Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.
J Inherit Metab Dis. 2012 Mar;35(2):363-7. doi: 10.1007/s10545-011-9390-9. Epub 2011 Sep 20.
Cerebral micro- and macro-vasculopathy have been described in Fabry disease (FD). Neuronal globotriaosylceramide accumulation in selective cortical and brain stem areas including the hippocampus has been reported by autopsy studies in FD, but clinical surrogates as well as the clinical relevance of these findings have not been investigated so far. We measured the hippocampus volumes in a group of clinically affected patients with FD and correlated the findings with the cognitive performance of the patients. Hippocampal volumes were determined manually on T1-weighted MR-images of 25 FD patients (age 36.5 ± 11.0 years) and 20 age-matched controls. Additionally, individual white matter (WM) and gray matter (GM) volumes were measured using brain segmentation analyses. After controlling for age, white matter lesion (WML) volume, and WM/GM-volumes hippocampal volumes were significantly decreased in FD. These findings were substantially more pronounced in a subgroup of men with FD. WM and WM/GM volumes, and memory function did not significantly differ between patients and controls. In patients with FD hippocampal volumes were neither significantly correlated to WML volume nor to WM or WM/GM volumes. Hippocampus atrophy was not driven by the WML or other brain tissue atrophy and seems to correlate with the neuronal involvement in FD. In this young to middle-aged Fabry cohort the hippocampus degeneration was functionally compensated without memory impairment. Longitudinal studies are needed to determine whether this degenerative component in FD will progress and, in concert with the individual WML-load, predict subsequent cognitive decline.
脑微血管和大血管病变已在法布里病（FD）中被描述。尸检研究报道，在 FD 中神经元Globotriaosylceramide 在选择性皮质和脑干区域（包括海马体）积累，但目前尚未研究这些发现的临床替代物及其临床相关性。我们测量了一组患有 FD 的临床受影响患者的海马体体积，并将这些发现与患者的认知表现相关联。在 25 名 FD 患者（年龄 36.5 ± 11.0 岁）和 20 名年龄匹配的对照组的 T1 加权磁共振图像上手动测量海马体体积。此外，使用脑分割分析测量个体的白质（WM）和灰质（GM）体积。在控制年龄、白质病变（WML）体积和 WM/GM 体积后，FD 患者的海马体体积明显减少。在 FD 男性亚组中，这些发现更为明显。WM 和 WM/GM 体积以及记忆功能在患者和对照组之间没有显著差异。在 FD 患者中，海马体体积与 WML 体积或 WM 或 WM/GM 体积均无显著相关性。海马体萎缩不是由 WML 或其他脑组织萎缩引起的，而是与 FD 中的神经元受累相关。在这个年轻到中年的 Fabry 队列中，海马体退化在功能上得到了补偿，而没有记忆障碍。需要进行纵向研究，以确定 FD 中的这种退行性成分是否会进展，并与个体的 WML 负荷一起预测随后的认知下降。
