Acute Disseminated Encephalomyelitis, Autoimmune Encephalitis (AE), Multiple Sclerosis
Conditions
Keywords
neuroimaging, autoimmune encephalitis, ADEM, magnetoencephalography, OPM-MEG
Brief summary
Over the past 20 years, doctors have gotten much better at spotting and treating brain conditions caused by the immune system attacking the body. These include illnesses like autoimmune encephalitis, ADEM, and multiple sclerosis. But even with better treatments, many patients-especially children-still struggle with long-term problems. Standard brain scans and tests often miss important issues like memory problems, emotional difficulties, trouble sleeping, and challenges with social behaviour. Early research using a special brain imaging technique (called MEG) has shown changes in brain networks that seem to be linked to poor memory. This study will use a new, advanced version of MEG that works even with very young children (as young as 2 years old). The goal is to better understand how these brain conditions affect children, compare them with other types of brain illness, and eventually use this technology to help predict outcomes and discover new ways to track brain health.
Detailed description
This study is an 8-year cross-sectional and observational cohort study involving the use of OPM-MEG, MEG, MRI and neuropsychology testing based at the Aston Institute of Health and Neurodevelopment, Birmingham, UK. Children and young people with immune and non-immune mediated neurological disease aged 2-15 years will be recruited locally (Birmingham Children's Hospital) and from London and Manchester. The longitudinal cohorts (n=25 in each, total n=50) will be those with immune- and non-immune mediated neurological disease within 9 months of diagnosis. They will be invited for 3 study visits (Study Visits 1, 2 and 3). The cross-sectional cohort (n=25) will be those with immune-mediated neurological disease at least 18 months after diagnosis. They will be invited to for one study visit (Study Visit 1). The study visits: At Study Visit 1 (Baseline), participants will undergo OPM-MEG, MEG and MRI as well as neuropsychology testing and questionnaire completion. Total time taken is 5 hours. This visit can be split into 2 visits within a 2 week window. At Study Visit 2 (2 years)and 3 (5 years) participants will undergo OPM-MEG, MEG and MRI and questionnaire completion. Total time taken is 3 hours. Participants travelling from outside the West Midlands will be offered overnight accommodation for Study Visits. The participants are welcome to have as many breaks as is necessary during each/any Study Visit. It is expected that breaks will last between 15 minutes to one hour. Refreshments will be available for the participants on the day and will ask in advance of the visit in case of any allergies. Aston University, where the IHN is based, has food outlets Tesco, Greggs and Costa Coffee available too. Another adult, aside from the research team, can be present during the research recordings.
Interventions
DEVICEOPM- Magnetoencephalography
To assess the changes in brain network function that occur in relation to immune and non-immune mediated brain disease, participants will undergo OPM-MEG recording. This will be conducted at all study visits. To assess the behavioural and functional changes following disease from the patient and caregiver perspective questionnaires will be completed on paper-based forms. These are all established outcomes measures used in our and others' previous studies in immune and non-immune mediated disease in children. The cryogenic MEG recording will also assess changes in brain dysfunction and will be directly comparable to the advanced OPM-MEG data. To assess the effect of disease on brain structures, participants will undergo MRI scanning at the IHN. To assess functional outcomes of immune and non-immune mediated disease, participants will undergo neuropsychology assessments.
Sponsors
Aston University
Birmingham Children's Hospital, United Kingdom
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is an 8-year cross-sectional and longitudinal prospective repeated measures observational study.
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
Yes
Inclusion criteria
* Individuals (age range 2 yrs to 16 years) who have received a diagnosis of immune-mediated neurological disease e.g. autoimmune encephalitis1, acute disseminated encephalomyelitis, multiple sclerosis. 2 * Individuals who have received a diagnosis of a non-immune mediated neurological disease (age range 2 yrs to 15 years 11 months) e.g. stroke. * Patients who can give informed consent/ assent and have a person with parental responsibility capable of giving informed consent on their behalf if aged \<16 years.
Exclusion criteria
* There is metal in the body or any other contraindication that precludes MRI scanning at IHN, or child usually requires sedation for clinical MRI scans. * Participant dissents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Detection of group differences over time in imaging metrics using OPM-MEG. | Baseline (Study Visit 1), 2 years (Study Visit 2), 5 years (Study Visit 3) | Change from Baseline in OPM-MEG Resting-State Delta-Band (1-4 Hz) Local Efficiency Local efficiency of resting-state brain networks derived from OPM-MEG recordings, computed from amplitude envelope correlation connectivity matrices (Desikan-Killiany atlas parcellation) using the Brain Connectivity Toolbox, compared between participants with immune-mediated and non-immune-mediated neurological disease across proportional connectivity thresholds (10-30%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Whole-Brain Cortical Thickness | Baseline, 2 years, 5 years | Mean cortical thickness across the whole brain, measured from T1-weighted MRI using FreeSurfer surface-based analysis, compared between disease groups. |
| Correlation Between Resting-State Network Graph Measures and Wechsler Working Memory Index Score | Baseline, 2 years, 5 years | Association between OPM-MEG/MEG-derived delta and theta local efficiency, global efficiency, and modularity values (particularly theta modularity) and Working Memory Index composite scores from the Wechsler Intelligence Scale for Children - Fifth Edition and the Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WISC-V/WPPSI-4), analyzed by multiple regression controlling for sex. On the WISC-V and WPPSI-IV, the theoretical minimum Full Scale IQ score is 40 and the maximum score is 160, with higher scores indicating better cognitive outcomes and stronger academic potential. |
| Diagnostic/Predictive Performance of Imaging Metrics for Clinical Outcome Group (mRS-Defined) | 2 years, 5 years | Sensitivity/specificity or area-under-curve of OPM-MEG, MEG, and MRI-derived metrics (local efficiency, modularity, cortical thickness) for classifying participants by modified Rankin Scale outcome category at follow-up. |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORSukhvir Wright
Aston University
Outcome results
None listed