Microstructural Injury to the Brainstem and Spinal Cord Determines Outcomes in CM and SM

Project 3: Abstract Chiari type I malformation (CM), defined for >100 years as cerebellar tonsillar ectopia through the foramen magnum, encompasses a broad array of radiological and clinical features, with patients ranging from essentially asymptomatic (i.e. incidental discovery) to suffering disabling neurological symptoms from cervicomedullary compression. Indeed, this oversimplified and outdated definition of CM depends solely on a single, static 2D sagittal MRI image, and fails to consider the complex and dynamic pathophysiology at the interface of CM pathology involving the cerebellum, brainstem, and spinal cord. The objective of this proposal is to predict long term outcomes in CM through understanding cerebrospinal fluid (CSF)-mediated microstructural injury. The Central Hypotheses are that: 1) Novel MRI measures of microstructural injury are associated with CM disease severity, functional outcome, and therapeutic response and 2) Brain-CSF circulation is altered in symptomatic CM, is associated with microstructural injury, and responds to neurosurgical treatment. To test these hypotheses, we will address the following Specific Aims: Specific Aim 1: Determine whether novel brainstem measures of microstructural injury reflect neurological impairments and predict long-term outcomes in patients with CM. Specific Aim 2: Determine CSF circulation in the brainstem, cerebellum and spinal cord through dynamic 4D CSF flow of the brain-CSF interfaces, their response to surgical treatment, and relationship to microstructural injury.