Montanaro Domenico, Vavla Marinela, Frijia Francesca, Coi Alessio, Baratto Alessandra, Pasquariello Rosa, Stefan Cristina, Martinuzzi Andrea
U.O. Dipartimentale e Servizio Autonomo di Risonanza Magnetica, Dipartimento di Neuroscienze dell'Età Evolutiva, IRCCS Fondazione Stella Maris, Pisa, Italy.
Child and Adolescent Neuropsychiatric Unit, Department of Women's and Children's Health, University Hospital of Padua, Padova, Italy.
Front Neurosci. 2024 Aug 13;18:1416093. doi: 10.3389/fnins.2024.1416093. eCollection 2024.
Hereditary Spastic Paraplegias (HSP) are genetic neurodegenerative disorders affecting the corticospinal tract. No established neuroimaging biomarker is associated with this condition.
A total of 46 patients affected by HSP, genetically and clinically evaluated and tested with SPRS scores, and 46 healthy controls (HC) matched by age and gender underwent a single-voxel Magnetic Resonance Spectroscopy sampling (MRS) of bilateral pre-central and pre-frontal regions. MRS data were analyzed cross-sectionally (at T and T) and longitudinally (T vs. T).
Statistically significant data showed that T mI/Cr in the pre-central areas of HSP patients was higher than in HC. In the left (L) pre-central area, NAA/Cr was significantly lower in HSP than in HC. In the right (R) pre-frontal area, NAA/Cr was significantly lower in HSP patients than in HC. HSP SPG4 subjects had significantly lower Cho/Cr concentrations in the L pre-central area compared to HC. Among the HSP subjects, non-SPG4 patients had significantly higher mI/Cr in the L pre-central area compared to SPG4 patients. In the R pre-frontal area, NAA/Cr was reduced, and ml/Cr was higher in non-SPG4 patients compared to SPG4 patients. Comparing "pure" and "complex" forms, NAA/Cr was higher in pHSP than in cHSP in the R pre-central and R pre-frontal areas. The longitudinal analysis, which involved fewer patients ( = 30), showed an increase in mI/Cr concentration in the L pre-frontal area among HSP subjects with respect to baseline. The patients had significantly higher SPRS scores at follow-up, with a significant positive correlation between SPRS scores and mI/Cr in the L pre-central area, while in bilateral pre-frontal areas, lower SPRS scores corresponded to higher NAA/Cr concentrations. To explore the discriminating power of MRS in correctly identifying HSP and controls, an inference tree methodology classified HSP subjects and controls with an overall accuracy of 73.9%, a sensitivity of 87.0%, and a specificity of 60.9%.
This pilot study indicates that brain MRS is a valuable approach that could potentially serve as an objective biomarker in HSP.
遗传性痉挛性截瘫（HSP）是一种影响皮质脊髓束的遗传性神经退行性疾病。目前尚无已确立的与该疾病相关的神经影像学生物标志物。
共有46例经基因和临床评估并采用痉挛性截瘫评定量表（SPRS）评分的HSP患者，以及46例年龄和性别匹配的健康对照（HC），接受了双侧中央前回和前额叶区域的单体素磁共振波谱采样（MRS）。对MRS数据进行横断面分析（在T1和T2时）和纵向分析（T1与T2对比）。
具有统计学意义的数据表明，HSP患者中央前回区域的T2时肌醇/肌酸（mI/Cr）高于健康对照。在左侧中央前回区域，HSP患者的N-乙酰天门冬氨酸/肌酸（NAA/Cr）显著低于健康对照。在右侧前额叶区域，HSP患者的NAA/Cr显著低于健康对照。与健康对照相比，HSP SPG4型患者左侧中央前回区域的胆碱/肌酸（Cho/Cr）浓度显著降低。在HSP患者中，非SPG4型患者左侧中央前回区域的mI/Cr显著高于SPG4型患者。在右侧前额叶区域，非SPG4型患者的NAA/Cr降低，mI/Cr高于SPG4型患者。比较“单纯型”和“复杂型”，右侧中央前回和右侧前额叶区域中，纯合型HSP（pHSP）的NAA/Cr高于复杂型HSP（cHSP）。涉及患者较少（n = 30）的纵向分析显示，HSP患者左侧前额叶区域的mI/Cr浓度相对于基线有所增加。随访时患者的SPRS评分显著更高，左侧中央前回区域的SPRS评分与mI/Cr之间存在显著正相关，而在双侧前额叶区域，较低的SPRS评分对应较高的NAA/Cr浓度。为了探索MRS正确识别HSP患者和对照的鉴别能力，一种推理树方法对HSP患者和对照进行分类，总体准确率为73.9%，灵敏度为87.0%，特异性为60.9%。
这项初步研究表明，脑部MRS是一种有价值的方法，有可能成为HSP的客观生物标志物。
