Clinical and instrumental evaluation of Botulinum Toxin type A safety profile in post stroke spasticity rehabilitation treatment

Post stroke spasticity (PSS) occurs approximately in 30% of stroke survivors. Spasticity varies from a subtle neurological sign to a gross increase in tone causing immobility of joints. PSS is associated with several complications, increasing care needs and utilisation of healthcare resources. Botulinum toxin type A (BoNT-A) has been considered as an effective and safe treatment for focal spasticity in stroke survivors, with low prevalence of complications, reversibility of effect, and efficacy in reducing spastic hypertonia. Recent studies estimated that a significant percentage of patients affected by PSS could benefit from higher doses than those permitted by current country directives. However, at present time, there is no general consensus on the maximum dose of BoNT-A in terms of safety and clinical interchangeability among the three commercially approved products (abobotulinumtoxinA, onabotulinumtoxinA, incobotulinumtoxinA). In light of these considerations, the aim of this thesis is to investigate the safety profile of BoNT-A high doses in the treatment of post stroke spasticity. In our research activity we investigated the clinical effect of this treatment in severely affected patients, focusing on both clinical and instrumental assessment of systemic effects of BoNT-A

Adjunctive treatment and BoNT-A for post-stroke spasticity: are we really focusing on the patient-centered goals?

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Is the outcome of diagnostic nerve block related to spastic muscle echo intensity? A retrospective observational study on patients with spastic equinovarus foot

Objective: To investigate the relationship between spastic calf muscles echo intensity and outcome of tibial nerve motor branches selective block in patients with spastic equinovarus foot. Design: Retrospective observational study. Patients: Forty-eight patients with spastic equinovarus foot. Methods: Each patient was given selective, diagnostic nerve block (lidocaine 2% perineural injection) of the tibial nerve motor branches. All patients were evaluated before and after block. Outcomes: spastic calf muscles echo intensity measured with the Heckmatt scale; affected ankle dorsiflexion passive range of motion; calf muscles spasticity measured with the modified Ashworth scale and the Tardieu scale (grade and angle). Results:  As to the outcome of tibial nerve selective diagnostic block (difference between pre- and post-block condition), the Spearman correlation showed a significant inverse association of the spastic calf muscles echo intensity with the affected ankle dorsiflexion passive range of motion (P=0.045

BoNT-A for post-stroke spasticity: guidance on unmet clinical needs from a Delphi panel approach

There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients' clinical condition. Patients monitoring is needed over time, a follow-up of 4-6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician's perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice

Rectus Femoris Characteristics in Post Stroke Spasticity: Clinical Implications from Ultrasonographic Evaluation

In stroke survivors, rectus femoris (RF) spasticity is often implicated in gait pattern alterations such as stiff knee gait (SKG). Botulinum toxin type A (BoNT-A) is considered the gold standard for focal spasticity treatment. However—even if the accuracy of injection is crucial for BoNT-A efficacy—instrumented guidance for BoNT-A injection is not routinely applied in clinical settings. In order to investigate the possible implications of an inadequate BoNT-A injection on patients' clinical outcome, we evaluated the ultrasound-derived RF characteristics (muscle depth, muscle thickness, cross-sectional area and mean echo intensity) in 47 stroke survivors. In our sample, we observed wide variability of RF depth in both hemiparetic and unaffected side of included patients (0.44 and 3.54 cm and between 0.25 and 3.16 cm, respectively). Moreover, our analysis did not show significant differences between treated and non-treated RF in stroke survivors. These results suggest that considering the inter-individual variability in RF muscle depth and thickness, injection guidance should be considered for BoNT-A treatment in order to optimize the clinical outcome of treated patients. In particular, ultrasound guidance may help the clinicians in the long-term follow-up of muscle quality

Real-World Adherence to OnabotulinumtoxinA Treatment for Spasticity: Insights From the ASPIRE Study.

Abstract Objective To identify baseline characteristics and treatment-related variables that affect adherence to onabotulinumtoxinA treatment from the Adult Spasticity International Registry (ASPIRE) study. Design Prospective, observational registry (NCT01930786). Setting International clinical sites. Participants Adults with spasticity (N=730). Interventions OnabotulinumtoxinA at clinician's discretion. Main Outcome Measures Clinically meaningful thresholds used for treatment adherent (≥3 treatment sessions during 2-year study) and nonadherent (≤2 sessions). Data analyzed using logistic regression and presented as odds ratios (ORs) with 95% confidence intervals (CIs). Treatment-related variables assessed at sessions 1 and 2 only. Results Of the total population, 523 patients (71.6%) were treatment adherent with 5.3±1.6 sessions and 207 (28.4%) were nonadherent with 1.5±0.5 sessions. In the final model (n=626/730), 522 patients (83.4%) were treatment adherent and 104 (16.6%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=1.84; CI, 1.06-3.21; P=.030) and use of orthotics (OR=1.88; CI, 1.15-3.08; P=.012). Baseline characteristics associated with nonadherence: history of diplopia (OR=0.28; CI, 0.09-0.89; P=.031) and use of assistive devices (OR=0.51; CI, 0.29-0.90; P=.021). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.43; CI, 0.26-0.72; P=.001) and clinician dissatisfaction with onabotulinumtoxinA to manage pain (OR=0.18; CI, 0.05-0.69; P=.012). Of the population with stroke (n=411), 288 patients (70.1%) were treatment adherent with 5.3±1.6 sessions and 123 (29.9%) were nonadherent with 1.5±0.5 session. In the final stroke model (n=346/411), 288 patients (83.2%) were treatment adherent and 58 (16.8%) were nonadherent. Baseline characteristics associated with adherence: treated in Europe (OR=2.99; CI, 1.39-6.44; P=.005) and use of orthotics (OR=3.18; CI, 1.57-6.45; P=.001). Treatment-related variables associated with nonadherence: treatment interval ≥15 weeks (OR=0.42; CI, 0.21-0.83; P=.013) and moderate/severe disability on upper limb Disability Assessment Scale pain subscale (OR=0.40; CI, 0.19-0.83; P=.015). Conclusions These ASPIRE analyses demonstrate real-world patient and clinical variables that affect adherence to onabotulinumtoxinA and provide insights to help optimize management strategies to improve patient care

Early Botulinum Toxin Type A injection for post-stroke spasticity: a longitudinal cohort study

Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke onset and initial BoNT-A injection has an effect on outcomes after PSS treatment. This multicenter, longitudinal, cohort study included stroke patients (time since onset <12 months) with PSS who received BoNT-A for the first time according to routine practice. The main outcome was the modified Ashworth scale (MAS). Patients were evaluated before BoNT-A injection and then at 4, 12, and 24 weeks of follow-up. Eighty-three patients with PSS were enrolled. MAS showed a significant decrease in PSS at 4 and 12 weeks but not at 24 weeks after treatment. Among the patients with a time between stroke onset and BoNT-A injection >90 days, the MAS were higher at 4 and 12 weeks than at 24 weeks compared to those injected ≤90 days since stroke. Our findings suggest that BoNT-A treatment for PSS should be initiated within 3 months after stroke onset in order to obtain a greater reduction in muscle tone at 1 and 3 months afterwards

The Lack of Systemic and Subclinical Side Effects of Botulinum Neurotoxin Type-A in Patients Affected by Post-Stroke Spasticity: A Longitudinal Cohort Study

Botulinum Neurotoxin type-A (BoNT-A) is the treatment of choice for focal post-stroke spasticity (PSS). Due to its mechanism of action and the administration method, some authors raised concern about its possible systemic diffusion leading to contralateral muscle weakness and autonomic nervous system (ANS) alterations. Stroke itself is a cause of motor disability and ANS impairment; therefore, it is mandatory to prevent any source of additional loss of strength and adjunctive ANS disturbance. We enrolled 15 hemiparetic stroke survivors affected by PSS already addressed to BoNT-A treatment. Contralateral handgrip strength and ANS parameters, such as heart rate variability, impedance cardiography values, and respiratory sinus arrythmia, were measured 24 h before (T0) and 10 days after (T1) the ultrasound (US)-guided BoNT-A injection. At T1, neither strength loss nor modification of the basal ANS patterns were found. These findings support recent literature about the safety profile of BoNT-A, endorsing the importance of the US guide for a precise targeting and the sparing of "critical" structures as vessels and nerves

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs.Clinical trial identifierNCT04673240

Long-term spasticity management in post-stroke patients: issues and possible actions—A Systematic Review with an Italian expert opinion

Spasticity is a well-known motor dysfunction occurring after a stroke. A group of Italian physicians' experts in treating post-stroke spasticity (PSS) reviewed the current scientific evidence concerning the state-of-the-art clinical management of PSS management and the appropriate use of botulinum toxin, aiming to identify issues, possible actions, and effective management of the patient affected by spasticity. The participants were clinicians specifically selected to cover the range of multidisciplinary clinical and research expertise needed to diagnose and manage PSS. When evidence was not available, the panel discussed and agreed on the best way to manage and treat PSS. To address the barriers identified, the panel provides a series of consensus recommendations. This systematic review provides a focused guide in the evaluation and management of patients with PSS and its complications. The recommendations reached by this panel of experts should be used by less-experienced doctors in real life and should be used as a guide on how to best use botulinum toxin injection in treating spasticity after a stroke