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.

Symptomatic Improvement of Diffuse Esophageal Spasm after Botulinum Toxin Injection / 대한소화기학회지

Diffuse esophageal spasm, an uncommon esophageal motility disorder, has recently been defined using high-resolution manometry. Patients with distal esophageal spasm usually complain of chest pain or dysphagia. The etiology and pathophysiology of this disorder are poorly known, and treatment options are limited. However, some options to improve symptoms are available, including endoscopic injection of botulinum toxin. Nevertheless, few reports have described the effects of endoscopic injection of botulinum toxin in patients with symptomatic diffuse esophageal spasm with clear endoscopic and high-resolution manometry images. Here, we report a case of diffuse esophageal spasm diagnosed with high-resolution manometry and treated by endoscopic injection of botulinum toxin with good results at the 7-month follow-up.

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.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease / Degeneração hepatocerebral adquirida e encefalopatia hepática: correlações e variedade de apresentações clínicas na doença hepática evidente e subclínica

Acquired hepatocerebral degeneration (AHD) and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE) can be even more complicated. We describe three cases of AHD (two having HE) with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

A degeneração hepatocerebral adquirida (AHD) e a degeneração hepatolenticular podem ter apresentações clínicas semelhantes, mas quando uma doença hepática crônica e achados motores atípicos coexistem, a distinção entre AHD e encefalopatia hepática (HE) pode ser ainda mais complicada. Descrevemos três casos de AHD (dois tendo HE) com diferentes achados em neuroimagem, doenças hepáticas distintas e apresentações motoras semelhantes, todos com hipertensão arterial e perda de peso antes das manifestações motoras. O diagnóstico e a fisiopatologia são comentados e comparados com relatos prévios. Concluímos que existem muitas correlações entre HE, degeneração hepatolenticular e AHD, mas a sobreposição de HE e AHD pode ser mais comum dependendo do conhecimento clínico e da acurácia dos critérios diagnósticos adotados para cada enfermidade. Como a AHD não é considerada prioridade na lista de transplante hepático, o prognóstico dos pacientes com AHD permanece ruim, e a interrupção do fluxo nos shunts portossistêmicos deve ser sempre considerada.

Restless legs syndrome in subjects with a knee prosthesis: evidence that symptoms are generated in the periphery

OBJECTIVE: There are no data adressing the prevalence of restless legs syndrome in subjects who have knee prosthesis. Therefore, we conducted a cross-sectional survey of subjects who underwent knee prosthesis surgery. METHOD: A total of 107 subjects (30 male, 77 female) were interviewed over the telephone regarding restless legs syndrome symptoms. If the patients exhibited symptoms of the syndrome, we conducted face-to-face interviews. Lastly, a therapeutic test with pramipexole was proposed for each subject. RESULTS: In our cohort, 7 males (23 percent) and 30 females (39 percent) had restless legs syndrome. Of these, 6 males and 23 females were submitted to face-to-face-interview. Of the males, 5 (83 percent) had restless legs after the knee surgeryexclusively in the operated leg- and reported no family restless legs history. One man had a prior case of bilateral restless legs syndrome, a positive family history and claimed exacerbation of symptoms in the operated leg. Among the females, 16 (69 percent) had restless legs prior to surgery. A total of 10 female patients reported bilateral symptoms, with fewer symptoms in the operated leg, while 6 displayed a worse outcome in the operated leg. The 7 females (31 percent) without restless legs prior to surgery and without a family history experienced symptoms only in the operated leg. All subjects responded favorably to the pramipexole therapeutic test. CONCLUSION: Our results suggest that secondary unilateral restless legs syndrome may ensue from knee prosthesis surgery and that the symptoms are generated in the peripheral nervous system.

Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson’s disease.

Hemibalismo invalidante transitorio como debut de diabetes mellitus / Transient hemiballism as the presenting symptom of diabetes mellitus: report of one case

Hemiballism is an uncommon neurological disorder characterized by uncontrollable movements of one lateral half of the body. We report a 56 years old male with a history of three weeks of polydipsia, polyuria and weight loss that, three days before consultation, started with hemiballism. A CAT scan without contrast showed a higher density in the lenticular nucleus and calcifications in caudate and lenticular nuclei. Diabetes was treated with regular insulin and hemiballism was controlled with neruoleptics. Ten days after admission a new CAT scan shows a partial regression of the lenticular lesion. After two months of follow up, the patient is asymptomatic.

The validation of the disease-specific questionnaire for health-related quality of life in Thai patients with hemifacial spasm.

OBJECTIVE: To investigate the reliability and validity of the Thai version of disease-specific health-related quality of life instrument for patients with hemifacial spasm (HFS) as well as their response to botulinum toxin treatment. MATERIAL AND METHOD: A Thai version of HFS-30 has been developed with the permission of the author. Thirty patients with HFS were asked to complete this Thai HFS-30, the 6-point disability scale before treatment and between four and six weeks after botulinum toxin injections. Peak improvement (0-100%) was subjectively assessed by each patient between four and six weeks after injection. They were also asked to answer the existing Thai SF-36 questionnaire before treatment to test its correlation with Thai HFS-30. Another group of ten patients completed the questionnaire and then a second identical copy after a 2-week interval. The reliability, validity, and responsiveness were subsequently analyzed. RESULTS: The Thai HFS-30 showed a Cronbach's alpha coefficient of 0.78 and no significant difference of a test-retest reliability. The total content validity was 0.88 (range 0.5-1.0). There were good correlations between both the Physical and Mental Health parts of the Thai HFS-30 and Thai SF-36 (p < 0.05 and p < 0.01, respectively). The Thai HFS-30 also demonstrated a response to treatment similar to the 6-point disability scale and the peak improvement. CONCLUSION: The Thai version of HFS-30 is a valid, reliable, and sensitive to change instrument for disease specific health-related quality of life assessment.

A Case of a Patient with Both Chorea and Restless Legs Syndrome

The patient was a 44-yr-old man with end-stage renal disease who had developed chorea as a result of hypoglycemic injury to the basal ganglia and thalamus and who was subsequently diagnosed with depression and restless legs syndrome (RLS). For proper management, the presence of a complex medical condition including two contrasting diseases, chorea and RLS, had to be considered. Tramadol improved the pain and dysesthetic restlessness in his feet and legs, and this was gradually followed by improvements in his depressed mood, insomnia, lethargy, and feelings of hopelessness. This case suggests that the dopaminergic system participates intricately with the opioid, serotoninergic, and noradrenergic systems in the pathophysiology of RLS and pain and indirectly of depression and insomnia.

Como a coréia de Sydenham é tratada no Rio de Janeiro? / How Sydenham's chorea is treated in Rio de Janeiro?

INTRODUÇÃO: A coréia de Sydenham é a principal causa de coréia adquirida na infância no Brasil. Assim, torna-se relevante saber como os médicos tratam os pacientes coréicos no nosso meio. OBJETIVO: Descrever a prática médica informada em coréia de Sydenham entre pediatras. MÉTODO: Estudo observacional descritivo seccional realizado por entrevistas feitas entre pediatras de emergência e especialistas dos hospitais públicos do Município do Rio de Janeiro. RESULTADOS: 74 por cento dos entrevistados referiu não usar escalas de gravidade; somente 81 por cento dos médicos fazem uso regular de penicilina benzatina; 64 por cento referem iniciar tratamento farmacológico; 28,3 por cento usam apenas o haloperidol para o tratamento. CONCLUSÃO: As escalas de gravidade não são usadas rotineiramente no atendimento de pacientes coréicos; há tendência à prescrição irregular de penicilina entre médicos mais jovens; o haloperidol é a droga mais prescrita entre os entrevistados.

BACKGROUND: Sydenham's chorea is the most common cause of acquired childhood chorea in Brazil. Thus it is relevant to know how physicians treat those patients. OBJECTIVE: To describe the practice patterns of Sydenham's chorea among pediatricians. METHOD: A descriptive study was undertaken using a questionnaire among specialists and emergency pediatricians who work in public hospitals of Rio de Janeiro district. RESULTS:74 percent of the physicians informed not to use any severity scale; 81 percent informed to always prescribe benzatine penicillin; 64 percent informed to begin pharmacological treatment for all patients; and Haloperidol was the most remembered drug among all physicians. CONCLUSION: Physicians do not use routinely severity scales in follow-up of choreic patients; there is a tendency of irregular prescription of benzatine penicillin by younger doctors; and 28.3 percent prescribe only haloperidol.

Effect of botulinum toxin injection for achalasia in Thai patients.

BACKGROUND: Achalasia is a disorder of the esophagus. The lower esophageal sphincter fails to relax and increases the loss of body peristalsis. It is an uncommon disease worldwide. Data regarding its treatment are derived mostly from North America and European countries. Few data regarding this treatment were available in Asia and no data about using botulinum toxin injection for this disease was available in Thailand. OBJECTIVE: To evaluate the efficacy of botulinum toxin in achalasia in Thai patients. MATERIAL AND METHOD: Eleven achalasia adult Thai patients with a mean age of 56.5 +/- 16.9 were studied. There are nine females and two males. The duration of symptom before treatment was 27.5 +/- 34.5 months. All patients receiving botulinum toxin injection at Siriraj hospital between 2001 and 2006 were retrospectively reviewed. Pretreatment of baseline lower esophageal sphincter, symptom score and body weight were compared. Time to second botulinum toxin injection or the need to receive treatment for recurrence was recorded to evaluate the time of recurrence. Adverse events from this procedure were collected. RESULTS: Eleven patients were involved in this study. One patient that received 40 units of botulinum toxin showed no response after a six months follow up. The other ten patients received botulinum toxin 80 units for each session and were enrolled in this study. All ten patients demonstrated good response to the first botulinum toxin injection and subsequent injections. Four patients received only one session of botulinum toxin injection during study period. Meanwhile, five patients received two sessions and only one patient required four sessions. Symptom score of all ten patients improved significantly compared with pretreatment score (7.3 +/- 1.3 for pretreatment and 0.4 +/- 0.5, 0.9 +/- 0.7 and 1.6 +/- 1.3 after 2 weeks, 3 months and 6 months, respectively). Body weight increased significantly when compared with pretreatment (47.7 +/- 6.5 Kg for pretreatment and 49.2 +/- 5.8, 50.5 +/- 6.4, and 50.7 +/- 5.8 Kg after 2 weeks, 3 months, and 6 months, respectively). Previous treatments prior botulinum toxin injection do not seem to influence the effect of this treatment. Mean time of recurrence is 444 +/- 132 days (270-718 days). Minor adverse events such as chest pain and reflux symptoms were seen in this therapy. CONCLUSION: Botulinum toxin injection in Thai achalasia patients is an effective, simple, and safe treatment. These results showed the similar outcomes as in Caucasian patients.

Hemichorea resulting from single enhancing computed tomography lesion.

A single small enhancing computerized tomographic lesion is a common finding in Indian patients with seizures, particularly focal seizures. A small single enhancing computed tomography lesion also presents with varied non-epileptic manifestations viz. focal neurological deficits, episodic vascular headache, syndrome of increased intracranial pressure, etc. Here we present a case of hemichorea resulting from single enhancing CT lesion. A 12-year-old female presented with acute onset abnormal movements involving right side of body. A clinical diagnosis of right hemichorea was made and patient was subjected to neuroimaging along with other investigations. CT scan showed a single ring-enhancing lesion with perifocal edema in left thalamic area suggestive of neurocysticercosis. Patient was treated with albendazole, steroids and haloperidol therapy. Patient showed marked improvement at follow-up after one month. Repeat CT scan revealed resolution of lesion. This case has been reported because hemichorea in young female is usually caused by post-streptococcal infection and it is quite rare presentation of small ring enhancing lesion.

Toxina botulínica no tratamento de distonias faciais: avaliação da eficácia e da satisfação dos pacientes ao longo do tratamento / Botulinum toxin in the treatment of facial dystonia: evaluation of its efficacy and patients' satisfaction along the treatment

OBJETIVO: Estudar a eficácia do tratamento com toxina botulínica nos pacientes com distonia facial e a satisfação com o tratamento ao longo do tempo. MÉTODOS: Estudo retrospectivo de 42 pacientes portadores de distonia facial acompanhados no setor de Plástica Ocular da Clínica Oftalmológica do Hospital das Clínicas da Universidade de São Paulo. RESULTADOS: Após as primeiras aplicações, 45,2 por cento dos pacientes deram notas entre 9-10 para melhora do espasmo, 35,7 por cento deram notas entre 7-8, 16,7 por cento deram notas entre 5-6 e apenas um paciente deu nota 4. Em relação ao intervalo de reaparecimento do espasmo, 4,8 por cento dos pacientes referiram entre 5-6 meses, 64,2 por cento entre 3-4 meses e 31 por cento entre 1-2 meses. Ao longo do tratamento, 76,1 por cento dos pacientes referiram manter a mesma nota sobre a melhora do espasmo, 19,1 por cento referiram melhora do resultado nas aplicações e apenas 4,8 por cento referiram piora da eficácia nas aplicações atuais. Quanto ao tempo de retorno do espasmo após aplicação, 64,2 por cento relataram não haver mudança ao longo do seguimento no serviço, 16,7 por cento relataram aumento e 19,1 por cento relataram diminuição do intervalo de remissão dos sintomas. Após aplicação, 19 por cento dos pacientes apresentaram efeitos colaterais e 73,8 por cento dos pacientes referiram desconforto apenas leve ou moderado em relação à aplicação. CONCLUSÕES: O uso da toxina botulínica foi eficaz e não houve alteração da eficácia ao longo do tempo. São poucos os efeitos colaterais e boa tolerância à administração. É boa alternativa para melhorar a qualidade de vida desses pacientes evitando a cegueira funcional causada por essas doenças.

Botulinum toxin: mechanisms of action

O propósito deste artigo é uma revisão dos mecanismos de ação da toxina botulínica (TB) relevantes para a compreensão do seu uso terapêutico. A ação da TB a nível molecular consiste na sua ligação extracelular a estruturas glicoprotéicas em terminais nervosos colinérgicos e no bloqueio intracelular da secreção de acetilcolina. A TB interfere no reflexo espinal de estiramento através do bloqueio de fibras musculares intrafusais causando redução da sinalização aferente veiculada por fibras Ia e II e do tono muscular. Portanto, o efeito da TB pode estar relacionado não somente à paresia muscular mas também à inibição reflexa espinal. A TB promove ainda o bloqueio de fibras autonômicas para músculos lisos e glândulas exócrinas. Apesar de ocorrer alguma difusão sistêmica após a aplicação intramuscular a TB não atinge o sistema nervoso central (SNC) devido ao seu peso molecular (não atravessa a barreira hematoencefálica) e à lentidão do seu transporte axonal retrógrado que permite a sua inativação. Os efeitos indiretos sobre o SNC são: inibição reflexa, reversão das alterações da inibição recíproca, da inibição intracortical e de potenciais evocados somatosensoriais. A redução da dor induzida por formalina sugere que a TB tenha efeito analgésico direto possivelmente mediado por bloqueio da substância P, do glutamato e do peptídeo relacionado ao gene da calcitonina.

Alien hand syndrome: contradictive movement and disorder of color discrimination.

A senile Chinese female patient with alien hand syndrome of vascular etiology is reported. This case exhibited contradictive movement, left-lateral paresis and disorder of color discrimination, which might be a new subtype of the alien limb syndrome.

Botulinum toxins: pharmacology and its current therapeutic evidence for use.

Botulinum toxins are, as a group, among the most potent neuromuscular toxins known, yet they are clinically useful in the management of conditions associated with muscular and glandular over-activity. Botulinum toxins act by preventing release of acetylcholine into the neuromuscular junction. While botulinum toxin type A is commonly available, different manufacturers produce specific products, which are not directly interchangeable and should not be considered as generically equivalent formulations. Type B is also available in the market. Each formulation of botulinum toxin is unique with distinct dosing, efficacy and safety profiles for each use to which it is applied. Botulinum toxin type A is the treatment of choice based on its depth of evidence in dystonias and most other conditions. Botulinum toxin type A is established as useful in the management of spasticity, tremors, headache prophylaxis and several other neurological conditions. Active research is underway to determine the parameters for which the type B toxin can be used in these conditions, as covered in this review. Botulinum toxin use has spread to several fields of medicine.