Effective Management of Adult Spasticity: Tailoring Botulinum Toxin Therapies
Spasticity, a common condition resulting from various neurologic disorders, including stroke, multiple sclerosis, spinal cord injury, cerebral palsy, and traumatic brain injury, has profound implications for patients’ quality of life.1 Characterized by increased muscle tone and exaggerated tendon jerks, spasticity leads to pain, difficulty maintaining hygiene, posture problems, and even complications such as joint contractures and possible permanent deformity. Beyond its physical effects, spasticity-related discomfort can have psychologic consequences that affect mood and self-esteem.2 The prevalence of spasticity in the United States and the rate at which it occurs from various causal conditions can be found in Figure 1.3,4
Pathophysiology and Clinical Presentations of Spasticity
Understanding the pathophysiology of spasticity and its clinical presentations are crucial for healthcare professionals to effectively address this challenging condition. While the exact mechanisms of spasticity remain somewhat elusive, current research provides valuable insights. A stroke can often lead to spasticity, as damage to the motor cortex and the corticospinal tract leads to initial muscle weakness, typically on 1 side of the body. Incoordination and joint immobilization may follow, along with neuroplastic changes, including the loss of cortical inhibition. Medial reticulospinal hyperexcitability may play a central role in spasticity, as it can result in elevated spinal motor neuron excitability and hyperreflexia. These adaptations may explain clinical features of spasticity, such as exaggerated stretch reflexes, velocity-dependent resistance to movement, muscle overactivity, and spontaneous motor unit firings.2
Muscle overactivity in a joint position at shortened muscle lengths contributes to limb immobilization and development of contractures, with accumulation of hyaluronan deposits further decreasing lubrication between collagen and muscle fibers and leading to increased perceived stiffness. This collective effect contributes to increased resistance or spastic hypertonia. Postural patterns that are common in patients with spasticity include elbow and finger flexion and equinovarus, which are usually representations of underlying imbalance or weakness and hypertonia. These postures can lead to skin issues, pressure sores, spastic foot drop, and abnormal gait patterns.2 Patients with upper limb spasticity encounter difficulties in posture, positioning, and performing routine tasks, whereas patients with lower limb spasticity may experience hindered mobility and modified gait, which can impair mobility, cause limb pain, and increase the risk for falls.1,3
Botulinum Toxin Therapy for Treating Spasticity
Effectively managing spasticity is vital for improving patients’ quality of life, alleviating symptoms, and enhancing function. Treatment options are diverse and tailored to each patient’s unique needs; they may include orthotics, assistive devices for walking, oral medications, intrathecal baclofen, botulinum toxin (BoNT) therapy, and surgeries or procedures.1 This article focuses on the use of BoNT in spasticity treatment.
BoNT therapy temporarily relaxes muscles by reducing acetylcholine neurotransmission.5 It is important to note that there are pharmacologic differences between different BoNT preparations, which should be considered when prescribing BoNT. It is also important to note that BoNT is efficacious for symptom control, but it does not play a role in disease modification.6 Effects of BoNT appear several days after injection and last approximately 3 months. Recurrence may result from regained neuromuscular junction function, necessitating injections every 3 to 4 months.2
BoNT therapy effectively benefits various patient populations, offering a better adverse-event profile than oral medications and more target specificity.2 Possible side effects include botulism-like syndrome, exaggerated muscle weakness, dysphagia, and difficulty with breathing or speech.7 Precise dosing and injection techniques are crucial to mitigate these risks; the appropriate muscle targets for BoNT therapy for spasticity can be found in Table 1.5
Approved Therapies for Spasticity: Expanding Treatment Horizons
The US Food and Drug Administration (FDA) has approved several BoNTs to address spasticity, offering healthcare professionals a range of options to tailor treatment to individual patient needs. Below are descriptions of BoNTs that are recommended for the treatment of spasticity.
OnabotulinumtoxinA
OnabotulinumtoxinA (onaBoNT-A) was first approved in 1989 for the treatment of blepharospasm and strabismus in adults, and it is now approved for 12 therapeutic indications. In July 2021, the FDA granted expanded approval to onaBoNT-A for 8 additional muscles for the treatment of upper limb spasticity in adults, including muscles in the elbow, forearm, intrinsic hand, and thumb muscles, as well as the use of ultrasound as a muscle localization technique, thereby enhancing treatment precision.3
OnaBoNT-A is approved for the treatment of spasticity in patients aged 2 years or older, which it achieves by inhibiting the release of acetylcholine, temporarily blocking nerve signals in muscles, and leading to a localized reduction in muscle activity. Common adverse events of onaBoNT-A when used to treat spasticity include pain in the extremity when used in adults and upper respiratory tract infection when used in pediatric patients.8
AbobotulinumtoxinA
AbobotulinumtoxinA (aboBoNT-A) first gained FDA approval in 2015 for the treatment of upper limb spasticity in adults; its approval was expanded in 2016 to children aged 2 years or older with lower limb spasticity, and expanded again in 2017 for the treatment of adults with lower limb spasticity.9 Similar to onaBoNT-A, aboBoNT-A inhibits the release of acetylcholine to achieve muscle relaxation and reduce spasticity.10
Common adverse reactions of aboBoNT-A when used for the treatment of spasticity include falls, muscular weakness, and pain in the extremity in adult patients treated for lower limb spasticity; muscular weakness in adult patients treated with upper limb spasticity; upper respiratory tract infection and pharyngitis in pediatric patients treated for upper limb spasticity; and nasopharyngitis, cough, and pyrexia in pediatric patients treated for lower limb spasticity. AboBoNT-A should be administered with care in patients aged 65 years or older, as this population has shown a greater frequency of concomitant disease, other drug therapies, and falls. It should also be noted that when used to treat adult patients for lower limb spasticity, muscle weakness was more frequently observed in women than in men.10
IncobotulinumtoxinA
IncobotulinumtoxinA (incoBoNT-A) was first approved by the FDA in 2009 and is indicated for the treatment of 5 conditions, including upper limb spasticity in both adult and pediatric patients, excluding spasticity caused by cerebral palsy. IncoBoNT-A is thought to work by binding to cholinergic nerve terminals, disrupting the release of SNAP25, which is a presynaptic target protein essential for the release of acetylcholine, thereby resulting in muscle relaxation and relief from spasticity.11
Common adverse reactions of incoBoNT-A to treat upper limb spasticity include seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection when treating adults, and nasopharyngitis and bronchitis when treating pediatric patients.11
RimabotulinumtoxinB
RimabotulinumtoxinB (rimaBoNT-B) is indicated for cervical dystonia and sialorrhea, but it has been determined to be probably safe and effective for the treatment of upper limb spasticity in adult patients.6,12 RimaBoNT-B works by binding to cholinergic nerve terminals, causing enzymatic cleavage of synaptic vesicle-associated membrane protein, a presynaptic target protein that is essential for the release of acetylcholine.12
Common adverse events of rimaBoNT include dry mouth, dysphagia, injection site pain, and headache.12 A summary of the BoNTs for the treatment of spasticity, including their FDA-approved indications, dosage, and administration for spasticity, can be found in Table 2.8,10-13
Guidelines and Recommendations
In 2016, the American Academy of Neurology published an update to their existing practice guidelines on the use of BoNTs in adult spasticity, based on new research findings.6
Upper Extremity Spasticity
AboBoNT-A, incoBoNT-A, and onaBoNT-A are deemed safe and effective for reducing adult upper limb spasticity and improving passive function, backed by multiple class I studies, and rimaBoNT-B is considered probably safe and effective for reducing adult upper limb spasticity. However, data on the efficacy of these drugs to improve active function related to adult upper limb spasticity were inadequate.6
Lower Extremity Spasticity
AboBoNT-A and onaBoNT-A are established as safe and effective treatments for reducing adult lower limb spasticity, based on multiple class I studies. However, data on the efficacy of these drugs to improve active function related to adult lower limb spasticity were inadequate.6
Techniques to Enhance BoNT Effectiveness
Various techniques have been explored to enhance the clinical effects of BoNTs. A study on onaBoNT-A found that high-volume, low-potency injections and endplate targeting into proximal upper extremity muscles are probably effective strategies for enhancing tone reduction in adult spasticity.6 While the superiority of any particular technique over another is yet to be established, studies consistently show that techniques involving electromyography, electrical stimulation, or sonography are more effective than anatomic localization through muscle palpation.2,5
Techniques to Enhance Tone Reduction
Both high-volume, low-potency injections of onaBoNT-A and endplate targeting of onaBoNT-A into proximal upper extremity muscles are probably effective for enhancing tone reduction in adult spasticity, as supported by 2 class I studies. However, there is insufficient evidence to determine the superiority of specific techniques for guiding BoNT injection placement, as outcomes from 1 class II study were inconsistent.6
Early Treatment
The timing of BoNT therapy initiation varies, with some studies suggesting that treatment as early as 3 to 6 months after disease onset can effectively manage muscle hypertonia and reduce the risk of later complications, such as contracture development. An exploratory, double-blind, randomized, placebo-controlled trial of aboBoNT-A demonstrated that early treatment significantly delayed time to reach reinjection criteria.2
References
1. Esquenazi A, Bavikatte G, Bandari DS, et al. Long-term observational results from the ASPIRE study: onabotulinumtoxinA treatment for adult lower limb spasticity. PM R. 2021;13(10):1079-1093. doi:10.1002/pmrj.12517
2. Whitcup SM, Hallett M, eds. Handbook of Experimental Pharmacology 263: Botulinum Toxin Therapy. Springer Nature; 2021. http://donglab.hms.harvard.edu/ewExternalFiles/bok_978-3-030-66306-3.pdf
3. FDA approves expanded BOTOX® (onabotulinumtoxinA) label to include eight new muscles to treat adults with upper limb spasticity. News release. AbbVie Inc. July 29, 2021. Accessed September 19, 2023. https://news.abbvie.com/news/press-releases/fda-approves-expanded-botox-onabotulinumtoxina-label-to-include-eight-new-muscles-to-treat-adults-with-upper-limb-spasticity.htm
4. Esquenazi A, Jost WH, Turkel CC, Wein T, Dimitrova R. Treatment of adult spasticity with Botox (onabotulinumtoxinA): development, insights, and impact. Medicine (Baltimore). 2023;102(S1):e32376. doi:10.1097/MD.0000000000032376
5. Chiu SY, Burns MR, Malaty IA. An update on botulinum toxin in neurology. Neurol Clin. 2021;39(1):209-229. doi:10.1016/j.ncl.2020.09.014
6. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(19):1818-1826. doi:10.1212/WNL.0000000000002560
7. Santamato A. High doses of botulinum toxin type A for the treatment of post-stroke spasticity: rationale for a real benefit for the patients. Toxins (Basel). 2022;14(5):332. doi:10.3390/toxins14050332
8. Botox®. Prescribing information. Allergan USA, Inc; 2023. Accessed September 19, 2023. https://www.rxabbvie.com/pdf/botox_pi.pdf
9. Ipsen announces FDA approval of Dysport® (abobotulinumtoxinA) for the treatment of lower limb spasticity in adults. News release. Ipsen Biopharmaceuticals. June 16, 2017. Accessed September 19, 2023. https://www.ipsen.com/canadafr/blog/press-releases/ipsen-announces-fda-approval-of-dysport-abobotulinumtoxina-for-the-treatment-of-lower-limb-spasticity-in-adults/
10. Dysport®. Prescribing information. Ipsen Biopharmaceuticals, Inc; 2023. Accessed September 19, 2023. https://www.galderma.com/us/sites/default/files/2023-05/Dysport_USA_PI.pdf
11. Xeomin®. Prescribing information. Merz Pharmaceuticals; 2021. Accessed September 19, 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=ccdc3aae-6e2d-4cd0-a51c-8375bfee9458&type=display
12. Myobloc®. Prescribing information. Solstice Neurosciences; 2021. Accessed September 19, 2023. https://www.myoblochcp.com/sites/g/files/othskp1146/files/2023-06/MYOBLOC_PI.pdf
13. 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(7):1303-1311. doi:10.1016/j.apmr.2014.03.016
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Reviewed October 2023
