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Thèse Aurélie Ruet

"Prédiction du diagnostic et du pronostic aux stades précoces de Sclérose en Plaques"

Le 7 novembre 2012

"Diagnostic and Pronostic Predictors in the Early Stages of Multiple Sclerosis"

Multiple sclerosis (MS) is the most frequent chronic, disabling, non-traumatic neurologic disease of young adults in France. Relapsing-remitting MS (RRMS) is the most frequent phenotype of this disease. The diagnosis of RRMS is based on the demonstration of the dissemination of lesions in space and time after a first typical clinical event, which is called a clinically isolated syndrome (CIS). The 2 main objectives of this thesis were, first, to investigate predictors of an early diagnosis of MS after a typical CIS and, second, to provide support for cognitive impairment as a potentially useful prognostic marker in the early stages of MS.

The first article reported the results obtained in a retrospective study that included a homogeneous sample of 114 patients with a spinal cord CIS. The diagnosis of MS was predicted by 3 independent factors: ≤40 years of age, positive for oligoclonal bands in the cerebrospinal fluid or a raised IgG index, and ≥3 periventricular lesions at the time of the CIS.

In the second article, a confirmation of the validity of these 3 predictive factors was provided through a large prospective study that included 652 patients with a CIS, regardless of the anatomical location of the lesions. Notably, these predictive factors achieved the same accuracy as the dissemination in space criteria which were proposed in the McDonald criteria for the prediction of the diagnosis of MS. Once an MS diagnosis is established, the main challenge is to assess the severity of the disease, and early clinical predictors of long-term disability are still lacking. The anatomical substrate of the disabilities that are accumulated in MS appears primarily to be cumulative axonal loss. Cognitive impairment is frequent in MS, even at the early stages of the disease, and has been associated with MRI markers of diffuse brain damage. Therefore, cognitive impairment appears to be an interesting candidate as a prognostic factor in the early stages of MS.

In the third article, the relationship between cognitive impairment and MRI parameters reflecting early diffuse brain damage was confirmed in a 7-year longitudinal study of 44 newly diagnosed RRMS patients.

In the fourth article, the ability of the cognitive impairment detected after RRMS diagnosis in this sample of patients to predict the progression of disability over time supported the prognostic value of cognitive deficits in early MS.

In the fifth article, cognitive assessments were performed on patients with 2 clinical phenotypes of MS with different prognoses: RRMS and primary progressive MS (PPMS)The extent and the severity of cognitive deficits were greater in the 41 PPMS patients compared to the 60 RRMS patients; this finding supports the relationship between cognitive impairment and widespread brain damage.

..In the sixth article, the prognostic value of cognitive dysfunction in MS was illustrated through the negative impacts of cognitive deficits on the qualities of life and vocational statuses of 48 patients living with MS who were followed for 7 years. Finally, as cognitive deficits were shown to have the potential to predict early disability in patients with MS, and early disability is known to be relevant to predicting long-term disability in MS, the detection of cognitive deficits appears to be a priority in managing patients with MS and adapting early-stage therapeutic strategies. Information processing speed (IPS) is the main cognitive domain impaired in MS that has clinical implications.

In the seventh article, the ability of a new, in-house cognitive tool called the computerised speed cognitive test to detect lowered processing speed was assessed in a validation study using samples obtained from 101 patients with MS and 415 healthy subjects.

This test was clinically relevant and had excellent reliability, ecological validity, and predictive value for detecting IPS impairment in patients with MS.

Keywords: Multiple sclerosis, Diagnostic, Prognostic, Cognition, Information Processing Speed.


Last Publications

Cognitive impairment, health-related quality of life and vocational status at early stages of multiple sclerosis: a 7-year longitudinal study.Ruet A, Deloire M, Hamel D, Ouallet JC, Petry K, Brochet B.J Neurol. 2012 Oct 19. [Epub ahead of print]

MRI predictors of cognitive outcome in early multiple sclerosis.Deloire MS, Ruet A, Hamel D, Bonnet M, Dousset V, Brochet B.Neurology. 2011 Mar 29;76(13):1161-7. Erratum in: Neurology. 2012 Feb 21;78(8):608.

High-risk syndrome for neuromyelitis optica: a descriptive and comparative study.Collongues N, Marignier R, Zéphir H, Blanc F, Vukusic S, Outteryck O, Fleury M, Ruet A, Borgel F, Thouvenot E, Moreau T, Defer G, Derache N, Pelletier J, Audoin B, Debouverie M, Labauge P, Gout O, Camu W, Brassat D, Brochet B, Vermersch P, Confavreux C, de Seze J.Mult Scler. 2011 Jun;17(6):720-4. Epub 2011 Jan 14.

Predictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndrome.Ruet A, Deloire MS, Ouallet JC, Molinier S, Brochet B.Mult Scler. 2011 Mar;17(3):312-8. Epub 2010 Nov 11.

Long-term follow-up of neuromyelitis optica with a pediatric onset.Collongues N, Marignier R, Zéphir H, Papeix C, Fontaine B, Blanc F, Rodriguez D, Fleury M, Vukusic S, Pelletier J, Audoin B, Thouvenot E, Camu W, Barroso B, Ruet A, Brochet B, Vermersch P, Confavreux C, de Seze J.Neurology. 2010 Sep 21;75(12):1084-8.

Neuromyelitis optica in France: a multicenter study of 125 patients. Collongues N, , Ruet A,de Seze et al. J.Neurology. 2010 Mar 2;74(9):736-42.

Early cognitive impairment in multiple sclerosis predicts disability outcome several years later.Deloire M, Ruet A, Hamel D, Bonnet M, Brochet B.Mult Scler. 2010 May;16(5):581-7. Epub 2010 Mar 1.
Dernière mise à jour le 01.07.2013


Aurélie Ruet
Praticien attaché à la clinique de la Sclérose en Plaques.
Directeur de thèse:
Bruno Brochet
INSERM U.1049, Neuroinflammation
Klaus Petry

Aurélie Ruet a préparé sa thèse sous la direction de Bruno Brochet PU-PH, dans l'unité de Klaus Petry: Neuroinflammation, imagerie et thérapie de la Sclérose en Plaques. Inserm U 1049. Elle présentera : "Diagnostic and Prognostic Predictors in the Early Stages of Multiple Sclerosis".



Mme Iris-Katharina PENNER, Basel, Switzerland
Mr Jean PELLETIER, Marseille, France
Mme Maria-Pia AMATO, Florence, Italy
Mr Pierre CLAVELOU, Clermont-Ferrand, France
Mme Christine LEBRUN-FRENAY, Nice, France
Mr Bruno Brochet,Bordeaux, Directeur de thèse