brain CT scan images are multifocal, noncontrast enhancing hypodense lesions without mass effect, but MRI is far more sensitive than CT. The most common area of involvement is the cortical white matter of frontal and parieto occipital lobes, but lesions may occur anywhere in the brain, such as the basal ganglia, external capsule, and posterior cranial fossa structures such as the brain stem and cerebellum. Although typically multifocal, natalizumab-associated PML is often monofocal, predominantly in the frontal lobe. Treatment No drugs effectively inhibit or cure the virus infection without toxicity. Therefore, treatment aims at reversing the immune deficiency to slow or stop the disease progress. In patients on immunosuppression, this means stopping the drugs or using plasma exchange to accelerate the removal of the biologic agent that put the person at risk for PML. In HIV-infected people, this may mean starting highly active antiretroviral therapy (HAART). AIDS patients starting HAART after being diagnosed with PML tend to have a slightly longer survival time than patients who were already on HAART and then develop PML. Some AIDS patients with PML have been able to survive for several years, with HAART. A rare complication of effective HAART is immune reconstitution inflammatory syndrome (IRIS), in which increased immune system activity actually increases the damage caused by the JCV infection; although IRIS can often be managed with medication, it is extremely dangerous in PML. Cidofovir was studied as possible treatment for PML and has been used on a case-by-case basis, working in some, but not others. Cytarabine (also known as ARA-C), a chemotherapy drug used to treat certain cancers, has been prescribed on an experimental basis for a small number of non-AIDS PML patients, and stabilized the neurological condition of a minority of these patients. One patient regained some cognitive function lost as a result of PML. In June 2010, the first case report appeared of a PML patient being successfully treated with the antimalarial drug mefloquine with activity against the JC virus. The patient cleared the virus and had no further neurological deterioration. Two case reports of using interleukin-2 successfully have been published. Some success have been reported with mirtazapine, but this has not been demonstrated in clinical trials. A number of drugs work against JC virus in cell culture, but no proven, effective therapy is known in humans. For example, 1-O-hexadecyloxypropyl-cidofovir (CMX001), suppresses JCV, but has been found to have toxicity at