Botulinum Neurotoxin Type Research Articles

Physical therapy, intra-articular dextrose prolotherapy, botulinum neurotoxin, and hyaluronic acid for knee osteoarthritis: randomized clinical trial.

This study aimed to compare the efficacy of four treatments in the management of knee osteoarthritis. We carried out a randomized clinical trial with four study arms in an outpatient Department of Physical Medicine and Rehabilitation at a University Hospital. In total, 120 patients with knee osteoarthritis ≥50 years of age were randomly allocated to four groups. The primary outcome was knee pain in visual analog scale and the secondary outcome was the Knee Injury and Osteoarthritis Outcome Score. The exercise was prescribed daily for all participants throughout the study. For physical therapy (group 1), participants received superficial heat, transcutaneous electrical nerve stimulation and pulsed ultrasound. We administered a single intra-articular injection of botulinum neurotoxin type A (group 2) and three injections of hyaluronic acid (group 3) or 20% dextrose (group 4) to patients in the corresponding groups. Mixed analysis of variance showed that there was statistically significant difference between the groups in pain (P < 0.001), and Knee Injury and Osteoarthritis Outcome Score (P < 0.001). Pairwise between- and within-group comparisons showed that botulinum neurotoxin and dextrose prolotherapy were the most, and hyaluronic acid was the least efficient treatments for controlling pain and recovering function in patients. An intra-articular injection of botulinum toxin type A or dextrose prolotherapy is effective first-line treatments. In the next place stands physical therapy particularly if the patient is not willing to continue regular exercise programs. Our study was not very supportive of intra-articular injection of hyaluronic acid as an effective treatment of knee osteoarthritis.

IncobotulinumtoxinA for the treatment of spasticity in children with cerebral palsy \u2013 a retrospective case series focusing on dosing and tolerability

BackgroundIncobotulinumtoxinA (Xeomin®) is a botulinum neurotoxin type A with established efficacy in the treatment of upper-limb spasticity in adults. This retrospective case series in a university hospital setting aimed to elucidate the safety and tolerability of incobotulinumtoxinA for treatment of spasticity in children with cerebral palsy.MethodsParticipants received incobotulinumtoxinA injections up to a maximum total dose of 600 U, 24 U/kg body weight. Medical records were reviewed for key demographic information, incobotulinumtoxinA exposure, and adverse effects (AEs).ResultsSixty-nine children were included (mean age [SD], 8.3 [3.9] years; 44/69 [63.8%] male). One-hundred-and-ninety-one injections were administered, with mean (SD) of 2.8 (1.5) treatment cycles/participant and dosing interval of 6.0 (1.7) months. The number of muscles injected increased from 2.4 (1.2) at cycle 1 to 4.2 (1.9) at cycle 6. The mean (SD) total incobotulinumtoxinA dose increased from 191.7 (126.2) U, (8.5 [5.4] U/kg body weight) at cycle 1 to 368.0 (170.1) U, (9.9 [5.5] U/kg body weight) at cycle 6. Seventy four adverse effects (37.5% of injections) were reported, the most frequent was injection pain (93.2% of AEs). Only three AEs were considered directly treatment-related by injectors: muscle weakness, generalized weakness, and fever.ConclusionsOur clinical experience indicates that incobotulinumtoxinA is a well-tolerated treatment option for focal spasticity in children with cerebral palsy.Trial registrationAs the study was observational and retrospective, no EudraCT registration number was requested. The internal code assigned to the study in the administrative resolution was: 1143-N-15.

Anatomical Considerations When Treating Compensatory Hypertrophy of the Upper Part of the Masseter after Long-Term Botulinum Neurotoxin Type A Injections.

The masseter is the most targeted muscle when treating hypertrophy to produce a smooth face shape. Compensatory hypertrophy is a well known clinical sequela that occurs in botulinum neurotoxin (BoNT) treatments and is limited to the lower part of the masseter. Based on the masseteric hypertrophy procedure, which targets a confined area, we predicted the possibility of compensatory hypertrophy occurring in the upper part of the masseter. If the patient complains about an unexpected result, additional injections must be performed, but the involved anatomical structures have not been revealed yet. The aim of this study was to identify the morphological patterns of the masseter. Deep tendons were observed in most specimens of the upper part of the masseter and mostly appeared in a continuous pattern (69.7%). The superficial and deep tendons could be classified into a simply connected form and forms surrounding part of the muscle. In 45.5% of cases there were tendon capsules that completely enclosed the muscle, which can interfere with how the injected toxin spreads. Interdigitation patterns in which the tendons could be identified independently between the muscles were present in 9.1% of cases. The present findings provide anatomical knowledge for use when injecting BoNT into the masseter.

Voice analysis in adductor spasmodic dysphonia: Objective diagnosis and response to botulinum toxin

IntroductionAdductor-type spasmodic dysphonia is a task-specific focal dystonia characterized by involuntary laryngeal muscle spasms. Due to the lack of quantitative instrumental tools, voice assessment in patients with adductor-type spasmodic dysphonia is mainly based on qualitative neurologic examination. We evaluated patients with cepstral analysis and specific machine-learning algorithms and compared the results with those collected in healthy subjects. In patients, we also used cepstral analysis and machine-learning algorithms to investigate the effect of botulinum neurotoxin type A. MethodsWe investigated 60 patients affected by adductor-type spasmodic dysphonia before botulinum neurotoxin type A therapy and 60 age and gender-matched healthy subjects. A subgroup of 35 patients was also evaluated after botulinum neurotoxin type A therapy. We recorded the sustained emission of a vowel and a sentence by means of a high-definition audio recorder. Voice samples underwent cepstral analysis as well as machine-learning algorithm classification techniques. ResultsCepstral analysis was able to differentiate between healthy subjects and patients, but receiver operating characteristic curve analysis demonstrated that machine-learning algorithms achieved better results than cepstral analysis in differentiating healthy subjects and patients affected by adductor-type spasmodic dysphonia. Similar results were obtained when differentiating patients before and after botulinum neurotoxin type A therapy. Cepstral analysis and machine-learning measures correlated with the severity of voice impairment in patients before and after botulinum neurotoxin type A therapy. ConclusionsCepstral analysis and machine-learning algorithms are new tools that offer meaningful support to clinicians in the diagnosis and treatment of adductor-type spasmodic dysphonia.

Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a meta-analytic study.

Apart from the known efficacy of Botulinum Neurotoxin Type A (BoNT/A) in hyperactive striated and smooth muscles, different pain states have become potential targets of toxin effects. This present study determined the comparative toxin effectiveness in pain reduction among those patients injected with BoNT/A in muscle-based and in non-muscle-based conditions. Randomized controlled trials (RCTs) on the effect of BoNT/A on selected pain conditions were included. The conditions were spasticity and dystonia for muscle-based pain. For non-muscle-based pain, conditions included were painful diabetic neuropathy (PDN), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), and spinal cord injury (SCI). In view of possibly differing pathophysiology, myofascial pain, temporomandibular joint (TMJ), other joint or tendon pains, cervicogenic and lumbar pains, migraine and visceral pain syndromes were excluded. Standardized mean difference was used as the effect measure and computed with STATA. 25 RCTs were analyzed. Pooled estimates showed significantly lower pain score in the Treatment group (z = 5.23, p < 0.01, 95% CI = - 0.75, - 0.34). Subgroup analyses showed that BoNT/A significantly reduced both muscle-based (z = 3.78, p < 0.01, 95% CI = - 0.72, - 0.23) and non-muscle-based (z = 3.37, p = 0.001, 95% CI = - 1.00, - 0.27) pain. Meta-regression using four covariates namely dosage, route, frequency and duration was done which revealed that dosage significantly affects standardized mean differences, while the other three covariates were insignificant. The joint F-test was found to be insignificant (p value = 0.1182). The application of the model with these covariates does not significantly explain the derived heterogeneity of standardized mean differences. In conclusion, BoNT/A can be effectively used in muscle-based and non-muscle-based pain disorders. We detected no difference between the presence and magnitude of pain relief favoring muscle-based compared to non-muscle-based pain. Thus, we cannot say whether or not there might be independent mechanisms of toxin-induced pain relief for pain generated from either muscle or nerve hyperactivity.

A Moving Residual Limb: Botulinum Toxin to the Rescue.

Movement disorders post-amputation are a rare complication and can manifest as the jumping stump phenomenon, a form of peripheral myoclonus. The pathophysiology remains unknown and there is currently no standardized treatment. We describe the case of a 57-year-old male with unremitting stump myoclonus, starting one month after transtibial amputation, in his residual limb without associated phantom or neurological pain. The consequence of the myoclonus was a reduction in prosthetic wearing time. Failure to respond to oral medication led us to attempt the use of botulinum neurotoxin Type A injections in the involved muscles of the residual limb. Injection trials, over a two-year period, resulted in an improvement of movement disorder, an increased prosthetic wearing time and a higher satisfaction level of the patient. Injection of botulinum toxin type A should be considered as an alternative treatment for stump myoclonus to improve prosthetic wearing time and comfort.

A Phase I/II Randomized, Double Blind, Active-controlled, Single Center Clinical Trial for Evaluation of Safety and Efficacy of ATGC-110, An Intramuscularly Administered Clostridium Botulinum Neurotoxin Type A, in Adult Patients With Moderate to Severe Glabellar Frown Lines

A Phase I/II Randomized, Double Blind, Active-controlled, Single Center Clinical Trial for Evaluation of Safety and Efficacy of ATGC-110, An Intramuscularly Administered Clostridium Botulinum Neurotoxin Type A, in Adult Patients With Moderate to Severe Glabellar Frown Lines

Endocytosis, trafficking and exocytosis of intact full-length botulinum neurotoxin type a in cultured rat neurons

Botulinum toxin A (BoNT/A) is a potent neurotoxin that acts primarily by silencing synaptic transmission by blocking neurotransmitter release. BoNT/A comprises a light chain (LC/A) intracellular protease and a heavy chain (HC/A) composed of a receptor binding domain (HCC/A) and a translocation domain (HCN/A) that mediates cell entry. Following entry into the neuron, the disulphide bond linking the two peptide chains is reduced to release the LC/A. To gain better insight into the trafficking and fate of BoNT/A before dissociation we have used a catalytically inactive, non-toxic full-length BoNT/A(0) mutant. Our data confirm that BoNT/A(0) enters cortical neurons both in an activity-dependent manner and via a pathway dependent on fibroblast growth factor receptor 3 (Fgfr3) signalling. We demonstrate that both dynamin-dependent endocytosis and lipid rafts are involved in BoNT/A internalisation and that full-length BoNT/A(0) traffics to early endosomes. Furthermore, while a proportion of BoNT/A remains stable in neurons for 3 days, BoNT/A degradation is primarily mediated by the proteasome. Finally, we demonstrate that a fraction of the endocytosed full-length BoNT/A(0) is capable of exiting the cell to intoxicate other neurons. Together, our data shed new light on the entry routes, trafficking and degradation of BoNT/A, and confirm that trafficking properties previously described for the isolated HCC/A receptor binding domain of are also applicable to the intact, full-length toxin.

Non-toxic fragment of botulinum neurotoxin type A and monomethyl auristatin E conjugate for targeted therapy for neuroendocrine tumors.

Surgical resection is the only cure for neuroendocrine tumors (NETs). However, widespread metastases have already occured by the time of initial diagnosis in many cases making complete surgical removal impossible. We developed a recombinant heavy-chain receptor binding domain (rHCR) of botulinum neurotoxin type A that can specifically target synaptic vesicle 2 (SV2), a surface receptor abundantly expressed in multiple neuroendocrine tumors. Expression of neuroendocrine differentiation markers chromogranin A (CgA) and achaete-scute complex 1 (ASCL1) were signficantly reduced when treated with rHCR. rHCR conjugated to the antimitotic agent monomethyl auristatin E (MMAE) significantly suppressed proliferation of pancreatic carcinoid (BON) and medullary thyroid cancer cells (MZ) at concentrations of 500 and 300 nM respectively, while no growth suppression was observed in pulmonary fibroblasts and cortical neuron control cell lines. In vivo, rHCR-MMAE significantly reduced tumor volume in mouse xenografts with no observed adverse effects. These data suggest recombinant HCR (rHCR) of BoNT/A preferentially targets neuroendocrine cancer without the neurotoxicity of the full BoNT/A and that SV2 is a specific and promising target for delivering drugs to neuroendocrine tumors.

Agrin Influences Botulinum Neurotoxin A-Induced Nerve Sprouting via miR-144-agrin-MuSK Signaling

Botulinum neurotoxin (BoNT) has become a powerful therapeutic tool, and is extensively used in aesthetic medicine and in the treatment of neurological disorders. However, its duration of effect is limited, mainly owing to nerve sprouting. Inhibition of nerve sprouting to prolong the effective duration of BoNT is therefore of great clinical interest. However, appropriate interventional strategies to accomplish this are currently unavailable. In this study, we determined the role of the neurogenic regulator agrin in BoNT type A (BoNT/A)-induced nerve sprouting in a rat model. We then determined whether agrin could be used as an interventional target for prolonging the duration of effect of BoNT/A, and made a preliminary study of the upstream and downstream regulatory mechanisms by which agrin could influence the effective duration of BoNT/A. Our results showed that agrin was involved in the regulation of BoNT/A-induced nerve sprouting, and blocking of agrin function with anti-agrin antibody temporarily could delay muscle strength recovery and prolong the duration of BoNT/A effect. Moreover, agrin influenced the duration of BoNT/A effect by regulating downstream myogenic muscle-specific receptor tyrosine kinase (MuSK), and was simultaneously regulated by upstream miR-144. In conclusion, agrin could regulate BoNT/A-induced nerve sprouting through miR-144-agrin-MuSK signaling; it influences the effective duration of BoNT/A, and could find clinical application as an interventional target for prolonging the effect of BoNT/A.

Botulinum toxin in pain management of trigeminal neuralgia: literature review

ABSTRACT BACKGROUND AND OBJECTIVES: Botulinum neurotoxin type A has been an interesting therapeutic complement to the conventional treatment of neuralgia, especially in patients without satisfactory response to pharmacotherapy and/or surgical procedures. A detailed and comprehensive literature review its important for the description of the available evidence, allowing for a critical view on the topic. Therefore, this study's objective was to describe the scientific evidence on the use of botulinum toxin type A in the neuralgia treatment. CONTENTS: Pubmed and Scielo databases were searched using the descriptors: trigeminal neuralgia and botulinum toxin. Inclusion criteria were human studies (open-label, double-blind, randomized, and placebo-controlled trials) and reviews of the use of botulinum toxin type A in neuralgia treatment, published in English, Spanish or Portuguese from January 2008 to March 2020. Twenty-one articles met the inclusion criteria. Overall, studies demonstrated that botulinum toxin type A significantly reduced pain intensity and paroxysmal episodes, as well as improved quality of life. CONCLUSION: Use of botulinum toxin type A in treatment of refractory neuralgia shows promising results, but further studies are needed to increase the knowledge and consolidation of this therapeutic alternative.

Duplication of clostridial binding domains for enhanced macromolecular delivery into neurons.

Neurological diseases constitute a quarter of global disease burden and are expected to rise worldwide with the ageing of human populations. There is an increasing need to develop new molecular systems which can deliver drugs specifically into neurons, non-dividing cells meant to last a human lifetime. Neuronal drug delivery must rely on agents which can recognise neurons with high specificity and affinity. Here we used a recently introduced ‘stapling’ system to prepare macromolecules carrying duplicated binding domains from the clostridial family of neurotoxins. We engineered individual parts of clostridial neurotoxins separately and combined them using a strong alpha-helical bundle. We show that combining two identical binding domains of tetanus and botulinum type D neurotoxins, in a sterically defined way by protein stapling, allows enhanced intracellular delivery of molecules into neurons. We also engineered a botulinum neurotoxin type C variant with a duplicated binding domain which increased enzymatic delivery compared to the native type C toxin. We conclude that duplication of the binding parts of tetanus or botulinum neurotoxins will allow production of high avidity agents which could deliver imaging reagents and large therapeutic enzymes into neurons with superior efficiency.

Repurposing of FDA-Approved Drugs for Treating Iatrogenic Botulism: A Paired 3D-QSAR/Docking Approach†.

Botulinum neurotoxin (BoNT) is widely used for the treatment of spasticity, focal dystonia, chronic migraine, facial hemispasm, and facial aesthetic treatments. Generally, treatment with botulinum toxin is a safe procedure when conducted by clinicians with expertise, and local side effects are rare and transient. However, occasionally adverse effects can occur due to the spread of the drug to nontargeted muscles and organs, producing dry mouth, fatigue, and flu-like symptoms, up to signs of systemic botulism, which appears to be more frequent in children treated for spasticity than in adults. In silico 3D-QSAR and molecular docking studies were performed to build a structure-based model on selected potent known botulinum neurotoxin type A inhibitors; this was used to screen the US Food and Drug Administration (FDA) database. Thirty molecules were identified as possible light-chain BoNT/A inhibitors. In this study, we applied a well-established ligand- and structure-based methodology for the identification of hit compounds among a database of FDA-approved drugs. The identification of budesonide, protirelin, and ciclesonide followed by other compounds can be considered a starting point for investigations of selected compounds that could bypass much of the time and costs involved in the drug approval process.

Tables of Toxicity of Botulinum and Tetanus Neurotoxins.

Tetanus and botulinum neurotoxins are the most poisonous substances known, so much so as to be considered for a possible terrorist use. At the same time, botulinum neurotoxin type A1 is successfully used to treat a variety of human syndromes characterized by hyperactive cholinergic nerve terminals. The extreme toxicity of these neurotoxins is due to their neurospecificity and to their metalloprotease activity, which results in the deadly paralysis of tetanus and botulism. Recently, many novel botulinum neurotoxins and some botulinum-like toxins have been discovered. This large number of toxins differs in terms of toxicity and biological activity, providing a potential goldmine for novel therapeutics and for new molecular tools to dissect vesicular trafficking, fusion, and exocytosis. The scattered data on toxicity present in the literature require a systematic organization to be usable by scientists and clinicians. We have assembled here the data available in the literature on the toxicity of these toxins in different animal species. The internal comparison of these data provides insights on the biological activity of these toxins.

Editors' note: High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy

In the article “High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy,” Albrecht et al. investigated the prevalence of neutralizing antibodies (NAbs) against botulinum neurotoxin type A (BoNT/A) in a monocentric, observational cross-sectional study of 596 outpatients treated with BoNT/A over a mean of 5.3 years for different indications and found that 13.9% had measurable NAbs. The probability of developing NAbs increased with the single and cumulative dose of treatment and was associated with the BoNT/A formulation used, leading the authors to recommend avoiding booster injections and reducing the individual injected doses. In response, Dr. Jankovic notes that the authors did not mention other studies that showed a much lower frequency of NAbs, although after shorter periods of observation, and indicates that no data were provided regarding any correlation between the presence of NAbs and clinical response. In this regard, Dr. Jankovic notes that none of the patients in a previous study with blocking antibodies identified by the mouse protection assay (MPA) had any clinical response, suggesting that the MPA may be more clinically meaningful. In their reply, Albrecht et al. postulate that lower rates of NAbs in previous studies may relate to lower sensitivity of the MPA, lower BoNT doses used, and substantially shorter duration of treatment. In contrast to Dr. Jankovic's findings, they report that all their patients with NAbs opted to continue treatment and reported ongoing subjective benefit. Both the authors and Dr. Jankovic agree on the need for novel assays with higher sensitivity and specificity that are (ideally) not animal based. In another response, Mulroy et al. caution that the authors' conclusions may mislead readers into thinking that long-term treatment with frequent or repeated BoNT injections can result in clinical treatment failure. Like Dr. Jankovic, they too highlight the absence of data on clinical effectiveness in this study and note that NAb serostatus did not always correlate with clinical response in previous studies. They also seek to clarify the authors' disclosures, given that the study was funded by Merz Pharmaceuticals, which manufacturers one of the BoNT formulations studied. Replying to these comments, Albrecht et al. argue that there is consensus that the induction of NAbs should be avoided, as they are associated with reduced treatment response in several studies. They acknowledge that they do not have information about NAb induction with treatment intervals shorter than 10 weeks in their study, note the difficulty of comparing treatment efficacy across different indications, and concede that efficacy data were not available for all patients. They also state that pharmaceutical funding had no influence on the interpretation or analysis of their data. This correspondence highlights enduring uncertainty in the field regarding the clinical implications of NAbs as detected by existing animal-based assays. In the special article “Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis,” Rae-Grant et al. reported the findings of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology based on reviewing the evidence on starting, switching, and stopping disease-modifying therapies for clinically isolated syndrome, relapsing-remitting MS, and progressive forms of MS. In response, Dr. Tran, on behalf of Genentech, argues that the report did not make it clear that data on annualized relapse rate reduction and relative risk of in-study disability progression for ocrelizumab (presented along with other therapies in figures 1 and 3) were from direct comparisons with subcutaneous interferon-β-1a 44 μg 3 times weekly in 2 phase 3 randomized, double-blind, double-dummy trials. In response, Dr. Rae-Grant agrees that this information should have been included, but notes that statements in the text of the summary and in a key accompanying table acknowledged the superior efficacy of ocrelizumab compared with interferon- β-1a 3 times weekly. Dr. Rae-Grant also notes that data on subgroup analysis of treatment of highly active MS with ocrelizumab were not available at the time of publication of the systematic review.

ELISA Based Detection of Botulinum Neurotoxin Type F in Red Meat and Canned Fish

Botulinum neurotoxin (BoNT) is the most toxic protein molecule so far known to animals and humans, due to its extreme toxicity, CDC has been listed as category ‘A' Biological warfare agents. In India, there is no commercial detection system available for the detection of botulism. The present study was aimed to develop an ELISA based detection system for botulinum neurotoxin serotype F in red meat and canned fish. Polyclonal antibodies were generated against the recombinant BoNT/F LC protein and IgG was purified. Sandwich ELISA system was successfully optimized with LOD of ~ 7.8 ng/ml in PBS. Similarly, different concentrations of BoNT/F were spiked in red meat and canned fish and extracted the toxin and the detection LOD was achieved for red meat ~ 62 ng/ml and for canned fish ~ 31 ng/ml. The developed detection system is highly specific. The developed assay will be useful for the screening of botulinum toxins in a large number of food samples.

Magnetic quantum dot based lateral flow assay biosensor for multiplex and sensitive detection of protein toxins in food samples

Protein toxins, such as botulinum neurotoxin type A (BoNT/A) and staphylococcal enterotoxin B (SEB), easily pollute food and water and are ultra-toxic to humans and animals, thus requiring a sensitive on-site detection method. In this study, we reported a novel lateral flow assay (LFA) strip on the basis of magnetic quantum dot nanoparticles (MagQD NPs) for sensitive and multiplex protein toxin detection in food samples. A new type of MagQD NP was prepared by fixing the dense carboxylated QDs on the surface of polyethyleneimine-modified Fe3O4 magnetic NPs (MNPs) and applied in LFA with the following functions: capture and enrich target toxins from sample solutions and serve as advanced fluorescent labels for the quantitative determination of targets on the strip. Through this strategy, the assay realized quantified BoNT/A and SEB detection in 30 min with the limits of detection of 2.52 and 2.86 pg/mL, respectively. The selectivity and the ability of quantitative analysis of the method were validated in real food samples, including milk and juice. This MagQD-LFA biosensor showed considerable potential as a point-of-care testing tool for the sensitive detection of trace toxins.

Assessing stability of Xeomin botulinum neurotoxin type A and comparing baseline efficacy with two week stored reconstructed drug

Assessing stability of Xeomin botulinum neurotoxin type A and comparing baseline efficacy with two week stored reconstructed drug

Assessment of Anticholinergic Use After Fading of BTX-A Effects in Refractory Idiopathic Overactive Bladder: A Prospective Blinded Randomized Trial.

PurposeTo evaluate the efficacy and safety of re-treatment with anticholinergics on refractory idiopathic overactive bladder (OAB) previously treated with intravesical botulinum neurotoxin type A (BTX-A) injections.MethodsOne hundred patients were initially managed by intravesical injections of 100 IU of BTX-A. After the effects of BTX-A faded, patients were randomized into 2 groups: group A patients received solifenacin (10 mg) for 12 weeks (study group), while group B patients received placebo treatment for 12 weeks (control group), then subsequently received solifenacin (10 mg) for another 6 weeks. All patients underwent preoperative urodynamic testing. Patients were asked to complete the validated overactive bladder symptoms score (OABSS) and incontinence quality of life (I-QoL) instruments after the effects of intravesical BTX-A faded and at 12 weeks of follow-up. Univariate and multivariate analyses of the factors affecting treatment response were conducted.ResultsAt 12 weeks of follow-up, in group A, all OABSS items, including the total score, had improved significantly (P<0.0001). Group A had lower frequency and amplitude of detrusor overactivity and detrusor leak point pressure (P<0.0001, P=0.03, and P=0.01, respectively). Cystometric capacity also increased significantly (P=0.007), as did all I-QoL parameters. In a comparison of patients with failed treatment and patients with successful treatment, female sex, repeated intravesical BTX-A injections, and increased bladder capacity were statistically significant (P=0.001, P=0.0001, and P=0.002, respectively). Repeated intravesical BTX-A injections and increased bladder capacity were independent factors predicting treatment success.ConclusionsIn patients with refractory idiopathic OAB, reuse of anticholinergics could be an effective treatment option in patients after the effects of BTX-A fade. Repeated intravesical BTX-A injections and increased cystometric capacity could affect treatment response.

SERS-Based Immunoassays for the Detection of Botulinum Toxins A and B Using Magnetic Beads.

Rapid and sensitive detection of botulinum neurotoxins (BoNTs) is important for immediate treatment with proper antitoxins. However, it is difficult to detect BoNTs at the acute phase of infection, owing to its rarity and ambiguous symptoms. To resolve this problem, we developed a surface-enhanced Raman scattering (SERS)-based immunoassay technique for the rapid and sensitive detection of BoNTs. Magnetic beads and SERS nanotags as capture substrates and detection probes, respectively, and Nile Blue A (NBA) and malachite green isothiocyanate (MGITC) as Raman reporter molecules were used for the detection of two different types of BoNTs (types A and B), respectively. The corresponding limits of detection (LODs) were determined as 5.7 ng/mL (type A) and 1.3 ng/mL (type B). Total assay time, including that for immunoreaction, washing, and detection, was less than 2 h.