A systematic review of the perspectives of botulinum toxin use on the quality of life of neurological patients with drooling.

OBJECTIVE: To investigate the effectiveness of botulinum toxin in the salivary glands of patients with neurological impairment and drooling and its impact on the quality of life. MATERIALS AND METHODS: This systematic review was registered with the International Prospective Register of Systematic Reviews (CRD 42,023,435,242) and conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. An electronic search was performed in the PubMed/MEDLINE, Embase, Scopus, Cochrane Library, and clinical trial databases until August 2023, no language restriction. Cohort studies and randomized clinical trials of patients diagnosed with drooling and neurological impairment who used botulinum toxin on the salivary gland were included, which evaluated subjective quality of life parameters. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and Risk of Bias 2 tools. The certainty of the evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Eight studies involving 317 patients were included. All studies, through subjective parameters, suggested the effectiveness of botulinum toxin in reducing drooling, resulting in an improvement in the quality of life. Three studies demonstrated improvements in swallowing and four in cases of respiratory diseases. Two clinical trials had a high risk of bias, whereas one had low risk. The five cohort studies that were evaluated had a high risk of bias. The certainty of the evidence was considered low. CONCLUSIONS: Based on the patient/caregivers' perception of improvement in drooling, dysphagia, and respiratory symptoms, it can be inferred that botulinum toxin application reduces subjective drooling in neurologically compromised patients. Its impact contributes to the general well-being and quality of life. CLINICAL RELEVANCE: Injection of botulinum toxin into the salivary glands can be considered an alternative technique to surgical or medicinal approaches in reducing drooling. It is effective, less invasive and without significant side effects. It promotes a positive impact on the well-being and quality of life of neurological patients.

The use of shear-wave elastography for the assessment of muscle spasticity in patients with cerebral palsy, a systematic review.

We explore the use of shear wave elastography (SWE) for assessing muscle stiffness and treatment response in cerebral palsy (CP) children by way of a systematic review. SWE offers real-time muscle stiffness measurements, showing significant differences between CP patients and controls. Studies suggest that SWE can be used to follow muscle stiffness post-botulinum toxin treatment, correlating with clinical improvement. However, methodological variations and small sample sizes prevent comparison between different studies. Standardized protocols could enhance SWE's clinical utility. In conclusion, SWE holds promise for CP management, though standardized methodologies and larger studies are needed to validate its efficacy and integration into clinical practice.

Adverse effect of botulinum toxin-A injections on mandibular bone: A systematic review and meta-analysis.

INTRODUCTION: Botulinum toxin-A (BTX) is a potent neurotoxin that is emerging in the scope of dental practice for its ability to temporarily paralyse musculature and reduce hyperfunction. This may be desirable in diseases/disorders associated with hyperactive muscles such as the muscles of mastication, most implicated in painful temporomandibular disorders (TMDs). The use of BTX extends beyond its indications with off-label use in TMD's and other conditions, while potential adverse effects remain understudied. BTX is well-established hindlimb paralysis model in animals leading to significant bone loss with underlying mechanisms remaining unclear. The objective of this study is to systematically review the literature for articles investigating changes in mandibular bone following BTX injections and meta-analyse available data on reported bone outcomes. METHODS: Comprehensive search of Medline, Embase and Web of Science retrieved 934 articles. Following the screening process, 36 articles in animals and humans were included for quantitative synthesis. Articles in human individuals (6) and three different animal species (14) presented mandibular bone outcomes that were included in the meta-analysis. RESULTS: The masseter and temporalis muscles were frequently injected across all species. In humans, we observe a decrease of about 6% in cortical thickness of mandibular regions following BTX injection with no evident changes in either volume or density of bone structures. In animals, bone loss in the condylar region is significantly high in both cortical and trabecular compartments. DISCUSSION: Our analysis supports the concept of BTX-induced bone-loss model in animal mandibles. Further, bone loss might be confined to the cortical compartments in humans. Most studies did not address the reality of repeated injections and excessive dosing, which occur due to the reversible action of BTX. More rigorous trials are needed to draw a full picture of potential long-term adverse effects on bone.

Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (µV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.

Foodborne Botulism, Canada, 2006-20211.

During 2006-2021, Canada had 55 laboratory-confirmed outbreaks of foodborne botulism, involving 67 cases. The mean annual incidence was 0.01 case/100,000 population. Foodborne botulism in Indigenous communities accounted for 46% of all cases, which is down from 85% of all cases during 1990-2005. Among all cases, 52% were caused by botulinum neurotoxin type E, but types A (24%), B (16%), F (3%), and AB (1%) also occurred; 3% were caused by undetermined serotypes. Four outbreaks resulted from commercial products, including a 2006 international outbreak caused by carrot juice. Hospital data indicated that 78% of patients were transferred to special care units and 70% required mechanical ventilation; 7 deaths were reported. Botulinum neurotoxin type A was associated with much longer hospital stays and more time spent in special care than types B or E. Foodborne botulism often is misdiagnosed. Increased clinician awareness can improve diagnosis, which can aid epidemiologic investigations and patient treatment.

Botulism after intragastric botulinum toxin injections for weight reduction.

Although-considering the risk-benefit ratio-botulinum neurotoxin A (BoNT/A) is unequivocally recommended to treat severe neurological diseases such as dystonia, this has not yet been determined for its endoscopic intragastric injection aimed at weight reduction in obesity. However, severe adverse effects of intragastric BoNT/A had not yet been reported, prompting some European countries to endorse its (off-label) use and treat patients transnationally. We here present three cases of botulism after intragastric BoNT/A injections for obesity treatment in a Turkish hospital. Patients presented with cranial nerve affection, bulbar symptoms, and descending paresis, and benefited from treatment with BoNT antitoxin and pyridostigmine. We assume that iatrogenic botulism was induced by overdosing in combination with toxin spread via the highly vascularized gastric tissue. Of note, within a few weeks, more than 80 cases of iatrogenic botulism were reported across Europe after identical intragastric BoNT/A injections. These cases demonstrate the risks of BoNT/A injections if they are not applied within the limits of evidence-based medicine. There is a need for international guidelines to define the indication and a safe dosing scheme, especially in the context of medical tourism.

Delineation and histological examination of the intramuscular innervation of the platysma: Application to botulinum neurotoxin injection.

This study aimed to identify the whole innervation pattern of the platysma using the Sihler's staining, and the axonal composition profile of the sensory-motor anastomosis identified by immunofluorescence assays. The findings provide a comprehensive understanding of the neural anatomy of the platysma and facilitate efficient and safe manipulation for neurotoxin injection. Ten fixed and two fresh hemifaces were included in this study. Sihler's staining was used to the study 10 fixed hemifaces and two fresh hemifaces were used for immunofluorescence assays. In all cases, the cervical branch of facial nerve (Cbr) broadly innervated the platysma, and the marginal mandibular branch of facial nerve (MMbr) provided supplementary innervation to the uppermost part of the platysma. The transverse cervical nerve (TCN), great auricular nerve (GAN), and supraclavicular nerve (SCN) were observed in the lower half of the platysma. In 30% of all cases, there was a communicating loop between the Cbr and TCN. In 20% of all the cases, a communicating branch joined between the Cbr and GAN. For successful esthetic rejuvenation procedures, a clinician should consider the Cbr distribution to the overall platysma and additionally innervation by individual nerves (MMbr, GAN, TCN, and SCN) to the middle and lower portions of the platysma muscle.

Unilateral Hypofunction of the Masseter Leads to Molecular and 3D Morphometric Signs of Atrophy in Ipsilateral Agonist Masticatory Muscles in Adult Mice.

Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx, MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d-7d for Myogenin. Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry.

[Bladder augmentation in the era of botulinum toxin: Indications and results]. / L'entérocystoplastie d'agrandissement à l'ère de la toxine botulique : indications et résultats.

AIM: To determine the surgical indication and results of bladder augmentation (BA) during the last decade in a neurourology center in the era of intradetrusor botulinum toxin injection. MATERIAL: We conducted a retrospective study that included patients with BA between January 1, 2012 and December 31, 2022 in our centre. We collected pre-operative demographic, clinical, and urodynamic data, BA indication, and associated procedures. We analyzed early and late complications as well as continence and postoperative voiding mode in patients with first BA in a neurological pathology context. RESULTS: We performed 77 BA over the study period. The main indication was neurogenic overactive bladder, which was secondarily resistant to botulinum toxin. The main associated procedure was continent cutaneous diversion (n=31, 57.4%). Among patients who had a first BA for neurogenic bladder, 34 patients had early complications (50%) including 12 patients with≥Clavien 3 complications (17.6%). After a median follow-up of 33 [14; 55] months, 23 patients had late complications (33.8%) and 59 patients had complete continence (86.8%). CONCLUSION: In the era of botulinum toxin, the main indication of BA is the secondary failure of botulinum toxin for overactive neurogenic bladder. The BA provided continence in 86.8% of patients. It remains however an intervention with a significant rate of severe complications whose indication must be discussed by a multidisciplinary team. LEVEL OF EVIDENCE: Weak.

Feasibility of Awake Intravesical Botulinum Toxin Injection in Pediatric Neurogenic Bladder.

PURPOSE: Cystoscopic injection of botulinum neurotoxin (BoNT) is typically performed under general anesthesia in pediatric patients with neurogenic bladder, accumulating anesthetic exposures and operating room costs. As most of these patients already tolerate clean intermittent catheterization (CIC), it has become our practice to offer a trial of awake injection. We report our initial experience here. We hypothesized that higher sensory level, female sex and absence of mental health issues or cognitive delay might predict successful first awake injection and decreased operative times. MATERIALS AND METHODS: Surgical records from 2 academic hospitals from 2018-2020 were reviewed. Generalized linear models were fit to determine predictors of success and procedural length. RESULTS: Trial of awake injection was offered to 22 patients. Eighteen patients (8 female, 10 male, 4-20 years old) elected to proceed. All 18 patients were managed with CIC at baseline, 14 had anxiety or behavioral issues, 10 had cognitive delay and 7 had sensory level below S2. Two patients (11%) required conversion to general anesthesia and one of these subsequently opted for a repeat awake injection trial. Fifteen of the 18 patients (83%) had or planned subsequent injections awake. Of the remaining, 1 proceeded to bladder augment, 1 is considering ileovesicostomy and 1 requested subsequent injections under anesthesia. No intraoperative complications occurred. CONCLUSIONS: Awake BoNT injection is feasible in pediatric patients with neurogenic bladder managed with CIC, even in the setting of intact sensation, well-managed mental health issues or cognitive delay, thereby increasing the viability of BoNT as an early tool in the management of neurogenic bladder.

Distinguishing Features of the Urinary Bacterial Microbiome in Patients with Neurogenic Lower Urinary Tract Dysfunction.

PURPOSE: We aimed to characterize the urinary microbiome of catheterizing patients with neurogenic lower urinary tract dysfunction (NLUTD) and to evaluate differences based on type of bladder management or frequency of urinary tract infections. MATERIALS AND METHODS: This is a prospective, cross-sectional study of urine samples from asymptomatic, catheterizing patients with neurogenic lower urinary tract dysfunction who used either clean intermittent catheterization or indwelling catheters. Patients without symptoms of urinary tract infection provided a catheterized urine sample for urinalysis, culture and bacterial community microbiome analysis. RESULTS: A total of 95 patients submitted urine for analysis, of whom 69 had sufficient sequence reads (>1,203) for microbiome analysis. Cases with low bacterial signal amplification were associated with use of vaginal estrogen, no intradetrusor botulinum toxin A use and no growth on standard urine culture. The most abundant operational taxonomic units were from the phylum Proteobacteria, classified as Enterobacteriaceae and Escherichia. Alpha diversity varied among those who used indwelling catheters vs clean intermittent catheterization, and those who underwent botulinum toxin A injection vs not. On linear discriminate analysis, the relative abundance of the operational taxonomic units identified as Pseudomonas was higher among patients using indwelling catheters relative to clean intermittent catheterization. The operational taxonomic unit identified as Aerococcus was at a higher relative abundance among males compared to females. CONCLUSIONS: Enterobacteriaceae and Escherichia were the most abundant genera in the urinary microbiome of patients with neurogenic lower urinary tract dysfunction. Urinary microbiome diversity varied based on bladder management type. Future clinical correlations between microbiome of neurogenic patients and clinical presentation may help guide treatment strategies.

Intravesical Instillation of OnabotulinumtoxinA in the Treatment of Refractory Overactive Bladder in Participants with Urinary Incontinence.

PURPOSE: Intradetrusor injections of onabotulinumtoxinA are efficacious for the treatment of overactive bladder with urgency urinary incontinence in adults refractory to or intolerant of anticholinergics. Delivery of onabotulinumtoxinA via instillation would reduce the need for intradetrusor injections. The objective of this trial was to assess the efficacy and safety of intravesical instillation of an onabotulinumtoxinA + hydrogel admixture. MATERIALS AND METHODS: After review of a stage 1 safety phase by an independent committee, participants were recruited into stage 2 and randomized to either onabotulinumtoxinA 100, 300, 400, or 500 U, or placebo, all with hydrogel admixture. End points included change from baseline to week 12 in the number of urinary incontinence episodes (primary); micturition, urgency urinary, and nocturia episodes/day; volume voided per micturition; proportion of participants with a ≥50% decrease from baseline in urinary incontinence episodes/day; and Overactive Bladder Questionnaire total score. Adverse events were reported. RESULTS: Change from baseline to week 12 in number of urinary incontinence episodes was -2.72 with placebo and ranged from -0.89 to -1.85 in the onabotulinumtoxinA + hydrogel treatment groups. No difference from placebo was observed for any efficacy end point. The proportions of participants with treatment-emergent adverse events were similar among all groups, with asymptomatic bacteriuria the highest reported (6.7%-15.5%). There were no reports of urinary retention or elevated post-void residual volume. CONCLUSIONS: Intravesical instillation of an onabotulinumtoxinA + hydrogel admixture for the treatment of refractory overactive bladder was well tolerated, but it showed no improvement over placebo.

Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats.

BACKGROUND: Botulinum toxin A (BTX-A) has a variety of uses in medicine. Some evidence suggests that intracavernosal (ic) BTX-A injection administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) could effectively treat erectile dysfunction (ED) in insufficient responders to PDE5-Is. AIM: To provide experimental pharmacological evidence for the use of onabotulinumtoxinA ic alone or in combination with PDE5-Is for difficult-to-treat ED. We thus compared the effects of BTX-A ic alone and BTX-A ic combined with PDE5-I iv, and a placebo treatment ic or iv. METHODS: Erectile function was evaluated following cavernous nerve electrical stimulation (6 V, 1-millisecond pulse, 45-second duration) at different frequencies (0, 2, 3, 4, 5, 7.5, and 10 Hz) in 4 groups (n = 8 / group) of anesthetized, spontaneously hypertensive rats, a robust animal model of ED of vascular origin. Rats were treated by onabotulinumtoxinA 10U or saline ic 1 week prior to erectile function testing and sildenafil (0.3 mg/kg) or saline iv 4 minutes prior to testing. Frequency-response curves were compared with a 2 way ANOVA. OUTCOMES: Both onabotulinumtoxinA ic, and sildenafil iv significantly improved erectile responses in spontaneously hypertensive rats, however the effect was greatly amplified when the treatments were combined. RESULTS: Intracavernosal pressure and/or mean arterial pressure ratios were significantly increased by sildenafil and onabotulinumtoxinA ic versus the control condition. OnabotulinumtoxinA 10U ic combined with sildenafil iv significantly potentiated erectile responses. Area under the curve and/or mean arterial pressure ratio increased by 19% with sildenafil iv, by 15% with onabotulinumtoxinA ic and by 58% with the combined treatment following cavernous nerve electrical stimulation at 6V, 1 ms, 10 Hz: these stimulation parameters elicited the maximal erectile response. CLINICAL TRANSLATION: These data provide a pharmacological rationale for the combined administration of onabotulinumtoxinA ic and sildenafil iv since the effects of both treatments were potentiated when their administration was combined. STRENGTHS & LIMITATIONS: First evidence of a synergistic pro-erectile effect of BTX-A combined with PDE5-I, however the mechanism behind the pro-erectile effect of BTX-A ic remains hypothetical. CONCLUSIONS: These results support further studies into the mechanisms behind the pro-erectile effect of BTX-A ic, as well as multicenter randomized control trials to evaluate the safety and efficacy of BTX-A ic combined with sildenafil for difficult-to-treat ED. Giuliano F., Joussain C., Denys P., et al. Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats. J Sex Med 2022;19:899-906.

Efficacy and safety of intradetrusor botulinum toxin injections for idiopathic overactive bladder syndrome in patients with an artificial urinary sphincter.

PURPOSE: To assess the efficacy and safety of intradetrusor botulinum toxin type A injections (IBTI) for idiopathic overactive bladder (iOAB) in non-neurological adults with an artificial urinary sphincter (AUS). MATERIALS AND METHODS: We retrospectively selected, in the 11 French centers, members of a collaborative network (GENULF (Groupe d'étude de neuro-urologie de langue francaise)), the patients who had had an artificial urinary sphincter implantation and who had subsequently developed iOAB requiring IBTI. This study was approved by the French association of urology ethics committee (no 2018012). RESULTS: Between 2006 and 2020, 33 patients were included from 5 French centers. Mean follow-up after the first IBTI was 47 months. The average age of the studied population was 68 years, with 70% of females. A complete resolution of symptoms at optimal IBTI dose was experienced by 21 (64%) patients. Seven (21%) patients had partial improvement. Five non-responder patients (15%) had no improvement at all. Maximum cystometric bladder capacity was 240 ml pre-IBTI and 335 ml post IBTI. Discontinuation free survival at 60 months was 50%. Two erosions occurred during the 6 months following an IBTI both in male patients with a perineal implantation. There were four AUS balloon perforations that occurred during the 6 months following an IBTI, all of them in female patients. CONCLUSIONS: IBTI has a good efficacy for the treatment of iOAB in patients with an AUS. However, both patients and practicians must be aware of the risk of rare and usually mild complications.

Pathophysiology, assessment, and treatment of overactive bladder symptoms in patients with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is prevalent, difficult to treat, and has close symptom overlap with overactive bladder (OAB). A review of the pathophysiology, assessment, and treatment of IC/BPS patients with overlapping OAB symptoms has not been summarized recently in the published literature. METHODS: A review of the published literature on the overlap of IC/BPS and OAB was conducted using MeSH terminology (1992-2022). RESULTS: The pathophysiology of IC/BPS is not fully understood. Animal research has found the bladder trigone and base are richly populated by afferent fibers, including many small unmyelinated C-fibers that may be upregulated in IC/BPS. Successful therapies with multimodal effects on OAB symptoms in patients with IC/BPS are likely to exert beneficial effects on both pain and lower urinary tract symptoms. Potentially efficacious therapies for the treatment of OAB in IC/BPS include pelvic floor physical therapy, oral pharmacotherapy (antimuscarinics and beta-3 agonists), sacral neuromodulation, percutaneous tibial nerve stimulation, and botulinum toxin A (BTA). Antimuscarinics and beta-3 agonists have yielded partial efficacy in IC/BPS, although may help differentiate symptoms of OAB from those associated with IC/BPS. The transvaginal trigone treatment (T3) intradetrusor injection approach allows for delivery of therapeutics to the bladder without the need for a cystoscope and appears to be feasible. CONCLUSIONS: Further research is needed to understand the pathophysiology of IC/BPS and symptom overlap with OAB, which in turn should enable the development of more personalized therapeutics.

The use of onabotulinumtoxinA to treat idiopathic overactive bladder in elderly patients is in need of study.

BACKGROUND: Injecting onabotulinumtoxinA (BoTN-A) into the bladder has been established as an effective treatment of overactive bladder (OAB) and well-tolerated by patients. However, there evidence suggests the efficacy and safety of this treatment may decrease with age due to increased comorbidities and frailty. This study's objective was to establish empirical evidence regarding age-related differences in outcomes related to BoTN-A for the treatment of idiopathic OAB. METHODS: MEDLINE, EMBASE, and the Cochrane Central Registry for Controlled Trials were systematically searched. Results were restricted to randomized control trials of BoTN-A bladder injections for the treatment of idiopathic OAB. The resulting articles' abstracts were screened independently by two reviewers. Those passing the screen were reviewed in full. Articles were excluded if participants were <18 years old, diagnosed with neurogenic overactivity, or treated with both oral medications and BoTN-A; if the frequency and severity of OAB symptoms were not specified; or, if symptoms were not stratified by age. RESULTS: The initial search resulted in 1572 articles; 166 were reviewed in full. None met all inclusion/exclusion criteria. However, 21 studies met all criteria except age stratification. Authors were contacted to obtain raw data to perform an independent age-based analysis, but sufficient data was not received. CONCLUSION: While the initial systematic review did not generate the expected results, it did reveal that age-related outcomes of BoTN-A for the treatment of OAB are significantly under-studied. Given that the prevalence of OAB increases with age, this is an important knowledge gap. Our article explains the rationale for further study in this area.

Cognitive Performance After Facial Botulinum Toxin Treatment in a Cohort of Neurologic Patients: An Exploratory Study.

OBJECTIVE: To investigate higher cognitive functions after mimicry changes after facial botulinum toxin (BTX) injections, we tested verbal and nonverbal reasoning in patients with blepharospasm or hemifacial spasm before and after their long-term botulinum toxin treatment. DESIGN: Explorative, nonrandomized, clinical trial. SETTING: Patients receiving ambulatory care and control participants from the general community. PARTICIPANTS: Volunteer sample (N=84) of patients (n=21) with blepharospasm or hemifacial spasm who received facial BTX injections. Control participants included patients (n=30) with cervical dystonia who received cervical BTX injections and individuals without neurological disorders (n=33). INTERVENTIONS: The 2 groups receiving injections were tested before and 3 weeks after their treatment. The group without neurological disorders received no injections. MAIN OUTCOME MEASURES: Verbal and nonverbal reasoning scores. RESULTS: The key unexpected finding was that patients who received facial BTX injections perform significantly worse in nonverbal reasoning tasks, when compared with those who did not receive injections (P=.022). There was no significant difference in the baseline reasoning scores and at follow-up for verbal reasoning between the 3 groups. There was no correlation between toxin dose and reasoning scores (verbal: P=.132; nonverbal: P=.294). CONCLUSIONS: Because of potential confounders, the results do not yet allow any conclusion on causality. Further research is needed to confirm our findings.

Cost Efficiency Analysis for Spasticity Management Based on Physician Botulinum Toxin Prescribing Habits.

OBJECTIVE: To estimate differences in botulinum toxin type A (BoNT-A) treatment costs per patient for spasticity-injecting physicians, with a focus on physicians' use of alternative BoNT-A agents other than onabotulinumtoxinA. DESIGN: Retrospective cohort study. SETTING: National Medicare data for fee-for-service beneficiaries in 2017. PARTICIPANTS: A total of 116 physicians, 6829 BoNT-A procedures, and 3051 patients were included in this analysis. Most physicians were physiatrists (84%) and used only onabotulinumtoxinA (82%). INTERVENTIONS: Type of BoNT-A selected by physicians was the independent variable of interest. Included physicians were separated into 2 groups: (1) onabotulinumtoxinA only injectors and (2) abobotulinumtoxinA and/or incobotulinumtoxinA injectors (may still use onabotulinumtoxinA). MAIN OUTCOME MEASURE: Average cost per patient per year. RESULTS: The total average BoNT-A cost per patient per year was significantly less for physicians who used abobotulinumtoxinA and/or incobotulinumtoxinA vs those who used only onabotulinumtoxinA ($3684 vs $4739; P=.01). Patients' average annual out-of-pocket costs also reflected a similar difference ($855 vs $1082; P=.02) between the groups. Doses used and numbers of injections per patient per year were not significantly different between groups. CONCLUSIONS: The present analysis demonstrated lower cost per patient for both the payer and patient when physicians used types of BoNT-A other than onabotulinumtoxinA for spasticity. Nevertheless, most physicians in this spasticity-focused study used exclusively onabotulinumtoxinA, the most expensive BoNT-A available. Reasons for this are complex and include history on the market and approved indications beyond those associated with spasticity. However, future research should continue to identify such issues with a goal of finding solutions to improve cost inefficiencies.

Clinical Efficacy of Botulinum Toxin in the Treatment of Plantar Fasciitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy of botulinum toxin A (BTX-A) for the treatment of plantar fasciitis through a meta-analysis of randomized controlled trials (RCTs) focusing on pain and functional outcomes since current literature has supported a potential benefit of BTX-A. DATA SOURCES: The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched until December 2020 for RCTs reporting the effects of BTX-A injections on plantar fasciitis. The complementary literature search included Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and greylit.org. STUDY SELECTION: Only RCTs assessing the effect of BTX-A injections on pain, functional improvement, or plantar fascia thickness in patients with plantar fasciitis were included. Multiple researchers carried out the screening process of the 413 records. DATA EXTRACTION: Data were extracted independently and in duplicate using a standardized data extraction format. Information was contrasted by a third observer. DATA SYNTHESIS: BTX-A injections resulted in significant pain relief (mean difference, -2.07 [95% CI, -3.21 to -0.93]; P=.0004; I2=97%) and functional improvement (standardized mean difference, 1.15 [95% CI, 0.39-1.91]; P=.003; I2=87%). A subanalysis indicated that pain relief was sustained at 12 months while functional improvement remained significant after 0-6 months. The results were not affected by a single study after sensitivity analysis. The site of injection and the use or not of ultrasound-guided injections may account for potential sources of interstudy heterogeneity. CONCLUSIONS: This meta-analysis suggests both a statistically significant and a clinically meaningful improvement on plantar fasciitis symptoms after BTX-A treatment.

Investigating Inducible Muscle Overactivity in Acquired Brain Injury and the Impact of Botulinum Toxin A.

OBJECTIVE: To investigate the pattern of change in muscle overactivity during repetitive grasp/release using dynamic computerized dynamometry (DCD; objective 1) and the effect of botulinum toxin A (BTX-A; objective 2). DESIGN: Secondary analysis of an observational cohort study. SETTING: Hospital outpatient spasticity management service. PARTICIPANTS: A convenience sample (N=65), comprising adults with upper motor neuron syndrome affecting the arm after acquired brain injury (ABI; n=38) and participants without ABI (n=27). INTERVENTIONS: After clinical assessment, a subgroup of participants with ABI (n=28) underwent BTX-A injections as part of their spasticity management. MAIN OUTCOME MEASURES: Post hoc DCD data processing extracted the values of minimum force generation between 10 sequential contractions. The pattern of change was analyzed. RESULTS: The ABI injected group exerted greater force at baseline than both other groups (ABI injected=1.04 kg, ABI noninjected=0.74 kg, participants without ABI=0.53 kg; P=.011). After the first contraction, minimum force values increased for all groups and were greatest in the ABI injected group. With subsequent cycles, the group without ABI showed a linear pattern of decreasing force generation, whereas both ABI groups showed a quadratic increasing pattern, which was of greater magnitude in the ABI injected group. After injection, values for the ABI injected group showed a 51% reduction in inducible muscle overactivity (P=.003) to magnitudes similar to those of the ABI noninjected group. CONCLUSIONS: This study showed that hand relaxation deteriorated during repetitive movements in people with spasticity, a feature hypothesized to adversely influence everyday hand function. After BTX-A injection, the magnitude but not the pattern of this inducible muscle overactivity improved.