Gait of a deafferented subject without

large myelinated sensory fibers

below the neck
Y. Lajoie, PhD; N. Teasdale, PhD; J.D. Cole, MD; M. Burnett, PhD; C. Bard, PhD; M. Fleury, PhD;
R. Forget, PhD; J. Paillard, PhD; and Y. Lamarre, MD, PhD

Article abstract-We evaluated the gait pattern of a deafferented subject who suffered a permanent loss of large sensory
myelinated fibers below the neck following an acute episode of purely sensory neuropathy 21 years ago. The subject has
developed several strategies to achieve a secure gait, namely: (1) a reduction of the degrees of freedom by freezing the knee
articulations during the stance phase, (2) a preservation of body balance by enlarging his base of support, and (3) visual
monitoring of his step by stabilizing the head-trunk linkage together with a characteristic forward tilt. As a result, the
gait of the deafferented subject lacks the fluidity of normal gait. Compared with normal subjects, the gait pattern of the
deafferented subject is characterized by a shorter cycle length, a longer cycle duration, a slower speed, and a lower
cadence. Using a dual-task paradigm, the attentional demands for walking were particularly important (as indexed by
longer probe reaction times) during the double-support phase, suggesting that the deafferented subject uses the double-
support phase as a transitory stable phase to update cognitively the postural features necessary for generating his next
step.
NEUROLOGY 1996;47: 109-1 15

Walking is a highly practiced activity, often consid-
ered to be automatically controlled. Nevertheless,
continuous regulation and integration of sensory in-
puts of various origin is required to preserve the
postural balance and to achieve a permanent adapta-
tion to a n ever-changing environment. Experiments
with experimental animals have led to significant
understanding of these Pathology
may also offer unique opportunities to evaluate the
role of sensory feedback in human motor control pro-
cesses, especially patients suffering partial or acute
loss of proprioception and touch, as observed in the
sensory neuropathy syndrome. This syndrome,
which follows a n acute infection of unknown origin,
is presumably associated with a cross-reaction be-
tween antibody t o the foreign antigen and the sen-
sory neurons of larger myelinated fibers. The struc-
tural loss is definitive and most patients do not show
any recovery of nerve function, although they gener-
ally develop compensatory strategies by using substi-
tutive feedback channels, mainly v i ~ u a l . Studies
~-~ of
such cases may lead to a better understanding of the
way and the extent to which cognitive strategies and
supplementary sources of information overcome the
lack of muscular and cutaneous proprioception in the
control of coordinated actions.
We recently have had the opportunity to study a
rare case of extensive sensory neuropathy. This deaf-
ferented subject is deprived of all contingents of
large myelinated sensory fibers below the neck. In
spite of this drastic loss of somesthetic and proprio-
ceptive information, he recovered a walking capacity8
that prompted us to analyze carefully the kinematics
of his walking pattern and to measure the atten-
tional cost of his performance compared with that of
normal subject^.^ Attention is often considered, a t
least by cognitive theorists, as a n extension of sen-
sory processes,'O thus providing a link for studying
the interdependence between sensorimotor and cog-
nitive systems for the control of posture. Compared
with control subjects, we wanted to examine whether
the deafferented subject, because of the extensive
loss of sensory information, needs to allocate a
greater portion of his attentional resources to the
walking task. Without going into the specific details
of cognitive resource models, there are three basic
assumptions to the use of such models: (1) central
processing capacity is limited, (2) performing a task
requires a given portion of this capacity, and (3) if
two tasks performed simultaneously require more
than the total capacity, the performance on one or
both will be affected negatively.11-13When the pri-
mary task (walking in the present experiment) is
unaffected by the introduction of a probe reaction

From the Laboratoire de Performance Motrice Humaine (Drs. Lajoie, Teasdale, Bard, and Fleury), Universite Laval, Quebec, Canada; the Department of
Clinical Neurophysiology (Drs. Cole and Burnett), Poole Hospital, Poole, England; the Ecole de Readaptation (Dr. Forget), Universite de Montreal, Montreal,
Canada; the Laboratoire de Neurobiologie du Mouvement (Dr. Paillard), CNRS, Marseille, France; and the Centre de Recherche en Sciences Neurologiques
(Dr. Lamarre), Universite de Montreal, Montreal, Canada.
Supported by various Natural Sciences and Engineering Research Council of Canada and Quebec's Formation de Chercheur et Aide a la Recherche grants.
Received July 6, 1995. Accepted in final form December 15, 1995.
Address correspondence and reprint requests to Dr. Yves Lajoie, Laurentian University, School o f Human Movement, Ramsey Lake Road, Sudbury, Ontario,
Canada P3E 2C6.
Copyright 0 1996 by the American Academy of Neurology 109
time task (discrete secondary task, consisting of a
simple reaction time t o an auditory or visual stimu-
lus), an increased probe reaction time reflects an
increased attentional load.11~14Using this general ap-
proach, walking requires more cognitive processing
than simple sitting or upright standing p o s t ~ r e . ~ . ~and
In the present experiment, we used a dual-task ex-
perimental paradigm similar to that employed by
Lajoie et al. and ~ t h e r s l ~to- ’examine
~ how much
attention the deafferented subject needed to allocate
to the walking task.
Methods. The deafferented subject (1.W.; aged 40 years)
suffered a permanent loss of large sensory myelinated fi-
bers following an acute episode of purely sensory neuropa-
thy at the age of 19. There was no recovery and this epi-
sode left him without light touch or proprioception below
the neck. Neurophysiologic tests showed no sensory nerve
action potentials and no H reflex below the neck.8 In con-
trast, muscle power and bulk were normal, a s was concen-
tric needle electromyography. Cutaneous-muscular re-
flexes were absent.’* He had a similar perception of pain,
heat, and cold over his unaffected head and over his af-
fected body, suggesting that there was significant sparing
of small myelinated and unmyelinated fibers. His percep-
tion of muscle fatigue and aching were normal. A more
detailed clinical description of the case can be found else-
where. ’!’
The data reported come from two different sessions of
testing spanning a period of 2 years. In a first session, the
subject walked a t his own pace across a laboratory floor.
The gait was recorded using a CODA motion analysis sys-
tem. Markers were placed on the shoulders, elbows, wrists,
hips, knees, ankles, and feet. The position of each marker
was output a t a sample rate of 200 Hz. The monitoring
system comprised three scanners with divergent beams in
the X, Y, and Z axes. The lateral two scanners were 1 m
apart. By a reflectant system and comparison with the
emitting scanner, i t was possible to reconstruct position
within the three dimensions. Six cycles were recorded, of
which the middle three cycles were quantilied. In a second
session, the subject walked on an 8-m long pathway pro-
viding the recording of approximately seven walking cy-
cles. The subject’s shoes were equipped with conductive
material under the heel and toes of each foot. Contacts
with the pathway, covered with aluminum-wire netting,
were digitally coded to provide accurate temporal values
corresponding to the onset and offset of right and left sin-
gle-support and double-support phases. The horizontal foot
displacement of the two feet was recorded via small mono-
filament wires attached to the rear of each shoe cover.
Each wire was wrapped around a plastic wheel (30-cm
circumference)fixed onto a gear-box system having a 4.6:l
ratio. A 10-turn high-precision potentiometer was mounted
on the shaft of the rotating axis and provided a voltage
proportional to the distance covered. The wires were main-
tained stable with a constant resistance spring (0.66 N)
fixed into the rotating mechanisms. This low resistance
served only to prevent the wires from shivering; it did not
affect the walking and was not perceived by the subject.
The system provided a resolution of 3 mm. Additional gait
parameters were recorded with a 3D Selspot two-camera
system. The sampling rate was 500 Hz and cameras were
110 NEUROLOGY 47 July 1996
positioned on the left side of the subject (20 feet from the
subject, 27 feet apart). The camera placement allowed the
recording of a little more than one complete walking cycle
(i.e., the third walking cycle). Active infrared markers also
were placed on the left shoulder, elbow, hip, knee, ankle,
~ J foot.
~ Electromyographic activity from the vastus late-
ralis, medial hamstring, tibialis anterior, and medial gas-
trocnemius were also recorded with the use of AgfAgC1
surface electrodes with preamplification a t the source
(Therapeutics Unlimited). The signals were full-wave rec-
tified and integrated (2.5 msec time constant). All signals
were sampled at 500 Hz.
For comparison purposes, kinematics and electromyo-
graphic normative data were taken from Winter.“’ The
mean of the young adults (n = 11)for Winter’s normative
data was 24.9. Subjects walked a t their natural cadence
and data were collected on a minimum of eight walking
trials.
To evaluate the mental load required for locomotion, the
deafferented subject walked a t his preferred pace and was
asked to consider the walking task as the primary task.
The secondary task was to respond as rapidly as possible
to an auditory stimulus (1 kHz, 50 msec duration) with a
vocal response (“top’’).The subject wore a helmet equipped
with a microphone. The analog signal from the microphone
was used to detect the onset of the verbal response. Reac-
tion times (RTs) were evaluated by computing the tempo-
ral difference between the presentation of the stimuli and
the onset of the verbal responses. Signals from foot con-
tacts and the microphone were sampled at 500 Hz. In
addition, the secondary task was performed alone when
the subject was seated. For the sitting task, 10 stimuli
were given following one of five randomly presented prepa-
ratory periods: 3, 3.5, 4,4.5, and 5 sec. Before the walking
trials, the subject familiarized himself with the walking
environment (five practice trials ). After these trials, data
were collected for six trials without the secondary task
(control condition). These trials served to establish the
subject’s walking pattern. Then, the subject performed 24
trials. The stimuli were randomly presented ( 3 to 5 sec-
onds after a verbal warning) on left foot toe off (i.e., a t the
onset of the single-support condition of the third walking
cycle; 10 trials) or on left foot heel contact (i.e., a t the onset
of the double-support condition of the third walking cycle;
10 trials). Four catch trials (i.e., without stirnulus) served
to prevent any anticipation. The data of Lajoie et al.,”
wherein eight healthy young adults (five men and three
women, mean age = 26.0, range 22 to 34 years) were
tested in similar conditions, were used for comparison pur-
poses.
Results. Kinematics of the gait. Figure 1 presents stick
figures of the gaits of the deafferented subject and a con-
trol subject viewed from the sagittal plane. Several differ-
ences between the deafferented subject and the control
subject are observed. The shoulder of the deafferented sub-
ject tilted forward during t h e beginning of the step-
through phase (i.e., onset of the double-support phase),
and the knee was locked before and during weight-bearing
by that foot. The gait of the deafferented subject was also
characterized by a wider base of support. Table 1 presents
cycle length, cycle duration, speed, and cadence of the
deafferented subject’s walking pattern for the two sessions.
Data for the second session are taken from the control

Figure 1. Stick figures of gait pattern viewed from the
sagittal plane for the deafferented (bottom portion of the
figure) and an age-matched control subject (top portion of
the figure).
trials (i.e., walking without a secondary task). For compar-
ison purposes, normative data from Winter2" and Lajoie e t
al.9 also are presented. Compared with normal subjects,
our subject had a shorter cycle length, a longer cycle dura-
tion, a slower speed, and a lower cadence. The deafferented
subject walked similarly in the two sessions, indicating
well-established and stable gait. Data obtained for the sec-
ond session were submitted to separate one-tailed t tests
(mean of a subject compared with a population). Results
are presented in table 1.
Electromyographic activity when walking. The electro-
myographic patterns of four major muscles involved in
walking are presented in figure 2. They are also compared
with the normative data of Winter.20To allow a compari-
son with controls, EMG signals obtained for the third cycle
(second session, control trials without stimulus) were time-
base normalized to 100% of the cycle. Clear differences
between the deafferented subject's EMG patterns and the
controls were observed. The vastus lateralis (VL) shows a
significant level of activation for about 75% of the walking
cycle while it is solicited for only 25% of the cycle in normal
subjects, with a peak of activity a t weight acceptance (at
Table I Cycle length, cycle duration, speed, and cadence for the deafferented subject and control subjects
DeafTerented subject
(Session 1) (Session 2)
Average SD Average
Cycle length (mm) 1,340 56 1,355
Cycle duration (msec) 1,276 10 1,335
Speed (m/sec) 1.05 0.053 1.005
Cadence (steplmin) 94.0 1.2 89.0
* Significant differences with normative data (p < 0.05).
t Winter's data are temporally normalized and speed and cycle duration variability are not available for computing t statistics.
about 10%of the cycle). Winter20 has proposed that the VL
activity serves to control the amount of knee flexion and to
assist in the extension of the knee in mid-stance. To insure
stability when the leg is weight-bearing, the deafferented
subject contracts the VL for a longer period (i.e., from 0 to
40% of the cycle). This activity may explain why he shows
no flexion of the knee as the foot strikes the ground. For
the deafferented subject, the medial hamstring (MH)
shows a peak level of activation a t 45% of the cycle (i.e.,
late in SS while the leg was in stance phase); controls, on
the other hand, have no significant activity during this
portion of the cycle. The VL and MH are biarticulate mus-
cles that serve to stabilize the hip and the leg. For the
deafferented subject, the peak MH activation may serve to
stabilize the trunk in the forward tilt position. The deaffer-
ented subject adopts this position presumably to permit
vision of the lower segments throughout the walking cycle.
The EMG pattern of the tibialis anterior shows major dif-
ference a t the beginning of the walking cycle. The deaffer-
ented subject's muscle is relatively silent compared with a
peak activation in controls. For controls, the peak activa-
tion serves to maintain the ankle in a dorsiflexed position.
The deafferented subject walks with the medial surface of
the foot pointed forward, creating less need for foot reten-
tion near heel contact. Finally, the medial gastrocnemius
of the deafferented subject shows a similar pattern of ac-
tivity to that of normal subjects.
Attentional demands necessary for walking. An essen-
tial prerequisite of the double-task methodology is that the
addition of the secondary task (i.e., the verbal response to
the auditory stimulus) does not modify the primary task
(i.e., walking). For this reason, the average cycle length,
duration, speed, and cadence, when probes were given in
single- and double-support conditions, were compared with
the control no-stimulus condition (table 2). The kinematic
parameters were similar across the three walking condi-
tions. The deafferented subject did not modify his walking
pattern when stimuli were presented, therefore validating
the RTs as a representative index of the attentional de-
mands for walking.
Data for the controls are taken from Lajoie et al.9 In the
seated position, our subject was faster than most control
subjects to react to the auditory stimuli (166 msec versus
235 msec, respectively; t, = 1.69, p > 0.05). When walking,
the deafferented subject's RTs were similar to those of
controls when the stimuli were given in the single-support
phase (371 msec versus 321 msec, respectively; t, = 1.10,
Winterz0 Lajoie et al.9
SD Average SD Average SD
32 1,560" 100 1,546 160
26 1,090t - 1,102" 40
0.016 1.436t - 1.41" 0.14
2.0 110.5" 8.3 110.0" 4.1
July 1996 NEUROLOGY 47 111
 400 -
350 -
300 -
250 -
200
150
50 100
50

250
200 1 A

50
5 0
1 I I I I I
v

c.9 Tibialis anterior

2
250

150 -
300
100 -
200
50 150
100
0 - 50
0

Medial g a s t r o c n e m i u s
250

Figure 2. Normalized elt?ctromyo-

graphic activity (average and stan-
100 dard deviation) of the vnstus latera-
50 lis, medial hamstring, tibialis
0 anterior, and medial gastrocnemius
muscles for the deafferented (left por-
tion of the figure) and control (right
portion of the figure) suhjects. Data
for control subjects are taken from
I I
.I , I Winter's normative datat>ase."' The
EMG data are time-basp normalized
to 100% of the stride befbre ensemble
averaged.

Table 2 Parameters for three walking conditions"

~ ~ ~ ~~ ~~ ~~ ~ ~ ~ ~

No-stimulus
~~~ ~~~~
ss ~~ ~~~
DS
.~

Average SD Average SD Average SD

~ ~ ~ ~ ~_________~ ~. ~ ~~~~ ~~

Cycle duration (msec) 1,335 26 1,335 29 1,350 26

Cycle amplitude (mm) 1,278 45 1,346 45 1,346 40
Speed ( d s e c ) 0.95 0.016 1.008 0.014 0.99 0.013
Cadence (stepdmin) 89.9 2.0 89.8 2.3 88.9 1.8
-. ~ ~~ ~

'I: Cycle length, cycle duration, speed, and cadence in the control no-stimulus condition and when stimuli were given at toe-off (onset (if'
the single-support phase-SS) and at heel-contact (onset of the double-support phase-DS) for the deafferented subject.
112 NEUROLOGY 47 July 1996
p > 0.05). When the stimuli were given in the double-
support phase, however, the deafferented subject was con-
siderably slower to respond to the stimuli than controls
(402 msec versus 270 msec, respectively; t, = 2.7, p <
0.05). Compared with controls, the slower RTs observed
when stimuli were given at the onset of the double-support
phase suggest that this phase requires an increased atten-
tional load.
Discussion. The deafferented subject has devel-
oped several strategies to achieve a secure gait: (1)a
reduction of the degrees of freedom (normally con-
trolled by local peripheral loops in the control of pos-
ture) by “bracing” himself while moving; (2) a preser-
vation of body balance by enlarging his base of
support; (3) the visual monitoring of his step by sta-
bilizing the head-trunk linkage together with a char-
acteristic forward tilt. Compared with normal sub-
jects, the gait pattern of our subject is characterized
by a shorter cycle length, a longer cycle duration, a
slower speed, and a lower cadence. This general gait
pattern is reminiscent of the gait adaptations ob-
served for elderly people. For the elderly, these adap-
tations serve chiefly to produce a more secure and
less destabilizing gait and an energy-efficient speed
of p r o g r e s ~ i o n . ~ ~ - ~ ~
Following the classical distinction introduced by
H ~ s s walking
,~~ is the product of two interactive
mechanisms: (1) the ereismatic or postural compo-
nent that provides the support for the propulsive
force and postural adjustment for preserving overall
body orientation in the field of gravity forces, and (2)
the teleokinetic or instrumental component, that is,
the goal-directed displacement of body and limb^.^"^^
Reference frames may be the basis for the underly-
ing mechanisms necessary to insure that the body
and the limbs are rightly positioned with regard t o
environmental landmark^.^^^^^.^^ Two such frames are
generally considered: (1) a n egocentric reference
frame regarded as a dynamic structure that stems
from a continuous updating of the relative positions
of the body segments by way of static and dynamic
proprioceptive signals, and that tunes the motor
commands for spatially oriented movements; and (2)
an exocentric reference frame that derives from a
memory-based internal construct built from extract-
ing the stable covariant features of the visual envi-
ronment that remain stable as the body moves.29
One of our initial basic assumptions concerning
the state of the deafferented subject is that a dy-
namic egocentric frame of reference, which needs a
permanent updating of the postural schema, is no
longer available in complete absence of muscular
proprioception. Consequently, to monitor and evalu-
ate the relative position of the body segments with
respect to the world frame, the deafferented subject
must rely on alternative strategies mainly based on
the visual exocentric frame of reference. From a
qualitative viewpoint, this is corroborated by the
deafferented subject’s self-report that walking re-
quires a constant visual monitoring. The RTs ob-
served for this subject show that the supplementary
strategies used to compensate for the absence of pro-
prioception increase the mental load. The double-
support phase of his walking cycle is more attention-
demanding than that of control subjects, whereas no
differences were found in the single-support phase.
This strongly suggests that the deafferented subject
uses the double-support phase as a transitory stable
phase for generating his next step, on the basis of
cognitively updated postural features. These opera-
tions, presumably automatic in normal subjects,
heavily load the deafferented subject’s cognitive sys-
tem (as indexed by the longer RTs). Conversely, the
single-support phase does not produce a different
load in our subject and the control subjects. This
phase is mainly conducted with passive forces and
appears to require less or no on-line r e g ~ l a t i o n . ~ ~ ~ ~
Previous results obtained in pointing tasks with
another deafferented subject support the hypothesis
that a dynamic egocentric frame of reference, which
needs a permanent updating of the postural schema,
is not available in complete absence of muscular pro-
~ ~ subject, G.L., suffers a perma-
p r i o ~ e p t i o n .(This
nent and specific loss of the large sensory myelinated
fibers in the four limbs following two episodes of
sensory polyneuropathy that affected her whole body
below the nose. The illness resulted in a total loss of
the senses of touch, vibration, pressure, and kines-
thesia, as well as in absent tendon reflexes in the
four limbs. Motor nerve conduction velocities and
needle EMG investigation of the muscles of the arm
are She is now 47 and these observations
have been confirmed and have proven stable for the
past 17 years.) Moreover, the model of “coherent cop-
ies,” proposed by Droulez and D a r l ~ t accounts
,~~ for
the capacity of the visual system and of visual kines-
thesis to complement the direct proprioceptive infor-
mation originating from the muscular sensors, or
even more, to provide a valid substitute when the
dedicated sensors are temporarily or completely dis-
abled.35 M i t t l e ~ t a e d t proposed
~ ~ . ~ ~ that, in normal
subjects, the head is referred to the “idiotropic vec-
tor” as an internal egocentric reference related to the
trunk main axis. Conversely, our subject is more
likely to use a head-centered frame to which his
deafferented trunk and body segments (albeit vividly
represented in a “visual body image”) can be referred
via neck afferent information. This strategy allows
the leading head segment, which is visually an-
chored on stable environmental landmarks, to steer
the locomotion of the deafferented body.
Further empiric observations support this view-
point. Indeed, the deafferented subject G.L., com-
pletely devoid of neck proprioception, in contrast to
I.W., cannot walk unassisted, mainly because of her
inability to maintain balance without support, in
spite of being able to stabilize her head with respect
to the environment via visual and vestibular cues.
This observation suggests a crucial role for neck pro-
prioception in articulating the ereismatic and teleo-
kinetic constraints of locomotion and the functional
July 1996 NEUROLOGY 47 113
leading role of a stabilized head in the featuring of
the body schema.zR.38,39 BerthozZfiand Berthoz and
P O Z Z suggested
O~~ that the brain uses the head as a
stabilized inertial guidance platform and as a mobile
frame of reference to provide all the necessary re-
quirements for generating coordinate multilimb ac-
tivities. For this purpose, and owing to continuous
changes of the forces exerted on the musculoskeletal
system by gravity during body displacement, a con-
tinuous updating of the internal representation of
head motion appears mandatory. Compelling evi-
dence now exists to show that the vestibular system
cooperates with the visual system to compute central
configuration of head motion and position in
pace.^"-^^ Such a mechanism is obviously preserved
in both deafferented subjects. However, because of
the preservation of his neck afferents information,
our subject alone can elaborate efficient but costly
cognitive strategies to meet the postural require-
ments for walking.
Acknowledgments
The interest and cooperation of the deafferented subject is grate-
fully acknowledged. Special thanks to Benoit Genest and Gilles
Bouchard for programming and technical assistance, respectively.
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Motor neuropathy due to docetaxel and

paclitaxel
Ronnie J. Freilich, MD, FRACP; Casilda Balmaceda, MD; Andrew D. Seidman, MD;
Michael Rubin, MD, FRCP(C1; and Lisa M. DeAngelis, MD

Article abstract-Paclitaxel and docetaxel are novel chemotherapeutic agents that promote the polymerization and
inhibit the depolymerization of microtubules. Sensory neuropathy is common with these agents, particularly paclitaxel.
We evaluated 64 patients treated with these drugs; 54 were followed prospectively. Eleven (17%, including six of the 54
prospectively followed patients) developed muscle weakness that was predominantly proximal. The weakness was idiosyn-
cratic, occurring at any stage of treatment, had a variable course, and was reversible upon cessation of drug. All patients
developed symptoms or signs of taxane-induced sensory neuropathy. Weakness was likely neuropathic in origin; electro-
diagnostic studies suggested a distal axonopathy in some patients and proximal denervation (anterior horn cell or nerve
root) in others.
NEUROLOGY 1996;47:115-1 18

Paclitaxel and docetaxel are novel chemotherapeutic
agents with activity against several malignancies. 1-8
The drugs exert their antineoplastic activity by pro-
moting the polymerization and inhibiting the depoly-
merization of m i c r o t ~ b u l e s but
, ~ by differing mecha-
nisms; paclitaxel alters the number of protofilaments
in microtubules whereas docetaxel does not."'
Peripheral neuropathy occurs with paclitaxel
doses 2200 mg/m2; severity is associated with in-
creased cumulative dose, and becomes dose-limiting
at doses 2250 mg/m2.11-15 Paclitaxel produces a pre-
dominantly sensory neuropathy,16although a senso-
rimotor neuropathy is more common than originally
appreciated.I5 Weakness is usually mild and distal,
but proximal or more generalized weakness has been
reported.13.16Myalgias are common with high doses
of paclitaxel, and myopathy has occurred in patients
treated with a combination of high-dose paclitaxel
and cisplatin."J5
Early phase I and I1 studies suggested that do-
cetaxel neuropathy is uncommon (frequency 0 to
17%), mild to moderate in severity, often reversible,
and predominantly sensory. Symptoms began at cu-
mulative doses of 50 to 720 mg/m2, occurring espe-
cially in patients treated previously with cispla-
However, two prospective studies of 82
tin.'0.17-21
patients suggest that sensory neuropathy is more
frequent (49 to 67%) than initially reported.22,23Re-
cently, New et aLZ0described 10 of 186 (5.3%) pa-
tients with mild proximal and distal weakness due to
docetaxel peripheral neuropathy and Hilkens et al.")
observed a comparable frequency of distal weakness
in patients receiving docetaxel. Neither study de-
scribed myalgias or a proximal pattern of weakness
in patients taking docetaxel. We identified 11 pa-
tients treated with docetaxel or paclitaxel who devel-
oped substantial muscle weakness, predominately
proximal, in association with a sensory neuropathy.
Methods. Sixty-four patients were evaluated, 60 treated
with docetaxel and four treated with paclitaxel. Fifty-four
patients treated with docetaxel on phase I1 protocols were
followed prospectively for neurologic complications (34
breast, 20 ovarian cancer). In addition, six patients treated
with docetaxel for non-small cell lung cancer on a phase I1
protocol were referred for possible neuropathy, and four
patients who developed muscle weakness while receiving
paclitaxel for breast cancer were also examined.
The initial dose of drug was determined by protocol for
the three groups of patients receiving docetaxel: 100
mg/mz as a 1-hour intravenous infusion every 3 weeks for

From the Departments of Neurology (Drs. Freilich, Balmaceda, and DeAngelis) and Medicine (Dr. Seidman). Division of Solid Tumor Oncology, Breast and
Gynecologic Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, and the Department of Neurology (Dr. Rubin), Cornell University Medical
College, New York, NY.
Supported in part by Rhone-Poulenc Rorer. A.D.S. is the recipient of a Career Development Award from the American Society of Clinical Oncology.
Presented in part a t the 46th Annual Meeting of the American Academy of Neurology, Washington, DC, May 1994.
Received August 4, 1995. Accepted in final form December 20, 1995.
Address correspondence and reprint requests to Dr. Lisa M. DeAngelis, Chief, Neurology Service, Department of Neurology. Memorial Sloan-Kettering
Cancer Center, 1275 York Avenue, New York, NY 10021.
Copyright 0 1996 by the American Academy of Neurology 115
 Gait of a deafferented subject without large myelinated sensory fibers below the
neck
Y. Lajoie, N. Teasdale, J. D. Cole, et al.
Neurology 1996;47;109-115
DOI 10.1212/WNL.47.1.109

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