Progressive Multifocal Leukoencephalopathy: What is PML? Part One

Patient Expert

Progressive Multifocal Leukoencephalopathy (PML) is a rare, opportunistic infection of the central nervous system (CNS) caused by a reactivation of the JC (John Cunningham) virus.   PML is a brain disorder that affects the white matter part of the brain, specifically targeting the cells that make myelin (oligodendrocytes).   A majority of adults have been exposed to the JC Virus at some point in their lives.   However, PML is a very rare disease which typically does not affect healthy individuals.

Who gets PML?

Persons with lowered immune systems are at increased risk of developing the brain disorder which can result in severe disability or sometimes death.   Causes of lowered immune systems associated with PML include HIV-1 infection or AIDS (acquired immune deficiency syndrome) (80% of cases), cancers such as Hodgkin's disease or lymphoma (18%), chronic corticosteroid or immunosuppressive therapy for organ transplant (5%), and use of immunosuppressant drugs in certain patients with inflammatory autoimmune diseases (2%) (Palazzo, 2012).

Individuals with autoimmune diseases such as MS, RA, lupus, and vasculitis are at increased risk of PML, primarily due to some of the drug therapies used to treat these autoimmune diseases which alter the immune system and may allow a reactivation of the JC virus.   However, cases of PML in patients using select disease-modifying drugs is still very rare.   Even more rarely, PML has occurred in RA patients who haven't taken any disease-modifying drugs or biologics.

What are the symptoms of PML?

Symptoms of PML are neurological in nature and can vary greatly.   Common PML symptoms are similar to MS symptoms and may include clumsiness, weakness, sensory alterations, vision loss, impaired speech, cognitive deterioration, or even personality changes.   Symptoms may occur suddenly or evolve slowly over several weeks to months.

How is PML diagnosed?

The diagnosis of PML typically involves looking for characteristic white matter lesions on magnetic resonance imaging (MRI) scan and the presence of JC virus in a patient's cerebrospinal fluid.   The diagnosis may also be made following brain biopsy and observation of the progressive course of the disease.

Anytime patients with RA or MS experience new or worsening neurological symptoms, they should report the symptoms to their doctors.   It is important to accurately diagnose PML so that treatment can begin quickly.   I have told my family members that if I suddenly can't walk, talk, see, or think clearly, or my personality suddenly changes, to please take me to the ER immediately and mention my diseases and current treatments so that I will be tested for PML.

How is PML treated?

There is no known cure for PML.   Treatment for PML in autoimmune patients includes plasma exchange and a reconstitution of the immune system.   Treatment to eliminate the presence of any immunosuppressant disease-modifying drugs from the patient's system is often conducted.   Some patients may develop immune reconstitution inflammatory syndrome (IRIS) which is treated with high-dose corticosteroids.

In Part Two, the incidence of PML in patients with autoimmune rheumatic diseases will be discussed, including those using Rituxan or other disease-modifying drugs.

NINDS Progressive Multifocal Leukoencephalopathy Information Page.   Accessed May 28, 2013.

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Molloy ES.   PML and rheumatology: The contribution of disease and drugs. Cleveland Clinic Journal of Medicine Nov 2011;78(Suppl 2):S28-S32. doi: 10.3949/ccjm.78.s2.07

Molloy ES, Calabrese LH.   Progressive Multifocal Leukoencephalopathy Associated With Immunosuppressive Therapy in Rheumatic Diseases: Evolving Role of Biologic Therapies.   Arthritis & Rheumatism 2012 Sep;64(9):3043-3051.   doi: 10.1002/art.34468.

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Wenning W, Haghikia A, et al.   Treatment of Progressive Multifocal Leukoencephalopathy Associated with Natalizumab.   N Engl J Med 2009; 361:1075-1080. doi: 10.1056/NEJMoa0810257.