M. Matilde Inglese MD, Presenter: Nothing to Disclose

Annette Obolevich Nusbaum MD, Abstract Co-Author: Nothing to Disclose

Orit Neudorfer MD, Abstract Co-Author: Nothing to Disclose

Alice Kim, Abstract Co-Author: Nothing to Disclose

Gregory Pastores, Abstract Co-Author: Nothing to Disclose

Edwin Kolodny MD, Abstract Co-Author: Nothing to Disclose

Oded Gonen PhD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Tay-Sachs disease (TSD) is an inborn lysosomal glycosphingolipid (GSL) storage disorder characterized by accumulation of ganglioside GM2 due to the deficiency of β-hexosaminidase A. Gangliosides are found predominantly in gray matter and localized mostly in neurons. However, in the adult form of TSD, a progressive cerebellar atrophy represents the only abnormality detectable on conventional imaging. The aim of this study was to assess the presence and the extent of neuro/axonal injury in the normal-appearing gray and white matter of patients with late-onset TSD by means of proton MR spectroscopic imaging (MRSI).

T2-weigheted MRI (TR/TE: 4500/104 ms) and 2D multivoxel proton MR spectroscopy (1H-MRS) with TR/TE:1500/144 ms, were performed in 9 patients with TSD (6 men, 3 women; mean age 38; range 20-57 yrs) and in the same brain regions of 5 healthy controls (3 men and 2 women; mean age 39; range 29-52 yrs). Since cerebellum is the only brain region remarkably affected on routine MRI, quantitative measures of N-acetylaspartate (NAA) levels were obtained from voxels in the thalamus, putamen, and normal-appearing white matter (NAWM) of the occipital lobe and corpus callosum. Differences in metabolite concentrations between corresponding brain regions in patients and controls were evaluated with a non-parametric test.

T2W images revealed dramatic cerebellar atrophy, the radiological hallmark of late-onset TSD. The NAA levels were significantly lower in thalamus (33%), putamen (41%), occipital lobe (47%) and corpus callosum (38%) of the TSD patients compared to analogous regions in the healthy controls (p<0.05)

In TSD patients, MRSI can detect neuro/axonal damage in both gray and white matter even in absence of morphological abnormalities on conventional imaging. Since glycosphingolipid accumulation can be reduced by a pharmacological agent (N-butyldeoxynojirimycin), proton MRSI might be the most sensitive and specific technique for detecting and quantifying the neuro/axonal injury status and monitoring the response to current and future treatments.

Inglese, M, Nusbaum, A, Neudorfer, O, Kim, A, Pastores, G, Kolodny, E, Gonen, O, et al, , Neuronal and Axonal Injury in Late-Onset Tay-Sachs Disease: A MRI and Proton MR Spectroscopy Study.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4413760.html