Multicenter Prospective Study Analyzing the Occurrence of Multiple Sclerosis Relapses Without Radiological Evidence: Myth or Reality?

Condition(s) studied

Investigational drug(s) / intervention(s)

Early Cerebro-spinal MRI: 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.

Biomarker Assessment: 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

Clinical and Neuropsychological Evaluations: 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.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Proportion of RRMS Patients with Absence or Presence of Gadolinium-Enhancing Lesion(s) on Brain and Spinal Cord MRI — performed between Day 0 and Day 6
  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.

Trial sites (8)

More University Hospital, Strasbourg, France trials in France

Other trials for the same condition