Prognosis Value of the Neuronal Damage in Early Multiple Sclerosis
Prognosis Value of the Neuronal Damage in Early Multiple Sclerosis
In this study the investigators will use PET and 11C-Flumazenil to visualize and quantify
 neuronal injury in the cortex and the deep gray matter of Multiple Sclerosis patients at an
 early stage. The investigators will follow up patients to determine the prognostic value of
 this neuronal injury.
It is now well admitted that multiple sclerosis (MS), which is an inflammatory demyelinating
 disease of the central nervous system (CNS) is not restricted to white matter, but also
 involves grey matter, either the cortex or the deep grey matter. The progression of grey
 matter atrophy measured by MRI during disease course represents an interesting prognosis
 marker for long term progression, but this marker lack sensitivity and is hard to interpret
 at the individual level.

 In the EAE animal models, an early neuronal damage has been described, characterized both by
 a synaptic and dendritic loss and by a neuronal apoptosis.

 These data strongly suggest that the occurrence of an early neuronal damage during MS course
 could represent a major prognosis marker. Therefore there is a crucial need for the
 development of imaging techniques, aimed at visualizing and quantifying neuronal damage in
 early MS. To date MRI techniques are not able to specifically assess neuronal pathology in
 vivo.

 In this prospective project we will determine the chronology of appearance and the prognosis
 value of the neuronal damage measured by PET with 11C-Flumazenil, concerning further grey
 matter atrophy progression and disability progression among a cohort of MS patients with
 recent onset.

 Four groups of subjects will be included: i) patients with a RRMS evolving since less than 5
 years (revised Mc Donald criteria, n=20); ii) patients with a RRMS evolving since more than 5
 years and less than 10 years (n=20); iii) patients with a primary progressive MS (PPMS)
 evolving since less than 10 years (n=20); iv) Healthy volunteers matched for age and sex (2/3
 matched with RRMS patients; 1/3 matched with PPMS patients).

 Each subject will pass a neurologic examination, a neuropsychological testing, a first PET
 examination with 11C-Flumazenil, a multimodal MRI, with conventional sequences (3DT1, 3D T2
 and FLAIR, pre and post contrast T1) and non conventional sequences (MTR, DTI, protonic
 spectroscopy).

 All patients will be followed prospectively with one visit/year consisting in clinical
 neurological, and neuropsychological evaluations as well as multimodal MRI.

 For healthy volunteers a second PET 11C-Flumazenil will also be performed to assess
 reproducibility and evolution (50% after 1 month, 50% after 1 year).

 This study will allow to assess on a larger sample followed prospectively (5 years) the
 prognosis value of abnormalities detected and quantified by PET with 11C-Flumazenil on
 further grey matter atrophy progression on MRI and disability progression (EDSS, MSFC,
 cognitive status). It will also precise the chronology of appearance and the evolution of
 neuronal damage in MS, and determine the reproducibility of this technique. Results should
 provide a new and more efficient prognosis marker for early MS.
Inclusion Criteria:

 Four groups of subjects will be included:

 -  patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria,
 n=20);

 -  patients with a RRMS evolving since more than 5 years and less than 10 years (n=20);

 -  patients with a primary progressive MS (PPMS) evolving since less than 10 years
 (n=20);

 -  Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3
 matched with PPMS patients).

 Exclusion Criteria:

 -  Lack of social insurance

 -  Pregnancy

 -  Age > 55

 -  Therapy with benzodiazepine