Window On the Brain: Diagnostic, Therapeutic, and Prognostic Sonication of Patients With Disorders of Consciousness
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 4
- 主要终点
- Brain ultrasonography measures
研究概览
简要总结
Disorders of consciousness (DOC) diagnosis suffers from the difficulty to measure the level of consciousness due to the variability associated with behavioural assessments and the difficulty in detecting the residual level of consciousness in patients who do not show any behavioural signs during the behavioural assessment. This issue could be overcome by using instrumental tools, that are expensive and not always available in clinical settings. The ultrasound-based techniques could represent a valid low-cost and more feasible alternative to deep the knowledge about physio-pathological mechanisms underlying DOC and their chronicization. These techniques could be tailored to treat acute and chronic DOC patients from a personalised medicine perspective. Improving the knowledge, management and care pathways of DOC patients and finding new therapeutic options would benefit not only patients but also public health systems.
详细描述
After acquired brain injuries, Disorders of Consciousness (DOC) may occur and persist for up to many years. DOC range from Unresponsive Wakefulness Syndrome (UWS; presence of reflexive behaviours) to the emergence from Minimally Conscious State (eMCS; presenting signs of functional communication and/or object use). A correct diagnosis affects the legal decisions, prognosis, and potential therapeutic and rehabilitative interventions. Although DOC diagnosis relies on behavioural assessment (Coma Recovery Scale-Revised; CRS-R), several studies highlight the importance of instrumental tools (e.g., neuroimaging and electrophysiology) for improving diagnosis and prognosis despite their complexity, high costs, and low availability. The ultrasound techniques can represent a valid alternative, allowing both to acquire bedside structural and functional data with low costs and less invasiveness, and perform stimulation to boost consciousness improvement and/or recovery. However, limited evidence exists to date about the use of ultrasound techniques for clinical characterization of DOC patients, and only one registered trial is exploring the effectiveness of ultrasound stimulation for consciousness recovery in this clinical population. For these reasons, we aim to explore the brain functioning and morphology with direct ultrasound (US) in DOC patients, providing both anatomical and functional information in real-time. Specifically, the measures extracted from US examination might provide data regarding DOC's physiopathology in a bedside and affordable manner. Moreover, although clinical trials with low-intensity ultrasound modulation of subcortical structures and thalamic nuclei are already in progress, targeting is still empirical. Thus, understanding US parameters in DOC could provide the ground to improve deep brain structures' targeting, tailoring low-intensity ultrasound parameters according to patient's specific needs for improving their level of consciousness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria:
- •an established diagnosis of DOC (UWS or MCS according to the CRS-R criteria and/or a CRS-R total score ≤22) following severe acquired brain injury;
- •age>18 years old;
- •written informed consent obtained from each patient's representative.
排除标准
- •previous psychiatric, neurological, or drug abuse history;
- •on-going mechanical ventilation.
- •From the population enrolled for aim 1, we plan to select ten patients
- •Inclusion criteria:
- •18<age<65 years;
- •medical stability over the previous 30 days;
- •presence of the following US variables: low brain stiffness, high elasticity, and adequate level of tissue perfusion;
- •written informed consent obtained from each patient's representative;
- •structural integrity of both thalami as assessed by MRI.
- •Exclision criteria:
- •contraindications to MRI examination;
- •presence of decompressive craniectomy or cranioplasty performed within 30 days;
- •presence of epileptogenic features on the EEG and/or drug resistant epileptic crisis history;
- •presence of severe muscoloskeletal impairments which are likely to interfere with the correct positioning required for the intervention.
研究组 & 干预措施
Chronic patients (DOC duration >=1 year)
- Assessment with US technique to characterized the pathophysiological features of chronic DOC
- For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention:
Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices
干预措施: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention (Device)
Post-acute patients (DOC duration <1 year)
- Assessment with US technique to characterized the pathophysiological features of post-acute DOC and explore its predictive value for chronicization
- For the Interventional part of the project, the selected patients in this arm will be treated with a single session of US neuromodulation and the following measures will be collected before and after the intervention:
Coma Recovery Scale-revised; Resting state fMRI; EEG-based neurophysiological indices
干预措施: Ultrasound technique for diagnosis; Focused Ultrasound Stimulation for intervention (Device)
结局指标
主要结局
Brain ultrasonography measures
时间窗: T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients)
These data are based on ultrasound parameters extracted from the ultrasound assessment protocol
次要结局
- Level of Consciousness(T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients))
- Neuroendocrine, inflammatory, and nutritional markers derived from a blood sample(T0 (time of enrolment))
- EEG connectivity measures(T0 (time of enrolment))
- Coma-to-Community outcome measures(T0 (time of enrolment) and T1 (at 6 months from the enrolment for the chronic patients; at 1 year from the acute event for the post-acute patients))