Tozlu Ceren, Jamison Keith, Kang Yeona, Rua Sandra Hurtado, Kaunzner Ulrike W, Nguyen Thanh, Kuceyeski Amy, Gauthier Susan A
Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Department of Mathematics, Howard University, Washington DC, USA.
bioRxiv. 2025 Jan 3:2025.01.03.627857. doi: 10.1101/2025.01.03.627857.
To explore whether the inflammatory activity is higher in white matter (WM) tracts disrupted by paramagnetic rim lesions (PRLs) and if inflammation in PRL-disrupted WM tracts is associated with disability in people with multiple sclerosis (MS).
Forty-four MS patients and 16 healthy controls were included. 18 kDa-translocator protein positron emission tomography (TSPO-PET) with the C-PK11195 radioligand was used to measure the neuroinflammatory activity. The Network Modification Tool was used to identify WM tracts disrupted by PRLs and non-PRLs that were delineated on MRI. The Expanded Disability Status Scale was used to measure disability.
MS patients had higher inflammatory activity in whole brain WM compared to healthy controls (p=0.001). Compared to patients without PRLs, patients with PRLs exhibited higher levels of inflammatory activity in the WM tracts disrupted by any type of lesions (p=0.02) or PRLs (p=0.004). In patients with at least one PRL, inflammatory activity was higher in WM tracts highly disrupted by PRLs compared to WM tracts highly disrupted by non-PRLs (p=0.009). Elevated inflammatory activity in highly disrupted WM tracts was associated with increased disability in patients with PRL (p=0.03), but not in patients without PRL (p=0.2).
This study suggests that patients with PRLs may exhibit more diffuse WM inflammation in addition to higher inflammation along WM tracts disrupted by PRLs compared to non-PRLs, which could contribute to larger lesion volumes and faster disability progression. Imaging PRLs may serve to identify patients with both focal and diffuse inflammation, guiding therapeutic interventions aimed at reducing inflammation and preventing progressive disability in MS.
探讨在被顺磁性边缘病变（PRL）破坏的白质（WM）束中炎症活性是否更高，以及PRL破坏的WM束中的炎症与多发性硬化症（MS）患者的残疾是否相关。
纳入44例MS患者和16名健康对照。使用带有C-PK11195放射性配体的18 kDa转运蛋白正电子发射断层扫描（TSPO-PET）来测量神经炎症活性。使用网络修改工具识别在MRI上描绘的被PRL和非PRL破坏的WM束。使用扩展残疾状态量表来测量残疾程度。
与健康对照相比，MS患者全脑WM中的炎症活性更高（p = 0.001）。与没有PRL的患者相比，有PRL的患者在被任何类型病变或PRL破坏的WM束中表现出更高水平的炎症活性（p = 0.02）。在至少有一个PRL的患者中，与被非PRL高度破坏的WM束相比，被PRL高度破坏的WM束中的炎症活性更高（p = 0.009）。在有PRL的患者中，高度破坏的WM束中炎症活性升高与残疾增加相关（p = 0.03），但在没有PRL的患者中则不然（p = 0.2）。
本研究表明，与非PRL相比，有PRL的患者除了在被PRL破坏的WM束中有更高的炎症外，可能还表现出更弥漫的WM炎症，这可能导致更大的病变体积和更快的残疾进展。对PRL进行成像可能有助于识别既有局灶性炎症又有弥漫性炎症的患者，指导旨在减少炎症和预防MS患者进行性残疾的治疗干预。
