The effect of botulinum toxin A on the function of a person with poststroke quadriplegia.

Key Words: Botulinum toxins, Cerebrovascular disorders, Functional training and activities, Injections, Muscle, Quadriplegia.

Movement dysfunction and functional limitations may be sequelae of a cerebrovascular accident (CVA). Muscle weakness as a result of diminished agonist recruitment has been demonstrated in people following a CVA and could be a major factor contributing to movement dysfunction.[1] Changes in volitional limb and trunk movement can influence the ability to complete a functional task. Another type of post-cva movement impairment that has been reported less frequently is strong involuntary movement of a limb in the opposite direction to that being volitionally attempted. For example, a person may have strong elbow extension after volitional elbow flexion has been initiated. Depending on the type of involuntary movement, functional tasks may be easier or more difficult to complete. A person who experiences excessive lower-limb extensor contractions, for example, may learn to use the contractions for assuming and maintaining a standing position. The same extensor overactivity, however, could be strong enough to move a flexed lower limb into extension and disrupt a person's ability to put on pants over the feet.

A possible explanation for the involuntary movement is a disruption of reciprocal inhibition.[2] In the absence of pathology, antagonist muscles are inhibited during an agonist contraction. The amount of inhibition is modulated according to the desired motor outcome. Limb stabilization, for example, requires different modulation of agonists and antagonists than does strong unidirectional limb movement. In people with central nervous system disorders, the correct modulation of antagonistic inhibition during volitional agonistic movement may not occur.[2]

In cases in which involuntary movement appears to be interfering with the performance of a task, pharmacologic treatments often are used to reduce the involuntary movement. Medications used for the control of involuntary movement can be orally administered or injected intramuscularly. Oral medications such as baclofen (Lioresal), dantrolene (Dantrium), and diazepam (Valium) often are used but may cause fatigue, lethargy, cognitive changes, and generalized limb weakness.[3] Alcohol or phenol can be used for nerve blocks to obtain a selective muscle effect[4] but can cause long-term axonal or other tissue damage.[5] Botulinum toxin A (Botox) is another type of intramuscular blocking agent that can be injected to cause selective muscle paralysis without many of the side effects seen with other drugs.[5]

Botulinum toxin A is one of the neurotoxins produced by the bacterium Clostridium botulinum, which, if ingested, causes widespread paralysis. Botulinum toxin A acts by inhibiting the release of acetylcholine at the neuromuscular junction site.[5] Very small doses of botulinum toxin A have been injected to cause therapeutic and selective muscle paralysis in people With torticollis,[6] extraocular muscle dysfunction,[6] dystonias,[6] multiple sclerosis,[7-9] spinal cord injury,[7] cerebral palsy,[10-11] or poststroke hemiparesis.[12-14] The effect of local paralysis is observed within 24 to 72 hours after injection, with the duration of paralysis being approximately 8 to 12 weeks.[5] The duration and extent of paralysis depends on the amount of botulinum toxin A injected.

Most reports demonstrate that botulinum toxin A injections result in improved resting limb position (less hip adduction in a supine position or less knee flexion in a supine or sitting position). Reports also have shown that increased range of motion occurs at the joints traversed by the injected muscles. Data documenting improvement following botulinum toxin A injections in people with movement disorders related to stroke or traumatic brain injury are less available. In one study of 40 adult subjects with chronic neurological disorders, botulinum toxin A was injected into selected upper- and lower-extremity muscles.[12] Although the researchers found that increased range of motion and improved resting limb position occurred as a result of injecting the muscles, functional changes were minimal and there was no major difference in Barthel Index scores.[12] Gait improvements following foot and ankle injections of botulinum toxin A in 10 subjects with neurological disorders were reported, but not described, by Denger et al.[14] Changes in the amount of assistance needed or in the use of orthotic or assistive devices for ambulation were not discussed.

Functional changes have been documented after botulinum toxin A injections in adults following strokes. Das and Park[13] described eight people with,poststroke hemiplegia who received injections to the biceps brachii, flexor digitorum profundus, and flexor carpi ulnaris muscles and who demonstrated increases of approximately 10 to 15 points on the Barthel Index. Conversely, Barthel Index scores did not change in a study by Hesse et al[15] in which nine subjects with left hemiparesis were injected with botulinum toxin A in the brachialis, biceps brachii, flexor digitorum profundus and superficialis, and flexor carpi ulnaris muscles. Although three subjects reported self-care improvements, these changes were not reflected in the Barthel Index scores.

Borg-Stein et al[9] reported the results of botulinum toxin A injections in two adults with multiple sclerosis. One subject was able to walk in the parallel bars without a scissoring gait pattern following injection of the adductor muscles. The other subject exhibited severe flexor spasms of the lower extremities that interfered with transfers and sitting balance before botulinum toxin A injections. Following injection into the hamstring muscles, her ability to sit on the edge of a mat or bed increased from 5 1/2 minutes (with assistance) to more than 30 minutes (without assistance). She could transfer with a sliding board, whereas previously she required the use of a Hoyer lift.

Improvements in gait have been reported in children with cerebral palsy after botulinum toxin A injections to selected lower-extremity muscles.[10,11] In a randomized double-blind trial, 6 children with cerebral palsy received injections of botulinum toxin A and 6 children received injections of a placebo into the gastrocnemius or tibialis posterior muscles.[10] Prior to the injections, all 12 subjects exhibited equinovarus or equinovalgus positioning of the foot when walking. The authors reported, but did not describe, gait improvements in 5 of the 6 children who received the botulinum toxin A injections and in 2 of the 6 children who received placebo injections. In another study of 26 children with cerebral palsy, the gastrocnemius or hamstring muscles were injected with botulinum toxin A.[11] Parents and therapists reported, but did not describe, gait improvements in 11 of 14 subjects in whom the hamstring muscles were injected. Two of the 3 nonambulatory subjects became nonfunctional ambulators, and 1 subject became a functional ambulator. Nonfunctional and functional ambulation were not defined by the authors.

In summary, although data are scarce, research has shown that botulinum toxin A can positively affect functional activities of people with central nervous system disorders. Most authors, however, have not reported whether their subjects received physical therapy or occupational therapy in conjunction with the injections. When therapy was provided, neither the possible effects of therapy nor the type of therapy were described. The purpose of this case report is to describe the changes in rolling, assuming supine and sitting positions, transfers, and ambulation abilities in a 50-year-old man following botulinum toxin A injections into the biceps brachii and quadriceps femoris muscles and a 2-week rehabilitation period. The subject had sustained a CVA 5 months earlier.

Patient History

The patient was a 50-year-old man who was admitted to an acute care facility with the onset of limb weakness, dysphagia, and dysarthria. He was diagnosed with a brain-stem infarction with resultant quadriparesis. He had no documented cognitive deficits. His medical history included arteriosclerosis, a myocardial infarction, chronic obstructive pulmonary disease, bronchitis, and a coronary artery bypass graft 3 years prior to the CVA.

The patient was transferred to a rehabilitation unit 1 month after his CVA for an intensive therapeutic program including physical therapy, occupational therapy, and communication services. At the time of admission, he required the assistance of two people for bed mobility and transfers. He was nonambulatory. Motor control of his extremities was characterized by quadriparesis and stong involuntary upper-extremity flexion and lower-extremity extension during attempts at joint movement or functional tasks. Prior to rolling, for example, the patient could place both legs into a slightly flexed position with his feet flat on the bed. He could initiate reaching for the bed rail. As soon as his arm began to move, his elbows flexed and his legs forcefully extended at the hip and knee, preventing him from maintaining the flexed position that he needed.

Any attempts to modify the movement sequence for rolling resulted in continued upper-extremity flexion and lower-extremity extension. Excessive muscle activity also occurred when he attempted to stand. As he leaned forward in preparation for standing, his legs would involuntarily extend at the hip and knee and he would plantar flex. The combination of the hip, knee, and ankle movement resulted in a bodily movement backward onto the mat or wheelchair. He was unable to support himself on a standard walker because of the involuntary elbow flexion, and his toes dragged on the ground during the swing phase of gait. Despite many attempts at altering the movement sequence for functional activities, he was unable to alter the extent of the involuntary movement. Some changes did occur by placing platforms on the walker to support his flexed forearms when walking and by using polypropylene ankle-foot orthoses to maintain his ankles in a neutral position, reduce the backward thrust during the sit-to-stand movement, and allow greater foot clearance when walking.

The patient's goal, which was the focus of physical therapy during his initial rehabilitation, was to reduce the amount of physical assistance needed for activities that he would be doing at home; for moving in bed and getting in and out of bed; and for unsupported sitting, standing, and walking. Physical therapy included training in bed mobility and transfers. The patient's height was 1.8 m (6 ft) and his weight was 86.2 kg (190 lb). To prevent injury to him and to us, sit-to-stand and standing activities were initiated by using a standing table. He moved out of the standing table for these activities once we believed that two people could safely assist him. Sitting-balance activities occurred on the edge of the mat and hospital bed. Gait training began when two therapists and two aides could safely support him and assist in advancing his legs and walker.

Table 1.
Functional Independence Measure Scores'
                                             2            6
                                             Weeks        Weeks
                              Pre-           Post-        Post-
Category                      injection      injection    injection

Transfers
  Bed/chair/wheelchair        2              4            4
  Toilet                      1              2            2
  Tub/shower                  2              2            2

Locomotion
  Walk                        2              4            4
  Wheelchair                  6              6            6
  Stairs                      1              1            1

"Scoring[15]: 1-total assistance: subject expends <25% of the effort or requires assistance of two people, does not walk a minimum of 15.2 m (50 ft). 2--maximal assistance: subject expends [greater than or equal to]25% but <50% of the effort to perform the task, walks a minimum of 15.2 m, requires assistance of one person only. 3--moderate assistance: subject expends [greater than or equal to]50% but <75% of the effort to perform the task, walks a minimum of 45.7 m (150 ft). 4--minimal contact assistance: subject expends [greater than or equal to]75% of the effort to perform the task, walks a minimum of 45.7 m. 5--supervision or setup: subject has no physical contact; requires setup, cueing, or coaxing to perform task; walks a minimum of 45.7 m. 6--modified independence: subject has no helper, uses assistive device, walks a minimum of 45.7 m. 7--complete independence: subject has no helper, uses no device, walks a minimum of 45.7 m.

Although the patient's wife and teenage daughter were willing to learn to provide the care that the patient would need at home, transportation problems prevented them from participating in his therapy on a daily basis. Family education was emphasized on the days that his family could attend therapy. Weekend passes began I month following his admission to the rehabilitation unit.

Throughout the course of his initial rehabilitation, it was the opinion of the rehabilitation team (physical therapist, occupational therapist, nurse case manager, physiatrist, recreational therapist, and speech pathologist) that the involuntary muscle activation during volitional movement was interfering with progress, specifically dressing, rolling, assuming sitting and supine positions, transfers, and walking. Two oral pharmacologic agents were tried but were unsuccessful in decreasing the excessive movement. Baclofen produced paranoia, and dantrolene did not produce an observable effect.

After consulting with a neurologist who was familiar with botulinum toxin A, the rehabilitation team decided that botulinum toxin A injections into the patient's biceps brachii muscles might reduce the involuntary elbow flexion occurring with volitional movement and allow him to use the bed rails for rolling, to push up on his arms for sitting up from a supine position, to reach for the wheelchair armrest during transfers, and to use a conventional walker. The team believed that injections into the patient's quadriceps femoris muscles would reduce the excessive lower-extremity extension when rolling and assuming sitting and supine positions. If this occurred, we surmised that less physical assistance from a caregiver would be needed.

The patient decided to return home for about a month before receiving the botulinum toxin A injections. He told the rehabilitation team that he needed a break from the intensive therapy and wanted to attend to personal matters. He was discharged from the rehabilitation unit 4 months after his CVA, with plans for future botulinum toxin A injections. At the time of discharge, he required total assistance of one person for toilet transfers and maximal assistance of one person for bed, chair, and wheelchair transfers. He walked 9.1 m (30 ft) with a bilateral platform rolling walker with maximal assistance of one person. Level of assistance is defined by the Functional Independence Measure (FIM)16 (Tab. 1).

One month later (5 months post-cva), the patient was readmitted for upper- and lower-extremity botulinum toxin A injections and additional rehabilitation. At that time, his functional level had not changed. The patient continued to require substantial physical assistance from one caregiver for bed mobility, transfers, and walking. When rolling onto his side, his arms flexed as he reached for the bed rail and lower-extremity extension prevented him from pushing with his legs. When attempting to bring his upper body into an upright position during the transition from a supine to a sitting position, his arms would flex as he attempted to push. When assuming a supine position from a sitting position, the patient's legs would move involuntarily into extension from flexion and he was unable to lift his legs up onto the bed. His elbows flexed each time he attempted to use them to push into a standing position from a Sitting position. When walking, he used two walker platforms to support his flexed arms and ankle-foot orthoses to maintain a neutral ankle position during the swing phase of gait. The patient's physical therapy goals were to reduce the level of dependence for bed mobility and wheelchair-to-bed transfers and to walk with a standard walker.

Evaluation Procedures

The patient was evaluated prior to his botulinum toxin A injections, 2 weeks after injections, and then as an outpatient (6 weeks after injections). We chose the following evaluative methods: (1) administration of the FIM,[16] (2) description of the limb positions observed during functional tasks, (3) measurement of walking speed, and (4) administration of the Sickness Impact Profile (SIP).[17] The same physical therapist, who had been trained to administer the FIM, performed all of the evaluations.

Functional Independence Measure

The FIM is an ordinal-scale measurement instrument, which can be used to assess seven levels of dependence in the categories of self-care, sphincter control, mobility, locomotion, communication, and social cognition.[16] The FIM was designed to evaluate the burden of care.[16] Hamilton et al[18] have reported interrater reliability values (intraclass correlation coefficients) for the seven-level FIM ranging from .75 (substale scores) to .90 (total score). In that study, reliability was assessed by two or more trained clinicians who rated 306 patients from 24 inpatient rehabilitation facilities.

Functional Evaluation

Limb positions during rolling, sitting up, lying down, transfers, and walking were video recorded by the same therapist during all evaluation sessions. The videotapes were used to confirm observations of the patient's ability to hold on to the bed rail when rolling and to hold on to the wheelchair armrest and bed rail for transfers.

Walking Speed

The patient's walking speed was determined by asking him to walk as fast as he could along an 11.9-m (39-ft) walkway. We used the middle 5.8 m (19 ft) to determine the walking speed. Test-retest reliability for walking speed in people with neurological disorders has been reported to range between .94 and .99 (Pearson correlation coefficients).[19] Prior to the injections, the patient walked with the bilateral platform rolling walker that he had used at home. Two weeks after the injections, the patient was evaluated while he used both the bilateral platform walker and a unilateral (left-side) platform rolling walker. Six weeks after his injections, his walking speed was measured using only the unilateral platform rolling walker because that was what he had chosen to use at home.

Patient Perception of Disability

The SIP is a multidimensional health status questionnaire.[17] It consists of 136 items in 12 categories: ambulation, mobility, body care and movement, emotional behavior, social interaction, communication, alertness behavior, sleep and rest, eating, home management, recreation and pastimes, and employment. The SIP can be self-administered or administered by an interviewer in 20 to 30 minutes. Each test item checked by the patient has a preassigned value. The values for all checked items in the profile are added, divided by the maximum score (1,003), and multiplied by 100 to provide the interviewer with an "overall score.' The physical dimension score is calculated similarly, with the values added from the mobility, ambulation, and body care and movement categories, divided by the maximal score (356.4), and multiplied by 100. The psychosocial dimension score is calculated the same way and is composed of scores from the social interaction, alertness behavior, emotional behavior, and communication categories. The maximum psychosocial dimension score is 365.7. The higher the score, the greater the level of perceived disability. The test-retest reliability coefficient (r) of the overall score was reported to be .8820 on a form of the SIP that contained 146 items. Since that study of reliability, 10 items have been deleted from the SIP and no reliability information is available about the use of this form of the SIP with people who have neuromuscular or chronic neurological disabilities. For our report, the same therapist administered the SIP each time by interviewing the patient.

Injections

After completion of the physical therapy evaluation, the patient received the botulinum toxin A (Botox) injections. He received 75 U in both biceps brachii muscles, 55 U in the left quadriceps femoris muscle, and 60 U in the right quadriceps femoris muscle. In a study by Borg-stein and Stein,[5] 1 U was the amount of toxin that killed 50% of a group of 18 to 20 female Swiss-Webster mice. To avoid the risk of deterioration of the patient's standing and walking abilities due to a change in quadriceps femoris muscle activity, a minimal dose of Botox was injected into the quadriceps femoris muscles. We believed that the patient's preinjection walking and standing abilities were aided by the stability provided by the involuntary extensor movement. It was unclear to us how much of a decrease in involuntary movement could occur before compromising the patient's standing and walking.

Postinjection Treatment

After the injections, the patient received occupational therapy and physical therapy. Occupational therapy focused on dressing and fine motor activities. Physical therapy focused on practice of rolling, sitting up, lying down, transfers, and walking. The patient received approximately 30 to 45 minutes of physical therapy twice a day. He practiced bed mobility and transfer skills in his hospital room. Walking was practiced in the physical therapy gym. We encouraged the patient's active participation through our (the therapists') idea sharing and verbal exploration of alternative methods for accomplishing particular functional tasks. For example, bed ladders, different body positions in bed, and bed rails were tried for rolling and assuming sitting and lying. positions. With the patient, we discussed and tried walking with axillary and forearm crutches, walkers with and without wheels, and walkers with and without platforms in addition to walking without any assistive device. The patient was most satisfied with a trial-and-error method to learn what worked best for him. These activities were followed with suggestions from the physical therapist. The patient practiced an activity until he was satisfied with his performance or became fatigued or excessively frustrated.

Results

Functional Independence Measure

The only change in the patient's FIM scores was in the area of transfers and walking (Tab. 1). Two weeks after his injections, he required less assistance and consequently was rated higher for bed, wheelchair, and toilet transfers. His FIM walking score improved because he was able to walk a greater distance, at least 45.7 m (150 ft) as compared with his maximum preinjection walking distance of less than 15.2 m (50 ft), although the level of physical assistance required was the same. His bed mobility and transfer ability remained the same as before injections.

Functional Evaluation

Improvements in the patient's limb positions during functional tasks were noted 2 and 6 weeks after the injections. He could extend his arms sufficiently to hold on to the right or left bed rail during rolling and supine-to-sitting transitional movements; however, he still required physical assistance to complete,the task. He could also reach for and hold on to the Wheelchair armrest for a transfer. Although he still required physical assistance to maintain balance while walking, he walked farther (by more than 30.5 [100 ft]) and held on to the walker with his right hand, eliminating the need for a platform on the right side of the walker. Improvements were confirmed by videotape obser-vation.

Walking Speed

The patient's walking speed with the bilateral platform rolling walker 2 weeks after the injections was 0.009 m/s (0.03 ft/s) faster than his preinjection walking speed (Tab. 2). Walking speed with the bilateral platform walker was not measured 6 weeks after injections because he was not using that walker at home. The patient was not able to use a unilateral platform rolling walker prior to his Botox injections. Between 2 and 6 weeks postinjection, using a unilateral (left-side) platform rolling walker, walking speed improved by 0.007 m/s (0.03 ft/s). Although the patient preferred the unilateral platform rolling walker, his walking speed with it was 0.03 m/s (0.1 ft/s) longer than with the bilateral walker 2 weeks postinjection. He preferred the unilateral platform walker because it allowed him the use of his right arm despite the longer walking time.

Sickness impact Profile

The SIP was administered to the patient prior to the injections and 2 weeks and 6 weeks after the injections (Tab. 3). The results of the SIP administered 6 weeks after the injections indicated that the patient (1) spent less time sleeping and dozing throughout the day, (2) had improved balance, (3) had increased ease with dressing, (4) had decreased irritability with himself, (5) was doing more things to care for his family, and (6) had improved appetite.

Discussion

We believe that the decrease in involuntary elbow flexion, particularly in the right upper extremity, resulted in the following gains: a smaller assistive device required for walking and the need for less physical assistance during rolling and transfers. There was minimal change in the patient's lower-extremity involuntary movement during rolling, transfers, or transitions between sitting and standing. He continued to require the ankle-foot orthoses when walking. Although the amount of physical assistance required after the injections was less than before the injections, he needed the assistance just as frequently. The patient believed that as a result of the injections, he had a better appetite and improved dressing skills. He perceived that he was more alert during the day, less irritable, and able to do more things for his family.

Botulinum toxin A reduces the amount of neurotransmitters released at the neuromuscular junction site, consequently reducing muscular activity. Theoretically, if enough toxin is injected, the alteration in muscular activity would be great enough to result in lessjoint and limb movement. In this patient's case, we hoped that the involuntary upper- and lower-limb movement during attempts at volitional movement would diminish as a consequence of the physiological effect of the botulinum toxin A on the biceps brachii and quadriceps femoris muscles. Involuntary flexion decreased enough in one elbow to cause functional change; however, little change occurred in the lower extremities. This lack of change might have been due to the dosage amount injected into the lower extremities. Only 55 to 60 U of Botox was injected into the quadriceps femoris muscles of this 1.8-m-tall, 86.2-kg man.

In other studies,[8-13,15] dosage amounts for the lower extremities have ranged from 50 to 200 U, with the majority of the subjects (mostly children) receiving at least 160 U in the gastrocnemius muscle. Our patient's involuntary lower-limb extension assisted him in maintaining an upright position and he did not want this ability compromised, so a lower dosage was injected into his quadriceps femoris muscles. The amount of botulinum toxin A injected into the patient's quadriceps femoris muscles did not change his ability to maintain an upright position, but neither did it assist in reducing his involuntary movement. Whether, with additional injections, the involuntary movement would have been further reduced and greater improvements made is beyond our ability to assess. We assume, however, that given a greater reduction in involuntary movement, the agonist muscles would be strong enough to complete the functional task. This assumption may be incorrect in light of recent research regarding inadequate motor unit recruitment in the agonists in people poststroke.[1] Weakness of the prime movers may be responsible for the inability to accomplish motor tasks; if so, reducing the involuntary movement would have little effect on the measured outcomes.

We also believe that the observed changes in rolling, assuming sitting and lying positions, transfers, and walking were a result of the botulinum toxin A injections and the therapy combined. The botulinum toxin A reduced the patient's involuntary limb movement, and the physical therapy allowed him to most effectively use the change in limb control. We believe that the increase in physical activity during the 2-week postinjection rehabilitation period was primarily responsible for the increase in distance that he could walk (less than 15.2 m [50 ft] versus 45.7 m [150 ft]). A walker with one platform is approximately 0.45 to 0.9 kg (1-2 lb) lighter than a walker with two platforms, which also may have contributed to his ability to walk farther. The changes that this patient experienced as a result of the botulinum toxin A injections are similar to the changes reported by other investigators where gains were made that reduced the amount of physical assistance required but that did not result in independent performance of tasks or changes in measured functional outcomes.[9,12-15]

For many patients, the issue of physical dependency dictates discharge location. If caregivers are unavailable or the amount of physical assistance required is more than caregivers can manage, then institutional placement is often necessary. Botulinum toxin A might be useful in providing an opportunity to evaluate change in individuals for whom the availability or capability of existing caregivers is questionable. Reduction in physical strain on some caregivers may allow patients to continue living in their own homes for a longer period of time.

This was our first experience with a person with CVA-induced quadriplegia who received botulinum toxin A injections. We believe that when contemplating the use of this type of treatment, all aspects of the person's lifestyle need to be considered. Although independence was not achieved by this patient following the botulinum toxin A injections, certain changes did occur that were important to him and his caregivers.

Table 3.
Sickness impact Profile Scores"'
                                   2 Weeks        6 Weeks
                        Pre-       Post-          Post-
Category                injection  injection      injection

Physical dimension      39.3       40.74          39.1
Psychosocial
  dimension             15.47      14.44           9.13
Overall                 29.17      31.67          26.64

Acknowledgments

We thank the patient and his family for allowing specific information about his medical status to be discussed and published. We also express our appreciation to Dr Jean Held for her careful and thoughtful reviews of our manuscript.

References

[1] Gowland C, deBruin H, Basmajian JV, et al. Agonist and antagonist activity during voluntary upper-limb movement in patients with stroke. Phys Ther. 1992;72:624-633.

[2] Leonard CT, Moritani T, Hirschfeld H, Forssberg H. Deficits in reciprocal inhibition of children with cerebral palsy as revealed by H reflex testing. Dev Med Child Neurol. 1990;32:974-984.

[3] Physicians' Desk Reference. 49th ed. Montvale, NJ: Medical Economics Co; 1995.

[4] Awad EA, Awad OE, eds. Injection Techniques for Spasticity. Minneapolis, Minn: Awad EA; 1993.

[5] Borg-Stein J, Stein. . Pharmacology of botulinum toxin and implications for use in disorders of muscle tone. J Head Trauma Rehabil. 1993;8:103-106.

[6] Jankovic J, Brin M. Therapeutic uses of botulinum toxin. N Engl J Wed. 1991;324:1186-1193.

[7] Albany K, Pine ZM, Cava T, et al. Treatment of spasticity with botulinum toxin-a injections. Neurology Report of the American Physical Therapy Association. 1993;17(4):17. Abstract.

[8] Snow BJ, Tsui JKL, Bhatt MH, et al. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol. 1990;28:512-515.

[9] Borg-stein J, Pine ZM, Miller JR, Brin MF. Botulinum toxin for the treatment of spasticity in multiple sclerosis: new observations. Am J Phys Med Rehabil 1993;72:364-368.

[10] Koman LA, Mooney JF, Smith BP, et al. Management of spasticity iA cerebral palsy with botulinum--A. toxin: report of a preliminary, randomized, double-blind trial. J Pediatr Orthop. 1994; 14:299-230.

[11] Cosgrove A, Corry I, Graham H. Botulinum toxin in the management of the lower limb in cerebral palsy. Dev Med Child Neurol. 1994;36:386-396.

[12] Das TK. Botulinum toxin in treating spasticity. Br J Clin Pract. 1989;43:401-402.

[13] Das TK, Park DM. Effect of treatment with botulinum toxin on spasticity. Postgrad Med. J. 1989;65:208-210.

[14] Denger R, Neyer U, Wohlfarth K, et al. Local botulinum toxin in the treatment of spastic drop foot. J Neurol. 1992;239:375-378.

[15] Hesse S, Friedrich H, Domasch D, Mauritz KH. Botulinum toxin therapy for upper limb flexor spasticity: preliminary results. Journal of Rehabilitation Science. 1992;5:98-102.

[16] Guide for the Uniform Data Set for Medical Rehabilitation Adult FIM), Version 4.0. Buffalo, NY. State University of New York at Buffalo/UB Foundation Activities Inc; 1993.

[17] Bergner M, Bobbitt RA, Carter WB, Gilson BS. The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981;19:787-805.

[18] Hamilton B, Laughlin JA, Fiedler RC, Granger C. Interrater reliability of the seven-level Functional Independence Measure (FIM). Scand J Rehabil Med. 1994;26:115-119.

[19] Holden MK, Gill KM, Magliozzi MR, et al. Clinical gait assessment in the neurologically impaired: reliability and meaningfulness. Phys Ther. 1984;64:35-40.

[20] Pollard WE, Bobbitt RA, Bergner M, et al. The Sickness Impact Profile; reliability of a health status measure. Med Care. 1976;14:146-155.

SJ Cromwell, PT, is Advanced Clinician, Fletcher Allen Health Care, University Health Center Campus, Burlington, VT 05401 (USA). Address all correspondence to Ms Cromwell.

VL Paquette, PT, is Physical Therapist, Fletcher Allen Health Care, Medical Center Hospital of Vermont Campus, Burlington, VT 05401.