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Proton NMR spectroscopy of cerebral metabolic alterations in infantile peroxisomal disorders
H Bruhn1, B Kruse, G C Korenke
1Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Insights
Proton MR spectroscopy (MRS) reveals neuronal loss and developmental impairment in infants with Zellweger syndrome variants. This noninvasive technique assesses brain changes, including those linked to liver dysfunction.
Area of Science:
- Neurology
- Biochemistry
- Medical Imaging
Background:
- Zellweger syndrome is a peroxisomal disorder affecting multiple organs, including the brain.
- Neuropathological changes in Zellweger syndrome are not fully understood.
- Noninvasive assessment of cerebral metabolism is crucial for understanding disease progression.
Observation:
- Localized proton MR spectroscopy (MRS) was used to study cerebral metabolism in healthy infants and those with Zellweger syndrome variants.
- N-acetylaspartate levels were markedly decreased in various brain regions of affected infants.
- Elevated glutamine, decreased myo-inositol, and mobile lipids/cholesterol were observed in some patients.
Findings:
- Proton MRS demonstrated impaired neuronal development and neuronal loss in infants with Zellweger syndrome.
- Metabolic alterations in the brain correlated with hepatic dysfunction in some cases.
- The study identified specific biomarkers for neuropathological aspects of Zellweger syndrome.
Implications:
- Proton MRS is a valuable, safe tool for assessing brain abnormalities in Zellweger syndrome.
- This technique can aid in diagnosing and monitoring neuropathological consequences.
- Findings contribute to a better understanding of the neurological impact of peroxisomal disorders.
Abstract:
Noninvasive studies of cerebral metabolism were performed with use of localized proton MR spectroscopy (MRS) in both healthy controls (n = 4, age 6 weeks to 2 years) and infants (n = 4, age 3-15 months) who had impaired peroxisomal functions classified as variants of Zellweger syndrome. All patients revealed a marked decrease of N-acetylaspartate in white and gray matter, thalamus, and cerebellum, indicating impairment of normal neuronal development as well as neuronal loss. In two cases an increase of cerebral glutamine and a decrease of the cytosolic polyol myo-inositol in gray matter and striatum reflected the impact of a concomitant effect on hepatic function. Two cases 3 and 6 months of age exhibited a notable elevation of mobile lipids and/or cholesterol in white matter. These patients with severe disease died within 4 weeks after the MRS examination. While an increase of free fatty acids generally associated with a lysosomal storage disease was not consistently observed by proton MRS of brain, this technique provides a convenient and safe tool for the direct assessment of neuropathologic aspects of Zellweger syndrome such as neuronal degeneration, demyelination, and consequences of compromised liver function.