Schneider Ruth, Bellenberg Barbara, Hoepner Robert, Ellrichmann Gisa, Gold Ralf, Lukas Carsten
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Department of Diagnostic and Interventional Radiology and Nuclear Medicine, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Front Neurol. 2017 Sep 5;8:454. doi: 10.3389/fneur.2017.00454. eCollection 2017.
Progressive multifocal leukoencephalopathy (PML) is a severe complication of immunosuppressive therapies, especially of natalizumab in relapsing-remitting multiple sclerosis (MS). Metabolic changes within PML lesions have not yet been described in natalizumab-associated PML in MS patients.
To study metabolic profiles in natalizumab-associated PML lesions of MS patients by H magnetic resonance spectroscopy (H-MRS) at different stages during the PML course. To assess changes associated with the occurrence of the immune reconstitution inflammatory syndrome (IRIS).
20 patients received H-MRS and imaging at 3 T either in the pre-IRIS, IRIS, early-post-PML, or late post-PML setting. Five of these patients received individual follow-up examinations, including the pre-IRIS or IRIS phase. Clinical worsening was described by changes in the Karnofsky Performance Scale (KPS) and the expanded disability status scale (EDSS) 1 year before PML and scoring at the time of H-MRS.
In PML lesions, increased levels of the Lip/Cr ratio, driven by rising of lipid and reduction of Creatine, were found before the occurrence of IRIS ( = 0.014) with a maximum in the PML-IRIS group ( = 0.004). By contrast, marked rises of Cho/Cr in PML lesions were detected exclusively during the IRIS phase ( = 0.003). The Lip/Cr ratio decreased to above-normal levels in early-post-PML ( = 0.007, compared to normal appearing white matter (NAWM)) and to normal levels in the late-post-PML group. NAA/Cho was reduced compared to NAWM in the pre-IRIS, IRIS, and early-post-PML group. In NAA/Cr, the same effect was seen in the pre-IRIS and early-post-PML group. These cross-sectional results were confirmed by the individual follow-up examinations of four patients. NAA/Cho, Cho/Cr, and the lipid rise relative to NAWM in PML lesions were significantly correlated with the residual clinical worsening (KPS change) in post-PML patients (Spearman correlations ρ = 0.481, = 0.018; ρ = -0.505, = 0.014; and ρ = -0.488, = 0.020).
H-MRS detected clinically significant dynamic changes of metabolic patterns in PML lesions during the course of natalizumab-associated PML in MS patients. Lip/Cr and Cho/Cr may provide additional information for detecting the onset of the IRIS phase in the course of the PML disease.
进行性多灶性白质脑病（PML）是免疫抑制治疗的严重并发症，尤其是在复发缓解型多发性硬化症（MS）中使用那他珠单抗治疗时。MS患者中那他珠单抗相关PML病变内的代谢变化尚未见报道。
通过氢磁共振波谱（H-MRS）研究MS患者那他珠单抗相关PML病变在PML病程不同阶段的代谢谱。评估与免疫重建炎症综合征（IRIS）发生相关的变化。
20例患者在IRIS前、IRIS期、PML早期或PML后期接受了3T场强的H-MRS和成像检查。其中5例患者接受了个体随访检查，包括IRIS前或IRIS期。通过PML前1年的卡氏功能状态量表（KPS）和扩展残疾状态量表（EDSS）变化以及H-MRS检查时的评分来描述临床恶化情况。
在PML病变中，IRIS发生前（P = 0.014），由于脂质升高和肌酸降低，Lip/Cr比值升高，在PML-IRIS组达到最高（P = 0.004）。相比之下，仅在IRIS期检测到PML病变中Cho/Cr显著升高（P = 0.003）。PML早期Lip/Cr比值降至高于正常水平（与正常白质（NAWM）相比，P = 0.007），PML后期组降至正常水平。与NAWM相比，IRIS前、IRIS期和PML早期组的NAA/Cho降低。在NAA/Cr方面，IRIS前和PML早期组也有同样的变化。4例患者的个体随访检查证实了这些横断面结果。PML病变中NAA/Cho、Cho/Cr以及相对于NAWM的脂质升高与PML后患者的残余临床恶化（KPS变化）显著相关（Spearman相关性ρ = 0.481，P = 0.018；ρ = -0.505，P = 0.014；ρ = -0.488，P = 0.020）。
H-MRS检测到MS患者那他珠单抗相关PML病程中PML病变代谢模式的临床显著动态变化。Lip/Cr和Cho/Cr可能为检测PML病程中IRIS期的发作提供额外信息。
