Rocca Maria A, Agosta Federica, Sormani Maria P, Fernando Kryshani, Tintorè Mar, Korteweg Tijmen, Tortorella Paola, Miller David H, Thompson Alan, Rovira Alex, Montalban Xavier, Polman Chris, Barkhof Frederik, Filippi Massimo
Neuroimaging Research Unit, Dept. of Neurology, Scientific Institute and University Ospedale, San Raffaele, Via Olgettina, 60, 20132 Milan, Italy.
J Neurol. 2008 May;255(5):683-91. doi: 10.1007/s00415-008-0776-z. Epub 2008 Feb 18.
To define the extent of overall brain damage in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to identify non-conventional magnetic resonance (MR) metrics predictive of evolution to definite MS.
Brain conventional and magnetization transfer (MT) MRI scans were obtained from 208 CIS patients and 55 matched healthy controls, recruited in four centres. Patients were assessed clinically at the time of MRI acquisition and after a median period of 3.1 years from disease onset. The following measures were derived: T2, T1 and gadolinium (Gd)- enhancing lesion volumes (LV), normalized brain volume (NBV), MTR histogram-derived quantities of the normal-appearing white matter (NAWM) and grey matter (GM).
During the follow-up, 43 % of the patients converted to definite MS. At baseline, a significant inter-centre heterogeneity was detected for T2 LV (p = 0.003), T1 LV (p = 0.006), NBV (p < 0.001) and MTR histogram-derived metrics (p < 0.001). Pooled average MTR values differed between CIS patients and controls for NAWM (p = 0.003) and GM (p = 0.01). Gdactivity and positivity of International Panel (IP) criteria for disease dissemination in space (DIS), but not NAWM and GM MTR and NBV, were associated with evolution to definite MS. The final multivariable model retained only MRI IP criteria for DIS (p = 0.05; HR = 1.66, 95 % CI = 1.00-2.77) as an independent predictor of evolution to definite MS.
Although irreversible tissue injury is present from the earliest clinical stages of MS, macroscopic focal lesions but not "diffuse" brain damage measured by MTR are associated to an increased risk of subsequent development of definite MS in CIS patients.
确定临床孤立综合征（CIS）提示多发性硬化（MS）患者的全脑损伤程度，并识别可预测发展为确诊MS的非常规磁共振（MR）指标。
从四个中心招募了208例CIS患者和55名匹配的健康对照，对其进行脑部常规和磁化传递（MT）MRI扫描。在MRI采集时以及疾病发作后中位时间3.1年对患者进行临床评估。得出以下测量值：T2、T1和钆（Gd）增强病变体积（LV）、标准化脑体积（NBV）、从MTR直方图得出的正常白质（NAWM）和灰质（GM）的量。
随访期间，43%的患者转变为确诊MS。在基线时，检测到T2 LV（p = 0.003）、T1 LV（p = 0.006）、NBV（p < 0.001）和从MTR直方图得出的指标（p < 0.001）存在显著的中心间异质性。CIS患者和对照之间，NAWM（p = 0.003）和GM（p = 0.01）的合并平均MTR值存在差异。Gd活性以及国际专家组（IP）疾病空间扩散（DIS）标准的阳性结果与发展为确诊MS相关，但NAWM和GM的MTR以及NBV与发展为确诊MS无关。最终的多变量模型仅保留MRI的IP DIS标准（p = 0.05；HR = 1.66，95%CI = 1.00 - 2.77）作为发展为确诊MS的独立预测指标。
尽管在MS的最早临床阶段就存在不可逆的组织损伤，但MTR测量的宏观局灶性病变而非“弥漫性”脑损伤与CIS患者随后发展为确诊MS的风险增加相关。
