Marcelo Miranda

Association of GST M1 null polymorphism with Parkinson's disease in a Chilean population with a strong Amerindian genetic component

We have studied the association of a null mutation of Glutathione Transferase M1 (GST M1*0/0) with Parkinsons disease (MIM 168600) in a Chilean population with a strong Amerindian genetic component. We determined the genotype in 349 patients with idiopathic Parkinsons disease (174 female and 175 male; 66.84+/-10.7 years of age), and compared that to 611 controls (457 female and 254 male; 62+/-13.4 years of age). A significant association of the null mutation in GST M1 with Parkinsons disease was found (p=0.021), and the association was strongest in the earlier age range. An association of GSTM1*0/0 with Parkinsons disease supports the hypothesis that Glutathione Transferase M1 plays a role in protecting astrocytes against toxic dopamine oxidative metabolism, and most likely by preventing toxic one-electron reduction of aminochrome.

Lrrk2 mutations in South America : A study of Chilean Parkinson's disease

Pathogenic substitutions in the leucine-rich repeat kinase 2 protein (Lrrk2), R1441G and G2019S, are a prevalent cause of autosomal dominant and sporadic Parkinsons disease in the Northern Spanish population. In this study we examined the frequency of these two substitutions in 166 Parkinsons disease patients and 153 controls from Chile, a population with Spanish/European-Amerindian admixture. Lrrk2 R1441G was not observed, however Lrrk2 G2019S was detected in one familial and four sporadic Parkinsons disease patients. These findings suggest Lrrk2 G2019S may play an important role in Parkinsons disease on the South American Continent and further studies are now warranted.

CADASIL presenting with a movement disorder: A clinical study of a Chilean kindred

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular disease that usually begins with migraine, followed by repeated strokes and progressive dementia. We describe an unusual clinical presentation of this condition in members of a Chilean family with an established NOTCH3 mutation. We report early clinical, neuropsychological, transcranial ultrasound, magnetic resonance imaging (MRI), cerebral blood flow, and skin biopsy findings on these patients. Of the patients, 2 presented with facial dystonia, 1 of whom had abnormal single photon emission computed tomography and transcranial ultrasound studies after normal brain MRI scans. Our report emphasizes that CADASIL must be considered in the study of patients with secondary dystonia.

Forme fruste of neuroleptic malignant syndrome associated with the use of sertraline.

Selective serotonin reuptake inhibitors (SSRI) are widely used to treat depression because of their efficacy and fewer side effects. However, some patients treated with them have experienced worsening of existing parkinsonian symptoms, de novo emergence of parkinsonism or the appearance of other movement disorders [1,2]. According to the safety information available from the sertraline database [3], there are few reports in the literature regarding the development of a neuroleptic malignant-like syndrome (NMLS) resulting from SSRI use. Neuroleptic malignant syndrome (NMS) is produced by blockade of dopamine receptors, whereas NMLS is usually due to thewithdrawalof dopaminergic therapy inParkinson’s disease (PD) or the use of drugs that do not typically behave like neuroleptics [1,2]. NMS and NMLS are characterized by four major features: fever, rigidity, autonomic instability, and altered level of consciousness [2]. These clinical features are accompanied by laboratory findings of increased creatine phosphokinase levels (CPK) [2]. Notably, not infrequently, patients exhibit only someof these features [4]. These cases have been called “forme fruste of NMS” or atypical NMS [2]. The diagnosis of NMS should also be considered when more subtle signs are present [2,4]. We report the case of a patient who presented with acute facial/cranial dystonia and mild parkinsonism associated with a rise in CPK after starting sertraline therapy. We believe these symptoms represent a forme fruste of NMS following the initial use of sertraline. A 75-year-old depressed but otherwise healthy woman on no other medications and no past history of psychotropic used, was prescribed sertraline 25 mg daily for 2 days and 50 mg daily thereafter. On the fourth day of treatment, she presented with bruxism, severe dysarthria and dysphagia. The following day, she reported leg stiffness and slowed gait. Sertraline was discontinued, but her symptoms continued and she underwent brainMRI, complete blood cell counts, blood biochemistry, immunological tests and cerebrospinal fluid examination, whichwere all normal. CPK levels reached 400 U/L (normal< 200 U/L) during the first week following discontinuation of sertraline and subsequently increased to 1070 U/L in 10 days. CPK returned to normal over the next 3 weeks. Her neurologic examination showed no evidence of cognitive changes, and no meningeal signs. The main findings were the presence of facial dystonia, bruxism, severe dysarthria, mild blepharospasm and limb

Degeneración córtico-basal: 5 casos clínicos

Se presentan 5 pacientes con un cuadro clinico de degeneracion corticobasal (DCB); son los primeros casos publicados en nuestro pais. Todas eran mujeres en la 6a o 7a decada de vida; en 4 la distonia comenzo por el brazo derecho. El curso fue lentamente progresivo, con parkinsonismo (rigidez, akinesia, alteraciones posturales y disartria), demencia de tipo frontal y apraxias (constructiva en todas, ideomotora bilateral y oral en una, el defecto motor impidio su evaluacion en varios casos). En dos casos se comprobo una afasia no fluente. Cuatro pacientes presentaron alteraciones oculomotoras, con lentitud de los movimientos sacadicos y ausencia de nistagmo optokinetico. En una de ellas existio una agnosia visual aperceptiva y en el ultimo caso se comprobo un defecto del campo visual. En ningun caso fue posible una evaluacion fina de la sensibilidad, la sensibilidad dolorosa estuvo siempre conservada. La tomografia computada cerebral y la resonancia nuclear magnetica mostraron una atrofia asimetrica moderada; en 2 casos con SPECT se demostro una gran hipoperfusion asimetrica. La revision de la literatura permite concluir que la DCB es una entidad bien definida desde el punto de vista patologico, pero el cuadro clinico tradicional puede deberse a DCB propiamente tal, enfermedad de Pick, de Alzheimer, Jacob-Creutzfeldt, paralisis supranuclear progresiva, o infartos cerebrales. Por otra parte, casos comprobados con autopsia han sido diagnosticados en vida como enfermedad de Parkinson o Alzheimer, paralisis supranuclear progresiva, como demencia frontotemporal

Síndrome de Piernas Inquietas: Actualización Clínica

Antecedentes: El Sindrome de Piernas Inquietas (SPI) se caracteriza por una sensacion desagradable en las piernas que lleva a la imperiosa necesidad de moverlas, ocurre en reposo y es de preferencia nocturna. Su frecuencia varia entre 215% de la poblacion general adulta y 2030% en pacientes uremicos en dialisis. No existe mayor informacion sobre este cuadro en nuestro medio. Un reciente trabajo nacional da una frecuencia estimativa de 13% en la poblacion general adulta y 27% en los pacientes uremicos en dialisis. Objetivo: Analizar caracteristicas clinicas del SPI y recientes avances en su estudio y tratamiento. Se analiza la fisiopatologia del sindrome en base a una hipofuncion dopaminergica y las diversas alternativas de sustitucion dopaminergica disponible. En nuestro medio el SPI es tan frecuente como en series internacionales y esta subdiagnosticado. Esta revision enfatiza la necesidad de mayor reconocimiento de esta condicion ya que existe terapia farmacologica eficaz

Terapia neuroprotectora de la Enfermedad de Parkinson

With the current limitations on treating Parkinson’s disease, neuroprotection should be looked at as a possible way of slowing the varying processes involved in the onset of the disease. A review was made of the work of NINDS experts, who evaluated 59 drugs resulting from their Medline and Pub Med search. Twelve drugs, those considered the most promising, were included in the final analysis. We look at such substances as caffeine, coenzyme q10, estrogens, minocycline, nicotine, rasagiline-selegiline, and ropinirole-pramipexole. These agents acted dissimilarly, but favorably, on some of the disease’s processes or on its underlying pathogenesis, although the mechanisms involved and the duration of the beneficial effects were not clear. The challenge is to overcome the difficulties that make the results of the few current studies uncertain, using new methods, such as transgenic models, to maintain hope for effective future treatments.

El anillo de Kayser-Fleischer como signo diagnóstico en la Enfermedad de Wilson

La Enfermedad de Wilson es un cuadro paradigmatico en la Neurologia, ya que ha permitido a los clinicos entender la relacion entre los ganglios de la base y los trastornos del movimiento. Los neurologos consideran esta enfermedad al realizar el diagnostico diferencial de un trastorno del movimiento, aunque el diagnostico final es raramente formulado dado lo inusual del cuadro. En esta nota, describimos la importancia del anillo de Kayser-Fleischer como una herramienta util en el diagnostico de enfermedad de Wilson, incluyendo imagen descriptiva de las caracteristicas de este signo clinico