An interventional study of Early Cerebro-spinal MRI and Biomarker Assessment in Multiple Sclerosis, RRMS and Multiple Sclerosis (MS) - Relapsing-remitting, sponsored by University Hospital, Strasbourg, France. Not yet recruiting at 8 sites in France. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-04-22.
Sponsored by University Hospital, Strasbourg, France · Not applicable, Interventional, and Diagnostic
The MYTH-MS study is a multicenter prospective study investigating the occurrence of clinical relapses in patients with relapsing-remitting multiple sclerosis (RRMS) in the absence of radiological activity on MRI.
While MS relapses are typically associated with gadolinium-enhancing lesions on MRI, some patients present with acute neurological symptoms without radiological correlates, referred to as acute clinical events with stable MRI (ACES). The frequency, mechanisms, and clinical relevance of these events remain unclear due to limitations in previous studies.
The primary objective is to determine the proportion of RRMS patients experiencing a relapse without gadolinium-enhancing lesions on early brain and spinal MRI. Secondary objectives include identifying clinical, radiological, biological, and psychological predictors, assessing neurologists' diagnostic accuracy, and evaluating clinical outcomes such as disability, cognition, and quality of life over a 6-month follow-up.
A total of 136 patients with recent neurological exacerbations will be included. Each participant will undergo clinical assessment, cognitive and psychological evaluation, and early MRI, with follow-up at 6 months. An ancillary study will explore blood biomarkers (NfL, GFAP, and circulating DNA) to help differentiate true inflammatory relapses from ACES.
This study aims to improve the understanding and diagnosis of MS exacerbations and to optimize patient management by reducing misdiagnosis and unnecessary treatments.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by relapses corresponding to episodes of new or worsening neurological symptoms. These relapses are typically associated with focal inflammatory activity detectable on magnetic resonance imaging (MRI) as gadolinium-enhancing lesions. However, in clinical practice, a subset of patients presents with symptoms suggestive of relapse without corresponding radiological findings, referred to as acute clinical events with stable MRI (ACES). The clinical significance, underlying mechanisms, and frequency of these events remain uncertain.
The MYTH-MS study is a multicenter, prospective cohort study designed to determine the proportion of patients with relapsing-remitting MS (RRMS) who experience a clinical relapse without gadolinium-enhancing lesions on early brain and spinal MRI. The study also aims to better characterize these events by identifying associated clinical, radiological, biological, and psychological factors.
Eligible participants are adults with RRMS presenting with recent neurological worsening suggestive of a relapse. At inclusion, patients will undergo standardized clinical evaluation, including neurological examination, disability assessment, cognitive testing, and patient-reported outcomes related to quality of life and psychological status. An early brain and spinal MRI with gadolinium injection will be performed within a defined time window following symptom onset.
The study will also assess the diagnostic performance of neurologists by comparing their clinical judgment regarding the presence of radiological activity and the likelihood of a true relapse versus a pseudo-relapse, along with their level of diagnostic confidence.
Participants will be followed for six months to evaluate clinical outcomes, including disability progression, cognitive performance, quality of life, and psychological parameters, and to assess the impact of relapse treatment according to MRI findings.
An ancillary biological study will be conducted to evaluate circulating biomarkers of neuronal and glial injury (e.g., neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], and circulating cell-free DNA). These biomarkers will be analyzed at baseline and follow-up to explore their potential role in distinguishing inflammatory relapses from ACES.
By providing a comprehensive characterization of MS exacerbations with and without radiological activity, this study aims to improve diagnostic accuracy, reduce uncertainty in clinical decision-making, and optimize therapeutic strategies in patients with RRMS.
Exclusion Criteria:
Other: Early Cerebro-spinal MRI · Diagnostic Test: Biomarker Assessment · Diagnostic Test: Clinical and Neuropsychological Evaluations
A standardized MRI of the brain and spinal cord with gadolinium injection. Performed very early during an acute neurological exacerbation, specifically between Day 0 and Day 6 (J0 to J6). To detect the presence or absence of gadolinium-enhancing lesions, which is the study's primary endpoint. Includes Susceptibility Weighted Imaging (SWI) to look for paramagnetic rim lesions and post-gadolinium FLAIR sequences to detect leptomeningeal enhancement.
Routine blood and urine tests, including CRP, blood count, and urinalysis (leukocytes, nitrites) to rule out infections that could cause a pseudo-relapse. Ancillary Study Biomarkers: For consenting patients, blood samples are collected to measure specific molecular markers: NfL (Neurofilaments): A marker of axonal damage. GFAP (Glial Fibrillary Acidic Protein): A marker of astrocytic activation. cfDNA (Cell-free DNA): Used to assess cellular stress or death
Also known as: biological markers, NfL, GFAP, and cfDNA
Standardized Scales: * EDSS (Expanded Disability Status Scale): Used to measure the degree of neurological disability at inclusion and at the 6-month follow-up. * SDMT (Symbol Digit Modalities Test) and CSCT (Computerized Speed Cognitive Test): Used to assess cognitive processing speed. Functional Disorder Screening: A specific clinical examination is conducted to identify positive signs of Functional Neurological Disorders (FND/TNF), which may mimic a relapse.
Proportion of RRMS Patients with Absence or Presence of Gadolinium-Enhancing Lesion(s) on Brain and Spinal Cord MRI
This measure evaluates the frequency of "Acute Clinical Events with Stable MRI" (ACES). Participants undergo a standardized MRI of the brain and spinal cord using gadolinium contrast medium within a strict window of 0 to 6 days following the onset of a suspected neurological relapse. The primary finding is defined as the absence of any gadolinium-enhancing lesions (which indicate active inflammation) despite the presence of clinical symptoms. Data is reported as the percentage of the total cohort meeting these criteria, assessed through a centralized radiological review using a standardized reading grid. This allows for a precise characterization of clinical relapses that lack immediate radiological confirmation.
Time frame: performed between Day 0 and Day 6
Plan to share: No
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University Hospital, Strasbourg, France