METHODS: Six symptomatic gCJD patients and N=60 healthy relatives of gCJD patients were included. Participants underwent genetic testing for the E200K mutation, MRI scans at 3T and a lumbar puncture (LP) for t-tau. Diffusion tensor imaging (DTI) metrics were calculated along WM tracts.
RESULTS: gCJD patients demonstrated higher mean diffusivity (MD), radial diffusivity (RD) and lower fractional anisotropy (FA) values compared with healthy relatives in several WM tracts (p<0.05). Out of the healthy relatives, 50% (N=30) were found to be carriers of the E200K mutation. T-tau levels in cerebrospinal fluid (CSF) were above the normal range (>290 pg/mL) in N=8 out of 23 carriers who underwent an LP. No significant differences in FA, MD, axial diffusivity (AD) and RD were detected between healthy mutation carriers (HMC) and healthy non-carriers within the WM tracts. Finally, significantly higher FA and lower MD, RD and AD along several WM tracts were found in HMC with elevated t-tau compared with HMC with normal t-tau (p<0.05).
CONCLUSIONS: DTI abnormalities along WM tracts were found in healthy E200K mutation carriers with elevated t-tau in CSF. Longer follow-up is required to determine whether these subtle WM alterations are predictive of future conversion to symptomatic gCJD.
BACKGROUND: NCT05746715.
方法:纳入6例有症状的gCJD患者和N=60例gCJD患者的健康亲属。参与者接受了E200K突变的基因检测,MRI扫描在3T和腰椎穿刺(LP)的t-tau。沿着WM束计算扩散张量成像(DTI)度量。
结果:gCJD患者表现出更高的平均扩散率(MD),径向扩散率(RD)和较低的分数各向异性(FA)值与健康亲属在几个WM束(P<0.05)。在健康的亲戚中,发现50%(N=30)是E200K突变的携带者。在接受LP的23名携带者中,N=8名脑脊液(CSF)中的T-tau水平高于正常范围(>290pg/mL)。FA无显著差异,MD,在WM区域内的健康突变携带者(HMC)和健康非携带者之间检测到轴向扩散率(AD)和RD。最后,显著较高的FA和较低的MD,与正常t-tau的HMC相比,在t-tau升高的HMC中发现了沿多个WM束的RD和AD(p<0.05)。
结论:在CSF中t-tau升高的健康E200K突变携带者中发现了沿着WM束的DTI异常。需要更长时间的随访以确定这些细微的WM改变是否可以预测将来转化为有症状的gCJD。
背景:NCT05746715。