![](images/global/clr_pxl.gif) | Progressive Multifocal LeukoencephalopathyJuly 2007 ![](images/global/clr_pxl.gif) | Background | ![](images/global/clr_pxl.gif) | Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system (CNS) to which immunocompromised hosts are vulnerable. It is caused by the JC virus, a polyomavirus that infects and lyses oligodendrocytes. Disease is thought to result from reactivation of latent infection. Among HIV-infected patients, PML occurs most frequently in those with CD4 counts of <100 cells/µL. They typically present with deficits of the cerebrum and brainstem, such as cognitive decline, focal weakness, and cranial nerve palsies, which progress over the course of subsequent weeks. Among untreated patients, the interval between the first manifestation of neurologic symptoms and death may be as short as 3-4 months. Although the prognosis for patients with PML has improved with the use of potent antiretroviral therapy (ART), there is no specific treatment for PML and mortality rates remain high. Patients who survive PML are likely to have permanent neurologic deficits. Whereas PML in the absence of ART usually is not an inflammatory condition, initiation of ART may cause an immune reconstitution-like syndrome, involving new or worsening neurologic deficits and inflammatory changes seen on brain imaging and biopsy specimens. (See chapter Immune Reconstitution Syndrome.) The initiation of ART in a patient with late-stage HIV-related disease may even unmask previously silent PML. Although many patients with inflammatory PML improve or at least stabilize, some suffer exacerbation of symptoms, rapid progression of disease, and death. | ![](images/global/clr_pxl.gif) |
![](images/global/clr_pxl.gif) | SOAP (Subjective, Objective, Assessment, Plan) | ![](images/global/clr_pxl.gif) | ![](images/global/clr_pxl.gif) | Subjective | ![](images/global/clr_pxl.gif) | The patient or a caregiver may note symptoms such as weakness, gait abnormalities, difficulties with speech, visual changes (eg, field deficits, nystagmus, and blindness), altered mental status, personality changes, and seizures. The onset is likely to be subacute, though neurologic disturbances may be profound. | ![](images/global/clr_pxl.gif) |
![](images/global/clr_pxl.gif) | Objective | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | Measure vital signs. | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | Perform a full physical examination, including a thorough neurologic and mental status and evaluation. Look for focal or nonfocal neurologic deficits, particularly cranial nerve abnormalities, visual field defects, weakness, gait abnormalities, and abnormalities in cognitive function, speech, or affect. The patient typically is alert, and deficits are likely to be multiple. | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | Review previous laboratory values, particularly CD4 count (usually is <100 cells/µL in patients with PML). | ![](images/global/clr_pxl.gif) |
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![](images/global/clr_pxl.gif) | Treatment | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | There is no specific treatment for JC virus. Potent ART with effective immune reconstitution is the only treatment that may be effective for patients with PML. Even with ART, however, mortality rates approach 50%, and neurologic deficits are unlikely to be reversible. | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | Initiate ART for patients who are not already receiving treatment. It is not clear whether antiretroviral agents with good CNS penetration are more effective than those that are less likely to cross the blood-brain barrier. | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | For patients who are on ART with incomplete virologic suppression, change the ART regimen appropriately to achieve virologic suppression, if possible. For patients on ART with poor immunologic response, consider changing or intensifying therapy with the goal of improved immunologic recovery. (See chapter Antiretroviral Therapy.) | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | If symptoms are caused by immune reconstitution, consider adding corticosteroids (eg, dexamethasone) to help decrease inflammation. | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | Depending on the patient's cognitive and physical status, he or she may need a care provider in the home to assure that medications are taken on schedule. | ![](images/global/clr_pxl.gif) | ![bullet](images/global/bullet.gif) | The patient is likely to need supportive care for personal hygiene, nutrition, safety, and prevention of accidents or injury; refer as indicated. | ![](images/global/clr_pxl.gif) |
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![](images/global/clr_pxl.gif) | Patient Education | ![](images/global/clr_pxl.gif) | |
When a diagnosis of PML has been established or suspected, the clinician should initiate a discussion of plans for terminal care (including wills, advanced directives, and supportive care and services) with the patient and family members or caregivers. Supportive treatment will be necessary for an undetermined period of time, and hospice referral should be considered if the patient does not show clinical improvement in response to ART. | If the patient is receiving ART, the clinician should be sure that family members or friends are taught about the medications and are able to help the patient with adherence. |
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![](images/global/clr_pxl.gif) | References | ![](images/global/clr_pxl.gif) | ![](images/global/clr_pxl.gif) | The appearance of external hyperlinks does not constitute endorsement by the Department of Veterans Affairs of the linked Web sites, or the information, products or services contained therein. | ![](images/global/clr_pxl.gif) | ![](images/global/clr_pxl.gif) |
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