United States Department of Veterans Affairs

VA Home

About VA

Organizations

Apply Online

Locations

Contact VA

National HIV/AIDS Program

	Providers' Home > Clinical Manual > Diseases > Article	Enlarge Text Size:

Disease-Specific Treatment

Progressive Multifocal Leukoencephalopathy

July 2007

Contents

Background

SOAP (Subjective, Objective, Assessment, Plan)

Treatment

Patient Education

References

Background

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.

SOAP (Subjective, Objective, Assessment, Plan)

Subjective

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.

Objective

	Measure vital signs.

	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.

	Review previous laboratory values, particularly CD4 count (usually is <100 cells/µL in patients with PML).

Assessment

Rule out other causes of the patient's neurologic changes. A partial differential diagnosis includes:

	CNS lymphoma

	Toxoplasmosis

	HIV encephalopathy

	HIV dementia

	Other (non-HIV) forms of dementia

	Cerebrovascular disease

	Neurosyphilis

	CNS opportunistic infection (eg, tuberculosis, cryptococcosis, and cytomegalovirus)

	Multiple sclerosis

Plan

Diagnostic Evaluation

Definitive diagnosis requires a brain biopsy and identification of characteristic pathological changes, or detection of JC virus DNA in cerebrospinal fluid (CSF) of patients with radiographic and clinical findings consistent with PML.

Presumptive diagnosis often is made on the basis of clinical presentation, brain imaging, and laboratory tests. A brain biopsy should be considered with patients for whom a diagnosis is unclear.

Radiographic studies

CNS imaging may reveal changes typical of PML, but is nonspecific. Magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for detecting PML. PML presents as single or multiple hypodense lesions in the subcortical white matter, with no surrounding edema. On MRI, lesions show increased T2 signal and little or no enhancement with gadolinium. On CT, PML lesions typically are nonenhancing. In some patients, and particularly in patients taking ART, PML lesions may show inflammatory changes, such as enhancement.

CSF evaluation

	CSF cell count, protein level, and glucose level generally are normal or show mild pleocytosis and slightly elevated protein.

	A JC virus polymerase chain reaction (PCR) assay is approximately 75-85% sensitive; detection of JC virus in a patient whose clinical presentation and radiographic imaging results are consistent with PML is adequate to make a diagnosis. A negative result with JC virus PCR does not rule out PML.

Other studies

	Other diagnostic tests should be performed as indicated to rule out other potential causes of the patient's symptoms.

	A brain biopsy should be considered if the diagnosis is unclear.

Treatment

	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.

	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.

	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.)

	If symptoms are caused by immune reconstitution, consider adding corticosteroids (eg, dexamethasone) to help decrease inflammation.

	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.

	The patient is likely to need supportive care for personal hygiene, nutrition, safety, and prevention of accidents or injury; refer as indicated.

Patient Education

Key teaching points

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.

References

	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.

	Aksamit AJ. Review of progressive multifocal leukoencephalopathy and natalizumab. Neurologist. 2006 Nov;12(6):293-8.

	Centers for Disease Control and Prevention, National Institutes of Health, HIV Medicine Association/Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents. MMWR Recomm Rep. 2004 Dec 17; 53(RR15);1-112.

	Koralnik IJ. New insights into progressive multifocal leukoencephalopathy. Curr Opin Neurol. 2004 Jun;17(3):365-70.

	Ragland J. Progressive multifocal leukoencephalopathy. AIDS Clin Care. 1993 Mar;5(3):17-19.

	Wyen C, Lehmann C, Fatkenheuer G, et al. AIDS-related progressive multifocal leukoencephalopathy in the era of HAART: report of two cases and review of the literature. AIDS Patient Care STDS. 2005 Aug;19(8):486-94.