Prosperini Luca, de Rossi Nicola, Scarpazza Cristina, Moiola Lucia, Cosottini Mirco, Gerevini Simonetta, Capra Ruggero
Dept. of Neurology and Psychiatry, Sapienza University, Viale Dell'Università, Rome, Italy.
Multiple Sclerosis Centre, Spedali Civili di Brescia, Via Ciotti, Montichiari, Brescia, Italy.
PLoS One. 2016 Dec 20;11(12):e0168376. doi: 10.1371/journal.pone.0168376. eCollection 2016.
The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV).
To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions.
An Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated.
Ten patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01).
Our findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival rate, and confirm the utility of MRI as a surveillance tool for NTZ-treated patients.
单克隆抗体那他珠单抗（NTZ）是治疗多发性硬化症（MS）患者的一种高效药物。然而，这种药物会增加进展性多灶性白质脑病（PML）的发病风险，PML是由约翰·坎宁安多瘤病毒（JCV）引起的中枢神经系统（CNS）机会性感染。
描述39例MS患者（28例女性，11例男性）在平均接受39次输注后发生与NTZ相关的PML的12个月临床病程。
一项意大利独立合作的储存库倡议收集并分析了社会人口统计学、临床、磁共振成像（MRI）数据，以及在被诊断为患有与NTZ相关的PML患者的脑脊液（CSF）样本中检测到的JCV-DNA拷贝数。通过扩展残疾状态量表测量的残疾进展情况，在开始使用NTZ时、PML诊断时以及PML诊断后2、6和12个月进行评估。还研究了PML诊断时的临床和辅助临床特征对最终结局的影响。
10例患者（25.6%）在接受24次NTZ输注之前被诊断出PML。在6例患者（15.4%）中，PML疑似诊断是基于高度提示性的MRI表现，而临床状况没有任何可检测到的变化（无症状性PML）。在有症状性PML的患者中，出现认知症状的患者（n = 12）比有其他神经症状的患者（n = 21）诊断更快（p = 0.003）。在12个月的观察期内，3例患者（7.7%）死亡，生存率为92.3%。无症状性PML、MRI检测到的脑受累范围更局限和钆增强，以及较低的病毒载量与更好的残疾结局相关（p值<0.01）。
我们的研究结果支持早期PML诊断、有限的CNS受累和免疫恢复的初始迹象与更好的结局和更高的生存率相关，并证实了MRI作为监测接受NTZ治疗患者的工具的实用性。
