Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
Team Biostatistics and Big Medical Data, IDA Lab Salzburg, Paracelsus Medical University, Salzburg, Austria.
J Neurol. 2024 Jan;271(1):374-385. doi: 10.1007/s00415-023-11924-7. Epub 2023 Sep 20.
BACKGROUND/OBJECTIVE: The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria.
Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome.
As of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132 months (median 76 months) was available in 11/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6/11.
The number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare.
背景/目的：在多发性硬化症（MS）中使用那他珠单抗（NAT）可能会因进行性多灶性脑白质病（PML）而变得复杂，这是一种罕见且危及生命的机会性脑部感染。我们旨在分析 PML 恢复后 MS 的病程，以及奥地利 NAT 相关 PML（NAT-PML）的长期结果。
基于全国性奥地利 MS 治疗登记处（AMSTR）和 MS 中心的病例识别，进行回顾性研究，并对患者病历进行审查。扩展残疾状况量表（EDSS）用于衡量神经残疾和结果。
截至 2022 年 12 月，我们在奥地利发现了 15 例 NAT-PML 病例；只有 20%的病例发生在 2016 年之后，当时开始加强警惕。两名患者未从急性 PML 中存活下来，另外一名患者在五年后死亡，死亡率为 20%。癫痫发作仅发生在 EDSS 明显增加的患者中。怀疑 PML 时脑磁共振成像（MRI）上的钆增强与 PML 后神经残疾的微小变化有关。15 例中有 11 例可获得长达 132 个月（中位数 76 个月）的长期随访。总体 EDSS 中位数从 PML 前的 3.5 增加到最后评估时的 6.5。关于观察期间的炎症性 MS 相关疾病活动，只有一名患者经历了 MS 复发，另一名患者有两个 Gd 增强的脑部病变。3 名患者在 PML 后三年内转化为进行性 MS，6/11 名患者的 EDSS 进一步增加。
随着时间的推移，NAT-PML 病例的数量正在减少。尽管许多患者与 PML 前相比积累了严重的持续性神经功能缺陷，但 PML 恢复后的炎症性 MS 相关疾病活动很少见。
