约翰霍普金斯大学的神经影像学研究揭示了莱姆病治疗后患者的功能和结构异常
10/26/2022
In a study using specialized imaging techniques, 约翰霍普金斯大学医学研究人员报告说，莱姆病治疗后患者的“白质”和其他脑组织生理学发生了显著变化, 在每年感染莱姆病的近50万美国人中，有10%到20%受到这种疾病的影响.
The study’s findings, published October 26 in the journal PLOS ONE, substantiate and help validate that memory, 以及治疗后莱姆病患者长期经历的其他认知困难, are linked to functional and structural changes in the brain.
Lyme disease, whose early symptoms may include a characteristic rash, flu-like aches and fever, joint pain, and fatigue, is treated using a rigorous course of antibiotics, which usually clears the illness.
However, 那些被认为是长期患者，在抗生素治疗结束后莱姆病症状仍在继续, 这种情况是一种以疲劳为特征的慢性疾病, muscular pain, insomnia, depression and cognitive difficulties, such as trouble with concentration and memory. 这些个体通常没有明显的临床或实验室证据表明正在发生的问题.
为了确定他们所怀疑的大脑功能的长期变化，这些变化可能导致某些持续的莱姆病症状, 约翰霍普金斯医学院神经病学、精神病学和行为科学系的研究人员, in collaboration with the Lyme Disease Research Center, used functional MRI (fMRI) scans of the brain, a technology that detects changes in brain blood flow. 这些扫描使研究人员能够实时跟踪大脑的变化.
“治疗后莱姆病症状的客观生物学测量通常不能用常规的核磁共振成像来识别, CT scans, or blood tests,” says researcher John Aucott, M.D., 约翰霍普金斯莱姆病临床研究中心主任，约翰霍普金斯大学医学院医学副教授. “We needed to expand our methods of evaluation,” he adds.
Spearheaded by lead author Cherie Marvel, Ph.D., 研究小组招募了12名治疗后的莱姆病患者, and 18 participants without a history of Lyme, to undergo fMRI scans while performing a short-term memory task.
成像测试显示额叶异常活动, 大脑的一个区域，负责认知任务，如记忆、回忆和集中注意力. 参与者被要求记忆和回忆大写和小写字母, as well as the alphabetical order of multiple letters.
Notably, the researchers say, 图像显示了两组大脑白质中额叶活动的差异, which normally does not show up in fMRI scans, as this tissue operates with less blood flow than gray matter. White matter is crucial for moving information around the brain, 就像铁轨一样，帮助将信息传递到火车站, or gray matter.
“我们看到额叶的某些区域活动不足，而其他区域则过度活跃, which was somewhat expected,” says Marvel, an associate professor of neurology. “然而，在没有治疗后莱姆病的小组中，我们没有看到同样的白质活动.”
To confirm this finding, 研究人员对所有12名莱姆病患者和18名非莱姆病患者中的12名使用了第二种称为扩散张量成像(DTI)的成像方法. DTI检测脑组织内水运动的方向. 这种独特的方法证实了他们的fMRI发现，并揭示了新的发现:水正在扩散, or leaking, 沿着患者的轴突——神经元向其他神经元传递电信号的延伸——在fMRI中发现的相同的白质区域.
令人惊讶的是，研究人员还发现，在他们研究的治疗后的莱姆病患者中，白质轴突渗漏与较少的认知缺陷和更好的结果相关.
研究人员认为，他们在白质中看到的活动增加可能反映了治疗后莱姆病患者有益的免疫反应, as it correlated with better disease outcomes. However, 这一发现也与治疗后莱姆病患者需要更长的时间来完成记忆任务有关. 研究人员表示，这表明白质反应可能是一种适应性反应, 但是白质的生理和功能已经改变了, which could come at a cost.
“与不同领域的专家合作解决这个问题给了我们这些新发现, and will hopefully answer our remaining questions, 特别是关于轴突渗漏和白质激活在治疗后莱姆病中的作用,” she says.
Marvel和Aucott说，这项研究可能有助于阐明神经系统莱姆病的潜在机制和潜在治疗目标. 他们的发现也可能与其他类型的感染相关的慢性疾病有关, including long COVID and chronic fatigue syndrome.
该项目的资金是由一位匿名捐赠者提供给约翰·奥科特的.
The research team also includes Kylie Alm, Deeya Bhattacharya, Alison Rebman, Arnold Bakker, Jason Creighton, Erica Kozero, Arun Venkatesan, and Prianca Nadkarni of Johns Hopkins Medicine; as well as Owen Morgan who is now at Cornell University.
The authors declare no competing interests.