By Igor Koralnik, MD
“I take care of HIV-infected people who have neurological problems and I do research on progressive multifocal leukoencephalopathy.” This is my typical answer to the question: “What kind of a doctor are you? “Which most often elicits raised eyebrows, puzzled looks and a polite, “Oh, this is so interesting! Now what is it that you are actually doing?”
Most people know that neurologists take care of patients with stroke, seizure, Parkinson’s or Alzheimer’s, but few are aware of the multiple neurological complications of HIV infection. Even fewer have ever heard of progressive multifocal leukoencephalopathy or PML.
So I tell them that I got interested in this area when I was a med student at the beginning of the HIV epidemic. During my first forays on the wards, I saw so many young people coming down with all kinds of neurological diseases of the brain, spinal cord and nerves. Those diseases were either caused directly by HIV, or by other opportunistic infectious agents that took advantage of the patients’ lower immune defense caused by AIDS. This is when I decided to specialize in the neurological complications of HIV, and, by extension, to the care of patients with infections of the nervous system.
The paradox of PML
One of these infectious agents is JC virus, named according to the initials of a patient with PML. After his death, researchers in the U.S. isolated the virus from his brain. JC virus is a fascinating paradox: innocuous in healthy people, it resides in the majority of us as a lifelong infection in the kidneys and gets excreted in the urine without causing any disease; deadly in immunosuppressed individuals, it destroys the white matter of the brain in multiple areas, causing a variety of neurological deficits including paralysis, blindness, language dysfunction and seizures. There is no specific treatment for JC virus. Only half of patients who develop PML survive more than one year.
Before the AIDS epidemic, PML was an obscure, back-of-the-textbooks disease affecting only rare immunosuppressed patients with leukemias or organ transplant recipients. However, up to 5 percent of AIDS patients were initially found to develop PML. As antiretroviral treatments became widely available, leading to the recovery of the immune system in HIV-infected patients, the incidence of PML dropped again.
Surprisingly, for the past 10 years, the fastest-growing population with PML is on the opposite end of the immune spectrum. Indeed, PML now affects patients with hyperactive immune systems presenting with autoimmune diseases such as multiple sclerosis. In those patients, JC virus reactivation is triggered by immunomodulatory medications, which aim at preventing bad lymphocytes from attacking the normal components of the brain. However, these medications also prevent good lymphocytes from fighting against reactivation of latent viruses, leading, in some cases, to PML. Therefore, this rare disease has paradoxically become one of the biggest obstacles for the development of a new class of medications.
Despite these new developments, PML remains an orphan disease. Patients and their families are always devastated by this diagnosis, especially if they live in an area devoid of expertise in this field. They often travel long distances to be evaluated in our clinic and participate in our research studies. We also receive a steady stream of emails and phone calls from all over the world requesting second opinions or advice. I call these remote consultations coming outside of regular referral networks, “cyberconsults.” There are many challenges and limitations to those cyberconsults. However, they also provide the deep satisfaction of helping patients worldwide who do not have access to similar expertise locally. They also contribute to the training of my fellows who will constitute the next generation of PML experts.
Serving the underserved
So why did I select this unconventional clinical subspecialty of neurology and choose to focus my research on a rare disease? Because HIV-infected patients remain, in many areas, an underserved population, in which minorities of all kinds are often overrepresented. Due to the steady development of new antiretrovirals, the side effects of those medications, and the ability of HIV to develop resistance mutations, this is an extremely dynamic clinical field. This definitely keeps me on my toes.
In addition, doing research on PML forces me to expand my horizons into the virological, immunological, histopathological and neuroradiological aspects of this disease. Furthermore, although it is a rare condition, it can be used as a model to study much broader and universal principles such as demyelination, neuroinflammation, neurodegeneration and epileptogenesis.
After more than 20 years at Harvard Medical School in Boston, I am thrilled to come to Chicago as chair of the Department of Neurological Sciences, and to become a member of the Rush family.