Effects Of Botulinum Neurotoxin Research Articles

Cellular and molecular mechanisms involved in the analgesic effects of botulinum neurotoxin: A literature review.

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain-related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain-related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature.

Equine grass sickness is associated with major abnormalities in the ultrastructure of skeletal neuromuscular junctions.

Equine grass sickness (EGS) is a frequently fatal multisystem neuropathy of equids. The aetiology is unknown; proposed causes include toxicoinfection with Clostridium botulinum and a mycotoxicosis. The effect of EGS on the organisation and structural integrity of the skeletal neuromuscular junction (NMJ), the target of botulinum neurotoxins (BoNTs), is unknown. To compare the organisation and structural integrity of skeletal NMJs from EGS horses, control horses and one horse with a presumptive diagnosis of botulism. Blinded, retrospective case control. NMJs in samples of diaphragm or intercostal muscle from six EGS horses, three control horses and one equine botulism case were compared using electron microscopy, morphometry and confocal light microscopy. A significantly higher percentage of EGS NMJs had abnormal morphology (EGS 72.2%, 95% CI 55.6-84.4; Controls 6.9%, 1.7-23.8; OR 35.1, 8.47-244.8; p < 0.001). EGS NMJs had a significantly lower mean volume fraction occupied by synaptic vesicles (SVs) (EGS 18.7%, 12.6-28.0; Controls 36.3%, 20.8-63.4; p = 0.024). EGS NMJs had evidence of accelerated SV exocytosis and SV depletion, accumulation of neurofilament-like material in terminal boutons and/or bouton degeneration. NMJs from the botulism horse had dense packing of SVs towards the presynaptic membrane active zone, consistent with BoNT intoxication, but had absence of the abnormalities identified in EGS NMJs. Group sizes were limited by difficulties obtaining suitably processed samples. Ages of control and EGS horses differed. Botulism was diagnosed based on clinical and post mortem findings. EGS is associated with major changes in skeletal NMJ ultrastructure that are inconsistent with the effects of BoNTs. SV depletion may reflect increased exocytosis coupled with reduced repopulation of SVs via anterograde axonal transport and endocytosis, consistent with the action of an excitatory presynaptic toxin and/or neurotransmitter reuptake inhibitor. Skeletal NMJs represent a previously unrecognised target for the toxin that causes EGS.

Effectiveness and safety of botulinum neurotoxin for treating dyssynergic defecation: A systematic review and meta-analysis

Dyssynergic defecation (DD) is a common cause of chronic constipation. Owing to the lack of a comprehensive synthesis of available data on the effectiveness of botulinum neurotoxin (BoNT) for treating DD, we performed a systematic review and meta-analysis. We searched the PubMed, Embase, and Cochrane databases from inception to May 9, 2023. The outcomes comprise short-term and long-term symptom improvement, various anorectal function measurements, complications of fecal incontinence, and symptom improvement after repeated BoNT injections. A meta-analysis comparing BoNT injection with either surgery or biofeedback (BFB) therapy in treating DD was also conducted. Subgroup analysis and meta-regression were performed to identify possible moderator effects. We included five randomized controlled trials, seven prospective studies, and two retrospective observational studies. Short-term potential improvement in symptoms (event rate [ER], 66.4%; 95% CI, 0.513 to 0.783) was identified, but in the long-term (>12 months), this effect was decreased (ER, 38.2%; 95% CI, 0.267 to 0.511). Short-term improvements in objective anorectal physiologic parameters were also observed. Repeated BoNT injection was effective for patients with symptom recurrence. Subgroup analysis revealed enhanced long-term symptom improvement with high-dose BoNT, but this treatment also increased the risk of complications and recurrence compared with low doses. The effectiveness, complications, and recurrence of symptoms associated with BoNT injection and surgery did not differ significantly. BoNT injection significantly provided short-term symptom improvement but also heightened the risk of incontinence compared with BFB therapy. Our systematic review and meta-analysis indicated that BoNT could be beneficial for short-term symptom improvement in patients with DD, but this effect tended to decline 12 months after injection. Standardized BoNT intervention protocols remain warranted. Among the several treatments for DD, we concluded that BoNT injection is not inferior to other options considering its effectiveness in relieving symptoms, the associated complication development, and the risk of symptom recurrence.

Effect of epigallocatechin gallate nanoemulsion on submandibular salivary glands following application of botulinum neurotoxins in albino rats: potential therapeutic effects

Background: Injecting botulinum neurotoxin (BoNT) into the salivary glands is a common treatment for certain diseases. Green tea's active compound, epigallocatechin-3-gallate (EGCG), has been linked to a variety of health benefits, including the reduction of free radicals and inflammation. This study compared the effects of BoNT and BoNT/EGCG on the submandibular salivary glands (SMG) histology and ultrastructure. Methods: Both BoNT and BoNT/EGCG nanoemulsions were injected into the submandibular salivary glands (SMGs) in adult male albino rats, which were then euthanized, and the right SMGs were thoroughly dissected and prepared for histological, immunohistochemical, and transmission electron microscopic analysis. Results: When compared to the BoNT group, the BoNT/EGCG nanoemulsion group significantly improved SMG acinar and ductal cells using both H&amp;E and immunohistochemical stainings. Ultrastructural findings of the BoNT/EGCG nanoemulsion group revealed marked improvement in the SMG structure, almost normal acini, and striated ducts. Conclusion: Salivary gland histological structures are significantly altered after BoNT administration, but the addition of EGCG causes only minor alterations and can be used to treat hyperfunction.

Botulinum Toxin-A Treatment of Post-Stroke Spasticity Is Associated with Changes in Interhemispheric Parietal Cortex Connectivity (P12-8.001)

<h3>Objective:</h3> To assess resting-state functional connectivity (rsFC) of the ipsilesional superior parietal lobule (SPL) and intraparietal sulcus (IPS) using functional magnetic resonance imaging (fMRI) in chronic stroke patients with hemiparesis both with and without post-stroke spasticity (PSS) and to explore the relationship between SPL/IPS resting-state functional connectivity (rsFC) and PSS severity. <h3>Background:</h3> Posts-stroke spasticity hampers effective rehabilitation of the paretic arm and lowers the quality of life. Effective PSS treatment with botulinum neurotoxin (BoNT) is associated with transient decrease in task-related fMRI activation of the ipsilesional SPL and IPS. We hypothesized that this would be reflected in changes in rsFC of the SPL/IPS. <h3>Design/Methods:</h3> Fourteen chronic stroke patients with upper limb weakness and PSS (the PSS group) and 8 patients with comparable weakness but no PSS (the control group) underwent clinical and spasticity evaluation and 3 fMRI examinations, at baseline (W0) and 4 and 11 weeks after BoNT (W4 and W11, respectively). Seed-based rsFC of the atlas-based SPL and IPS was evaluated using a group×time interaction analysis and the change in rsFC of SPL/IPS was correlated with change in PSS (modified Ashworth scale), integrity of the ipsilesional somatosensory afferent pathway (evoked potential N20 latency), and age. <h3>Results:</h3> In the PSS group, transient improvement in PSS was associated with increase in rsFC between the ipsilesional IPS and the contralesional SPL at W4. The interhemispheric connectivity was negatively correlated with PSS severity at baseline and with PSS improvement at W4. These changes in the posterior parietal interhemispheric rsFC suggest that previously observed task-related changes in SPL/IPS were independent of actual task performance. <h3>Conclusions:</h3> We propose adaptation of the internal forward model as the possible underlying mechanism and discuss its potential association with increased limb use or improved motor performance, as well as its potential contribution to the clinical effects of BoNT. <b>Disclosure:</b> The institution of Prof. Hlustik has received research support from Czech Health Research Council (AZV CR). Dr. Hok has nothing to disclose. Tomas Veverka has nothing to disclose. Markéta Trnecková has nothing to disclose. Pavel Otruba has nothing to disclose. Jana Zapletalova has nothing to disclose. Zbynek Tudos has nothing to disclose. Prof. Lotze has received publishing royalties from a publication relating to health care. Dr. Kanovsky has nothing to disclose.

Anatomical Proposal for Botulinum Neurotoxin Injection for Horizontal Forehead Lines.

The frontalis muscle is situated across the forehead and is a representative target muscle for botulinum neurotoxin (BoNT) injections aimed at treating horizontal wrinkles in this region. However, a lack of anatomical information regarding the shape and thickness of the frontalis may lead to unexpected adverse effects, such as ptosis and samurai eyebrows, caused by the lack of detail on anatomical variation. Achieving the maximum effect using the minimal amount of BoNT requires a precise injection into the frontalis muscle. The anatomical factors associated with BoNT injection into the frontalis muscle have been reviewed in the current study. Up-to-date understanding of the localization of the BoNT injection point according to an updated understanding of the anatomy leads to more accurate localization of the injection point into the frontalis muscle. Optimal injection sites have been provided for the frontalis muscle, and the injection method has been recommended. The authors suggest optimal injection sites according to the external anatomical landmarks of the forehead. Furthermore, these proposals could aid in a more precise procedure that avoids the deleterious effects of BoNT.

Motor Unit Number Estimation in Spastic Biceps Brachii Muscles of Chronic Stroke Survivors Before and After BoNT Injection.

The study aims to characterize the motor unit (MU) loss in spastic biceps brachii muscle (BBM) of chronic stroke survivors before and after botulinum neurotoxin (BoNT) injection. High-density weighted average (HDWA) motor unit number estimation (MUNE) was employed to estimate the number of functioning motor units of BBMs of eight chronic stroke survivors 1-week before (1st visit) and 3-week after (2nd visit) BoNT injection based on the surface electromyography (sEMG) signals recorded during voluntary contraction and supramaximal electrical stimulation. Significant lower MUNE was estimated from the spastic BBMs compared to the non-spastic MUNEs during two visits. A surprisingly higher MUNE was obtained from the spastic side during the 2nd visit after BoNT injection. The HDWA MUNE technique can be employed to characterize the motor unit loss in spastic muscle caused by upper motor neuro lesions at contraction level up to 30% MVC, but may fail to detect the MU loss caused by the chemodenervation effect of BoNT due to the non-uniform denervation of small and large size MUs. This study presents the first effort to evaluate the applicability of HDWA MUNE technique to characterize the MU loss in the spastic muscle following stroke and the subsequent BoNT injection for the treatment of post-stroke spasticity. The finding of this study suggests that HDWA MUNE can be a sensitive approach to detect the MU loss in spastic muscles after stroke, but the large inter-subject MUNE variability after the BoNT injection should be interpreted with caution.

Interhemispheric parietal cortex connectivity reflects improvement in post-stroke spasticity due to treatment with botulinum toxin-A

In post-stroke spasticity (PSS), effective treatment with botulinum neurotoxin (BoNT) is associated with transient decrease in activation of the ipsilesional superior parietal lobule (SPL) and intraparietal sulcus (IPS). We hypothesized that this would be reflected in changes in resting-state functional connectivity (rsFC) of the SPL/IPS. Our aim was therefore to assess rsFC of the ipsilesional SPL/IPS in chronic stroke patients with hemiparesis both with and without PSS and to explore the relationship between SPL/IPS rsFC and PSS severity. To this end, fourteen chronic stroke patients with upper limb weakness and PSS (the PSS group) and 8 patients with comparable weakness but no PSS (the control group) underwent clinical evaluation and 3 fMRI examinations, at baseline (W0) and 4 and 11 weeks after BoNT (W4 and W11, respectively). Seed-based rsFC of the atlas-based SPL and IPS was evaluated using a group×time interaction analysis and a correlation analysis with PSS severity (modified Ashworth scale), integrity of the ipsilesional somatosensory afferent pathway (evoked potential N20 latency), and age. In the PSS group, transient improvement in PSS was associated with increase in rsFC between the ipsilesional IPS and the contralesional SPL at W4. The interhemispheric connectivity was negatively correlated with PSS severity at baseline and with PSS improvement at W4. We propose adaptation of the internal forward model as the putative underlying mechanism and discuss its possible association with increased limb use, diminished spastic dystonia, or improved motor performance, as well as its potential contribution to the clinical effects of BoNT.

The effect of botulinum neurotoxin A on soft-tissue complications in intraoral reconstructions

Intraoral reconstruction has become more common in recent years. Patients may suffer from complications because of hypersalivation. This issue can be overcome with an aid aimed at reducing saliva production. In this study, patients who underwent flap reconstruction were examined. The aim was to compare the complication rates between those who were administered with botulinum neurotoxin type A (BTXA) to the salivary glands before the reconstruction and those who were not. Patients who underwent flap reconstruction between January 2015 and January 2021 were included in the study. The patients were divided into 2 groups. BTXA was applied to the parotid and submandibular glands in the 1st group at least 8 days before the operation to reduce the salivary secretion. BTXA application was not applied to the patients in the 2nd group before the operation. A total of 35 patients were included in the study. There were 19 patients in group 1 and 16 patients in group 2. The tumor type in both groups was squamous cell carcinoma. For patients in the 1st group, salivary secretion decreased in an average of 3.84 days. In the statistical analysis, no significant difference was found between the groups in terms of age, comorbidity, smoking-complication development, and comorbidity-complication development. When infection was excluded, there was a significant difference in the development of complications between the groups. BTXA application before the operation is beneficial to minimize complications in patients who plan to undergo elective intraoral reconstruction.

The Effectiveness and Safety of Botulinum Neurotoxin in Obstetric Brachial Plexus Injury: A Systematic Review and Meta-Analysis.

Obstetric brachial plexus injury, also known as neonatal brachial plexus injury, is not unusual in newborns. Given the lack of a comprehensive synthesis of the available data on the effectiveness of botulinum neurotoxin (BoNT) in treating children with obstetric brachial plexus injury, we conducted a systematic review and meta-analysis. We searched PubMed, Embase, Web of Science, and Cochrane databases from inception to 25 November 2022. Outcomes were function of the shoulder and elbow joints, muscle power of the deltoid, biceps brachii and triceps brachii, and the recurrence rate of subluxation or dislocation after reduction of the shoulder joint after BoNT application. Meta-regression was conducted to assess the moderator effect of age. We included 11 case series and 2 cohort studies. Passive range of motion of shoulder external rotation (standardized mean difference [SMD], 0.678; 95% confidence interval [95%CI], 0.423 to 0.934), Active Movement Scale for shoulder external rotation (SMD, 0.47; 95%CI, 0.131 to 0.808), and active range of motion of elbow extension (SMD, 2.445; 95%CI, 1.556 to 3.334) increased significantly after BoNT. However, the modified Gilbert scale for shoulder abduction (SMD, 1.239; 95% CI, -0.2 to 2.678), the Toronto score for active elbow flexion (SMD, 1.099; 95% CI, -0.053 to 2.252), muscle power of deltoid (SMD, 0.675; 95% CI, -0.599 to 1.949), biceps brachii (SMD, 0.225; 95% CI, -0.633 to 1.083), and triceps brachii (SMD, 1.354; 95% CI, -1.493 to 4.202) did not reach statistical significance. The moderator effect of age was not significant (p = 0.88). Meta-analysis was not done for recurrence rate of subluxation or dislocation due to insufficient data. In conclusion, our data support BoNT use in patients with obstetric brachial plexus injury. However, definite conclusions cannot be drawn due to small sample size and the lack of randomized controlled trials. More research is warranted to clarify the effectiveness of BoNT in patients with obstetric brachial plexus injury by using standardized injection protocols and outcome measurements.

How Does Botulinum Toxin Inhibit Itch?

Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized clinical trials have been conducted with controversial results, and the beneficial effects of BoNTs against itch are mainly based on case studies and case series. These studies are valuable in presenting the potential application of BoNTs in chronic pruritic conditions, but due to the nature of these studies, they are categorized as providing lower levels of evidence or lower grades of recommendation. To obtain approval for the anti-pruritic indication of BoNTs, higher levels of evidence are required, which can be achieved through conducting large-scale and well-designed studies with proper control groups and established careful and reliable primary and secondary outcomes. In addition to clinical evidence, presenting the mechanism-based antipruritic action of BoNTs can potentially strengthen, accelerate, and facilitate the current efforts towards further investments in accelerating the field towards the potential approval of BoNTs for itchy conditions. This review, therefore, aimed to provide the state-of-the-art mechanisms underlying the anti-itch effect of BoNTs from basic studies that resemble various clinical conditions with itch as a hallmark. Evidence of the neuronal, glial, and immune modulatory actions of BoNTs in reducing the transmission of itch are presented, and future potential directions are outlined.

Effectiveness of Botulinum Neurotoxin in Treatment of Scoliosis among Children and Adolescents: A Systematic Review and Meta-Analysis.

Scoliosis refers to a three-dimensional deviation in the axis of the spine. Muscle imbalance is believed to play a role in scoliosis. Botulinum neurotoxin (BoNT) can reduce muscle overactivity and may have the potential to ameliorate spinal scoliosis. This study investigated the effectiveness of intramuscular BoNT injection in vertebral curve correction and reviewed the possible influencing factors. PubMed, Medline, Cochrane Central Register of Controlled Trials, Web of Science, Airiti Library, and Index of the Taiwan Periodical Literature System databases were searched from inception until 7 September 2022 for eligible studies. The main outcome was the change in Cobb angle after BoNT application. Subgroup analysis was conducted according to differences in study designs, etiology of scoliosis, and methods used for target muscle selection. We enrolled three studies including 31 participants aged between 2 and 18 years. The meta-analysis revealed no significant reduction in the Cobb angle after BoNT injection (standardized mean difference, −0.783, 95% CI, −2.142 to 0.576). Study designs (p = 0.011) and methods used for target muscle selection (p = 0.017) but not etiology of scoliosis (p = 0.997) reached statistical significance between subgroups. In conclusion, the current meta-analysis does not support the application of BoNT in children and adolescents with scoliosis. However, a decisive conclusion could not be made due to high between-study heterogeneity and small sample size. More randomized controlled trials with appropriate target muscle selection and standard outcome measurement should be conducted to examine the efficacy of botulinum neurotoxin in treating scoliosis. INPLASY ID: INPLASY202290031.

Short- and Long-term Central Action of Botulinum Neurotoxin Treatment in Laryngeal Dystonia.

Background and ObjectivesLaryngeal dystonia (LD) is isolated task-specific focal dystonia selectively impairing speech production. The first choice of LD treatment is botulinum neurotoxin (BoNT) injections into the affected laryngeal muscles. However, whether BoNT has a lasting therapeutic effect on disorder pathophysiology is unknown. We investigated short-term and long-term effects of BoNT treatment on brain function in patients with LD.MethodsA total of 161 participants were included in the functional MRI study. Statistical analyses examined central BoNT effects in patients with LD who were stratified based on the effectiveness and duration of treatment.ResultsPatients with LD who were treated and benefited from BoNT injections had reduced activity in the left precuneus compared with BoNT-naive and treatment nonbenefiting patients. In addition, BoNT-treated patients with adductor LD had decreased activity in the right thalamus, whereas BoNT-treated abductor patients with LD had reduced activity in the left inferior frontal cortex. No statistically significant differences in brain activity were found between patients with shorter (1–5 years) and longer (13–28 years) treatment durations. However, patients with intermediate treatment duration of 6–12 years showed reduced activity in the right cerebellum compared with patients with both shorter and longer treatment durations and reduced activity in the right prefrontal cortex compared with patients with shorter treatment duration.DiscussionOur findings suggest that the left precuneus is the site of short-term BoNT central action in patients with LD, whereas the prefrontal-cerebellar axis is engaged in the BoNT response in patients with intermediate treatment duration of 6–12 years. Involvement of these structures points to indirect action of BoNT treatment on the dystonic sensorimotor network through modulation of motor sequence planning and coordination.

Treatment of spasticity in patients with the consequences of traumatic brain injury

Up to 16–20% of patients with a history of traumatic brain injury (TBI), regardless of its severity, suffer from pronounced spasticity, cognitive, vestibular and motor disorders. At the same time, data on the effectiveness of botulinum neurotoxin (BoNT) in the treatment of post-traumatic spasticity is lacking.Objective: to assess the effectiveness of peripheral myorelaxants (botulinum neurotoxin type A) in the treatment of past-traumatic spasticity.Patients and methods. 21 male patients aged 25 to 48 years with post-traumatic spastic hemiparesis (at least 6 months after the injury) were examined. 450 to 850 U (mean – 650 U) of BoNT (incobotulinumtoxin) was injected into the spastic muscles of the upper and lower extremities. The follow-up assessment of spasticity and paresis was performed 24±3 days after BoNT injection. Patterns of spasticity were studied: shoulder adduction, elbow joint flexion, forearm pronation, hand and finger flexion, hip adduction, shin flexion, foot flexion, toe flexion. The following methods were used: original methods of manual testing (MMT) of spasticity, Tardieu scale (TS), modified Ashworth scale (MAS), Medical Research Council Scale (MRCS) to assess paresis.Results and discussion. 24±3 days after incobotulotoxin administration, we observed a significant 1.5–2-fold decrease in spasticity angle (xS) and a reduction in the angle of neuromuscular reactivity (xV3) by 15–30° in all the studied patterns. Changes of xV1 (muscle extensibility) and xA (muscle strength) were not significant. No adverse reactions were observed. The use of MMT and TS has shown its effectiveness and specificity in the evaluation of spasticity and effectiveness of BoNT, and in the dynamics of muscle condition.Conclusion. The study showed the feasibility of using MMT and TS in the evaluation and assessment of spasticity, as well as the effectiveness and safety of incobotulinumtoxin (Xeomin) in dosages from 450 to 850 U in the treatment of spasticity of the upper and lower extremities in patients with the consequences of TBI.

Evaluation of MR-Tractography Findings in Hemifacial Spasm Patients Injected with Botulinum Neurotoxin.

Botulinum neurotoxin (BoNT) is a potent biological toxin extracted from Clostridium Botulinum bacteria. BoNT injection is mainly used for medical purposes; it is frequently used for cosmetic purposes as well. The hypothesis that frequent application of this treatment modality may also affect the central nervous system constitutes the subject of our study. We aimed to demonstrate the possible central effects of BoNT in hemifacial spasm patients. Diffusion tensor imaging was used for this study. Patients were divided into two groups, and the measured values for each determined bilateral neuroanatomic region were compared within the relevant group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were found to be closer to the pathological values in the right motor cortex and in the left internal capsule areas of the patients who were injected with BoNT into the left side, in the left motor cortex area of the patients who were injected with BoNT into the right side. No significant changes were detected in other regions. Botulinum neurotoxin administration in patients with hemifacial spasms may cause some changes in the central nervous system as well as peripheral effects. In the case of similar studies supporting pathological changes, BoNT treatment modalities or appropriate indications may be reviewed, and regulation on excessive cosmetic use may be in question.

Botulinum toxin in the masseter muscle: Lingering effects of denervation.

Botulinum neurotoxins (BoNTs) are paralytic agents used to treat a variety of conditions in jaw muscles. Although their effect is considered temporary, there are reports of persistent functional changes. Using rabbits that received BoNT injection in one masseter muscle, the recovery of neuromuscular connection was investigated using nerve stimulation to evoke an electromyographic (EMG) response, and the recovery of muscle fibers was investigated using histological morphometry and bromodeoxyuridine (BrdU) immunohistochemistry. One month after treatment, evoked EMG was greatly reduced in both amplitude and duration, indicating that little reinnervation had taken place. Muscle fibers were atrophied and collagenous tissue was increased. Three months after treatment, evoked EMG duration was normal, indicating that at least some neuromuscular junctions were functional. Histologically, some muscle fibers were hypertrophied, some were still atrophied, and some appeared to have died. Fibrosis was still apparent amid slight increases in dividing cells and regenerating fibers. The histological effects of BoNT were evident although attenuated at a distance of about 1cm from the injection level, but no regional differences could be discerned for the evoked EMGs. In conclusion, there were persistent muscular deficits seen 3months after BoNT treatment that may have been caused by the failure of some affected muscle fibers to become reinnervated.

Passive Properties of the Wrist and Fingers Following Chronic Hemiparetic Stroke: Interlimb Comparisons in Persons With and Without a Clinical Treatment History That Includes Botulinum Neurotoxin.

Background: Neural impairments that follow hemiparetic stroke may negatively affect passive muscle properties, further limiting recovery. However, factors such as hypertonia, spasticity, and botulinum neurotoxin (BoNT), a common clinical intervention, confound our understanding of muscle properties in chronic stroke.Objective: To determine if muscle passive biomechanical properties are different following prolonged, stroke-induced, altered muscle activation and disuse.Methods: Torques about the metacarpophalangeal and wrist joints were measured in different joint postures in both limbs of participants with hemiparetic stroke. First, we evaluated 27 participants with no history of BoNT; hand impairments ranged from mild to severe. Subsequently, seven participants with a history of BoNT injections were evaluated. To mitigate muscle hypertonia, torques were quantified after an extensive stretching protocol and under conditions that encouraged participants to sleep. EMGs were monitored throughout data collection.Results: Among participants who never received BoNT, no significant differences in passive torques between limbs were observed. Among participants who previously received BoNT injections, passive flexion torques about their paretic wrist and finger joints were larger than their non-paretic limb (average interlimb differences = +42.0 ± 7.6SEM Ncm, +26.9 ± 3.9SEM Ncm, respectively), and the range of motion for passive finger extension was significantly smaller (average interlimb difference = −36.3° ± 4.5°SEM; degrees).Conclusion: Our results suggest that neural impairments that follow chronic, hemiparetic stroke do not lead to passive mechanical changes within the wrist and finger muscles. Rather, consistent with animal studies, the data points to potential adverse effects of BoNT on passive muscle properties post-stroke, which warrant further consideration.

Long-term adherence and self-perceived therapy effect of botulinum neurotoxin in different neurological disorders

Long-term adherence and self-perceived therapy effect of botulinum neurotoxin in different neurological disorders

The Botulinum Treatment of Neurogenic Detrusor Overactivity: The Double-Face of the Neurotoxin.

Botulinum neurotoxin (BoNT) can counteract the highly frequent involuntary muscle contractions and the uncontrolled micturition events that characterize the neurogenic detrusor overactivity (NDO) due to supra-sacral spinal cord lesions. The ability of the toxin to block the neurotransmitter vesicular release causes the reduction of contractions and improves the compliance of the muscle and the bladder filling. BoNT is the second-choice treatment for NDO once the anti-muscarinic drugs have lost their effects. However, the toxin shows a time-dependent efficacy reduction up to a complete loss of activity. The cellular mechanisms responsible for BoNT effects exhaustion are not yet completely defined. Similarly, also the sites of its action are still under identification. A growing amount of data suggest that BoNT, beyond the effects on the efferent terminals, would act on the sensory system recently described in the bladder mucosa. The specimens from NDO patients no longer responding to BoNT treatment displayed a significant increase of the afferent terminals, likely excitatory, and signs of a chronic neurogenic inflammation in the mucosa. In summary, beyond the undoubted benefits in ameliorating the NDO symptomatology, BoNT treatment might bring to alterations in the bladder sensory system able to shorten its own effectiveness.

Whole body vibration combined with botulinum neurotoxin A injection in the treatment of spastic diplegic cerebral palsy

Objective To observe the effect of combining whole body vibration with botulinum neurotoxin A injections on tiptoe and the gross motor function of children with spastic diplegic cerebral palsy. Methods Sixty spastic diplegic children with tipped foot aged between 2 to 5 were equally divided into a control group and an experimental group randomly. The control group received 3 IU/kg botulinum neurotoxin A injections to the medial and lateral heads of the gastrocnemius muscle. Then 5 daily courses of conventional training were administered 5 days a week for 3 weeks beginning 24 hours after the injections. The experimental group additionally received 2min of whole body vibration 3 or 4 times per day with one-minute rests, 5 days per week for 5 weeks. All of the children were assessed before the experiment and 1, 3 and 6 months later using the modified Tardieu scale (MTS) and the R1 and R2 ankle and dimensions D and E of the gross motor function measurement scale (GMFM-88). Results There were no significant differences between the two groups before the treatment. Afterward, the average MTS, R1, R2 and GMFM-88 scores of both groups were significantly improved. The average MTS, R1 and R2 scores of the experimental group after treatment were significantly better than the control group′s averages. The average GMFM-88 score of the experimental group was not significantly different from that of the control group after 1 month, but after 3 and 6 months significant differences emerged. Conclusion Whole body vibration improves the effectiveness of botulinum neurotoxin A injections in relieving tiptoe and improving the gross motor function of children with spastic diplegic cerebral palsy. Key words: Cerebral palsy; Whole body vibration; Botulinum neurotoxin A; Tipped foot; Gross motor function