Abstract：
BACKGROUND: MRI is an important tool for disease diagnosis of Creutzfeldt-Jakob disease (CJD), yet its role in identifying preclinical stages of disease remains unclear. Here, we explored subtle white matter (WM) alterations in genetic CJD (gCJD) patients and in asymptomatic E200K mutation carriers using MRI, depending on total tau protein (t-tau) levels in CSF.
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.
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.
摘要：
背景：MRI是克雅氏病（CJD）疾病诊断的重要工具，然而，其在确定疾病临床前阶段中的作用尚不清楚。这里,我们使用MRI研究了遗传性CJD（gCJD）患者和无症状E200K突变携带者的细微白质（WM）改变，取决于CSF中的总tau蛋白（t-tau）水平。
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。
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。
