Developing Advanced Neuroimaging for Clinical Evaluation of Autoimmune Encephalitis
- Conditions
- Anti-N-Methyl-D-Aspartate Receptor EncephalitisAutoimmune Encephalitis
- Interventions
- Other: Not applicable - non-interventional study
- Registration Number
- NCT05280600
- Lead Sponsor
- King's College London
- Brief Summary
Autoimmune encephalitis is brain inflammation caused by the immune system mistakenly reacting against proteins in the brain. The commonest form is called NMDAR-antibody encephalitis (N-methyl-D-aspartate receptor antibody encephalitis), a rare condition which mainly affects children and young people and causes difficulties in memory, thinking and mental health which can have significant long-term impacts on education, employment and quality of life.
In this project we will use advanced magnetic resonance imaging (MRI) to measure changes in the structure, function and chemistry of the brains of children and young people who are in early recovery from NMDAR-antibody encephalitis and other forms of immune-mediated encephalitis. We will investigate if MRI measurements in patients differ from those in healthy people, and if they can help predict patient outcome one year later, assessed by tests of memory, thinking, mental health and functioning in daily life.
- Detailed Description
This study aims to develop non-invasive, in vivo measures of neurobiological dysfunction derived from the overarching hypothesis that dysfunction of inhibitory interneurons alters the cerebral concentrations of gamma-aminobutyric acid (GABA) and glutamate (Glu) and underlies T2 changes and deficient connectivity in functional networks in early recovery from NMDAR-antibody encephalitis. Our ambition is to identify the best potential prognostic biomarkers from these neurometabolite measurements and structural and functional MRI.
Our primary objective is to test the following specific hypotheses in children and young people with NMDAR-antibody encephalitis:
* Hypothesis 1: GABA is decreased, and Glu increased, on MR spectroscopy of the medial temporal lobe and medial prefrontal cortex in NMDAR-antibody encephalitis.
* Hypothesis 2: Local GABA and Glu are correlated with (i) resting-state functional MRI (fMRI) based functional connectivity and (ii) parameter map-based microstructural changes. Specifically, we hypothesise that (i) GABA is positively correlated and Glu inversely correlated with functional connectivity, assessed by whole-brain mapping of the default mode network and seed-based analysis of hippocampal-frontal connectivity; and (ii) Glu is positively correlated and GABA inversely correlated with median T2 values within the hippocampus.
* Hypothesis 3: Local neurometabolites, network measures and microstructural changes predict cognitive, psychiatric and functional outcome at one year. Specifically, we hypothesise that medial temporal Glu, GABA and hippocampal T2 predict memory performance, and prefrontal Glu and GABA predict attention, executive function and fluid intelligence.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Antibody-negative autoimmune encephalitis Not applicable - non-interventional study Children and young people (ages 8-24 years) with a diagnosis of autoantibody-negative but probable autoimmune encephalitis or definite autoimmune limbic encephalitis. Healthy control Not applicable - non-interventional study Healthy children and young people (ages 8-24 years). NMDAR-antibody encephalitis Not applicable - non-interventional study Children and young people (ages 8-24 years) with a diagnosis of NMDAR-antibody encephalitis.
- Primary Outcome Measures
Name Time Method Structural MRI Baseline Quantitative MRI parameter maps including measurement of median T2 values in the hippocampus
Resting-state fMRI Baseline Whole-brain mapping of the default mode network and seed-based analysis of hippocampal-frontal connectivity
Cerebral concentrations of GABA and glutamate at the prefrontal cortex and left medial temporal lobe Baseline Measured with MR spectroscopy - stimulated echo acquisition mode (STEAM) sequence
- Secondary Outcome Measures
Name Time Method Wechsler Abbreviated Scale of Intelligence 2nd Edition (WASI-II) Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
CANTAB (Cambridge Cognition, UK): Paired Associates Learning Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
Prodromal Questionnaire Brief Version (PQ-B) Baseline (all groups), 1 year (patients) Questionnaire-based psychiatric symptom score (lower score indicating better outcome)
Patient Health Questionnaire (PHQ-9) Baseline (all groups), 1 year (patients) Questionnaire-based psychiatric symptom score (lower score indicating better outcome)
Generalized Anxiety Disorder 7-item Scale (GAD-7) Baseline (all groups), 1 year (patients) Questionnaire-based psychiatric symptom score (lower score indicating better outcome)
CANTAB (Cambridge Cognition, UK): Intra-Extra Dimensional Set Shift Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
CANTAB (Cambridge Cognition, UK): Stockings of Cambridge Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
Rey Auditory Verbal Learning Test (RAVLT) Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
Doors & People Test Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
CANTAB (Cambridge Cognition, UK): Rapid Visual Information Processing Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
CANTAB (Cambridge Cognition, UK): Spatial Span Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
CANTAB (Cambridge Cognition, UK): Stop Signal Task Baseline (all groups), 1 year (patients) Cognitive test (higher score indicating better outcome)
Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales Baseline (all groups), 1 year (patients) Questionnaire-based functional outcome score (higher score indicating better outcome)
PedsQL Multidimensional Fatigue Scale Baseline (all groups), 1 year (patients) Questionnaire-based functional outcome score (higher score indicating better outcome)
Behaviour Rating Inventory of Executive Function (BRIEF) Baseline (all groups), 1 year (patients) Questionnaire-based functional outcome score (lower score indicating better outcome)
Conners 3 Short Form / Conners' Adult ADHD Rating Scale Baseline (all groups), 1 year (patients) Questionnaire-based functional outcome score (lower score indicating better outcome)
Trial Locations
- Locations (1)
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, Greater London, United Kingdom