Table of ContentsView AllTable of ContentsSymptomsCausesDiagnosisTreatmentPrevention
Table of ContentsView All
View All
Table of Contents
Symptoms
Causes
Diagnosis
Treatment
Prevention
Progressive multifocal leukoencephalopathy (PML) is a serious disease in which theJohn Cunningham (JC) virusinfects multiple areas of the brain, damaging it as the infection rapidly worsens and causing lasting consequences—not uncommonly, death. While PML is very rare, some disease-modifying therapies (DMTs) used totreat multiple sclerosis (MS)can increase your risk of developing it. However, other people are at risk—not only people with MS.
The effects of PML can progress rapidly, but it is usually a subacute (slow but steady) progress. However, it is nonetheless important to be vigilant about seeking medical attention if you start to experience any indications of this disease. It is crucial that one seeks an experienced specialist for an assessment, as this is a very rare disease of very complex cases.
Alex Dos Diaz / Verywell
Symptoms of PML vary because the infectiousencephalitiscan involve any region of the brain. They may include:
Even though PML is an infection, it doesn’t usually cause a fever.
Complications
The condition worsens quickly and causes a number of serious complications if it isn’t treated, including:
PML has about a 70-percent survival rate. Early diagnosis offers you the best chance for a good outcome should you develop this disease.
However, if your immune system is weakened—for example, because of immunosuppressive medication use, the virus might reactivate, causing a brain infection.
DMTs (also known as DMDs, or disease-modifying drugs) used for MS are taken on a regular basis to prevent anMS exacerbation (relapse). Tysabri and Tyruko (natalizumab) are the DMTs with the greatest risk for PML.Other immunosuppressive MS medications, includingGilenya (fingolimod), Tecfidera (dimethyl fumarate), Lemtrada (alemtuzumab), andOcrevus (ocrelizumab)may increase the risk as well.
Interferons such asAvonex (interferon beta-1a)andBetaseron (interferon beta-1b)do not increase the risk of PML. And corticosteroids, which are used during an MS exacerbation, are also not associated with PML.
Other people (not just MS patients) get PML. Important other groups include those with AIDS, people who have received organ transplants, and people with other diseases needing a biological prescription.
The symptoms of PML are often similar to those of an MS relapse. Though this can make identifying PML challenging, certain characteristics of your experience can help a healthcare provider make the call.
For example, if you have sensory changes in one arm or leg, or if you experience muscle cramping in your hand without any other symptoms, you are more likely to be having an MS relapse than diagnosed with PML.
If you have new symptoms or major changes in behaviorthat you have not experienced before, this is more likely PML than an MS relapse.
However, these are simply clues, not hard-and-fast rules.
Diagnostic Tests Used to Identify PML in MS
Imaging and Procedures
Both MS and PML produce lesions in the brain, and the lesions of PML generally look different than MS lesions on amagnetic resonance imaging (MRI)scan. They may be described as atypical, diffuse, or patchy.
Alumbar puncture (spinal tap)may detect the presence of JC virus in the cerebrospinal fluid (CSF), although the absence of JC virus in your CSF does not rule out the possibility that you could have PML.
In some instances, a brain biopsy is done to examine an area of abnormality in the brain. This can help distinguish between a brain tumor or encephalitis, particularly if your condition continues to worsen despite treatment.
The treatment for PML includes several steps, the most important of which is discontinuation of your DMT. This process is generally done fairly abruptly, and while necessary, it’s important to know that abrupt discontinuation of a DMT can cause its own consequences.
As you explore additional options that may be considered below, know that, even with the best treatment, PML can be fatal. Survivors are highly likely to experience long-term consequences, such as personality changes, seizures, and neurological deficits. Additional therapies for these issues are likely.
Never stop taking your MS medication without your healthcare provider’s OK.
Plasmapheresis
You may needplasmapheresisto remove the disease-modifying therapy from your system. Plasmapheresis is a process of plasma exchange. The blood is removed from your body, filtered through a machine to remove certain substances, (such as antibodies or drugs), and returned to your body.
Plasmapheresis is safe, but it is exhausting, and it is normal to feel run down while going through the process.
A New DMT
Because you can have an MS relapse after discontinuing your DMT, you may need to start another one within a few weeks. Selection of the next DMT is a complex process, requiring a balance between taking a medication strong enough to control your MS while avoiding the risk of PML.
Antiviral Medication
If your PML is widespread throughout your brain, or if does not appear to be resolving quickly, you may need treatment for the viral infection. An antiviral medication, maraviroc, which is typically used for HIV patients, has been considered a treatment for the infectious JC-virus encephalitis as well. However, note that maraviroc is currently only an experimental drug at this time.
Immunosuppressive Medication
You may also need to take medication to prevent a complication called PML immune reconstitution inflammatory syndrome (IRIS). This can occur when your DMD is abruptly withdrawn and your immune system suddenly increases its function after having been suppressed.
Treatment with an immunosuppressive medication such as a corticosteroid may be necessary to prevent a harmful immune response to the JC virus.
Treatment of PML is quite complicated, requiring a fine balance between managing the infection, preventing an MS relapse, and thwarting a rebound immune effect.
Prevention of PML is based on a few strategies.Pre-testing for JC-virus antibodiesin the blood is recommended prior to treatment with Tysabri, and you may have an antibody test before treatment with other DMTs associated with PML risk as well.
Verywell / Cindy Chung
Again, the presence of JC-virus antibodies does not mean that you will develop PML, but it confirms that you have the virus in your body.
Keep in mind that about 80% of the population has JC-Virus antibodies, so testing positive is expected.
Other preventative measures include avoiding the DMTs that are associated with PML if you have taken immunosuppressive medications in the past. Experts suggest that taking DMTs associated with PML for less than nine months may be safe, and recommend not taking the medications associated with PML risk for a prolonged period of time.
A Word From Verywell
There are many therapies for MS, and you should be sure to discuss the risks and benefits of your MS medication with your healthcare provider. If you are taking Tysabri, Tyruko, Gilenya, Tecfidera, Ocrevus, or Lemtrada and notice any new or worsening symptoms, contact your healthcare provider right away. While your symptoms may not always indicate PML, immediate medical evaluation is necessary because of the life-threatening nature of this rare brain infection.
In addition, if you are experiencing any symptoms of PML (even if you do not have MS), be sure to seek a specialized healthcare provider, as PML is a very complex disease. As with any condition, early intervention is key.
9 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.David. M, Beoit J.Infectious Disease Diagnosis. [Place of publication not identified]: Springer; 2018.Paz S, Branco L, Pereira M, Spessotto C, Fragoso Y.Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.Epidemiol Health. 2018;40:e2018001. doi:10.4178/epih.e2018001Yukitake M.Drug-induced progressive multifocal leukoencephalopathy in multiple sclerosis: A comprehensive review.Clinical and Experimental Neuroimmunology. 2018;9:37-47. doi:10.1111/cen3.12440Progressive Multifocal Leukoencephalopathy (PML) - Neurologic Disorders - MSD Manual Professional Edition. MSD Manual Professional Edition.Boster A, Hreha S, Berger J et al.Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis.Arch Neurol. 2009;66(5). doi:10.1001/archneurol.2009.31Berger J, Aksamit A, Clifford D et al.PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section.Neurology. 2013;80(15):1430-1438. doi:10.1212/wnl.0b013e31828c2fa1Miskin D, Herman S, Ngo L, Koralnik I.Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy.J Neurovirol. 2015;22(4):464-471. doi:10.1007/s13365-015-0414-3Steiner I, Benninger F.Maraviroc in PML-IRIS.Neurology - Neuroimmunology Neuroinflammation. 2017;4(2):e331. doi:10.1212/nxi.0000000000000331Gheuens S, Smith D, Wang X, Alsop D, Lenkinski R, Koralnik I.Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.Neurology. 2012;78(18):1390-1393. doi:10.1212/wnl.0b013e318253d61eAdditional ReadingFaulkner M.Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf. 2015;14(11):1737-48. doi: 10.1517/14740338.2015.1093620.Hodecker SC, Stürner KH, Becker V, Elias-Hamp B, Holst B, Friese MA, et al.Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS.Neurol Neuroimmunol Neuroinflamm. 2017 Feb 8;4(2):e325. doi: 10.1212/NXI.0000000000000325.Wijburg MT, Witte BI, Vennegoor A, Roosendaal SD, Sanchez E, Liu Y, et al.MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumabpharmacovigilance. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1138-45. doi: 10.1136/jnnp-2016-313772.
9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.David. M, Beoit J.Infectious Disease Diagnosis. [Place of publication not identified]: Springer; 2018.Paz S, Branco L, Pereira M, Spessotto C, Fragoso Y.Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.Epidemiol Health. 2018;40:e2018001. doi:10.4178/epih.e2018001Yukitake M.Drug-induced progressive multifocal leukoencephalopathy in multiple sclerosis: A comprehensive review.Clinical and Experimental Neuroimmunology. 2018;9:37-47. doi:10.1111/cen3.12440Progressive Multifocal Leukoencephalopathy (PML) - Neurologic Disorders - MSD Manual Professional Edition. MSD Manual Professional Edition.Boster A, Hreha S, Berger J et al.Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis.Arch Neurol. 2009;66(5). doi:10.1001/archneurol.2009.31Berger J, Aksamit A, Clifford D et al.PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section.Neurology. 2013;80(15):1430-1438. doi:10.1212/wnl.0b013e31828c2fa1Miskin D, Herman S, Ngo L, Koralnik I.Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy.J Neurovirol. 2015;22(4):464-471. doi:10.1007/s13365-015-0414-3Steiner I, Benninger F.Maraviroc in PML-IRIS.Neurology - Neuroimmunology Neuroinflammation. 2017;4(2):e331. doi:10.1212/nxi.0000000000000331Gheuens S, Smith D, Wang X, Alsop D, Lenkinski R, Koralnik I.Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.Neurology. 2012;78(18):1390-1393. doi:10.1212/wnl.0b013e318253d61eAdditional ReadingFaulkner M.Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf. 2015;14(11):1737-48. doi: 10.1517/14740338.2015.1093620.Hodecker SC, Stürner KH, Becker V, Elias-Hamp B, Holst B, Friese MA, et al.Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS.Neurol Neuroimmunol Neuroinflamm. 2017 Feb 8;4(2):e325. doi: 10.1212/NXI.0000000000000325.Wijburg MT, Witte BI, Vennegoor A, Roosendaal SD, Sanchez E, Liu Y, et al.MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumabpharmacovigilance. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1138-45. doi: 10.1136/jnnp-2016-313772.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
David. M, Beoit J.Infectious Disease Diagnosis. [Place of publication not identified]: Springer; 2018.Paz S, Branco L, Pereira M, Spessotto C, Fragoso Y.Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.Epidemiol Health. 2018;40:e2018001. doi:10.4178/epih.e2018001Yukitake M.Drug-induced progressive multifocal leukoencephalopathy in multiple sclerosis: A comprehensive review.Clinical and Experimental Neuroimmunology. 2018;9:37-47. doi:10.1111/cen3.12440Progressive Multifocal Leukoencephalopathy (PML) - Neurologic Disorders - MSD Manual Professional Edition. MSD Manual Professional Edition.Boster A, Hreha S, Berger J et al.Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis.Arch Neurol. 2009;66(5). doi:10.1001/archneurol.2009.31Berger J, Aksamit A, Clifford D et al.PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section.Neurology. 2013;80(15):1430-1438. doi:10.1212/wnl.0b013e31828c2fa1Miskin D, Herman S, Ngo L, Koralnik I.Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy.J Neurovirol. 2015;22(4):464-471. doi:10.1007/s13365-015-0414-3Steiner I, Benninger F.Maraviroc in PML-IRIS.Neurology - Neuroimmunology Neuroinflammation. 2017;4(2):e331. doi:10.1212/nxi.0000000000000331Gheuens S, Smith D, Wang X, Alsop D, Lenkinski R, Koralnik I.Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.Neurology. 2012;78(18):1390-1393. doi:10.1212/wnl.0b013e318253d61e
David. M, Beoit J.Infectious Disease Diagnosis. [Place of publication not identified]: Springer; 2018.
Paz S, Branco L, Pereira M, Spessotto C, Fragoso Y.Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.Epidemiol Health. 2018;40:e2018001. doi:10.4178/epih.e2018001
Yukitake M.Drug-induced progressive multifocal leukoencephalopathy in multiple sclerosis: A comprehensive review.Clinical and Experimental Neuroimmunology. 2018;9:37-47. doi:10.1111/cen3.12440
Progressive Multifocal Leukoencephalopathy (PML) - Neurologic Disorders - MSD Manual Professional Edition. MSD Manual Professional Edition.
Boster A, Hreha S, Berger J et al.Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis.Arch Neurol. 2009;66(5). doi:10.1001/archneurol.2009.31
Berger J, Aksamit A, Clifford D et al.PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section.Neurology. 2013;80(15):1430-1438. doi:10.1212/wnl.0b013e31828c2fa1
Miskin D, Herman S, Ngo L, Koralnik I.Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy.J Neurovirol. 2015;22(4):464-471. doi:10.1007/s13365-015-0414-3
Steiner I, Benninger F.Maraviroc in PML-IRIS.Neurology - Neuroimmunology Neuroinflammation. 2017;4(2):e331. doi:10.1212/nxi.0000000000000331
Gheuens S, Smith D, Wang X, Alsop D, Lenkinski R, Koralnik I.Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS.Neurology. 2012;78(18):1390-1393. doi:10.1212/wnl.0b013e318253d61e
Faulkner M.Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf. 2015;14(11):1737-48. doi: 10.1517/14740338.2015.1093620.Hodecker SC, Stürner KH, Becker V, Elias-Hamp B, Holst B, Friese MA, et al.Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS.Neurol Neuroimmunol Neuroinflamm. 2017 Feb 8;4(2):e325. doi: 10.1212/NXI.0000000000000325.Wijburg MT, Witte BI, Vennegoor A, Roosendaal SD, Sanchez E, Liu Y, et al.MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumabpharmacovigilance. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1138-45. doi: 10.1136/jnnp-2016-313772.
Faulkner M.Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf. 2015;14(11):1737-48. doi: 10.1517/14740338.2015.1093620.
Hodecker SC, Stürner KH, Becker V, Elias-Hamp B, Holst B, Friese MA, et al.Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS.Neurol Neuroimmunol Neuroinflamm. 2017 Feb 8;4(2):e325. doi: 10.1212/NXI.0000000000000325.
Wijburg MT, Witte BI, Vennegoor A, Roosendaal SD, Sanchez E, Liu Y, et al.MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumabpharmacovigilance. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1138-45. doi: 10.1136/jnnp-2016-313772.
Meet Our Medical Expert Board
Share Feedback
Was this page helpful?Thanks for your feedback!What is your feedback?OtherHelpfulReport an ErrorSubmit
Was this page helpful?
Thanks for your feedback!
What is your feedback?OtherHelpfulReport an ErrorSubmit
What is your feedback?
