Every minute, someone in the world is diagnosed with encephalitis—inflammation of the brain—and in children, the autoimmune form of the disease can leave lasting damage even after successful treatment. This project tackles a frustrating clinical puzzle: why do some acute symptoms like seizures resolve completely, while others—such as sleep disorders and neuropsychiatric problems—become chronic? The researcher has already mapped how autoantibodies disrupt synapses and circuits in rodent models, and found distinct brain network changes in children who survived paediatric autoimmune encephalitis. The central hypothesis is that acute cellular and synaptic changes disrupt neuro-immune communication, leading to persistent structural and network alterations in the brain. If successful, this work could identify shared biological targets for new therapies that prevent long-term disability. That would directly improve the daily lives of children who currently face years of cognitive, behavioural, and sleep problems after their initial recovery. The research combines preclinical cellular studies with longitudinal brain imaging in patients, aiming to bridge the gap between molecular mechanisms and real-world outcomes.
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Worldwide, one person every minute is diagnosed with encephalitis. An autoimmune cause is now as common as infectious (~27%). Autoimmune encephalitis (AE) patient outcomes remain static despite increasing recognition and earlier immunotherapy. Children are disproportionality poorly affected. My key goal in this CDA is to address the gap in our understanding why some acute AE symptoms resolve (e.g., seizures) but others become chronic (e.g., neuropsychiatric and sleep disorders), even when successfully treated at presentation. I have mapped acute AE symptoms in pre-clinical rodent models discovering convergence in pathophysiological autoantibody action at synaptic and circuit levels. My preliminary clinical Magnetoencephalography (MEG) studies in long-term survivors of paediatric AE show distinct brain network changes that correlate with cognitive measures. My hypothesis: Paediatric AE causes distinct acute cellular and synaptic changes, disrupting neuro-immune crosstalk, resulting in persistent brain structural and network changes which underlie the chronic symptoms. In pre-clinical AE models, I will characterise the mechanisms underlying these chronic AE neurological symptoms (e.g., sleep and neuropsychiatric disorders) at cellular, synaptic, and network levels. In paediatric AE patients I will examine longitudinal brain network changes. Combining these cross-species data will identify common pathophysiological targets for therapeutic intervention to reduce morbidity and improve long-term outcomes.
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