目的:多发性硬化症(MS)中的认知障碍(CI)是常见的,并由炎症和神经退行性过程之间复杂的相互作用决定。我们的目的是调查脑脊液小白蛋白(PVALB),在诊断时测量,可能对MS患者具有预后作用。
方法:在这项队列研究中,在诊断时(T0)对所有患者进行了PVALB和NF-L水平的CSF分析,并结合物理,认知,和MRI评估后平均4年的随访(T4)从诊断。认知表现用全面的神经心理电池进行评估:两者都是全球性的(认知正常,CN,轻度CI、mCI和重度CI、sCI)和域认知状态(正常/记忆受损,注意力/信息处理速度,和执行功能)被考虑。使用3TMRI扫描仪获取皮质厚度和灰质体积数据。
结果:共纳入72例MS患者。诊断时,在4年的随访后,那些身体残疾恶化的患者的PVALB水平更高(p=0.011)。sCI患者的CSFPVALB水平高于CN(p=0.033)。此外,较高的PVALB水平与较差的整体认知(p=0.024)和记忆功能(p=0.044)显著相关.提出了诊断时PVALB水平的初步临床阈值(2.57ng/mL),这最大化了展示CI的风险(特别是,sCI)在后续行动中,灵敏度为91%(特异性为30%)。与NF-L的这些关联没有发现显着结果。此外,诊断时PVALB水平较高的患者在随访时表现出更高的认知(p=0.024)和整体疲劳(p=0.043).最后,较高的PVALB水平也与额下回T4时更明显的CTh/体积显着相关(p=0.044),中央后回(p=0.025),额极(p=0.042),颞横回(p=0.008),和小脑皮质(p=0.041)和右丘脑的更高萎缩(改变T0-T4)(p=0.038),果皮皮质(p=0.009),舌回(p=0.045),和内侧额回(p=0.028)。
结论:诊断时CSF中的小白蛋白水平与认知之间存在显着关联,临床,和神经放射学恶化后4年的随访支持的观点,除了Nf-L,可能代表一种新的潜在预后生物标志物,反映自疾病早期阶段发生的MS神经退行性过程。
OBJECTIVE: Cognitive impairment (CI) in multiple sclerosis (MS) is frequent and determined by a complex interplay between inflammatory and neurodegenerative processes. We aimed to investigate whether CSF parvalbumin (PVALB), measured at the time of diagnosis, may have a prognostic role in patients with MS.
METHODS: In this cohort study, CSF analysis of PVALB and Nf-L levels was performed on all patients at diagnosis (T0) and combined with physical, cognitive, and MRI assessment after an average of 4 years of follow-up (T4) from diagnosis. Cognitive performance was evaluated with a comprehensive neuropsychologic battery: both global (cognitively normal, CN, mildly CI, mCI, and severely CI, sCI) and domain cognitive status (normal/impaired in memory, attention/information processing speed, and executive functions) were considered. Cortical thickness and gray matter volume data were acquired using 3T MRI scanner.
RESULTS: A total of 72 patients with MS were included. At diagnosis, PVALB levels were higher in those patients who showed a worsening physical disability after 4 years of follow-up (p = 0.011). CSF PVALB levels were higher in sCI patients than in CN (p = 0.033). Moreover, higher PVALB levels significantly correlated with worse global cognitive (p = 0.024) and memory functioning (p = 0.044). A preliminary clinical threshold for PVALB levels at diagnosis was proposed (2.57 ng/mL), which maximizes the risk of showing CI (in particular, sCI) at follow-up, with a sensitivity of 91% (specificity 30%). No significant results were found for these associations with Nf-L. In addition, patients with higher levels of PVALB at diagnosis showed higher cognitive (p = 0.024) and global fatigue (p = 0.043) at follow-up. Finally, higher PVALB levels also correlated significantly with more pronounced CTh/volume at T4 in the inferior frontal gyrus (p = 0.044), postcentral gyrus (p = 0.025), frontal pole (p = 0.042), transverse temporal gyrus (p = 0.008), and cerebellar cortex (p = 0.041) and higher atrophy (change T0-T4) in the right thalamus (p = 0.038), pericalcarine cortex (p = 0.009), lingual gyrus (p = 0.045), and medial frontal gyrus (p = 0.028).
CONCLUSIONS: The significant association found between parvalbumin levels in the CSF at diagnosis and cognitive, clinical, and neuroradiologic worsening after 4 years of follow-up support the idea that parvalbumin, in addition to Nf-L, might represent a new potential prognostic biomarker, reflecting MS neurodegenerative processes occurring since early disease stages.