McConnell Brain Imaging Centre, Montreal Neurological Institute Hospital, and Department of Neurology and Neurosurgery, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, ND20, Cleveland, Ohio 44195, USA.
Centre for Intelligent Machines, McGill University, 3480 Rue University, Montréal, QC H3A 2A7, Canada. NeuroRx Research, 3575 Park Avenue, Suite #5322, Montreal, Quebec H2 × 4B3, Canada; NeuroRx Research, 3575 Park Avenue, Suite #5322, Montreal, Quebec H2 × 4B3, Canada.
Mult Scler Relat Disord. 2024 Jan;81:105123. doi: 10.1016/j.msard.2023.105123. Epub 2023 Nov 10.
The phenomenon of pseudoatropy after initiation of anti-inflammatory therapy is believed to be reversible, but a rebound in brain volume following cessation of highly-effective therapy has not been reported.
To evaluate brain volume change in a treatment interruption study (RESTORE) in which relapsing-remitting multiple sclerosis (RRMS) patients were randomized to switch from natalizumab to placebo, from natalizumab to once-monthly intravenous methylprednisolone (IVMP), or to remain on natalizumab.
T2 lesion volume (T2LV), baseline normalized brain volumes, and follow-up percent brain volume changes (PBVC) were calculated. Approximate T2 relaxation-time (pT2) was calculated within the brain mask and the T2 lesions to estimate changes in water content. Linear mixed effects models were used to detect differences in T2LV, pT2 in whole brain, pT2 in T2-weighted lesions, and PBVC among the placebo, natalizumab, and IVMP groups. We also estimated contributions of T2LV and pT2 (in whole brain and T2 lesions) to PBVC.
T2LV increased in the placebo group (by 0.66 ml/year, p<0.0001) and IVMP (+1.98 ml/year, p = 0.05) groups relative to the natalizumab group. The rates of PBVC were significantly different: -0.239%/year with continued natalizumab and +0.126 %/year after switch to placebo (p = 0.03), while the IVMP group showed brain volume loss (-0.74 %/ year, p = 0.08). pT2 was not statistically different between the groups (p ≥ 0.29) and did not have significant effects on PBVC (p ≥ 0.25).
The increase in the brain volume in patients witching from natalizumab to placebo is consistent with reversal of so-called pseudoatrophy after starting natalizumab.
人们认为，在开始抗炎治疗后出现的假性萎缩现象是可逆的，但尚未有报道称，在停止高效治疗后，大脑体积会出现反弹。
在一项治疗中断研究（RESTORE）中评估脑容量变化，该研究将复发缓解型多发性硬化症（RRMS）患者随机分配至停用那他珠单抗改为安慰剂组、停用那他珠单抗改为每月一次静脉注射甲基强的松龙（IVMP）组或继续使用那他珠单抗组。
计算 T2 病变体积（T2LV）、基线正常脑容量和随访时脑容量变化百分比（PBVC）。在脑掩模内和 T2 病变内计算近似 T2 弛豫时间（pT2），以估计水含量的变化。采用线性混合效应模型检测安慰剂组、那他珠单抗组和 IVMP 组间 T2LV、全脑 pT2、T2 加权病变内 pT2 和 PBVC 的差异。我们还估计了 T2LV 和 pT2（全脑和 T2 病变内）对 PBVC 的贡献。
与那他珠单抗组相比，安慰剂组（每年增加 0.66ml，p<0.0001）和 IVMP 组（每年增加 1.98ml，p=0.05）的 T2LV 增加。PBVC 率差异显著：持续使用那他珠单抗组为-0.239%/年，转换为安慰剂组为+0.126%/年（p=0.03），而 IVMP 组显示脑容量损失（-0.74%/年，p=0.08）。各组间 pT2 无统计学差异（p≥0.29），对 PBVC 无显著影响（p≥0.25）。
从那他珠单抗转换为安慰剂的患者脑容量增加与开始那他珠单抗治疗后所谓的假性萎缩逆转一致。
