**Fixed Price** Measuring and Modifying Cortical Hyperexcitability in Patients at High Risk for Acquired Epilepsy

This project’s aim is to demonstrate that patients with Progressive Multifocal Leukoencephalopathy (PML) and epilepsy have increased cortical excitability at the presumed seizure focus, as measured via TMS-EEG, relative to patients with PML without epilepsy, and relative to healthy controls. An additional aim is to show that cortical hyperexcitability is present prior to seizure onset in patients with PML who subsequently develop epilepsy, and to show that cortical excitability increases further after the development of epilepsy. At Northwestern, the following four patient populations will be investigated: 1. Patients with PML and epilepsy (n = 7) 2. Patients with established PML without epilepsy, and without risk factors (e.g. new diagnosis; neuroimaging markers) for developing epilepsy (n = 7) 3. Patients with PML without epilepsy, but with either a new diagnosis or otherwise with clinical or imaging features to suggest a high risk for developing epilepsy (n = 10) 4. Healthy control subjects (n = 15). Northwestern will be doing the screening and baseline activities outlined in the protocol combined with the TMS-EEG to measure cortical excitability for a maximum of four TMS-EEG visits, occurring up to two years apart.