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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CIS patients | Experimental | 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 |
|
| Control | Active Comparator | 50 Healthy controls |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clinical assessment | Other | Expanded Disability Status Scale (EDSS), ambulation test and Multiple Sclerosis functional composite (MSFC). Medications will be recorded. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Index of orientation-dispersion (IOD) | 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). | At baseline (day 0) |
| Index of Neurite density (ND) | 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). | At baseline (day 0) |
| Measure | Description | Time Frame |
|---|---|---|
| Diffusion parameters : Index of orientation-dispersion | This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls). | At baseline (day 0) |
| Diffusion parameters : Neurite density |
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Inclusion Criteria:
- PATIENTS:
- HEALTHY CONTROLS
Exclusion Criteria:
- PATIENTS:
- HEALTHY CONTROLS
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| Name | Affiliation | Role |
|---|---|---|
| Aurélie RUET, MD, PhD | University Hospital, Bordeaux | Principal Investigator |
| Eric FRISON, MD, PhD | University Hospital, Bordeaux | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Bordeaux - service de neurologie | Bordeaux | France |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| Neuropsychological evaluation | Other | cognitive tests exploring episodic memories, information processing speed, attention/concentration and working memory. |
|
| Psychological evaluation | Other | included questionnaires for depression, anxiety, fatigue, cognitive complaint and reserve |
|
| MRI Evaluation | Device | Diffusion including NODDI, 3DT1 with and without gadolinium, 3D-FLAIR before and after gadolinium infusion, 3D White Matter nulled-MPRAGE, 3D Double-Inversion recovery sequences-weighted imaging and Resting state functional MRI |
|
This parameter is measured in thalamus and cerebellum from NODDI imaging blind to the nature of the patient's group (CIS patients and controls). |
| At baseline (day 0) |
| Diffusion parameters : Fractional Anisotropy | This parameter is measured in dentate gyrus of hippocampus, thalamus and cerebellum from diffusion imaging blind to the nature of the patient's group (CIS patients and controls). | At baseline (day 0) |
| Diffusion parameters : Mean diffusivity | This parameter is measured in dentate gyrus of hippocampus, thalamus and cerebellum from diffusion imaging blind to the nature of the patient's group (CIS patients and controls). | At baseline (day 0) |
| Atrophy parameters | Normalized total brain volume and normalized total WM and total GM volumes and in hippocampus, thalamus and cerebellum from 3D-T1, 3D-DIR, 3D-WMn-MPRAGE in CIS patients and controls in double-blind. | At baseline (day 0) |
| Lesion volume | Normalized volume of lesions double-blind measured by a semi-automatic method based on 3 D Fast Fluid-attenuated inversion-recuperation (3D-FLAIR) and 3 D Double Inversion Recovery (3D-DIR) in whole brain and in the hippocampus, thalamus and cerebellum. | At baseline (day 0) |
| Inflammatory activity | The inflammatory activity will be the number of T1-gadolinium enhancing lesions in whole brain and in the hippocampus, thalamus and cerebellum. | At baseline (day 0) |
| Connectivity | The seed-based connectivity is measured between hippocampus and others cerebral regions (Thalamus, cerebellum…) from Diffusion Tensor Imaging (DTI) and resting state functional imaging. | At baseline (day 0) |
| Verbal episodic memory test | California Verbal Learning Test-Second version (CVLT-II) | At baseline (day 0) |
| Visual episodic memory score | Brief Visual Memory Test-Revised (BVMT-R) and Memonic Similarity Task (MST) : visuospatial memory tests (2 scores pour BVMT-R, 3 scores pour MST) | At baseline (day 0) |
| Information processing speed and attention score | Computerized Speed Cognitive Test (CSCT) and TAP | At baseline (day 0) |
| Working memory score | Paced-Auditory-Serial-Addition-Test (PASAT) and span | At baseline (day 0) |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |