A Window Into the Mind-brain-body Interplay: Development of Diagnostic, Prognostic Biomarkers and Rehabilitation Strategies in Functional Motor Disorders

Michele Tinazzi, MD, PhD3 个研究点分布在 1 个国家目标入组 450 人开始时间: 2023年5月31日最近更新: 2024年3月26日

适应症

试验速览

阶段: 不适用
状态: 招募中
发起方
入组人数: 450
试验地点: 3
主要终点: Simplified Functional Movement Disorders Rating Scale (S-FMDRS) score

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Functional motor disorders (FMD) are prevalent and highly disabling conditions characterized by abnormal movements (functional weakness, tremor, dystonia) significantly altered by distractive manoeuvres and incongruent with movement disorders seen in specific neurological diseases. FMDs are still misunderstood, diagnosed with delay, and not adequately treated, leading to reduced independence and high healthcare costs. Symptoms are physiologically associated with voluntary movement (distractibility, resolution with placebo) but are reported as involuntary. How this happens is yet a matter of debate. Identifying diagnostic and prognostic disease-specific biomarkers is an unmet need. The investigators will investigate motor, exteroceptive and interoceptive domains in a large cohort of FMD patients by a comprehensive set of behavioural, neurophysiological, and MRI tests. Ad-hoc eXplainable Artificial Intelligence (XAI) methods will develop disease-specific diagnostic and prognostic biomarker algorithms.

详细描述

Functional motor disorders (FMD) are part of the broad spectrum of functional neurological disorders characterized by abnormal movements (functional limb weakness, tremor, dystonia) significantly altered by distractive manoeuvres and incongruent with movement disorders seen in specific neurological diseases. FMDs have a high prevalence, are still misunderstood, diagnosed with a long delay, and not adequately treated, leading to high degrees of disability and poor quality of life with increasing social and economic costs. The old concept of psychological factors as the primary cause (conversion disorder) has been abandoned due to the lack of evidence about their causal role. According to a predictive coding account, the emerging idea is that symptoms and disability in FMD may depend on dysfunctions of a specific neural system integrating interoception, exteroception, and motor control. The idea underpins the investigator's proposal that FMD symptoms are perceptions of the state of the body. Besides the main pathophysiological features (abnormal attentional focus, beliefs/expectations, and sense of agency), the lived experience of symptoms and their resulting disability may depend on a specific neural system integrating motor, exteroceptive and interoceptive domains. Therefore, dysfunction within this system can cause and sustain motor and non-motor symptoms in FMD. Three-stage research will be conducted. A large cohort of patients with a definite diagnosis of FMD (n=150) and healthy controls (n=150) will be investigated by behavioural, neurophysiological, and MRI tests to collect biomarkers in the motor, exteroceptive and interoceptive domains. Computational modelling of the behavioural, neurophysiological, and MRI biomarkers will be developed through eXplainable Artificial Intelligence (XAI) methods through a data mining approach (machine learning) to implement a diagnostic algorithm biomarker (objective 1). A cohort of patients with "organic" motor disorders (n=75) will undergo the same behavioural, neurophysiological, and MRI tests belonging to the resulting biomarker-based diagnostic algorithm for validation (objective 2). Finally, the modulation of the resulting biomarker-based diagnostic algorithm after rehabilitation and the correlations of motor and non-motor symptoms (NMSs) with clinical improvement will be investigated in a sub-group of patients with FMD to explore the predictive value (objective 3). Our proposal consists of 6 work packages (WP), all integrated to deliver our stated objectives over the project's lifetime to achieve these objectives. Communication and dissemination activities will include the project's visual identity, public website, social media, videos, and press releases. Our proposal will inform the research and clinical community on disease-specific biomarkers for diagnosing and prognosis patients with FMD. The proposed approach has significant potential to disentangle some of the poorly understood features of these disorders, potentially providing a platform for more fundamental insights into brain functioning and the development of precision medicine approaches in their management. The proposed approach can also give the clinicians validated examinations to make a correct early diagnosis. This will improve the management of FMD with a positive impact on the patient's disability and the socio-economic costs of the illness.

研究设计

研究类型: Observational
观察模型: Cohort
时间视角: Prospective

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

未提供

排除标准

未提供