Age-Related Changes in a Patient With Pelizaeus-Merzbacher Disease Determined by Repeated 1 H-Magnetic Resonance Spectroscopy

Abstract

A boy with Pelizaeus-Merzbacher disease underwent repeated evaluations by 3-Tesla ¹H-magnetic resonance spectroscopy (MRS). The patient showed overlap of the PLP1. Individuals selected as normal controls for ¹H-magnetic resonance spectroscopy consisted of healthy age-matched children. For ¹H-magnetic resonance spectroscopy, the center of a voxel was positioned in the right parietal lobe. ¹H-magnetic resonance spectroscopy was performed when the patient was 2, 6, 14, and 25 months old. γ-Aminobutyric acid concentration in early childhood was increased compared with that in normal controls. However, the γ-aminobutyric acid concentration in the Pelizaeus-Merzbacher disease patient was normalized at 14 and 25 months. No remarkable changes were observed in choline-containing compounds concentration at any time. These results suggest that the changes in metabolite concentrations during growth can reflect the pathological condition of Pelizaeus-Merzbacher disease. Furthermore, the lack of change in the choline-containing compounds concentration can be useful for differentiating Pelizaeus-Merzbacher disease from other white matter disorders.

Keywords

white matter disorders dysmyelinating disorders choline-containing compounds

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References

Seitelberger

. Pelizaeus-Merzbacher disease. In: Vinken

Bruyn

, eds. Handbook of Clinical Neurology, Vol 10: Leukodystrophies and Poliodystrophies. Amsterdam: North Holland; 1970:150–202.

Hudson

. Pelizaeus-Merzbacher disease and the allelic disorder X-linked spastic paraplegia type 2. In: Scriver

Beaudet

Sly

Valle

, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York: McGraw-Hill; 2001:5789–5798.

Barkovich

. Concepts of myelin and myelination in neuroradiology. AJNR Am J Neuroradiol. 2000;21:1099–1109.

Mescher

Tannus

Johnson

Garwood

. Solvent suppression using selective echo dephasing. J Magn Reson Series A. 1996;123:226–229.

Mescher

Merkle

Kirsch

. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 1998;11:266–272.

Takanashi

Inoue

Tomita

. Brain N-acetylaspartate is elevated in Pelizaeus-Merzbacher disease with PLP1 duplication. Neurology. 2002;58:237–241.

Takanashi

Sugita

Osaka

. Proton MR spectroscopy in Pelizaeus-Merzbacher disease. AJNR Am J Neuroradiol. 1997;18:533–535.

Hanefeld

Brockmann

Pouwels

. Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys- and hypomyelination. Neurology. 2005;65:701–706.

Kurata

Itoh

Uchiyama

. Clinical symptoms and characteristic MR spectroscopic findings in Pelizaeus-Merzbacher disease [in Japanese]. No To Hattatsu(Tokyo). 2000;32:503–508.

10.

Pizzini

Fatemi

Barker

. Proton MR spectroscopic imaging in Pelizaeus-Merzbacher disease. AJNR Am J Neuroradiol. 2003;24:1683–1689.

11.

Grodd

Krägeloh-Mann

Klose

. Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy. Radiology. 1991;181:173–181.

12.

Spalice

Popolizio

Parisi

. Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease. Pediatr Radiol. 2000;30:171–175.

13.

Bonavita

Schiffmann

Moore

. Evidence for neuroaxonal injury in patients with proteolipid protein gene mutations. Neurology. 2001;56:785–788.

14.

Eichler

Barker

Cox

. Proton MR spectroscopic imaging predicts lesion progression on MRI in X-linked adrenoleukodystrophy. Neurology. 2002;58:901–907.

15.

van der Voorn

Pouwels

Salomons

. Unraveling pathology in juvenile Alexander disease: serial quantitative MR imaging and spectroscopy of white matter. Neuroradiology. 2009;51:669–675.

16.

Brockmann

Dechent

Wilken

. Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology. 200 3;60:819–825.

17.

Martin

Sevin

Lazarus

. Toward a better understanding of brain lesions during metachromatic leukodystrophy evolution. AJNR Am J Neuroradiol. 2012;33:1731–1739.

18.

Cakmakci

Pekcevik

Yis

. Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature. Eur J Radiol. 2010;74:e161–e171.

19.

Sijens

Oudkerk

, Reijngoud DJ, et al. ¹H MR chemical shift imaging detection of phenylalanine in patients suffering from phenylketonuria (PKU). Eur Radiol. 2004;14:1895–1900.

20.

Mano

Ono

Kaminaga

. Proton MR spectroscopy of Sjögren-Larsson's syndrome. AJNR Am J Neuroradiol. 1999;20:1671–1673.

21.

Pouwels

Brockmann

Kruse

. Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS. Pediatr Res. 1999;46:474–485.

22.

Takanashi

Saito

Aoki

. Increased N-acetylaspartate in model mouse of Pelizaeus-Merzbacher disease. J Magn Reson Imaging. 2012;35:418–425.

23.

Suhy

Rooney

, Goodkin DE, et al. ¹H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS. Mult Scler. 2000;6:148–155.

24.

Brand

Richeter-Landsberg

Leibfritz

. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci. 1993;15:289–298.

25.

Miller

Haxhiu

Georgiadis

. Proteolipid protein gene mutation induces altered ventilatory response to hypoxia in the myelin-deficient rat. J Neurosci. 2003;23:2265–2273.