The Potential Therapeutic Effects of Botulinum Neurotoxins on Neoplastic Cells: A Comprehensive Review of In Vitro and In Vivo Studies.

A systematic review of the literature found fifteen articles on the effect of a botulinum toxin on neoplastic cell lines and eight articles on in vivo neoplasms. The reported in vitro effects rely on high doses or the mechanical disruption of cell membranes to introduce the botulinum neurotoxin into the cell cytoplasm. The potency of the botulinum neurotoxin to intoxicate non-neuronal cells (even cell lines expressing an appropriate protein receptor) is several orders of magnitude lower compared to that to intoxicate the primary neurons. The data suggest that the botulinum toxin disrupts the progression of cancer cells, with some studies reporting apoptotic effects. A majority of the data in the in vivo studies also showed similar results. No safety issues were disclosed in the in vivo studies. Limited studies have suggested similar anti-neoplastic potential for the clostridium difficile. New modes of delivery have been tested to enhance the in vivo delivery of the botulinum toxin to neoplastic cells. Careful controlled studies are necessary to demonstrate the efficacy and safety of this mode of anti-neoplastic treatment in humans.

Clinical neurophysiology in the treatment of movement disorders: IFCN handbook chapter.

In this review, different aspects of the use of clinical neurophysiology techniques for the treatment of movement disorders are addressed. First of all, these techniques can be used to guide neuromodulation techniques or to perform therapeutic neuromodulation as such. Neuromodulation includes invasive techniques based on the surgical implantation of electrodes and a pulse generator, such as deep brain stimulation (DBS) or spinal cord stimulation (SCS) on the one hand, and non-invasive techniques aimed at modulating or even lesioning neural structures by transcranial application. Movement disorders are one of the main areas of indication for the various neuromodulation techniques. This review focuses on the following techniques: DBS, repetitive transcranial magnetic stimulation (rTMS), low-intensity transcranial electrical stimulation, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), and focused ultrasound (FUS), including high-intensity magnetic resonance-guided FUS (MRgFUS), and pulsed mode low-intensity transcranial FUS stimulation (TUS). The main clinical conditions in which neuromodulation has proven its efficacy are Parkinson's disease, dystonia, and essential tremor, mainly using DBS or MRgFUS. There is also some evidence for Tourette syndrome (DBS), Huntington's disease (DBS), cerebellar ataxia (tDCS), and axial signs (SCS) and depression (rTMS) in PD. The development of non-invasive transcranial neuromodulation techniques is limited by the short-term clinical impact of these techniques, especially rTMS, in the context of very chronic diseases. However, at-home use (tDCS) or current advances in the design of closed-loop stimulation (tACS) may open new perspectives for the application of these techniques in patients, favored by their easier use and lower rate of adverse effects compared to invasive or lesioning methods. Finally, this review summarizes the evidence for keeping the use of electromyography to optimize the identification of muscles to be treated with botulinum toxin injection, which is indicated and widely performed for the treatment of various movement disorders.

Botulinum Toxin Treatment for Cancer-Related Disorders: A Systematic Review.

This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT's effect on pain at the site of surgery or radiation. All 13 published studies on this issue indicated reduction or cessation of pain at these sites after local injection of BoNTs. Twelve studies addressed the effect of BoNT injection into the pylorus (sphincter between the stomach and the first part of the gut) for the prevention of gastroparesis after local resection of esophageal cancer. In eight studies, BoNT injection was superior to no intervention; three studies found no difference between the two approaches. One study compared the result of intra-pyloric BoNT injection with preventive pyloromyotomy (resection of pyloric muscle fibers). Both approaches reduced gastroparesis, but the surgical approach had more serious side effects. BoNT injection was superior to saline injection in the prevention of esophageal stricture after surgery (34% versus 6%, respectively, p = 0.02) and produced better results (30% versus 40% stricture) compared to steroid (triamcinolone) injection close to the surgical region. All 12 reported studies on the effect of BoNT injection into the parotid region for the reduction in facial sweating during eating (gustatory hyperhidrosis) found that BoNT injections stopped or significantly reduced facial sweating that developed after parotid gland surgery. Six studies showed that BoNT injection into the parotid region prevented the development of or healed the fistulas that developed after parotid gland resection-parotidectomy gustatory hyperhidrosis (Frey syndrome), post-surgical parotid fistula, and sialocele. Eight studies suggested that BoNT injection into masseter muscle reduced or stopped severe jaw pain after the first bite (first bite syndrome) that may develop as a complication of parotidectomy.

Botulinum toxin for motor disorders.

Botulinum neurotoxins are a group of biological toxins produced by the gram-negative bacteria Clostridium botulinum. After intramuscular injection, they produce dose-related muscle relaxation, which has proven useful in the treatment of a large number of motor and movement disorders. In this chapter, we discuss the utility of botulinum toxin treatment in three major and common medical conditions related to the dysfunction of the motor system, namely dystonia, tremor, and spasticity. A summary of the existing literature is provided along with different techniques of injection including those recommended by the authors.

Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review.

Objectives: The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population. Materials and Methods: We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options. Results: Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion. Conclusion: This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.

Botulinum Toxin Treatment of Motor Disorders in Parkinson Disease-A Systematic Review.

This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed disorders include the common motor disorders in PD such as tremor, focal foot dystonia, rigidity and freezing of gait (FOG). In the area of Parkinson tremor, two newly described evaluation/injection techniques (Yale method in USA and Western University method in Canada) offer efficacy with low incidence of hand and finger weakness as side effects. Blinded studies conducted on foot dystonia of PD indicate that botulinum toxin injections into toe flexors are efficacious in alleviating this form of dystonia. Small, blinded studies suggest improvement of Parkinson rigidity after botulinum toxin injection; proof of this claim, however, requires information from larger, blinded clinical trials. In FOG, the improvement reported in open label studies could not be substantiated in blinded investigations. However, there is room for further controlled studies that include the proximal lower limb muscles in the injection plan and/or use higher doses of the injected toxin for this indication.

Movement Disorders in Chronic Kidney Disease - A Descriptive Review.

OBJECTIVES: The objective of this study is to describe the mechanism of damage to subcortical structures in chronic kidney disease (CKD) and to describe the range of movement disorders associated with CKD. MATERIALS AND METHODS: We have reviewed the Medline literature up to January of 2020 using key words movement disorders and chronic kidney disease. The reviewed articles were studied for mechanisms of subcortical damage in CKD as well as type of the reported movements, their frequency and updated treatment. RESULTS: The search revealed 183 articles most of them dealing with restless legs syndrome. The damage to basal ganglia in CKD resulted from several mechanisms including accumulation of nitro tyrosine caused by reactive oxygen species and action of uremic toxins leading to endothelial damage and dysfunction of blood-brain barrier. Involuntary movements in CKD include restless legs syndrome (RLS), myoclonus, asterixis, dystonia, chorea, tremor, and Parkinsonism. CONCLUSIONS: Chronic kidney disease can cause several abnormal involuntary movements via damaging basal ganglia and subcortical structures. The most common movement disorders in CKD are RLS, myoclonus and asterixis. Restless legs syndrome and myoclonus when severe, need and respond to treatment. Movement disorders in CKD improve with improvement of kidney function.

Botulinum Neurotoxins and Cancer-A Review of the Literature.

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed.

Novel Botulinum Toxin Injection Protocols for Parkinson Tremor and Essential Tremor - the Yale Technique and Sensor-Based Kinematics Procedure for Safe and Effective Treatment.

Background: Hand tremor associated with Parkinson disease (PD) and essential tremor (ET) can often become challenging to treat in clinical practice. Local injections of botulinum toxin-A (BoNT-A) for hand tremor is an evolving field with newer injection techniques being utilized in clinical studies. The utility of BoNT-A therapy for ET and PD-tremor however, has been questioned based on the high incidence of finger and hand weakness after treatment. Method: The study includes detailed analysis of the techniques utilized in BoNT injection in ET and PD tremor. Results: There were 4 high-quality investigations which consisted of Class I or II double-blind placebo-controlled trials and one medium-quality study that was a prospective, open label, class III investigation. Discussion: This paper discusses two recently developed technology-based injection methods for BoNT-A therapy of ET and PD tremor, which includes comprehensive EMG screening of forearm and arm muscles with selective injections (Yale method) and the whole arm kinematic tremor assessment developed by Jog et al. In recent years, controlled, blinded studies of these two methods have shown significant post-injection reduction of finger, hand and whole limb tremor compared to the previously published controlled clinical trials not using these methodologies.

Recent Progresses in Application of Membrane Bioreactors in Production of Biohydrogen.

Biohydrogen is a clean and viable energy carrier generated through various green and renewable energy sources such as biomass. This review focused on the application of membrane bioreactors (MBRs), emphasizing the combination of these devices with biological processes, for bio-derived hydrogen production. Direct biophotolysis, indirect biophotolysis, photo-fermentation, dark fermentation, and conventional techniques are discussed as the common methods of biohydrogen production. The anaerobic process membrane bioreactors (AnMBRs) technology is presented and discussed as a preferable choice for producing biohydrogen due to its low cost and the ability of overcoming problems posed by carbon emissions. General features of AnMBRs and operational parameters are comprehensively overviewed. Although MBRs are being used as a well-established and mature technology with many full-scale plants around the world, membrane fouling still remains a serious obstacle and a future challenge. Therefore, this review highlights the main benefits and drawbacks of MBRs application, also discussing the comparison between organic and inorganic membranes utilization to determine which may constitute the best solution for providing pure hydrogen. Nevertheless, research is still needed to overcome remaining barriers to practical applications such as low yields and production rates, and to identify biohydrogen as one of the most appealing renewable energies in the future.

Botulinum Toxin in Restless Legs Syndrome-A Randomized Double-Blind Placebo-Controlled Crossover Study.

BACKGROUND: Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to 12%. Previous small studies with onabotulinumtoxin A (OnaA) for RLS have shown inconsistent results. METHODS: Twenty-four patients with an International RLS score (IRLS) of >11 (moderate-severe) were enrolled in this blinded, placebo-controlled crossover study. Twenty-one patients completed the evaluations at 4, 6, and 8 weeks after each injection. One-hundred units of Incobotulinumtoxin A (IncoA) or normal saline were injected into tibialis anterior, gastrocnemius, and biceps femoris muscles each side. RESULTS: Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ≤20) score was significant at four weeks (p = 0.0036) and six weeks (p = 0.0325) following IncoA administration compared to placebo. Additionally, there was significant improvement in pain score at six weeks as measured by Visual Analogue Scale (p = 0.04) and the Johns Hopkins Quality of Life Questionnaire (p = 0.01) in the IncoA group. Definite or marked improvement on Patient Global Impression of Change was seen in 7 out of 21 patients in the IncoA group vs. 1 out of 21 patients in the placebo group at 4 weeks (p = 0.012). CONCLUSION: IncoA injection lead to a reduction in severity of RLS symptoms, pain score, and quality of life, without any adverse effects.

Uremia induces upregulation of cerebral tissue oxidative/inflammatory cascade, down-regulation of Nrf2 pathway and disruption of blood brain barrier.

Chronic kidney disease (CKD) results in various central nervous systems (CNS) disorders including cognitive dysfunction, depression, anxiety, movement disorders, seizures and encephalopathy. Uremic retention products, oxidative stress, inflammation and impaired blood-brain barrier have been implicated as the major mediators of CKD-induced CNS disorders. However, mechanisms of CKD-induced cerebral tissue oxidative stress, inflammation and impaired blood brain barrier have not been fully elucidated and were explored. Male Sprague Dawley rats underwent sham operation or 5/6 nephrectomy and were observed for 10 weeks. Arterial pressure, body weight, and renal function were monitored. Under general anesthesia the animals' cerebral cortex was harvested. Nuclear translocations of NF-κB and Nrf2 and their key target gene products, neuronal, endothelial and inducible NO synthase (NOS) isoforms, markers of oxidative, nitrosative and myeloperoxidase reactions, fibrosis mediators and key protein constituents of capillary endothelial junctional complex were determined by Western blot analysis. The CKD rats exhibited reduced body weight, hypertension, elevated serum urea and creatinine concentrations. Compared to control group cerebral cortex of the CKD group showed activation (increased nuclear translocation) of NF-κB, elevation of pro-oxidant and pro-inflammatory molecules, diminished nuclear translocation of Nrf2 and expression of cytoprotective antioxidant molecules and depletion of the key protein constituents of endothelial junctional complex. In conclusion CKD results in the cerebral tissue activation of inflammatory and oxidative pathways, inhibition of antioxidant and cytoprotective system and erosion of cerebral capillary junctional complex, events that contribute to CNS dysfunction and impaired blood brain barrier.

Botulinum toxin in essential hand tremor - A randomized double-blind placebo-controlled study with customized injection approach.

INTRODUCTION: To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of essential hand tremor. In essential tremor and Parkinson's disease tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor but a high percentage of patients (30-70%) develop moderate to severe hand weakness which has limited its use in clinical practice. METHODS: This study was performed from July 2013 to July 2016 on 33 subjects. This is a double-blind, placebo-controlled, crossover trial injecting 80-120 units of IncoA into 8-14 hand and forearm muscles using a customized approach. The subjects were followed for 28 weeks. The treatment efficacy was evaluated by the Fahn Tolosa Marin tremor rating score and NIH genetic criteria for tremor severity at 4 and 8 weeks after each of the two sets of treatments. Hand strength was assessed by an ergometer. RESULTS: There was statistically significant improvement in clinical rating score of tremor at 4 and 8 weeks following the IncoA injection. CONCLUSION: In this study, injection of IncoA treatment via a customized approach improved essential tremor on the clinical scales and patient's perception with a low occurrence of significant hand weakness.

Botulinum Toxin Treatment of Movement Disorders.

Botulinum neurotoxins (BoNTs) are now among the most widely used therapeutic agents in clinical medicine with indications applied to the fields of movement disorders, pain disorders, and autonomic dysfunction. In this literature review, the efficacy and utility of BoNTs in the field of movement disorders are assessed using the criteria of the Guideline Development Subcommittee of the American Academy of Neurology. The literature supports a level A efficacy (established) for BoNT therapy in cervical dystonia and a level B efficacy (probably effective) for blepharospasm, hemifacial spasm, laryngeal dystonia (spasmodic dysphonia), task-specific dystonias, essential tremor, and Parkinson rest tremor. It is the view of movement disorder experts, however, that despite the level B efficacy, BoNTs should be considered treatment of first choice for blepharospasm, hemifacial spasm, laryngeal, and task-specific dystonias. The emerging data on motor and vocal tics of Tourette syndrome and oromandibular dystonias are encouraging but the current level of efficacy is U (undetermined) due to lack of published high-quality studies.

Botulinum toxin treatment of pain syndromes -an evidence based review.

This review evaluates the existing level of evidence for efficacy of BoNTs in different pain syndromes using the recommended efficacy criteria from the Assessment and Therapeutic Subcommittee of the American Academy of Neurology. There is a level A evidence (effective) for BoNT therapy in post-herpetic neuralgia, trigeminal neuralgia, and posttraumatic neuralgia. There is a level B evidence (probably effective) for diabetic neuropathy, plantar fasciitis, piriformis syndrome, pain associated with total knee arthroplasty, male pelvic pain syndrome, chronic low back pain, male pelvic pain, and neuropathic pain secondary to traumatic spinal cord injury. BoNTs are possibly effective (Level C -one class II study) for female pelvic pain, painful knee osteoarthritis, post-operative pain in children with cerebral palsy after adductor release surgery, anterior knee pain with vastus lateralis imbalance. There is a level B evidence (one class I study) that BoNT treatment is probably ineffective in carpal tunnel syndrome. For myofascial pain syndrome, the level of evidence is U (undetermined) due to contradicting results. More high quality (Class I) studies and studies with different types of BoNTs are needed for better understanding of the role of BoNTs in pain syndromes.

The nature, consequences, and management of neurological disorders in chronic kidney disease.

Perhaps no other organ in the body is affected as often and in as many ways as the brain is in patients with chronic kidney disease (CKD). Several factors contribute to the neurological disorders in CKD including accumulation of uremic toxins, metabolic and hemodynamic disorders, oxidative stress, inflammation, and impaired blood brain barrier among others. The neurological disorders in CKD involve both peripheral and central nervous system. The peripheral neurological symptoms of CKD are due to somatic and cranial peripheral neuropathies as well as a myopathy. The central neurological symptoms of CKD are due to the cortical predominantly cortical, or subcortical lesions. Cognitive decline, encephalopathy, cortical myoclonus, asterixis and epileptic seizures are distinct features of the cortical disorders of CKD. Diffuse white matter disease due to ischemia and hypoxia may be an important cause of subcortical encephalopathy. A special and more benign form of subcortical disorder caused by brain edema in CKD is termed posterior reversible encephalopathy. Subcortical pathology especially when it affects the basal ganglia causes a number of movement disorders including Parkinsonism, chorea and dystonia. A stimulus-sensitive reflex myoclonus is believed to originate from the medullary structures. Sleep disorder and restless leg syndrome are common in CKD and have both central and peripheral origin. This article provides an overview of the available data on the nature, prevalence, pathophysiology, consequences and treatment of neurological complications of CKD.

Botulinum Toxin in Parkinson Disease Tremor: A Randomized, Double-Blind, Placebo-Controlled Study With a Customized Injection Approach.

BACKGROUND: In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor, but many patients (30%-70%) develop moderate to severe hand weakness, limiting the use of onabotulinumtoxinA in clinical practice. OBJECTIVE: To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for the treatment of tremor in PD. PATIENTS AND METHODS: In this double-blind, placebo-controlled, crossover trial, 30 patients each received 7 to 12 (mean, 9) IncoA injections into hand and forearm muscles using a customized approach. The study was performed from June 1, 2012, through June 30, 2015, and participants were followed for 24 weeks. Treatment efficacy was evaluated by the tremor subsets of the Unified Parkinson's Disease Rating Scale and the Patient Global Impression of Change 4 and 8 weeks after each of the 2 sets of treatments. Hand strength was assessed using an ergometer. RESULTS: There was a statistically significant improvement in clinical rating scores of rest tremor and tremor severity 4 and 8 weeks after the IncoA injection and of action/postural tremor at 8 weeks. There was a significant improvement in patient perception of improvement at 4 and 8 weeks in the IncoA group. There was no statistically significant difference in grip strength at 4 weeks between the 2 groups. CONCLUSION: Injection of IncoA via a customized approach improved PD tremor on a clinical scale and patient perception, with a low occurrence of significant hand weakness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02419313.

Botulinum Toxin Treatment in Multiple Sclerosis-a Review.

Purpose of review The purpose of this review is to provide updated information on the role of botulinum neurotoxin (BoNT) therapy in multiple sclerosis (MS). This review aims to answer which symptoms of multiple sclerosis may be amenable to BoNT therapy. Recent findings We searched the literature on the efficacy of BoNTs for treatment of MS symptoms up to April 1st 2017 via the Yale University Library's search engine including but not limited to Pub Med and Ovis SP. The level of efficacy was defined according to the assessment's criteria set forth by the Subcommittee on Guideline Development of the American Academy of Neurology. Significant efficacy was found for two indications based on the available blinded studies (class I and II) and has been suggested for several others through open-label clinical trials. Summary There is level A evidence (effective- two or more class I) that injection of BoNT-A into the bladder's detrusor muscle improves MS-related neurogenic detrusor overactivity (NDO) and MS-related overactive (OA) bladder. There is level B evidence (probably effective- two class II studies) for utility of intramuscular BoNT-A injections for spasticity of multiple sclerosis. Emerging data based on retrospective class IV studies demonstrates that intramuscular injection of BoNTs may help other symptoms of MS such as focal tonic spasms, focal myokymia, spastic dysphagia, and double vision in internuclear ophthalmoplegia. There is no data on MS-related trigeminal neuralgia and sialorrhea, two conditions which have been shown to respond to BoNT therapy in non-MS population.

RimabotulinumtoxinB in sialorrhea: systematic review of clinical trials.

OBJECTIVE: The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a systematic review of clinical trials. METHODS: A systematic literature review was performed to identify randomized controlled trials and other comparative clinical studies of BoNT-B for the treatment of sialorrhea published in English between January 1999 and December 2015. Medical literature databases (PubMed, Cochrane Library, and EMBASE) were searched and a total of 41 records were identified. Of these, six primary publications that evaluated BoNT-B for the treatment of sialorrhea met criteria and were included in the final data report. SYNTHESIS: Total BoNT-B doses ranged from 1500 to 4000 units for sialorrhea. Most of the studies in sialorrhea showed statistically significant benefits of BoNT-B versus placebo (range 4-19.2 weeks). BoNT-B was generally well tolerated across the individual studies; most adverse events reported were considered unrelated to treatment. Adverse events considered potentially associated with BoNT-B included: dry mouth, change in saliva thickness, mild transient dysphagia, mild weakness of chewing and diarrhea. CONCLUSIONS: BoNT-B significantly reduces sialorrhea at doses between 1500 and 4000 units. The relatively mild dose-dependent adverse events suggest both direct and remote toxin effects.

Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain.

Chronic low back pain is a debilitating condition with a complex and multifactorial pathophysiology. Botulinum neurotoxins (BoNTs) have strong analgesic effects, as shown in both animal models of pain and in human beings. A randomized, double-blind, placebo-controlled, parallel format study to investigate the efficacy of abobotulinum toxin A (aboA) in chronic low back pain was conducted. The study cohort consisted of 18 patients who received 100 units of aboA into each of the five lumbar extensor spinae muscles unilaterally or bilaterally (total dose 500 to 1000 units), and 19 who received normal saline of the same volume. The level of pain and quality of life were assessed using the visual analogue scale (VAS) and three questionnaires including the Oswestry Low Back Pain Disability Questionnaire (OLBPDQ). Patients' perception of improvement was recorded via patient global impression of change (PGIC). The primary outcome measure, the proportion of responders with VAS of <4 at 6 weeks, was not met, but the data was significantly in favor of aboA at 4 weeks (p = 0.008). The total Oswestry score representing quality of life improved in the aboA group compared to the placebo group (p = 0.0448). Moreover, significantly more patients reported their low back pain as "much improved" in the abobotulinum toxin A group (0.0293).