“单纯型”肾上腺脑白质营养不良患者脑轴索性病变的光谱学证据

Spectroscopic evidence of cerebral axonopathy in patients with "pure" adrenomyeloneuropathy.

作者信息

Dubey P, Fatemi A, Barker P B, Degaonkar M, Troeger M, Zackowski K, Bastian A, Smith S A, Pomper M G, Moser H W, Raymond G V

机构信息

Departments of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, USA.

出版信息

Neurology. 2005 Jan 25;64(2):304-10. doi: 10.1212/01.WNL.0000149514.13580.84.

DOI:10.1212/01.WNL.0000149514.13580.84

PMID:15668429

Abstract

BACKGROUND

Adrenomyeloneuropathy (AMN) is the adult variant of X-linked adrenoleukodystrophy. The disease pathology is usually limited to spinal cord and peripheral nerves, and when this is the case, it is referred to as "pure" AMN. Histopathology shows cerebral involvement even in pure AMN; however, not much is known about the nature, extent, and clinical relevance of these findings.

OBJECTIVE

To investigate brain involvement in AMN patients with normal MRI, employing multislice MR spectroscopic imaging.

METHODS

Twelve men with pure AMN were compared with 19 age-matched healthy volunteers. Metabolite ratios (N-acetylaspartate [NAA]/choline [Cho], NAA/creatine [Cr], and Cho/Cr) were measured from seven brain regions. Global metabolite ratios were generated as an average of these seven regional ratios. The Expanded Disability Status Scale (EDSS) was used for neurologic evaluation.

RESULTS

The patients with AMN showed reduced global NAA/Cho (AMN 1.40 +/- 0.16 vs controls 1.75 +/- 0.34; p = 0.003)) and global NAA/Cr (AMN 2.32 +/- 0.13 vs controls 2.62 +/- 0.43; p = 0.03). Regionally, NAA/Cho was lowered in the internal capsule (AMN 1.30 +/- 0.20 vs controls 1.69 +/- 0.37; p = 0.002) and in parieto-occipital white matter (AMN 1.45 +/- 0.19 vs controls 1.78 +/- 0.55; p = 0.04). NAA/Cr was lowered in parieto-occipital white matter (AMN 2.34 +/- 0.31 vs controls 2.83 +/- 0.71; p = 0.04). EDSS demonstrated an inverse association with global NAA/Cr (r = -0.65, p = 0.02) and NAA/Cr in centrum semiovale (r = -0.73, p = 0.006) and in parieto-occipital white matter (r = -0.64, p = 0.02). Cho/Cr was not significantly elevated.

CONCLUSIONS

(1)H-MR spectroscopic imaging is able to detect biochemical abnormalities suggestive of axonal damage even in the brains of patients with pure adrenomyeloneuropathy. The axonopathy is most prominent in internal capsule and parieto-occipital white matter and may contribute to clinical disability.

摘要

背景

肾上腺脑白质营养不良成人型（AMN）是X连锁肾上腺脑白质营养不良的成人变异型。该病的病理通常局限于脊髓和周围神经，在这种情况下，被称为“纯”AMN。组织病理学显示，即使是纯AMN也存在脑受累；然而，对于这些发现的性质、程度和临床相关性知之甚少。

目的

采用多层磁共振波谱成像技术研究MRI正常的AMN患者的脑受累情况。

方法

将12例纯AMN男性患者与19名年龄匹配的健康志愿者进行比较。测量7个脑区的代谢物比率（N-乙酰天门冬氨酸[NAA]/胆碱[Cho]、NAA/肌酸[Cr]和Cho/Cr）。将这7个区域比率的平均值作为整体代谢物比率。采用扩展残疾状态量表（EDSS）进行神经学评估。

结果

AMN患者的整体NAA/Cho降低（AMN为1.40±0.16，对照组为1.75±0.34；p = 0.003），整体NAA/Cr降低（AMN为2.32±0.13，对照组为2.62±0.43；p = 0.03）。局部来看，内囊的NAA/Cho降低（AMN为1.30±0.20，对照组为1.69±0.37；p = 0.002），顶枕白质的NAA/Cho也降低（AMN为1.45±0.19，对照组为1.78±0.55；p = 0.04）。顶枕白质的NAA/Cr降低（AMN为2.34±0.31，对照组为2.83±0.71；p = 0.04）。EDSS显示与整体NAA/Cr呈负相关（r = -0.65，p = 0.02），与半卵圆中心的NAA/Cr呈负相关（r = -0.73，p = 0.006），与顶枕白质的NAA/Cr呈负相关（r = -0.64，p = 0.02）。Cho/Cr没有显著升高。