RESUMO
Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a complex neuromigrational disorder including ependymal cysts, leptomeningeal and subcortical heterotopia, polymicrogyria, multifocal cerebral calcifications, agenesis of the corpus callosum, and spongiform changes in brainstem and cerebellum. Intractable lactic acidosis, causing death on the first day of life, was associated with severely reduced activities of complex I and complex IV. The neuropathological and biochemical findings are closely similar to those reported previously. The findings confirm a distinct genetic syndrome of disrupted brain development with TORCH-like calcifications, and a complex neuronal migration disorder associated with a multicomplex disorder of the respiratory chain.
Assuntos
Acidose Láctica/congênito , Encéfalo/anormalidades , Deficiência de Citocromo-c Oxidase/patologia , Complexo I de Transporte de Elétrons/deficiência , Acidose Láctica/patologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
With immunohistochemical staining methods on cryostat sections we investigated the brains of three patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type, one of the cerebral beta/A4 amyloid diseases. Immunostaining for beta/A4 protein revealed numerous non-fibrillar beta/A4 depositions (amorphous or diffuse plaques) in the brain parenchyma in addition to extensive vascular amyloid deposition. All amorphous plaques contain complement proteins and alpha 1-antichymotrypsin but activated microglial cells expressing major histocompatibility (MHC) class II antigens HLA-DR and leucocyte adhesion molecules belonging to the lymphocyte-function-associated antigen (LFA)-1 family are virtually absent in cortical gray matter. Our findings are discussed from the view that a cascade of events including acute phase proteins and activated microglial cells are involved in classical amyloid plaque formation.
Assuntos
Proteínas de Fase Aguda/análise , Peptídeos beta-Amiloides/análise , Amiloidose/patologia , Hemorragia Cerebral/patologia , Neuroglia/patologia , Precursores de Proteínas/análise , Receptores de Superfície Celular/análise , Adulto , Precursor de Proteína beta-Amiloide , Amiloidose/metabolismo , Córtex Cerebral/química , Córtex Cerebral/patologia , Hemorragia Cerebral/metabolismo , Proteínas do Sistema Complemento/análise , Antígenos HLA-DR/análise , Humanos , Antígeno-1 Associado à Função Linfocitária/análise , Macrófagos/patologia , Pessoa de Meia-Idade , alfa 1-Antiquimotripsina/análiseRESUMO
This study was designed to investigate the role of serum proteins, microglia, glial fibrillary acidic protein (GFAP) positive cells and dystrophic neurites in the genesis of cerebral amyloid. Using A4 protein antisera, we found an amorphous non-congophilic, form of plaque, which was not seen in Bielschowsky silver staining or Bodian impregnations. GFAP-positive glial cells, cells immunolabelled for some macrophage markers and dystrophic neurites were detected in congophilic plaques with crystalline amyloid, but not in the amorphous, non-congophilic plaques. The presence of alpha l-antichymotrypsin, complement factors and P component, but not of common serum proteins in both the amorphous and congophilic plaques, indicates that these three proteins may have a pathogenetic role in amyloid formation. Amorphous plaques may be the earlier forms of plaque and consequently, the presence of reactive cells and dystrophic neurites may be secondary phenomena.