Pablo Venegas

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.

Olfactory deficits and cognitive dysfunction in Parkinson's disease

Background: Olfactory deficits and executive dysfunction have been reported in Parkinson’s disease (PD). However, the association between these deficits has not been thoroughly examined. Methods: We studied 44 PD subjects and 17 age-matched controls. In PD subjects, symptoms were assessed with the Unified Parkinson’s Disease Rating Scale and the Hoehn and Yahr scale. Cognition in both groups was assessed by a neuropsychological battery. Olfactory identification and sensitivity was evaluated with the Sniffin’ Sticks® test and olfactory detection threshold, respectively. Results: PD subjects showed significant deficits in olfactory function and working memory, executive function, speed of information processing, visuospatial skills and phonological verbal fluency tests when compared with the control group. Moreover, there was a significant correlation between olfactory sensory deficits and executive dysfunction. In PD patients with up to 12 months of motor symptoms, results were equivalent. Conclusion: Our preliminary results suggest a significant association between olfactory deficits and impairments of executive functions in PD.

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.

Successful response to intravenous immunoglobulin as rescue therapy in a patient with Hashimoto's encephalopathy

The authors describe the case of a 61-year-old woman who was admitted to our intensive care unit (ICU) due to impaired consciousness associated with generalised seizures. Her cerebrospinal fluid, electrolytes, acid-base analysis, and common laboratory and toxicology tests were normal. An MRI ruled out the presence of stroke or haemorrhage but showed severe leukoencephalopathy. Parkinsons disease, Creuzfeld–Jacob disease, vascular alterations, cancer, and rheumatological and metabolic diseases were evaluated and excluded. In view of her history of hypothyroidism despite adequate hormonal replacement and clinical behaviour, Hashimotos encephalopathy was considered. Anti-thyroperoxidase levels were above 3000 IU/ml. The patient received 5 g of methylprednisolone followed by prednisone, but after a favourable initial response, returned to a comatose state. However, after administration of intravenous immunoglobulin (IVIG) 2 g/kg, the patient recovered with resolution of neurological symptoms and was discharged from the ICU 4 days after finishing IVIG treatment.

Deterioro cognitivo leve y enfermedad de Alzheimer inicial en adultos mayores

The early detection of dementia carries implications for clinical management of patients and their families, and it is of utmost concern if an effective pharmacological treatment is to be found. We report the final clinical diagnosis of 36 seniors who complained (or were accused) of forgetfulness. In the Initial Mini-Mental State Examination they scored 25 to 30 out of 30 points and could be diagnosed as having Mild Cognitive Impairment without dementia; preclinical Alzheimers disease was suspected. Clinical observation (from 6 to 70 months, mean 31) showed that the clinical condition of 15 patients clearly worsened; these were diagnosed as likely Alzheimers disease patients. Eleven suffered from emotional disturbances and improved with pharmacological and psychosocial treatment; ten of the patients had a static condition and remained in the Mild Cognitive Impairment category. We discuss the frontiers between normal aging, Mild Cognitive Impairment and Alzheimers disease; we remark the difficulties in the differential diagnosis. Most of the patients with Alzheimers disease were anosognosics with regard to the memory impairment; this could be a useful clinical point. We also underscore the usefulness of a neuropsychological assessment and the need for continued longitudinal evaluation of subjects with questionable dementia. In the next years, progress in neuropsychological, radiological and biological examinations will lead to improve diagnoses

Deterioro cognitivo leve: seguimiento de 10 casos

En una experiencia clinica inicial, de 36 sujetos diagnosticados como deterioro cognitivo leve (DCL), con un seguimiento clinico de 31 meses promedio, 15 evolucionaron a demencia de tipo Alzheimer, 11 mejoraron y se diagnosticaron como trastornos emocionales, y 10 permanecieron como DCL estables (Donoso et al. 2001). Un seguimiento de 2 anos adicionales del ultimo grupo permitio ver que 5 evolucionaron hacia una demencia (EA probable o mixta); uno mejoro, otro resulto ser una paralisis supranuclear progresiva, y solo 3 se mantuvieron estables. De estas experiencias se extraen dos conclusiones principales. Primero, que el diagnostico del DCL no es facil y puede confundirse con trastornos emocionales en adultos mayores. La segunda es que la mayoria de ellos corresponde a una fase inicial de la EA, sin demencia. Nuestros comentarios son dos. El primero es que no se necesitaria tener una demencia para sospechar o diagnosticar una EA probable. El segundo, que el diagnostico precoz del DCL permitiria tomar algunas medidas que tal vez impidan o posterguen la aparicion de la demencia.

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

Trastornos autonómicos en enfermedad de Parkinson

El concepto actual de la Enfermedad de Parkinson (EP) comprende una serie de trastornos no motores. Entre estos, la disautonomia es un problema frecuente y que afecta la calidad de vida de los pacientes. Se revisan las manifestaciones disautonomicas mas frecuentes en la esfera cardiovascular, gastrointestinal, genito-urologica y cutanea. Se discute su posible rol como factor de riesgo, como sintoma promotor y sus implicancias en la etiopatogenia de la EP. Presentamos lineas generales en cuanto al enfrentamiento de los principales sindromes asociados, en base a la mas bien escasa evidencia disponible, y a nuestra experiencia como equipo

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