Objective

Our study aimed to quantify structural changes in relation to metabolic abnormalities in the cerebellum, thalamus, and parietal cortex of patients with late-onset GM2-gangliosidosis (LOGG), which encompasses late-onset Tay-Sachs disease (LOTS) and Sandhoff disease (LOSD).

Methods

We enrolled 10 patients with LOGG (7 LOTS, 3 LOSD) who underwent a neurological assessment battery and 7 age-matched controls. Structural MRI and MRS were performed on a 3 T scanner. Structural volumes were obtained from FreeSurfer and normalized by total intracranial volume. Quantified metabolites included N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), and combined glutamate-glutamine (Glx). Metabolic concentrations were corrected for partial volume effects.

Results

Structural analyses revealed significant cerebellar atrophy in the LOGG cohort, which was primarily driven by LOTS patients. NAA was lower and mI higher in LOGG, but this was also significantly driven by the LOTS patients. Clinical ataxia deficits (via the Scale for the Assessment and Rating of Ataxia) were associated with neuronal injury (via NAA), neuroinflammation (via mI), and volumetric atrophy in the cerebellum.

Interpretation

The decrease of NAA in the cerebellum suggests that, in addition to cerebellar atrophy, there is ongoing impaired neuronal function and/or loss, while an increase in mI indicates possible neuroinflammation in LOGG (more so within the LOTS subvariant). Quantifying cerebellar atrophy in relation to neurometabolic differences in LOGG may lead to improvements in assessing disease severity, progression, and pharmacological efficacy. Lastly, additional neuroimaging studies in LOGG are required to contrast LOTS and LOSD more accurately.

中文翻译：

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迟发性 GM2 神经节苷脂沉积症的磁共振成像和光谱学

客观的

我们的研究旨在量化与迟发性 GM2 神经节苷脂沉着症 (LOGG) 患者小脑、丘脑和顶叶皮质代谢异常相关的结构变化，包括迟发性 Tay-Sachs 病 (LOTS) 和 Sandhoff 病。丢失）。

方法

我们招募了 10 名 LOGG 患者（7 名 LOTS，3 名 LOSD），他们接受了神经系统评估组和 7 名年龄匹配的对照。结构 MRI 和 MRS 在 3 T 扫描仪上进行。结构体积从 FreeSurfer 获得，并通过颅内总体积标准化。量化的代谢物包括N-乙酰天冬氨酸 (NAA)、胆碱 (Cho)、肌醇 (mI)、肌酸 (Cr) 和组合的谷氨酸-谷氨酰胺 (Glx)。针对部分体积效应校正代谢浓度。

结果

结构分析显示 LOGG 队列中有显着的小脑萎缩，这主要是由 LOTS 患者驱动的。LOGG 中的 NAA 较低而 mI 较高，但这也受到 LOTS 患者的显着推动。临床共济失调缺陷（通过共济失调评估和评定量表）与小脑神经元损伤（通过 NAA）、神经炎症（通过 mi）和体积萎缩相关。

解释

小脑中 NAA 的减少表明，除了小脑萎缩外，神经元功能和/或损失正在持续受损，而 mI 的增加表明 LOGG 中可能存在神经炎症（在 LOTS 子变体中更是如此）。量化与 LOGG 中神经代谢差异相关的小脑萎缩可能会改善评估疾病严重程度、进展和药理功效。最后，需要在 LOGG 中进行额外的神经影像学研究，以更准确地对比 LOTS 和 LOSD。