RESUMEN
BACKGROUND: Influence of folate/homocysteine conversion is considered to be important in the pathogenesis of Parkinson's disease (PD). However, association of the folate metabolic pathway gene polymorphisms with PD susceptibility remains unclear. METHODS: To test this possibility in PD, we conducted a hospital-based case-control study constituting 211 patients and 218 age- and sex-matched controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR A1049G and C1783T) genes and assess the association between these genotype polymorphisms and PD risk using logistic regression analysis. RESULTS: Of these four non-synonymous polymorphisms, the MTRR 1049GG variant was significantly associated with PD susceptibility (OR=3.17, 95%CI=1.08-9.35). Furthermore, we stratified our patients based on the MTHFR 677TT genotype in different strata, a significant association between the joint effect of polymorphisms and PD risk was observed in those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR A2756G (P<0.05). CONCLUSION: Our findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.
Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Ferredoxina-NADP Reductasa/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Enfermedad de Parkinson/genética , Polimorfismo Genético , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/enzimología , Taiwán/etnologíaRESUMEN
BACKGROUND: Gamma-glutamyl carboxylation, a reaction essential for the biosynthesis of vitamin K-dependent coagulation factors, requires the participation of the gamma-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKORC1), and NAD(P)H:quinone oxidoreductase (NQO1). We evaluated the role of these genotype polymorphisms in patients with large-artery atherosclerotic stroke. METHODS: In this hospital-based case-control study, 117 patients who were categorized as having large-artery atherosclerotic stroke and 115 age- and gender-matched controls were recruited. Genotyping determination for the GGCX1 (Gln325Arg), NQO1 (Pro187Ser), and VKORC1 (rs9923231) polymorphisms was performed. The associations of genotype with ischemic stroke (IS) risk were examined. RESULTS: A higher genotypic frequency of NQO1 C609T was found in the controls than in the patients, manifesting a 0.47-fold risk reduction in IS (95% CI=0.25-0.87). A tendency toward a reduced IS risk was statistically significant in those subjects who carried a greater number of the NQO1, GGCX, and VKORC1 polymorphisms (aOR=0.58, P(trend)=0.005). The synergistic effect of multiple genes on risk reduction was more significant in a subset of patients who were not alcoholics and who were non-smokers (P<0.05). CONCLUSIONS: Compartmentation of coagulation factor metabolism may account for the preferential role of NQO1, GGCX, and VKORC1 polymorphisms to lower the risk for large-artery atherosclerotic stroke.
Asunto(s)
Aterosclerosis/genética , Ligasas de Carbono-Carbono/genética , Oxigenasas de Función Mixta/genética , NAD(P)H Deshidrogenasa (Quinona)/genética , Polimorfismo Genético/genética , Accidente Cerebrovascular/genética , Anciano , Anciano de 80 o más Años , Aterosclerosis/enzimología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/enzimología , Arteria Cerebral Media/patología , Factores de Riesgo , Accidente Cerebrovascular/enzimología , Accidente Cerebrovascular/patología , Vitamina K Epóxido ReductasasRESUMEN
Neurological complications due to the uremic state or hemodialysis, contribute to the important cause of mortality in patients with uremia. Despite continuous advances in uremic treatment, many neurological complications of uremia, like uremic encephalopathy, peripheral neuropathy and myopathy fail to fully respond to hemodialysis. Moreover, hemodialysis or kidney transplantation may even induce neurological complications. Hemodialysis can directly or indirectly be associated with Wernicke's encephalopathy, dialytic dementia, dysequilibrium syndrome, cerebrovascular accidents, osmotic myelinolysis and mononeuropathy. Renal transplantation can give rise to rejection encephalopathy and acute femoral neuropathy. The use of immunosuppressive drugs after renal transplantation can cause reversible posterior leukoencephalopathy encephalopathy. The clinical, pathophysiological and therapeutical aspects of central nervous system, peripheral nervous system and myopathy complications in uremia are reviewed.
Asunto(s)
Enfermedades del Sistema Nervioso/etiología , Uremia/complicaciones , Encefalopatías/etiología , Trastornos Cerebrovasculares/etiología , Humanos , Trastornos del Movimiento/etiología , Mielinólisis Pontino Central/etiología , Enfermedades del Sistema Nervioso Periférico/etiología , Encefalopatía de Wernicke/etiologíaRESUMEN
OBJECTIVE: To identify the midlife risk factors for subtypes of dementia newly developed later in life. METHODS: A nested case-control study was conducted on 157 demented cases and 628 comparison cases selected from 40,636 men and women who were enrolled from 1982 to 1992. Four comparison cases were frequency-matched on age, time at enrollment (within 6 months), gender, and residential township. Midlife risk factors included vascular risk factors (body mass index [BMI], total cholesterol, total triglycerides, blood glucose, cerebrovascular accident [CVA] history, diabetes mellitus history, and hypertension history), cigarette smoking, and alcohol consumption. Dementia assessments were ascertained through the computerized data linkage from National Health Insurance Database from 2000 to 2002 and clinically confirmed by neurologists or psychiatrists. Conditional logistic regression analysis was used to estimate the matched odds ratio (OR) and its 95% confidence intervals (CI) for each risk factor. RESULTS: A J-shaped relationship was observed between BMI (kg/m(2)) and dementia. The multivariate-adjusted ORs (95% CI) of developing dementia were 1.84 (1.02-3.33), 1.87 (1.08-3.23) and 2.44 (1.39-4.28), respectively, for BMIs of <20.5, 23.0-25.4, >or=25.5 compared with a BMI of 20.5-22.9 as the referent group (OR = 1.0). Similar findings were observed for Alzheimer disease (AD) and vascular dementia (VaD). The association between obesity (BMI >or=25.5) and both AD and VaD was statistically significant among cigarette smokers but not among nonsmokers. Additionally, history of CVA was a significant risk factor for VaD, but not for AD. CONCLUSION: Being underweight, being overweight, and a cerebrovascular accident in midlife may increase the risk of dementia in late life.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Demencia Vascular/epidemiología , Demencia/epidemiología , Evaluación Geriátrica/estadística & datos numéricos , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Enfermedad de Alzheimer/etiología , Glucemia/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Colesterol/sangre , Estudios de Cohortes , Recolección de Datos/estadística & datos numéricos , Demencia/etiología , Demencia Vascular/etiología , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/epidemiología , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Estadística como Asunto , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Taiwán , Triglicéridos/sangreRESUMEN
BACKGROUND: Hypothetic mechanism of the individual vulnerability to oxidative stress through metabolism of environmental xenobiotics and genotypic polymorphisms has been considered to promote the development of Parkinson's disease (PD). In this case-control study, we determined the role of manganese-containing superoxide dismutase (MnSOD) and NAD(P)H: quinone oxidoreductase 1 (NQO1) genes in PD risk in a population with high prevalence of pesticide exposure. METHODS: From southwestern region of Taiwan, we enrolled 153 patients with idiopathic PD and 155 healthy control subjects matched for age, sex and origin. Detailed questionnaires of face-to-face interviews among these subjects were collected. PCR-based restriction fragment length polymorphism (RFLP) assays were used to determine the genotypes of MnSOD (-9 T>C) and NQO1 (609 C>T) genes. RESULTS: Exposure to pesticides associated with PD was significant among patients with an increased odds ratio (OR) of 1.69 (95%CI, 1.07-2.65), and this association remained significant after adjustment for age, sex, and cigarette smoking (aOR=1.68, 95%CI, 1.03-2.76, P=0.023). Considering genetic factors, there were no significant differences in frequencies of both genotypes of MnSOD and NQO1 polymorphisms between PD patients and the control subjects (P>0.05). However, this difference in genotype distribution was significant among subjects who had been exposed to pesticide, with aOR of 2.49 (95%CI, 1.18-5.26, P=0.0072) for MnSOD C allele and aOR of 2.42 (95%CI, 1.16-4.76, P=0.0089) for NQO1 T allele, respectively. Moreover, among subjects exposed to pesticide, the combined MnSOD/NQO1 variant genotype was significantly associated with a 4.09-fold increased risk of PD (95%CI, 1.34-10.64, P=0.0052). CONCLUSION: Susceptible variants of MnSOD and NQO1 genes may interact with occupational pesticide exposure to increase PD risk in southwestern Taiwanese.
Asunto(s)
NAD(P)H Deshidrogenasa (Quinona)/genética , Enfermedad de Parkinson/etiología , Plaguicidas/toxicidad , Polimorfismo Genético , Superóxido Dismutasa/genética , Anciano , Estudios de Casos y Controles , Exposición a Riesgos Ambientales , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno , RiesgoRESUMEN
Claude's syndrome caused by dorsal midbrain lesion is characterized by ipsilateral third nerve palsy and contralateral ataxia. To date, reports in the literature concerning Claude's syndrome associated with the midbrain paresis of horizontal gaze are rare. A 62-year-old man suddenly developed left third cranial nerve palsy, right lateral gaze palsy, and right ataxia. Intact Bell's phenomenon and preserved right horizontal oculocephalic reflex suggested the lateral gaze palsy in the right eye was supranuclear in nature. Magnetic resonance imaging (MRI) revealed an infarction in the left dorsomedial midbrain. Although the red nucleus has often been suggested as the lesion site responsible for Claude's syndrome, a lesion of the superior cerebellar peduncle just below and medial to the red nucleus could be responsible for this syndrome. This case demonstrates neurological heterogeneity of midbrain infarction.
Asunto(s)
Infartos del Tronco Encefálico/complicaciones , Enfermedades del Nervio Oculomotor/etiología , Ataxia/etiología , Infartos del Tronco Encefálico/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The manifestation of Parkinson's disease (PD) is characterized by bradykinesia, resting tremor, and rigidity. The etiology of PD remains unknown. Recently several studies suggest that some environmental and genetic factors may be related to the cause of PD. Genetic variation in xenobiotic metabolizing enzymes involved in the disposition of pesticides, such as paraoxonase I (PON 1), may increase the risk of PD. We investigated the association between PON1 polymorphism, pesticides exposure and risk of Parkinson's disease in Taiwanese population. METHODS: We enrolled 162 controls and 125 patients with idiopathic PD. Histories of exposures to environmental factors and other information were collected with a questionnaire filled out during a face-to-face interview with the subject. The data included years of farming, drinking water sources, occupational exposures to pesticides, duration and the initial age of the pesticides exposure. Buccal mucosa cells are collected from each subject and PON1 polymorphism at codon 54 (L and M alleles) is studied with PCR-based restriction fragment length polymorphism (RFLP) analysis. RESULTS: There is significant association between the risk of PD and exposure to pesticides (OR=1.72, 95% CI=1.07-2.75). On the otherhand, no significant differences are found in PON1 genotype or allelic distribution between PD and control groups. We further investigated participants who had reported exposure to pesticides and found that the frequency distribution of PON1 genotypes did not differ significantly between patients and controls. CONCLUSION: The present survey reveals the close relationship between exposure to pesticides and Parkinson's disease. There are no significant differences in the distribution of PON1 genotypes between cases and controls.
Asunto(s)
Arildialquilfosfatasa/genética , Exposición Profesional/efectos adversos , Enfermedad de Parkinson/etiología , Plaguicidas/efectos adversos , Polimorfismo Genético , Anciano , Anciano de 80 o más Años , Susceptibilidad a Enfermedades , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Paraneoplastic neurological syndromes are uncommon, however; their diagnosis is of major practical importance. Any portion of the nervous system may be involved in paraneoplastic syndromes. There is increasing evidence that the pathogenesis of many paraneoplastic neurological syndromes appears to be an immune reaction against antigen shared by the cancer and the nervous system. The identification of antibodies in the serum or cerebrospinal fluid in the central nervous system of paraneoplastic syndrome patient confirms the clinical diagnosis of paraneoplastic syndrome, and allows early identification of an underlying tumor at a stage when it is localized and more amenable to treatment. Cancer therapy (surgery, radiotherapy, chemotherapy) seems to be the most efficient treatment for the paraneoplastic neurological symptoms. Immunomodulatory therapy (intravenous immunoglobulin, plasmapheresis, immunosuppression) can halt or even reverse the neurological syndrome. The recent advances in understanding of the autoimmune pathology of these disorders should lead to more effective treatment options.
Asunto(s)
Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Autoanticuerpos/sangre , Encefalomielitis/inmunología , Humanos , Pruebas Inmunológicas , Síndrome Miasténico de Lambert-Eaton/inmunología , Trastornos de la Motilidad Ocular/inmunología , Degeneración Cerebelosa Paraneoplásica/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Síndromes Paraneoplásicos del Sistema Nervioso/terapia , Síndrome de la Persona Rígida/inmunologíaRESUMEN
Hypertensive encephalopathy rarely presented with widespread edema in the cerebral white matters, deep structures and whole brainstem. A 80-year-old woman manifested as high arterial blood pressure, visual disturbance, severe headache, nausea, and vomiting. T2-weighted and fluid-attenuated inversion recovery magnetic resonance imaging showed high signal-intensity lesions in the cerebral white matter, cerebellum, basal ganglia, thalamus, and brainstem. Diffusion-weighted brain MRI did not show hyperintense signals in these lesions. These findings suggested the pathological basis of vasogenic edema. After control of hypertension, clinical symptoms and these edematous lesions on MRI gradually reduced.