Early Administration of Botulinum Toxin for Poststroke Spasticity

Poststroke spasticity is a motor condition that can cause muscle stiffness, involuntary contractions, and pain. Damage to the brain due to a stroke can lead to this condition. Treating poststroke spasticity may include the use of BoNT/A, a drug that can help maintain range of motion of the limb. David M. Simpson, MD, FAAN, is professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City, New York. He is director of the Neuromuscular Diseases Division, director of the Clinical Neurophysiology Laboratories, and director of the Neuro-AIDS Program. As a researcher, his work has focused on the safety and effectiveness of the high-concentration capsaicin patch in the treatment of certain types of painful peripheral neuropathy. In this article, Dr Simpson discusses the safety and effectiveness of BoNT/A in the treatment of poststroke spasticity.

A small study of 52 participants with spasticity following stroke determined that BoNT/A therapy was most effective when initiated within the first 3 months.¹ What is the importance of turning to BoNT/A earlier?

One of the benefits of BoNT/A in the treatment of spasticity is maintaining range of motion of the limb, and maintaining range of motion is an important principle in preventing the development of contracture. It makes sense to consider the use of BoNT/A earlier, with 1 of the goals being to prevent the development of contracture. The longer the patient is spastic with limited range of motion of the limb, and the longer they go without treatments such as BoNT/A, physical therapy, occupational therapy, and nursing, the more likely it is that they will develop a fixed contracture, which is much more difficult to treat.

A key issue is getting patients access to this treatment. The majority of patients with spasticity who might benefit from BoNT/A do not have access for many reasons; there might not be a trained physician in their area, or there may be financial and insurance barriers. The second major barrier is primary care physicians not knowing that this is an available and effective therapy. Finally, we need proper training of an adequate number of injectors, along with more research, to reduce the many barriers in the field and improve patient outcomes.

Spasticity and contractures after stroke are common but can improve with BoNT/A therapy. Given that the Tardieu Scale lacks sensitivity in identifying early onset of spasticity,² what are the qualitative and quantitative markers clinicians can look for in follow-up care to determine whether spasticity is improving with BoNT/A?

We look at the patient holistically, assessing several variables that impact their status and their function. We look at symptoms: are they having pain or difficulty maintaining limb position with bracing, physical therapy, or occupational therapy? We look at their function — their ability to use the limb — whether it be reaching or grasping with the arm or walking with the leg.

Then we examine the patient. We look at the range of motion of the joints and the muscle tone, measured as resistance to passive stretch using the Modified Ashworth Scale. We also look at their ability to use the limb voluntarily, whether it be passive function (what we do for the patient) or active function (what the patients do for themselves). All these elements then factor into our decision to use BoNT/A and where to make the injections. Later, these factors help us when looking for the results of treatment.

According to the limited available research, BoNT/A is most effective at preventing contracture due to spasticity when administered in the acute (1 to 7 days) or early subacute (7 days to 3 months) time frames.³ Within that wide time range, what factors in a clinical evaluation can help determine the optimal time to begin treatment? What factors do you use to decide the initial dosing and placement of injections?

Decisions about dosing and placement are based predominantly on a patient’s clinical picture. If the elbow has severe flexion spasticity, then our target could be the biceps, brachialis, or brachioradialis muscles. If the wrist is flexed, we can inject the wrist flexors, or if the patient is clenched in the hand, we can inject the finger and thumb flexors — those are the types of targets that we can approach.

Dosing really is case by case because — unlike some other indications for BoNT/A such as chronic migraine, where there is a standard recommended dose — spasticity has to be individualized for every patient based on their clinical appearance, the joints affected, their functional deficits, and how much of a dosage we may put into different muscles.

The US Food and Drug Administration (FDA) has the ceiling dose for onabotulinumtoxinA at 400 units for upper and lower limbs and abobotulinumtoxinA at 1000 units for upper limbs and 1500 units for upper and lower limbs.^4,5 However, clinicians often go higher than the ceiling dose, according to their best medical judgment. I have often injected patients at higher doses than the FDA label because both the medical literature and my personal experience support it. I was a co-investigator on the TOWER study (ClinicalTrials.gov identifier: NCT01603459), in which we escalated doses to 800 units in patients with poststroke spasticity, and it showed safety and efficacy at that high, off-label dose.⁶

Safety always comes first, so we need to be cautious when starting therapy in any patient. I generally will start the patient with an on-label dose just to ensure safety and tolerability, and then in subsequent visits I may go higher. In terms of spacing visits, the FDA labels indicate no fewer than 12 weeks between injections,^4,5 but this is not to say we cannot inject earlier safely. In clinical trials in upper limb dystonia in musicians, we injected booster doses at week 2 and week 4, showing safety, efficacy, and no production of neutralizing antibodies, which is 1 of the concerns with frequent doses.⁷ However, the other limitation is the issue of reimbursement; most insurers will not reimburse earlier than 3-month intervals, which is an important factor to consider.

Given that contractures and stiffness are reduced for just 6 weeks following BoNT/A and begin to worsen in the period that follows, how can dosing be managed over time to provide optimal outcomes? ²

Every patient is an individual, and we see how they do with each treatment cycle. When we see the patient in follow-up, we base our decisions on how they did earlier. We may decide to inject higher doses; we may inject different muscles. Modifying the treatment paradigm over time is not uncommon.

I tell patients that the treatment path involves a learning curve. We do not know exactly how they are going to respond early on, so we are going to modify treatment over time. I also try to encourage reasonable expectations, because patients sometimes come in expecting a miracle drug to cure them. I have to tell them, “This is not a cure; it is a treatment to improve spasticity.” If the patient’s expectations are set too high, they may be very disappointed and not want to continue treatment. We know that adherence to treatment is poor, as published data show a very high dropout rate for this protocol.⁸
 
We emphasize that there is no guarantee regarding how long it will take to get better and that it can take numerous cycles to see improvement. Often, the first few treatment cycles show dramatic improvement, and then the patient may not even notice the improvements with maintenance therapy because they have forgotten how bad they were when we first started. It takes time to get to that maintenance therapy, but after 3 cycles, we want them to show substantial improvement. If they do not show any improvement by 3 cycles, I begin to worry that this may not be the right treatment for them.

Do you see a clinical difference in patients’ BoNT/A response depending on the body parts impacted by spasticity? If so, how does that guide you when delivering treatment?

What is more important than the muscle location is the skill of injectors. Spasticity and other limb injections are challenging because the injector needs to know the anatomy very well and they need to know how to target the needle using techniques such as ultrasound, EMG, or electrical stimulation. If they do not have that skill set, they may not get optimal results.

We recommend using targeting techniques for virtually all limb muscles. You might argue that some muscles, such as the biceps, are easier to target than others, but even there, targeting is extremely important. Certain muscles are very challenging to properly inject, such as individual fascicles of muscles of the finger flexors, so targeting is essential.
 
The choice of equipment used to target the muscles depends on the experience and training of the injector. We have done a systematic head-to-head study comparing ultrasound to electrical stimulation in targeting of the upper limb in spasticity and dystonia, and we found they delivered relatively similar results.⁹ I feel pretty confident that any targeting technique is superior to nontargeted, surface anatomy guidance.
 
This Q&A was edited for clarity and length.

Disclosures

David M. Simpson, MD, reported affiliations with Shionogi USA, Inc; Vertex Pharmaceuticals, Inc; AbbVie, Inc; and Alexion Pharmaceuticals, Inc.

References

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4. Botox^®. Prescribing information. Allergan, Inc; 2023. Accessed March 27, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/103000s5327lbl.pdf

5. Dysport^®. Prescribing information. Ipsen Biopharm Limited; 2023. Accessed March 27, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125274s125lbl.pdf

6. Wissel J, Bensmail D, Ferreira JJ, et al. Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: the TOWER study. Neurology. 2017;88(14):1321-1328. doi:10.1212/WNL.0000000000003789

7. Frucht SJ, George MC, Pantelyat A, et al. Incobotulinum toxin-A in professional musicians with focal task-specific dystonia: a double blind, placebo controlled, cross-over study. Tremor Other Hyperkinet Mov (N Y). 2024;14:32. doi:10.5334/tohm.903

8. Simpson DM, Bouchard J, Page S, Spurden D, Goldfarb S, Patel AT. Botulinum neurotoxin treatment dynamics and persistence over 2 years in patients with cervical dystonia or spasticity: a retrospective claims database analysis. Toxicon. 2024;237(suppl 1):107489. doi:10.1016/j.toxicon.2024.107489

9. Hauret I, Dobija L, Givron P, Goldstein A, Pereira B, Coudeyre E. Effectiveness of ultrasound-guided vs electrical-stimulation-guided botulinum toxin injections in triceps surae spasticity after stroke: a randomized controlled study. J Rehabil Med. 2023;55:jrm11963. doi:10.2340/jrm.v55.11963