Neurology and Neurometabolic Unit, Department of Neurological and Behavioural Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
J Neurol. 2011 Dec;258(12):2240-7. doi: 10.1007/s00415-011-6106-x. Epub 2011 May 29.
The goal of this work was to assess brain structural and metabolic abnormalities of subjects with SPG11 and their relevance to clinical disability by using quantitative magnetic resonance (MR) metrics. Autosomal recessive hereditary spastic paraplegia (AR-HSP) with thin corpus callosum and cognitive decline is a complex neurological disorder caused by mutations in the SPG11 gene in most cases. Little is known about the process leading to corticospinal and white matter degeneration. We performed conventional MRI/MR spectroscopic imaging ((1)H-MRSI) examinations in 10 HSP patients carrying an SPG11 mutation and in 10 demographically matched healthy controls (HC). We measured in each subject cerebral white matter hyperintensities (WMHs), normalized global and cortical brain volumes, and (1)H-MRSI-derived central brain levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr). Clinical disability was assessed according to patients' autonomy in walking. Conventional MRI showed WMHs in all patients. Global brain volumes were lower in patients than in HC (p < 0.001). Decreased values were diffusely found also in cortical regions (p < 0.01). On (1)H-MRSI, NAA/Cr values were lower in SPG11 patients than in HC (p = 0.002). Cho/Cr values did not differ between patients and HC. Cerebral volume decreases and NAA/Cr in the corona radiata correlated closely with increasing disability scores (p < 0.05). Quantitative MR measures propose that widespread structural and metabolic brain damage occur in SPG11 patients. The correlation of these MR metrics with measures of patients' disease severity suggests that they might represent adequate surrogate markers of disease outcome.
本研究旨在通过定量磁共振（MR）指标评估 SPG11 患者的脑结构和代谢异常及其与临床残疾的相关性。常染色体隐性遗传性痉挛性截瘫（AR-HSP）伴胼胝体变薄和认知功能下降是一种复杂的神经系统疾病，大多数情况下是由 SPG11 基因突变引起的。目前对于导致皮质脊髓和白质变性的过程知之甚少。我们对 10 名携带 SPG11 突变的 HSP 患者和 10 名年龄匹配的健康对照者（HC）进行了常规 MRI/MR 光谱成像（1H-MRSI）检查。我们在每位受试者中测量了脑白质高信号（WMHs）、正常化的全脑和皮质脑体积，以及 1H-MRSI 衍生的中央脑 N-乙酰天冬氨酸（NAA）和胆碱（Cho）与肌酸（Cr）的比值（NAA/Cr 和 Cho/Cr）。根据患者的步行自主能力评估临床残疾。常规 MRI 显示所有患者均存在 WMHs。患者的全脑体积低于 HC（p < 0.001）。皮质区域也广泛存在脑体积减少（p < 0.01）。在 1H-MRSI 上，SPG11 患者的 NAA/Cr 值低于 HC（p = 0.002）。患者和 HC 之间的 Cho/Cr 值没有差异。大脑体积减少和放射冠 NAA/Cr 与残疾评分的增加密切相关（p < 0.05）。定量 MR 测量表明，SPG11 患者存在广泛的脑结构和代谢损伤。这些 MR 指标与患者疾病严重程度的相关性表明，它们可能是疾病结果的合适替代标志物。
