Amato Maria Pia, Portaccio Emilio, Goretti Benedetta, Zipoli Valentina, Battaglini Marco, Bartolozzi Maria Letizia, Stromillo Maria Laura, Guidi Leonello, Siracusa Gianfranco, Sorbi Sandro, Federico Antonio, De Stefano Nicola
Department of Neurology, University of Florence, Viale Morgagni, 85-50134 Florence, Italy.
Arch Neurol. 2007 Aug;64(8):1157-61. doi: 10.1001/archneur.64.8.1157.
We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.
To assess the relevance of gray matter changes over time to changes in cognition in RRMS.
A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis.
Two university MS clinics.
Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5).
We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.
We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9).
Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.
我们之前报道过，早期复发缓解型（RR）多发性硬化（MS）伴轻度认知障碍患者的新皮质体积会选择性减少，皮质体积与认知指标之间具有良好的相关性。
评估RRMS患者灰质随时间变化与认知变化之间的相关性。
2.5年后的纵向调查。每位患者接受了与基线时相同的磁共振成像（MRI）检查；使用多发性硬化症的Rao简短可重复神经心理测试电池组重新评估认知表现。
两家大学的MS诊所。
在参与最初横断面研究的41例RRMS患者中，28例可进行随访评估（18名女性；平均±标准差年龄，37.1±8.9岁；平均±标准差MS病程，7.3±2.9年；平均±标准差扩展残疾状态量表评分，1.8±1.5）。
我们在传统T1加权MRI上测量了脑体积变化百分比、标准化皮质体积（NCV）变化和标准化深部灰质体积变化，以及在T2加权MRI上测量了病灶负荷变化。使用Rao简短可重复测试电池组中未通过的测试数量将患者分类为认知恶化、稳定或改善。
我们在28例认知恶化患者中识别出12例，在28例稳定或改善患者中识别出16例。这些亚组在平均±标准差脑体积变化百分比（-2.1%±1.2%对-1.3%±1.3%；P = 0.11）、标准化深部灰质体积变化（-2.1±2.8 mL对-0.6±3.1 mL；P = 0.60）以及T2加权MRI上的病灶负荷变化（1.9±2.6 mL对1.6±2.3 mL；P = 0.73）方面没有差异。然而，恶化患者的NCV变化显著高于稳定或改善患者（-43.0±18.9 mL对-17.8±26.6 mL；P = 0.007）。在恶化患者中，NCV变化与语言流畅性测试表现相关（r = 0.73；P < 0.001）。在回归模型中，只有NCV变化与认知表现恶化显著相关（优势比，0.8；95%置信区间，0.7 - 0.9）。
进行性新皮质灰质丢失与MS相关的认知障碍有关，可能是RRMS中认知表现恶化的一个敏感标志物。
