Doi:10.1016/s0003-9993(02)04906-7

Intrathecal Baclofen in Subjects With Spastic Hemiplegia:
Assessment of the Antispastic Effect During Gait

Olivier Re´my-Ne´ris, MD, PhD, Vincent Tiffreau, MD, Ste´phane Bouilland, MD, Bernard Bussel, MD
ABSTRACT. Re´my-Ne´ris O, Tiffreau V, Bouilland S, 2003 by the American Congress of Rehabilitation Medi- Bussel B. Intrathecal baclofen in subjects with spastic cine and the American Academy of Physical Medicine and hemiplegia: assessment of the antispastic effect during gait.
Arch Phys Med Rehabil 2003;84:643-50.
Objective: To determine whether leg muscle stiffness is
PENN AND KROIN1 FIRST SHOWED that long-term ad-
measurably reduced after intrathecal baclofen (ITB) in subjects ministration of intrathecal baclofen (ITB) with implantable pumps reduces spasticity in nonambulatory subjects with spinal Design: Nonrandomized trial.
cord injury (SCI). Since then, numerous studies have assessed Setting: Inpatient multidisciplinary rehabilitation unit in
the functional benefit of ITB in spastic subjects with SCI2 and with cerebral palsy3 (CP) and in spastic adults with brain Participants: Seven consecutive subjects with spastic hemi-
injury.4,5 Meythaler et al6 recently showed that continuous plegia having Ashworth Scale scores for their quadriceps and delivery of ITB decreases spastic hypertonia due to stroke. ITB can provide some functional improvements to nonambulatory Intervention: Subjects were given ITB by lumbar puncture
subjects whose spasticity is of cerebral origin,7 but most of the improvements do not influence gait,8 although the walking Main Outcome Measures: Triceps and quadriceps Ash-
capacity of some subjects improved. This inconsistent im- worth scores, gait analysis at preferred and maximal speed provement can be attributed to orthopedic conditions, loss of measured by a motion analysis system with 2 forceplates, and voluntary motor control, decreased muscle stiffness if the sub- electromyographic recording of leg muscles before and 4 hours jects used hypertonia to stay upright,9 or persistent muscle after ITB. The slopes of the moment-angle curves were mea- sured on the hemiplegic side at the onset of ankle and knee The muscle hypertonia of subjects with central nervous flexion to assess muscle stiffness during walking. Pre- andpost-ITB spatiotemporal, kinetic, and kinematic data were system lesions may have several explanations. Muscle contrac- compared by using a nonparametric test (Wilcoxon signed-rank tures and altered muscle mechanical properties contribute to muscle hypertonia in subjects with spasticity.10,11 Spasticity, Results: Ashworth scores of the quadriceps and triceps of all
defined as a velocity-dependent increase in the tonic stretch subjects decreased significantly after ITB. Maximal walking reflex,12 is often associated with dystonia, rigidity, spasms, and speed increased significantly, with a significant increase in myoclonus6,13 in subjects with acquired brain lesions. All these stride length, but the preferred walking speed was unchanged.
neural mechanisms can contribute to muscle hypertonia. But Minimal knee extension and maximal ankle flexion were the they have very different effects in static and dynamic condi- only kinematic data significantly different (increased) after tions, and there seems to be little correlation between patho- ITB. The slope of the ankle moment-angle curve decreased logic responsiveness to muscle stretch measured at rest and significantly after ITB at preferred gait speed; it also decreased motor impairment assessed under natural conditions during at maximal gait speed in all but 1 subject. Of the 4 available motion.14-16 Thus, a clinically identified reduced spasticity at moment-angle curves, 3 showed decreased knee extensor mus- rest after ITB does not automatically result in improved func- cle stiffness. The duration of the bursts of spastic muscles tional skills, and any such improvement cannot be easily cor- related with reduced muscle stiffness. Quantitative studies on Conclusion: Acute ITB improved walking and reduced
the neural components of spastic hypertonia in humans usually muscle stiffness at both the ankles and knees on the spastic use electromyographic recordings and measurements of the hemiplegic side of our subjects. Electromyographic findings amplitude of reflex responses. Electromyographic recording of suggest that some of the post-ITB reduction in muscle stiffness the spontaneous activity of muscles during gait cannot be the might be attributed to decreased spasticity.
only means of assessing the neural components of a disorder Key Words: Baclofen; Gait; Hemiplegia; Muscle spasticity;
because electromyographic activity reflects normal voluntary muscle discharge and hyperactive reflex responses, both ofwhich contribute to the muscle resistance.17,18 The resistancedue to muscle stretch and muscle contraction during gait can beevaluated from joint moments that result from the interplay ofagonist and antagonist forces.19 The coupling of kinematics, From Groupe Hopale, Motion Analysis Laboratory, and Department of Physical kinetics, and electromyography thus seems to be the best way Medicine, Berck sur Mer (Re´my-Ne´ris Tiffreau, Bouilland), and Assistance Publique to assess the contribution of the neural component of muscle Hopitaux de Paris, Department of Physical Medicine, Hoˆpital Raymond Poincare, hypertonia during gait in subjects with spastic CP.17,18 ITB produces a significant decrease in spastic hypertonia at 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 author(s) or upon any rest in subjects with acquired cerebral lesions.6,13,20 The present organization with which the author(s) is/are associated.
study was therefore undertaken to determine whether acute ITB Reprint requests to Olivier Re´my-Ne´ris, MD, Centre Calve, Groupe Hopale, 72 injections improved the gait of subjects with spastic hemiplegia Esplanade Parmentier, 62600 Berck sur mer, France, e-mail: Oremyneris@hopale.com. and reduced the muscle stiffness measured during gait from 0003-9993/03/8405-7488$30.00/0doi:10.1016/S0003-9993(03)04906-7 Arch Phys Med Rehabil Vol 84, May 2003
INTRATHECAL BACLOFEN AND HEMIPLEGIA, Re´my-Ne´ris
Table 1: Subjects’ Characteristics
NOTE. Significance was evaluated with a Wilcoxon signed-rank test.
Abbreviation: SD, standard deviation.
The kinematic variables for hip, knee, ankle, and spatiotem- poral measure (walking speed, length of the stride, single and Participants
double support stance times) were calculated for the pretreat- This investigation was performed on 7 subjects with hemi- ment and posttreatment sessions. Vertical forces (Fz) were plegia (6 men, 1 woman; mean age, 40y; range, 20 – 64y). It used to determine the onset and end of the support phase.
was approved by the medical ethics committee of Ambroise Because 2 parallel, large (length, 1200mm) forceplates were Pare´ Hospital, and informed consent was obtained from each used, 2 or more heel strikes on a forceplate were obtained for subject before he/she entered the trial. Data on the subjects, the each limb to determine a complete gait cycle.
cause of their disability, time after illness, and initial Ashworth One purpose of the present study was to determine whether Scale scores for the triceps and quadriceps are summarized in acute ITB injections reduced the muscle stiffness exhibited table 1. The tibialis anterior and hamstring tone were free of during gait, as measured by biomechanical parameters. Frigo et spasticity. The mean time after illness was 5.2 years (range, al19 studied the reproducibility of the coupling of joint angles 1–14y). The hemiplegia was caused by stroke in 4 subjects, and ankle and knee moments in unimpaired subjects. The traumatic brain injury (TBI) in 2, and CP in the last subject. All slopes of the resulting moment-angle curve, which can be subjects had hyperactive ankle and knee-jerk reflexes and a related to the force-length relationship that describes the stiff- minimum Ashworth score of 2 of 5 for the quadriceps.
ness of muscles, can be used to infer the resistance offered by All participants were able to walk without hand support for the joint during rotation. We used the same method and cal- a minimum distance of 10m. They were all on oral antispastic culated internal joint moments by using the inverse dynamics drugs that were not sufficient to reduce leg muscle tone. Their technique. Analysis of the joint moment-angle curve and of the current antispastic treatment was not changed during the study.
electromyographic activity gives a quantitative indication ofspasticity during gait.17,18 Because joint moments assess the General Experimental Procedure
resultant force applied to the joints center of rotation, this All subjects were given a test bolus of 50␮g baclofen by method cannot distinguish the action of 1 muscle from that of lumbar puncture. Ashworth scores for the quadriceps and tri- the others, but measures their combined, overall action. Surface ceps were measured, and a free 10-m walk was performed electromyography registers the muscle activity of superficial before and 4 hours after injection. The dose of baclofen was muscles. The electromyographic activity of some muscles that increased by 50␮g if the mean Ashworth scores for the quad- might be spastic and contribute to the joint moment might not riceps and triceps decreased by less than 1 point after this first be considered. Despite these limitations and because the stron- dose. Three of 7 subjects needed a 100-␮g dose, but none ger muscles that contribute most to joint moments are super- ficial (triceps, tibialis anterior, quadriceps, hamstrings), joint The subjects were tested again after a 48-hour washout moments and electromyographic activity recordings are in- period using the appropriate dose of baclofen, injected intra- creasingly being used to assess spasticity.21-23 This approach thecally. Ashworth scores for both the quadriceps and triceps seems a reasonable way to assess changes in spasticity after were measured just before and 4 hours after the intrathecal ITB during gait. The markers and electrodes were not removed injection of baclofen; gait was also assessed by using the Vicon between the pre- and post-ITB gait measurements so that we motion analysis system,a 2 forceplates, and electromyography.
could assess the reliability of joint moments and electromyo- Each subject underwent 2 sessions of 10 trials walking at their graphic recordings. The slopes of the moment-angle curves, own pace at preferred and maximal speeds over 10m. Data which are features of the changes in muscle tone during muscle were recorded with a 60-Hz sampling rate. Markers were stretch before and after ITB, were compared for each subject.
placed over the anterior superior iliac spine, trochanter, lateral The present study focused on spasticity of the flexor and knee condyle, mid lateral thigh, lateral malleolus, mid lateral extensor muscles of the ankle and knee. Therefore, only the shank, heel, and second metatarsal to define the segments of the kinematic and kinetic data for the ankle, knee, and hip flexion thigh, shank, and foot. The markers enabled 3-dimensional are reported. Muscles are phasically activated and passively motion analysis of the legs. Electromyographic recordings, stretched by joint motion during walking. The period of the gait with surface electrodes, were made of the vastus lateralis, cycle during which the triceps is stretched is illustrated in biceps femoris, tibialis anterior, and soleus.
figure 1. Because all subjects showed a toe-heel or a flat-foot Arch Phys Med Rehabil Vol 84, May 2003
INTRATHECAL BACLOFEN AND HEMIPLEGIA, Re´my-Ne´ris
cannot be proved, pre- and post-ITB data were compared bymeans of a nonparametric test (Wilcoxon signed-rank test).
Post-ITB data were considered significantly different frompre-ITB data for P less than .05.
Table 1 shows the quadriceps and triceps Ashworth scores.
The spasticity at rest, as indicated by the triceps and quadricepsdata for the hemiplegic side, was significantly reduced in allsubjects after the appropriate dose of baclofen (mean quadri-ceps, 3.3 vs 1.3; mean triceps, 3.4 vs 2.1; see table 1). Thedecrease in spasticity was greater for the quadriceps than forthe triceps.
The preferred gait velocity increased significantly after ITB (pre-ITB, .53Ϯ.29m/s; post-ITB, .60Ϯ.34). The maximum gaitspeed increased (pre-ITB, .82Ϯ0.4m/s; post-ITB, .93Ϯ.45m/s)but was not statistically significant. The mean increase inmaximum gait speed Ϯ standard deviation (SD) was.15Ϯ.08m/s in the 6 of 7 subjects whose gait velocity increased Fig 1. Gait characteristics of S3 before baclofen. (A) Changes in the
(table 2). Subject S5 was the only patient whose maximal gait ankle joint angle (solid line) and Fz (dotted line) during walking. The
time period (arrow in both graphs) is the beginning of the gait cycle

speed decreased greatly (pre-ITB, 1.04m/s; post-ITB, 0.9m/s).
just after the heel strike that corresponds to stretching of the
This subject’s preferred gait speed increased slightly after ITB triceps. (B) The ankle moment increased regularly. Fz and the ankle
(from .65m/s to .68m/s). He said he felt tired at the time of moment are expressed as a percentage of the body weight (% BW).
evaluation, although most subjects felt they walked more easily The gait cycle is normalized (100%).
after ITB. The increase in walking speed correlated with asignificant increase in stride length at both preferred (mean strike, ankle dorsiflexion (the stretching phase of the triceps) increase Ϯ SD, .05Ϯ.03m) and maximal walking speeds (mean started at the onset of the gait cycle. Because the single support increase, .11Ϯ.09m). The stride frequency did not change phase varied from subject to subject, depending on knee un- steadiness, ankle clonus, or knee hyperextension, we consid- Kinetic and kinematic data (maximum, minimum, ampli- ered only the loading phase (first double support phase) in this tudes) for the hip, knee, and ankle of the affected and unaf- study of the ankle moment-angle curve. Knee flexion (quadri- fected sides were compared before and after baclofen. There ceps stretching phase) started during the double support phase was great subject-to-subject variability. The data did not that preceded swing. Because some subjects showed 20° of change significantly after ITB at the preferred walking speed.
minimal knee flexion, we compared the knee moment-angle The minimal knee flexion at maximal walking speed Ϯ SD curves during stretching of the quadriceps in all subjects from increased significantly after ITB (pre-ITB, Ϫ1.1°Ϯ5.9°; post- 20° to the end of the knee flexion (fig 2).
ITB, 3.1°Ϯ7.7°), as did maximal ankle dorsiflexion (table 3).
Statistical Analysis
Ankle Moment
Data from the experiments are presented as means of the 10 Figure 3 shows the ankle flexion during the gait cycle and consecutive trials. Because the normal distribution of the data the ankle angle-moment correlation during the initial phase of Fig 2. Gait characteristics of S1
before baclofen. (A) Changes
in the knee joint angle (solid
line) and Fz (dotted line) dur-
ing a gait cycle. The period (ar-
row in both graphs) is the end
of the loading time of the gait
cycle just before toe off. (B) The
knee moment decreased dur-
ing knee flexion in this sub-
ject. Fz and the knee moment
are expressed as a percentage
of the body weight (% BW).
The gait cycle is normalized
(100%).

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INTRATHECAL BACLOFEN AND HEMIPLEGIA, Re´my-Ne´ris
Table 2: Spatiotemporal Data at Preferred and Maximum Walking Speeds Before and After ITB
Abbreviation: NS, not significant.
* Significance was evaluated with a Wilcoxon signed-rank test.
the stance phase corresponding to the stretch of the triceps was sustained throughout ankle dorsiflexion. It decreased only surae at the preferred walking speed in S3. A small plantar- when the plantarflexion began. ITB produced a decrease in the flexion appeared at the onset of the gait cycle after ITB. This electromyographic activity of the soleus at the onset of the gait corresponds to a retrieval of the heel-toe gait pattern by S3, cycle. The duration of the burst was shortened until the middle whose pre-ITB walking pattern was toe-heel.
Data for all subjects are shown in table 3. Maximal dorsi- All but 1 subject (S5) showed a decrease in the slope of the flexion of the ankle on the hemiplegic side did not change after ankle moment-angle curve during ankle dorsiflexion (Pϭ.08) ITB at preferred walking speed, and it increased slightly at maximal walking speed Ϯ SD (10.3°Ϯ11.4° vs 13.0°Ϯ11.1°;see table 3). The slope of the moment-angle curve during Knee Moment
triceps stretching (see Methods) was significantly reduced. The Subjects S2 and S4, for whom kinetic data were available, maximal flexion velocity did not change significantly at either had a stiff leg with a knee flexion that was too small to describe walking speed. The slope of the ankle-moment curves of the 6 a knee angle-moment curve. Conventionally, knee moments subjects with spasticity for whom kinetic data were available at are negative when the resulting force causes knee extension preferred walking speed decreased significantly after ITB (see (opening of the popliteal angle) and positive when it causes table 3). The decrease in the ankle moment-angle curve during triceps stretching did not correlated significantly with the in- The slopes of the knee moment-angle curves increased after crease in walking speed (Spearman test). Figure 4 shows the ITB in all subjects for whom knee moments could be calculated ankle motion and electromyographic activity of the ankle flexor at preferred and maximal gait speeds (S1, S3, S5, S7; fig 5), and extensor before and after ITB for S1. The soleus electro- except for S3 at maximal gait speed (see table 3). This pattern myographic activity before ITB was maximal at heel strike and indicated a decrease in knee extensor tension or an increase in Table 3: Ankle and Knee Kinematics and Slope of the Moment-Angle Curve Before (Pre) and After (Post) ITB
NOTE. Significance tested with a Wilcoxon signed-rank test.
Abbreviations: AU, arbitrary units; MAD, maximal ankle dorsiflexion; MFV, maximal ankle flexion velocity; MKF, minimal knee flexion duringsupport phase; NA, not available; Slope AMC, slope of the ankle angle-moment curve during the initial phase of dorsiflexion (during stretchingof the soleus, see Methods); Slope KMC, slope of the knee moment-angle curve after 20° of knee flexion in 7 subjects with spastic hemiplegiabefore and after ITB at preferred and maximal walking speed.
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INTRATHECAL BACLOFEN AND HEMIPLEGIA, Re´my-Ne´ris
Fig 3. Ankle dorsiflexion (A)
before (dotted line) and after
(solid line) ITB at preferred
walking speed in S3. The ini-
tial plantarflexion is restored.
The maximal dorsiflexion is
unchanged after ITB. (B) The
slope of the moment-angle
correlation is reduced.

knee flexor tension during the same period (pre- and post-ITB) at preferred gait speed, with a 19-fold increase. It also in- of the knee flexion. Subject S3 showed small changes at both creased slightly at maximal gait speed.
gait speeds (see table 3, fig 5). The knee moment-angle curves The electromyographic activity of the flexor and extensor of S1 and S7 (see fig 5) changed markedly after ITB at both muscles correlated with the calculated joint moment. The elec- gait speeds: the slope increased 3.7-fold in S1 and was reversed tromyographic burst seen in the biceps femoris in S1 and S7 in S7. Before ITB, the knee moment increased throughout knee (fig 6A) before ITB continued until the end of the stance phase.
flexion in S7. After ITB, it decreased as in other subjects. The This type of increased flexor muscle activity can offset the knee slope of the knee moment-angle curve for S5 changed greatly extension moment caused by knee flexion and explain the Fig 4. Ankle flexion and elec-
tromyographic activity of the
soleus and tibialis anterior (A)
before ITB and (B) after ITB in
S1 during a gait cycle. Abbre-
viation: HS, heel strike.

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INTRATHECAL BACLOFEN AND HEMIPLEGIA, Re´my-Ne´ris
Fig 5. Mean moment-angle
curves of the knee during knee
flexion (see fig 2) in 4 hemiple-
gic subjects with a knee flexion
more than 20° during the swing
phase before ITB (dashed lines)
and after ITB (solid lines). Joint
moments are expressed as a
percentage of the body weight
(% BW).

almost zero knee moment in these subjects before ITB. The spasticity is of cerebral origin.5,6,8,13,20,24-27 Subjects with spas- vastus lateralis of the same subjects showed a burst of electro- tic hemiplegia after TBI8,13,20 and stroke20,27 all showed im- myographic activity at the beginning of knee flexion, and it proved function. But some controversy exists about the im- increased during knee flexion when the electromyographic provement in ambulant subjects. Some have shown an burst in the biceps decreased (see fig 6A). This increased improvement in gait pattern,8,24 while others suggested that electromyographic activity of knee extensors might explain the intrathecal antispastic therapy is contraindicated in some sub- increased knee-extension moment during knee flexion. The jects who use muscle stiffness to stay upright.9 Our subjects burst of electromyographic activity in the biceps femoris was with hemiplegia walked significantly faster only at maximal dramatically shorter after ITB, and there was no activity during walking speed, because their strides were longer. The kine- knee flexion (fig 6B). There was some electromyographic ac- matic and kinetic data for our subjects with spasticity varied tivity in the vastus lateralis during knee flexion, but the elec- greatly. Administration of ITB resulted in an increased maxi- mal ankle flexion and a significantly decreased knee hyperex-tension at maximal gait speed.
DISCUSSION
One of the most characteristic features of spastic gait is how it varies for a given subject and between subjects.28 De Quer- Gait Improvement
vain et al29 showed that subjects with hemiplegia could have ITB is considered an effective way to reduce spastic hyper- several types of gait patterns, and we did not choose 1 specific tonia that is resistant to oral medication in subjects whose gait pattern in our study. The great variability also noticed by Fig 6. The patterns of vastus
lateralis and biceps femoris ac-
tivation (A) before ITB and (B)
after ITB in S1. The biceps fem-
oris was activated throughout
the stance phase until the initial
flexion of the knee before ITB
and not after ITB. The vastus
lateralis activation during knee
flexion decreased after ITB. The
gait cycle is expressed in arbi-
trary units (AU).

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INTRATHECAL BACLOFEN AND HEMIPLEGIA, Re´my-Ne´ris
previous researchers30-32 looking for improved objective gait increased walking speed with decreased muscle stiffness, they parameters after antispastic treatment might partly explain the clearly suggest that a marked reduction in muscle stiffness lack of change shown by any subject at preferred walking might help to improve walking, as was found for spastic speed after ITB. Gait in subjects with spasticity has usually subjects with continuous ITB infusion.8,24 But such an infusion been assessed at preferred walking speed.8,32-34 We showed a might also be pernicious in subjects who use their stiffness to significant velocity increase and significant kinematic changes only at maximal walking speed. Thus, it might be more suitable Spasticity is a velocity-dependent increase in the stretch to assess any therapeutic intervention for this population at this reflex.12 Because gait velocity slightly increased and the peak walking speed. This needs further investigation.
ankle and knee flexion velocities did not decrease after ITB, we The increased walking speed was due to a significant in- can assume that the decrease in muscle stiffness after ITB was crease in stride length and no change of cadence. Although we not due to a change in muscle stretch velocity. Nor were small saw no significant increase in hip flexion amplitude, the in- changes in ankle flexion velocity and the decreased slopes of creased stride length might indicate easier muscle stretch, be- the ankle moment-angle curves correlated. The decreased elec- cause of decreased spasticity. Gerszten et al8 reported an im- tromyographic activity in the ankle and knee extensors at the provement in the gait of some subjects with spasticity after onset of muscle stretch (ie, the onset of ankle dorsiflexion for continuous ITB. This increased gait capacity might be due to the triceps and knee flexion for the quadriceps) might be increased walking speed or to lower energy consumption re- attributed to the decreased voluntary muscle contraction or to sulting from better walking mechanical conditions and reduced ITB-induced changes in reflex electromyographic amplitude.
energy cost to stretch muscles that would have been weakened Our experimental design cannot dissociate these 2 mecha- by ITB. Subjects with spasticity have a high oxygen uptake nisms. Nevertheless, the post-ITB loss of the electromyo- relative to the work performed.35-38 Our subject S5, the only graphic burst of the soleus throughout ankle flexion strongly subject with impaired walking speed, reported feeling fatigued, suggests that ITB released inappropriate muscle stretch reflexes while all other subjects found walking easier. However, this in these subjects. The simultaneous decrease in muscle stiff- study focused on a biomechanical assessment after ITB, so we ness indicated by the angle-moment curves could be due to cannot comment on subjective improvement in walking after decreased spasticity. The reduced electromyographic activity of the vastus lateralis during knee flexion after ITB seems toresult from the same mechanisms.
Muscle Stiffness
In unimpaired persons muscle stiffness during motion results CONCLUSION
from the passive viscoelastic properties of muscle and concen-tric or excentric muscle contractions. Two mechanisms may Acute ITB improved the walking of adults with hemiplegia disrupt normal muscle contraction in subjects with spasticity: whose leg spasticity did not respond to oral antispastic medi- one is histologic transformations that alter the viscoelastic cation. The decrease in muscle stiffness and the loss of some properties,10,11,39 and the other is released segmental spinal characteristic spastic electromyographic features after ITB sug- pathways (for a review, see Pierrot-Deseilligny40). Subjects gest that the improved walking after ITB can be attributed to with supraspinal lesions of various origins that affect the legs39 reduced stretch reflexes. Further investigation is now needed to and arms41 show altered muscle viscoelastic properties. The determine whether these changes produced by acute ITB also Ashworth Scale42 clinically assesses resistance to passive occur after continuous ITB infusion.
stretch41 but cannot discriminate between muscle changes andthe release of segmental spinal pathways. Our subjects had no References
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a. Vicon Motion Systems, 14, Minns Business Park, West Way, Ox- Continuously infused intrathecal baclofen over 12 months for Arch Phys Med Rehabil Vol 84, May 2003

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