N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase

Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression. Recently generated data in the nur7 mouse model of Canavan disease suggests loss of aspartoacylase function results in compromised energetic integrity prior to oligodendrocyte death, abnormalities in myelin content, spongiform degeneration, and motor deficit. The present study utilized a next-generation “oligotropic” adeno-associated virus vector (AAV-Olig001) to quantitatively assess the impact of aspartoacylase reconstitution on developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a window of postnatal development preceding gross histopathology and deteriorating motor function. Long-term effects included increased oligodendrocyte numbers, a global increase in myelination, reversal of vacuolation, and rescue of motor function. Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoacylase

Nuclear Magnetic Resonance - NMR

Nuclear magnetic resonance (NMR) is a noninvasive diagnostic technique that gives cross-sectional images of biologic objects without the use of ionizing radiation. A certain property of atomic nuclei, their ability to behave as little magnets, makes NMR imaging possible. The nuclei behave in a specific way when they are ""acted upon"" by magnetic forces

Digital Subtraction Arteriography

Digital subtraction arteriography (DSA) is used to visualize vessels by means of image subtraction using digital radiographic machine. An ubtra-arterial or intravenous injection of contrast material is utilized with the intravenous being less invasive. DSA is possible because of recent advances in the application of computer technology to television, image intensification and digital electronics

CT Anatomy - Geniculocalcarine System

Prior to the advent of computed tomography (CT), there was no diagnostic modality available that could demonstrate in vivo the entire visual pathway and directly reveal the presence of lesions. Thus, the clinico-anatomic pathologic correlation of visual pathway lesions remained primarily the domain of the neuropathDlogist

Diagnostic Nuclear Magnetic Resonance

While the effect of the revolution in diagnosis created by the X-ray computed tomography (CT) is still sweeping the medical world, another modality-- nuclear magnetic resonance (NMR) -- has begun to command attention and is generating mounting excitement throughout the medical community. This is mainly because of the following three points: (1) NMR is an imaging modality that uses no ionizing radiation and therefore may be nonhazardous; (2) it reveals much higher intrinsic contrast between soft tissues than X-ray CT; and, (3) it has the potential to measure biochemical and metabolic parameters

Utility of magnetic resonance imaging in the evaluation of the child with central diabetes insipidus.

Because of the association of central diabetes insipidus (CDI) and occult neoplasia, magnetic resonance imaging (MRI) is an important component of the diagnostic evaluation of a child with CDI. In more than 90% of these children, MRI (T1 weighted-image, without contrast) demonstrates an absence of the normal hyperintensity of the posterior pituitary. In one third of patients, the pituitary stalk is also thickened, suggesting infiltrative disease. Of those with a thickened stalk, the etiology of the CDI remains undetermined in about 60% of patients, whereas histiocytosis and occult germinoma each account for approximately 15-20% of patients. In contrast, germinoma is infrequent (3%) in children with CDI and an MRI showing a normal infundibular stalk, though histiocytosis still accounts for 15-20% of patients. In this paper, a diagnostic approach in children with CDI is proposed