Hippocampal Microstructure Assessed by a New MRI Sequence and Episodic Memory at the Early Stage of Multiple Sclerosis: Comparison Between Patients After a Clinically Isolated Syndrome (CIS) and Controls
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Index of Neurite density (ND)
研究概览
简要总结
Clinically isolated syndrome (CIS) can evolve into multiple sclerosis. In CIS patients, episodic memory is frequently impaired. Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. A recent MRI imaging of diffusion called NODDI (Neurite Orientation Dispersion and Density Imaging) can measure specifically microstructural abnormalities and map the axons in the white matter (WM) and dendrites in the grey matter (GM). The aim of this study is to evaluate microstructural abnormalities in the dentate gyrus of the hippocampus in CIS patients compared to controls.
详细描述
Cognitive deficiencies could occur after a first clinical event of the central nervous system suggestive of MS called clinically isolated syndrome (CIS). Cognitive impairment concerned several cognitive domains including episodic memory, attention, working memory and executive functions. It is recognized the negative impact of cognitive impairment on quality of life and vocational status in patients living with MS. Slowness of information processing speed is the main cognitive dysfunction observed in MS seen at the earliest stage of the disease. Recently an international group of MS experts has explain IPS and episodic memory as the minimal cognitive assessment in patients with MS. Visuospatial and verbal episodic memory deficits have been observed in 18 to 28% of patients assessed after a CIS.
Memory disorders could be preceded by microstructural abnormalities without visible atrophy in hippocampus. A recent MRI imaging of diffusion called NODDI (Neurite Orientation Dispersion and Density Imaging) can measure specifically microstructural abnormalities and map the axons in white matter and dendrite in the gray matter. No study has used the NODDI in CIS patients and very few studies have been conducted in MS.
The hypothesis is that the dentate gyrus is the anatomical substrate of early episodic memory dysfunction in patients included after a CIS.
The identification of predictive MRI biomarker of memory impairment would be a useful and clinically relevant prognostic marker at the early stage of MS. This biomarker could contribute to determine the prognosis of the disease and could help for the monitoring of the patients in clinical practice and clinical trials.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- PATIENTS:
- •Men and Women,
- •Age 18-60 years,
- •Native French language,
- •Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially beginning multiple sclerosis (MS) whatever the mode of presentation,
- •Between 60 and 180 days from the onset,
- •At least two clinically silent lesions on their T2-weighted brain or spinal MRI scan with a size of least 3 mm, at least one of which being cerebral, ovoid, or periventricular,
- •Willing to participate and to sign informed consent.
- •- HEALTHY CONTROLS
- •Men and Women,
- •Age 18-60years,
- •Native French language,
- •Willing to participate and to sign informed consent.
排除标准
- •- PATIENTS:
- •Prior documented neurological episode suggestive of MS,
- •History of neurological disease and/or other neurological diseases,
- •Psychiatric diseases,
- •Known chronic systemic diseases as judged by the investigator,
- •Alcohol or other addiction to toxic,
- •Disabling visual or motor problems preventing participation to neuropsychological assessments,
- •Acquisition disorders : Dyslexia, Dysphasia, Dyscalculia and dyspraxia,
- •Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment less than 30 days,
- •Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, claustrophobia),
- •Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily,
- •Illiteracy, is unable to count or to read,
- •Pregnant or breastfeeding women,
- •Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).
- •- HEALTHY CONTROLS
- •History of neurological disease and/or neurological diseases,
- •Psychiatric diseases,
- •Known chronic systemic diseases as judged by the investigator,
- •Alcohol or other addiction to toxic,
- •Acquisition disorders: Dyslexia, Dysphasia, Dyscalculia and dyspraxia,
- •Known cognitive impairment or Prior neuropsychological testing with the same tests less than one year,
- •Hypnotic or anxiolytic or antidepressive treatment,
- •Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily,
- •Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, claustrophobia) or refusing MRI,
- •Illiteracy, unable to count or to read,
- •Pregnant or breastfeeding women,
- •Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).
研究组 & 干预措施
Control
50 Healthy controls
干预措施: Neuropsychological evaluation (Other)
CIS patients
Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially suggestive of multiple sclerosis (MS) whatever the mode of presentation
干预措施: Clinical assessment (Other)
CIS patients
Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially suggestive of multiple sclerosis (MS) whatever the mode of presentation
干预措施: Neuropsychological evaluation (Other)
CIS patients
Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially suggestive of multiple sclerosis (MS) whatever the mode of presentation
干预措施: Psychological evaluation (Other)
CIS patients
Clinically isolated neurological syndrome (CIS) compatible with a demyelinating inflammatory episode within the central nervous system, potentially suggestive of multiple sclerosis (MS) whatever the mode of presentation
干预措施: MRI Evaluation (Device)
Control
50 Healthy controls
干预措施: Psychological evaluation (Other)
Control
50 Healthy controls
干预措施: MRI Evaluation (Device)
结局指标
主要结局
Index of Neurite density (ND)
时间窗: At baseline (day 0)
This parameter is measured in the dentate gyrus of hippocampus from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
Index of orientation-dispersion (IOD)
时间窗: At baseline (day 0)
This parameter is measured in the dentate gyrus of hippocampus from NODDI imaging blind to the nature of the patient's group (CIS patients and controls).
次要结局
- Diffusion parameters : Index of orientation-dispersion(At baseline (day 0))
- Inflammatory activity(At baseline (day 0))
- Diffusion parameters : Neurite density(At baseline (day 0))
- Diffusion parameters : Mean diffusivity(At baseline (day 0))
- Atrophy parameters(At baseline (day 0))
- Verbal episodic memory test(At baseline (day 0))
- Information processing speed and attention score(At baseline (day 0))
- Working memory score(At baseline (day 0))
- Diffusion parameters : Fractional Anisotropy(At baseline (day 0))
- Lesion volume(At baseline (day 0))
- Visual episodic memory score(At baseline (day 0))
- Connectivity(At baseline (day 0))