Botulinum Toxin and Deep Brain Stimulation in Dystonia.

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

Botulinum Toxin as a Treatment for Feeding Difficulties in Young Children.

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, decreases in tube feeding, and need for repeat injections. The χ2 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; 57 patients (67%) had partial or complete improvement in symptoms after IPBI. Among 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 = .004) and fewer patients receiving postpyloric feeds after IPBI compared with before (12/55 vs 21/55; P = .01). Twenty-six patients (31%) received repeat IPBI within 1 year, with only 6 patients receiving IPBI more than twice. CONCLUSIONS: IPBI is safe and effective in young children. Children with enteral tubes show improvement in oral feeding and reduction in need for postpyloric feeding after IPBI.

Can the positions of the spastic upper limb in stroke survivors help muscle choice for botulinum toxin injections?

Motor impairments in stroke survivors are prevalent and contribute to dependence in daily activities, pain and overall disability, which can further upper-limb disability. Treatment with botulinum toxin A (BoNT-A) is indicated for focal spasticity and requires knowledge of biomechanics and anatomy to best select muscles to be injected in the limb. OBJECTIVE We aimed to describe the frequency of posture patterns in a Brazilian sample of stroke survivors and correlate them with recommendations of muscle selection for treatment with BoNT-A. METHODS Fifty stroke patients with spastic upper limbs scheduled for neuromuscular block were photographed and physically examined, to be classified by three independent evaluators according to Hefter's classification. Muscles that were injected with BoNT-A by their routine doctors were retrieved from medical charts. RESULTS Pattern III and IV were the most common (64.7%, 21.6%). We further subclassified pattern III according to the rotation of the shoulder, which effectively interfered in muscle choice. The muscles most frequently treated were shoulder adductors and internal rotators, elbow flexors and extensors, in forearm, the pronator teres and finger and wrist flexors, and, in the hand the adductor pollicis. CONCLUSION Frequencies of upper-limb postures differed from previous reports. Other clinical features, besides spasticity, interfered with muscle choice for BoNT-A injection, which only partially followed the recommendations in the literature.

Botulinum toxin as a treatment for short bowel syndrome in rats

Purpose: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. Methods: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C control). Results: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. Conclusion: This may provide a new promising approach to the surgical treatment of SBS.(AU)

Can the positions of the spastic upper limb in stroke survivors help muscle choice for botulinum toxin injections? / A posição do membro superior de indivíduos com doença cerebrovascular pode auxiliar na escolha de músculos para a injeção de toxina botulínica?

ABSTRACT Motor impairments in stroke survivors are prevalent and contribute to dependence in daily activities, pain and overall disability, which can further upper-limb disability. Treatment with botulinum toxin A (BoNT-A) is indicated for focal spasticity and requires knowledge of biomechanics and anatomy to best select muscles to be injected in the limb. Objective: We aimed to describe the frequency of posture patterns in a Brazilian sample of stroke survivors and correlate them with recommendations of muscle selection for treatment with BoNT-A. Methods: Fifty stroke patients with spastic upper limbs scheduled for neuromuscular block were photographed and physically examined, to be classified by three independent evaluators according to Hefter's classification. Muscles that were injected with BoNT-A by their routine doctors were retrieved from medical charts. Results: Pattern III and IV were the most common (64.7%, 21.6%). We further subclassified pattern III according to the rotation of the shoulder, which effectively interfered in muscle choice. The muscles most frequently treated were shoulder adductors and internal rotators, elbow flexors and extensors, in forearm, the pronator teres and finger and wrist flexors, and, in the hand the adductor pollicis. Conclusion: Frequencies of upper-limb postures differed from previous reports. Other clinical features, besides spasticity, interfered with muscle choice for BoNT-A injection, which only partially followed the recommendations in the literature.

RESUMO As deficiências motoras que ocorrem nos indivíduos com doença cerebrovascular (DCV) são prevalentes e contribuem para dependência, dor e incapacidade, o que pode atrasar a reabilitação do membro superior e sua funcionalidade. O tratamento com toxina botulínica do tipo A (BoNT-A) é indicado para a espasticidade focal e requer conhecimento da biomecánica e anatomia para melhor selecionar os músculos a serem injetados. Objetivo: Descrever a frequência de padrões posturais numa amostra de brasileiros com sequelas de DCV e correlacioná-los com as recomendações de seleção de músculos. Métodos: Cinquenta pacientes com comprometimento do membro superior devido a DCV do ambulatório de bloqueios neuromusculares foram fotografados e examinados para categorização de acordo com a Classificação de Hefter. Os músculos tratados pelos seus médicos de rotina foram obtidos a partir dos prontuários. Resultados: Os padrões III e IV de Hefter foram mais comuns (64,7%; 21,6%). Nós propusemos a subclassificação do padrão III de acordo com a rotação do ombro, pois isso interferiu na escolha dos músculos tratados. Os músculos tratados com maior frequência foram os adutores e rotadores internos do ombro; flexores e extensores do cotovelo; no antebraço, o pronador redondo, flexores dos dedos e do carpo e na mão, o adutor do polegar. Conclusão: As frequências das posições do membro superior diferiram de relatos prévios. Além da espasticidade, outros fatores interferiram na escolha dos músculos tratados, que seguiram parcialmente as recomendações da literatura.

[Tratamientos estéticos. Posición de la Academia Nacional de Medicina de México].

In Mexico there is a proliferation of "centers for aesthetic medicine" that offer different treatments with laser beam, mesotherapy and hyaluronic acid and botulinum toxin injections. In numerous centers of this type, offered and performed by medical personnel that are neither trained or certified to ensure the quality of services. The National Academy of Medicine of Mexico and the National Normative Council for Medical Specialties (CONACEM) communicate their posture on this matter.

En México existe una proliferación de "centros de medicina estética" que ofrecen tratamientos diversos con rayos láser, mesoterapia, ácido hialurónico e inyecciones con toxina botulínica por personal médico que no está capacitado ni certificado para asegurar la calidad de los servicios. La Academia Nacional de Medicina y el Comité Normativo Nacional de Consejos de Especialidades Médicas (CONACEM) comunican su postura al respecto.

Toxina botulínica para tratamento da sialorreia nos pacientes com doença de Parkinson / Botulinum toxin for treatment of sialorrhea in patients with Parkinson's disease

A sialorreia/ptialismo é um sintoma não motor frequente da doença de Parkinson, que pode causar impacto na saúde e na qualidade de vida dos pacientes. O sintoma decorre da combinação da disfagia com disautonomia e, muitas vezes, também do efeito adverso de drogas frequentemente utilizadas no tratamento de sintomas da doença, como por exemplo, os antipsicóticos atípicos e os inibidores da acetilcolinesterase. Diversas opções terapêuticas são utilizadas na prática clínica para controle da sialorreia, dentre elas, drogas anticolinérgicas ou antagonistas dos receptores adrenérgicos, injeção de toxina botulínica, cirurgia, radioterapia e terapias comportamentais e fonoaudiológicas. Este trabalho faz uma revisão das propostas terapêuticas até o presente momento para controlar a secreção de saliva dos pacientes com doença de Parkinson. A injeção de toxina botulínica nas glândulas salivares guiada por ultrassom é a opção com mais evidência de eficácia e segurança, de acordo com os últimos estudos.

Sialorrhea is a frequent nonmotor symptom in Parkinson´s disease (PD) that influences the patients' health and quality of life. The symptom arises from a combination of difficulty in swallowing saliva, autonomic dysfunction or as a side effect of frequent used drugs to control symptoms of the disease, as for example, atypical antipsychotics and acetylcholinesterase inhibitors. In clinical practice, different therapeutic approaches are used to control sialorrhea, such as anticholinergic or beta adrenergic antagonistic drugs, botulinum toxin injection, surgery, radiotherapy, behavioral psychotherapy and speech therapy. This paper reviews the therapeutic options available until now to control the loss of saliva from PD patient. Botulinum toxin injection in the salivary glands guided by ultrasound shows the best efficacy and security profile, according to the last published data.

Toxina botulínica: compuestos emergentes en Chile / Botulinum toxin: compounds emerging in Chile

Botulinum toxin A is a vastly used therapy for treatment or management of a variety of health conditions. We are talking about a biological compound which is nowadays manufactured by many different laboratories, with distinct and specific characteristics for each one of their products. Although research and use of this toxin have been worldwide established for many years , in Chile we have been using it for over twenty years and since then its uses have been expanding to many fields. During the last few years, new toxins from different laboratories have been incorporated to our country, being necessary to know about them, their similarities and differences as well as to be aware of the uses that are approved or not for each particular drug. (AU)

Vocal Parameters and Self-Perception in Individuals With Adductor Spasmodic Dysphonia.

OBJECTIVE: The study aimed to compare and correlate perceptual-auditory analysis of vocal parameters and self-perception in individuals with adductor spasmodic dysphonia before and after the application of botulinum toxin. STUDY DESIGN: This is a prospective cohort study. METHODS: Sixteen individuals with a diagnosis of adductor spasmodic dysphonia were submitted to the application of botulinum toxin in the thyroarytenoid muscle, to the recording of a voice signal, and to the Voice Handicap Index (VHI) questionnaire before the application and at two time points after application. Two judges performed a perceptual-auditory analysis of eight vocal parameters with the aid of the Praat software for the visualization of narrow band spectrography, pitch, and intensity contour. RESULTS: Comparison of the vocal parameters before toxin application and on the first return revealed a reduction of oscillation intensity (P = 0.002), voice breaks (P = 0.002), and vocal tremor (P = 0.002). The same parameters increased on the second return. The degree of severity, strained-strangled voice, roughness, breathiness, and asthenia was unchanged. The total score and the emotional domain score of the VHI were reduced on the first return. There was a moderate correlation between the degree of voice severity and the total VHI score before application and on the second return, and a weak correlation on the first return. CONCLUSIONS: Perceptual-auditory analysis and self-perception proved to be efficient in the recognition of vocal changes and of the vocal impact on individuals with adductor spasmodic dysphonia under treatment with botulinum toxin, permitting the quantitation of changes along time.

Aesthetic and Non-aesthetic Indications for Orbicularis Oculi Myectomy.

INTRODUCTION: Crows' feet wrinkles are caused by the action of the orbicularis oculi muscle on overlying skin. Treatment options range from botulinum toxin to a multitude of surgical methods. We first described our technique in 2003 and refined it in 2006. We highlight the evolution of our technique and look at our results to assess the effectiveness of our technique. OBJECTIVE: The aim of this article is to show our experience of 13 years in 134 patients with our technique of orbicularis oculi myectomy. METHODS: From September 2000 to July 2013, we operated on 134 patients with an age range of 28-77 years. Of these patients, 104 had myectomies via lifting and 22 via a blepharoplasty approach. Five patients had myectomies for treatment of blepharospasm and a further three patients to restore symmetry in facial palsy. An evaluation of the results was performed by two medical students. RESULTS: Our results showed reduction of the wrinkles in all cases. For the statistical analysis the Wilcoxon test was performed. The p value was less than 0.001 showing a significant reduction of crows' feet wrinkles in both sides when the orbicularis myectomy was performed, via blepharoplasty or lifting. For myectomy performed for blepharospasm or facial palsy, the statistical analysis was not done due to the low numbers. CONCLUSION: In the appropriate patient, orbicularis oculi myectomy is an effective and long-term treatment for crows' feet wrinkles with a low risk of complications and high patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Protective potential of recombinant non-purified botulinum neurotoxin serotypes C and D.

Botulinum neurotoxin (BoNT) serotypes C and D are responsible for cattle botulism, a fatal paralytic disease that results in great economic losses in livestock production. Vaccination is the main approach to prevent cattle botulism. However, production of commercially available vaccines (toxoids) involves high risk and presents variation of BoNT production between batches. Such limitations can be attenuated by the development of novel nontoxic recombinant vaccines through a simple and reproducible process. The aim of this study was to evaluate the protective potential of recombinant non-purified botulinum neurotoxin serotypes C and D. Bivalent vaccines containing 200 µg rHCC and rHCD each were formulated in three different ways: (1) purified antigens; (2) recombinant Escherichia coli bacterins; (3) recombinant E. coli cell lysates (supernatant and inclusion bodies). Guinea pigs immunized subcutaneously with recombinant formulations developed a protective immune response against the respective BoNTs as determined by a mouse neutralization bioassay with pooled sera. Purified recombinant antigens were capable of inducing 13 IU/mL antitoxin C and 21 IU/mL antitoxin D. Similarly, both the recombinant bacterins and the cell lysate formulations were capable of inducing 12 IU/mL antitoxin C and 20 IU/mL antitoxin D. These values are two times as high as compared to values induced by the commercial toxoid used as control, and two to ten times as high as the minimum amount required by the Brazilian Ministry of Agriculture, Livestock and Food Supply (MAPA), respectively. Therefore, we used a practical, industry-friendly, and efficient vaccine production process that resulted in formulations capable of inducing protective immune response (neutralizing antitoxins) against botulism serotypes C and D.

Perfil de dispensação da toxina botulínica para tratamento da espasticidade: dados nacionais brasileiros / Dispensing profile of botulinum toxin for treating spasticity: Brazilian national data

Os fisiatras especializados no tratamento de espasticidade foram reunidos para um painel de discussão a respeito do uso de toxina botulínica (TB) na rede pública de diferentes estados do Brasil. Os dados analisados durante a discussão do Datasus demonstram um baixo perfil de demanda desse produto dispensado pelo Sistema Único de Saúde (SUS), com uma heterogeneidade na distribuição da TB nos estados brasileiros. Esse quadro parece se configurar principalmente por falta de uma política pública devidamente planejada, como a falta de unificação e normatização dos centros de distribuição, pela falta ou inadequação da remuneração do procedimento de aplicação da TB aos centros de tratamento, de modo padronizado pela tabela SUS e escassez de médicos capacitados para realizá-lo junto à falta de centros de reabilitação multidisciplinar habilitados. O uso de toxina botulínica com finalidade terapêutica no Brasil teve início nos anos 90, para tratamento de distonia e de espasticidade. Atualmente, é empregada em diferentes condições clínicas, porém, apesar da crescente demanda e indicações ao longo dos anos, há poucos relatos ou publicações sobre seu uso e benefício para pacientes atendidos pela Sistema Único de Saúde (SUS). Para abordar esse tema, em maio de 2015, na cidade de São Paulo, fisiatras de diferentes estados do Brasil se encontraram e discutiram a relevância da toxina botulínica no tratamento de espasticidade

The physiatrists specialized in treating spasticity were brought together for a panel discussion about the use of botulinum toxin (BT) in the public system in different states of Brazil. The data analyzed during the discussion of Datasus demonstrate a low-demand profile of the product dispensed by the Unified Health System (SUS), with heterogeneity in the distribution of TB in the Brazilian states. This scenario seems to be set up mainly for lack of a properly planned public policy, such as lack of unification and standardization of distribution centers, the lack or inadequacy of TB compensation proceeding to treatment centers, in a standardized manner by SUS and shortage of trained doctors to do it together with the lack of qualified multidisciplinary rehabilitation centers. The use of botulinum toxin for therapeutic purposes in Brazil began in the 90s, to treat dystonia and spasticity. It is currently employed in different clinical conditions; however, despite growing demand and indications over the years, there are few reports or publications on its use and benefit to patients served by the Unified Health System (SUS). To address this issue, in May 2015, in São Paulo, physiatrists from different states of Brazil met and discussed the relevance of botulinum toxin in treating spasticity

Management of oromandibular dystonia on a chorea acanthocytosis: a brief review of the literature and a clinical case.

BACKGROUND: Chorea acanthocytosis is an extremely rare neurodegenerative condition characterized by neuropsychiatric disturbances, movement disorders, neuropathy, seizures, and acanthocytosis. In this case report, the authors will present the management of the oromandibular movement disorders associated with this disease. CASE DESCRIPTION: This case report describes the focal management of the severe orofacial manifestations associated with this condition. The therapeutic approach adopted to reduce the severe oromandibular movements, dysphagia, and the numerous oral ulcers was selective electromyography (EMG)-guided botulinum toxin application to the inferior head of the lateral pterygoid muscles and masseters. This would be applied to control severe and sudden oromandibular dystonia. RESULTS: Through this procedure, the authors were able to reduce these severe oral manifestations, which had a major impact on the patient's quality of life, and temporarily improve vital functions, such as mastication, deglutition, and speech articulation. CONCLUSIONS: Electromyography-guided botulinum toxin application may be a useful tool in the multimodal management of this condition.

Differences between motor point and innervation zone locations in the biceps brachii. An exploratory consideration for the treatment of spasticity with botulinum toxin.

BACKGROUND: Botulinum toxin (BTX) acts on the neuromuscular junction which can be located by the innervation zone (IZ). Clinically, the motor point (MP) is homologous to the IZ and it is used as the injection site of BTX. Differences in the effectiveness of the application of BTX between MP and IZ locations have been determined. OBJECTIVE: Compare the location of the MP obtained using electrical stimulation and the location of the IZ using a linear surface electrodes array on the biceps brachii muscle. METHODS: The biceps brachii muscle of twenty men was assessed. The MP was located using the torque measurement generated by electrical stimulation. The IZ was detected using a linear surface electrodes array. RESULTS: A difference between the MP and the IZ positions (75.8 vs. 86.5mm, delta 10.7 mm; p=0.003, post-hoc power 0.89) was observed. DISCUSSION: The magnitude of the difference between the MP and the IZ may be clinically relevant. The IZ location using surface electromyography as a guide to optimize BTX injection is proposed.

Combined treatment with botulinum toxin and hyaluronic acid to correct unsightly lateral-chin depression.

With aging, anatomical changes are observed in the face. In the lower third, these changes are expressed as ptosis of the angle of the mouth, lip enhancement groove mentalis; decrease in concavity between the jaw and neck and very noticeable platysmal banding. The repeated contraction of muscles of the lateral-chin together with the band platysmal side form what are called a marionette groove. Treating the whole lateral-chin area can result in a more harmonious aspect of the face when compared with treatment of a marionette groove in isolation. In this paper we describe combined treatment of the lateral chin area using botulinum toxin and fillers.

Combined treatment with botulinum toxin and hyaluronic acid to correct unsightly lateral-chin depression* / Tratamento combinado com toxina botulínica e ácido hialurônico para correção da depressão inestética lateral mentoniana

With aging, anatomical changes are observed in the face. In the lower third, these changes are expressed as ptosis of the angle of the mouth, lip enhancement groove mentalis; decrease in concavity between the jaw and neck and very noticeable platysmal banding. The repeated contraction of muscles of the lateral-chin together with the band platysmal side form what are called a marionette groove. Treating the whole lateral-chin area can result in a more harmonious aspect of the face when compared with treatment of a marionette groove in isolation. In this paper we describe combined treatment of the lateral chin area using botulinum toxin and fillers.

Com o envelhecimento observamos mudanças anatômicas na face. No terço inferior essas mudanças se expressam como ptose do ângulo da boca; acentuação do sulco lábio mentoniano; diminuição da concavidade entre a mandíbula e o pescoço e formação de bandas platismais bem evidentes. A contração repetida dos músculos da região latero-mentoniana juntamente com a banda platismal lateral, forma o que chamamos de sulco de marionette. Ao tratarmos toda região latero-mentoniana conseguimos um resultado mais harmônico, quando comparado com o tratamento isolado do sulco de marionette. Nesse artigo apresentamos o tratamento combinado da região latero mentoniana com o uso de toxina botulínica e preenchedores.