Comparing the real-world effectiveness of botulinum toxin type A injections across distinct poststroke muscle hyper-resistance patterns

 

But botox DOES NOTHING TO CURE SPASTICITY!

Obviously these researchers don't think much of the ridiculous opinion of Dr. William M. Landau!

Spasticity After Stroke: Why Bother? Aug. 2004)

Comparing the real-world effectiveness of botulinum toxin type A injections across distinct poststroke muscle hyper-resistance patterns

• 

  Xuncan Liu 1

• 

  Chen Chen 2

• 

  Yanmin Ju 1

• 

  Liang Zhao 1

• 

  Guoxing Xu 1

• 

  Yinxing Cui 1

• 

  He Li 1

• 

  Xiaowei Chen 1

• 

  Zhenlan Li 1*

• 1. Department of Rehabilitation, The First Hospital of Jilin University, Changchun, Jilin, China

• 2. Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin, China

Abstract

Background: 

Post-stroke muscle hyper-resistance is produced by both neurogenic (spasticity) and non-neurogenic (contracture) factors. BoNT-A is the most effective intervention for post-stroke spasticity, yet whether concomitant contracture alters its therapeutic benefit remains unclear.

Aims: 

To compare BoNT-A effectiveness in plantar-flexor hyper-resistance stratified by contracture.

Methods: 

We retrospectively reviewed stroke survivors with spastic hemiplegia and ankle plantar-flexor hyper-resistance who received BoNT-A injections. Patients were stratified into two groups according to the presence of restricted passive ankle dorsiflexion: the spasticity group (PROM limitation <7°) and the spasticity-with-contracture group (PROM limitation ≥7°). Outcomes were assessed at baseline and at 2, 4 and 12 weeks post-injection, including the Modified Ashworth Scale (MAS) for plantar-flexors, Brunnstrom Recovery Stage (BRS), Fugl–Meyer Assessment (FMA) lower-extremity subscore and Barthel Index (BI).

Results: 

A total of 107 patients were enrolled—54 in the spasticity group and 53 in the spasticity-with-contracture group. Baseline comparison revealed a significantly longer disease duration in the spasticity-with-contracture group; other characteristics were comparable. Both groups achieved improvements in MAS and BRS at all three follow-up visits. FMA and BI improved in the spasticity group at 4 and 12 weeks, whereas the spasticity-with-contracture group showed improvement only at 12 weeks. Between-group analyses indicated that MAS and BRS scores were consistently better in the spasticity group at each time point; although median FMA and BI were numerically higher in this group, the differences did not reach statistical significance.

Conclusion: 

BoNT-A markedly reduces(NOT CURES!) post-stroke hyper-resistance and enhances motor function and activities of daily living; by contrast, concomitant contracture is associated with delayed and attenuated improvement in MAS and BRS.

More at link.

Optimizing Recovery: An Opportunity to Improve Access to Post-stroke Rehabilitation Care in Rural Settings

 

'ACCESS' has almost nothing to do with recovery! ARE YOU THAT BLITHERINGLY STUPID? 100% RECOVERY PROTOCOLS ARE NEEDED!

Optimizing Recovery: An Opportunity to Improve Access to Post-stroke Rehabilitation Care in Rural Settings

Kiera Murphy • Sarahrose Jonik • Andrew J. Rothka • Neyha Cherin

Published: June 13, 2025 DOI: 10.7759/cureus.85939 Peer-Reviewed Cite this article as: Murphy K, Jonik S, Rothka A J, et al. (June 13, 2025) Optimizing Recovery: An Opportunity to Improve Access to Post-stroke Rehabilitation Care in Rural Settings. Cureus 17(6): e85939. doi:10.7759/cureus.8593

Abstract

Post-stroke spasticity (PSS) is a debilitating sequela that can lead to significant pain, severe functional decline, worse health outcomes, higher mortality rates, and increased healthcare costs. Botulinum toxin (BTX) injections are a widely recognized treatment modality to combat PSS. Not surprisingly, given that BTX administration requires a specialized provider and in-person visits, patients in rural communities are often unable to receive this vital intervention.

We present the case of a 59-year-old male who suffered a left ischemic thalamic stroke resulting in severe PSS. He was initially taken to a large academic center for his stroke care, followed by a two-week inpatient rehabilitation stay, during which he made significant progress. Unfortunately, once discharged to his rural community, he was lost to follow-up. Over time, he developed painful upper and lower extremity spastic hemiparesis, which impaired his ability to ambulate, complete independent activities of daily living (ADLs), and led to severe depression. Fortunately, the patient’s neighbor noted a significant decline in function and quality of life, prompting her to bring him to her Physical Medicine and Rehabilitation provider for possible intervention. Due to the kindness of his neighbor, the patient was able to reestablish care two hours away, allowing him to initiate BTX injections and address the unique challenges posed by his worsening spasticity.(Botox does nothing to cure spasticity, so you're leaving this patient disabled!)

In response to the patient’s rural residence, the authors developed a post-stroke telehealth follow-up protocol to ensure continuous virtual monitoring between in-person BTX injections. This case illustrates the potential of telemedicine to bridge the gap in care for patients residing in rural areas by leveraging the growing availability of internet access. We discuss the successful implementation of this telehealth follow-up protocol and propose it as a sustainable model for delivering essential care to underserved rural populations.

Introduction

Stroke is the leading cause of long-term adult disability in the United States, affecting over 700,000 people annually [1]. Despite remarkable advances in research aimed at improving mortality outcomes, the comorbid complications from the initial neurologic insult - such as post-stroke spasticity (PSS) - continue to plague stroke survivors. According to the American Stroke Association, 25%-43% of stroke survivors experience PSS [2]. PSS commonly develops within the first three months post-stroke, with younger patients noted to be at higher risk [2]. When unchecked, uncontrolled spasticity can result in debilitating functional outcomes, severe pain, and impaired quality of life [3]. The scientific literature emphasizes early intervention, including botulinum toxin (BTX) injections, as paramount to minimizing the morbidity and mortality associated with PSS [4]. However, despite these advancements, translating research findings into real-world applications remains challenging - particularly for patients residing in rural areas. Existing disparities in rural healthcare access - such as provider shortages, limited access to specialists, and transportation barriers - exacerbate this gap, often leaving patients without timely or appropriate interventions. We hypothesize that vastly disproportionate access to standard medical care and resource availability, based on location of residence, is a major reason for this disconnect.

Efficacy of Botulinum Toxin Combined With Rehabilitation Treatments In The Treatment of Post-Stroke Spasticity: A Systematic Review and Network Meta-Analysis

 

You say nothing on whether any of this cured the spasticity. Survivors want spasticity cured, not managed or treated!  You'll want spasticity cured when you are the 1 in 4 per WHO that has a stroke!

 You won't like Dr. William M. Landau's uninformed 'expert' opinion after your stroke.  Survivors would immediately disabuse him of that notion. When comeuppance hits him with his stroke he'll regret his ideas on the matter. 

His statement from here:

Spasticity After Stroke: Why Bother? Aug. 2004 

The latest here:

Efficacy of Botulinum Toxin Combined With Rehabilitation Treatments In The Treatment of Post-Stroke Spasticity: A Systematic Review and Network Meta-Analysis

Meihua Ke, Dongxia Li, […], and Jianjun Long https://orcid.org/0009-0009-6058-8946 longjianjun@szu.edu.cn+6View all authors and affiliations

OnlineFirst

https://doi.org/10.1177/10538135241290110

• • Abstract
  • Introduction
  • Materials and methods
  • Results
  • Discussion
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  • Acknowledgments
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Abstract

Background

There is growing interest in the combination of botulinum toxin (BoNT) and rehabilitation techniques for the treatment of post-stroke spasticity. Nevertheless, systematic evaluations of this approach are scarce.

Objective

To systematically evaluate the efficacy of BoNT combined with rehabilitation techniques for post-stroke spasticity.

Methods

The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched from their inception to May 2024 for randomized controlled trials of BoNT combined with rehabilitation treatments for post-stroke spasticity. Reductions in the Modified Ashworth Scale (MAS) score at short-term and medium-term weeks after treatment were calculated.

Results

Eighteen studies were analyzed. Regarding the short-term effect of BoNT combined with rehabilitation treatments on post-stroke spasticity, the top one ranked combination treatments were BoNT plus conventional therapy (CT) and splinting. The results showed that two evidence networks regarding the medium-term efficacy of BoNT combined with rehabilitation treatments for post-stroke spasticity. The top one ranked combination treatments for Network A were BoNT plus CT and electrical stimulation, and for Network B, BoNT plus casting.

Conclusions

The limited quantity of literature included in these studies did not permit the ordering of probabilities. Consequently, these results must be interpreted with caution and further validated using high-quality studies.

Introduction

Stroke is the second-leading cause of death and the third-leading cause of disability (GBD 2019 Stroke Collaborators, 2021). From 1990 to 2019, the absolute numbers of stroke morbidity and mortality increased by 70% and 43%, respectively (GBD 2019 Stroke Collaborators, 2021; Krishnamurthi et al., 2020; Martin et al., 2024). Spasticity is the most common complication of stroke, with a prevalence ranging from 30% to 80% among stroke survivors(Shi et al., 2019). Spasticity can lead to dysfunction of the patient's muscle movement, causing pain and postural abnormalities, which greatly diminishes their quality of life and places added strain on their caregivers(O'Dell, 2023; Santamato et al., 2019). When the patient's lower limbs are in spasm, the knee joints are involuntarily straightened, the ankle joints are turned inward when the soles of the feet touch the ground, and the supportive phases of the lower limbs on the affected side are shortened, resulting in the hemiplegic gait of “walking in a circle”(Santamato et al., 2019). A prolonged state of spasticity can lead to contracture of the Achilles tendon, and constant abnormal pressure during walking can cause pressure sores(Li & Francisco, 2021). Continued activation of spastic calf muscles during weight-bearing has been linked to the development of foot drop(Li & Francisco, 2021). Increased upper extremity flexor tone can lead to flexion of the elbow, wrist, and finger joints. Spasticity affecting the hands and wrists is a particularly problematic form of spasticity, as it can significantly impair activities of daily living, including dressing and personal hygiene (Lee et al., 2024; Ye et al., 2023). Therefore, it is imperative to identify effective methods for alleviating the challenges posed by spasticity after stroke.

Spasticity is a movement disorder that is defined by a velocity-dependent increase in the stretch reflex and the presence of abnormal tendon reflexes(Sheean, 2002). Current treatment options for poststroke spasticity include exercise, oral spasticity medications, physical therapy, botulinum toxin (BoNT) injections, and surgery(Thibaut et al., 2013). Among these, BoNT-A is the treatment of choice for focal spasticity affecting the upper and lower extremities(Wissel et al., 2009). BoNT-A is a metalloproteinase that provides transient chemical innervation to injected muscles by inhibiting the presynaptic release of acetylcholine at the neuromuscular junctions(Brin et al., 1987). BoNT-A injections exert various effects on spastic muscles, including neural and non-neural components associated with elevated tone, muscle strength, and motor performance(Chen et al., 2022). Several studies have demonstrated that BoNT-A injections can reduce muscle tone, address muscle imbalance, and enhance muscle function(Sun et al., 2019).

Nevertheless, there is evidence that in some patients, the response to BoNT-A therapy may diminish over time (Pitcher et al., 2015). To enhance the effects of BoNT-A, researchers have proposed various techniques to improve clinical outcomes. These include stretching(Allart et al., 2022), intensive rehabilitation(Hara et al., 2018), casting (Farag et al., 2020), repetitive transcranial magnetic stimulation(Shao et al., 2022), robotic assistance (RA) (Cotinat et al., 2024),electrical stimulation (ES) (Baricich et al., 2019), extracorporeal shock wave (ESWT) (Du et al., 2024), constraint-induced movement therapy(Nasb et al., 2021), isokinetic training(Cinone et al., 2019), and repetitive facilitative exercise(Hokazono et al., 2022). The link between BoNT-A and rehabilitation is widely accepted. However, there is no consensus regarding which combination therapy is most effective. Consequently, there is growing interest in the combination of BoNT-A and rehabilitation techniques for the treatment of post-stroke spasticity. Nevertheless, there is a dearth of systematic evaluations of this therapeutic approach. In light of these considerations, the objective of this study was to conduct a network meta-analysis of the existing literature on post-stroke spasticity. The objective of this study was to compare the efficacy of BoNT-A with different rehabilitative therapies and to provide evidence-based medical recommendations for optimizing the outcome of combined therapy for patients with post-stroke spasticity.

More at link.

Botulinum Toxin Injections for Stroke Rehabilitation

 But botox DOES NOTHING TO CURE SPASTICITY!

I'm 18 years post stroke and the spasticity hasn't diminished one bit!

Obviously these researchers don't think much of the ridiculous opinion of Dr. William M. Landau!

Spasticity After Stroke: Why Bother? Aug. 2004)

The latest here:

Botulinum Toxin Injections for Stroke Rehabilitation 

Stroke affects around 800,000 Americans every year, and has a variety of sequelae across many organ systems.¹ Often, strokes can result in chronic paresis and spasticity, which are significant contributors to long-term disability.² Patients with hemiparesis can experience mild to severe gait dysfunctions that can leave them unable to ambulate or function normally.³ Post-stroke spasticity of the lower extremities can lead to equinovarus deformity that makes ambulation difficult and impairs balance and a normal gait cycle.⁴ Spastic hemiparesis can also contribute to these gait dysfunctions and can affect walking velocity due to atypical muscle activation, causing an increase in tonic stretch reflexes and muscle hypertonicity.^3,5

Treatments for spastic hemiparesis vary from oral antispasticity medications, shock wave therapy, botulinum toxin injections and many more.⁶ Ultrasound-guided botulinum toxin injections have increased in popularity due to the ability for focal injection and the absence of side effects—such as sedation—which are prevalent with generalized antispasticity medications.⁷ Use of both botulinum toxin A and B injections for chemodenervation has proven effective(NOT TRUE! It doesn't cure spasticity!) in treatment of spasticity in adults and children.⁸

AbobotulinumtoxinA (aboBoNT-A; Dysport, Galderma Laboratories) is FDA approved for use in treatment of hypertonic muscles in spastic paresis. Botulinum toxin is a neurotoxin produced by Clostridium botulinum, a spore-forming Bacillus bacterium that is gram-positive and anaerobic.⁹ The heavy chain of the toxin binds to the receptors on the presynaptic surface of cholinergic nerve terminals and are taken into the cell. The disulfide bond between the heavy and light chains is broken, and the light chain interacts with SNARE (soluble N-ethylmaleimide–sensitive factor attachment) proteins.⁵,⁹ This prevents fusion and exocytosis of the acetylcholine vesicles into the synaptic terminal. The onset of action is between 24 and 72 hours, but the binding is irreversible, so effects remain until two to three months later when new nerve terminals and synaptic contacts are created.⁹ This time line allows for more targeted treatments in stroke patients, as injection frequency can be tailored to a patient’s needs.

In 2003, a class I study examined calf muscle hypertonicity and aboBoNT-A effects on walking rehabilitation. A total of 234 participants who had previous strokes received different doses of aboBoNT-A over 12 weeks. Investigators measured stepping rate and two-minute walking distance, as well as calf spasticity, limb pain and use of walking aids. They found small but significant improvements across the measured parameters, concluding that botulinum toxin injections are a safe and helpful form of rehabilitation therapy.¹⁰

A paper published in 2021 examined repeated aboBoNT-A injections effects on walking velocity in people with spastic hemiparesis.¹¹ The study was conducted on adults with hemiparesis; the treatment involved one intramuscular injection of 1,000 to 1,500 units of aboBoNT-A or placebo. Participants were between 18 and 80 years of age with spastic hemiparesis and only one brain injury or stroke prior to study enrollment. They had comfortable barefoot walking velocities of 0.1 to 0.8 meters per second (with 0.1-0.4 meters per second considered to be household ambulators, and 0.4-0.8 considered as limited ambulators). The injection was given in the gastrocnemius–soleus muscle complex, with additional injections in other muscles, depending on the clinician’s judgment. The study ran for up to 18 months with five injections. Results varied based on the number of injections, as expected, but overall the comfortable barefoot walking velocities had a mean improvement of 0.14 meters per second.¹¹ This improvement moved many of the participants from the household ambulation category into community ambulators.

Botulinum toxin injections are widely accepted in their use for post-stroke spasticity. However, dosing and frequency are not standardized, and more studies need to establish treatment algorithms and clinical guidelines.¹² Although botulinum toxin therapy should be highly specialized to the patient due to varying levels of post-stroke spasticity, guidelines would help decrease iatrogenic conditions. A study published in 2021 examined the increase of high doses of botulinum toxin A administration and the risks for severe side effects.¹³ The study concluded that doses up to 840 units were effective and safe, although the American-European Consensus Conference recommended that doses do not exceed 600 units.¹⁴ The investigators also said higher doses may be applicable in certain patients, but recognized that more studies need to be done in this area to enable safer use of the injections and better patient outcomes.¹³

Overall, botulinum toxin injections have been proven to help with spasticity and muscle tone in stroke patients. Current studies have focused specifically on improved spasticity and hypertonicity but less on quality of life and functional improvements.⁴ In a systematic review published in 2018, investigators recognized the need for studies that examine botulinum toxin’s ability to improve functional outcomes.^4,12 Spasticity is just one variable in the overall rehabilitation of post-stroke patients. To establish the positive impact of botulinum toxin on overall rehabilitation of the lower limb, further research must be done.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection

 But depression is a secondary problem post stroke; solve the primary problem of 100% recovery and all these secondary problems disappear! Does anyone in stroke actually think?

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection

Xiao-Yan Feng^1,2Ting-Ting Shen¹Qian-Chang Wu¹Jun Wang¹Ping Ni¹Jing Liu¹Xu-Ping Zhou^1*Hua Hu^1*Wei-Feng Luo^1*

• ¹Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
• ²Department of Neurology, Wuxi No.2 People's Hospital, Jiangnan University Medical Center, Wuxi, China

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD.

Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment.

Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000).

Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Introduction

Stroke is a cerebrovascular event resulting from a sudden interruption of blood supply to the brain, causing irreversible tissue damage. This condition encompasses thrombotic, embolic, or hemorrhagic events. A common complication of stroke is post-stroke depression (PSD), a mood disorder characterized by persistent emotional depression and loss of interest (1). Psychiatrists have observed PSD for nearly a century, and since the 1970s, numerous studies have been conducted to investigate this condition. PSD is a prevalent and manageable complication of stroke (2), with meta-analyses estimating its prevalence to range from 18 to 33% (3, 4). Werheid discovered an intriguing pattern where depressive symptoms in stroke patients tend to worsen in the first 6 months, improve within a year, and then worsen again after the second year (5). PSD can increase disability and mortality rates, reduce rehabilitation efficiency, and lead to a decline in motor function and quality of life, placing a burden on both families and society (6). The clinical manifestations of PSD can be classified into core and non-core symptoms. Core symptoms consist of low mood, anhedonia, and fatigue, while non-core symptoms include cognitive impairment, sleep disturbances, unexplained pain, sexual dysfunction, appetite changes, and gastrointestinal issues. However, due to the diverse and non-specific nature of these symptoms, diagnosis and treatment of PSD are often overlooked or delayed (2).

Research studies have shown that prompt administration of antidepressant therapy after a stroke can prevent the development of PSD (7). Additionally, antidepressant therapy can improve the prognosis of stroke patients, including cognitive and executive functions, thereby enhancing their quality of life (8). It is worth noting that a randomized placebo-controlled trial has established that the benefits of antidepressants can extend beyond emotional symptoms. Patients who received antidepressants demonstrated better motor recovery compared to the control group, leading to a significant increase in the proportion of patients achieving partial or complete living independence (9). As a result, early detection of PSD and timely use of antidepressants are crucial for effective stroke management. However, traditional antidepressants often fail to meet clinical needs due to their slow onset of action and adverse side effects, such as hepatotoxicity, nephrotoxicity, gastrointestinal discomfort, cognitive decline, etc. (10). An increasing number of studies have demonstrated the efficacy of Botulinum Toxin A (BoNT-A) in the treatment of depression. Clinical randomized controlled trials have consistently confirmed the safety and effectiveness of BoNT-A as an antidepressant therapy (11). Building upon this previous research, we recruited PSD patients who met the inclusion criteria to receive BoNT-A for antidepressant treatment, with the traditional antidepressant Sertraline serving as the control group in our study.

Botulinum toxin use in patients with post-stroke spasticity: a nationwide retrospective study from France

You say nothing on whether any of this cured the spasticity. Survivors want spasticity cured, not managed or treated!  You'll want spasticity cured when you are the

1 in 4 per WHO that has a stroke!

 You won't like Dr. William M. Landau's uninformed 'expert' opinion after your stroke.  Survivors would immediately disabuse him of that notion. When schadenfreude hits him with his stroke he'll regret his ideas on the matter. 

His statement from here:

Spasticity After Stroke: Why Bother? Aug. 2004

Botulinum toxin use in patients with post-stroke spasticity: a nationwide retrospective study from France

Jonathan Levy^1,2* Pierre Karam³ Anne Forestier⁴ Jean-Yves Loze⁴ Djamel Bensmail^1,2

• ¹Department of Physical and Rehabilitation Medicine, Raymond-Poincaré Teaching Hospital, AP-HP, Université Paris-Saclay, Garches, France
• ²Unité INSERM 1179, University of Versailles Saint-Quentin-en-Yvelines, Montigny-Le-Bretonneux, France
• ³PKCS, Ecully, France
• ⁴Ipsen, Boulogne-Billancourt, France

Background: Current guidelines recommend intramuscular botulinum toxin type A (BoNT-A) injection as first-line treatment for spasticity, a frequent and impairing feature of various central nervous system (CNS) lesions such as stroke. Patients with spasticity commonly require BoNT-A injections once every 3 to 4 months. We conducted a nationwide, population-based, retrospective cohort study, using the French National Hospital Discharge Database (PMSI), to describe BoNT-A use for spasticity in clinical practice in France between 2014 and 2020. The PMSI database covers the whole French population, corresponding to over 66 million persons.

Methods: We first searched the PMSI database for healthcare facility discharge of patients who received BoNT-A injections between 2014 and 2020, corresponding to the first set. For each BoNT-A-treated patient, we identified the medical condition for which BoNT-A may have been indicated. Another search of the PMSI database focused on patients admitted for acute stroke between 2014 and 2016 and their spasticity-related care pathway (second set). Overall, two subpopulations were analysed: 138,481 patients who received BoNT-A injections between 2014 and 2020, and 318,025 patients who survived a stroke event between 2014 and 2016 and were followed up until 2020.

Results: Among the 138,481 BoNT-A-treated patients, 53.5% received only one or two BoNT-A injections. Most of these patients (N = 85,900; 62.0%) received BoNT-A because they had CNS lesions. The number of patients with CNS lesions who received ≥1 BoNT-A injection increased by a mean of 7.5% per year from 2014 to 2019, but decreased by 0.2% between 2019 and 2020, corresponding to the COVID-19 outbreak. In stroke survivors (N = 318,025), 10.7% were coded with post-stroke spasticity, 2.3% received ≥1 BoNT-A injection between 2014 and 2020, and only 0.8% received ≥3 injections within the 12 months following BoNT-A treatment initiation, i.e., once every 3 to 4 months.

Conclusion: Our analysis of the exhaustive PMSI database showed a suboptimal implementation of BoNT-A treatment recommendations in France. BoNT-A treatment initiation and re-administration are low, particularly in patients with post-stroke spasticity. Further investigations may help explain this observation, and may target specific actions to improve spasticity-related care pathway.

Study Reveals How Botox Breaches Brain Cells

Is your doctor familiar with this? And why is your doctor prescribing botox? It doesn't directly help recovery.  It makes your doctor look like something is being done but that's all it does, 'looks'.

And why use botox for stroke anyway, it provides no functional improvement.

 My botox shots did nothing to improve my arm use, because botox does nothing directly to fix the brain problem that causes spasticity.

Does Spasticity Reduction by Botulinum Toxin Type A Improve Upper Limb Functionality in Adult Post-Stroke Patients? A Systematic Review of Relevant Studies December 2022 

In this study from December 2022 is this line: No improvement in global functionality of activity daily living was observed.

Study Reveals How Botox Breaches Brain Cells

Summary: Researchers have cracked the mystery behind how the Botulinum neurotoxin type-A, also known as Botox, infiltrates neurons. The toxin utilizes a small complex formed by a receptor called Synaptotagmin 1, along with two other clostridial neurotoxin receptors, to enter synaptic vesicles in neurons.

This infiltration interrupts nerve-to-muscle communication, leading to paralysis. The findings, which provide a complete picture of Botox’s method of operation, will aid in identifying new therapeutic targets for botulism treatment.

Key Facts:

1. Researchers discovered that a receptor called Synaptotagmin 1, in collaboration with two other receptors, helps Botox enter neurons.
2. Once inside the neurons, Botox disrupts communication between nerves and muscle cells, causing paralysis.
3. The study’s insights could lead to the identification of new therapeutic targets to treat botulism.

Source: University of Queensland

Researchers from The University of Queensland have determined how Botox—a drug made from a deadly biological substance—enters brain cells.

Professor Frederic Meunier and Dr. Merja Joensuu at UQ’s Queensland Brain Institute have discovered the specific molecular mechanism by which the highly deadly Botulinum neurotoxin type-A, more widely known as Botox, enters neurons.

The research is published in The EMBO Journal.

“We used super-resolution microscopy to show that a receptor called Synaptotagmin 1 binds to two other previously known clostridial neurotoxin receptors to form a tiny complex that sits on the plasma membrane of neurons,” Professor Meunier said.

The discovery means new therapeutic targets can be identified to develop effective treatments for botulism—a rare but potentially fatal bacterial infection. Credit: Neuroscience News

“The toxin hijacks this complex and enters the synaptic vesicles which store neurotransmitters critical to communication between neurons.

“Botox then interrupts the communication between nerves and muscle cells, causing paralysis.”

The discovery means new therapeutic targets can be identified to develop effective treatments for botulism—a rare but potentially fatal bacterial infection.

“Now we know how this complex allows the toxin internalization, we can block interactions between any two of the three receptors to stop the deadly toxins from getting into neurons,” Professor Meunier said.

The injectable drug Botox was originally developed to treat people with the eye condition strabismus, but was quickly found to alleviate(NOT CURE!) migraine, chronic pain, and spasticity disorders.

Now, it’s regularly used in plastic surgeries and is commonly known as a cosmetic treatment to smooth wrinkles.

Dr. Joensuu said just how the neurotoxin worked to relax muscles has previously been difficult to track.

Examining the role of intrinsic and reflexive contributions to ankle joint hyper-resistance treated with botulinum toxin-A

 Wrong goal! Survivors want spasticity cured not just analyzed. WILL YOU PLEASE FOR ONCE ACTUALLY SOLVE STROKE FOR SURVIVORS?

Examining the role of intrinsic and reflexive contributions to ankle joint hyper-resistance treated with botulinum toxin-A

• Ronald C. van’t Veld,
• Eline Flux,
• Wieneke van Oorschot,
• Alfred C. Schouten,
• Marjolein M. van der Krogt,
• Herman van der Kooij,
• Marije Vos-van der Hulst,
• Noël L. W. Keijsers &
• Edwin H. F. van Asseldonk 

Journal of NeuroEngineering and Rehabilitation volume 20, Article number: 19 (2023) Cite this article

• Metrics details

Abstract

Background

Spasticity, i.e. stretch hyperreflexia, increases joint resistance similar to symptoms like hypertonia and contractures. Botulinum neurotoxin-A (BoNT-A) injections are a widely used intervention to reduce spasticity. BoNT-A effects on spasticity are poorly understood, because clinical measures, e.g. modified Ashworth scale (MAS), cannot differentiate between the symptoms affecting joint resistance. This paper distinguishes the contributions of the reflexive and intrinsic pathways to ankle joint hyper-resistance for participants treated with BoNT-A injections. We hypothesized that the overall joint resistance and reflexive contribution decrease 6 weeks after injection, while returning close to baseline after 12 weeks.

Methods

Nine participants with spasticity after spinal cord injury or after stroke were evaluated across three sessions: 0, 6 and 12 weeks after BoNT-A injection in the calf muscles. Evaluation included clinical measures (MAS, Tardieu Scale) and motorized instrumented assessment using the instrumented spasticity test (SPAT) and parallel-cascade (PC) system identification. Assessments included measures for: (1) overall resistance from MAS and fast velocity SPAT; (2) reflexive resistance contribution from Tardieu Scale, difference between fast and slow velocity SPAT and PC reflexive gain; and (3) intrinsic resistance contribution from slow velocity SPAT and PC intrinsic stiffness/damping.

Results

Individually, the hypothesized BoNT-A effect, the combination of a reduced resistance (week 6) and return towards baseline (week 12), was observed in the MAS (5 participants), fast velocity SPAT (2 participants), Tardieu Scale (2 participants), SPAT (1 participant) and reflexive gain (4 participants). On group-level, the hypothesis was only confirmed for the MAS, which showed a significant resistance reduction at week 6. All instrumented measures were strongly correlated when quantifying the same resistance contribution.

Conclusion

At group-level, the expected joint resistance reduction due to BoNT-A injections was only observed in the MAS (overall resistance). This observed reduction could not be attributed to an unambiguous group-level reduction of the reflexive resistance contribution, as no instrumented measure confirmed the hypothesis. Validity of the instrumented measures was supported through a strong association between different assessment methods. Therefore, further quantification of the individual contributions to joint resistance changes using instrumented measures across a large sample size are essential to understand the heterogeneous response to BoNT-A injections.

Background

Botulinum neurotoxin-A (BoNT-A) injections are currently the most frequently used clinical intervention for focal spasticity [1,2,3]. Spasticity is a common symptom after various brain and neural injuries, such as spinal cord injury (SCI) or stroke, referring to an exaggerated stretch reflex, i.e. stretch hyperreflexia [4, 5]. Spasticity is perceived as an increased joint resistance to movement, i.e. joint hyper-resistance. BoNT-A injections are used clinically to reduce muscle activity and hence spasticity [1]. BoNT-A injections reduce muscle activity by inhibiting the release of acetylcholine at the neuromuscular junction, which chemically denervates the exposed muscle fibers. BoNT-A effects reduce after 2 to 4 months due to nerve sprouting and muscle re-innervation [1].

Clinical evaluation of BoNT-A injections has shown a significant reduction in joint resistance after 2–8 weeks using the modified Ashworth scale (MAS) [6,7,8]. With the MAS, currently a common clinical test, clinicians evaluate overall joint resistance, which can physiologically include tissue characteristics, and tonic and reflexive muscle activity [5, 9,10,11]. For the MAS, a single passive movement profile is repeatedly applied, whereas movements with varying characteristics, e.g. slow and fast velocities, are required to unravel joint resistance contributions. Therefore, the MAS can clinically only evaluate spasticity indirectly and cannot distinguish between spasticity and other symptoms as involuntary background activity, shortened soft tissue, contractures and muscle fibrosis [4, 12, 13]. Furthermore, the MAS has a questionable reliability, especially when applied at the lower limb [11, 14]. Hence, the clinical effect of BoNT-A injections on spasticity is poorly understood, while BoNT-A injections are a frequently used clinical intervention for spasticity.

Quantification of the intrinsic and reflexive contributions to joint hyper-resistance is essential to understand the beneficial and adverse effects of BoNT-A injections and support clinical decision making. BoNT-A injections can, for example, have side-effects and should ideally only be administered to patients who suffer from increased reflexive contributions to joint hyper-resistance [15]. Objective information on both intrinsic and reflexive joint resistance can support clinical decision making and help evaluate treatment effects [5]. The intrinsic resistance represents the combination of tissue-related non-neural and tonic neural contributions to joint resistance [10]. The reflexive resistance, representing the phasic neural contributions, can be used as measure for spasticity. Model-based processing of neuromechanical responses can be used to unravel and quantify the intrinsic and reflexive contributions [10, 16,17,18,19,20]. Furthermore, instrumentation and motorization using robotic devices can improve precision, consistency and objectivity of the applied movements and measurements [21,22,23].

Model-based evaluation of BoNT-A effects on joint hyper-resistance contributions have been applied using neuromechanical models [24,25,26,27]. These studies showed conflicting results on BoNT-A effects with either no change or a significant reduction of the reflexive resistance observed after injection. The neuromechanical modelling approaches used limited experimental datasets measured over the full passive range of motion (pROM), similar to current clinical measures. The subsequent joint resistance estimation primarily relies on a priori knowledge and simplifying assumptions. As a result, these methodologies are sensitive to incomplete model definitions and imperfect a priori knowledge [17, 18, 20]. Furthermore, the lack of a gold standard complicates interpretation of the reported conflicting results [5, 28, 29]. Besides the selected model, differences in reported BoNT-A effects may also be influenced by participant heterogeneity, the experimental setup, and the assessed joint. Given the conflicting results and lack of a gold standard, investigating fundamentally different approaches to assess joint hyper-resistance is of interest to improve understanding of BoNT-A effects.

An alternative approach to assess BoNT-A effects on joint hyper-resistance contributions is data-driven modelling. Data-driven modelling evaluation of BoNT-A effects on joint hyper-resistance contributions could be executed using system identification [10, 16, 30, 31]. For example, the parallel-cascade (PC) system identification technique has shown the ability to discriminate spastic participants from controls and paretic from non-paretic joints [30, 32]. The PC technique has also shown good group-level responsiveness during the evaluation of several clinical treatments, like functional electrical stimulation-assisted walking, Tizanidine and robot-assisted gait training [33,34,35]. Currently, no system identification results have been reported on BoNT-A effects. Contrary to neuromechanical modelling, the system identification techniques previously tested in a clinical setting used rich experimental datasets measured over only a limited portion of the pROM [30,31,32,33,34,35]. As intrinsic and reflexive joint resistance depend on joint angle, the obtained joint resistance estimates do not characterize the full pROM [36].

The goal of this paper was to distinguish the contribution of intrinsic and reflexive ankle joint resistance for participants treated with BoNT-A injections to reduce spasticity. We hypothesized that reflexive joint resistance decreases 6 weeks after injection, while returning close to baseline after 12 weeks [24, 25]. Due to the reduced reflexive joint resistance, we also expected the overall joint resistance to decrease 6 weeks after injection, while returning close to baseline after 12 weeks [6,7,8]. In absence of a gold standard, the joint resistance contributions were assessed using multiple joint resistance measures with different characteristics and limitations. Joint resistance contributions were estimated using clinical measures (MAS/Tardieu Scale) [9, 37], an instrumented spasticity test (SPAT) [22, 23] and a parallel-cascade (PC) system identification technique [10, 30]. To support validity of the measures used, the linear association between the various outcome measures was investigated.