Clinical utility of brain MRS imaging of patients with adult-onset non-cirrhotic hyperammonemia

Andrew B Stergachis, Joel B Krier, Sai K Merugumala, Gerard T Berry, Alexander P Lin, Andrew B Stergachis, Joel B Krier, Sai K Merugumala, Gerard T Berry, Alexander P Lin

Abstract

Adult-onset non-cirrhotic hyperammonemia (NCH) is a rare, but often fatal condition that can result in both reversible and irreversible neurological defects. Here we present five cases of adult-onset non-cirrhotic hyperammonemia wherein brain magnetic resonance spectroscopy (MRS) scans for cerebral glutamine (Gln) and myo-inositol (mI) levels helped guide clinical management. Specifically, we demonstrate that when combined with traditional brain magnetic resonance imaging (MRI) scans, cerebral Gln and mI MRS can help disentangle the reversible from irreversible neurological defects associated with hyperammonemic crisis. Specifically, we demonstrate that whereas an elevated brain MRS Gln level is associated with reversible neurological defects, markedly low mI levels are associated with a risk for irreversible neurological defects such as central pontine myelinolysis. Overall, our findings indicate the utility of brain MRS in guiding clinical care and prognosis in patients with adult-onset non-cirrhotic hyperammonemia.

Keywords: BG, Basal ganglia; Cerebral glutamine; Cerebral myo-inositol; Gln, Glutamine; Magnetic resonance spectroscopy; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; NCH, Non-cirrhotic hyperammonemia; Non-cirrhotic hyperammonemia; PCG, Posterior cingulate gyrus; PWM, Parietal white matter; Urea cycle disorder; mI, Myo-inositol.

Conflict of interest statement

All authors declare that they have no conflict of interest.

© 2021 Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Representative spectra from patient 1 from the three regions of interest measured in each patient. Left: Voxel location shown on T1 MPRAGE images. Right: MR spectra with metabolite fit for myo-inositol (mI), N-acetylaspartate (NAA), and glutamine (Gln).
Fig. 2
Fig. 2
Time course of plasma ammonia and glutamine levels as well as brain glutamine levels in (a) patient 2 and (b) patient 4. Plasma ammonia levels are in red, plasma glutamine levels in purple and brain glutamine levels from the PCG blue. Reference ranges for all three metabolites are indicated by dashed lines and shaded boxes. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 3
Fig. 3
Comparison of brain glutamine and myo-inositol levels between brain MRS scans in (a) patient 2, (b) patient 4, and (c) patient 1. Brain glutamine levels from the PCG are in blue, and brain myo-inositol levels from the PCG are in orange. Reference ranges for both metabolites are indicated by dashed lines and shaded boxes. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
Association between cerebral myo-inositol levels and irreversible neurological outcomes. (a) Scatterplot showing the relationship between brain MRS myo-inositol and glutamine levels. P-value and Pearson's correlation also displayed. (b) plot showing the initial brain MRS myo-inositol level within the PCG region, as well as any long-term neurological sequalae or MRI findings of demyelination.

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Source: PubMed

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