A Unified Mechanism for Functional Neurological Symptoms

功能性神经症状的统一机制

• 批准号: MR/M02363X/1
• 负责人: Mark Edwards
• 金额: $ 84.35万
• 依托单位: St George's, University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM02363X%2F1
• 关键词: Unified; Mechanism; Functional; Neurological; Symptoms

From the earliest medical records to the present day, doctors have separated out a group of patients from those with a typical "organic" cause for their physical symptoms. These patients have had many labels: "hysteria","conversion", "medically unexplained", "functional". Patients with functional symptoms are seen across primary care and all medical specialities, but are particularly common in neurological practice. Here they make up about 16% of those seen in neurology outpatient clinics, making functional neurological symptoms (FNS) one of the commonest diagnosis of neurology outpatients. People with these symptoms are, as a group, as disabled and experience as poor a quality of life as patients with Parkinson's disease or multiple sclerosis. Despite this, clinical services for such patients are poorly developed, research into causes of symptoms and treatment is very limited, and attitudes in society and within medicine to patients with functional symptoms are often poor.With this work, we want to test a new theory for how functional symptoms can arise from the brain. One of the difficulties in understanding functional symptoms is that the brain and the rest of the nervous system appears to be intact, despite severe symptoms. Indeed in patients with some types of symptoms, for example people with limb weakness, it is possible to demonstrate on examination that the apparently weak limb can generate normal power, even though the patient cannot get this to happen him or herself. We believe it is vitally important for research and development of better diagnosis and treatment for us to understand how functional symptoms are produced by the brain. We have previously developed a theory that we believe provides a reasonable mechanism for how symptoms are produced. We have already gathered evidence that supports this theory in patients who have functional symptoms affecting movement (e.g. weakness, tremor) and sensation (e.g. numbness). We now want to move forward and test if this theory can also account for symptoms experienced by people with chronic fatigue syndrome and non-epileptic attack disorder. Chronic fatigue syndrome is a disabling condition characterised by persistent fatigue in the absence of a clear medical cause. We believe that fatigue in chronic fatigue syndrome may occur because of abnormal activation of a network of structures in the brain that are usually involved in signalling the presence of infection and inflammation in the body and which give rise to a common set of symptoms experienced by everyone (and indeed across species) when infection or inflammation occur (known as the "sickness response"). This sickness response is usually short-lived, but we believe that the system could be abnormally activated in people with chronic fatigue syndrome in the absence of any ongoing infection or inflammation in the body. Non-epileptic attack disorder is a common cause of fit-like episodes which can be prolonged and very frequent. We know that these attacks are different from epilepsy, as there is no epileptic activity on brainwave (EEG) recordings performed during such attacks, but it is not known what is happening in the brain prior to and during attacks that could be responsible for the symptoms. We believe that changes in the brain's focus of attention in an abnormal way towards the body is an important part of triggering the attacks, and we will test this in our study.If our theory is correct, then when people get better with treatment then we should see corresponding changes in the way the brain is working. We will therefore test if particular aspects of brain function which our theory predicts are involved in generating functional symptoms become more normal when people with functional symptoms go through successful treatment. This would be a key step in proving or disproving our theory for how functional symptoms can be produced by the brain, and will help with future treatment development.

从最早的医疗记录到今天，医生已经将一组患者从那些典型的身体症状的“有机”原因中分离出来。这些患者有很多标签：“歇斯底里”、“皈依”、“医学解释不清”、“功能性”。有功能性症状的患者在初级保健和所有医学专科都可以看到，但在神经科实践中尤其常见。在这里，它们约占神经科门诊患者的16%，使功能性神经症状(FNS)成为神经科门诊患者最常见的诊断之一。有这些症状的人作为一个群体，与帕金森氏症或多发性硬化症患者一样残疾，生活质量也很差。尽管如此，为这类患者提供的临床服务还很落后，对症状原因和治疗的研究非常有限，社会和医学界对功能性症状患者的态度往往很差。通过这项工作，我们想要测试一种新的理论，即功能性症状是如何从大脑产生的。理解功能性症状的困难之一是，尽管症状严重，但大脑和神经系统的其余部分似乎完好无损。事实上，在有某些类型症状的患者中，例如肢体无力的人，在检查时可能会证明，表面上脆弱的肢体可以产生正常的能量，即使患者自己无法做到这一点。我们认为，了解大脑是如何产生功能性症状的，对于研究和开发更好的诊断和治疗至关重要。我们之前已经提出了一种理论，我们认为该理论为症状的产生提供了一种合理的机制。我们已经收集了支持这一理论的证据，这些患者具有影响运动(例如虚弱、震颤)和感觉(例如麻木)的功能性症状。我们现在想要进一步测试这一理论是否也能解释患有慢性疲劳综合症和非癫痫发作障碍的人所经历的症状。慢性疲劳综合症是一种致残状态，其特征是在没有明确的医学原因的情况下持续疲劳。我们认为，慢性疲劳综合症中疲劳的发生可能是因为大脑中一个结构网络的异常激活，这些结构通常涉及到体内感染和炎症的存在，并在感染或炎症发生时引起每个人(甚至跨物种)都经历的一系列共同症状(称为“疾病反应”)。这种疾病反应通常是短暂的，但我们认为，在身体没有任何持续感染或炎症的情况下，慢性疲劳综合征患者的系统可能会异常激活。非癫痫发作障碍是发作样发作的常见原因，这种发作可能会持续很长时间，而且非常频繁。我们知道，这些发作与癫痫不同，因为在此类发作期间进行的脑波(EEG)记录中没有癫痫活动，但尚不清楚发作前和发作期间大脑中发生的可能导致这些症状的变化。我们认为，大脑注意力向身体异常集中的变化是引发攻击的重要部分，我们将在研究中对此进行测试。如果我们的理论是正确的，那么当人们通过治疗好转时，我们应该会看到大脑工作方式的相应变化。因此，我们将测试，当有功能性症状的人经过成功的治疗后，我们理论预测的与产生功能性症状有关的大脑功能的特定方面是否会变得更加正常。这将是证明或反驳我们关于大脑如何产生功能性症状的理论的关键一步，并将有助于未来的治疗开发。

项目成果

Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders.

• DOI: 10.1001/jamaneurol.2018.1264
• 发表时间: 2018-09-01
• 期刊: JAMA neurology
• 影响因子: 29
• 作者: Espay AJ;Aybek S;Carson A;Edwards MJ;Goldstein LH;Hallett M;LaFaver K;LaFrance WC Jr;Lang AE;Nicholson T;Nielsen G;Reuber M;Voon V;Stone J;Morgante F
• 通讯作者: Morgante F

Functional neurological symptoms: welcome to the new normal.

功能性神经系统症状：欢迎来到新常态。

• DOI: 10.1136/practneurol-2015-001310
• 发表时间: 2016
• 期刊: Practical neurology
• 影响因子: 2.8
• 作者: Edwards MJ

A Preliminary Report of Physiological and Perceptual Changes during Exercise in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

肌痛性脑脊髓炎/慢性疲劳综合征患者运动期间生理和知觉变化的初步报告

• 发表时间: 2018
• 作者: Allington AE