From the Turku Brain and Mind Center (O. Liesmäki, J.K., O. Likitalo, E.G.E., A.B.-G., J.A., I.S., E.M.M., P.Y., J.J.), Clinical Neurosciences, University of Turku; Neurocenter (O. Liesmäki, J.K., O. Likitalo, J.A., E.M.M., S.R., P.Y., J.J.), Turku University Hospital, Finland; Center for Brain Circuit Therapeutics (M.U.F.), Brigham & Women's Hospital, Boston, MA; and Department of Neurology (M.U.F.), University Hospital Wuerzburg, Germany.
Neurology. 2024 Sep 24;103(6):e209803. doi: 10.1212/WNL.0000000000209803. Epub 2024 Aug 29.
Ataxia is primarily considered to originate from the cerebellum. However, it can manifest without obvious cerebellar damage, such as in anterior circulation stroke, leaving the mechanisms of ataxia unclear. The aim of this study was to investigate whether stroke lesions causing limb ataxia localize to a common brain network.
In this prospective cohort study, adult patients with new-onset stroke with visible lesions on CT or MRI from Turku University Hospital, Finland, were clinically examined (1) after their stroke while still admitted to the hospital (baseline) and (2) 4 months later (follow-up) to assess limb ataxia. Lesion locations and their functional connectivity, computed using openly available data from 1,000 healthy volunteers from the Brain Genome Superstruct Project, were compared voxel-by-voxel across the whole brain between patients with and without ataxia, using voxel-based lesion-symptom mapping and lesion network mapping. The findings were confirmed in an independent stroke patient cohort with identical clinical assessments.
One hundred ninety-seven patients (mean age 67.2 years, 39%) were included in this study. At baseline, 35 patients (68.3 years, 34%) had and 162 (67.0 years, 40%) did not have new-onset acute limb ataxia. At follow-up, additional 4 patients had developed late-onset limb ataxia, totalling to 39 patients (68.6 years, 36%) with limb ataxia at any point. One hundred eighteen patients (66.2 years, 40%) did not have ataxia at any point (n = 40 with missing follow-up data). Lesions in 54% of the patients with acute limb ataxia were located outside the cerebellum and cerebellar peduncles, and we did not find an association between specific lesion locations and ataxia. Lesions causing acute limb ataxia, however, were connected to a common network centered on the intermediate zone cerebellum and cerebellar peduncles (lesion connectivity in patients with vs without acute limb ataxia, < 0.05). The results were similar when comparing patients with and without ataxia at any point, and when excluding lesions in the cerebellum and cerebellar peduncles ( < 005). The findings were confirmed in the independent stroke dataset (n 96), demonstrating an OR of 2.27 (95% CI 1.32-3.91) for limb ataxia per standard deviation increase in limb ataxia network damage score.
Lesions causing limb ataxia occur in heterogeneous locations but localize to a common brain network.
共济失调通常被认为起源于小脑。然而，在某些情况下，即使小脑没有明显损伤，也会出现共济失调，例如在前循环卒中时，其发病机制尚不清楚。本研究旨在探讨导致肢体共济失调的卒中病灶是否定位于共同的脑网络。
本前瞻性队列研究纳入了芬兰图尔库大学医院新发病灶性卒中且 CT 或 MRI 可见病灶的成年患者。在卒中后 1) 住院期间（基线）和 2) 4 个月后（随访）进行临床检查，以评估肢体共济失调。使用 Brain Genome Superstruct 项目中 1000 名健康志愿者的公开可用数据，对患者的病灶位置及其功能连接进行计算，通过基于体素的病灶-症状映射和病灶网络映射，对有和无共济失调患者的全脑进行逐像素比较。在具有相同临床评估的独立卒中患者队列中对研究结果进行了验证。
本研究共纳入 197 名患者（平均年龄 67.2 岁，39%）。基线时，35 名患者（68.3 岁，34%）出现新发急性肢体共济失调，162 名患者（67.0 岁，40%）无新发急性肢体共济失调。随访时，另外 4 名患者出现迟发性肢体共济失调，总计有 39 名患者（68.6 岁，36%）在任何时间点均有肢体共济失调。118 名患者（66.2 岁，40%）在任何时间点均无共济失调（40 名患者因随访数据缺失）。有急性肢体共济失调的患者中，54%的病灶位于小脑和小脑脚之外，且我们未发现特定病灶位置与共济失调之间存在关联。然而，导致急性肢体共济失调的病灶与以小脑间区和小脑脚为中心的共同网络相连（有急性肢体共济失调的患者与无急性肢体共济失调的患者相比，病灶连通性 < 0.05）。当比较任何时间点有和无共济失调的患者，以及当排除小脑和小脑脚病灶时，结果相似（< 0.05）。在独立的卒中数据集（n=96）中验证了这些发现，表明肢体共济失调网络损伤评分每增加一个标准差，肢体共济失调的比值比为 2.27（95%CI 1.32-3.91）。
导致肢体共济失调的病灶发生于异质部位，但定位于共同的脑网络。
