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Introduction : Thoracic outlet syndrome (TOS) causes neurogenic symptoms in 95% of the cases due to neurovascular bundle compression. The treatment goal is the decompression of the neurovascular structures. In the last decade, non-surgical treatments have been evaluated as a treatment option for spastic syndromes and thoracic outlet syndrome. In this study we report the use of botulinum toxin (BTX-A) injection as a diagnostic tool to identify the pectoral minor syndrome, and as a less aggressive treatment-option. Methods : An observational cohort study of patients with neurogenic thoracic outlet syndrome who underwent sonographically guided chemodenervation of pectoral minor muscle with botulinum toxin. Follow-up includes clinical evaluation at one month, 3 months and 6 months after the procedure. Clinical evaluation was made with clinical questionnaire. In case of patients with partial improvement of the symptoms, a second infiltration of BTX-A was performed. The categorical variables were shown as percentages, and the continuous variables as mean and standard deviation (SD). For the comparison of categorical variables, the Fisher's exact test was used. Statistical analysis was performed using the SPSS version 20.0 program. We consider p Results : A total of twenty-six patients were diagnosed with thoracic outlet syndrome in this period, and 20 accomplished the inclusion criteria. Seven patients were excluded (1 due to neoplasia, 2 did not sign the informed consent, 1 due to neoplasia, 2 did not sign the informed consent, 1 was lost during the follow-up and 3 due to anomalies of the first rib secondary to fractures and cervical rib and 1 was lost during the follow-up), therefore a sample of 13 patients aged between 24 and 55 years was obtained. The most common type of procedure performed was the single injection of 50 IU of botulinum toxin. Four patients were infiltrated in two occasions due to partial improvement in symptoms at one-month follow-up. Clinical stability was found at three months and at six months follow-up. Conclusion : The ultrasound-guided botulinum injection of the pectoralis minor muscles provides symptoms relief in patients with pectoral minor syndrome, and could be considered a safe tool in the diagnosis of the pectoralis minor syndrome within the spectrum of thoracic operculum syndrome.

Spasmodic dysphonia is a chronic voice disorder that is characterized by involuntary spasms of the laryngeal muscles during speech production. Botulinum toxin injection into to the laryngeal muscles is the most common and effective treatment of choice for symptoms of spasmodic dysphonia. We present a 44-year-old man with adductor spasmodic dysphonia who was diagnosed as having upper airway obstruction in a polysomnographic examination during sleep after a botulinum toxin injection.

This study aimed to investigate the effect of preoperative botulinum toxin (BTX) injection on intraoperative abnormal muscle response (AMR) in patients with hemifacial spasm (HFS). A total of 104 patients (32 men, 72 women) who underwent microvascular decompression (MVD) for HFS were included in this study. A total of 62 patients without and 42 patients with preoperative BTX treatments were assigned to group A and group B, respectively. AMR recordings were obtained from the orbicularis oculi and mentalis muscles by stimulation of the marginal mandibular branch and zygomatic branch of the facial nerve, respectively. The intraoperative AMR monitoring findings and therapeutic effects were compared between groups A and B. The rates of the patients with unavailable AMRs recorded from the orbicularis oculi muscles in group B (38.1%) were significantly higher than those in group A (14.5%, p = 0.006). Moreover, in cases with over 4 times BTX injection, the recordings of AMR from the orbicularis oculi muscles were poorer than the cases with less BTX injection (p = 0.001). There were no significant differences in the rates of the patients with unavailable AMRs recorded from the mentalis muscles between the two groups. There were no significant differences in the surgical results obtained between the two groups. Preoperative BTX injections should be less than 4 times to ensure effective AMR monitoring. MVD using AMR monitoring is useful for patients with HFS who were previously treated by BTX as well as those who were not treated.

BACKGROUND There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. OBJECTIVES To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). PATIENTS AND METHODS A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP-2&3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&Q2) were completed at 2-, 6-, and 12-weeks post treatment. RESULTS Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p

Clostridium botulinum causes infant and adult intestinal botulism by colonizing in the intestine and producing botulinum neurotoxin (BoNT). Antimicrobial agents are not currently used for treatment due to the potential facilitation of BoNT production and bacterial cell lysis, which releases toxins into the intestinal lumen. In this study, we analyzed effects of four antibiotics on the viability of and BoNT production by four C. botulinum group I strains. Our results indicate that metronidazole rapidly reduced their viability without enhancing BoNT production. Antibiotics with these properties may promote elimination of C. botulinum from the intestines while maintaining low levels of BoNT. This article is protected by copyright. All rights reserved.

Botulism is a neuroparalytic disease caused by a neurotoxin produced by Clostridium botulinum. This study aimed to genetically characterize C. botulinum strain isolated from the first case of infant botulism in Korea reported on June 17, 2019. We isolated C. botulinum strain CB-27 from a stool sample of the patient and analyzed the toxin types and toxin gene cluster compositions of the strain using a mouse bioassay, real-time PCR, and genome sequencing. Toxin gene cluster analysis showed that strain CB-27 possesses a C. botulinum neurotoxin type A harboring an unexpressed B gene. Although the nucleotide and amino acid sequences of toxin genes as well as the toxin gene cluster arrangements in strain CB-27 were identical to those of the known strain CDC_69094, the total nucleotide sequences of the toxin gene clusters of CB-27 differed from those of CDC_69094 by 0.47%, indicating genetic diversity of toxin gene clusters of CB-27 among other previously reported C. botulinum strains. To our knowledge, this is the first description of a C. botulinum strain with two separate toxin gene clusters in Korea.

A case of a purely eccrine nevus in an adolescent patient presenting with focal hyperhidrosis on an area comprising the left forearm and the dorsal aspect of the left hand is described. No clinically evident lesions were identifiable. Dermatopathologic findings were subtle, showing only a slight increase in the number of eccrine glands. Clinicopathological correlation was paramount to achieve the diagnosis.

BACKGROUND Laryngeal dystonia (LD), or spasmodic dysphonia (SD), is a neurological disorder characterized by focal dystonia or involuntary spasms of the laryngeal muscles and associated voice symptoms. It is typically treated with injection of botulinum toxin (BoNT) that weakens the affected muscles. AIMS The primary purpose of this qualitative study was to explore participants' experience of living with LD and BoNT treatment. The secondary purpose was to examine those experiences as a function of participants' scores on the Communicative Participation Item Bank (CPIB). Results will enhance our understanding of restrictions in communicative participation, assist in planning intervention targeting these restrictions and aid in clinical interpretation of CPIB scores. METHODS & PROCEDURES Semi-structured interviews using a phenomenological tradition and focusing on BoNT treatment and communicative participation were conducted with 26 people with LD who are on established BoNT treatment regimens. Interviews were recorded, transcribed, coded and analysed inductively. Participants were categorized by CPIB scores into groups ranging from none to extensive participation restrictions. Both self- and expert ratings of voice were obtained. OUTCOMES & RESULTS Participants with different levels of CPIB scores had different experiences related to communicative participation in the context of BoNT treatment. These differences were organized into the following topics: BoNT and voice; attitudes toward participation; coping strategies; and advice. For all participants except those in the least restricted and most restricted groups, expert ratings of voice did not relate to CPIB scores. CONCLUSIONS & IMPLICATIONS Although most participants report improved voice with BoNT treatment, many participants experienced lingering restrictions in communicative participation, some to a severe extent. Participants reported coping with these restrictions in many ways; some of these strategies were more successful than others. Those with restricted participation recommended more support for daily life and the emotional toll of LD, as well as support for family members. This support might be offered by speech-language pathologists. WHAT THIS PAPER ADDS What is already known on the subject Participants with different levels of CPIB scores had different experiences related to communicative participation in the context of BoNT treatment. What this study adds to the existing knowledge Although most participants report improved voice with BoNT treatment, many participants experienced lingering restrictions in communicative participation, some to a severe extent. What are the potential or actual clinical implications of this work? SLP services that take a participation-focused approach to intervention and use multi-factorial approaches to help clients maximize their life participation in the context of LD are well within the SLP scope of practice. SLPs can help clients find and use their optimal voices within the constraints of the dystonia and BoNT effects.

Focal hand dystonia (FHD) is usually adult-onset focal dystonia that can be associated with marked occupational and functional disability leading to reduced quality of life. Relevant studies on treatment options for FHD, their limitations, and current recommendations were reviewed using the PubMed search until March 31, 2021. Besides, the reference lists of the retrieved publications were manually searched to explore other relevant studies. and conclusion Currently, botulinum toxin has the best evidence for treatment of FHD, and 20–90% of patients experience symptomatic improvement. However, its benefit is often limited by the reduction of muscle tonus acting on the muscle spindle. Different surgical modalities that have been used to treat focal hand dystonia include lesional surgery, deep brain stimulation, and magnetic resonance–guided focused ultrasound thalamotomy. Recent studies exploring the role of behavioral techniques, sensorimotor training, and neuromodulation for the treatment of focal hand dystonia have reported good outcomes, but larger studies are required before implementing these interventions in practice.

Spasticity is the most common motor disturbance in cerebral palsy (CP). Lockdown in the COVID-19 outbreak has profoundly changed daily routines, and similarly caused the suspension of spasticity treatment plans. Besides, the delay in botulinum toxin (BoNT) injection, which is important in the management of focal spasticity, led to some problems in children. This consensus report includes BoNT injection recommendations in the management of spasticity during the COVID-19 pandemic in children with CP. In order to develop the consensus report, physical medicine and rehabilitation (PMR) specialists experienced in the field of pediatric rehabilitation and BoNT injections were invited by Pediatric Rehabilitation Association. Items were prepared and adapted to the Delphi technique by PMR specialists. Then they were asked to the physicians experienced in BoNT injections (PMR specialist, pediatric orthopedists, and pediatric neurologists) or COVID-19 (pediatric infectious disease, adult infectious disease). In conclusion, the experts agree that conservative management approaches for spasticity may be the initial steps before BoNT injections. BoNT injections can be administered to children with CP with appropriate indications and with necessary precautions during the pandemic.

Aim To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia. Method Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE. Results Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non‐randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis. Interpretation Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta‐analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain.Meta‐analysis suggests that DBS may improve motor function.Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals.ITB and DBS may improve quality of life.No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis., What this paper adds Meta‐analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain.Meta‐analysis suggests that DBS may improve motor function.Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals.ITB and DBS may improve quality of life.No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis. This article's abstract has been translated into Spanish and Portuguese. Follow the links from the abstract to view the translations.

Lesch-Nyhan syndrome is a genetic metabolic disorder often involving dystonia and self-mutilating behavior. This case report describes a 13-year-old boy with Lesch-Nyhan syndrome and self-mutilating behavior who received botulinum toxin injections to his bilateral masseter muscles after failing multiple other treatments. Following injections, the patient had reduction in self-biting, along with improvements in speech, mastication and feeding observed in speech therapy. Botulinum toxin injections to the masseters may help to improve oromotor function and reduce self-mutilating behaviors in children with Lesch-Nyhan syndrome who have failed more conservative treatments, providing opportunity for improved functional status and patient safety. Further investigation is indicated to establish optimal dosing. Additionally, the mechanism for the reduction of self-mutilating behavior is unclear and justifies additional investigation.

Spasticity is a common and disabling symptom in patients with multiple sclerosis (PwMS): as highlighted by many epidemiological studies, it is often a severe and not well treated. Despite the availability of evidence-based spasticity management guidelines, there is still great variability in everyday therapeutic approach, especially for the most complex cases. In our single-centre study, we retrospectively evaluated PwMS-treated nabiximols and botulinum toxin injections (BTI) from July 2015 to April 2019. Clinical and demographic data were collected. The severity of spasticity and spasms was recorded by modified Ashworth Scale (mAS) and Penn Spasm Frequency Scale (PSFS) at baseline and after 1 month of treatment. We evaluated 64 treatments for MS-related spasticity: 28 patients were treated with BTI and 36 patients with nabiximols. We found that both BTI and nabiximols are effective in reducing mAS (nabiximols, BTI: p < 0.001), PSFS frequency (nabiximols: p = 0.001, BTI: p = 0.008) and intensity (nabiximols: p = 0.001, BTI p = 0.016). No differences were found when directly comparing the efficacy of the two treatments, except for a statistical trend favouring BTI on spasms intensity (p = 0.091). Eleven patients were treated with both BTI and nabiximols, and only four patients continued both treatments. All dropouts were due to inefficacy of at least one of the two therapies. Our single-centre experience highlights that both BTI and nabiximols are effective in treating multiple sclerosis-related spasticity; however, BTI treatment may be more effective on spasms intensity. Combined nabiximols and BTI treatment could represent a therapeutic option for severe spasticity.

Treatment options for refractory overactive bladder (OAB) following behavioral modifications and oral OAB medications remain limited. Up to 33% of women fail botulinum toxin injections (Amundsen et al. Eur Urol. 74(1):66–73, 7). This study evaluates the effectiveness of combining oral OAB agents with botulinum toxin in subjects who failed botulinum toxin therapy alone. This is a retrospective observational study. Eligible women were those who received botulinum toxin injections for OAB between 2013 and 2018 at one academic institution. Women were given the option of oral medications as add-back therapy following failed treatment with botulinum toxin alone. Treatment response was a subjective outcome, with subjects reporting being satisfied or unsatisfied. The primary outcome was the proportion of subjects who achieved satisfactory treatment response with the combination of oral OAB medications and botulinum toxin injections. A subanalysis was performed to further investigate any risk factors associated with poor response to combination treatment. Variables were analyzed using chi-squared or Fisher’s exact test and Student's t-test or Mann-Whitney U when appropriate. A total of 107 charts were reviewed. Forty-five (48%) women failed botulinum toxin alone as a treatment; 26 (29%) elected to try one or more oral OAB medications. Of the 26 women who received the combination treatment, 17 (65%) reported satisfaction and 9 (35%) remained unsatisfied. Risk factors associated with treatment failure were not identified. This is an initial report on adding back oral OAB meds to patients who have failed botulinum toxin injections suggesting there may be a role for add-back oral OAB medications.

BACKGROUND: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb weakness, dysarthria, emotional lability, and respiratory failure. Since normal salivary production is 0.5 L to 1.5 L daily, loss of salivary clearance due to dysphagia leads to salivary pooling and sialorrhea, often resulting in distress and inconvenience to people with MND. This is an update of a review first published in 2011. OBJECTIVES: To assess the effects of treatments for sialorrhea in MND, including medications, radiotherapy and surgery. SEARCH METHODS: On 27 August 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov and the WHO ICTRP. We checked the bibliographies of the identified randomized trials and contacted trial authors as needed. We contacted known experts in the field to identify further published and unpublished papers. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi‐RCTs, including cross‐over trials, on any intervention for sialorrhea and related symptoms, compared with each other, placebo or no intervention, in people with ALS/MND. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified four RCTs involving 110 participants with MND who were described as having intractable sialorrhea or bulbar dysfunction. A well‐designed study of botulinum toxin B compared to placebo injected into the parotid and submandibular glands of 20 participants showed that botulinum toxin B may produce participant‐reported improvement in sialorrhea, but the confidence interval (CI) was also consistent with no effect. Six of nine participants in the botulinum group and two of nine participants in the placebo group reported improvement (risk ratio (RR) 3.00, 95% CI 0.81 to 11.08; 1 RCT; 18 participants; low‐certainty evidence). An objective measure indicated that botulinum toxin B probably reduced saliva production (in mL/5 min) at eight weeks compared to placebo (MD −0.50, 95% CI −1.07 to 0.07; 18 participants, moderate‐certainty evidence). Botulinum toxin B may have little to no effect on quality of life, measured on the Schedule for Evaluation of Individual Quality of Life direct weighting scale (SEIQoL‐DW; 0‐100, higher values indicate better quality of life) (MD −2.50, 95% CI −17.34 to 12.34; 1 RCT; 17 participants; low‐certainty evidence). The rate of adverse events may be similar with botulinum toxin B and placebo (20 participants; low‐certainty evidence). Trialists did not consider any serious events to be related to treatment. A randomized pilot study of botulinum toxin A or radiotherapy in 20 participants, which was at high risk of bias, provided very low‐certainty evidence on the primary outcome of the Drool Rating Scale (DRS; range 8 to 39 points, higher scores indicate worse drooling) at 12 weeks (effect size −4.8, 95% CI −10.59 to 0.92; P = 0.09; 1 RCT; 16 participants). Quality of life was not measured. Evidence for adverse events, measured immediately after treatment (RR 7.00, 95% CI 1.04 to 46.95; 20 participants), and after four weeks (when two people in each group had viscous saliva) was also very uncertain. A phase 2, randomized, placebo‐controlled cross‐over study of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate (DMQ) found that DMQ may produce a participant‐reported improvement in sialorrhea, indicated by a slight improvement (decrease) in mean scores for the primary outcome, the Center for Neurologic Study Bulbar Function Scale (CNS‐BFS). Mean total CNS‐BFS (range 21 (no symptoms) to 112 (maximum symptoms)) was 53.45 (standard error (SE) 1.07) for the DMQ treatment period and 59.31 (SE 1.10) for the placebo period (mean difference) MD −5.85, 95% CI ‐8.77 to ‐2.93) with a slight decrease in the CNS‐BFS sialorrhea subscale score (range 7 (no symptoms) to 35 (maximum symptoms)) compared to placebo (MD –1.52, 95% CI ‐2.52 to ‐0.52) (1 RCT; 60 participants; moderate‐certainty evidence). The trial did not report an objective measure of saliva production or measure quality of life. The study was at an unclear risk of bias. Adverse events were similar to other trials of DMQ, and may occur at a similar rate as placebo (moderate‐certainty evidence, 60 participants), with the most common side effects being constipation, diarrhea, nausea, and dizziness. Nausea and diarrhea on DMQ treatment resulted in one withdrawal. A randomized, double‐blind, placebo‐controlled cross‐over study of scopolamine (hyoscine), administered using a skin patch, involved 10 randomized participants, of whom eight provided efficacy data. The participants were unrepresentative of clinic cohorts under routine clinical care as they had feeding tubes and tracheostomy ventilation, and the study was at high risk of bias. The trial provided very low‐certainty evidence on sialorrhea in the short term (7 days' treatment, measured on the Amyotrophic Lateral Scelerosis Functional Rating Scale‐Revised (ALSFRS‐R) saliva item (P = 0.572)), and the amount of saliva production in the short term, as indicated by the weight of a cotton roll (P = 0.674), or daily oral suction volume (P = 0.69). Quality of life was not measured. Adverse events evidence was also very uncertain. One person treated with scopolamine had a dry mouth and one died of aspiration pneumonia considered unrelated to treatment. AUTHORS' CONCLUSIONS: There is some low‐certainty or moderate‐certainty evidence for the use of botulinum toxin B injections to salivary glands and moderate‐certainty evidence for the use of oral dextromethorphan with quinidine (DMQ) for the treatment of sialorrhea in MND. Evidence on radiotherapy versus botulinum toxin A injections, and scopolamine patches is too uncertain for any conclusions to be drawn. Further research is required on treatments for sialorrhea. Data are needed on the problem of sialorrhea in MND and its measurement, both by participant self‐report measures and objective tests. These will allow the development of better RCTs.

Purpose This report describes the clinical course of the traumatic chiasmal syndrome and treatment of diplopia due to the hemifield-slide phenomenon. Case report A 20-year-old male with decreased vision in both eyes following blunt head trauma was referred to the neuro-ophthalmology clinic. Neuroimaging revealed disruption of the optic chiasm and skull base fracture. After partial vision recovery, the patient noticed complete bitemporal hemianopia. Three months later, he was exotropic and complained of diplopia and difficulty in near visual tasks. His symptoms were successfully controlled by injection of botulinum toxin A in both lateral rectus muscles. Conclusions There is some potential for improvement in vision in patients with traumatic chiasmal syndrome. Botulinum toxin could be used in patients with the hemifield-slide phenomenon to predict the sensory outcome of surgery and relieve the bothersome symptoms.

Botulinum toxin (BT) has been successfully used for many years to treat various muscle hyperactivity disorders including dystonia and spasticity. Its dosing is guided by dosing tables describing target muscles and dose ranges. To refine the BT dosing, we wanted to analyse how contextual factors may influence the injector's final dosing decision.In a retrospective review of real-life data of 1170 BT treatments, we studied the influence of various contextual factors on the BT doses in 21 arm muscles of 252 patients receiving BT therapy for different muscle hyperactivity disorders.We found that BT arm doses are significantly higher in treatment of spasticity than in treatment of dystonia. We also found that spontaneous arm dystonia requires higher BT doses in a proximal application pattern, whereas task specific writer's cramp requires considerably reduced BT doses with a distal application pattern. Injections of non-arm muscles influence the BT dosing in arm muscles only marginally.Our study demonstrates that BT dosing does not only depend on the particularities of the individual target muscle injected, such as its volume and its static or phasic function. BT dosing and its application pattern rather depend on additional contextual factors such as the aetiology and pathophysiology of the muscle hyperactivity treated. These contextual factors need to be included in dosing tables and may improve the outcome of BT therapy.

Objective The main objective of this study was to define and verify anatomo-sonographic landmarks for ultrasound-guided injection of botulinum toxin into the longissimus capitis (LC) and splenius cervicis (SC) muscles. Methods and results After a preliminary work of anatomical description of the LC and SC muscles, we identified these muscles on two cadavers and then on a healthy volunteer using ultrasound and magnetic resonance imaging (MRI) to establish a radio-anatomical correlation. We defined an anatomo-sonographic landmark for the injection of each of these muscles. The correct positioning of vascular glue into the LC muscle and a metal clip into the SC muscle of a fresh cadaver as verified by dissection confirmed the utility of the selected landmarks. Discussion For the LC muscle, the intramuscular tendon of the cranial part of the muscle appears to be a reliable anatomical landmark. The ultrasound-guided injection can be performed within the cranial portion of the muscle, between the intra-muscular tendon and insertion into the mastoid process at dens of the axis level. For the SC muscle, the surface topographic landmarks of the spinous processes of the C4–C5 vertebrae and the muscle body of the levator scapulae muscle seem to be reliable landmarks. From these, the ultrasound-guided injection can be carried out laterally by transfixing the body of the levator scapulae. Conclusion The study defined two cervical anatomo-sonographic landmarks for injecting the LC and SC muscles.

Prolonged remission of dystonia occurs rarely; however, well-documented cases are lacking. We report the clinical characteristics and course of four patients with botulinum toxin (BoNT)-associated prolonged remission of idiopathic cervical dystonia. Mean age at onset was 40 years. All had a relatively short duration of symptoms (mean 10.3 months), and with remission occurring after ≤ 3 treatments with BoNT. At last examination, the remission duration was 2–5 years. In the two cases that subsequently relapsed after 4–5 years, there was an altered phenomenology and worsened severity than at the onset. Recognizing this rare phenomenon has valuable clinical implications.

Patients with neurogenic lower urinary tract dysfunction (NLUTD) experience urinary incontinence with or without difficult urination, which might promote recurrent urinary tract infection (UTI) and exacerbate upper urinary tract function. Nonetheless, appropriate bladder management has been shown to reduce urological complications and improve quality of life. In addition to pharmacological therapy and surgical intervention, botulinum toxin A (BoNT-A) has been widely utilized in NLUTD. The therapeutic efficacy of detrusor BoNT-A injections for neurogenic detrusor overactivity due to spinal cord injury (SCI), multiple sclerosis, or other central nervous system lesions, such as cerebrovascular accident, Parkinson disease, early dementia, and pediatric NLUTD due to myelomeningocele, has been well established, with repeated BoNT-A injections every 6 to 9 months being necessary to maintain its therapeutic effects. Urethral BoNT-A injection can decrease urethral sphincter resistance and facilitate efficient voiding in patients with NLUTD who wish to preserve self-voiding. Detrusor BoNT-A injection can also decrease the occurrence of autonomic dysreflexia in patients with SCI, even after failed augmentation enterocystoplasty, with additional benefits including reduced UTI episodes and preserved renal function with repeated injections. However, this treatment does have some side effects. Complete informed consent for BoNT-A injection therapy with full disclosure of its potential complications should therefore be obtained before this procedure is undertaken.

OBJECTIVE: To determine the effectiveness of intrapyloric botulinum toxin injection (IPBI) for treatment of feeding disorders and associated gastrointestinal symptoms in very young children. STUDY DESIGN: A single-center retrospective study of patients 2 months to 5 years old who received IPBI at Boston Children’s Hospital from May 2007 to June 2019 was performed. Charts were reviewed for demographic data, comorbidities, symptoms leading to IPBI, oral and tube feeding data, symptom improvement after IPBI, and need for repeat injections. The primary outcome was symptom improvement at the first gastroenterology clinic visit following IPBI. Secondary outcomes included improvement in oral feeding, reduction in tube feeding, and need for repeat injections. Chi-square or Fisher exact tests and multivariate logistic regression were used to identify factors associated with symptomatic improvement. RESULTS: A total of 85 patients who received 118 injections were included in the final analysis; 57patients (67%) had partial or complete improvement in symptoms after IPBI. Amongst the 55 patients with enteral tubes, there was an improvement in feeding, with more patients receiving at least some oral feeds after IPBI compared with before (26/55 vs. 15/55, P = 0.004) and fewer patients receiving post-pyloric feeds after IPBI compared with before (12/55 vs. 21/55, P = 0.01). Twenty-six patients (31%) received repeat IPBI within one year, with only six patients receiving IPBI more than twice. CONCLUSION: IPBI is safe and effective in young children. Children with enteral tubes show improvement in oral feeding and reduction in need for post-pyloric feeding after IPBI.

Botulinum neurotoxins (BoNTs) are the most potent toxins known and they cause the paralytic disease botulism in humans and animals. In order to diagnose botulism, active BoNT must be detected in biological material. Endopep-MS is a sensitive and selective method for serum samples, based on antibody capture, enzymatic cleavage of target peptides, and detection of cleavage products using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). In many cases of animal botulism, serum samples are not available or they do not contain detectable amounts of BoNT and liver sampling is an alternative for postmortem examinations. However, the Endopep-MS method is impaired by the inherent protease activity of liver samples. In the presented study, the Endopep-MS method has been successfully modified and validated for analysis of cattle, horse, and avian liver samples, introducing a combination of a salt washing step and a protease inhibitor cocktail. These modifications resulted in a substantial decrease in interfering signals and increase in BoNT-specific signals. This led to a substantial improvement in sensitivity for especially BoNT-C and C/D which are among the most prominent serotypes for animal botulism. Botulism was diagnosed with the new method in liver samples from dead cattle and birds from outbreaks in Sweden. Graphical Abstract Electronic supplementary material The online version of this article (10.1007/s00216-020-03001-z) contains supplementary material, which is available to authorized users.

Cervical dystonia (CD) is a focal dystonia characterized by involuntary contractions of neck muscles that result in patterned movements and abnormal postures of the head and neck that have a directional quality. CD is the most common form of dystonia presenting to the movement disorders clinic. Botulinum toxin is an effective treatment for cervical dystonia. It has become the first-line treatment for cervical dystonia with a satisfactory relief of symptoms reported in more than 80% of the cases. Multiple small and large scale studies proven that fact and provided Class-A evidence for the benefit. However, 20% of the patients discontinue treatment due to adverse effects, treatment failure and other reasons. With the proper knowledge of toxins and the anatomy of the neck, much better results can be achieved with fewer and self-limiting adverse effects as compared to other modalities. However, the expert consensus recommendations are lacking to guide clinicians for optimal use of botulinum toxin for cervical dystonias. This paper discusses the different available treatments, botulinum injection techniques and the adverse effects involved with the procedure.

Abnormalities of the upper airway anatomy are an underrecognized cause of obstructive sleep apnea. We present a unique case of a 51-year-old man with episodic sleep-maintenance insomnia and oromandibular dystonia requiring botulinum toxin injections of the temporalis and masseter muscles. He underwent multiple sleep studies and was found to have obstructive sleep apnea temporally associated with the severity of dystonia symptoms and dosing of botulinum toxin. CITATION: Hsu N, Hsieh C, Thomas A, Chang M. Obstructive sleep apnea due to oromandibular dystonia and treated with botulinum toxin. J Clin Sleep Med. 2020;16(7):1209–1212.

Introduction. Cervical dystonia is the most frequent form of focal dystonia. It is characterised by involuntary muscular contractions resulting in abnormal head/neck and shoulder movements and postures, which can be associated with tremor and pain. Local intramuscular injections of botulinum toxin type A (BoNT-A) is the treatment of choice, being both effective and well-tolerated. However, a considerable number (c. 30%) of patients discontinue this treatment. The aim of this review was to analyse the factors possibly responsible for treatment failures of cervical dystonia (CD), with special regard to the new classification known as the ‘Col-Cap’ concept and non-motor symptoms. Clinical implications. Several factors analysed in this review are responsible for effective treatment: proper diagnosis of dystonia and exclusion of pseudodystonias, correct recognition of dystonia pattern and identification of new patterns according to the Col-Cap concept, muscle selection and precise injections under electromyography (EMG) and/or ultrasonography (US) guidance. Furthermore, concomitant diagnosis and treatment of non-motor symptoms such as depression, anxiety, fatigue, sleep problems, phobias and stigmatisation are crucial in obtaining the best overall effect of the treatment. Primary and secondary immunisation and non-responsiveness seem to be marginal problems nowadays due to a low potential of new BoNT-A formulations to produce neutralising antibodies. Future directions. There is a need for new and relevant scales combining the Col-Cap concept patterns with non-motor symptoms and quality of life. There is also a lack of specific rehabilitation protocols which could enhance BoNT-A treatment results.

Botulinum neurotoxins (BoNTs) are potent toxins produced by Clostridium bacteria that are responsible for the illness botulism and are listed as bioterrorism agents. BoNT serotype E (BoNT/E) is one of four BoNT serotypes that cause human botulism and is the second most frequent cause of foodborne botulism. Rapid detection and discrimination of BoNT serotypes implicated in human disease are critical for ensuring timely treatment of patients and identifying sources of toxins, but there have been few reported detection methods for BoNT/E and even fewer methods usable for BoNT serotyping. We report a nanobiosensor based on Forster resonance energy transfer (FRET) between semiconductor nanocrystals (quantum dots, QDs) and dark quencher-labeled peptide probes to detect biologically active BoNT/E in aqueous media. The peptide probes contain a specific cleavage site for active BoNT/E. QD photoluminescence, which changes intensity due to FRET when the peptide probe is cleaved, was used to indicate toxin presence and quantity. The detection of a BoNT/E light chain (LcE) and holotoxin was observed within 3 h. The limits of detection were 0.02 and 2 ng/mL for LcE and holotoxin, respectively. The nanobiosensor shows good specificity toward the target in tests with nontarget BoNT serotypes. The high sensitivity, simple operation, short detection time, and ability to be used in parallel with probes developed for other BoNT serotypes indicate that the nanobiosensor will be useful for rapid BoNT/E detection and serotype discrimination in food analysis.

Objectives Half of patients with amyotrophic lateral sclerosis experience sialorrhea due to facial weakness. Although anticholinergic medications are first-line therapy, they often lead to unacceptable side effects. Radiation therapy and botulinum toxin may be considered when medical management fails. In this systematic review, we investigated the effectiveness of these interventions. Methods Eligible studies were retrieved from PubMed and Scopus databases up to March 2017 along with hand-searching of references from primary articles. Results Fourteen studies (N = 138) examined the benefits of botulinum toxin. Studies varied in salivary glands treated, dosages used, and the use of botulinum toxin subtype A or B. A majority of studies showed benefit after treatment. Although most studies reported only mild adverse effects, 2 case studies revealed severe complications including recurrent TMJ dislocations and rapid deterioration in bulbar function. Ten studies (N = 171) examined the benefits of radiation. Most studies reported improvement with only mild adverse events reported. Conclusions Both radiation and botulinum toxin are effective treatments for sialorrhea in patients with amyotrophic lateral sclerosis and should be considered when medical management fails. Radiation may offer longer duration of symptom improvement with fewer complications.

Botulinum toxin is a neurotoxin produced by Clostridium botulinum and some other relative species. It causes a lethal disease called botulism. It can enter the body via infections by Clostridium (e.g. wound and children botulism) or by direct contact with the toxin or eating contaminated food (food-borne botulism). Botulinum toxin is also considered as a relevant biological warfare agent with an expected high number of causalities when misused for bioterrorist or military purposes. The current paper surveys the actual knowledge about botulinum toxin pathogenesis, the manifestation of poisoning, and current trends in diagnostics and therapeutics. Relevant and recent literature is summarized in this paper.

Tardive dyskinesia (TD) is an iatrogenic condition that encompasses a wide phenomenological spectrum of movement disorders caused by exposure to dopamine receptor blocking agents (DRBAs). TD may cause troublesome or disabling symptoms that impair quality of life. Due to frequent, often inappropriate, use of DRBAs, TD prevalence rates among patients exposed to DRBAs continue to be high. The judicious use of DRBAs is key to the prevention of TD, reduction of disease burden, and achieving lasting remission. Dopamine-depleting vesicular monoamine transporter type 2 inhibitors are considered the treatment of choice of TD.

Objectives Long-term facial paralysis results in degeneration of the distal nerve segment and atrophy of the supplied muscles. Options for these patients include free muscle transfer, temporalis myoplasty, and botulinum toxin injections for smile reanimation. In this study we aimed to evaluate the subjective and objective outcomes of these procedures. Materials and Methods In our study, we retrospectively analyzed smile symmetry in patients with facial palsy (n=8) who underwent facial reanimation procedures. Results Subjective analysis showed high satisfaction in seven out of eight patients. Objective analysis showed statistically significant improvement postoperatively in both vertical and horizontal smile symmetry at rest and during maximum smile (P

Many transient facial nerve insults, including Bell's palsy, Ramsay Hunt syndrome, Lyme-associated facial paralysis, and temporal bone fractures, ultimately lead to nonflaccid facial palsy (NFFP). NFFP is associated with significant functional, aesthetic, psychological, and social impairments. However, algorithms for comprehensive management of this entity are not well developed and are rapidly evolving. Herein, we present our current approach to NFFP, with the goal of providing a framework that may be applied to this complex patient population.

AIMS To examine the effectiveness and safety of using a CAD/CAM-derived injection guide for botulinum neurotoxin block of the sphenopalatine ganglion for trigeminal neuralgia treatment. METHODS Ten patients with second-division trigeminal neuralgia who did not respond to submucosal administration of botulinum neurotoxin were enrolled in this study. The target point around the sphenopalatine fossa was determined after fusion of computed tomography data with a scan of a maxillary model using a software program for dental implant surgery. A CAD/CAM-derived injection guide was fabricated. The guide was affixed to the patient's maxilla, and a needle was inserted to an exactly analyzed depth. Subsequently, 50 units of botulinum neurotoxin were injected. Pain intensity evaluated using a visual analog scale and pain frequency were measured. RESULTS By using the guides, sphenopalatine ganglion block with botulinum toxin was performed 18 times without any complications. The visual analog scale score (8.1 ± 1.0) and pain frequency (19.4 ± 8.8 times/day) decreased (to 1.9 ± 1.4 and 4.9 ± 5.4 times/day, respectively) significantly (P < .001). After 4 weeks, the mean subjective improvement achieved was 77.5% ± 13.8%, and all patients responded to treatment. CONCLUSION Even without prior experience of sphenopalatine ganglion block, the CAD/CAM-derived guide enabled the accurate and safe administration of botulinum neurotoxin to the sphenopalatine ganglion for the treatment of trigeminal neuralgia.

Introduction: Though many unanswered questions about the pathophysiology of Tourette Syndrome remain, several pharmacotherapies for tics have been studied, with varying results in terms of efficacy and the strength of evidence.Areas covered: This literature review encompasses pharmacotherapies for tics. The pharmacotherapies discussed in this review include: alpha agonists, antipsychotics, topiramate, botulinum toxin, and dopamine depleters.Expert opinion: Once the presence of tics is confirmed and psychoeducation and support are provided to patients and caregivers, one must examine the degree of tic-related impairment and the presence of psychiatric comorbidities. These factors influence treatment decisions as the presence of comorbidity and related impairment may shift the treatment target. When selecting a medication for tics, the presence of ADHD (the most frequent comorbidity) strengthens the case for choosing an alpha agonist. The case for antipsychotic medications is strongest when tic-related impairment is severe and/or the tics are refractory to more conservative measures. All medications require drug safety monitoring procedures and reevaluation over time.

Synkinesis is a negative sequela of facial nerve recovery. Despite the necessity of effective treatment, controversy exists regarding optimal management and outcome reporting measures. The goals of this study were to evaluate the current synkinesis literature and compare effectiveness of treatment modalities. A search of biomedical databases was performed in May 2019. Full-text English language articles of cohort studies or randomized controlled trials on synkinesis treatment were eligible for inclusion. Reviews, animal studies, and those without assessment of treatment effect were excluded. We found 592 unique citations; 33 articles were included in the final analyses. Nine studies focused on botulinum toxin (BTX-A), 7 on surgery, 5 on physical therapy (PT), and 12 on multimodal therapy. The Sunnybrook Facial Grading System was the most frequently used outcome measure (17 studies, 51.5%). All treatment modalities improved outcomes. Chemodenervation studies showed an average improvement of 17.8% (range 11 to 33.3%) in the respective outcome measures after treatment. PT improved by 29.7% (range 14.6 to 41.2%), surgery by 16.6% (range 4.7 to 41%) and combination therapy by 20.4% (range 5.13 to 37.5%). Only 21 studies (63.6%) provided data on adverse outcomes. There are lack of high evidence level data for robust comparisons of post-paretic synkinesis treatments, however, this condition is likely effectively treated non-surgically and requires the support of a specialized multi-disciplinary team. Adoption of standardized patient evaluation and outcome reporting methods are necessary for robust comparative effectiveness studies.

Background. Cervical dystonia (CD) is a neurological movement disorder characterized by involuntary contractions of the cervical musculature and is known to be associated with proprioceptive dysfunction in dystonic/nondystonic limbs. Objectives. We examined how neck botulinum neurotoxin (BoNT) injection affects wrist proprioception and the corresponding sensorimotor cortical activity in CD. Method. Wrist position sense acuity of the dominant (right) hand was evaluated in 15 CD and 15 control participants. Acuity measures were a psychophysical position sense discrimination threshold (DT; based on passive joint displacement) and joint position matching error (based on active movement). Cortical activity during the motor preparation period of the active joint position matching was examined using electroencephalography. Results. In their symptomatic state, patients demonstrated a significantly higher wrist proprioceptive DT, indicating an abnormal passive wrist position sense. Yet BoNT injections had no significant effect on this threshold. During active joint position matching, errors were significantly larger in patients, but this difference vanished after the administration of BoNT. Motor preparation of active wrist position matching was associated with a significantly higher rise of β-band (13-30 Hz) power over contralateral somatosensory-motor cortical areas in patients. This excessive cortical activity significantly declined post-BoNT. Conclusion. Wrist proprioceptive perception during passive/active movements is abnormal in CD. An excessive rise of premotor/motor cortical β-oscillations during motor planning is associated with this proprioceptive dysfunction. Neck BoNT injections normalized the cortical processing of proprioceptive information from nonsymptomatic limbs, indicating that local injections may affect the central mechanisms of proprioceptive function in CD.

Background : Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in 2 clinical studies of cardiac surgery patients, without new safety observations. Methods : The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. Conclusion : The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

As medical care advances, there is a growing number of adult patients with cerebral palsy. The spastic form is characterized by muscle hypertonicity, hyperreflexia, and spasticity, which are associated with worse quality of life, poor functionality, and pain. This literature review attempts to explore the existing treatments for spasticity in cerebral palsy to provide insight into potential treatments in the adult population. The types of treatments are broadly categorized into physical therapy, pharmacologic treatments, botulinum toxin, surgical treatments, and alternative options.

Background: Complex ventral hernias following laparotomy present a unique challenge in that repair is hindered by the lateral tension of the abdominal wall. A novel approach to overcome this is the “chemical component separation” technique. Here, botulinum toxin A (BTA) is instilled into the muscles of the abdominal wall. This induces flaccid paralysis and effectively reduces tension in the wall, allowing the muscles to be successfully joined in the midline during surgery. We describe a method where a large incisional hernia was repaired using this technique and review the variations in methodology. Case report: A woman in her mid-40s developed a ventral hernia in the setting of a previous laparotomy for a small bowel perforation. Computed tomography (CT) of the abdomen demonstrated an 85 (Width) × 95 mm (Length) ventral hernia containing loops of the bowel. Pre-operative botulinum toxin A administration was arranged at the local interventional radiology department. A total of 100 units of BTA were instilled at four sites into the muscular layers of the abdominal wall under CT-fluoroscopic guidance. She underwent an open incisional hernia repair 4 weeks later, where the contents were reduced and the abdominal wall layers were successfully joined in the midline. There was no clinical evidence of hernia recurrence at 3-months follow-up. Conclusion: Low-dose BTA effectively facilitates the surgical management of large ventral incisional hernias. There is, however, significant variation in the dosage, concentration and anatomical landmarks in which BTA is administered as described in the literature. Further studies are needed to assess and optimise these variables.

Botulinum toxin has proven safe and effective when used correctly. This review examines the evidence that could support its expanded use.

Botulinum neurotoxins (BoNTs) are notorious toxins and powerful agents and can be lethal, causing botulism, but they are also widely used as therapeutics, particularly to treat neuromuscular disorders. As of today, the commercial BoNT treatments available are from native A or B serotypes. Serotype F has shown efficacy in a clinical trial but has scarcely been used, most likely due to its medium duration of effect. Previously, the uniqueness of the light chain of the F7 subtype was identified and reported, showing an extended interaction with its substrates, VAMPs 1, 2 and 3, and a superior catalytic activity compared to other BoNT/F subtypes. In order to more extensively study the properties of this neurotoxin, we engineered a modified F7 chimera, mrBoNT/F7-1, in which all the regions of the neurotoxin were identical to BoNT/F7 except the activation loop, which was the activation loop from BoNT/F1. Use of the activation loop from BoNT/F1 allowed easier post-translational proteolytic activation of the recombinant protein without otherwise affecting its properties. mrBoNT/F7-1 was expressed, purified and then tested in a suite of in vitro and in vivo assays. mrBoNT/F7-1 was active and showed enhanced potency in comparison to both native and recombinant BoNT/F1. Additionally, the safety profile remained comparable to BoNT/F1 despite the increased potency. This new modified recombinant toxin F7 could be further exploited to develop unique therapeutics to address unmet medical needs.

Botulinum neurotoxins (BoNTs) are proteins produced by bacteria of the Clostridium family. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism. There are seven serotypes of BoNT (serotypes A-G); BoNT-A and BoNT-B are the botulinum toxin serotypes utilized for therapeutic applications. Treatment with BoNT injections is used to manage chronic medical conditions across multiple indications. As with other biologic drugs, immunogenicity after long-term treatment with BoNT formulations may occur, and repeated use can elicit antibody formation leading to clinical nonresponsiveness. Thus, approaching BoNT treatment of chronic conditions with therapeutic formulations that minimize stimulating the host immune response while balancing patient responsiveness to therapy is ideal. Immunogenicity is a clinical limitation in many settings that use biologic drugs for treatment, and clinically relevant immunogenicity reduction has been achieved through engineering smaller protein constructs and reducing unnecessary formulation components. A similar approach has influenced the evolution of BoNT formulations. Three BoNT-A products and one BoNT-B product have been approved by the Food and Drug Administration (FDA) for therapeutic use: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB; a fourth BoNT-A product, daxibotulinumtoxinA, is currently under regulatory review. Additionally, prabotulinumtoxinA is a BoNT-A product that has been approved for aesthetic indications but not therapeutic use. Here, we discuss the preclinical and clinical immunogenicity data that exist within the scientific literature and provide a perspective for considering immunogenicity as a key factor in choice of BoNT formulation.

Botulinum neurotoxins (BoNTs) are the most potent toxins known and are also utilized to treat a wide range of disorders including muscle spasm, overactive bladder, and pain. BoNTs’ ability to target neurons determines their specificity, potency, and therapeutic efficacy. Homologous synaptic vesicle membrane proteins synaptotagmin-1 (Syt1) and synaptotagmin-2 (Syt2) have been identified as receptors for BoNT family members including BoNT/B, DC, and G, but their contributions at physiologically relevant toxin concentrations in vivo have yet to be validated and established. Here we generated two knockin mutant mouse models containing three designed point-mutations that specifically disrupt BoNT binding in endogenous Syt1 or Syt2, respectively. Utilizing digit abduction score assay by injecting toxins into the leg muscle, we found that Syt1 mutant mice showed similar sensitivity as the wild type mice, whereas Syt2 mutant mice showed reduced sensitivity to BoNT/B, DC, and G, demonstrating that Syt2 is the dominant receptor at skeletal neuromuscular junctions. We further developed an in vivo bladder injection assay for analyzing BoNT action on bladder tissues and demonstrated that Syt1 is the dominant toxin receptor in autonomic nerves controlling bladder tissues. These findings establish the critical role of protein receptors for the potency and specificity of BoNTs in vivo and demonstrate the differential contributions of Syt1 and Syt2 in two sets of clinically relevant target tissues., Author summary Establishing receptors that mediate binding and entry of toxins into host cells is fundamental to understanding the specificity of toxins. The in vivo contribution of candidate receptors can be difficult to elucidate if they are critical for survival. Such a limitation exists for botulinum neurotoxins (BoNTs), a family of bacterial toxins. They are potential bioterrorism agents and are also used to treat growing numbers of medical conditions. Previous studies identified synaptotagmin-1 (Syt1) and homologous synaptotagmin-2 (Syt2) as receptors for BoNT members including type B, G, and DC. However, as Syt1 and Syt2 are essential for survival of animals, there is no viable loss-of-function animal model to establish their role in vivo. Here we created and evaluated two mutant mouse lines containing designed point-mutations in endogenous Syt1 or Syt2, respectively, that specifically disrupt toxin binding. Using these tailor-made mouse models, we demonstrated that Syt2 is the dominant receptor for BoNT/B, DC, and G at skeletal muscle neuromuscular junctions, whereas Syt1 is the dominant receptor in autonomic nerves in bladder tissues. These findings validate the role of Syt1 and Syt2 as toxin receptors in animal models and reveal their differential contributions in two clinically relevant tissues.

Detection of botulinum neurotoxin or isolation of the toxin producing organism is required for the laboratory confirmation of botulism in clinical specimens. In an effort to reduce animal testing required by the gold standard method of botulinum neurotoxin detection, the mouse bioassay, many technologies have been developed to detect and characterize the causative agent of botulism. Recent advancements in these technologies have led to improvements in technical performance of diagnostic assays; however, many emerging assays have not been validated for the detection of all serotypes in complex clinical and environmental matrices. Improvements to culture protocols, endopeptidase-based assays, and a variety of immunological and molecular methods have provided laboratories with a variety of testing options to evaluate and incorporate into their testing algorithms. While significant advances have been made to improve these assays, additional work is necessary to evaluate these methods in various clinical matrices and to establish standardized criteria for data analysis and interpretation.

Botulinum neurotoxins (BoNTs) are potent inhibitors of synaptic vesicle fusion and transmitter release. The natural target of BoNTs is the peripheral neuromuscular junction (NMJ) where, by blocking the release of acetylcholine (ACh), they functionally denervate muscles and alter muscle tone. This leads them to be an excellent drug for the therapy of muscle hyperactivity disorders, such as dystonia, spasticity, and many other movement disorders. BoNTs are also effective in inhibiting both the release of ACh at sites other than NMJ and the release of neurotransmitters other than ACh. Furthermore, much evidence shows that BoNTs can act not only on the peripheral nervous system (PNS), but also on the central nervous system (CNS). Under this view, central changes may result either from sensory input from the PNS, from retrograde transport of BoNTs, or from direct injection of BoNTs into the CNS. The aim of this review is to give an update on available data, both from animal models or human studies, which suggest or confirm central alterations induced by peripheral or central BoNTs treatment. The data will be discussed with particular attention to the possible therapeutic applications to pathological conditions and degenerative diseases of the CNS.

Background To describe and understand the experiences and beliefs of caregivers of children with cerebral palsy following botulinum toxin injection. Methods A descriptive case study approach with focus group interviews was employed. A semi-structured questionnaire was conducted to collect data. Twenty-one caregivers of children (3-13 years old) with cerebral palsy were recruited with a maximum variation sampling strategy to gain insight through different perspectives. Qualitative analysis with verbatim transcripts was analysed using a thematic approach. Findings Four themes emerged from qualitative analyses: acceptance of diagnosis, perceptions about treatment, caregivers' experiences with the health environment, and feelings and thoughts after the treatment. Conclusions This study highlights caregivers' requests for information about the possible long-term effect of botulinum toxin, as well as information and support to provide the best rehabilitation programme immediately after injection.

In post-stroke hemiparesis, neural impairment alters muscle control, causing abnormal movement and posture in the affected limbs. A decrease in voluntary use of the paretic arm and flexed posture during rest also induce secondary tissue transformation in the upper limb muscles. To obtain a specific, accurate, and reproducible marker of the current biological status of muscles, we collected visible (VIS) and short-wave Infrared (SWIR) reflectance spectra in vivo using a portable spectroradiometer (350–2500 nm), which provided the spectral fingerprints of the elbow flexors and extensors. We compared the spectra for the affected and unaffected sides in 23 patients with post-stroke hemiparesis (25–87 years, 8 women) and eight healthy controls (33–87 years, 5 women). In eight patients, spectra were collected before and after botulinum toxin injection. Spectra underwent off-line preprocessing, principal component analysis, and partial least-squares discriminant analysis. Spectral fingerprints discriminated the muscle (biceps vs. triceps), neurological condition (normal vs. affected vs. unaffected), and effect of botulinum toxin treatment (before vs. 30 to 40 days vs. 110 to 120 days after injection). VIS-SWIR spectroscopy proved valuable for non-invasive assessment of optical properties in muscles, enabled more comprehensive evaluation of hemiparetic muscles, and provided optimal monitoring of the effectiveness of medication.

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known and can induce respiratory failure requiring long-term intensive care. Treatment of botulism includes the administration of antitoxins. Monoclonal antibodies (mAbs) hold considerable promise as BoNT therapeutics and prophylactics, due to their potency and safety. A three-mAb combination has been developed that specifically neutralizes BoNT serotype A (BoNT/A), and a separate three mAb combination has been developed that specifically neutralizes BoNT serotype B (BoNT/B). A six mAb cocktail, designated G03-52-01, has been developed that combines the anti-BoNT/A and anti-BoNT/B mAbs. The pharmacokinetics and neutralizing antibody concentration (NAC) of G03-52-01 has been determined in guinea pigs, and these parameters were correlated with protection against an inhalation challenge of BoNT/A1 or BoNT/B1. Previously, it was shown that each antibody demonstrated a dose-dependent mAb serum concentration and reached maximum circulating concentrations within 48 h after intramuscular (IM) or intraperitoneal (IP) injection and that a single IM injection of G03-52-01 administered 48 h pre-exposure protected guinea pigs against an inhalation challenge of up to 93 LD50s of BoNT/A1 and 116 LD50s of BoNT/B1. The data presented here advance our understanding of the relationship of the neutralizing NAC to the measured circulating antibody concentration and provide additional support that a single IM or intravenous (IV) administration of G03-52-01 will provide pre-exposure prophylaxis against botulism from an aerosol exposure of BoNT/A and BoNT/B.

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INTRODUCTION: Abdominal spasms are involuntary contractions that can be caused by denervation due to spinal cord injury. We present a case that benefited from botulinum toxin injections. CASE PRESENTATION: A 42-year-old male patient was followed up due to spinal cord injury that developed secondary to burst fracture in the 6th thoracic vertebra as a result of falling off the train in 1996, was classified as International Standards for Neurological Classification of SCI (ISNCSCI) T8 American Spinal Injury Association Impairment Scale (AIS) grade-B. His complaint of contraction and spasms in his abdominal muscles has been present for 2 years but has escalated significantly in the last 3 months. His complaint of contraction and spasms in his abdominal muscles has been present for 2 years but has escalated significantly in the last 3 months. He used oral baclofen 20 mg three times a day for the complaint of contraction, but his complaints did not completely disappear. The use of a baclofen pump was recommended to the patient in his previous visits, but the patient did not accept it. Due to the lack of alternatives and considering the local nature of the complaints, we planned botulinum toxin injection for the patient’s bilateral internal oblique and external oblique abdominal muscles with ultrasonography guidance. He benefited significantly from botulinum toxin injection, and his complaints decreased. CONCLUSION: In selected patients with spinal cord injury, ultrasound guided botulinum toxin injections to external and internal oblique muscles can be a safe alternative.

Objective To perform a systematic review of the diagnosis and treatment of patients with pulsatile tinnitus secondary to middle ear myoclonus. Databases reviewed PubMed, EMBASE, and Scopus. Methods A systematic review was performed using standardized methodology. Computerized and manual searches were performed to identify studies of all ages (patients) who had middle ear myoclonus (intervention). All study designs were assessed. Extracted data included demographics, clinical features, duration of followup as well as the diagnosis and reversibility of symptoms with medical or surgical intervention. Studies were included if they included subjects with middle ear myoclonus. Exclusion criteria included letters/commentaries and reviews. Results Twenty articles representing 115 subjects with middle ear myoclonus were included. The mean age was 29.7 (range 6–67). The follow-up period ranged from 5 weeks to 36 months. Primary treatment consists of medical therapy utilising anxiolytics, antiepileptics, botulinum toxin and surgical treatment involving division of middle ear muscular tendon(s). In total, 60 patients underwent middle ear muscular tenotomies, with division of both stapedius and tensor tympani tendons being the most prevalent (88%). Limitations in the data arose from study design, related comorbidities such as palatal myoclonus, and concomitant drug administration. No study provided any objective criteria to diagnose this condition or evaluate post-treatment outcome. Conclusion Middle ear myoclonus is an entity that is poorly assessed in the literature. There is a lack of consensus regarding the criteria and strategies for both diagnosing and treating this condition. Although level of evidence of current studies remains modest, it is felt that a stepwise approach is deemed best, with therapeutic decisions being made on an individual basis, evaluating each patient's specific circumstances and priorities.