Progressive multifocal leukoencephalopathy (PML), also known as progressive multifocal leukoencephalitis, is a rare and usually fatal viral disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations. It occurs almost exclusively in people with severe immune deficiency, such as transplant patients on immunosuppressive medications, patients receiving certain kinds of chemotherapy, patients receiving natalizumab (Tysabri) for multiple sclerosis, psoriasis patients on long-term efalizumab (Raptiva) or AIDS patients. It is caused by a virus, the James Canyon (JC) virus, which is normally present and kept under control by the immune system. Immunosuppressive drugs prevent the immune system from controlling the virus.
A 50-year-old lady was referred for retinal evaluation to rule out AIDS-related retinal or ocular disorders. She complained of some disturbance in vision in both eyes since 15 days. She was a known case of AIDS since 10 years on treatment with Tab. Viraday (combination of Tenofovir, Emtricitabine and Efavirine) 1 per day. Her CD4 count was 128 cells/mm. She had no other neurological symptoms. Her vision in both eyes was 20/40, N/6. Anterior segment examination revealed no abnormality. There were no signs of uveitis. There was no relative afferent papillary defect (RAPD). Her intraocular pressure was 12 mm Hg in both eyes. Fundus examination showed no abnormality. There was no cytomegalovirus (CMV) retinitis. Optic nerves appeared normal.
A visual field examination using 30-2 program on Oculus – Center Field perimeter was performed to rule out lesions along the visual pathway, as clinical examination could not explain the visual loss or the symptoms. It showed good reliability in both eyes and a left homonymous hemianopia [Figs. 1 and 2]. Magnetic Resonance Imaging (MRI) of brain was done to determine the cause of homonymous hemianopia, such as infarct/bleed or space-occupying lesion. MRI scan showed irregular white matter hyperintensity in the right occipital lobe and a hyperintense lesion in the left frontoparietal region in the subcortical and periventricular white matter [Fig. 3]. It also showed irregular white matter hyperintensity and a large area of increased T2-weighted and decreased T1-weighted signal in the left frontal lobe posteriorly involving the subcortical white matter and extending into the centrum semiovale and corona radiata, without enhancement or mass effect. A radio diagnosis of PML was made.
She was referred to a neurologist for evaluation. Her neurological evaluation showed no abnormality. A cerebrospinal fluid (CSF) tap was advised for Polymerase Chain Reaction (PCR) evaluation for JC virus. But the patient refused to undergo the same.
PML is a progressive fatal demyelinating disorder associated with oligodendroglial infection by the human papovavirus JC. It is seen as a complication of many immunocompromised states. Occasional cases are described in pregnancy, and some cases may have no identifiable evidence of immunosuppression.
PML, first described by Astrom et al. (1958), manifests as progressive decline in neurologic function. The causative agent, the JC virus, invades oligodendroglial cells, causing multiple foci of demyelination. Primary JC virus infection occurs in childhood and is asymptomatic. JC virus antibodies are detectable in approximately 50–70% of the adult population. After the primary infection, JC virus remains latent in kidneys and lymphoid organs. Up to 64% of healthy adults have shedding of JC virus in urine in the absence of any clinical symptoms, suggesting that asymptomatic active JC virus infection is common in immunocompetent persons.
The presenting symptoms in a case of PML are focal deficits like mental deterioration, speech disturbance, ataxia, paralysis, hemiparesis, facial weakness, memory failure, and also ophthalmic symptoms like nystagmus, homonymous hemianopia and diplopia with cranial nerve palsy in one eye and cortical blindness in the other eye. Previously reported cases are different from the one we are presenting here, as our patient had come with nonspecific visual complaints and no other neurological symptoms. Visual symptoms are common in PML, but not in isolation. However, PML should also be suspected in the differential diagnosis of apparently healthy patients with focal deficits, like our patient who had no other symptoms except some visual disturbances in both eyes which she could not categorize. The purpose of presenting this case was to highlight the fact that we, as ophthalmologists, may be the first to see patients with PML and we should have a high degree of suspicion in an appropriate clinical setting. This would help us to carry out necessary tests such as visual field examination and, if necessary, an MRI scan to arrive at a diagnosis of PML which is a potentially life-threatening disease but may be helped by highly active anti-retroviral therapy (HAART). PML should be kept in mind along with other ocular manifestations, such as CMV retinitis, which are commoner. Diagnosis of PML may be difficult. Because a large percentage of the population is seropositive for JC virus, the presence of antibodies to JC is not of diagnostic value. CSF identification of JC virus by PCR is useful and studies suggest a sensitivity of 95% and specificity of 90–99%. The MRI findings are characteristic in PML, with a high T2 signal and a low T1 signal which does not enhance with gadolinium and has no mass effect. Brain biopsy is the only definitive way to make the diagnosis.
PML is uniformly fatal, and the survival rate is only a few months following the diagnosis. There are recent reports of improved survival following aggressive HAART in HIV, and specific JC antiviral treatment with interferon α or cidofovir favor early diagnosis. Hence, we should consider PML in all patients who present with progressive neurological deficits (such as visual field defects) which are usually, but not always multifocal. If JC virus is absent in the CSF, brain biopsy should be considered.
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