OBJECTIVE: To determine whether N-acetylaspartate (NAA) is reduced in patients with Salla disease, a neurodegenerative disorder. BACKGROUND: 1H MRS allows the brain metabolism to be studied noninvasively in vivo. N-acetyl (NA) is composed primarily of NAA, which is regarded as a neuronal marker. The NA signal in 1H MRS is reduced in several neurodegenerative disorders. Increased NA signal has thus far only been found in Canavan's disease as a result of NAA accumulation in the brain tissue. In Salla disease, an autosomal recessive free sialic acid storage disorder, N-acetylneuraminic acid (NANA), accumulates in lysosomes of brain tissue. METHODS: The authors studied eight patients with Salla disease (age range, 6 to 44 years) and eight age-matched healthy volunteers using quantitative 1H MRS. The spectra were obtained from two selected 8-cm3 volumes of interest localized in the basal ganglia and in the parietal white matter using conventional 1.5-T MRI equipment. The spectral resonance lines of NA groups, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed quantitatively. All MR images were evaluated to verify the state of myelination. RESULTS: 1H MRS from parietal white matter revealed 34% higher NA and 47% higher Cr concentrations, and a 35% lower Cho concentration in the patients with Salla disease compared with the age-matched control subjects. The patients had a 22% higher water content in their parietal white matter, whereas in the basal ganglia the water concentrations did not differ significantly. In the patients' basal ganglia the Cr concentration was 53% higher. CONCLUSIONS: NAA is considered to be a neuronal marker that, except for Canavan's disease, has been found or assumed to be either stable or reduced. However, in Salla disease the high NA signal may have a contribution from accumulated lysosomal NANA, which offsets the possible loss of NAA. The high Cr is in line with the increased glucose uptake found in our earlier 2-fluoro-2-deoxy-D-glucose-PET study, reflecting increased energy demand. It is worth noting that in a conventional 1H MRS ratio-based analysis these underlying abnormalities would have remained undetected. Our study thus emphasizes the importance of a quantitative assessment of metabolite concentrations in 1H MRS for detecting altered brain metabolism.
OBJECTIVE: To determine whether N-acetylaspartate (NAA) is reduced in patients with Salla disease, a neurodegenerative disorder. BACKGROUND:1H MRS allows the brain metabolism to be studied noninvasively in vivo. N-acetyl (NA) is composed primarily of NAA, which is regarded as a neuronal marker. The NA signal in 1H MRS is reduced in several neurodegenerative disorders. Increased NA signal has thus far only been found in Canavan's disease as a result of NAA accumulation in the brain tissue. In Salla disease, an autosomal recessive free sialic acid storage disorder, N-acetylneuraminic acid (NANA), accumulates in lysosomes of brain tissue. METHODS: The authors studied eight patients with Salla disease (age range, 6 to 44 years) and eight age-matched healthy volunteers using quantitative 1H MRS. The spectra were obtained from two selected 8-cm3 volumes of interest localized in the basal ganglia and in the parietal white matter using conventional 1.5-T MRI equipment. The spectral resonance lines of NA groups, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed quantitatively. All MR images were evaluated to verify the state of myelination. RESULTS:1H MRS from parietal white matter revealed 34% higher NA and 47% higher Cr concentrations, and a 35% lower Cho concentration in the patients with Salla disease compared with the age-matched control subjects. The patients had a 22% higher water content in their parietal white matter, whereas in the basal ganglia the water concentrations did not differ significantly. In the patients' basal ganglia the Cr concentration was 53% higher. CONCLUSIONS:NAA is considered to be a neuronal marker that, except for Canavan's disease, has been found or assumed to be either stable or reduced. However, in Salla disease the high NA signal may have a contribution from accumulated lysosomal NANA, which offsets the possible loss of NAA. The high Cr is in line with the increased glucose uptake found in our earlier 2-fluoro-2-deoxy-D-glucose-PET study, reflecting increased energy demand. It is worth noting that in a conventional 1H MRS ratio-based analysis these underlying abnormalities would have remained undetected. Our study thus emphasizes the importance of a quantitative assessment of metabolite concentrations in 1H MRS for detecting altered brain metabolism.
Authors: John R Moffett; Brian Ross; Peethambaran Arun; Chikkathur N Madhavarao; Aryan M A Namboodiri Journal: Prog Neurobiol Date: 2007-01-05 Impact factor: 11.685
Authors: Maria Zulfiqar; Doris D M Lin; Marinette Van der Graaf; Peter B Barker; Jill A Fahrner; Sandrine Marie; Eva Morava; Lonneke De Boer; Michel A A P Willemsen; Eileen Vining; Alena Horská; Udo Engelke; Ron A Wevers; Gustavo H B Maegawa Journal: J Magn Reson Imaging Date: 2012-10-10 Impact factor: 4.813
Authors: N Aula; P Salomäki; R Timonen; F Verheijen; G Mancini; J E Månsson; P Aula; L Peltonen Journal: Am J Hum Genet Date: 2000-08-17 Impact factor: 11.025
Authors: A Rossi; R Biancheri; F Zara; C Bruno; G Uziel; M S van der Knaap; C Minetti; P Tortori-Donati Journal: AJNR Am J Neuroradiol Date: 2007-11-01 Impact factor: 3.825
Authors: Liisa E Paavola; Anne M Remes; Pirkko H Sonninen; Vesa V Kiviniemi; Tapio T Korhonen; Kari Majamaa Journal: Case Rep Neurol Med Date: 2012-11-22