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Project title
Comprehensive neuroimaging characterization of neurodegeneration and brain plasticity in children with Rasmussen Syndrome
Supervisors names
Torsten Baldeweg
Suresh Pujar
Project outline
Background: Rasmussen syndrome (RS) is a rare paediatric progressive disease characterized by atrophy of one cerebral hemisphere and associated neurological deficits, such as drug-resistant epileptic seizures, progressive hemiparesis and cognitive deterioration (ref 1,2), presumed due to an underlying immune process. The medical treatment of RS is challenging and includes anti-epileptic medications and anti-inflammatory therapy. Hemidisconnection of the affected side of the brain is the only effective cure for seizures with long-term seizure freedom in 70-80% of cases. The rate of progression of the disease and factors associated with it are not well understood and is not known why some patients do not benefit from hemidisconnection (ref 3).
Aims/ Objectives: GOSH has been treating one of the largest cohorts of children with this condition. We are proposing to conduct a retrospective review of this unique cohort with the aim to characterize the neuroimaging progression in relation to clinical, neuropsychological and surgical outcomes. This project has the potential to inform future management of this devastating disorder: quantitative MRI analysis to identify the earliest signs of regional volume loss would enable early diagnosis and therefore starting early treatment, which will have an impact on outcomes.
Methods: Longitudinal analysis of high-resolution structural MRI scans will be performed for evidence of neurodegeneration (cortical thickness and subcortical volume estimation). These changes will be compared with quantitative analysis of serial EEG and neuropsychological data, to create individualized disease profiles for each patient. A major focus will be the characterization of changes in the unaffected hemisphere and if those changes are predictive of surgical outcomes. A further critical question is the characterization of brain plasticity by mapping the changes in language dominance using serial function MRI and its predictive value for postoperative language functions.
Timeline: The prospective PhD will be joining a multidisciplinary team based at GOSICH and GOSH who are involved in the care of patients with RS. In addition, the student will be working with an international research collaboration who have recently joined forces to combat this disease. The student will spend the first year learning the principles of longitudinal MRI analysis. The student will spend the latter two years conducting further data collection and analyses of structural and functional imaging, with particular interest to relationships with postoperative outcomes.
References: 1. Varadkar et al. Lancet Neurol. 2014 Feb;13(2):195-205. 2. Rudebeck et al. Epilepsia. 2018 Jun;59(6):1210-1219. 3. Pellegrin et al. Neurology. 2021 Jan 12;96(2):e267-e279.
Contact
Torsten Baldeweg email: t.baldeweg@ucl.ac.uk