[ApoE polymorphisms and dopaminergic replacement therapy in Parkinson's disease]. / Polimorfismos de apoE y reemplazo dopaminérgico en enfermedad de Parkinson.

BACKGROUND: The expression of apolipoprotein E (apoE) polymorphisms has been proposed as a risk factor for early development of psychotic symptoms in patients with Parkinson's disease. The association between apoE polymorphisms and motor complications is controversial. The aim was to determine the association between apoE polymorphisms and its allele frequency with the development of complications secondary to dopaminergic replacement therapy. METHODS: We evaluated 231 patients with the diagnosis of Parkinson's disease. The presence of motor complications secondary to treatment was determined by a neurologist, and the genotypification of apoE polymorphisms was performed. Descriptive statistics and chi-squared test were used. RESULTS: Genotype ?3/?3 was expressed in 80.5 % of the sample; there was no association between genotype or allele frequency of apoE polymorphisms and the development of psychosis or dyskinesia. Patients who expressed the ?2 allele showed a tendency to develop motor fluctuations, but without reaching statistical significance (p = 0.08). CONCLUSIONS: ApoE polymorphisms are not associated with the development of complications from dopaminergic replacement therapy.

INTRODUCCIÓN: se ha propuesto que la expresión de los polimorfismos de la apolipoproteína E (apoE) es un factor predisponente para el desarrollo temprano de psicosis en los pacientes con enfermedad de Parkinson. La relación entre el genotipo de la apoE y el desarrollo de complicaciones motoras es controvertida. El objetivo de esta investigación fue determinar la relación entre los polimorfismos de la apoE y su frecuencia alélica y el desarrollo de complicaciones secundarias al reemplazo dopaminérgico. MÉTODOS: se evaluaron 231 pacientes con diagnóstico de enfermedad de Parkinson. La presencia de complicaciones fue determinada por un neurólogo y se realizó la genotipificación de los polimorfismos de la apoE. Se utilizó la chi cuadrada para determinar la relación entre la presencia o ausencia de las complicaciones estudiadas y el genotipo de la apoE. RESULTADOS: se identificó el genotipe ?3/?3 en 80.5 % de la muestra. No existió relación entre el genotipo o la frecuencia alélica de los polimorfismos de la apoE y el desarrollo de psicosis o discinesias. Los pacientes que expresaron el alelo ?2 mostraron una tendencia al desarrollo de fluctuaciones, pero sin significación estadística (p = 0.08). CONCLUSIONES: los polimorfismos de la apoE no se relacionaron con el desarrollo de complicaciones derivadas del reemplazo dopaminérgico. El tratamiento de la enfermedad de Parkinson se basa principalmente en la administración de precursores de la dopamina (como la levodopa) o de agonistas dopaminérgicos.

[Incidence and determinants of levodopa-induced dyskinesia in a retrospective cohort of Mexican patients with Parkinson's disease]. / Incidencia y determinantes de discinesias inducidas por levodopa en una cohorte retrospectiva de pacientes mexicanos con enfermedad de Parkinson.

UNLABELLED: BACKGROUND. Levodopa-induced dyskinesia is one of the main complications and limitations of the treatment of patients with Parkinson's disease. OBJECTIVE: To determine the incidence and risk factors involved in the development of dyskinesias in a retrospective cohort of Mexican patients with Parkinson's disease. MATERIAL AND METHODS: We reviewed a total of 601 cases of Parkinson's disease patients treated at the National Institute of Neurology and Neurosurgery in the period between January 1990 and June 2010; 482 of them had history of exposure to levodopa. RESULTS: The follow-up was equivalent to 4,392 person-years. 154 patients had dyskinesias at some point in the evolution of the disease. The person-time incidence was 35 cases per 1,000 person-years. The onset of motor symptoms before 50 years of age and levodopa doses > or = 600 mg of levodopa were the main risk factors for early development of dyskinesia (HR of 1.01 [95% CI 1.0 to 1.01, p = 0.001] and HR 1.10 [95% CI 1.04 to 1.23, p = 0.04], respectively]. CONCLUSION: The main determinants of dyskinesias were present early age of onset of motor symptoms and the dose of levodopa. Knowledge of these factors will improve the management planning.

[Incidence of motor fluctuations in a retrospective cohort of Mexican patients with Parkinson's disease]. / Fluctuaciones motoras en enfermedad de Parkinson.

BACKGROUND: motor fluctuations induced by dopamine replacement therapy are among the main complications of the treatment of patients with Parkinson's disease. Our objective was to determine the incidence of motor fluctuations in a retrospective cohort of Mexican patients with Parkinson's disease. METHODS: we reviewed the files of 584 cases of Parkinson's disease patients treated at the National Institute of Neurology and Neurosurgery between 1990 and 2010. We registered the demographic and clinical data to analyze the disease course. RESULTS: the follow-up was of 4736 person-years. 33.9 % of patients (n = 198) had motor fluctuations at some point in the evolution of the disease. The rate of person-time incidence was 43 cases per 1000 person-years. The daily dose of levodopa equivalents greater than 600 mg/d and the use of levodopa were the main risk factors for early development of motor fluctuations (HR 1.40 [95 % CI = 1.07 to 1.83, p < 0.001] and HR 1.61 [95 % CI = 1.17 to 2.23, p = 0.004], respectively). CONCLUSIONS: the main determinants of early development of motor fluctuations are the levodopa equivalent daily dose and the quantity and early use of levodopa.

Clinical and molecular features of familial and sporadic cases of von Hippel-Lindau disease from Mexico.

BACKGROUND: von Hippel-Lindau disease (VHL) is an uncommon autosomal dominant condition predisposing to the development of tumours in a variety of body organs and caused by germline mutations in VHL, a tumour suppressor gene located on 3p. Up to 60% of VHL patients show ocular involvement with retinal hemangioblastoma being the most common observed lesion. In this study, we describe the clinical and genetic characteristics of two familial and one apparently non-familial case of VHL ascertained at our institution. METHODS: Clinical evaluation included ophthalmologic examination and imaging exams for tumours identification; molecular analysis consisted of PCR amplification of the complete VHL gene coding sequence (three exons) and automated nucleotide sequencing. RESULTS: A total of eight affected subjects were demonstrated to carry a causative mutation in VHL. Affected subjects from family #1 had a c.245G > C change, predicting a p.R82P substitution, affected individuals from family #2 were shown to have a c.266T > C change, leading to a p.L89P missense substitution, whereas the apparently non-familial case had a c.298-299insA mutation. One subject from family #2 was a non-penetrant carrier. No ocular anomalies were found in two adult affected subjects carrying the p.L89P mutation. CONCLUSION: Considerable interfamilial and intrafamilial clinical variability as well as one instance of non penetrance were recorded in these VHL disease cases. Three different mutations were demonstrated, including the c.298-299insA one base insertion, which has been previously described in two unrelated families from our country. Although additional studies are needed, our data suggest that this insertion could be a 'founder' mutation.