Combination of Botulinum Toxin and Physical Therapy to increase functional mobility in a

patient with Multiple Sclerosis: Case Report

Amanda VidemsekCleveland State University

Abstract

Background and Purpose

Multiple sclerosis (MS), a disabling, progressive disease of the central nervous system,

affects more than 2.3 million individuals worldwide. The symptoms caused by MS impact an

individual’s mobility, ability to perform daily activities and participate in life events. The

purpose of this case report is to assess the effectiveness of botulinum toxin in combination with

stretching, strengthening, and neuromuscular re-education to increase functional mobility.

Case Description

A 41-year-old Caucasian male diagnosed with exacerbating-remitting MS in November

2011 (EDSS level 6.5) participated in this case report. The patient received botulinum toxin

injection in February 2017 in his right gastrocnemius due to increased spasticity interfering with

gait pattern. The patient presented to physical therapy with complaints of weakness, pain,

cramping in lower extremities, impaired mobility, and a history of falls. The patient ambulates

with a RollatorTM.

Outcomes

Timed Up and Go (TUG) and 5-Time Sit to Stand were the two main outcome measures

used. The TUG time increased from 12.8 seconds to 15.5 seconds from the initial evaluation to

discharge, respectively. The 5-Time Sit to Stand time also increased from 25 seconds to 25.6

seconds, from initial evaluation to discharge. The patient continued to demonstrate gait

deviations and decreased strength in left lower extremity compared to right.

Discussion

No significant improvements were noted in regard to standardized outcome measures;

TUG and 5-Time Sit to Stand. These results may be influenced by fluctuations in the patient’s

functional status, compliance with home exercises, increased heat affecting fatigue levels, and/or

the effects of the botulinum toxin injection beginning to wear off. Functional mobility and a

patient’s ability to participate in daily activities should be the focus of a physical therapy plan of

care.

Manuscript word count = 3022

Background and Purpose

Multiple sclerosis (MS) is a disabling, progressive, non-curable disease of the central

nervous system that affects more than 2.3 million individuals worldwide.1,2 During the disease

course, the immune system attacks the myelin sheaths that encapsulate nerve fibers, interrupting

the communication between the brain and the body.2 The disease progression is unpredictable,

although the most frequent course is relapsing-remitting with recurring attacks that alternate with

periods of remission.3 Common symptoms of MS include muscle weakness, increased fatigue,

muscle spasticity, gait abnormalities, visual deficits, numbness and tingling, dizziness,

bladder/bowel problems, pain, cognitive changes, and depression.1 Eventually, the natural course

of progression leads to permanent neurologic deficits.3 Although there is no cure for MS at this

time, many effective treatment options are available in an attempt to shorten the duration of

attacks and/or to treat a disabling symptom of the disease4. Pharmaceutical treatment as well as

non-pharmaceutical interventions such as exercise and physical therapy play an important role in

symptom management3.

Spasticity, the most frequently reported symptom in patients with MS, which can cause

significant pain, limit mobility, and decrease a patient’s quality of life5. The most widely used

treatment for focal muscle spasticity is botulinum toxin injected directly into the affected

muscle5. This treatment option avoids the accompanying sedation and generalized weakness that

is associated with oral medications for spasticity5. Botox injections target the neuromuscular

junction by blocking the release of acetylcholine, causing temporary muscle paralysis lasting

approximately 3-4 months5,6. Due to its temporary effects, botulinum toxin injection is solemnly

a treatment performed in isolation, but in combination with various physical therapy

interventions7. M Giovannelli et al, demonstrated a relevant role for physical therapy in

combination with botulinum toxin Type A injection to improve the overall response to the

injection through participation in an exercise and stretching program. In this study, the Modified

Ashworth Scale (MAS) was used to detect a decrease in spasticity at an impairment level7. This

decrease in spasticity offers physical therapists a period of time to provide interventions to

improve functional mobility that were not previously possible due to the significant muscle tone

changes.7 There is limited research looking at the improvement in functional mobility of patients

with multiple sclerosis after receiving botulinum toxin injection along with physical therapy

interventions at an activity and participation level.

The World Health Organization’s International Classification of Functional, Disability,

and Health (WHO-ICF) is a conceptual framework that describes the disablement process

through six dimensions of function which include health condition, body structure, activity,

participation, environmental factors, and personal factors (Figure 1.) 8 This model considers

biological, personal, and social perspectives and illustrates the complex relationship between

these various factors8. The ICF model is used with this case as a tool to organize and classify the

patients function and contextual factors and to assist the therapist with clinical decision making.

This case report is beneficial to demonstrate how the ICF model can be used to evaluate patients

with MS and assist with providing interventions that impact the activity and participation

limitations that this population is faced with daily. The purpose of this case report is to assess the

effectiveness of botulinum toxin in combination with stretching, strengthening, and

neuromuscular re-education to increase functional mobility in a patient with multiple sclerosis.

Figure 1.World Health Organization’s International Classification of Functioning, Disability and Health Model8

Case Description: Patient History and Systems Review

The patient was a 41-year-old Caucasian male diagnosed with exacerbating-remitting

multiple sclerosis in November 2011. Diagnosis was made based on MRI imaging. The current

EDSS level is 6.5; Walks with bilateral support about 20 meters. The patient participated in

physical therapy intermittently since the diagnosis and was recently referred back to physical

therapy in February 2017 following botulinum toxin injection into the right gastrocnemius

muscle due to increased spasticity that interfered with gait (100 units of Botox injected into 4

sites in right gastrocnemius). The plan is to repeat the injection in 3 months with 200 units of

Botox. Current medications include 10mg oral baclofen daily and Tysabri infusions initiated in

2013.

The patient presented to physical therapy with complaints of muscle weakness, pain,

cramping in lower extremities, and the decreased ability to perform functional abilities. Patient

has a history of multiple falls and reports difficulty with daily activities due to mobility deficits.

The patient ambulates using a standard cane or RollatorTM at a modified independent level,

depending on his fluctuation in functional status. The patient’s past medical history includes

hypertension, anxiety, depression, supraventricular tachycardia and alcohol abuse. Patient lives

in a single-story house with his wife and two children and works full-time from home. Patient

stated that his goal for therapy was to “get stronger and make sure that I am exercising in the

proper way for someone who has multiple sclerosis.”

Clinical Impression #1

The primary problem in this case lies within the activity and participation domains of the

ICF model (Table 2.). Primary impairments as a result of a neurological disease caused gait

pattern deviations and increased fatigue with ambulation which impacts the patient’s functional

mobility and ability to participate in life events with his family. Based on the information

gathered during the patient interview regarding the patient’s medical history, the diagnosis of

multiple sclerosis in 2011, progressive weakness, fatigue, and lower extremity spasticity, the

initial clinical impression of the patient’s problems are most likely from a neurologic origin.

The treatment of patients with multiple sclerosis is within the scope of practice of a physical

therapist and is classified into pattern 5E: Impaired Motor Function and Sensory Integrity

Associated with Progressive Disorders of the Central Nervous System9.

Appropriate examination tests and measures were chosen based on the neurologic

diagnosis and relevant information gathered during the patient interview while using the ICF

framework to organize and classify data collected. The plan for the examination was to assess

impairments initially at a body structure domain level by looking at muscle strength and

spasticity and then continuing with evaluation of functional tasks and activities including

ambulation, transfers, and balance.

Examination

A thorough chart review and a patient interview was conducted to gather pertinent

information about the patient’s prior level of function, medication history, disease progression,

home set-up, and goals for therapy. After the patient interview, an assortment of tests and

measures were performed with intent to support or dispute clinical impression 1. Significant

findings from the examination are listed in Table 1.

Lower extremity manual muscle testing (MMT) was performed to assess for muscle

weakness that may influence ambulation and cause gait deviations. MMT of hip flexion, knee

extension, knee flexion, and ankle dorsiflexion conducted in a seated position with lower

extremities hanging off the side of the plinth. The patient was in a supine position with ankles

supported under a small bolster for muscle testing of ankle inversion, eversion, and plantar

flexion. Since the patient presented to physical therapy after a botulinum toxin injection, it was

pertinent to assess spasticity as it may impact gait and functional mobility. Spasticity of the

lower extremity muscles was tested using the Modified Ashworth Scale (0-4) with the patient in

a supine position on the plinth10. The physical therapist assessed the patient’s functional mobility

throughout the examination by evaluating the level of assistance required when performing

transfers and bed mobility activities (Table 1). Gait analysis was completed during observation

of the patient ambulating in the hallway during the 10-meter walk test trials (Table 1).

Table 1. Results of Tests and Measures at Initial Evaluation and Discharge

Initial Evaluation DischargeStrength Testing(MMT)

Right Left Right Left

Hip Flexion 4+/5 4-/5

Knee Extension 4/5 4/5

Knee Flexion 5/5 4+/5

Ankle Dorsiflexion 2+/5 2-/5 2+/5 2+/5

Ankle Plantarflexion 4/5 3+/5 4/5 3+/5

Ankle Inversion 4+/5 3+/5 4+/5 3+/5

Ankle Eversion 4+/5 3+/5 4+/5 3+/5

Spasticity Right Left Right Left

Knee Extensors 0 0 Not tested Not tested

Knee Flexors 0 0 Not tested Not tested

Hip Adductors 0 0 Not tested Not tested

Ankle Plantarflexors 1+ 1+ Not tested Not tested

Functional MobilityBed mobility Sit to Supine Independent Sit to Supine Independent

Supine to Sit Independent Supine to Sit IndependentRolling Independent Rolling Independent

Transfers Sit to stand Independent with difficulty

Sit to stand Independent with difficulty

Ambulation Modified Independent with standard cane

Modified independent with use of rollator

Gait AnalysisAssistance Level Modified Independent Modified Independent

Device Standard CaneLeft ankle AFO

RollatorTM; Left ankle AFO

Deviations Decreased cadence, limited ankle dorsiflexion, decreased foot clearance, left hip hike and circumduction, left knee hyperextension in mid-stance, increased reliance on upper extremity support on RollatorTM, fatigued after approx. 25 feet of ambulation

Decreased cadence, limited ankle dorsiflexion, decreased foot clearance, left circumduction, left knee hyperextension in mid-stance, increased reliance on upper extremity support on RollatorTM, quickly fatigued after approx. 40 feet of ambulation

Safety Awareness Poor safety awareness with use of cane; Impulsive

Slightly improved safety awareness with use of RollatorTM; Impulsive at times

Three standardized outcome measures were selected and administered during the initial

evaluation, including the 10-meter Walk Test to assess gait speed, Timed up and Go (TUG), 5-

Time Sit to Stand. All results are illustrated in Table 4.

The TUG was performed to assess the patient’s functional mobility, gait, and fall risk

which associates with the activity domain of the ICF model. The patient was asked to stand up,

walk around the cone placed at a distance of 3-meters, walk back to the chair, and sit down as

fast and as safe as he could. The patient was given two attempts and the average time was

recorded as the final score. The patient used a RollatorTM during this test. The TUG is validated

as a with strong convergent validity as a measure of functional mobility for patients with

multiple sclerosis11. Compared to the timed 25-foot walk test which is the most commonly used

measure to assess walking ability in this population, the TUG seems to be a more complete and

meaningful measure of functional mobility11.

The 5-time sit to stand test was performed to measure functional lower extremity

strength. The patient was asked to stand up and sit down 5 times as fast as he could with his arms

across his chest. The therapist recorded the amount of time it took the patient to perform 5 sit-to-

stand transfers. A change of > 2.3 seconds was identified as a cut off score that provided the best

discrimination of sensitivity (67.7%) and specificity (66.2%) for identification of patients that

made clinical improvement11.

The 10-meter walk test was conducted in the hallway with tape on the walls that

indicated the starting and ending position. The patient was unaware of the markings and was

asked to walk the distance of the hallway at his preferred walking speed. The therapist timed the

patient and the recorded the time and calculated the gait speed. The patient used his RollatorTM

for this test. There is adequate to excellent correlation with dependence with mobility at

comfortable speed (r = 0.34 - 0.74)13.

Clinical Impression #2

Based on the information gathered during the examination, through the assessment of

muscle strength, functional mobility, spasticity, and gait deviations, the initial clinical impression

was confirmed and the patient continues to be appropriate for this case report. The ICF model

was used to organize and classify the patients function and to assist the therapist in differential

diagnosis and clinical decision making (Table 2). The diagnosis of multiple sclerosis was

established by MRI imaging, which confirms that the primary problems causing decreased

activity and participation are of neurologic origin. Lower extremity spasticity and fatigue has

impacted the patient’s gait pattern, ability to ambulate long distances, ability to keep up with

family members, and has caused falls. The next plan of action in this case is to proceed with

physical therapy. Interventions include stretching, strengthening, endurance, neuromuscular re-

education, balance, gait training, education on perceived exertion, and assistive device safety

awareness education7,14,3. The goal of physical therapy intervention in combination with

botulinum toxin injection is to improve the patient’s functional mobility on an activity level by

demonstrating a decrease in TUG score.

Table 2. The World’s Health Organization’s International Classification of Functioning, Disability and Health (WHO-ICF) Model Applied to the Evaluation of a Patient with Multiple Sclerosis

ICF Dimension/Domain

Health Condition

Body Structure and Function

Activities Participation

Multiple Sclerosis

Stiffness/Spasticity in left lower extremity

Difficulty with ambulation Unable to keep up with family members when walking in the community

Weakness in bilateral lower extremities

Difficulty with transfers (sit to stand)

Increased time needed to perform transfers when attending children’s sporting events

Pain in lower extremities Inability to maintain sitting position for prolonged periods of time

Interruptions at work

Balance deficits Difficulty performing self-care activities

Increased reliance on family members to assist with self-care activities

Contextual FactorsPersonal

Age Past medical history Fitness and exercise routine Anxiety/depression Self-motivation/self-efficacy

Environmental Positive family support system Single-level home Coping style – previous abuse of alcohol Work environment – ability to work from home Availability of medical equipment and assistive devices Weather changes - heat intolerance

Intervention

Based on the initial evaluation, the plan of care was determined to be one visit per week

for 2 months. The interventions would include a combination of therapeutic

exercise/strengthening, ROM/flexibility, gait training/mobility, neuromuscular re-education, and

endurance training along with a home exercise program and education on multiple sclerosis

exercise guidelines. The patient participated in six physical therapy sessions lasting 45 minutes

each, including the initial evaluation, over an eight-week period. The patient was also provided a

home exercise program in addition to the six physical therapy sessions.

A warm-up was performed at the beginning of each therapy session using a recumbent

stepper (SciFit). The interventions began with therapeutic exercises in a supine and seated

position focused on lower extremity strength, gastrocnemius stretching, and instruction on

abdominal bracing. The patient required consistent cueing to slow down and take breaks in

between exercises to decrease the risk of fatigue. The therapist initiated education at the first

session, emphasizing the importance of rest breaks, not exercising too much, and instructing the

patient to listen to his own body. Therapeutic exercise parameters are detailed in Table 3.

Exercises were progressed based on patient tolerance and quality of movement during each

exercise. If the patient returned to physical therapy session and reported that he had minimal

soreness from the previous session and was able to perform all the home exercises without pain

or increased fatigue, then the interventions were slowly progressed. By increasing the amount of

repetitions and progressing from a supine, to sitting, to standing position, the therapeutic

exercises were progressed based on the patient’s response and ability to perform exercises with

good movement quality. Neuromuscular re-education exercises were slowly introduced to focus

on weight bearing without knee hyperextension to promote a more normalized, efficient gait

pattern. The neuromuscular exercises included lateral stepping, tandem stance, tandem walking

and forward walking over canes in parallel bars for increased safety. Verbal cues, tactile cues,

demonstration, and use of mirror feedback was incorporated during weight bearing exercises to

assist the patient with proprioception and body awareness.

Interventions denoted with an ‘*’ in Table 3 were incorporated into the patient’s Home

Exercise Program (HEP). The patient was instructed on the exercise in the clinic using verbal

and tactile cues for proper performance and then the patient was given written instructions with a

picture of each exercise for reference when performing exercises at home. HEP instructions

included reps, sets, and frequency along with education on pacing and taking breaks to decrease

fatigue.

Table 3. Interventions Therapeutic

Exercise3/27/2017 3/29/2017 4/03/2017 4/05/2017 4/17/2017 (discharge)

SciFit 5 min, arms + legs, Level 1

5 min, arms + legs, Level 1

5 min, arms + legs, Level 2

6 min, arms + legs, Level 2

8 min, arms + legs, Level 2

Total gym Calf stretch:5 x 30 second hold left leg

Calf stretch:5 x 30 second hold left leg

Calf stretch: 5 x 30 second hold left legSquats: 10 x 2 sets; second set with orange Theraband around thighs

Calf stretch:5 x 30 second hold left leg

Calf stretch:5 x 30 second hold left leg

Bridge* 10 x 3 sec hold 10 x 5 sec hold 10 x 5 second hold 10 x 5 second holdAbdominal (Abd) Bracing*

X10; Max cues for proper breathing

5 x 5 second hold; Max cues for proper breathing

HEP HEP

Abd. bracing with knee fallout*

X5 each leg X10 each leg HEP X10 each leg

Abd. bracing with marching

X10 alternating legs

X10 alternating legs

Clam shells* X10 each leg X10 each leg HEP X10 each legHeel raises* Seated:

X10 bilaterallyStanding: X10 with Max bilateral UE support in parallel bars

Standing: X10; Max UE support in parallel bars

Standing:5 x 2 sets bilaterally

Marching Seated:X20 alternating legs

Standing:X20; one hand support in parallel bars

Standing:X20; one hand support in parallel bars

Standing:X20 alternating legs; bilateral UE support in parallel bars

Standing mini squats

X10 with maximum upper extremity support

5 x 2 sets; Max UE support in parallel bars

Standing hamstring (HS), curls hip ABD, hip flexion

HS curls: X5 each leg; Max UE support in parallel bars

HS curls: X5 each leg; Max UE support in parallel barsHip ABD: X6 each leg; bilateral UE support in parallel bars

HS curls: X10 each leg; Bilateral UE support in parallel bars

HS curls: 5 x 2 sets each legHip ABD: 5 x 2 sets each legHip Flexion: 5 x 2 sets; right leg only

Forward Step-ups X10 each leg with bilateral UE support; 4-inch step

Neuromuscular Re-education

3/27/2017 3/29/2017 4/03/2017 4/05/2017 4/17/2017 (discharge)

Lateral stepping 6 x 10 ft with bilateral UE support in parallel bars; Verbal and tactile cues to minimize left knee hyperextension during WB

6 x 10 ft with bilateral UE support in parallel bars; Verbal and tactile cues to minimize left knee hyperextension during weight bearing

6 x 10 ft with bilateral UE support in parallel bars; Verbal and tactile cues to minimize left knee hyperextension during weight bearing

Tandem Stance*

Tandem Walking

Stance: 20-sec hold x1 with left leg forward; 20-sec hold x1 with right leg forward; Intermittent bilateral UE support in parallel bars

Walking: 6 x 10 feet with bilateral UE support; cues to minimize left knee hyperextension during weight bearing

Forward stepping over canes

8 x 10 feet; 3 canes; bilateral UE support in parallel bars; step over gait pattern

* denotes exercises given in HEP

Outcomes

Multiple outcome measures were performed at the initial evaluation and again performed

at discharge to demonstrate any progress made during the physical therapy plan of care. Two

outcome measures assessed at discharge were the TUG and 5-Time Sit to Stand. The results are

listed in Table 4. The average TUG time increased from 12.8 seconds to 15.5 seconds from the

initial evaluation to discharge, respectively. The 5-Time Sit to Stand time also increased from 25

seconds to 25.6 seconds, from initial evaluation to discharge. The 10-Meter Walk Test was not

performed at discharge. There was no significant improvement in the 5-Time Sit to Stand or

TUG scores when compared to the initial evaluation.

Along with the above standardized outcomes, tests and measures performed at the initial

evaluation were again performed at subsequent progress notes and at discharge to show progress

towards the patient’s goals. The results are listed in Table 1. These measures included lower

extremity manual muscle testing, bed mobility and transfer assessment, and gait deviation

analysis. No significant improvements were noted in regard to lower extremity strength or

change functional mobility. The patient’s left lower extremity remained weaker than his right

lower extremity. The patient is independent for all bed mobility and transfers and is modified

independent to ambulate with a RollatorTM. In addition to these standardized measures, the

patient’s perception of improvement was also recorded at time of discharge.

“I feel that I have gotten better at the abdominal bracing since I started therapy. I feel

that I know what exercises I need to be doing at home even though I know I do not

perform them often enough. The heat has really been affecting me lately. I feel tired more

often. I do feel that therapy has been helping with my leg strength.”

Table 4. Outcome Measure ResultsFunctional Outcome Measures

Initial Examination Discharge MDC/Cut-off scores

Timed Up and Go 12.8 seconds 15.5 seconds > 13.5 seconds indicates increased fall risk for community dwelling adults15

5-Time Sit to Stand

25 seconds 25.6 seconds > 2.3 second decrease is cut-off score for identification that patient made clinical improvement11

10-Meter Walk Test

13.2 seconds with use of standard cane

Not established

Gait Speed = 0.76 seconds

Not tested at discharge

Discussion

There are limited studies looking at functional mobility improvements in patients with

multiple sclerosis after botulinum toxin injections and physical therapy interventions. There are

no current studies that use the ICF model for a patient with multiple sclerosis to organize a

patient’s plan of care and assess impairments on an activity and participation level instead of a

body structure impairment level. Prior studies assess the benefits of botulinum toxin injection in

conjunction with physical therapy interventions by considering spasticity by measuring a change

in the Modified Ashworth Scale (MAS) score.7

This case report strived to assess the effectiveness of botulinum toxin injection in

combination with physical therapy interventions to increase functional mobility in a patient with

multiple sclerosis. Timed Up and Go and 5-Time Sit to Stand standardized outcome measures

were administered at the initial evaluation and at discharge to evaluate possible changes in

functional mobility. Measuring success from an activity and participation level associated with

the ICF model emphasizes the main focus of a plan of care when working with individuals with

multiple sclerosis. Along with spasticity, which is the most frequently reported symptom with

MS, symptoms associated with MS lead to gait deviations and immobility which can be

frustrating to individuals.5,16 The interventions incorporated into this patient’s plan of care

address the lower extremity strength deficits, left lower extremity spasticity, balance

impairments, difficulty with transfers/ambulation, and gait deviations.

There were no significant improvements noted from the initial evaluation to discharge in

regard to the standardized outcome measures; TUG and 5-Time Sit to Stand. These results may

be due to a multitude of varying factors. Such factors include day to day fluctuations in the

patient’s functional status, patient’s compliance and consistency with his home exercise

program, increased heat that affected the patient’s performance and fatigue levels, or the

possibility that the effects of the botulinum toxin injection were beginning to wear off. The

patient received the injection in February 2017 and the effects of the injection typically last for 3-

4 months.5,6 Recent studies show that elevated body temperature in individuals with relapsing-

remitting MS was linked to increased fatigue.17 All of these factors may have contributed to the

lack of improvement during the patient’s physical therapy plan of care and at discharge.

Debolt at el, was able to show a 12.7% improvement in the participant’s TUG score after

an 8-week home-based resistance exercise program compared to a control group.16 Unfortunately,

the current case report was not able to replicate these results in an outpatient physical therapy

setting. Therapeutic exercise, neuromuscular re-education, and stretching in conjunction with

botulinum toxin injections did not increase functional mobility in a patient with multiple

sclerosis based on the protocol used in this case report. Furthermore, this case report does

demonstrate the benefits of using the ICF model as a conceptual framework to organize and

classify a patient’s function and demonstrate the complex relationship between the various

factors. The ICF model can assist with physical therapists with the clinical decision-making

process.8

More studies are required to determine a feasible and effective exercise protocol to

improve functional mobility in patients with multiple sclerosis. One recommendation for future

research would be to develop a more intensive protocol that included ROM/flexibility,

therapeutic exercise/strengthening, and neuromuscular re-education after botulinum toxin

injection. Based on feasibility, a duration of 10-14 days of intensive therapy followed by a home

exercise program may be more ideal to enhance the effects of the injection. Higher frequency

interventions may demonstrate more significant improvements in the functional mobility of

patients with multiple sclerosis.

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