Lyme Neuroborreliosis

近几十年来我国痴呆症疾病负担居高不下,未来发病和死亡人数将持续上升,女性人群和老年人群疾病负担重,低龄人群发病风险急剧上升。中国疾病预防控制中心之前发表于《柳叶刀》杂志上的研究指出，痴呆已经是位列中风、缺血性心脏病、慢性阻塞性肺病、肺癌之后的第五大致死疾病。在我国，人口老龄化已经是近年来不容忽视的一个问题了。2022年《政府工作报告》中指出：中国人口老龄化规模大、程度深、速度快。2020年，我国65岁以上老龄人口已达到1.91亿，占总人口比重为13.5%，相当于全球约每4个老年人中就有一个中国人（以2022年11月15日联合国公布的80亿计算）。全球老龄化趋势  图源：搜狐网很多人都认为，目前还没有药物和办法能彻底逆转痴呆症病情，其实不然，我们平常说的老年痴呆一般是指阿尔茨海默病，它只占所有痴呆类型的60%~70%，这种类型是不可逆的。但临床中还有一些痴呆可以通过治疗逆转病情，甚至部分痴呆是可以治愈的，可达7-13%，发现并治疗后可以改写这类痴呆患者的人生。下面我们来了解一下哪些是可治性痴呆（认知障碍）及如何识别。一、哪些病因的痴呆是可以逆转1.药物相关性痴呆。药物相关性痴呆是一种可能由多种药物引起的认知障碍。这种情况可能出现在长期服用某些心血管疾病药物的患者身上，例如地高辛等。此外，抗胆碱能药物，如苯海索、阿米替林、奥昔布宁等，部分抗精神病药物，如吩噻嗪类的氯丙嗪、舒必利及利培酮等，抗癫痫药物，如妥泰、丙戊酸盐类药物、苯巴比妥等，以及某些药物（如苯二氮卓类）的相关副作用和毒品使用都可能导致认知能力明显下降。然而，通过调整用药，这种痴呆症状可以得到明显改善。2.感觉器官问题如听力减退和视力障碍可能引发认知障碍，影响信息处理和记忆。使用助听器和眼科治疗能有效改善这些症状，提升认知功能。3.有些癫痫患者可能经历认知下降或短暂性遗忘，因为癫痫发作导致认知波动。定期使用抗癫痫药物治疗可以控制癫痫，改善认知功能。4.某些代谢性疾病可能导致痴呆，如甲状腺功能减退、甲状旁腺功能亢进、肺性脑病、肝病、吸收不良、恶性贫血、酗酒，以及维生素和微量元素缺乏，尤其是维生素B1和B12缺乏引起的痴呆。通过对病因进行治疗，这些可逆转的痴呆症状可以得到改善。5.抑郁情绪导致假性痴呆。予以抗抑郁药物及配合认知行为等治疗，情绪改善后其假性痴呆可完全治愈。抑郁症是痴呆发生的独立危险因素，不及时治疗很容易发展为真正痴呆。6.正常颅压脑积水或者低颅压导致的脑下垂导致的痴呆。正常压力脑积水临床上比较常见，多是脑脊液动力学改变引起脑室周围脑组织受压引起，痴呆一般以执行功能等为主。在疾病早期，如果积水能够得到及时解决，压迫解除，脑室周围组织及时恢复正常，认知障碍往往能很好逆转。所以，当老人出现记忆力减退、运动障碍、大小便失禁等症状时，切勿简单认定就是老年痴呆病。其实脑积水很容易辨别，去医院做一个脑部CT就能筛查。图源：搜狐网+参考来源67.颅内占位性病变。如肿瘤、硬膜下血肿，行手术后认知障碍可好转。8.脑血管疾病所致的认知障碍。如蛛网膜下腔出血、房颤患者反复的栓塞导致血管性的认知障碍、血管性卒中、硬脑膜动静脉瘘。9.特殊感染性疾病所致的痴呆。如神经梅毒、艾滋病、神经莱姆病均可导致认知障碍，经相应的抗感染治疗后痴呆可得到改善。10.自身免疫性认知障碍。这是由免疫介导认知功能受损相关的一组复杂性疾病，典型的临床症状为认知受损伴有其他神经系统表现，在起病时也可仅表现为孤立的认知受损。包括自身免疫性脑炎相关的自身免疫性痴呆，类神经变性疾病相关的自身免疫性痴呆。11.睡眠障碍尤其是睡眠呼吸暂停、睡眠增多症患者，容易出现明显的记忆、反应力下降，无法胜任学习工作。给予睡眠呼吸暂停患者夜间持续正压通气持续治疗后患者睡眠、情绪障碍改善后其认知症状可以完全缓解。睡眠增多的患者可行多导睡眠监测找寻病因，对因对症治疗后也可明显改善其认知症状。二、以下警示征象可考虑逆转的痴呆： 1. 快速进展的认知下降。其中约20%是可治的。在快速进展的认知障碍的病因中自身免疫性认知障碍诊断明确后治疗效果和临床预后较好，故需注意及时识别。自身免疫性脑炎认知障碍临床提示：（1）急性/亚急性起病（数天/周），波动性或快速进展病程；（2）有很强的自身免疫性疾病个人/家族史（一级亲属）；（3）有肿瘤史，肿瘤风险因素，或近期出现不明原因体重下降；（4）病毒感染样前驱症状（如发热、恶心、呕吐和疲乏）；（5）新发癫痫或难治性癫痫；（6）系统性自身免疫疾病的血清学检测证据；（7）炎症性脑脊液发现（细胞增多、寡克隆带/高IgG指数）或炎症MRI表现（增强病灶）；（8）提示性的神经影像学异常；（9）脑电图发现癫痫样放电活动。2.发病年龄比预期年轻。3.认知水平显著波动。4.急性或慢性高风险暴露。比如在原有变性疾病或者其他颅内器质性的基础上合用高风险药物，或者酗酒、毒品、毒物暴露史都会导致认知明显下降。5.高风险行为接触史，包括过去、现在的性病史梅毒、艾滋病等。6.神经系统查体发现的无法解释或超出预期的体征的痴呆。如正常颅压脑积水性痴呆。7.当痴呆患者的认知测试结果与其临床表现不一致时，可能需要寻找可逆性痴呆的原因。对于新诊断的痴呆患者，如果他们的认知测试表现比临床病史预期的好或者差，我们应特别关注以下方面的筛查：情绪障碍、睡眠障碍、用药史、感官受损（如听力和视力），以及药物、毒物或酒精的暴露情况。这些因素都可能对痴呆患者的认知能力产生重要影响，因此值得密切关注和筛查。总之，一些因素都可能对痴呆患者的认知能力产生重要影响，并且在适当的处理下是可以改善的。了解和识别这些可逆性痴呆的原因对于提供适当的治疗和护理至关重要。然而，我们也要认识到，痴呆的可逆性可能需要综合的评估和干预，因为不同的患者有不同的特点和情况。进一步的研究和努力将有助于我们更好地理解和应对这些导致可逆痴呆的原因，为患者提供更好的照护和支持。参考来源：熊屹立,于宝乙,刘声悦,等.中国痴呆症疾病负担研究及未来预测分析[J].现代预防医学, 2023.王琼,周帅,侯芳芳,等.痴呆症的流行病学及预防措施[J].中国临床保健杂志,2021,24(06):747-751.HUANG Y,WANG Y,WANG H,et al. Prevalence ofmental disorders in China: a cross-sectional epidemiological study[J].Lancet Psychiatry，2019,6( 3) : 211-224． JIA L,QUAN M,FU Y,et al.Dementia in China: epidemiology,clinical management,and research advances[J].Lancet Neurol,2020,19( 1): 81-92．李莉霞.有些痴呆可逆转.中国医学人文,2021-03.[1]李靖.有一种"老年痴呆"是可逆的——访南京脑科医院神经外科副主任医师胡新华[J].江苏卫生保健, 2022(005):000.庄仲伟 上海科技馆 痴呆 ≠ 阿尔兹海默症，这类“老年痴呆”其实能治好仅供学习交流！授权转载及爆料请联络梅斯医学管理员，微信号：xiaoju_0328最近微信改版，经常有读者朋友错过推送，星标★ “梅斯神经新前沿”，及时接收每篇新鲜出炉的推文！● 除了他汀，还有哪些药物可以逆转动脉粥样硬化斑块？● 《中国血脂管理指南（基层版2024年）》图文梳理●小脑的解剖与定位诊断↓点击下方“阅读原文”，下载梅斯医学APP吧！

April 19, 2024 -- Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, recently announced publication of a laboratory study showing that fibroblast growth factor receptor (FGFR) inhibitors may be appropriate as anti-inflammatory supplementary treatment for neurological Lyme disease, for which there are no universally effective treatments. Published in the peer-reviewed journal Frontiers in Immunology, this study shows FGFRs are activated in response to both live and non-viable Lyme bacteria in preclinical brain tissue models. Further, inhibition of FGFR1, FGFR2, and FGFR3 may help mitigate the neuroinflammatory and neuropathogenic effects of infection by the bacteria that causes Lyme disease, Borrelia burgdorferi. “Our research shows a potential connection between neurological Lyme disease and several other neurological conditions, and this common pathway may explain why Lyme can be confused with many other conditions. Increasing our knowledge of FGFRs and their effect on the brain will help us understand the common mechanisms that may underlie Lyme disease and other neurological diseases,” said Geetha Parthasarathy, PhD, assistant professor at Tulane National Primate Research Center, Tulane School of Medicine, and a Bay Area Lyme Foundation 2019 Emerging Leader Award winner. “This data shows that FGFRs can be novel targets of anti-inflammatory therapeutics in Lyme patients with persistent neuroinflammation.” “Our findings from this and our previous studies also offer important insight that may help to explain why some patients still experience chronic neurological symptoms even after a short course of antibiotics,” added Dr. Parthasarathy. Her previous studies have shown that Borrelial remnants can be neuropathogenic in nervous tissues. In this study, Dr. Parthasarathy and her team demonstrated that FGFR receptors 1, 2, and 3 are activated in response to both live and non-viable B. burgdorferi when added to ex vivo nervous tissues and that these receptors are proinflammatory; this inflammation can lead to apoptosis, or cell death. As FGFRs are also implicated in other neurological conditions, activation of such pathways in the nervous system by Borrelial remnants can likely contribute to these neurological conditions even after removal of live infection. “Lyme neuroborreliosis, or neurological Lyme, causes the most disabling symptoms in Lyme disease, yet there has been relatively little study of the disease mechanisms caused by the infection. There has long been a question about whether the persistent neurological symptoms of Lyme disease are caused by live bacteria or bacterial remnants. This study not only answers this question by demonstrating that both live and non-viable bacteria may cause these symptoms, and also suggests that inhibition of certain FGFRs may offer a path to effective treatments,” said Wendy Adams, research grant director, Bay Area Lyme Foundation. “We desperately need treatment options for the brain fog, sleep disturbance, neuropsychiatric disorders, and memory and functional deficits that can disable people with advanced stages of Lyme,” added Adams. In this study, two research compounds, an FGFR1 inhibitor and an FGFR1-3 inhibitor, were effective in downregulating inflammation in response to live Lyme bacterium in the frontal cortex of the brain and the dorsal root ganglion. The FGFR1 inhibitor was efficacious in downregulating the inflammatory response in both the frontal cortex and dorsal root ganglion in response to non-viable Borrelia bacterial remnants, but the FGFR1-3 inhibitor was less so. FGFRs also play a role in many developmental and metabolic disorders and cancer. While there are currently FDA approved FGFR inhibitors for cancer, those drugs would most likely not be suitable for use in Lyme disease patients because of their toxicity profile. However, based on further findings in the study, the researchers believe that two biologics (such as monoclonal antibodies) may be needed to effectively curb persistent neuroinflammation and pathology in the central nervous system and peripheral nervous system of neurological Lyme patients. Funding for this study was provided by the Bay Area Lyme Foundation, with support from Project Lyme and TNPRC base grant P51 OD011104. The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and may also be passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates. Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439. The content above comes from the network. if any infringement, please contact us to modify.

Blocking certain fibroblast growth factor receptors is shown to be effective in reducing inflammation and cell death caused by neurological Lyme infection in laboratory studiesPORTOLA VALLEY, Calif., April 18, 2024 (GLOBE NEWSWIRE) -- Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, recently announced publication of a laboratory study showing that fibroblast growth factor receptor (FGFR) inhibitors may be appropriate as anti-inflammatory supplementary treatment for neurological Lyme disease, for which there are no universally effective treatments. Published in the peer-reviewed journal Frontiers in Immunology, this study shows FGFRs are activated in response to both live and non-viable Lyme bacteria in preclinical brain tissue models. Further, inhibition of FGFR1, FGFR2, and FGFR3 may help mitigate the neuroinflammatory and neuropathogenic effects of infection by the bacteria that causes Lyme disease, Borrelia burgdorferi. “Our research shows a potential connection between neurological Lyme disease and several other neurological conditions, and this common pathway may explain why Lyme can be confused with many other conditions. Increasing our knowledge of FGFRs and their effect on the brain will help us understand the common mechanisms that may underlie Lyme disease and other neurological diseases,” said Geetha Parthasarathy, PhD, assistant professor at Tulane National Primate Research Center, Tulane School of Medicine, and a Bay Area Lyme Foundation 2019 Emerging Leader Award winner. “This data shows that FGFRs can be novel targets of anti-inflammatory therapeutics in Lyme patients with persistent neuroinflammation.” “Our findings from this and our previous studies also offer important insight that may help to explain why some patients still experience chronic neurological symptoms even after a short course of antibiotics,” added Dr. Parthasarathy. Her previous studies have shown that Borrelial remnants can be neuropathogenic in nervous tissues. In this study, Dr. Parthasarathy and her team demonstrated that FGFR receptors 1, 2, and 3 are activated in response to both live and non-viable B. burgdorferi when added to ex vivo nervous tissues and that these receptors are proinflammatory; this inflammation can lead to apoptosis, or cell death. As FGFRs are also implicated in other neurological conditions, activation of such pathways in the nervous system by Borrelial remnants can likely contribute to these neurological conditions even after removal of live infection. “Lyme neuroborreliosis, or neurological Lyme, causes the most disabling symptoms in Lyme disease, yet there has been relatively little study of the disease mechanisms caused by the infection. There has long been a question about whether the persistent neurological symptoms of Lyme disease are caused by live bacteria or bacterial remnants. This study not only answers this question by demonstrating that both live and non-viable bacteria may cause these symptoms, and also suggests that inhibition of certain FGFRs may offer a path to effective treatments,” said Wendy Adams, research grant director, Bay Area Lyme Foundation. “We desperately need treatment options for the brain fog, sleep disturbance, neuropsychiatric disorders, and memory and functional deficits that can disable people with advanced stages of Lyme,” added Adams. In this study, two research compounds, an FGFR1 inhibitor and an FGFR1-3 inhibitor, were effective in downregulating inflammation in response to live Lyme bacterium in the frontal cortex of the brain and the dorsal root ganglion. The FGFR1 inhibitor was efficacious in downregulating the inflammatory response in both the frontal cortex and dorsal root ganglion in response to non-viable Borrelia bacterial remnants, but the FGFR1-3 inhibitor was less so. FGFRs also play a role in many developmental and metabolic disorders and cancer. While there are currently FDA approved FGFR inhibitors for cancer, those drugs would most likely not be suitable for use in Lyme disease patients because of their toxicity profile. However, based on further findings in the study, the researchers believe that two biologics (such as monoclonal antibodies) may be needed to effectively curb persistent neuroinflammation and pathology in the central nervous system and peripheral nervous system of neurological Lyme patients. Funding for this study was provided by the Bay Area Lyme Foundation, and TNPRC base grant P51 OD011104. About Lyme disease The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and may also be passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates.  About Bay Area Lyme Foundation Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439. Media contact:  Tara DiMilia  Phone: 908-369-7168  Tara.DiMilia@tmstrat.com