From the Departments of Anatomy & Neurosciences (A.J.C.E., M.D.S., K.A.M., H.E.H., M.M.S., J.J.G.G.), Radiology and Nuclear Medicine (I.D., J.W.P., F.B., H.V.), and Neurology (I.D., B.M.J.U.), Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, Location VUmc, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.
Neurology. 2019 Oct 1;93(14):e1348-e1359. doi: 10.1212/WNL.0000000000008198. Epub 2019 Sep 4.
To determine which pathologic process could be responsible for the acceleration of cognitive decline during the course of multiple sclerosis (MS), using longitudinal structural MRI, which was related to cognitive decline in relapsing-remitting MS (RRMS) and progressive MS (PMS).
A prospective cohort of 230 patients with MS (179 RRMS and 51 PMS) and 59 healthy controls was evaluated twice with 5-year (mean 4.9, SD 0.94) interval during which 22 patients with RRMS converted to PMS. Annual rates of cortical and deep gray matter atrophy as well as lesion volume increase were computed on longitudinal (3T) MRI data and correlated to the annual rate of cognitive decline as measured using an extensive cognitive evaluation at both time points.
The deep gray matter atrophy rate did not differ between PMS and RRMS (-0.82%/year vs -0.71%/year, = 0.11), while faster cortical atrophy was observed in PMS (-0.87%/year vs -0.48%/year, < 0.01). Similarly, faster cognitive decline was observed in PMS compared to RRMS ( < 0.01). Annual cognitive decline was related to the rate of annual lesion volume increase in stable RRMS ( = -0.17, = 0.03) to the rate of annual deep gray matter atrophy in converting RRMS ( = 0.50, = 0.02) and annual cortical atrophy in PMS ( = 0.35, = 0.01).
These results indicate that cortical atrophy and cognitive decline accelerate together during the course of MS. Substrates of cognitive decline shifted from worsening lesional pathology in stable RRMS to deep gray matter atrophy in converting RRMS and to accelerated cortical atrophy in PMS only.
通过纵向结构 MRI 确定导致多发性硬化症（MS）病程中认知能力下降加速的病理过程，这与复发缓解型 MS（RRMS）和进展型 MS（PMS）的认知能力下降相关。
对 230 例 MS 患者（179 例 RRMS 和 51 例 PMS）和 59 例健康对照者进行前瞻性队列研究，平均随访 5 年（平均 4.9 年，标准差 0.94 年），其中 22 例 RRMS 患者转化为 PMS。在纵向（3T）MRI 数据上计算皮质和深部灰质萎缩以及病变体积增加的年增长率，并将其与在两次随访时使用广泛认知评估测量的认知能力下降的年增长率相关联。
PMS 和 RRMS 之间的深部灰质萎缩率没有差异（-0.82%/年与-0.71%/年， = 0.11），而 PMS 中皮质萎缩更快（-0.87%/年与-0.48%/年， < 0.01）。同样，与 RRMS 相比，PMS 中认知能力下降更快（ < 0.01）。在稳定的 RRMS 中，年度认知下降与年度病变体积增加率相关（ = -0.17， = 0.03），在转化型 RRMS 中与年度深部灰质萎缩率相关（ = 0.50， = 0.02），在 PMS 中与年度皮质萎缩率相关（ = 0.35， = 0.01）。
这些结果表明，在 MS 病程中，皮质萎缩和认知能力下降同时加速。在稳定的 RRMS 中，认知能力下降的底物从病变病理恶化转变为转化型 RRMS 中的深部灰质萎缩，以及 PMS 中的皮质加速萎缩。
