Prospective Longitudinal 1-year Study of the Correlation Between Cognitive Functioning in Patients With Clinically Isolated Syndrome Suggestive of Multiple Sclerosis and Disconnection in the Brain Assessed by MRI

Study Overview
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Brief Summary
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Clinically isolated demyelinating syndromes (CIS) can evolve into multiple sclerosis (MS). Cognitive deficiencies could occur at this early stage and concern mainly information processing speed (IPS) and their mechanisms are not fully understood. Diffusion Tensor Imaging (DTI) can help in the understanding of these mechanisms.

Detailed Description
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This is a prospective cohort, observational, longitudinal, monocentric study. This study will include 60 patients with CIS followed for 1 year and 60 healthy subjects.

Official Title
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Prospective Longitudinal 1-year Study of the Correlation Between Cognitive Functioning in Patients With Clinically Isolated Syndrome Suggestive of Multiple Sclerosis and Disconnection in the Brain Assessed by MRI:SCI-COG Study

Conditions
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Multiple Sclerosis, Clinically Isolated Demyelinating Syndromes, Cognitive Deficiencies, Brain MRI

Intervention / Treatment
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* Other: Brain MRI - Clinical and cognitive evaluation
* Other: Eye movement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: Men and Women ≥16 years Fluent French speaker 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 at least 3 mm, at least one of which being cerebral, ovoid, or periventricular Having a medical insurance Free and informed consent signed Controls: Men and Women ≥18 years Fluent French speaker Having a medical insurance Free and informed consent signed Exclusion Criteria: Patients: Prior documented neurological episode suggestive of MS. Other ongoing neurological diseases. Known chronic systemic diseases as judged by the investigator (for instance: lupus, Gougerot-Sjögren, sarcoidosis, sclerodermia, Crohn disease,…). Other causes (trauma, tumor, radiotherapy, infections, vascular diseases, neuromyelitis optica). Current dependence on alcohol or drugs. Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment less than 15 days MRI contra-indications. Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily. Controls: Known chronic psychiatric or neurologic diseases which could interfere with neuropsychological testing, not taking into account stable and mild depressive syndrome Known chronic systemic diseases as judged by the investigator (for instance: lupus, Gougerot-Sjögren, sarcoidosis, scleroderma, Crohn disease…). MS familial history Current dependence on alcohol or drugs Known cognitive impairment Prior neuropsychological testing with the same tests less than one year Dosage change, stop or start of hypnotic or anxiolytic or antidepressive treatment less than 2 months Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily. MRI contra-indications Steroid treatment less than one month (be taken orally or by infusion) at the dosage of 500mg daily.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient<br>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 | Other: Brain MRI - Clinical and cognitive evaluation<br>* Clinical evaluation (EDSS, MSFC) Cognitive evaluation with tests of information processing speed, attention, working memory, episodic memory and executive functions, assessment of confounding factors (depression (BDI) and anxiety (HAD), mood (EHD), fatigue (M-FIS) and assessment of quality of life (SEP-59) Brain MRI (3 Tesla): FLAIR, 3D MPRAGE T1 and DTI<br>Other: Eye movement<br>* Assessment of eye Movements (EyeBrain software) for only the group of 15 healthy subjects at baseline and at 12 months<br>|
| Experimental: Control<br>healthy subject | Other: Brain MRI - Clinical and cognitive evaluation<br>* Clinical evaluation (EDSS, MSFC) Cognitive evaluation with tests of information processing speed, attention, working memory, episodic memory and executive functions, assessment of confounding factors (depression (BDI) and anxiety (HAD), mood (EHD), fatigue (M-FIS) and assessment of quality of life (SEP-59) Brain MRI (3 Tesla): FLAIR, 3D MPRAGE T1 and DTI<br>Other: Eye movement<br>* Assessment of eye Movements (EyeBrain software) for only the group of 15 healthy subjects at baseline and at 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between fractional anisotropy (FA) value and cognitive z scores or cognitive impairment indexes for each domains | IPS, attention, working memory, episodic memory and executive functions), established by voxel-wise statistics (TBSS) in CIS patients | visit 2 - 1 year after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of skeleton of FA between CIS patients and healthy subjects |  | V2 - 1 year after the inclusion | 
| Comparison of cognitive scores at each test between CIS patients and controls |  | D0 and V2 - 1 year after the inclusion | 
| Proportion of patients with cognitive impairment (≥ 3 tests impaired) and correlations with anxiety, depressive syndrome and fatigue |  | D0 and V2 - 1 year after the inclusion | 
| Comparison of statistical maps of FA | mean cortical thickness and deep grey nuclei volumes with cognitive indexes in the 3 pre-define groups: cognitively preserved CIS patients at baseline and after one year; cognitively impaired CIS patients only after one year and cognitively impaired CIS patients at the two evaluations. | D0 and V2 - 1 year after the inclusion | 
| Correlations between cognitive scores and mean cortical thickness and deep grey nuclei volumes in CIS patients |  | D0 and V2 - 1 year after the inclusion | 
| Comparison of cognitive scores at each test and eye movements scores |  | D0 and V2 - 1 year after the inclusion |