Wise Adina, Ortega Roberto A, Raymond Deborah, Cervera Alessandra, Thorn Emma, Leaver Katherine, Russell David S, Bressman Susan B, Crary John F, Saunders-Pullman Rachel
Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, NY, United States.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Neurol. 2024 Aug 8;15:1450654. doi: 10.3389/fneur.2024.1450654. eCollection 2024.
variants have been associated with immune dysregulation as well as immune-related disorders such as IBD. A possible relationship between multiple sclerosis (MS) and PD has also been suggested. Further, neuropathologic studies of homozygous G2019S carriers with Parkinson's disease (PD) are rare, and there are no systematic reports of clinical features in those cases.
We investigated the co-occurrence of PD and MS in our research cohort and report on two cases of MS in PD as well as neuropathological findings for one.
MS preceded PD in 1.4% (2/138) of participants with G2019S variants, and in none (0/638) with idiopathic PD ( = 0.03). One case with MS and PD was a G2019S homozygous carrier, and neuropathology showed evidence of substantia nigra pars compacta degeneration and pallor without Lewy deposition, as well as multiple white matter lesions consistent with MS-related demyelination.
The increased prevalence of MS in PD further supports an important role for immune function for PD. This co-occurrence, while rare, suggests that MS may be an expression of the G2019S variant that includes both MS and PD, with MS predating features diagnostic of PD. The neuropathology suggests that the MS-related effects occurred independent of synuclein deposition. Importantly, and in addition, the neuropathological results not only support the MS diagnosis, but provide further evidence that Lewy body pathology may be absent even in homozygote carriers.
基因变异与免疫调节异常以及诸如炎症性肠病等免疫相关疾病有关。多发性硬化症（MS）与帕金森病（PD）之间也被认为可能存在某种关系。此外，对帕金森病（PD）纯合G2019S携带者的神经病理学研究很少，且尚无关于这些病例临床特征的系统性报告。
我们在研究队列中调查了PD和MS的共现情况，并报告了2例PD合并MS的病例以及1例的神经病理学发现。
在携带G2019S变异的参与者中，1.4%（2/138）的人MS先于PD出现，而在特发性PD患者中无一例（0/638）出现这种情况（P = 0.03）。1例MS合并PD患者是G2019S纯合携带者，神经病理学显示黑质致密部有变性和苍白，但无路易小体沉积，同时还有多个与MS相关脱髓鞘一致的白质病变。
PD中MS患病率的增加进一步支持了免疫功能在PD中的重要作用。这种共现情况虽然罕见，但表明MS可能是G2019S变异的一种表现形式，该变异包括MS和PD，且MS先于PD的诊断特征出现。神经病理学表明与MS相关的影响独立于α-突触核蛋白沉积而发生。重要的是，此外，神经病理学结果不仅支持MS的诊断，还进一步证明即使在纯合子携带者中也可能不存在路易小体病理改变。
