Neurology:多发性硬化,大脑网络有何变化

2021-10-28 Freeman MedSci原创

FC异常伴随着局部脑血流和结构连接的异常,

认知障碍影响了大约一半的多发性硬化症(MS)患者。虽然疾病机制尚未完全阐明,但静息态功能MRI(rsfMRI)研究显示,认知障碍和非障碍患者之间的功能连接(FC)存在差异。然而,rs-fMRI的一个缺点是缺乏有关FC异常的病理机制的信息,这限制了解释研究结果的能力。

有人在 "节点压力(nodal stress) "假说中提出,具有高连接性的网络区域,即所谓的 "枢纽 "或 "节点",其高活动性使其容易受到病理性的 "磨损",这可能是由于高代谢需求,这可能加速神经变性,导致网络功能失调。如果 "磨损 "的变化是造成FC异常的原因,我们希望在其他MR指标上也能看到异常。网络枢纽在功能和结构网络中都有很强的互连性,与活动相关的损害可望影响解剖学上的连接。

此外,如果节点损伤是由未满足的代谢需求引起的,这可能会影响脑血流(CBF)。通过收集扩散MRI和CBF数据以及rs-fMRI图像,因此可以确定FC异常是否与白质和灌注变化同时出现,这种共同出现的异常可以指出共同的潜在机制,从而为未来的研究方向提供信息。

藉此, 曼彻斯特大学的Danka Jandric等人,在复发性多发性硬化症患者(RRMS)的队列中测试了 "节点压力 "假说,以测试认知障碍患者的FC异常是否和下面几个因素共存:1)网络内空间重叠区域的解剖连接和CBF异常,2)相同的网络,3)来自静止状态网络的远端区域。

他们对102名复发缓解型多发性硬化症患者和27名健康对照者进行了多模态3T磁共振成像和神经心理学测试简易量表的评估。如果多发性硬化症患者在≥2项测试中得分低于对照组平均值≥1.5个标准差(n=55),则被归类为认知障碍,否则为认知保留(cognitively preserved)(n=47)。

通过独立成分分析和静止状态fMRI图像的双重回归来评估功能连接。脑血流图被估计,解剖学连接性是用解剖学连接图和扩散加权MRI的各向异性评估的。

脑血流和解剖连接的变化是在静止状态网络中评估的,这些网络显示了认知障碍的MS患者的功能连接异常。

他们发现:相对于认知受损的多发性硬化症患者,认知受损的多发性硬化症患者前部和后部默认模式网络的功能连接性明显下降,右侧和左侧额叶网络的功能连接性明显增加(TFCE校正后的P≤0.05,双侧的)。

显示功能异常的网络,在局部和远端显示出脑血流和解剖学连接的改变,但在重叠的地方没有。

这个研究的重要意义在于发现了:FC异常伴随着局部脑血流和结构连接的异常,但也证明这些影响并不完全发生在同一位置。多发性硬化症的脑网络功能连接的改变可能有一个共同的病理机制。


原文出处:
Jandric D, Lipp I, Paling D, et al. Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis. Neurology. Published online October 14, 2021:10.1212/WNL.0000000000012834. doi:10.1212/WNL.0000000000012834

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    2021-12-23 jml2009
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    2022-03-27 yinhl1978
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研究人员比较多发性硬化患者免疫病理亚型的临床特点,对547例经活检和/或尸检证实的中枢神经系统脱髓鞘患者进行免疫病理分型,进行性疾病与最初的免疫模式关系较小,并提示最终走向与慢性脱髓鞘相关的相似结局

Lancet Neurol:耐受性差,疗效阴性——不推荐贝沙罗汀治疗复发缓解型多发性硬化症(CCMR ONE)

研究不推荐使用贝沙罗汀治疗多发性硬化症患者,因为它的耐受性差,主要疗效结果为阴性。

拓展阅读

NNN:补体激活与多发性硬化症的病情严重程度有关

CIS/MS中经典补体和替代补体途径的中枢神经激活增加,并与鞘内IgM的产生有关。

JNNP:多发性硬化症疾病修饰疗法治疗后的认知处理速度和身体残疾轨迹

在这组积极接受治疗的 RRMS 患者中,患者的处理速度在 DMT 开始后的数年内保持稳定,而中度肢体残疾患者的肢体功能却在恶化。

Radiology:AI在多发性硬化皮质和皮质旁病变检测中的评估

使用人工智能(AI)的试点研究已经能够从常规临床MRI方案(即T1和质子密度/T2加权序列的组合)中生成人工DIR图像。

JAMA Neurology:儿童多发性硬化进展和复发活动

儿童期发病的多发性硬化患者在10年随访中不太可能出现PIRA(独立于复发活动的进展)。

JNNP:吸烟和被动吸烟都会对多发性硬化疾病活动和进展均有负面影响

本研究结果表明,吸烟和被动吸烟都会对多发性硬化症产生负面影响,确诊后戒烟可能是一项重要的二级预防措施。

2023年美国神经病学学会新兴科学年会| 外周血基因表达转录分析可预测原发进展型多发性硬化症的病情进展

转录组数据能正确预测未经治疗的 PPMS 患者的残疾进展和脑容量变化,这些患者可从早期治疗中获益。