OnabotulinumtoxinA for Post-Stroke Spasticity: Treatment Strategies and Limitations
The main constraint to botulinum toxin use for spasticity is dosage limitation.
Spasticity is a common occurrence following stroke, with an estimated 20% to 40% of patients developing spasticity that hampers activities of daily living (ADL). Lower limb spasticity in particular is associated with impairments of gait and mobility.1
Several types of therapy are available to facilitate post-stroke recovery of movement, including the use of botulinum toxin injections, as well as physical therapy and anti-spasmodic medications as first-line options. Other therapies such as ultrasound, magnetic stimulation, and transcutaneous electrical stimulation may be added to the treatment plan to improve motor performance, but no one treatment stands out as superior to the others. In the most severe and persistent cases, surgery is a final option.
Improvements with these therapies are often less than optimal, according to David M. Simpson, MD, FAAN, director, Clinical Neurophysiology Laboratories and director of the neuromuscular division, Icahn School of Medicine, Mount Sinai Medical Center in New York City. He told Neurology Advisor, “Treatment goals are individualized for each patient. In some more severely affected patients, only passive goals are possible, such as improvement in limb position, caregiver dressing, or applying braces. In others, higher level active functional goals are possible, such as improved arm use and gait.”
In an interview with Neurology Advisor, Randie M. Black-Schaffer, MD, MA, medical director of the stroke program, director of the Stroke Research and Recovery Institute at Spaulding Rehabilitation Hospital in Boston, Massachusetts, and assistant professor of physical medicine and rehabilitation, Harvard Medical School in Cambridge, Massachusetts, explained the common clinical approach to these rehabilitative therapies. “Typically, physical medicine and rehabilitation physicians (physiatrists) recommend physical therapy first to see if a regular stretching program for the spastic muscles will adequately control the muscle tone. If not, the second option is a trial of muscle relaxant medications, [al]though the sedative effects of these medications often limit or preclude their use in neurologically impaired patients. If neither of these approaches provides adequate relief, the next step would be to evaluate the patient for botulinum toxin injections and/or phenol nerve block.”
Botulinum Toxin Type A for Spasticity
“Botulinum toxin is proven as a safe and effective treatment for spasticity and is FDA [US Food and Drug Administration]-approved for that indication,” reported Dr Simpson, who is the co-investigator in several studies on botulinum toxin for upper limb spasticity.2-4 “While there are few head-to-head studies of other treatments, we have published a placebo-controlled trial showing superior tolerability and efficacy of onabotulinumtoxinA compared with oral tizanidine (TZD) for upper extremity spasticity,” he said.2 That study concluded that botulinum toxin was both safer and more effective than TZD in reducing tone and disfigurement in upper extremity spasticity and recommended that it be used as first-line therapy.2
“In the lower extremities, these injections are effective in reducing spastic equinovarus posturing, painful toe flexion, stiff knee, flexed knee posturing, and scissoring leg movements that can interfere with gait, positioning, and/or hygiene,” Dr Black-Schaffer said. “In the upper extremities, injections can reduce painful shoulder adduction, and hand clenching, as well as excessive elbow flexion.”
“The effect of injections usually starts 3 to 8 days after the injections, peaks at 2 to 3 weeks, and lasts for 2-1/2 to 3 months,” Dr Black-Schaffer noted, adding that, “There's no medical contraindication to repeated botulinum toxin injections in the same muscles over time. Gradually, after years of botulinum toxin injections to the same muscles, they develop some degree of atrophy, which may enable reduction of the dose.”
The main constraint to botulinum toxin use for spasticity is dosage limitation. Concerns over the potential development of resistant antibodies from too frequent injections that might reduce the therapeutic efficacy of the agent led to restrictions of total dosage to a maximum of 400 units every 3 months. As Dr Black-Schaffer pointed out, “Many patients after a stroke have spasticity throughout both their affected arm and affected leg, with many more muscles involved than a physician can inject, given that limitation. So, the physician must evaluate the patient carefully to decide which muscles it will be most helpful to inject and why.”
Dr Black-Schaffer outlined her rationale for determining when to use botulinum toxin following stroke. “The usual reasons for injecting [a patient] are to improve function or ease of ADL performance. For example, it is often possible to increase gait speed and cadence and reduce gait deviations such as inversion and hip hiking by injection of the plantar-flexor and invertor muscles of the effected leg,” she said. “A third reason is to reduce pain that may be caused by the muscle stiffness. An example is painful shoulder due to severe adductor tone in the arm, which can be significantly improved by botulinum toxin injection to the pectoralis major muscle. This may not improve the patient's ability to move the arm, but can reduce pain with passive abduction, [such] as for bathing and dressing.”
Phenol nerve block injections are also commonly used as a botulinum-toxin-sparing strategy, she reported, explaining that phenol nerve block is an older technique utilized extensively before botulinum toxin became available, that can have muscle-relaxing effects similar to botulinum toxin in large muscles, such as the hip adductors, plantar flexors, and invertors of the affected leg. Injecting phenol into the obturator nerve, for example, reduces contractility of all the hip adductor muscles, saving doses of botulinum toxin for other smaller sites phenol does not have effects on, according to Dr Black-Schaffer.
Dr Simpson pointed to the need to begin therapy when spasticity is first detected. “As soon as spasticity is functionally disabling, one might consider treatment with botulinum toxin,” he said. “Once spasticity has become established in a patient's muscles, it rarely resolves spontaneously,” Dr Black-Schaffer added.
Some patients, however, have such severe spasticity that 400 units of botulinum toxin provides little relief. “For those patients, there are additional treatment options, including the intrathecal baclofen pump and surgical lengthening of the tendons of specific spastic muscles. The baclofen pump can relieve muscle stiffness with less baclofen and less sedation than when the patient takes baclofen by mouth,” Dr Black-Schaffer said, adding that, “On the other hand, the baclofen pump is more effective for lower than upper extremity spasticity and requires visits to a specialized center several times per year for refills. In addition, there are several possible complications such as catheter dislodgement, breakage, and pump site infection, and the pump itself must be surgically replaced when its battery dies.”
- Nakawah MO, Lai EC. Post-stroke dyskinesias. Neuropsychiatr Dis Treat. 2016;12:2885-2893.
- Simpson DM, Gracies JM, Yablon SA, et al. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study. J Neurol Neurosurg Psychiatry. 2009;80:380-385.
- Gracies JM, Bayle N, Goldberg S, Simpson DM. Botulinum toxin type B in the spastic arm: a randomized, double-blind, placebo-controlled, preliminary study. Arch Phys Med Rehabil. 2014;95:1303-1311.
- Kaku M, Simpson DM. Spotlight on botulinum toxin and its potential in the treatment of stroke-related spasticity. Drug Des Devel Ther. 2016;10:1085-1099.