Neurology:结节性硬化(TSC)患儿早期MRI特征与继发癫痫、2岁前神经发育结局存在显著相关!

2022-03-08 Naomi MedSci原创

在患结节性硬化症(TSC)的婴儿中,早期脑MRI检测到的特征性TSC病变与临床癫痫的发展、出生后头两年的神经发育结果间存在显著的相关性。根据该研究结果,早期的脑MRI表现可以指导儿童TSC的临床治疗。

      结节性硬化症 (TSC) 是一种遗传性多系统疾病,估计新生儿的发病率为 1:6000。TSC 是由 TSC1 或 TSC2 的突变引起的基因,这两处基因分别编码hamartin和tuberin。 Hamartin-tuberin复合体抑制哺乳动物雷帕霉素靶标(MTOR)途径,该途径控制细胞的生长和增殖。脑部病变是该病的特征之一,可在超过90%的患者中发现,包括结节或皮质发育不良、脑白质异常,如放射状移行线、室管膜下结节和室管膜下巨细胞星形细胞瘤。

     在无髓化的脑磁共振成像 (MRI) 上,结节或皮质发育不良在 T1 加权序列上显示为高信号病变,在 T2W 序列上显示为低信号,而当大脑髓鞘化时,它们在 T1W 序列上为 T2W 高信号和 T1 低信号,结节可能钙化或发生囊肿样变化。径向迁移线 (RML) 从脑室表面延伸到皮层,主要位于皮层下白质,有时终止于皮层下结节。 它们被认为代表了在皮层迁移过程中停滞的异位神经元和神经胶质元素。室管膜下结节 (SEN) 是侧脑室室管膜表面的错构瘤性病变。 SEN 可随着时间的推移生长并发展为室管膜下巨细胞星形细胞瘤 (SEGA)

      癫痫是 TSC 最常见的神经系统表现之一,影响 85% 的患者;大多数人在出生后第1年癫痫发作,大约 40% 在 2 岁时发展为难治性癫痫。认知共病很常见,一半有学习障碍,三分之一有严重认知障碍。多种因素与癫痫和神经发育迟缓的风险增加有关,其中包括 TSC 基因突变、MRI 特征和脑电图异常的演变。通过提高对该综合征的认识和胎龄 20 周后在常规超声心动图上对心脏横纹肌瘤进行产前早期检测,TSC 的诊断被越来越多地在产前或出生后不久后即识别。

      TSC 的早期明确诊断需要在癫痫发作之前开始进行更彻底的随访,并能够迅速甚至预防性地开始抗癫痫治疗。在临床癫痫发作和神经发育障碍发生前早期诊断 TSC 的可能性使 TSC 成为研究癫痫发生和神经发育障碍的生物标志物的理想模型。FP7 资助的 EPISTOP 项目(评估癫痫遗传模型中 EPIl eptogenesiS 的临床和分子生物标志物的长期前瞻性研究——结节性硬化症 ComPlex,NCT02098759,http://clinicaltrials.gov,是一项多中心、长期、前瞻性随访研究,以评估 TSC 患者癫痫发生的临床和分子生物标志物。近日,这一发表在Neurology上的子研究拟确定不良癫痫和发育结果的早期 MRI 生物标志物。研究目包括:1)确定6个月以下、癫痫发作前癫痫的早期MRI生物标志物;2)将这些MRI生物标志物与2岁时的神经发育结果相关联。

      研究人员对小于6个月大的TSC婴儿进行了脑MRI检查。使用了跨中心的协调MRI方案,并通过神经心理评估和系列视频脑电图对儿童进行了密切监测。MRI表现为结节、放射状移行线、白质异常、囊肿、钙化、室管膜下结节(SEN)和室管膜下巨细胞星形细胞瘤(SEGA)。计算病灶与脑体积的比率,并将其与癫痫和两年后的神经发育结果相关联。

  • 77例TSC患儿行MRI检查,62例MRI足以进行容积分析。
  • 结节的存在和较高的结节/脑比率与临床癫痫的发生有关,与TSC基因突变和预防性治疗无关。
  • 两年后较高的结节/大脑比率与较低的认知和运动发育智商相关,而与TSC基因突变和癫痫的存在无关。

      在患有TSC的婴儿中,早期脑MRI检测到的特征性TSC病变与临床癫痫的发展以及出生后头两年的神经发育结果之间存在显著的相关性。根据该研究结果,早期的脑MRI表现可以指导儿童TSC的临床治疗。

      这项研究提供了I类证据,表明在患有TSC的婴儿中,早期脑MRI上特征性的TSC病变与出生后头两年的临床癫痫发作和神经发育结果之间存在显著的相关性。

文献来源:Hulshof HM, Kuijf HJ, Kotulska K, et al. Association of Early MRI Characteristics With Subsequent Epilepsy and Neurodevelopmental Outcomes in Children With Tuberous Sclerosis Complex [published online ahead of print, 2022 Jan 31]. Neurology. 2022;10.1212/WNL.0000000000200027. doi:10.1212/WNL.0000000000200027

 

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    2022-04-15 yinhl1978
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    2022-11-10 feifers
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    2022-03-08 仁术2021

    不错,学习了。

    0

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    2022-03-05 neurowu

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