Progressive Multifocal Leukoencephalopathy (PML) is an infectious, demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals with AIDS, leukemia, or in organ transplant recipients. PML has also been reported in patients with inflammatory or auto-immune diseases treated with immunomodulatory medications. PML is caused by a reactivation of the polyomavirus JC (JCV), which destroys oligodendrocytes, the myelin-producing cells in the brain. JCV is a benign virus, which infects the majority of healthy individuals without causing any disease.
The goal of these NIH-sponsored, IRB-approved studies is to characterize the immunological, virological and radiological prognostic factors of disease evolution. HIV-positive or HIV-negative immunosuppressed individuals will qualify for these studies if they have neurological symptoms and brain lesions suggestive of PML, or if they have a positive brain biopsy or detectable JCV DNA in their cerebrospinal fluid.
Clinical studies are conducted in conjunction with the basic research laboratories within Division of Neuro-Virology. To learn more the Division of Neuro-Immunology and its basic research work, please click here.
Study Title: Pathogenesis of Inflammation and seizures in PML
Purpose: To determine precisely which factors are associated with immune reconstitution inflammatory syndrome (IRIS) and the development of seizures in PML patients. One of our objective is to establish non-invasive markers of PML evolution by studying the brain metabolism in PML lesions using Magnetic Resonance Imaging (MRI), Magnetic Spectroscopy (MRS) and other advanced imaging modalities. Another objective is to predict the development of seizures in PML using high density array Electroencephalogram (EEG), which can then be used for preventive and therapeutic purposes. The goal of this study is to establish clear clinical guidelines for management of PML-IRIS patients as well as in developing therapeutic strategies for the treatment and prevention of IRIS and seizures.
Study Title: Measuring and Modifying Cortical Hyperexcitability in Patients with PML
Purpose: To see whether some patients with Progressive Multifocal Leukoencephalopathy (PML) have more excitable brains than people without PML, and whether this can help us identify which patients with PML develop seizures. Transcranial Magnetic Stimulation (TMS) with electroencephalography (EEG) and electromyography (EMG) are used to measure brain excitability. TMS is a noninvasive way of stimulating the brain, which uses a magnetic field, delivered in pulses, to cause activity in the brain. EEG, used routinely in clinical medicine to measure electrical activity in the brain, measures brain response to TMS, thereby measuring brain excitability. The goal is to understand brain excitability in people with PML, and how this relates to the development of seizures. This could lead to the future development of new tools to help diagnose and treat seizures in people with and without PML.
To read more about TMS, please click here.
If you are interested to refer a patient or if you have any questions about any of these studies, please feel free to contact Igor J. Koralnik, MD at 617-735-4460.