From the Department of Neurology (D.S., Zhijin Zhang, H.Z., Z.W., H.M., W.L., T.W., J.J., T.F.), Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases (D.S., Zhijin Zhang, Zhe Zhang, W.Z., N.W., Y.S., X.L., H.Z., Z.W., H.M., W.L., T.W., J.J., T.F.); Tiantan Neuroimaging Center of Excellence (Zhe Zhang, W.Z., N.W., Y.S., X.L., J.J.), and Department of Hepatology (S.Z.), Beijing Youan Hospital, Capital Medical University; Department of Neurology (T.Y.), Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders; Senior Department of Hepatology (Y.D.), the Fifth Medical Center of PLA General Hospital, Beijing, China; Hinda and Arthur Marcus Institute for Aging Research (J.Z.), Hebrew SeniorLife, Roslindale; Harvard Medical School (J.Z.), Boston, MA; Pacific Parkinson's Research Centre (J.S.T.L., A.J.S.), Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology and Centre of Clinical Neuroscience (P.D.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; Division of Neurology (A.J.S.), Department of Medicine, University of British Columbia, Vancouver, Canada; and Department of Neurology (X.W.), Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China.
Neurology. 2024 Jun 25;102(12):e209478. doi: 10.1212/WNL.0000000000209478. Epub 2024 Jun 3.
Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism.
Patients with WD, healthy participants with monoallelic variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution.
We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen.
The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD.
The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.
神经型威尔逊病（NWD）是一种罕见的遗传性疾病，缺乏无创且准确的生物标志物，可能会导致诊断错误或延迟。磁敏感加权成像（SWI）上观察到的皮质下金属沉积过多提示 NWD 存在特征性模式。7T SWI 具有亚毫米的空间分辨率和更高的对比度，可能能够更好地显示 NWD 中的金属沉积。在这项研究中，我们试图使用 7T SWI 来识别 NWD 中独特的金属沉积模式，并研究其诊断价值和潜在的病理生理机制。
招募了 WD 患者、携带单一染色体上单等位基因突变的健康参与者（杂合子）和健康对照（HC）。根据在研究过程中是否存在神经系统症状，将 NWD 和非-NWD（nNWD）定义为存在或不存在。还招募了具有类似临床表现或影像学表现的其他疾病患者，包括早发性帕金森病（EOPD）、多系统萎缩症（MSA）、进行性核上性麻痹（PSP）和神经变性伴脑铁沉积症（NBIA），并进行了探索性比较分析。所有参与者均接受了 7T T1、T2 和高分辨率 SWI 扫描。进行定量磁化率图和主成分分析以说明金属分布。
我们在 NWD 患者中发现了一种由苍白球外侧边界的高信号强度变化组成的线性信号强度变化，我们将其称为“高信号苍白球边缘征”。该特征在 41 名 NWD 患者中的 38 名中被检测到，在所有 31 名 nNWD 患者、15 名 EOPD 患者、30 名 MSA 患者、15 名 PSP 患者和 12 名 NBIA 患者中均为阴性；在 22 名杂合子携带者和 41 名 HC 中也为阴性。它区分 NWD 和 HC 的灵敏度为 92.7%，特异性为 100%。半定量量表测量的高信号苍白球边缘征严重程度与神经严重程度呈正相关（ρ=0.682，95%CI 0.467-0.821， < 0.001）。NWD 患者的壳核中显示出更高的磁化率，外侧苍白球和内侧壳核的区域权重较高。
高信号苍白球边缘征对 NWD 的诊断和鉴别诊断具有高灵敏度和优异的特异性。它与 NWD 中壳核中的特殊金属沉积模式有关，可被视为 NWD 的一种新的神经影像学生物标志物。
本研究提供了 II 级证据，表明 7T SWI MRI 上的高信号苍白球边缘征可以准确诊断神经型威尔逊病。
