Developing Advanced Neuroimaging for Clinical Evaluation of Autoimmune Encephalitis
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Anti-N-Methyl-D-Aspartate Receptor Encephalitis
- Sponsor
- King's College London
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- Structural MRI
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Structural MRI
Time Frame: Baseline
Quantitative MRI parameter maps including measurement of median T2 values in the hippocampus
Resting-state fMRI
Time Frame: 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
Time Frame: Baseline
Measured with MR spectroscopy - stimulated echo acquisition mode (STEAM) sequence
Secondary Outcomes
- Wechsler Abbreviated Scale of Intelligence 2nd Edition (WASI-II)(Baseline (all groups), 1 year (patients))
- CANTAB (Cambridge Cognition, UK): Paired Associates Learning(Baseline (all groups), 1 year (patients))
- Prodromal Questionnaire Brief Version (PQ-B)(Baseline (all groups), 1 year (patients))
- Patient Health Questionnaire (PHQ-9)(Baseline (all groups), 1 year (patients))
- Generalized Anxiety Disorder 7-item Scale (GAD-7)(Baseline (all groups), 1 year (patients))
- Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales(Baseline (all groups), 1 year (patients))
- CANTAB (Cambridge Cognition, UK): Intra-Extra Dimensional Set Shift(Baseline (all groups), 1 year (patients))
- CANTAB (Cambridge Cognition, UK): Stockings of Cambridge(Baseline (all groups), 1 year (patients))
- Rey Auditory Verbal Learning Test (RAVLT)(Baseline (all groups), 1 year (patients))
- Doors & People Test(Baseline (all groups), 1 year (patients))
- CANTAB (Cambridge Cognition, UK): Rapid Visual Information Processing(Baseline (all groups), 1 year (patients))
- CANTAB (Cambridge Cognition, UK): Spatial Span(Baseline (all groups), 1 year (patients))
- CANTAB (Cambridge Cognition, UK): Stop Signal Task(Baseline (all groups), 1 year (patients))
- PedsQL Multidimensional Fatigue Scale(Baseline (all groups), 1 year (patients))
- Behaviour Rating Inventory of Executive Function (BRIEF)(Baseline (all groups), 1 year (patients))
- Conners 3 Short Form / Conners' Adult ADHD Rating Scale(Baseline (all groups), 1 year (patients))