Wiebenga O T, Klauser A M, Schoonheim M M, Nagtegaal G J A, Steenwijk M D, van Rossum J A, Polman C H, Barkhof F, Pouwels P J W, Geurts J J G
From the Departments of Radiology and Nuclear Medicine (O.T.W., G.J.A.N., M.D.S., F.B.) Anatomy and Neurosciences (O.T.W., A.M.K., M.M.S., G.J.A.N., J.J.G.G.)
Anatomy and Neurosciences (O.T.W., A.M.K., M.M.S., G.J.A.N., J.J.G.G.).
AJNR Am J Neuroradiol. 2015 Jun;36(6):1116-23. doi: 10.3174/ajnr.A4252. Epub 2015 Mar 5.
The considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging.
In this explorative observational study, 25 patients with relapsing-remitting multiple sclerosis initiating natalizumab treatment were included and scanned every 6 months for 18 months. Additionally 18 matched patients with relapsing-remitting multiple sclerosis continuing treatment with interferon-β or glatiramer acetate were included along with 12 healthy controls. Imaging included short TE 2D-MR spectroscopic imaging with absolute metabolite quantification of total N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, myo-inositol, and glutamate. Concentrations were determined for lesional white matter, normal-appearing white matter, and gray matter.
At baseline in both patient groups, lower concentrations of total N-acetylaspartate and creatine and phosphocreatine were found in lesional white matter compared with normal-appearing white matter and additionally lower glutamate in lesional white matter of patients receiving natalizumab. In those patients, a significant yearly metabolite increase was found for lesional white matter total N-acetylaspartate (7%, P < .001), creatine and phosphocreatine (6%, P = .042), and glutamate (10%, P = .028), while lesion volumes did not change. In patients receiving interferon-β/glatiramer acetate, no significant change was measured in lesional white matter for any metabolite, while whole-brain normalized lesion volumes increased.
Patients treated with natalizumab showed an increase in total N-acetylaspartate, creatine and phosphocreatine, and glutamate in lesional white matter. These increasing metabolite concentrations might be a sign of enhanced axonal metabolism.
那他珠单抗对复发缓解型多发性硬化症患者具有显著的临床疗效，这可能是由于其对轴突功能可能产生的有益作用。在这项纵向研究中，通过磁共振波谱成像研究那他珠单抗对复发缓解型多发性硬化症患者神经元完整性标志物总N-乙酰天门冬氨酸的绝对浓度及其他脑代谢物的影响。
在这项探索性观察研究中，纳入了25例开始接受那他珠单抗治疗的复发缓解型多发性硬化症患者，并在18个月内每6个月进行一次扫描。此外，还纳入了18例继续接受干扰素-β或醋酸格拉替雷治疗的匹配复发缓解型多发性硬化症患者以及12名健康对照者。成像包括短TE二维磁共振波谱成像，对总N-乙酰天门冬氨酸、肌酸和磷酸肌酸、含胆碱化合物、肌醇和谷氨酸进行绝对代谢物定量分析。测定病变白质、正常白质和灰质中的浓度。
在两个患者组的基线时，与正常白质相比，病变白质中总N-乙酰天门冬氨酸、肌酸和磷酸肌酸的浓度较低，接受那他珠单抗治疗的患者病变白质中的谷氨酸浓度也较低。在这些患者中，病变白质总N-乙酰天门冬氨酸（7%，P <.001）、肌酸和磷酸肌酸（6%，P =.042）以及谷氨酸（10%，P =.028）每年有显著增加，而病变体积没有变化。在接受干扰素-β/醋酸格拉替雷治疗的患者中，病变白质中任何代谢物均未检测到显著变化，而全脑标准化病变体积增加。
接受那他珠单抗治疗的患者病变白质中的总N-乙酰天门冬氨酸、肌酸和磷酸肌酸以及谷氨酸有所增加。这些代谢物浓度的增加可能是轴突代谢增强的迹象。
