Department of Pediatric Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Neuroimage Clin. 2021;32:102793. doi: 10.1016/j.nicl.2021.102793. Epub 2021 Aug 24.
X-linked adrenoleukodsytrophy (ALD) is a genetic neuro-metabolic disorder, causing a slowly progressive myelopathy in adult male and female patients. New disease modifying therapies for myelopathy are under development. This calls for new (imaging) markers able to measure disease severity and progression in clinical trials. In this prospective cohort study, we measured cerebral metabolite levels with Magnetic Resonance Spectroscopy (MRS), and evaluated their potential as biomarkers for disease severity and neurodegeneration in ALD. We used a comprehensive protocol of 3T Magnetic Resonance Spectroscopic Imaging (MRSI) and 7T Single Voxel Spectroscopy (SVS) in a large cohort of adult ALD males without cerebral demyelination. One hundred seven baseline scans - 59 obtained in ALD patients (42 3T MRSI and 17 7T SVS) and 48 obtained in healthy male controls (32 3T MRSI and 16 7T SVS) - and 82 one and two-year follow-up scans (66 3T MRSI and 16 7T SVS) of ALD patients were included. Both protocols showed significantly lower concentration ratios of N-acetylaspartate/creatine (tNAA/tCr) and Glx (glutamine + glutamate)/tCr in the grey and white matter of patients, compared to controls. A novel finding is the higher level of inositol (Ins)/tCr and choline containing compounds (tCho)/tCr in ALD patients without cerebral demyelination. Furthermore, tNAA/tCr correlated strongly with clinical measures of severity of myelopathy. There was no detectable change in metabolite ratios after one-year or two-year follow-up. Our results imply that cerebral metabolite levels - and more specifically the tNAA/tCr ratio - measured with MRS, have potential value as (imaging) biomarkers in ALD.
X 连锁肾上腺脑白质营养不良（ALD）是一种遗传性神经代谢疾病，可导致成年男性和女性患者的进行性脊髓病。新的脊髓病修饰疗法正在开发中。这就需要新的（成像）标志物来衡量临床试验中的疾病严重程度和进展。在这项前瞻性队列研究中，我们使用磁共振波谱（MRS）测量了大脑代谢物水平，并评估了它们作为 ALD 疾病严重程度和神经退行性变的生物标志物的潜力。我们在没有脑脱髓鞘的成年 ALD 男性中使用了 3T 磁共振波谱成像（MRSI）和 7T 单体波谱（SVS）的综合方案。共纳入了 107 例基线扫描-59 例 ALD 患者（42 例 3T MRSI 和 17 例 7T SVS）和 48 例健康男性对照（32 例 3T MRSI 和 16 例 7T SVS），以及 82 例 ALD 患者的一年和两年随访扫描（66 例 3T MRSI 和 16 例 7T SVS）。两种方案均显示患者的灰质和白质中 N-乙酰天冬氨酸/肌酸（tNAA/tCr）和 Glx（谷氨酰胺+谷氨酸）/tCr 的浓度比明显低于对照组。一项新发现是在没有脑脱髓鞘的 ALD 患者中，肌醇（Ins）/tCr 和含有胆碱的化合物（tCho）/tCr 的水平较高。此外，tNAA/tCr 与脊髓病严重程度的临床测量密切相关。在一年或两年的随访后，代谢物比值没有可检测到的变化。我们的结果表明，使用 MRS 测量的大脑代谢物水平-特别是 tNAA/tCr 比值-在 ALD 中具有作为（成像）生物标志物的潜在价值。
