Abstract：
BACKGROUND: Cognitive impairment occurs from the earliest stages of multiple sclerosis (MS) and progresses over time. The introduction of disease modifying therapies (DMTs) has changed the prognosis for MS patients, offering a potential opportunity for improvement in the cognitive arena as well.
METHODS: 41 patients with relapsing-remitting multiple sclerosis (MS) were recruited to the study. Thirty patients were available for final follow-up and were included in the analysis. Baseline (BL) brain MRI including volumetry and neuropsychological tests were performed. Blood samples were collected at BL and follow-up (FU) and were tested for: vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM1), soluble platelet-endothelial CAM-1 (sPECAM1), and soluble intercellular CAM-1 (sICAM-1). Patients were invited for a final neuropsychological follow-up after a median of 6 years. Disease activity (relapses, EDSS increase, new/active brain lesions on MRI) was analysed between BL and FU.
RESULTS: The study group deteriorated in the Rey-Osterrieth Complex Figure (ROCF) test (p = 0.001), but improved significantly in three other tests, i.e. semantic fluency test (p = 0.013), California Verbal Learning Test (CVLT, p = 0.016), and Word Comprehension Test (WCT, p < 0.001). EDSS increase correlated negatively with semantic fluency and WCT scores (r = -0.579, p = 0.001 and r = -0.391, p = 0.033, respectively). Improvements in semantic fluency test and WCT correlated positively with baseline deep grey matter, grey matter, and cortical volumes (p < 0.05, r > 0). Higher EDSS on FU correlated significantly negatively with baseline left and right pallidum, right caudate, right putamen, right accumbens, and cortical volume (p < 0.05, r < 0). No significant relationship was found between the number of relapses and EDSS on FU or neuropsychological deteriorations. Improvements in WCT and CVLT correlated positively with baseline sPECAM1 and sVCAM1 results, respectively (r > 0, p < 0.05). Deterioration in ROCF test correlated significantly with higher levels of baseline VEGF and sVCAM1 (p < 0.05).
CONCLUSIONS: Brain volume is an important predictor of future EDSS and cognitive functions outcome. MS patients have a potential for improving in neuropsychological tests over time. It remains to be established whether this is related to successful disease modification with immunotherapy. Baseline volumetric measures are stronger predictors of cognitive performance than relapse activity, which yet again highlights the importance of atrophy in MS prognosis.
METHODS: 41 patients with relapsing-remitting multiple sclerosis (MS) were recruited to the study. Thirty patients were available for final follow-up and were included in the analysis. Baseline (BL) brain MRI including volumetry and neuropsychological tests were performed. Blood samples were collected at BL and follow-up (FU) and were tested for: vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM1), soluble platelet-endothelial CAM-1 (sPECAM1), and soluble intercellular CAM-1 (sICAM-1). Patients were invited for a final neuropsychological follow-up after a median of 6 years. Disease activity (relapses, EDSS increase, new/active brain lesions on MRI) was analysed between BL and FU.
RESULTS: The study group deteriorated in the Rey-Osterrieth Complex Figure (ROCF) test (p = 0.001), but improved significantly in three other tests, i.e. semantic fluency test (p = 0.013), California Verbal Learning Test (CVLT, p = 0.016), and Word Comprehension Test (WCT, p < 0.001). EDSS increase correlated negatively with semantic fluency and WCT scores (r = -0.579, p = 0.001 and r = -0.391, p = 0.033, respectively). Improvements in semantic fluency test and WCT correlated positively with baseline deep grey matter, grey matter, and cortical volumes (p < 0.05, r > 0). Higher EDSS on FU correlated significantly negatively with baseline left and right pallidum, right caudate, right putamen, right accumbens, and cortical volume (p < 0.05, r < 0). No significant relationship was found between the number of relapses and EDSS on FU or neuropsychological deteriorations. Improvements in WCT and CVLT correlated positively with baseline sPECAM1 and sVCAM1 results, respectively (r > 0, p < 0.05). Deterioration in ROCF test correlated significantly with higher levels of baseline VEGF and sVCAM1 (p < 0.05).
CONCLUSIONS: Brain volume is an important predictor of future EDSS and cognitive functions outcome. MS patients have a potential for improving in neuropsychological tests over time. It remains to be established whether this is related to successful disease modification with immunotherapy. Baseline volumetric measures are stronger predictors of cognitive performance than relapse activity, which yet again highlights the importance of atrophy in MS prognosis.
摘要：
背景：认知障碍从多发性硬化症（MS）的最早阶段开始发生，并随着时间的推移而发展。疾病改善疗法（DMT）的引入改变了MS患者的预后，也为认知领域的改进提供了潜在的机会。
方法：41例复发-缓解型多发性硬化（MS）患者被纳入研究。30名患者可用于最终随访，并被纳入分析。进行基线（BL）脑MRI，包括容积和神经心理学测试。在BL和随访（FU）时收集血样，并测试：血管内皮生长因子（VEGF），可溶性血管细胞粘附分子-1（sVCAM1），可溶性血小板内皮CAM-1（sPECAM1），和可溶性细胞间CAM-1（sICAM-1）。中位时间为6年后，患者被邀请进行最终的神经心理学随访。疾病活动（复发，EDSS增加,MRI上的新/活跃脑部病变）在BL和FU之间进行了分析。
结果：研究组在Rey-Osterrieth复合物图（ROCF）测试中恶化（p=0.001），但在其他三项测试中显著改善，即语义流畅性测试(p=0.013)，加州言语学习测试（CVLT，p=0.016),和单词理解测试(WCT，p<0.001)。EDSS增加与语义流畅性和WCT得分呈负相关（分别为r=-0.579，p=0.001和r=-0.391，p=0.033）。语义流畅性测试和WCT的改进与基线深灰质呈正相关，灰质,和皮质体积（p<0.05，r>0）。FU上较高的EDSS与基线左右苍白球呈显著负相关，右尾状,右壳核,右伏隔,皮质体积(p<0.05,r<0)。FU或神经心理学恶化的复发次数与EDSS之间没有显着关系。WCT和CVLT的改善与基线sPECAM1和sVCAM1结果呈正相关，分别为(r>0，p<0.05)。ROCF测试中的恶化与基线VEGF和sVCAM1的较高水平显着相关（p<0.05）。
结论：脑容量是预测未来EDSS和认知功能结果的重要指标。MS患者有可能随着时间的推移改善神经心理学测试。这是否与免疫疗法的成功疾病修饰有关还有待确定。基线体积测量比复发活动更能预测认知表现，这再次凸显了萎缩在MS预后中的重要性。
方法：41例复发-缓解型多发性硬化（MS）患者被纳入研究。30名患者可用于最终随访，并被纳入分析。进行基线（BL）脑MRI，包括容积和神经心理学测试。在BL和随访（FU）时收集血样，并测试：血管内皮生长因子（VEGF），可溶性血管细胞粘附分子-1（sVCAM1），可溶性血小板内皮CAM-1（sPECAM1），和可溶性细胞间CAM-1（sICAM-1）。中位时间为6年后，患者被邀请进行最终的神经心理学随访。疾病活动（复发，EDSS增加,MRI上的新/活跃脑部病变）在BL和FU之间进行了分析。
结果：研究组在Rey-Osterrieth复合物图（ROCF）测试中恶化（p=0.001），但在其他三项测试中显著改善，即语义流畅性测试(p=0.013)，加州言语学习测试（CVLT，p=0.016),和单词理解测试(WCT，p<0.001)。EDSS增加与语义流畅性和WCT得分呈负相关（分别为r=-0.579，p=0.001和r=-0.391，p=0.033）。语义流畅性测试和WCT的改进与基线深灰质呈正相关，灰质,和皮质体积（p<0.05，r>0）。FU上较高的EDSS与基线左右苍白球呈显著负相关，右尾状,右壳核,右伏隔,皮质体积(p<0.05,r<0)。FU或神经心理学恶化的复发次数与EDSS之间没有显着关系。WCT和CVLT的改善与基线sPECAM1和sVCAM1结果呈正相关，分别为(r>0，p<0.05)。ROCF测试中的恶化与基线VEGF和sVCAM1的较高水平显着相关（p<0.05）。
结论：脑容量是预测未来EDSS和认知功能结果的重要指标。MS患者有可能随着时间的推移改善神经心理学测试。这是否与免疫疗法的成功疾病修饰有关还有待确定。基线体积测量比复发活动更能预测认知表现，这再次凸显了萎缩在MS预后中的重要性。
