Intramuscular Injections Of Botulinum Neurotoxin Research Articles

Deep Brain Stimulation for Focal or Segmental Craniocervical Dystonia in Patients Who Have Failed Botulinum Neurotoxin Therapy-A Narrative Review of the Literature.

(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.

Improving the Efficacy of Botulinum Toxin for Cervical Dystonia: A Scoping Review.

Cervical dstonia (CD) is a chronic disorder with a significant detrimental impact on quality of life, requiring long-term treatment. Intramuscular injections of botulinum neurotoxin (BoNT) every 12 to 16 weeks have become the first-line option for CD. Despite the remarkable efficacy of BoNT as a treatment for CD, a significantly high proportion of patients report poor outcomes and discontinue the treatment. The reasons that drive sub-optimal response or treatment failure in a proportion of patients include but are not limited to inappropriate muscle targets and/or BoNT dosing, improper method of injections, subjective feeling of inefficacy, and the formation of neutralizing antibodies against the neurotoxin. The current review aims to complement published research focusing on the identification of the factors that might explain the failure of BoNT treatment in CD, highlighting possible solutions to improve its outcomes. Thus, the use of the new phenomenological classification of cervical dystonia known as COL-CAP might improve the identification of the muscle targets, but more sensitive information might come from the use of kinematic or scintigraphic techniques and the use of electromyographic or ultrasound guidance might ensure the accuracy of the injections. Suggestions are made for the development of a patient-centered model for the management of cervical dystonia and to emphasize that unmet needs in the field are to increase awareness about the non-motor spectrum of CD, which might influence the perception of the efficacy from BoNT injections, and the development of dedicated rehabilitation programs for CD that might enhance its effectiveness.

Use of AbobotulinumtoxinA in Adults with Cervical Dystonia: A Systematic Literature Review.

Cervical dystonia (CD) is a neurological movement disorder characterized by sustained involuntary muscle contractions. First-line therapy for CD is intramuscular injections of botulinum neurotoxin (e.g., abobotulinumtoxinA) into the affected muscles. The objective of this systematic literature review is to assess the clinical evidence regarding the effects of abobotulinumtoxinA for treatment of CD in studies of safety, efficacy, patient-reported outcomes, and economic outcomes. Using comprehensive electronic medical literature databases, a search strategy was developed using a combination of Medical Subject Heading terms and keywords. Results were reviewed by two independent reviewers who rated the level of evidence. The search yielded 263 publications, of which 232 were excluded for being duplicate publications, not meeting the selection criteria, or failing to meet predefined eligibility criteria, leaving a total of 31 articles. Clinical efficacy, patient-reported outcomes, and safety data were in 6 placebo-controlled trials (8 articles), 6 active-controlled trials, and 16 observational studies (17 articles). Data on health economic outcomes were provided in one of the clinical trials, in two of the observational studies, and in one specific cost-analysis publication. This review demonstrated that the routine use of abobotulinumtoxinA in CD is well-established, effective, and generally well-tolerated, with a relatively low cost of treatment.

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.

Treatment of Spasticity in Cerebral Palsy

The cerebral palsy diagnosis is a clinical one and it includes motor development delay, abnormal muscle tone and hyperreflexia. Muscle weakness, spasticity, loss of coordination, the continuation of the primitive reflexes and non-developed normal motor control are often seen in children with cerebral palsy. Spasticity is the velocity dependent increase in the resistance against passive muscle stretching. Spasticity treatment program should be established after detailed evaluation of degree and effects.Treatments to achieve optimal muscle tone include physical therapy and rehabilitation program, oral and injectable medications and surgical treatments. In the treatment of spasticity, a personalized physical therapy and rehabilitation program including stretching exercises should be in the treatment plans, absolutely. There is no consensus regarding the optimal application of pharmacotherapy for the treatment of spasticity in cerebral palsy. Oral medications such as baclofen, benzodiazepine, tizanidine and dantrolene can be used for the treatment of generalized spasticity. Oral drugs have significant side effects such as sedation and cognitive deficits. Chemodenervation with perineural phenol or ethanol injection or intramuscular injection of botulinum neurotoxin A can be used as treatment of localized spasticity. It is shown that botulinum neurotoxin type A is safe and effective in reducing spasticity in children. Most commonly used surgical technique for the treatment of spasticity in cerebral palsy is selective dorsal rhizotomy and it can be applied to selected cases. Treatment options that are used in the treatment of spasticity in cerebral palsy are discussed in this review

Rationale for using botulinum toxin A as an adjunct to upper limb rehabilitation in children with cerebral palsy.

Cerebral palsy describes a group of disorders of movement and posture that result from disturbances in the developing brain. Although the brain lesion is nonprogressive, the secondary physical symptoms change with time and growth. If left untreated, symptoms may result in the development of physical impairment and impede independent performance of daily tasks. Intramuscular injection of botulinum neurotoxin A is a relatively safe and effective adjunct to upper limb therapy. Botulinum neurotoxin A primarily aims to reduce muscle overactivity, thereby reducing the development of increased muscle stiffness that can lead to permanent changes. With a specific focus on the physiological action of botulinum neurotoxin A, this article describes the secondary symptoms of cerebral palsy and their different contributions. To highlight research directions and future implications for clinical practice, this article also documents the recent scientific evidence for upper limb botulinum neurotoxin A and proposes a preventive clinical model that aims to mitigate the effects of increasing upper limb impairment.

Alleviation of abnormal synaptic neurotransmitter release by cell-permeable form of the truncated SNAP-25 upon transcutaneous delivery

Abnormal releases of neurotransmitters result in movement disorders such as dystonia, chorea, tics, blepharospasm and wrinkle formation, and intra-muscular injection of Botulinum neurotoxin is widely used for the treatment of these complications. But it is potentially poisonous and must be intra-muscularly injected with precision by a well-trained physician. For novel therapeutic development with high safety profile and easy skin penetration for these complications, we generated Trans-X, a cell permeable form of the truncated SNAP-25 that is one of the SNARE complex for vesicle exocytosis of neuron. Upon topical administration, Trans-X efficiently penetrated through skin, reached the dermis layer and remained stable. Trans-X, which did not show any ocular or skin allergic sensitivity, can block the pre-synaptic neurotransmitter transport via acting as a competitive inhibitor of SNARE complex formation, and effectively induced muscle paralysis comparable to BOTOX® evaluated by measuring compound muscle action potential. Topical treatment of the facial skin with Trans-X in clinical study can prevent the wrinkle formation and improve the skin roughness. Therefore, our study suggests that Trans-X may be a convenient and effective medical and cosmetic treatment for local management of movement disorder without systemic toxicity.

Updates in the Treatment of Spasticity Associated With Cerebral Palsy

Spasticity affects up to 80% of patients with cerebral palsy (CP) and often plays a significant role in limiting the child's ability to function and participate in daily activities. The treatment of spasticity involves a multifaceted approach that includes pharmacological treatment with antispasmodics, physical therapy to maintain range of motion and prevent contractures, as well as a variety of orthopedic and neurosurgical interventions. Pharmacological agents currently used in clinical practice to treat spasticity in children have existed for almost two decades and continue to be used despite lack of solid evidence for their efficacy. Studies detailing safety profiles and optimal dosing in the pediatric population are greatly warranted. Intramuscular injection of botulinum neurotoxin is becoming increasingly popular for the treatment of segmental spasticity and current literature suggests it is safe and effective (Level A). Constraint-induced movement therapy (CIMT) and repetitive transcranial magnetic stimulation (rTMS) are emerging as effective interventions in improving motor function in hemiplegic CP. However, the role of these as of yet >interventions in reducing spasticity remains to be clarified.

Systemic Weakness After Therapeutic Injections of Botulinum Toxin A

The use of intramuscular injections of Botulinum neurotoxin A (BoNT-A) is common in the treatment of hypertonicity and movement disorders. Although most side effects are mild, systemic effects, manifested by generalized weakness distant from the site of injection, have been reported. Previously reported occurrences are discussed, and 3 new cases of patients, who developed systemic weakness after administration of BoNT-A (Botox), despite having tolerated similar injections on several previous occasions, are presented. A review of the literature and reported cases indicate that risk of developing systemic effects does not seem to be related to dose based on body weight. It may be more likely that risk for systemic effects is related to total injection dose and injection frequency. The results of our 3 patients would indicate that injections of greater than 600 units of Botox with follow-up injections occurring every 3 months may lead to an increased risk. We would recommend careful consideration of reinjection frequency if injections of greater than 600 units of Botox are given. Reduction in systemic side effects may occur if reinjection frequency occurs in intervals of 4 months or greater in these individuals.