisher exact test.

Arch Phys Med Rehabil Vol 89, May 2008

984 IMPACT OF 2 BOTULINUM TECHNIQUES, Mayer
Tardieu catch angle. The available range of motion
(ROM) at the elbow was measured with a handheld goniom-
eter.a Maximum passive elbow extension was performed at a
very slow rate so as not to trigger a spastic reaction that could
influence the degree of extension. To determine the Tardieu
catch angle, the examiner extended the elbow as rapidly as
possible and reported the angle at which a sudden palpable
increase in resistance (the catch) was perceived.20,21 Five con-
secutive trials were performed by an experienced physical
therapist and averaged to create the session’s value.
Ashworth Scale. The 5-point ordinal Ashworth Scale22
was used to measure passive resistance. Passive stretch of
elbow flexors was initiated at a velocity that would cover the
available ROM in 1 second23 if resistance to stretch was not
encountered by the examiner. This was assessed with a strain
gauge electrogoniometer.b Trials in which the measured veloc-
ity was more than 30% different from the target velocity were
discarded. The median value of 5 acceptable trials was used for
data analysis.
Electromyography. Surface electromyographic activity
was recorded from the biceps brachii, brachialis, and brachi-
oradialis during Ashworth maneuvers. Ag/AgCl electrodesc
were centered over the midbelly mound of the biceps. Brachi-
oradialis electrodes were placed 4cm distal to the elbow crease,
and brachialis electrodes were placed just medial to the biceps
tendon and proximal to the crease to minimize biceps crosstalk.
A ground electrode was placed on the back of the shoulder.
Electromyographic signals, sampled at 1kHz, were fed
through a MyoPac differential amplifier,d bandwidth filtered
(20 – 495Hz) and processed by DataPac 2K2 software.d RMS
values were calculated for each muscle on the interval between
20% and 80% of the amplitude of stretch, the most rapidly
changing portion of stretch. Five trials were averaged for each
session. One subject’s electromyographic value for the brachi-
oradialis during the third testing session was an extreme outlier
and was removed.
Protocol
Each patient was tested 3 times. Two baseline sessions took
place on separate days (mean ⫾ standard deviation [SD],
4.2⫾3d). At the end of the second session, each elbow was
randomized to an injection technique (described below) and
injections of BTX-A (Botox) were performed by the principal
investigator. A posttreatment session was conducted approxi-
mately 3 weeks later (mean, 23.5⫾4.4d). The examiner was
blind to injection technique assignments. Adverse events and
medication changes were monitored throughout the study.
Injection techniques: motor point injection technique. Ana-
tomically, a motor point is the most distal electrosensitive site
of a motor nerve that corresponds to its entry site into the
muscle or to an area where motor endplates cluster and where
minimal stimulating current generates a perceptible twitch of
muscle fibers.24,25 Single biceps and brachioradialis motor
points were first approximated by stimulating skin sites17 with
short-duration electric pulses at 1Hz (EZ Stim Model ES200e)
to optimize needle insertion site. After skin preparation with
iodine, alcohol, and a local anesthetic, a Teflon-coated 27-
gauge hypodermic needle, 38mm long, serving to stimulate the
motor point electrically as well as to inject it, was advanced
toward the motor point. Muscle twitches were monitored visu-
ally and by palpation. As the needle tip advanced closer to the
motor point, current intensity was turned down because less
was needed to generate a twitch. Injection was generally per-
formed when current intensity reached 0.3 to 0.2mA.
Injection techniques: distributed quadrants technique. Two
sites, the biceps tendon at the elbow crease and the distal end
Arch Phys Med Rehabil Vol 89, May 2008
of the anterior deltoid, were estimated by palpation. A longi-
tudinal line traversing the mound of the biceps muscle was
generated between these 2 sites. A midpoint perpendicular to
the longitudinal line was approximated, resulting in 4 sectors or
quadrants. A 27-gauge Teflon-coated hypodermic needle was
inserted toward the outer diagonal edge of each of the 4
quadrants, using auditory electromyography guidance to verify
that the needle tip was in muscle. The 4 needle sites, rectan-
gularly configured, were separated from each other by at least
5cm. The distributed quadrants technique for the brachioradia-
lis was performed with the forearm held in neutral. Injection
was performed at 2 sites along the long axis of the muscle, 2.5
and 5cm below the elbow crease, typically into the visible bulk
of the muscle using auditory electromyography guidance.
Dosing. Motor point injections occurred at 1 site in the
biceps (60U, 2.4mL) and 1 site in the brachioradialis (30U,
1.2mL). Distributed injections occurred at 4 sites in the biceps
and 2 sites in the brachioradialis (15U, 0.6mL per site). Thus,
total dose (90U) and volume (3.6mL) were constant for both
groups; only the injection sites and localization techniques
varied between groups.
Data Analysis
Baseline balance of the experimental groups was assessed
with the following tests: Student t test for age, days postinjury,
and maximum passive range of elbow extension; Pearson chi-
square and Fisher exact tests for sex, etiology, and chronicity;
and Mann-Whitney U test for Tardieu catch angle and electro-
myographic outcome measures. Where appropriate, effect sizes
(Cohen d) were also calculated as the difference of means
divided by the pooled SDs. For both Tardieu catch angle and
electromyography data, the 2 baseline sessions had high test-
retest reliability and were averaged to create a single baseline
value for each elbow. Baseline Ashworth scores were 3 for all
elbows studied.
Comparisons between injection techniques took baseline
values into account for each outcome measure. This was not
necessary for Ashworth scores, with all scores being 3 at
baseline. Thus, posttreatment Ashworth scores for the 2 groups
were compared by a Mann-Whitney U test. However, the
distribution of Tardieu catch angle and electromyography
scores violated statistical assumptions underlying statistical
adjustment by means of regression or analysis of covariance.
Therefore, log-transformed electromyography data were fit to a
general linear model using baseline electromyographic activity
and treatment group as predictors and session 3 electromyo-
graphic activity as the dependent variable. Tardieu catch angle
values required nonparametric stratification into 4 bins, and a
stratified Wilcoxon test was used to take baseline strata into
account when comparing the 2 treatment groups.
To assess the within-group effect of chemodenervation,
paired t tests were used for Tardieu catch angle, and electro-
myographic measures and effect sizes were also computed. A
Wilcoxon signed-rank test was used for the ordinal Ashworth
score. Finally, to assess the possible contribution of spontane-
ous recovery to treatment effects within groups, the entire
cohort of subjects was divided based on a median split of time
postinjury (median, 84d), regardless of injection technique.
Treatment effect sizes were calculated for these 2 groups
(defined as acute and chronic).
RESULTS
Baseline Characteristics of the Experimental Groups
Table 1 shows the characteristics of the motor point and
distributed quadrants groups at baseline. There were no signif-
 IMPACT OF 2 BOTULINUM TECHNIQUES, Mayer 985

Table 2: Effects of the Motor Point Injection (nⴝ18)

Outcome Measure Baseline Posttreatment Effect Size t17 P

TCA (deg) 102.9⫾11.9 76.8⫾21.1 1.52 4.99 ⬍.001

RMS EMG (mV)
Biceps 0.119⫾0.106 0.050⫾0.043 0.85 3.08 .007
Brachialis 0.070⫾0.054 0.053⫾0.074 0.26 1.53 .146
Brachioradialis 0.132⫾0.077 0.048⫾0.028 1.45 4.46 ⬍.001
Ashworth score 3 (3) 2 (0–2) 3.82* ⬍.001

NOTE. Values are mean ⫾ SD or median (range).

*Wilcoxon z.

icant differences between the groups in terms of demographic
features or baseline measures of hypertonia. Although 22 of 36
elbows had some level of flexion contracture, these contrac-
tures were well balanced between groups; furthermore, con-
tracture angle did not correlate with Tardieu catch angle at
baseline (r34⫽.03, P⫽.86) and so was unlikely to confound the
results. Ashworth scores are not shown in table 1 because all 36
elbows had scores of 3 at baseline.
Between-Group Treatment Effects
There were no significant differences between the 2 groups
for any of the outcome measures assessed. Median Ashworth
scores after treatment decreased by 1 point compared with
baseline for both groups (Mann-Whitney U test, P⫽.53). The
Tardieu catch angle posttreatment did not differ significantly
either when analyzed in a simple 2-sample Wilcoxon test
(P⫽.46) or when stratified by baseline Tardieu catch angle
(P⫽.31). Comparison of the log-transformed composite elec-
tromyography signal from the 3 elbow flexors did show a
significant effect of baseline electromyographic activity
(P⫽.003), with a slope of .465 (95% confidence interval [CI],
.192–.737), indicating larger-magnitude electromyographic
signals posttreatment for subjects with larger baseline electro-
myographic measures. However, the group difference was
small in magnitude (.046) (95% CI, .350 –.441) and nonsignif-
icant, corresponding to 4.5% lower electromyographic magni-
tude in the distributed quadrants group than the motor point
group after adjustment for baseline electromyographic activity.
Results were similar for electromyography data of individual
muscles as well.
Within-Group Treatment Effects
To make sure that a lack of difference between groups was
not due to ineffective treatment in both groups (ie, floor effects
related to the choice of a low treatment dose), we checked for
treatment effects within each group. For the motor point group,
a clinicophysiologic effect of toxin injection was observed at
the 3-week postintervention session (table 2). A significant
intervention effect was found for each outcome variable, with
the exception of electromyographic activity of the uninjected
brachialis muscle.
For the distributed quadrants group, a clinicophysiologic
effect of toxin injection was also observed at the 3-week
postintervention session (table 3). A significant intervention
effect was found for each outcome variable, including electro-
myographic activity of the uninjected brachialis muscle.
Effect of Spontaneous Recovery During the Study Period
To assess the possible contribution of spontaneous recovery
to treatment effects within groups, the entire cohort of subjects
was divided, based on a median split of time postinjury (84d),
regardless of injection technique. In chronic patients (n⫽18),
electromyography data showed a small effect size in the un-
treated brachialis (.09) but large effect sizes in toxin-treated
muscles (.86 –.95), suggesting that the medication had a large
impact unrelated to spontaneous recovery. In acute patients
(⬍84d, n⫽18), the corresponding effect sizes were increased
(brachialis, .65; treated muscles, 1.11–1.3). However, for Tar-
dieu catch angle, which measures hypertonia across the joint as
a whole, there was virtually no difference in effect size be-
tween acute (1.54) and chronic (1.57) patients.
DISCUSSION
In this study of 31 adults with acquired brain injury and
elbow flexor hypertonia, we found that localizing motor points
before injection was not superior to distributed electromyogra-
phy-guided injections when using low doses and high volumes
of BTX-A as specified. The lack of a significant group differ-
ence does not appear to be related to low statistical power,
because effect sizes reflecting group differences for the 3
outcome measures were small. Although there was no differ-
ence between groups, there was a robust treatment effect within
each group, as discussed later.
Our study, like others, found significant reductions in Ash-
worth scores.1,5,26-28 However, the ordinal Ashworth Scale
lacks sensitivity, and it measures nonneural as well as neural
components of resistance. More sensitive, continuous measures
may be able to distinguish between treatment techniques where

Table 3: Effects of the Distributed Injection (nⴝ18)

Outcome Measure Baseline Posttreatment Effect Size t17 P

TCA (deg) 105.1⫾9.6 74.4⫾28.7 1.44 4.49 ⬍.001

RMS EMG (mV)
Biceps 0.158⫾0.136 0.051⫾0.041 1.07 3.38 .004
Brachialis 0.091⫾0.068 0.056⫾0.058 0.56 2.52 .02
Brachioradialis 0.197⫾0.166 0.059⫾0.048 1.13 3.59 .002
Ashworth score 3 (3) 2 (0–3) 3.63* ⬍.001

NOTE. Values are mean ⫾ SD or median (range).

*Wilcoxon z.

Arch Phys Med Rehabil Vol 89, May 2008

986 IMPACT OF 2 BOTULINUM TECHNIQUES, Mayer
the Ashworth Scale cannot.29-32 We therefore included the
Tardieu catch angle in our study, a measure of the angle at
which a catch or sudden palpable resistance occurs during very
rapid passive stretch. Critically, this catch reflects neurally
mediated hypertonia33-36 and is considered a truer score of
spasticity than Ashworth scoring. In this study, the Tardieu
catch angle value was also significantly reduced for each tech-
nique, so we can conclude with greater confidence than we had
with Ashworth reduction that the toxin intervention truly had
an effect on the neural component of hypertonia.
The study also included a quantitative electromyography
measure to provide muscle-specific information, something
Ashworth and Tardieu catch angle measures cannot do. Our
findings indicate that each injection technique reduced the
biceps and brachioradialis activity significantly. The relation
between biceps endplates and its motor point is known from
Coërs’s work,15 but less is known regarding the brachioradialis.
Our finding of reduced brachioradialis electromyographic ac-
tivity suggests that the motor point technique may well be
creating access for toxin to the brachioradialis endplates. Of
additional interest is the finding of a moderate effect size
(Cohen d⫽.56) for the uninjected brachialis in the distributed
group. The distributed technique used 4 biceps needle inser-
tions compared with one for the motor point method. With
multiple sticks, depth of needle insertion has a greater chance
for variability, suggesting that leakage of toxin onto the bra-
chialis, which lies beneath the biceps, has a greater chance of
occurring. Alternatively, the distributed technique, covering
more areas of muscle, might favor toxin effect on broadly
distributed muscle spindles,37,38 which could account for more
widespread C5-6 segmental reduction of hypertonia, of which
the brachialis, a C5-6 muscle, could partake.
With respect to volume or dilution considerations, recent
investigations looked at the issue of high and low volumes at
constant dosing. Francisco et al39 compared 2 different vol-
umes for wrist and finger flexor spasticity, using the same dose
of BTX-A. Modified Ashworth Scale scores decreased signif-
icantly for both high- and low-volume groups with a nonsig-
nificant trend in favor of the high-volume preparation. Gracies
et al40 injected the biceps of chronic hemiplegics with high and
low volumes containing constant doses of BTX-A (160U). A
greater reduction in Tardieu angle was found in the high-
volume group. Gracies et al14 elsewhere reported that injecting
a small volume of BTX-A close to the neuromuscular junction
was more effective than injecting a similar volume at a distance
from the junction. However, injecting a large volume more
distant from the junction was as effective as a small volume
close to the neuromuscular junction. In our study, we used
large volumes with a dose three eighths that of the Gracies
study and achieved competitive reductions of our outcome
measures. These findings suggest that a low-dose, high-volume
strategy may be a consideration when treating UMNS patients
with many muscles to treat, especially when trying to stay
within total body dose guidelines. Finally, although the con-
sensus standard for volume has been “up to 1 cc per injection
site,”6(p157) we note that the maximum injection volume of
Gracies40 of 2mL (40U) and our volume of 2.4mL (60U)
resulted in no serious adverse events.
Study Limitations
Certain study limitations must be considered. We cannot be
certain about the relationship between distributed quadrants
sites and motor point sites because we did not identify motor
point sites of the distributed quadrants group. Moreover, spread
of toxin and mechanisms of diffusion are unknown variables.
Given the specified high volumes of this study, we may not
Arch Phys Med Rehabil Vol 89, May 2008
have come close to a floor effect with the low doses used—for
example, a low-dose, low-volume injection at the motor point
compared with similar dosing with a distributed technique
might have produced group differences.
The use of surface electromyography as a measure of muscle
specificity raises a number of concerns. Measurement of sur-
face electromyographic activity is subject to tissue impedance
variability across subjects, electrode placement variability
across test sessions, and cross-talk (electrode pickup of activity
from nearby nontarget muscles). Cross-talk is difficult to quan-
tify. Nevertheless, the finding of significant reduction of elec-
tromyographic activity of injected muscles within each group
indicates that the amount of cross-talk was not sufficient to
obscure an experimental effect. The much larger treatment
effect for the biceps and brachioradialis compared with the
uninjected brachialis also provides some evidence that surface
electromyography yields muscle-specific information.
Although oral antispasticity drugs were kept unchanged,
other medications taken by the patients might have affected
hypertonia. We examined a subset of 20 subjects (10 in each
group) who had no changes of medication in the postinterven-
tion period. Descriptive statistics for all outcome measures in
this subset were found to be similar to those of the full cohort
of subjects. Treatment effect sizes both between and within
groups were also similar. It seems unlikely that medication
changes could have confounded our results.
CONCLUSIONS
The impacts of 2 different injection techniques on elbow
flexor hypertonia were compared, using low-dose (60U in the
biceps, 30U in the brachioradialis), high-volume (2.4mL in the
biceps, 1.2mL in the brachioradialis) injections of BTX-A.
Single motor point and multisite distributed injections were
found to have similar impact at these doses and volumes.
Findings suggest that low-dose, high-volume strategies may
have a potential role in reducing drug cost and helping clini-
cians stay within accepted limits for total body dose in patients
with UMNS requiring many injections.
Acknowledgments: We gratefully acknowledge Caron Morita,
BA, for project supervision, Shane Eynon, PhD, for assistance with
data collection and management, and Inna Chervoneva, PhD, for
statistical consultation.
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Arch Phys Med Rehabil Vol 89, May 2008