Impact of Short Term OnabotulinumtoxinA Treatment on Dependency and Cost-of-Care in Patients with Spasticity Secondary to Upper Motor Neuron Syndrome

Research Article

Phys Med Rehabil Int. 2015;2(2): 1034.

Impact of Short Term OnabotulinumtoxinA Treatment on Dependency and Cost-of-Care in Patients with Spasticity Secondary to Upper Motor Neuron Syndrome

Gryfe P1* and Sharma S2

1Assistive Technology Clinic (ATC) at Sunnybrook Health Sciences Centre and the ATC Spasticity Management Clinic at Baycrest Health Sciences Centre, Toronto, ON

2Sunnybrook Health Science Centre, Department of Medicine, Division of Physiatry, Toronto, ON and ATC Spasticity Management Clinic, Baycrest Centre, Toronto, ON

*Corresponding author: Gryfe P, Clinical and Managing Director, Assistive Technology Clinic Baycrest Site, 3560 Bathurst St Toronto, ON

Received: January 08, 2015; Accepted: February 18, 2015 Published: February 19, 2015


Background: Central nervous system injury or neurodegenerative disease with associated upper motor neuron damage often produces spasticity, with patients having physical disability, pain, and limitations in their ability to perform activities of daily living.

Objective: This open-label, non-randomized trial of adult outpatients with spasticity evaluated the impact of a single injection of onabotulinumtoxinA (BOTOX®, Allergan, Inc.) compared to a wait-listed control group on caregiver dependency, cost, and pain scores.

Methods: A convenience sample of 67 patients participated in the study. 42 patients (mean age 50.8 ± 18.85 years) in a multidisciplinary outpatient adult spasticity management clinic received a single injection of onabotulinumtoxinA plus standard care. 25 age-matched (mean age 50.54 ± 18.38 years) wait-listed controls received standard care. At month 1 and 3 follow-up visits, surveys to assess dependency, cost, and pain were administered.

Results: Of the 67 patients, 7 (2 treatment group and 5 wait-listed group) were lost to follow-up. The average dose of onabotulinumtoxinA administered was 420 U (range 100 to 600 U). The 38 onabotulinumtoxinA-treated patients exhibited statistically significant improvements in their degree of dependency (8.23 hour per week reduction in caregiver assistance [p=0.001]), their community cost subscale (decrease of $157 per week [p=0.001]), and pain (5.2 point reduction [p=0.017]). Wait-listed control group subjects exhibited no significant changes.

Conclusions: These findings suggest that a single injection of onabotulinumtoxinA plus standard care produces significant improvements in caregiver dependency, cost, and pain in adults with spasticity due to upper motor neuron syndromes. A larger well-controlled, randomized, study is warranted.

Keywords: Onabotulinumtoxin A; Dependency; Cost; Pain


ADL: Activities of Daily Living; CP: Cerebral Palsy; CVA: CerebroVascular Accident; MAS: Modified Ashworth Scale; MPQ: McGill Pain Questionnaire; MS: Multiple sclerosis; NPCNA: Northwick Park Community Needs Assessment; NPDS: Northwick Park Dependency Score; PPI: Present Pain Index; PSW: Personal Support Worker; QALY: Quality Adjusted Life Year; SC: Standard care; SCI: Spinal cord injury; SD: Standard deviation; SF-36: Short Form 36-item; SFMPQ: Short Form McGill Pain Questionnaire; SIP: Sickness Impact Profile; TBI: Traumatic brain injury; UMNS: Upper motor neuron syndrome; VAS: Visual Analog Scale


Spasticity is characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks that occurs as a part of the upper motor neuron syndrome (UMNS) [1]. Spasticity may occur secondary to a wide variety of central nervous system injuries or neurodegenerative diseases such as cerebrovascular accident (CVA) or stroke, spinal cord injury (SCI), traumatic brain injury (TBI), multiple sclerosis (MS), cerebral palsy (CP), or anoxicischemic encephalopathy, with the epidemiology of spasticity being dependent upon its origins [1].

It is estimated that spasticity affects more than 12 million people worldwide. Reported prevalence rates range from 17% to 38% among post-stroke survivors [2,3,4,5,], 17% to 53% of those with MS [6,7,8], 40% to 78% of those with SCI [9,10,11,12,13,14]; and up to 34% of those with TBI [1,15].

Once developed, UMNS and spasticity can cause severe problems such as contractures and painful limb deformities that impact patient positioning, movement, skin integrity, seating and mobility, and their ability to perform activities of daily living (ADLs) [1]. As a result, patients with spasticity and UMNS may be highly dependent on caregivers; so much so, that some consider that spasticity as a secondary complication of the UMNS is more of a limiting factor than the actual disease itself. In addition, motor over-activity often interferes with patient and caregiver functions and has an impact on the patient’s overall health-related quality of life [16].

Botulinum toxin type A injection has been used to achieve therapeutic benefits across a wide range of clinical conditions, including that of spasticity associated with UMNS [17,18,19,20,21,22,23]. Ward et al recently reported that the use of botulinum toxin type A (onabotulinumtoxinA) added to standard care as part of a goal-oriented rehabilitation in post-stroke spasticity patients significantly increased passive goal achievement and was associated with higher levels of active function [23]. An evidencebased review and assessment of botulinum toxin type A reported a Level A recommendation for the use of the onabotulinumtoxinA formulation in upper limb spasticity as well as in lower limb spasticity [1]. The primary outcome measures assessed in the evaluated studies were those related to muscle tone using instruments such as the modified Ashworth Scale (MAS), and patient- and/or investigatorreported outcomes such as health-related quality of life and perceived improvements. Few if any studies assessed functional benefits of tone reduction or the degree of residual dependency patients experience with the treatment effect. This may be, in part, due to the notion that the problems experienced by patients with UMNS are so broad and individual that generic standard measures of function may not be sensitive to change [16]. Likewise, few studies have explored the economic impact of botulinum toxin A treatment. Three groups of investigators [24,25,26] explored the economic impacts of therapy; all concluding that further investigation was required to quantify caregiving and/or nursing utilization costs as they are likely to be major drivers of cost.

This study aimed to investigate the impact of a single treatment with onabotulinumtoxinA plus standard care (SC) on caregiver dependency, costs and pain, in patients with moderate-to-severe spasticity due to UMNS.


Study design

The study was an open-labeled, non-randomized evaluation of onabotulinumtoxinA (BOTOX®, Allergan, Inc.) plus standard care (SC) treatment and a wait-listed plus SC controlled group design that was approved by the Research Ethics Committee of Sunnybrook Health Sciences Centre, a large academic health sciences centre in Toronto, Ontario, Canada and the University of Toronto. The waitlisted plus SC controlled design was an ethical alternative to a placebocontrolled group. At the spasticity clinics in Toronto waiting lists may vary from 4 to 12 months in duration. This design afforded wait-listed patients to participate in the SC control group and compare these changes with those of patients in the onabotulinumtoxinA plus SC treatment group across equivalent time intervals. Inclusion of the wait-listed SC control group reduced possible reactive effects of the experimental procedure, consequently improving external validity for the pre-test/post-test design [27].

Patient recruitment

Patients with moderate-to-severe spasticity due to a UMNS were identified from various interdisciplinary outpatient clinics at Sunnybrook Health Sciences Center. Included patients were required to have spasticity that was interfering with ambulatory function or their ability to perform ADLs, were cognitively intact, able to provide informed consent, and able to speak English or had an English speaking caregiver.

Individuals excluded from participating were those: with pain having no significant effect on function; whose medical condition could be adversely affected by the receipt of botulinum toxin (eg, myasthenia gravis or Eaton-Lambert syndrome); with a fear of needles or pain sensitivity; who had received botulinum toxin injections within the last 4 months, or who had a surgical procedure for spasticity that required general anesthesia.

Potential subjects were contacted by research assistants via telephone. Subjects allocated to the wait-listed control group (CONT) provided verbal consent and were mailed the three questionnaires to complete (baseline data), with a second set of these three questionnaires completed after 1 to 3 months when they were seen in the clinic for the first time. Eligible subjects, or their authorized representative, allocated to the onabotulinumtoxinA treatment group (OBTA) were seen in the clinic where they provided consent after being informed by the clinic physiatrist of the injection procedure, its potential benefits and side effects. OBTA-treatment allocated subjects completed the three questionnaires prior to receiving the first (single) injection and recompleted these questionnaires at 1 to 3 months postinjection. Subjects in both allocation groups (i.e. OBTA or CONT) continued to receive their standard of care which included current oral medications ( ie. Baclofen™, Lioresol™, or Dantrium™) and regular occupational or physical therapy regimens ( ie. 2-3 times per week of OT and/or PT standard range of movement and stretching programs).

A total 215 patients were considered for study inclusion, with 148 being excluded due to not meeting inclusion criteria or other reasons (Figure 1). Of the 67 eligible patients, 41 were allocated to the onabotulinumtoxinA injection plus SC group and 26 were allocated to the wait-listed SC alone control group. The groups were similar with respect to mean age, percentages of males and females, and having an underlying UMNS.