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

NCT07545889 | Not Yet Recruiting

• 1 other identifier: RC25_0053
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Multiple Sclerosis; RRMS; Multiple Sclerosis (MS) - Relapsing-remitting

Keywords

Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis; Acute Clinical Events with Stable MRI (ACES); Gadolinium-enhancing lesions; MRI-negative relapse; Functional Neurological Disorder; Pseudo-relapse

Outcome Measures

Primary Outcomes (1)

• 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.

  performed between Day 0 and Day 6

Study Arms (1)

RRMS Patients with Acute Neurological Exacerbations

EXPERIMENTAL

Other: Early Cerebro-spinal MRI; Diagnostic Test: Biomarker Assessment; Diagnostic Test: Clinical and Neuropsychological Evaluations

Interventions

Early Cerebro-spinal MRI OTHER

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.

RRMS Patients with Acute Neurological Exacerbations

Biomarker Assessment DIAGNOSTIC_TEST

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

RRMS Patients with Acute Neurological Exacerbations

Clinical and Neuropsychological Evaluations DIAGNOSTIC_TEST

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.

RRMS Patients with Acute Neurological Exacerbations

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult aged 18 to 70 years.
• Relapsing-Remitting Multiple Sclerosis according to the McDonald 2024 criteria.
• Patient receiving disease-modifying therapy (DMT) for multiple sclerosis.
• Most recent EDSS score between 0 and 7.0, dating back less than 1 year.
• Patient presenting with a neurological exacerbation lasting more than 24 hours and less than 7 days (excluding fatigue and pain alone).
• Patient capable of understanding the objectives and risks associated with the study and who has provided informed consent.
• Patient affiliated with or a beneficiary of a social security health insurance scheme.

You may not qualify if:

• Primary progressive or secondary progressive multiple sclerosis.
• Diagnosis of chronic psychotic disorder.
• Infection within the past week.
• Body temperature \> 38.5°C at V0 (baseline visit).
• Chronic treatment with corticosteroids or immunosuppressants for another pathology.
• Contraindication to MRI or gadolinium.
• Uncontrolled cardiac, renal, or hepatic pathology.
• Pregnant or breastfeeding woman.
• Severe claustrophobia.
• Patient deprived of liberty (e.g., incarcerated).

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (8)

Hospices Civils de Colmar

Colmar, 68024, France

Location

CHU de Dijon Bourgogne

Dijon, 21079, France

Location

Centre Hospitalier de Haguenau

Haguenau, 67504, France

Location

Chr Metz-Thionville

Metz, 57085, France

Location

Grpe Hosp Region Mulhouse & Sud Alsace

Mulhouse, 68051, France

Location

CHU de Nancy

Nancy, 54035, France

Location

Chu Reims

Reims, 51092, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67098, France

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Conversion Disorder

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Somatoform Disorders; Mental Disorders

Central Study Contacts

Kévin BIGAUT, MCU-PH

CONTACT

+33 (0)3 88 12 85 68; kevin.bigaut@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: April 22, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 7, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)