Acute Disseminated Encephalomyelitis, Encephalitis Autoimmune
Conditions
Brief summary
Acute disseminated encephalomyelitis (ADEM) is a neuroinflammatory disorder of the central nervous system, manifesting itself as impaired consciousness, even to the point of coma, and multifocal neurological deficits. ADEM is the most common encephalitis in children. Moreover, 50-65% of ADEM in children is associated with the presence of anti-MOG antibodies (MOGAD). In fact, ADEM is the most frequent clinical presentation of MOGAD in children, 50-75% before the age of 10. The risk of recurrence is higher in pediatric MOGAD of ADEM manifestation, up to 30%, compared to myelitis or optic neuritis. Multiphasic MOGAD are more frequently associated with sequelae in 50-69% of cases, versus 4-32% for monophasic forms. In ADEM, cognitive and epileptic sequelae predominate. The 2020 European consortium and the 2022 national diagnosis and care protocol recommend the introduction of disease-modifying therapies as early as the second attack of the disease, or in the event of distant sequelae, in order to limit relapses and sequelae. However, these treatments take several months to take effect. There is currently no reliable predictive factor for MOGAD recurrence other than the persistence of an elevated blood anti-MOG antibody level (≥1:1280) at 1 year. The aim of this study is therefore to identify biomarkers associated with MOGAD recurrence from the first attack. To this end, we will study the transcriptome of circulating blood mononuclear cells by single-cell next-generation RNA sequencing in children with anti-MOGAD neuroinflammatory relapses. Anticipating the multiphasic trajectory of the disease would enable the introduction of early disease-modifying therapy to prevent recurrences and long-term sequelae. Furthermore, the discovery of a molecular and/or cellular signature would provide a better understanding of the pathophysiology of ADEM and MOGAD.
Interventions
OTHERBlood test
Drawing blood to realize biomarkers of disease course of MOGAD-ADEM and pathophysiology of ADEM (and MOGAD) : cellular and molecular signatures, inflammatory signaling.
Sponsors
University Hospital, Angers
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Prospective recruitment requires pre-inclusion because the characterization of antibodies allowing patients to be classified into these 3 groups is only done at a later stage.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Prospective recruitment Pre-inclusion criteria * Age at inclusion between 1 and 18 years (included) * First demyelinating event at inclusion, such as ADEM encephalitis, optic neuritis (NORB) or myelitis, or a combination of these conditions. * Informed consent signed by patient's legal representative * Patient affiliated to or benefiting from a social security scheme Inclusion criteria (confirmation of inclusion and follow-up in one of 3 groups) * MOGAD/ADEM group: presence of serum anti-MOG antibodies and diagnosis of ADEM (according to the International Pediatric Multiple Sclerosis Society Group (IPMSSG) criteria revised in 2013) at the first demyelinating attack. * Non-MOGAD/ADEM group: anti-MOG antibodies negative and diagnosis of ADEM at first demyelinating attack. * MOGAD/non-ADEM group: presence of serum anti-MOG antibodies and diagnosis of myelitis and/or NORB at first demyelinating attack. Retrospective recruitment General inclusion criteria * Age at inclusion between 1 and 18 years (inclusive) * Inclusion (signed consent of the patient's legal representative) in the biocollection from which the samples were taken at the latest at the time of management of a first demyelinating event of the ADEM encephalitis, optic neuritis (NORB) or myelitis type, or a combination of these disorders. * PBMC collected at the time of the first demyelinating event before any immunomodulatory treatment, cryopreserved and available in the biocollection. * Depending on the date of inclusion (if inclusion beyond 6 to 24 months after the first demyelinating event), samples taken at 6 months and then 24 months after the first demyelinating event available in the biocollection for the analyses planned in the study. * Informed consent signed by patient's legal representative * Patient affiliated to or benefiting from a social security scheme Inclusion criteria specific to the 3 study groups * MOGAD/ADEM group: presence of serum anti-MOG antibodies and diagnosis of ADEM (according to the International Pediatric Multiple Sclerosis Society Group (IPMSSG) criteria revised in 2013) at the first demyelinating attack. * Non-MOGAD/ADEM group: anti-MOG antibodies negative and diagnosis of ADEM at first demyelinating attack. * MOGAD/non-ADEM group: presence of serum anti-MOG antibodies and diagnosis of myelitis and/or NORB at first demyelinating attack. Non-inclusion criteria (prospective or retrospective recruitment): * Immunosuppressive therapy in the 6 months prior to treatment for a first demyelinating event. * Systemic corticosteroid therapy or immunomodulating doses of IV polyvalent immunoglobulin or plasma exchange within 3 months prior to treatment for a first demyelinating event. * Brain MRI not performed at diagnosis of first demyelinating event * Poor understanding of the French language
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood sample | Inclusion, 6 months, 24 months | 1 tube (approx. 5 mL) for children under 12 kg, 2 tubes (approx. 10 mL) for children between 12 kg and 20 kg, 4 tubes (approx. 20 mL) for children over 20 kg. Collected tubes are transferred to the investigator's Biological Resource Center (BRC) for sample preparation of the biocollection, if accepted in the consent form, and preparation of circulating blood mononuclear cells (PBMC). |
| Age | Inclusion | — |
| Personal or family history of inflammatory or dysimmune disease | Inclusion | — |
| Weight | Inclusion, 6 months, 24 months | Weight (kg) |
| EDSS (Expanded Disability Status Scale) | Inclusion, 6 months, 24 months | The neurological examination is divided into eight functional systems, 4 major (pyramidal, cerebellar, sensory, brainstem), 4 minor (sphincter, vision, mental and other). A numerical score of increasing severity (0 to 6 or 7) is given to each functional system (FS). The overall scale score is measured on a 20-level scale (0 to 10 per half-point). Up to level 3.5, the score obtained in each FS (Functional System) and the number of FS reached automatically determine the EDSS score. From 4 to 7, the definition of each level is also given by the walking disability (ability to walk without stopping, need for assistance). |
| Neurological episodes consistent with demyelinating relapse since previous visit | 6 months, 24 months | Number, date, neurological symptoms including chronic fatigue unusual for an individual of the same age, diagnosis of demyelinating relapse, type, hospitalization, treatment with intravenous corticosteroid bolus. |
Countries
France
Contacts
CONTACTNail BENALLEGUE, DOCTOR
PRINCIPAL_INVESTIGATORNail BENALLEGUE, DOCTOR
University Hospital, Angers
Outcome results
None listed