a life-threatening neurologic disease caused by the reactivation of JC virus.

| Epidemiology | • JC virus reactivation • Severe immunosuppression (eg, untreated AIDS) | | --- | --- | | Manifestations | • Confusion, paresis, ataxia, seizure | | Diagnosis | • MRI/CT of the brain with contrast: asymmetric non-enhancing, hypodense white matter lesions with no surrounding edema. • Lumbar puncture: CSF PCR positive for JC virus • Brain biopsy (rarely needed) | | Treatment | • Often fatal • If HIV positive: antiretroviral therapy |

JC virus is usually acquired in childhood and lies dormant in the kidneys and lymphoid tissue; most individuals remain asymptomatic.  However, those with severe immunocompromise (eg, AIDS with CD4 count <200/mm3) are at risk for reactivation.  Reactivated virus spreads to the CNS and lyses oligodendrocytes, causing white matter demyelination.

Symptoms include altered mental status, motor deficits, ataxia, and vision abnormalities (eg, diplopia).  CT of the brain with contrast usually reveals asymmetric,  Diagnosis requires lumbar puncture with cerebral spinal fluid evidence of JC virus (by polymerase chain reaction); brain biopsy is rarely required.

There is no specific treatment for PML, but initiation of antiretroviral therapy (in patients with AIDS) can sometimes prevent progression and death.  However, most patients have long-term neurologic sequalae.

• EDUCATIONAL OBJECTIVES

(Choice A)  Cerebral toxoplasmosis is the most common CNS infection in patients with untreated AIDS and often causes headache, confusion, fever, and focal deficits.  However, imaging typically reveals multiple ring-enhancing lesions with edema (not nonenhancing lesions with no edema).  Although this patient's positive Toxoplasma serology indicates previous exposure (which is quite common), it does not indicate reactivated/active disease.

(Choice C)  HIV-associated dementia can cause behavioral and personality changes in those not on antiretroviral therapy.  However, brain imaging with contrast usually shows diffuse brain atrophy, ventricular enlargement, and reduced attenuation of white matter structures.  The presence of focal, asymmetric white matter lesions in this case make HIV-associated dementia much less likely.

(Choice D)  Although primary CNS lymphoma is an AIDS-defining illness that occurs much more often in patients with advanced AIDS (compared to the general population), imaging usually reveals a single, well-defined, ring-enhancing lesion with surrounding edema.  The presence of multiple asymmetric lesions and lack of enhancement/edema makes primary CNS lymphoma unlikely.