Considerações a respeito da doença de Parkinson de início precoce revisão crítica da literatura A comprehensive critical review on early onset Parkinson's disease

Desde sua descrição, em 1817, a doença de Parkinson sempre foi entendida como enfermidade que afeta predominantemente indivíduos acima dos 55 anos. Entretanto, desde o final do século passado descreveram-se casos com início em idades precoces, abaixo dos 40 anos. Inúmeras séries de pacientes têm sido apresentadas, com as mais numerosas contando em torno de 60 casos. Tem havido muita controvérsia a respeito de alguns aspectos. Um deles diz respeito à própria denominação, sendo chamado por uns como parkinsonismo de início precoce, parkinsonismo jovem por outros e, ainda, doença de Parkinson de início precoce por outros tantos. Isto denota outra controvérsia sobre a verdadeira situação nosológica: trata-se da mesma doença de Parkinson, com as inclusões dos corpos de Lewy, que ocorre nos indivíduos mais idosos ou, diferentemente, trata-se de outras entidades, com anatomopatologia diversa? Esta a razão principal dos inúmeros estudos clínicos realizados nos pacientes deste grupo de início precoce, pois o número de estudos anatomopatológicos em tais pacientes é muito reduzido. Há evidências de que a maioria dos pacientes seja de doença de Parkinson clássica com início em idades mais jovens, apesar de uma série de descrições patológicas diferentes do habitual para esta enfermidade. Há maior encontro de casos familiares entre os pacientes jovens. Uma das características clínicas mais marcantes é o precoce e invariável aparecimento de complicações da levodopaterapia, como discinesias e flutuações. Por outro lado, parece haver uma evolução clínica mais lenta e favorável. São apresentadas, revistas e comentadas grande parte das séries que apareceram na literatura.<br>Since its original description Parkinson's disease has been considered as a clinical condition which affects older people. Nonetheless, since late in the last century, cases starting in very young age have been described. A great controversy has arisen concerning the real pathology in these cases and, consequently, how should they be named. Early or young onset parkinsonism, early or young onset Parkinson's disease, juvenile parkinsonism, all these terms have been used indistinguishable. There have been few pathological descriptions in early onset parkinsonism. Some show striking differences from the cases of older patients but others are very similar to what has been considered classical Parkison's disease. Younger starting age usually corresponds to greater possibility of other family members being affected. Dyskinesias and fluctuations due to chronic levodopa treatment are an early and almost invariable complication in the course of young patients. Comments on several aspects based on an extensive literature review are presented

Machado-Joseph disease op azorean ancestry in Brazil: the Catarina kindred neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the «Catarina» kindred

At the moment 9 seemingly independent families with the clinical diagnosis of MJD are known in Brazil. The largest family tree of Azorean ancestry contatins 622 individuals in 9 generations. 236 were examined, 39 found to be affected by two examiners. Pheno-types I, II and III were expressed by 12, 23 and 4 patients with age of onset by phenotypea being 10-48, 14-54 and 30-55 respectively. Although clinically more severe, juvenile onset type I disease did not show as severe a ponto-mesencephialic atrophy on MRI as the father with type II disease of similar symptomatic duration. None of the 8 patients examined with MRI showed olivary atrophy or pallidal abnormalities. 12 affected and 23 at risk were evaluated with neuropsychological tests. Attention was normal in both groups. Verbal memory scores were below normal in the affected and there was greater decay with time than in the risk group. Both scored below normal in identifying silluettes and constructional praxis. Visual memory scores were well below normal for both, with many rotations but no omissions or confabulations. A peculiar pattern of multiplying internal details called «the fly-eye effect» was observed in 6 affected and 8 at risk. Defective color distinction when multiple colors presented close to each other, in face of proper naming of individual colors («color simultantagnosia»), was looked for in 29 people. 4/10 affected and 4/19 at risk showed this phenomenon. Cognitive dysfunctions in this MJD family are prominent in the sphere of vision. Whether they constitute an early manifestation in those at risk and thus serve as a clinical identifier of the illnes is yet to be established. Depression was looked for in the history of the family with DSM III-R criteria and an atempt at quantification with the Montgomery-Asberg Rating Scale. There was no significant quantitative difference between affected and at risk. Once undeniably symptomatic however, the patients had no, or less depression than themselves before or tat the early stages of the illness. Covert depression was appropriately excluded. Fully established MJD in this family seemed to exert a protective effect from depression

Comparison between PET template-based method and MRI-based method for cortical quantification of florbetapir (AV-45) uptake in vivo

International audienc

Inhibition of NADPH Oxidase Activation in Oligodendrocytes Reduces Cytotoxicity Following Trauma

Spinal cord injury is a debilitating neurological disorder that initiates a cascade of cellular events that result in a period of secondary damage that can last for months after the initial trauma. The ensuing outcome of these prolonged cellular perturbations is the induction of neuronal and glial cell death through excitotoxic mechanisms and subsequent free radical production. We have previously shown that astrocytes can directly induce oligodendrocyte death following trauma, but the mechanisms regulating this process within the oligodendrocyte remain unclear. Here we provide evidence demonstrating that astrocytes directly regulate oligodendrocyte death after trauma by inducing activation of NADPH oxidase within oligodendrocytes. Spinal cord injury resulted in a significant increase in oxidative damage which correlated with elevated expression of the gp91 phox subunit of the NADPH oxidase enzyme. Immunohistochemical analysis confirmed the presence of gp91 phox in oligodendrocytes in vitro and at 1 week following spinal cord injury. Exposure of oligodendrocytes to media from injured astrocytes resulted in an increase in oligodendrocyte NADPH oxidase activity. Inhibition of NADPH oxidase activation was sufficient to attenuate oligodendrocyte death in vitro and at 1 week following spinal cord injury, suggesting that excitotoxicity of oligodendrocytes after trauma is dependent on the intrinsic activation of the NADPH oxidase enzyme. Acute administration of the NADPH oxidase inhibitor apocynin and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate channel blocker 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione significantly improved locomotor behavior and preserved descending axon fibers following spinal cord injury. These studies lead to a better understanding of oligodendrocyte death after trauma and identify potential therapeutic targets in disorders involving demyelination and oligodendrocyte death