Targets for treatment of dystonia caused by several etiologies. Meta analysis

Introducción: Para utilizar un meta-análisis de todos los casos reportados de la estimulación cerebral profunda (DBS) para ladistonía para determinar cuáles son los factores significativos resultados influencia relacionada con el destino. La escala demovimiento Burke-Fahn-Marsden (BFM), la medida más informado, fue elegida como la principal medida de resultado paraeste análisis. Material y Métodos: Una búsqueda en MEDLINE identificaron 137 pacientes que se sometieron a DBS para ladistonía en 24 estudios que tenían puntuaciones individuales BFM. Datos de los pacientes individuales, incluyendo la edad deinicio de la distonía, la edad de la cirugía, el género, la distribución de la distonía, la etiología de la distonía, la presencia decaracterísticas asociadas, anormalidad de las imágenes preoperatorias, cirugías estereotáxica anteriores, el núcleo estimulado,el tipo de anestesia que se utiliza, el tiempo de respuesta a la estimulación, y el momento de la evaluación de resultadosse introdujeron en una base de datos de SPSS para el análisis estadístico. Resultados: La media BFM cambio porcentual(mejora en la puntuación postoperatoria de la línea de base) fue 51,8% (rango - 34% a 100%). Significativamente se lograronmejores resultados con la estimulación del globo pálido interno (GPI) que con la estimulación de la parte posterior del núcleolateral ventral (VLP) del tálamo (p = 0,0001)...

Introduction: To use a meta-analysis on all reported cases of deep brain stimulation (DBS) for dystonia to reevaluate the good effect using the GPi as a target, which factors significant influence outcome related to the target. The Burke-Fahn-Marsden (BFM) movement scale, the most reported measure, was chosen as the primary outcome measure for this analysis. Material and Methods: Computerized MEDLINE searches on English literature search identified 137 patients who underwent BBS for dystonia in 24 studies that had individual BFM scores. The study was done with statistical analysis by intention to treat. Statistical analysis was made with a significant p- value of 0.05. For the comparison of pre- and postoperative scores, a test Wilcoxon signed was used. Results: The mean BFM percentage change (improvement in postoperative score from baseline) was 46.3 percent(range - 34 percent to 100 percent)...

Understanding dystonia: diagnostic issues and how to overcome them / Compreendendo a distonia: questões diagnósticas e como superá-las

ABSTRACT The diagnosis and treatment of dystonia are challenging. This is likely due to gaps in the complete understanding of its pathophysiology, lack of animal models for translational studies, absence of a consistent pathological substrate and highly variable phenotypes and genotypes. The aim of this review article is to provide an overview of the clinical, neurophysiological and genetic features of dystonia that can help in the identification of this movement disorder, as well as in the differential diagnosis of the main forms of genetic dystonia. The variation of penetrance, age of onset, and topographic distribution of the disease in carriers of the same genetic mutation indicates that other factors – either genetic or environmental – might be involved in the development of symptoms. The growing knowledge of cell dysfunction in mutants may give insights into more effective therapeutic targets.

RESUMO O diagnóstico e o tratamento da distonia podem ser desafiadores. Isso se dá provavelmente a pouca compreensão da fisiopatologia, a falta de modelos animais para estudos translacionais, ausência de um substrato patológico consistente e genótipo e fenótipo altamente variáveis. O objetivo deste artigo de revisão é fornecer uma visão geral dos aspectos clínicos, neurofisiológicos e genéticos de distonia que podem ajudar na identificação deste distúrbio do movimento, bem como no diagnóstico diferencial das principais formas de distonia hereditária. Há uma ênfase particular na nova definição e classificação da Internacional das Distonias, bem como as recentes descobertas dos mecanismos moleculares subjacentes em algumas formas de distonia primária. A variação de penetrância, idade de início, e distribuição topográfica da doença em portadores da mesma mutação genética indica que outros fatores - genéticos ou ambientais podem estar envolvidos no desenvolvimento dos sintomas. O conhecimento crescente sobre a disfunção celular em mutantes pode gerar insights sobre alvos terapêuticos mais eficazes.

Degeneración corticobasal: reporte de un caso / Corticobasal degeneration: a case report

Se presenta un caso de Degeneración Corticobasal en una paciente chilena de 48 años de edad. La evolución clínica fue progresiva, con parkinsonismo (rigidez, acinesia, alteraciones posturales, disartria), deterioro cognitivo, apraxia del vestir, apraxia constructiva e hipomimia. Además, la paciente presentaba afasia no fluente. Adicionalmente, fue diagnosticada con Síndrome Depresivo Crónico (SDC) y Trombosis Venosa Profunda (TVP) de la extremidad inferior izquierda. Se han descrito varios tipos de enfermedades neurodegenerativas en las últimas décadas, las cuales cumplen con distintas características patológicas y clínicas. Sin embargo, la diferenciación de estas, en la práctica, es compleja y se necesita de una apreciación clínica entrenada, evaluaciones clínicas detalladas, neuroimágenes y estudios de laboratorio para lograr llegar a un diagnóstico adecuado. Dentro de las principales enfermedades neurodegenerativas que se presentan con parkinsonismo encontramos las llamadas “taupatías”, que son la Degeneración Corticobasal (DCB) y la Parálisis Supranuclear Progresiva*(PSP)...

A case study of corticobasal degeneration in a Chilean 48 year old female patient is reported. The clinical course was progressive and included Parkinsonism (rigidity, akinesia, postural abnormalities, dysarthria), cognitive impairment, dressing apraxia, constructive apraxia and hypomimia. In addition, the patienth ad non Mfluent aphasia. Also, the patient was diagnosed with Chronic Depressive Syndrome and Deep Venous Thrombosis (DVT) of the left lower extremity. In recent decades, several types of neurodegenerative diseases* have been described. These diseases have different clinical and pathologic features. However, in practice, it is difficult to differentiate them from one another and, to reach an accurate diagnosis, advanced medical skills, detailed clinical evaluations of neuroimaging and laboratory studies are needed. “Tauopathies”, which are Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) are among the major neurodegenerative diseases occurring with Parkinsonism...

Noxious electrical stimulation of the pelvic floor and vagina induces transient voiding dysfunction in a rabbit survival model of pelvic floor dystonia

PURPOSE: Existing data supports a relationship between pelvic floor dysfunction and lower urinary tract symptoms. We developed a survival model of pelvic floor dysfunction in the rabbit and evaluated cystometric (CMG), electromyographic (EMG) and ambulatory voiding behavior. MATERIALS AND METHODS: Twelve female adult virgin rabbits were housed in metabolic cages to record voiding and defecation. Anesthetized CMG/EMG was performed before and after treatment animals (n=9) received bilateral tetanizing needle stimulation to the pubococcygeous (PC) muscle and controls (n=3) sham needle placement. After 7 days all animals were subjected to tetanizing transvaginal stimulation and CMG/EMG. After 5 days a final CMG/EMG was performed. RESULTS: Of rabbits that underwent needle stimulation 7 of 9 (78%) demonstrated dysfunctional CMG micturition contractions versus 6 of 12 (50%) after transvaginal stimulation. Needle stimulation of the PC musculature resulted in significant changes in: basal CMG pressure, precontraction pressure change, contraction pressure, interval between contractions and postvoid residual; with time to 3rd contraction increased from 38 to 53 minutes (p=0.008 vs. prestimulation). Vaginal noxious stimulation resulted in significant changes in: basal CMG pressure and interval between contractions; with time to 3rd contraction increased from 37 to 46 minutes (p=0.008 vs. prestimulation). Changes in cage parameters were primarily seen after direct needle stimulation. CONCLUSIONS: In a majority of animals, tetanizing electrical stimulation of the rabbit pelvic floor resulted in voiding changes suggestive of pelvic floor dysfunction as characterized by a larger bladder capacity, longer interval between contractions and prolonged contraction duration.

Jaw-opening oromandibular dystonia secondary to Wilson's Disease treated with botulinum toxin type A / Distonia oromandibular com abertura da boca secundária à doença de Wilson tratada com toxina botulínica tipo A

We have reported a case series of five patients with jaw-opening oromandibular dystonia secondary to Wilson's disease (WD), in which the patients were treated with botulinum toxin type A (BTX-A). In all cases, dystonia score was partially reduced three weeks after injections. The most common side effect was transient mild dysphagia. This preliminary study showed that jaw-opening oromandibular dystonia in WD may be partially responsive to the use of BTX-A.

Relata-se uma série de cinco casos de distonia oromandibular com abertura da boca, secundária à doença de Wilson, em que os pacientes foram tratados com toxina botulínica tipo A. Em todos os casos, a distonia oromandibular com abertura da boca foi parcialmente reduzida três semanas após as injeções. O efeito adverso mais comum foi a disfagia leve e transitória. Este estudo preliminar mostrou melhora parcial da distonia oromandibular com abertura da boca.

Psychogenic dystonia induced by peripheral trauma: case report

The origin of dystonia is a point of discussion since its first description. A cause-and-effect relationship between brain injury and subsequent movement disorder is well established, but the existence of such a relationship following peripheral injury has not been universally accepted. This paper has the objective to report a patient with fixed dystonic posture of the hand after peripheral trauma.

A origem da distonia continua sendo controversa como nas suas primeiras descrições. A relação de causa e efeito entre traumatismo craniano e distúrbios do movimento está bem estabelecida, no entanto, a existência de tal relação após trauma periférico não é amplamente aceita. Este trabalho tem por objetivo relatar um paciente com postura distônica fixa da mão após trauma periférico.

Meige's syndrome

The Meige's syndrome is characterized by the presence of bilateral, symmetrical, dystonic cramp of face muscles or muscles of middle line of body, the respiratory muscles and muscles of throat. The etiology of Meige's syndrome is uncertain. A disorder of basal ganglia function along with perhaps neurotransmitter imbalance [dopamine and acetylcholine] is likely to be the mechanism involved in the causation of this disorder. It is a rare condition and only a limited number of cases have been reported in literature. However, many patients may remain undiscovered or misdiagnosed. Our aim is to introduce a case of 68 years old man who was referred to neurology department with chief complaint of oromandibular dystonia and dysphasia. He was treated successfully with Botulinum toxin

Recurrent opisthotonus in catatonia: An atypical presentation.

Opisthotonus is known to occur in tetanus, rabies, cerebral malaria, neurosyphilis, acute cerebral injury and other medical conditions. Opisthotonus, so far, has not been reported in any major psychiatric disorder. Authors report a case of recurrent opisthotonus presenting concurrently with other catatonic signs which showed dramatic response to combination of lorazepam and electroconvulsive therapy (ECT). Clinicians should consider the possibility of catatonia in the differential diagnosis of opisthotonus since catatonia can be treated easily with benzodiazepines and ECT.

Determinants of Acute Dystonia in First Episode of Psychotic Patients Treated with Haloperidol and Centbutindole.

Objectives: To assess the factors affecting of acute dystonia in first episode psychotic patients taken haloperidol and centbutindole Method and Procedure: Total 54 patients (Schizophrenia, manic, psychotic) taken for the study from the psychiatry O.P.D. K.G.M.C Lucknow. The age group of patients were between the 17 to 55 years. This study was double blind and prospective. Patients were randomly administered Holoperidol (5 mg) TDS or Centbutindole (1.5 mg) TDS. The total period of study was 2 weeks, if any abnormal movements developed during this period the criteria for acute dystonia was applied. Tools: Semi structured proforma, International Classification of Disease — 10. Diagnostic and research criteria for neuroleptic induced acute dystonia, Scale for assessment of torsion dystonia. Beck and Refaelsen Mania Rating Scale: for manic patient only, Brief Psychiatric Rating Scale: On all patients was used. Result: The results show that acute dystonia was higher among the manic patients, younger age, married, male between the age group 17-25 year and duration of illness 1-3 months. It was also higher among those patients who have psychiatric family history.

Clinical features of dystonia in atypical parkinsonism / Características clínicas da distonia no parkinsonismo atípico

BACKGROUND: The association between Dystonia and Parkinson's disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE: To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD: A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn&Yahr scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS: The overall frequency of dystonia in our sample was 50 percent with 30.4 percent (n=7) in the MSA group, 62.5 percent (n=5) in the PSP group, and 100 percent (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION: In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50 percent) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.

INTRODUÇÃO: A associação de distonia e doença de Parkinson (DP) já foi bem estabelecida, principalmente para distonia focal em pé ou mão. Entretanto, há poucos dados quanto a distonia em pacientes com parkinsonismo atípico. OBJETIVO: Avaliar a freqüência e o padrão da distonia em um grupo de pacientes com parkisnonismo atípico (atrofia de múltiplos sistemas - AMS; paralisia supranuclear progressiva - PSP; degeneração corticobasal - DCB) e investigar se a distonia pode ser a manifestação inicial neste grupo. MÉTODO: Um total de 38 prontuários médicos foi revisado (n=23/grupo AMS; n=8/grupo PSP; n=7/grupo PSP) e os dados foram apresentados em médias/desvios padrões. As variaveis avaliadas foram: sexo, idade de início, duração da doença, primeiro sintoma, características clínicas da distonia e outros sinais neurológicos, resposta ao tratamento com levodopa, escala de Hoehn & Yahr >3 em 3 anos de doença, e achados de ressonância magnética. RESULTADOS: A frequência total de distonia em nosso grupo foi 50 por cento, sendo 30,4 por cento (n=7) no grupo AMS, 62.5 por cento (n=5) no grupo PSP e 100 por cento (n=8) no grupo DCB. Em nenhum dos pacientes, distonia foi o primeiro sintoma. Várias apresentações de distonia foram observadas: camptocormia, anterocólis, retrocólis, distonia oromandibular, em pé e mão. CONCLUSÃO: Em nossa série, distonia foi uma característica comum em pacientes com parkinsonismo atípico (freqüência de 50 por cento) e fez parte da história natural em todos os grupos, embora não tenha sido o sintoma inicial em nenhum deles. Anormalidades no exame de neuroimagem não necessariamente estão relacionadas a distonia focal, e o tratamento com levodopa não influenciou o padrão da distonia em nosso grupo de pacientes.

Hypomyelination with atrophy of the basal ganglia and cerebellum: case report

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare disease that has been recently described. It must be remembered as a possible etiology of leukoencephalopathies in children. We describe a typical case of H-ABC in a 11-month-old boy. He presents with global development delay, oral dyskinesia, and global dystonia and spasticity. Magnetic resonance imaging disclosed typical features of H-ABC and clinical laboratory tests were all negative. A slow neurological deterioration has been detected with worsening of involuntary movements.

A hipomielinização com atrofia dos núcleos da base e do cerebelo (H-ABC) é uma rara afecção que deve ser lembrada como possível diagnóstico das leucoencefalopatias de difícil definição etiológica. Descrevemos um típico caso de H-ABC em um menino de 11 meses, sem antecedentes de risco para lesão cerebral, que evoluiu com atraso psicomotor acompanhado de discinesia perioral, distonia e espasticidade generalizadas. A ressonância magnética do encéfalo sugere fortemente o diagnóstico de H-ABC e os exames complementares para pesquisar possíveis diagnósticos diferenciais são negativos. O curso clínico tem sido lentamente progressivo com ausência de ganhos motores e piora dos movimentos involuntários.

Hallervorden Spatz disease.

A nine-month-old infant presented with fever and loss of milestones. Examination revealed intermittent rigidity and dystonic movements. Magnetic resonance imaging (MRI) shows decreased signal intensity in globus pallidus and substantia nigra, indicative of iron deposition, suggesting Hallervorden Spatz Disease. The dopamine-neuromelanine system has been postulated to be the possible pathogenesis. Gene mapping has located the defect to be in the coding sequence of a gene called PANK-2. Prenatal diagnosis is possible. The case is reported because of its rarity and early presentation.

Dystonia as presenting manifestation of ataxia telangiectasia : a case report.

Ataxia telangiectasia is a genetically inherited multisystem disorder with predominant feature being telangiectasia and cerebellar ataxia. In this report, a family of three siblings suffering from ataxia telangiectasia is described. The proband presented with dystonia and dystonic myoclonus, both of which are rare presenting features of ataxia telangiectasia.

Distonia segmentar como manifestaçäo de angioma cavernoso: relato de caso / Segmental dystonia as manifestation of cavernous angioma: case report

A distonia é uma síndrome neurológica cuja etiologia costuma não ser bem definida. Relatamos caso de uma paciente que apresentou aos 16 anos de idade dificuldade para tocar piano, havendo um comprometimento progressivo da mão, antebraço e braço esquerdo que posteriormente evoluiu com crises de "ausência" e cefaléia. Realizou exames de imagem que evidenciaram angioma cavernoso na região temporal profunda direita (ínsula). É rara a associação entre essas duas enfermidades, não havendo na literatura relato de distonia segmentar associada a crises de pseudoausência e cefaléia com características migranosas secundária ao angioma cavernoso. Vinte e cinco por cento das distonias são secundárias, o que nos faz sugerir uma investigação mínima em neuroimagem.

Hallervorden-Spatz syndrome in two siblings diagnosed by clinical features and magnetic resonance imaging.

The Hallervorden-Spatz syndrome (HSS) is a rare condition characterized by extrapyramidal and pyramidal signs, dystonia, dysarthria, retinal degeneration, dementia and a progressive course. The development of magnetic resonance imaging (MRI) has increased the number of clinical and pathological reports of HSS. MRI pallidal abnormalities are called "eye of the tiger" signs. The combination of clinical features and MRI findings can be considered as highly suggestive of a diagnosis of HSS. Patient 1 was a 28 year old man who had been well until the age of 25 years. He developed dysarthria, difficulty with his gait and dystonia in his arms at the age of 28 years. Patient 2 was a 33 year old man who was the older brother of the first patient. He developed gait difficulty, tongue dystonia and dystonia of both arms at the age of 25 years. Each patient had spastic gait, dysarthria, dystonic posturing of both arms and generalized hyperreflexia, but no Kayser-Fleischer rings or retinitis pigmentosa. Blood chemistry, urine copper, serum copper and serum ceruloplasmin were all normal. MRI of the brain showed the "eye of the tiger" sign in the globus pallidus on T2 weighted images. These siblings had clinical features and MRI findings consistent with HSS. They are the first to be reported in Thailand.