RESUMO
BACKGROUND AND PURPOSE: Some 3%-10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years ('early' onset MS, EOMS). Optical coherence tomography is a non-invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age- or disease-duration-matched later onset MS (LOMS) and healthy controls (HCs). METHODS: In this observational cross-sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral-domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients. RESULTS: In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease-duration-matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients. CONCLUSIONS: These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS.
Assuntos
Esclerose Múltipla/patologia , Retina/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Idade de Início , Estudos Transversais , Feminino , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Neurônios Retinianos/patologiaRESUMO
The differential diagnosis of focal neuropathy continues to be one of the main tasks in peripheral neurology and clinical neurophysiology. In this respect a detailed medical history a topologically oriented clinical examination based on profound anatomical knowledge and a targeted neurophysiological examination are the cornerstones of successful diagnosis. Refined imaging techniques, such as sonography and magnetic resonance imaging provide - additional and valuable morphological information especially in atypical or unresolved cases. The aim of this overview is therefore to summarize the spectrum of focal neuropathy and diagnostic approaches, particularly in terms of a well-founded differential diagnosis.
Assuntos
Imageamento por Ressonância Magnética/métodos , Doenças do Sistema Nervoso Periférico/diagnóstico , Ultrassonografia/métodos , Diagnóstico Diferencial , Humanos , Exame NeurológicoRESUMO
This is the case of a 41 year old man, suffering general weakness and elevated liver enzymes, sensitive to a treatment with riboflavin and coenzyme Q(10). Tandem mass spectroscopy and molecular analysis reveal a multiple acyl-CoA-dehydrogenase deficiency (MADD) with two novel heterozygote missense mutations of the EFTDH gene.
Assuntos
Transporte de Elétrons/genética , Flavoproteínas Transferidoras de Elétrons/deficiência , Flavoproteínas Transferidoras de Elétrons/genética , Proteínas Ferro-Enxofre/deficiência , Proteínas Ferro-Enxofre/genética , Doenças Mitocondriais/enzimologia , Doenças Mitocondriais/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/enzimologia , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação de Sentido Incorreto/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/deficiência , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Adulto , Triagem de Portadores Genéticos , Humanos , Transtornos do Metabolismo dos Lipídeos/diagnóstico , Transtornos do Metabolismo dos Lipídeos/enzimologia , Transtornos do Metabolismo dos Lipídeos/genética , Masculino , Doenças Mitocondriais/diagnóstico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnósticoRESUMO
After acute injury of the central nervous system extracellular adenosine 5'-triphosphate (ATP) can reach high concentrations as a result of cell damage and subsequent increase in membrane permeability. Released ATP may act as a toxic agent, which causes cellular degeneration and death, mediated through P2X and P2Y receptors. Mechanisms underlying the various effects of purinoceptor modulators in models of cerebral damage are still uncertain. In the present study the effect of P2 receptor inhibition after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats was investigated. Rats received either the non-selective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) or artificial cerebrospinal fluid (ACSF) as control by the intracerebroventricular route. First, these treatments were administered 10 min before MCAO and subsequently twice daily for 1 or 7 days after MCAO. The functional recovery of motor and cognitive deficits was tested at an elevated T-labyrinth. The PPADS-treated group showed a significant reduction of paresis-induced sideslips compared with ACSF-treated animals. Infarct volume was reduced in the PPADS group in comparison with the ACSF group. A significant decrease in intermediately and profoundly injured cells in favour of intact cells in the PPADS group was revealed by quantification of celestine blue/acid fuchsin-stained cells in the peri-infarct area. The data provide further evidence for the involvement of P2 receptors in the pathophysiology of cerebral ischaemia in vivo. The inhibition of P2 receptors at least partially reduces functional and morphological deficits after an acute cerebral ischaemic event.
