Gorgich Enam Alhagh, Heidari Zahra, Mahmoudzadeh-Sagheb Hamidreza, Rustamzadeh Auob, Shabani Arash, Amirzadeh Ali, Haghi Ashtiani Bahram
Department of Anatomy, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr 99166-43535, Iran.
Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan 98167-43463, Iran.
ACS Chem Neurosci. 2025 Apr 16;16(8):1469-1480. doi: 10.1021/acschemneuro.4c00593. Epub 2025 Mar 29.
Amyotrophic lateral sclerosis (ALS) is a lethal neurological syndrome accompanied by selective degeneration of somatic motor neurons and neurochemistry alterations. Nevertheless, eye movement's nuclei are relatively spared from ALS damage. This survey was to probe metabolite changes in the primary motor cortex (PMC) and interstitial nucleus of Cajal (INC) of ALS patients using proton magnetic resonance spectroscopy (H-MRS). In this case-control study, 20 patients with ALS and 20 healthy controls underwent 1.5 T MRI and multivoxel H-MRS. H-MRS spectra to determine metabolite profiles including tNAA, mIns, tCr, tCho, and also tNAA/tCr, tNAA/tCho, and mIns/tNAA metabolite ratios from the PMC and INC were quantified via a point resolved spectroscopy pulse (PRESS) sequence in two groups. Further, the associations between H-MRS markers with forced vital capacity (FVC), ALS functional rating scale (ALSFRS-R), and disease progression rate (ΔFS) were investigated. In the PMC, tNAA and tNAA/tCr were significantly lower in ALS patients than the healthy controls, but mIns and mIns/tNAA were significantly greater in these patients ( < 0.05). In the INC, tCho and mIns concentrations, and mIns/tNAA ratio were significantly increased ( < 0.05) in ALS patients, while tNAA and tNAA/tCr ratio did not show significant discriminations between the two groups ( > 0.05). The PMC tNAA/Cr ratio is associated with ALSFRS-R ( = 0.001, = 0.71), FVC ( = 0.03, = 0.58), and ΔFS ( = 0.01, = -0.33). The mIns/tNAA ratio in PMC is also associated with ΔFS ( = 0.02, = 0.41). In the INC, tCho concentrations ( = 0.04, = -0.54) and mIns/tNAA ratio ( = 0.02, = -0.38) were negatively associated with ALSFRS-R and positively correlated with ΔFS ( = 0.01, = 0.33) and ( = 0.001, = 0.61), respectively. The study suggests that neurochemistry changes in ALS patients' brains are linked to selective neuronal vulnerability and the underlying pathophysiology of the disease.
肌萎缩侧索硬化症（ALS）是一种致命的神经综合征，伴有躯体运动神经元的选择性退化和神经化学改变。然而，眼球运动核相对免受ALS损伤。本研究旨在使用质子磁共振波谱（H-MRS）探究ALS患者初级运动皮层（PMC）和 Cajal间质核（INC）中的代谢物变化。在这项病例对照研究中，20例ALS患者和20名健康对照者接受了1.5T MRI和多体素质子磁共振波谱检查。通过点分辨波谱脉冲（PRESS）序列对两组来自PMC和INC的H-MRS波谱进行分析，以确定代谢物谱，包括总N-乙酰天门冬氨酸（tNAA）、肌醇（mIns）、总肌酸（tCr）、总胆碱（tCho），以及tNAA/tCr、tNAA/tCho和mIns/tNAA代谢物比率。此外，还研究了H-MRS标记物与用力肺活量（FVC）、ALS功能评定量表（ALSFRS-R）和疾病进展率（ΔFS）之间的关联。在PMC中，ALS患者的tNAA和tNAA/tCr显著低于健康对照者，但这些患者的mIns和mIns/tNAA显著更高（P<0.05）。在INC中，ALS患者的tCho和mIns浓度以及mIns/tNAA比率显著升高（P<0.05），而两组之间的tNAA和tNAA/tCr比率没有显著差异（P>0.05）。PMC中的tNAA/Cr比率与ALSFRS-R（P = 0.001，r = 0.71）、FVC（P = 0.03，r = 0.58）和ΔFS（P = 0.01，r = -0.33）相关。PMC中的mIns/tNAA比率也与ΔFS相关（P = 0.02，r = 0.41）。在INC中，tCho浓度（P = 0.04，r = -0.54）和mIns/tNAA比率（P = 0.02，r = -0.38）分别与ALSFRS-R呈负相关，与ΔFS呈正相关（P = 0.01，r = 0.33）和（P = 0.001，r = 0.61）。该研究表明，ALS患者大脑中的神经化学变化与选择性神经元易损性和疾病的潜在病理生理学有关。
