Search Results (7)

Botulinum neurotoxin-A (BoNT-A) injections are effective in reducing focal limb spasticity; however, their impact on strength and active function needs to be established. This review was a secondary analysis aimed at evaluating changes to active function in the context of muscle strength changes following BoNT-A intramuscular injection for adult upper and lower limb spasticity. The original review searched eight databases (CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Google Scholar, MEDLINE, PEDro, PubMed, Web of Science) and was conducted with methodology that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as described in section 6.2 of Gill et al. For this secondary analysis, no databases were searched; only further data were extracted. The current and preceding review were registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Twenty studies were screened for inclusion, and three studies were excluded because active function was not assessed in all participants. Seventeen studies (677 participants) met the inclusion criteria for analysis. Quality was examined using the PEDro scale and modified Downs and Black checklist and rated as fair to good. Pre- and post-BoNT-A injection strength (agonist, antagonist, and global), active function (activity), participation, and quality-of-life outcomes at short-, mid-, and long-term time points were extracted and analysed. Significant heterogeneity and limited responsiveness in strength and active function outcome measures limited the ability to determine whether changes in strength mediate an effect on active function. Further, variability in BoNT-A type and dose, adjunctive therapies provided, and variability in reporting limited analyses. Overall, no clear relationship existed between the change in muscle strength and active function following BoNT-A injections to the upper and lower limbs for focal spasticity in adult-onset neurological conditions. Full article

Background: Botulinum toxin (BoNT), produced by Clostridium botulinum, has transitioned from being a lethal neurotoxin to a versatile therapeutic agent. Its ability to inhibit neurotransmitter release by targeting Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptor (SNARE) proteins underpins its applications in treating conditions such as spasticity, dystonia, chronic pain, and overactive bladder. The clinical and pharmacological properties of BoNT have been extensively studied, with significant advancements in its therapeutic use, safety profile, and understanding of associated adverse effects. Objective: This comprehensive review aims to consolidate historical developments, molecular mechanisms, clinical applications, and challenges associated with BoNT, with a focus on expanding its therapeutic scope while ensuring safety and efficacy. Method: A narrative approach was used to analyze and synthesize insights from 155 references spanning experimental studies, clinical trials, and reviews. Key topics included BoNT’s historical milestones, mechanisms of action, therapeutic applications, and adverse events. Findings: BoNT demonstrates remarkable efficacy in a wide range of medical and cosmetic applications. In movement disorders such as dystonia and spasticity, it reduces muscle overactivity and improves functional outcomes. In chronic pain management, including migraines and neuropathic pain, BoNT significantly alleviates symptoms by modulating neurotransmitter activity. Cosmetic use for conditions like glabellar lines and hyperhidrosis highlights its precision and safety when administered appropriately. For conditions like strabismus and blepharospasm, BoNT effectively restores muscle control, reducing involuntary contractions. In urological applications, BoNT has proven to be an effective therapy for overactive bladder, offering significant symptom relief in refractory cases. However, concerns about long-distance effects, where the toxin may spread beyond the injection site to affect distant muscles or systems, have been reported in certain high-dose or sensitive populations. These findings emphasize the importance of dose optimization and patient-specific approaches. Adverse effects such as localized pain, hematoma, dysphagia, and systemic effects, particularly in high-risk groups, underscore the need for careful monitoring. The development of immunogenicity, leading to neutralizing antibodies, remains a challenge that impacts long-term therapeutic efficacy. Emerging research on novel serotypes, including BoNT/X, and innovations in delivery mechanisms, offer promising avenues to address current limitations. Advances in optimizing dosing regimens and refining injection techniques have also contributed to minimizing complications and improving outcomes across diverse patient populations. Conclusions: BoNT remains a cornerstone in neurology and cosmetic medicine, with its therapeutic potential still expanding. The balance between efficacy and safety, driven by innovations in formulation and application, underscores the importance of continued research. Future directions should focus on minimizing adverse effects, reducing immunogenicity, and exploring novel indications to further enhance its clinical utility. Full article

Background: Repetitive intramuscular injections of botulinum neurotoxin (BoNT) have become the treatment of choice for a variety of disease entities. But with the onset of BoNT therapy, the natural course of a disease is obscured. Nevertheless, the present study tries to analyze patients’ “suspected” course of disease severity under the assumption that no BoNT therapy had been performed and compares that with the “experienced” improvement during BoNT treatment. Methods: For this cross-sectional study, all 112 BoNT long-term treated patients in a botulinum toxin out-patient department were recruited who did not interrupt their BoNT/A therapy for more than two injection cycles during the last ten years. Patients had to assess the remaining severity of their disease as a percentage of the severity at onset of BoNT therapy and to draw three different graphs: (i) the CoDB-graph showing the course of severity of patient’s disease from onset of symptoms to onset of BoNT/A therapy, (ii) the CoDA-graph illustrating the course of severity from onset of BoNT/A therapy until recruitment, and (iii) the CoDS-graph visualizing the suspected development of disease severity from onset of BoNT/A therapy until recruitment under the assumption that no BoNT/A therapy had been performed. Three different types of graphs were distinguished: the R-type indicated a rapid manifestation or improvement, the C-type a continuous worsening or improvement, and the D-type a delayed manifestation or response to BoNT therapy. Four patient subgroups (cervical dystonia, other cranial dystonia, hemifacial spasm, and the migraine subgroup) comprised 91 patients who produced a complete set of graphs which were further analyzed. The “experienced” improvement and “suspected” worsening of disease severity since the onset of BoNT/A therapy were compared and correlated with demographical and treatment related data. Results: Improvement was significant (p < 0.05) and varied between 45 and 70% in all four patient subgroups, the “suspected” worsening was also significantly (p < 0.05) larger than 0, except in the migraine patients and varied between 10 and 70%. The “total benefit” (sum of improvement and prevented “suspected” worsening) was the highest in the other cranial dystonia group and the lowest in the migraine subgroup. The distributions of R-,C-,D-type graphs across CoDB-, CoDS-, and CoDB-graphs and across the four patient subgroups were significantly different. Conclusions: (i) Most BoNT long-term treated patients have the opinion that their disease would have further progressed and worsened if no BoNT/A therapy had been performed, (ii) The type of response to BoNT/A is different across different subgroups of BoNT/A long-term treated patients. Full article

Upper-limb spasticity, frequent after central nervous system lesions, is typically treated with botulinum neurotoxin type A (BoNT-A) injections to reduce muscle tone and increase range of motion. However, performing adjunct physical therapy post-BoNT-A can be challenging due to residual weakness or spasticity. This study evaluates the feasibility of hand therapy using a robotic hand orthosis (RELab tenoexo) with a mobile phone application as an adjunct to BoNT-A injections. Five chronic spastic patients participated in a two-session pilot study. Functional (Box and Block Test (BBT), Action Research Arm Test (ARAT)), and muscle tone (Modified Ashworth Scale (MAS)) assessments were conducted to assess functional abilities and impairment, along with usability evaluations. In the first session, subjects received BoNT-A injections, and then they performed a simulated unsupervised therapy session with the RELab tenoexo in a second session a month later. Results showed that BoNT-A reduced muscle tone (from 12.2 to 7.4 MAS points). The addition of RELab tenoexo therapy was safe, led to functional improvements in four subjects (two-cube increase in BBT as well as 2.8 points in grasp and 1.3 points in grip on ARAT). Usability results indicate that, with minor improvements, adjunct RELab tenoexo therapy could enhance therapy doses and, potentially, long-term outcomes. Full article

Background: The objective of this study was to provide evidence from a simple simulation. In patients with focal dystonia, an initial good response to botulinum neurotoxin (BoNT) injections followed by a secondary worsening does not necessarily arise from an antibody-induced secondary treatment failure (NAB-STF), but may stem from a “pseudo”-secondary treatment failure (PSEUDO-STF). Methods: The simulation of the outcome after BoNT long-term treatment was performed in four steps: 1. The effect of the first single BoNT injection (SI curve) was displayed as a 12-point graph, corresponding to the mean improvement from weeks 1 to 12. 2. The remaining severity of the dystonia during the nth injection cycle was calculated by subtracting the SI curve (weighted by the outcome after n − 1 cycles) from the outcome after week 12 of the (n − 1)th cycle. 3. A graph was chosen (the PRO curve), which represents the progression of the severity of the underlying disease during BoNT therapy. 4. The interaction between the outcome during the nth BoNT cycle and the PRO curve was determined. Results: When the long-term outcome after n cycles of BoNT injections (applied every 3 months) was simulated as an interactive process, subtracting the effect of the first cycle (weighted by the outcome after n − 1 cycles) and adding the progression of the disease, an initial good improvement followed by secondary worsening results. This long-term outcome depends on the steepness of the progression and the duration of action of the first injection cycle. We termed this response behavior a “pseudo”-secondary treatment failure, as it can be compensated via a dose increase. Conclusion: A secondary worsening following an initial good response in BoNT therapy of focal dystonia might not necessarily indicate neutralizing antibody induction but could stem from a “PSEUDO”-STF (a combination of good response behavior and progression of the underlying disease). Thus, an adequate dose adaptation must be conducted before diagnosing a secondary treatment failure in the strict sense. Full article

Background: Repetitive intramuscular injections of botulinum neurotoxin type A (BoNT/A) are the treatment of choice in patients with cervical dystonia (CD). As soon as BoNT therapy is initiated, the natural course of CD cannot be observed anymore. Nevertheless, the present study focuses on the “presumed” course of disease severity under the assumption that no BoNT therapy had been performed. The “experienced” benefit is compared with the “presumed” worsening. Methods: Twenty-seven BoNT/A long-term-treated CD patients were recruited. They had to assess the remaining severity of CD in percent of its severity at the start of BoNT therapy (RS-%). Then, they had to draw the course of severity from the onset of symptoms to the start of BoNT/A therapy (CoDB graph), as well as the course of severity from the start of BoNT/A therapy until the day of recruitment (CoDA graph). Then, they were instructed to presume the development of CD severity from the day of the start of BoNT/A therapy until the day of recruitment under the assumption that no BoNT/A therapy had been performed, and to assess the maximal severity they could presume in percent of the severity at the start of BoNT therapy (IS-%). Then, they had to draw the “presumed” development of CD severity (CoDI graph). The “experienced” change in disease severity and the “presumed” change since the start of BoNT/A therapy were compared and correlated with a variety of demographical and treatment-related data, including the actual severity of CD at the day of recruitment, which was assessed using the TSUI score and the actual dose per session (ADOSE). Results: No CD patients expected an improvement without BoNT therapy. “Presumed” worsening ((IS-%)-100) was about 50% in the mean and did not correlate with the “experienced” benefit (100-(RS-%)). However, IS-% was significantly correlated with ATSUI and ADOSE. Conclusion: Obviously, CD patients have the opinion that their CD would have further progressed and worsened if no BoNT/A therapy had been performed. Thus, the total benefit of BoNT/A therapy for a patient with CD is a combination of the “experienced” benefit under BoNT/A therapy and the prevented worsening of CD that the patient expects to occur without BoNT/A therapy. Full article

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin^®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A. Full article