Chapter 5-14: Progressive Multifocal Leukoencephalopathy

TEXTBOOK PRESENTATION

PML typically presents with progressive neurologic deficits, in particular weakness or gait disorders, over weeks to months. PML may also present with visual problems, headache, alterations in mental status, or dementia with focal signs.

DISEASE HIGHLIGHTS

1. Etiologic agent is JC virus, a polyomavirus (not to be confused with Creutzfeldt-Jakob disease, a prion-related illness).

2. Primary JC virus infection is common in childhood and usually asymptomatic, with seroprevalence of 39–69% among adults.

3. PML is much more common in AIDS than in non–HIV-infected immunosuppressed persons: before ART, PML developed in 3–7% of persons with AIDS. Profound immunosuppression allows latent JC virus in reticuloendothelial system and kidney to gain access to CNS and replicate.

4. Subsequent infection and lysis of the myelin-producing oligodendrocytes results in PML. Astrocytes may be infected.

5. Multifocal or unifocal white matter lesions seen, forming large plaques distributed asymmetrically.

6. Mean CD4TL count 84–104 cells/mcL: 25% of patients have CD4TL count > 200 cells/mcL

7. ART is the mainstay of treatment: 63% of patients started on ART because of PML survive > 2 years. A majority of them have either improvement or stabilization of neurologic function.

EVIDENCE-BASED DIAGNOSIS

1. History and physical exam

   1. Limb weakness: 50–70%

   2. Gait disorder: 26–64%

   3. Speech disorder: 31–51%

   4. Visual impairment (hemianopsia): 21–50%

   5. Seizures: 5–23%

   6. Headaches: 23%

   7. Cognitive abnormalities/mental status changes: 25–65%

   8. Cranial nerve palsies: 31%

2. Laboratory findings

   1. Serum antibodies to JC virus are not useful due to high prevalence of infection.

   2. CSF

      1. Routine studies may be normal or nonspecifically elevated.

      2. CSF PCR for JC virus DNA:

         1. 70–90% sensitive, 98% specific

         2. LR+ (average), 40; LR–, 0.20

         3. Some tests are more sensitive (detect low level of JC virus) and repeat analysis increases sensitivity to 90%.

         4. Sensitivity is diminished in patients receiving ART.

   3. CNS imaging

      1. Typically shows extensive multifocal patchy white matter demyelination with sparing of the cortical gray matter

      2. MRI more sensitive than CT scanning (CT 63% sensitive) (See Figure 5-5)

      3. Lesions hypodense on CT scanning, low intensity on T1-weighted MRI, hyperintense on T2-weighted MRI

      4. On imaging, lesions are restricted to the subcortical white matter, respecting the gray-white junction of the cerebrum.

      5. There is overlap in the MRI features of TE, PCL, and PML. However, certain features suggest PML:

         1. Lack of enhancement (except peri-plaque enhancement after starting ART, consistent with IRIS)

         2. Lack of mass effect

         3. Less well-circumscribed lesions

      6. MRI typically shows scalloping at gray-white matter interface (see Figure 5-5).

      7. CT scanning typically demonstrates white matter hypodense lesions.

      8. Brain biopsy: 100% specific but sensitivities only 64% to 96% due to sampling error

MRI is markedly superior to CT for diagnosis of PML.

TREATMENT

1. ART is associated with improvement or cure in some patients.

   1. Survival pre-ART averaged 4–6 months. Survival has improved to 60% since the introduction of ART.

   2. 80% of survivors have significant residual neurologic deficits

   3. Some patients receiving ART develop IRIS with worsening of symptoms and enhancement around the ...