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Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Conditions: Multiple Sclerosis
Interventions: imaging of energy dysfunction
Countries: France
In multiple sclerosis (MS), the sequence of events leading to irreversible neuro-axonal degeneration, which is a major determinant of clinical disability, is poorly understood. Recently, the key role of neuronal energy dysfunction in driving axonal degeneration has been highlighted. In the neuronal injury pathway triggered by inflammation and myelin disruption, multiple adaptive changes force the neuron to a temporary condition of "virtual hypoxia", characterized by a mismatch between energy demand and supply. If this condition of energy dysregulation is not reversed within an appropriate time-window, neurons enter an irreversible axonal degeneration. Two key questions on the relationship between early energy dysregulation and neurodegeneration remain unanswered: i) whether brain energy dysfunction measured at a given time point can predict the subsequent occurrence of neurodegeneration; ii) to what extent and for how long neurons can bear this "virtual hypoxia" before undergoing structural damage. Tracking the "energetic signature" of MS and defining its temporal distance from irreversible damage is essential for the development of neuroprotective therapies.The recent optimization of innovative magnetic resonance (MR)-based techniques such as sodium (23Na) MRI, phosphorus MR spectroscopy (31P-MRS), and diffusion-weighted 1H MRS (DW-MRS) has allowed the generation of promising in vivo data on cellular energy dysregulation in MS. The main objective of this project is to explore whether MR-derived metrics of energy dysregulation predict MR-derived parameters of cortical neurodegeneration developing over 2 years, as reflected by cortical atrophy. To address this key question, the Investigators will use a combination of 23Na MRI, 31P MRS, and DW-MRS associated with advanced MRI sequences to explore energy dysregulation in the sensorimotor region, and measurements of cortical atrophy in the same area after 24 months in 40 patients with either relapsing-remitting or progressive MS and 15 age- and gender-matched healthy controls. The Investigators will also test whether MR-derived metrics of energy dysregulation at study entry correlate, both cross-sectionally and longitudinally, with: i) global cortical atrophy; ii) functional cortical reorganization resulting from the condition of energy dysregulation, which precedes the occurrence of structural damage; iii) cortical demyelination and remyelination; iv) clinical, neuropsychological and biological measures.
Sex: ALL
Age: 18 Years to 55 Years
Healthy volunteers: Yes
Study type: INTERVENTIONAL
Inclusion Criteria for MS: 1. RR-MS patients with a disease duration of less than 10 years: * 18-55 years * clinically defined RR-MS according to the 2017 revised McDonald's criteria (MS diagnostic criteria 2017) * disease duration \<10 years * ability to understand the research objectives and the procedure details, and to sign the informed consent * affiliation with the French National Health Insurance, Universal Medical Coverage (CMU) or any equivalent 2. Patients with progressive MS (primary or secondary) of less than 10 years: * 18-55 years * clinically defined progressive MS according to the 2017 revised McDonald's criteria * disease duration \<10 years from the beginning of the progressive phase * ability to understand the research objectives and the procedure details, and to sign the informed consent * affiliation with the French National Health Insurance, Universal Medical Coverage (CMU) or any equivalent Inclusion Criteria for healthy controls: * 18-55 years (matched with patients) * no known general pathologies * ability to understand the research objectives and the procedure details, and to sign the informed consent * affiliation with the French National Health Insurance, Universal Medical Coverage (CMU) or any equivalent Exclusion Criteria for MS: * Pregnant or breastfeeding women * Last infusion of cyclophosphamide, mitoxantrone or methylprednisolone realized less than 1 month before inclusion * last clinical relapse less than one month before inclusion * severe cardiac, pulmonary, hepatic, hematologic renal, gastrointestinal disease, or cancer * contraindications to MRI: claustrophobia, pace-maker implant, any surgical ferromagnetic clips, ocular implants, any intraocular or intracranial metallic fragments, any metallic objects able to concentrate the radiofrequency field, cochlear implants, cardiac or brain stimulators, any tattoos or permanent makeup on the face, renal failure (exclusion criterion for gadolinium injection) patients not willing to be informed of any possible cerebral malformations incidentally discovered at the MRI exam * severe renal failure (clearance of creatinine \< 30ml/min) * history of allergic reactions to gadolinium salts * any other chronic neurological disorders associated * persons deprived of liberty by law or by administrative decision * Persons under legal protection Exclusion Criteria for healthy controls: * Pregnant or breastfeeding women * severe cardiac, pulmonary, hepatic, hematologic renal, gastrointestinal disease, or cancer * contraindications to MRI : claustrophobia, pace-maker implant, any surgical magnetic clips, ocular implants, any intraocular or intracranial metallic fragments, any metallic objects able to concentrate the radiofrequency field, cochlear implants, cardiac or brain stimulators, any tattoos or permanent makeup on the face * person not willing to be informed of any possible cerebral malformations incidentally discovered at the MRI exam * associated chronic neurological disorders * persons deprived of liberty by law or by administrative decision * Persons under legal protection
- Paris, France