Comparison of botulinum toxin and propranolol for essential and dystonic vocal tremors

OBJECTIVES: Vocal tremors, which cause social difficulties for patients, may be classified as resting or action tremors. Of the vocal action tremors, essential and dystonic tremors are the most common. Botulinum toxin and oral medications have been used to treat vocal tremors, but no comparative clinical trials have been performed. The aim of this study was to compare the effects of botulinum toxin injection and the oral administration of propranolol in the treatment of essential and dystonic vocal tremors. METHODS: This clinical trial recruited 15 patients, divided into essential and dystonic vocal tremor groups. Patients in both groups received successive treatment with botulinum toxin and propranolol. The treatments were administered at different times; the order of treatment was randomly selected. Patients were assessed with flexible nasofibrolaryngoscopy and with perceptual and acoustic voice evaluations. A statistical significance level of 0.05 (5%) was used. RESULTS: Botulinum toxin produced statistically significant improvements in perceptual measures of vocal instability in patients with dystonic vocal tremors compared with baseline values and treatment with propranolol. The acoustic measure of variability in the fundamental frequency was significantly lower in patients with dystonic vocal tremors after treatment with botulinum toxin. CONCLUSION: Essential and dystonic vocal tremors responded differently to treatment. Dystonic vocal tremors responded significantly to treatment with botulinum toxin but not oral propranolol. Essential vocal tremors did not respond significantly to either treatment, perhaps due to the small number of patients, which is a limitation of this research.

Clinical features and treatment with botulinum toxin in blepharospasm: a 17-year experience / Característica clínicas e tratamento com toxina botulínica em blefaroespasmo: experiência de 17 anos

OBJECTIVE: It was to analyze clinical aspects of patients with blepharospasm, including outcomes of botulinum toxin treatment. Additionally, clinical characteristics of isolated blepharospasm were compared to those of blepharospasm plus other movement disorders. METHODS: Clinical data recorded during 17 years were reviewed. The variables included age, gender, age of onset, past medical history, head trauma, smoking history, family history of dystonia, severity, duration of botulinum toxin relief and adverse effects. RESULTS: A total of 125 patients were included and 75.2% were female. The mean age of onset was 54.3 years; 89.6% of the individuals started with contractions in eye region, and 39.2% of them spread to lower face or neck. Isolated blepharospasm group was compared with blepharospasm-plus group for demographic and clinical features, and therapeutic outcomes, without significant differences. Botulinum toxin treatment improved the severity of contractions (p=0.01) with low rate of side effects (14%). CONCLUSIONS: Both groups - isolated blepharospasm and blepharospasm-plus - shared similar results concerning epidemiology, clinical features and therapeutic response to botulinum toxin.

OBJETIVOS: Analisar as características clínicas de pacientes com blefaroespasmo e os resultados do tratamento com toxina botulínica. Além disso, os pacientes foram divididos em dois grupos, blefaroespasmo isolado e blefaroespasmo associado a outros distúrbios do movimento, os quais foram comparados quanto a características clínicas e terapêuticas. MÉTODOS: Foram revisados prontuários dos últimos 17 anos. As variáveis consideradas foram idade, sexo, idade de início dos sintomas, antecedentes pessoais, história prévia de trauma crânio-encefálico, tabagismo, história familiar de distonia, gravidade do blefaroespasmo, duração do efeito da toxina botulínica e efeitos adversos. RESULTADOS: Foram incluídos 125 pacientes, dos quais 75,2% eram do sexo feminino. A média de idade do início dos sintomas era 54,3 anos; 89,6% dos pacientes tiveram início dos sintomas na região ocular e em 39,2% dos casos houve disseminação para face ou pescoço. Não houve diferenças significativas entre os grupos blefaroespasmo isolado versus blefaroespasmo-plus. O tratamento com toxina botulínica proporcionou melhora dos sintomas (p=0,01) com baixa incidência de efeitos adversos (14%). CONCLUSÕES: Ambos os grupos - blefaroespasmo isolado e blefaroespasmo-plus - apresentaram as mesmas características clínicas, epidemiológicas e resposta terapêutica à toxina botulínica.

Temporomandibular disorders in patients with craniocervical dystonia / Disfunção temporomandibular em pacientes com distonia craniocervical

Temporomandibular disorders are a set of musculoskeletal dysfunctions within the masticatory system, with multiple etiologies. OBJECTIVE: Since craniocervical dystonia can involve the same neuromuscular structure as the temporomandibular joint, we sought to assess the correlation between temporomandibular disorders and craniocervical dystonia. METHOD: We applied the Research Diagnostic Criteria for Temporomandibular Disorders to 42 patients with craniocervical dystonia, in order to identify orofacial pain and temporomandibular characteristics on the day of botulinum toxin injection. RESULTS: Twenty-two patients (52.3 percent) reported temporomandibular joint pain; 24 (57.1 percent), joint sounds; 20 (47.6 percent), masticatory muscle pain; and 21 (50 percent), diminished jaw mobility. The patients with oromandibular dystonia presented temporomandibular disorders more frequently than did patients with other types of craniocervical dystonia (p<0.001). CONCLUSION: Temporomandibular disorders occur frequently in patients with oromandibular dystonia. Further studies should address the proper treatment of temporomandibular disorders associated with dystonia.

As disfunções temporomandibulares são um conjunto de alterações musculoesqueléticas no sistema mastigatório de etiologia multifatorial. OBJETIVO: A distonia craniocervical pode envolver as mesmas estruturas neuromusculares da articulação temporomandibular. Nosso objetivo foi avaliar a correlação entre distúrbios temporomandibulares e distonia craniocervical. MÉTODO: Aplicamos o Critério Diagnóstico para Pesquisa em Disfunção Temporomandibular em 42 pacientes com distonia craniocervical a fim de identificar dor orofacial e características da articulação temporomandibular no dia da injeção de toxina botulínica. RESULTADOS: Vinte e dois pacientes (52,3 por cento) relataram dor na articulação temporomandibular, enquanto 24 apresentaram sons articulares (57,1 por cento), 20 dor na musculatura mastigatória (47,6 por cento) e redução da mobilidade mandibular foi observada em 21 pacientes (50 por cento). Os pacientes com distonia oromandibular apresentaram disfunção temporomandibular em maior frequência do que aqueles com outros tipos de distonia craniocervical (p<0,001). CONCLUSÃO: A disfunção temporomandibular é frequente em pacientes com distonia oromandibular. Novos estudos devem abordar o tratamento adequado das disfunções temporomandibulares associado à distonia.

Manejo con onabotulinumtoxin A del dolor y distonía focal en paciente tetrapléjico pediátrico / Pain and focal dystonia in a pediatric quadriplegic patient: management with onabotulinumtoxin A: a case report

Introduction: Focal dystonia can cause pain and interfere with rehabilitation goals and affect quality of life and family, in a pediatric patient with recent organic brain damage. Objective: This study examined the effects of onabotulinumtoxin A on focal dystonia, posture malalignment, and pain during the sub-acute phase. Method: At four mounths of progress, a 10 years old girl, with mixed quadriparesis secondary to tuberculous meningoencephalitis is presented. The patient was semi-conscious, malnourished, gastrostomized, and exhibited pain at upper right limb mobilization. Physical exam evidenced abnormal scapular posture, and fixed cephalic rotation. Initial treatmnt consisted of neurodevelopmental techniques added to oral antiespatic medication, with no clinical results. Subsequent treatment consisted of onabotulinumtoxin A infiltration, guide with electromyographic technique to those muscles that showed greater dystonic activity, mapped during previous evaluations. Pain was measured according to the Visual Pediatric Analogue Scale, and passive axial alignment and spasticity according to a modified version of the Ashworth Scale, pre and post treatment. Results: Two weeks after infiltration, the patient showed an objective decrease in pain during mobilization, and achieved aligned axial posture both while standing and sitting. At three months follows-up, patient maintained a decline in the dystonic pattern, which allowed adequate positioning to enable the integration of both upper limbs during activities, without pain interference. Discussion: The use of onabotulinumtoxin A could play a role in the management of focal dystonia and a secondary pain, during the sub-acute phase of organic brain damage.

Introducción: En un paciente pediátrico con daño orgánico cerebral reciente, la distonía focal puede ser causa de dolor que interfiera con los objetivos de rehabilitación y repercuta en la calidad de vida del paciente y su familia. Objetivo: Mostrar el efecto de la onabotulinumtoxin A sobre cuadro de distonía focal, con alteración postural y dolor en pacientes en etapa subaguda. Método: Presentamos a una niña de 10 años, portadora de tetraplejia mixta secundaria a meningoencefalitis tuberculosa, estado de mínima conciencia, desnutrición, gastrostomizada, de cuatro meses de evolución, quien presentaba dolor a la movilización de la extremidad superior derecha y al examen físico; se encontró compromiso postural de escápula y giro mantenido cefálico. Se inició manejo con técnicas de neurodesarrollo y antiespásticos orales sin respuesta clínica. Se efectuó infiltración de onabotulinumtoxin A con técnica de guía electromiográfica en los músculos que presentaron mayor descarga distónica mapeados en evaluación previa. Se objetivó el dolor según Escala visual análoga pediátrica, alineamiento pasivo axial y espasticidad según Escala modificada de Ashworth, pre y post procedimiento. Resultados: Tras dos semanas post infiltración, se objetivó paciente con disminución del dolor frente a la movilización, con postura alineada axial tanto en decúbito como sedente. A los tres meses mantenía disminución en hipertonía, posicionamiento adecuado que permitía actividades de integración de ambas extremidades superiores sin interferencia por dolor. Discusión: El uso de onabotulinumtoxin A puede cumplir función en el control de la hipertonía y en el control del dolor secundario, en un paciente de evolución subaguda posterior a daño cerebral adquirido.

Use of botulinum A toxin [BOTOX] in different types of facial dystonia

This study was carried out in the Eye Departments of Combined Military Hospital, Kharian and Military Hospital, Rawalpindi, from January 2007 to August 2008. To determine the effects of botulinum A toxin [Botox] injection in different types of facial dystonia. A total of 23 botulinum A toxin [Botox] injections were given in 13 patients including 7 males and 6 females. Patients were followed up at 1 week, 6 weeks and 6 months after the injection. The indications were essential blepharospasm in 4 [30.77%] cases and hemifacial spasms in 9 [69.23%] cases. Age ranged from 28 to 60 years [mean 41 +/- 12 years]. Four patients were given injections three times and 2 patients were injected twice. Onset of action of botulinum A toxin [Botox] was variable, starting on the same day in 3 patients while in the rest of patients it started on the next day. Mean duration of action was 12.77 weeks +/- 4.68 [range 6-23 weeks]. Dystonia improved in all the cases. Temporary slight facial paresis and lagophthalmos occurred in 3 [23%] cases while ptosis occurred in 2 [15.4%] cases. Two patients [15%] had mild ocular irritation and conjunctival congestion after injection, which settled with topical mild steroid [fluorometholone]. Botulinum A toxin [Botox] is useful treatment for different types of facial dystonia

Predisposition of genetic disease by modestly decreased expression of GCH1 mutant allele

Recently it was shown that single nucleotide polymorphisms (SNPs) can explain individual variation because of the small changes of the gene expression level and that the 50% decreased expression of an allele might even lead to predisposition to cancer. In this study, we found that a decreased expression of an allele might cause predisposition to genetic disease. Dopa responsive dystonia (DRD) is a dominant disease caused by mutations in GCH1 gene. The sequence analysis of the GCH1 in a patient with typical DRD symptoms revealed two novel missense mutations instead of a single dominant mutation. Family members with either of the mutations did not have any symptoms of DRD. The expression level of a R198W mutant allele decreased to about 50%, suggesting that modestly decreased expression caused by an SNP should lead to predisposition of a genetic disease in susceptible individuals.

Avaliação do filme lacrimal de pacientes com distonia facial durante tratamento com toxina botulínica tipo A / Lacrimal film evaluation of patients with facial dystonia during botulinum toxin type A treatment

OBJETIVO: Determinar o efeito da toxina botulínica no filme lacrimal em pacientes com distonia facial. MÉTODOS: Foram incluídos 24 pacientes portadores de blefaroespasmo essencial e espasmo hemifacial que receberam aplicação de toxina botulínica tipo A que foram submetidos à propedêutica do filme lacrimal previamente à aplicação e após, com 7 e 30 dias. RESULTADOS: Houve diminuição das queixas de olho seco trinta dias após a aplicação, entretanto, o tempo de ruptura do filme lacrimal e o teste de Schirmer não demonstraram variação significativa entre os períodos pré-tratamento e 1 mês da aplicação. Em relação ao teste de coloração com rosa bengala, todos os olhos que coraram no pré-tratamento, melhoraram na última avaliação. CONCLUSÃO: A injeção de toxina botulínica pode aliviar as queixas de olho seco nos pacientes com distonia facial pela provável ação de inibição do orbicular na sua função de bomba lacrimal.

Status dystonicus: study of five cases

O "Status Dystonicus" (SD) é uma situação clínica caracterizada por contratura muscular generalizada em pacientes com distonias. Relatamos cinco casos de SD, que ocorreram em dois pacientes com distonia associada à paralisia cerebral, um paciente com distonia segmentar primária, um com síndrome de Hallervorden-Spatz e um com doença de Wilson (DW). Três pacientes foram submetidos a tratamento em terapia intensiva com uso de propofol e midazolam e dois pacientes foram submetidos ao tratamento neurocirúrgico (um paciente com palidotomia bilateral e outro com estimulador cerebral profundo palidal bilateral). Em três casos foram identificados fatores desencadeantes: infecção, estresse acentuado e o uso de zinco no tratamento da DW. Em dois pacientes ocorreu melhora importante do quadro distônico, e outros três retornaram à situação clínica pré-SD.

Botulinum toxin in the treatment of writer's cramp.

BACKGROUND: Writer's cramp is a task specific focal dystonia. The treatment of writer's cramp is very disappointing. AIM: Study the effect of botulinum toxin (BTX) in the treatment of writer's cramp. MATERIAL AND METHODS: Sixteen patients of writer's cramp (15 men, 1 woman) with mean age of 35.75 years and mean duration of symptoms for 3.64 years received 22 treatment sessions of botulinum toxin-A (BTX). All patients were evaluated before, 3 and 12 weeks after BTX therapy on a rating scale from 0-4 for ease of writing, abnormal posture and pain (0 = normal, 4 = very severe disability). The speed of writing was also recorded before and 3 and 12 weeks after therapy. Each patient also gave a global subjective assessment 12 weeks after BTX therapy. RESULTS: Follow up was available after 19 treatment sessions. Significant improvement was seen in all the parameters studied i.e. abnormal posture (p = 0.0039), pain (p = 0.0092), ease of writing of (p = 0.0025) and speed of writing (p = 0.0025). An improvement of 50% or more was observed after 13 treatment sessions. Asymptomatic weakness in the injected limb was seen in all patients but four patients complained of weakness of fingers. The mean onset of improvement was 10.68 +/- 4.32 days and mean duration of effect was 9.47 +/- 5.34 weeks. CONCLUSION: BTX is effective in the treatment of writer's cramp. The draw-backs are short duration of action and prohibitive cost.

Long term use of botulinum toxin in focal dystonias and otherdisorders: experience at king khalid University Hospital

The long-term efficacy of Botulinun Toxin in the treatment of focal dystonias, hemifacial spasm and spasticity was assessed in all patients treated at King Khalid University Hospital between February 1991 and December 1998. A satisfactory response was initially obtained and later on sustained in the majority of patients with hemifacial and blepharospasm [91%], spasmodic torticollis [75%] and spasticity [61%]. In writer's cramp favourable response was restricted to a smaller group [22%], however this effect was sustained in most responders. Most patients with hemidystonia or generalized dystonia showed poor response inspite of using high doses. Peak responses were noted 4-5 weeks after treatment and the beneficial effect lasted for a mean of 14 weeks. In general, this benefit was persistent with repeated injections over 1.5-7 years of follow-up, with apparent tendency for total dose as well as side effects reduction. Local side effects were mild and short-lived, while systemic side effects were not observed. Botulinum toxin is a safe medication of considerable persistent benefits in treating hemifacial spasm, blepharospasm, spasmodic torticollis, certain group of writer's cramp and spasticity. Other potential indications for BTX-A use are reviewed