Case Report: Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection of cerebral white matter,caused by the John Cunningham virus (JCV). It was first described in the 1960s, but its incidence rose with the emergence of the human immunodeficiency virus (HIV) infection in 1980s where it was found in 3-7% of these patients.

Description: 50 years old African man presented with insomnia and generalized weakness for 7 days. Physical examination (PE) was remarkable for orientation to name, mild motor/ receptive aphasia and cranial nerves deficits (right upper quadrant field cut and right lower facial weakness). Laboratory revealed white blood cell count (WBC) of 1.91/nL, blood cultures and autoimmune work up were negative. CT head showed left parietal region subcortical edema. Magnetic resonance imaging (MRI) (See Figure 1) showed ill-defined hyper intensity in the left posterior parietal subcortical white matter and left sub insular areas.HIV positive. Lumber puncture and Cerebrospinal fluid (CSF) studies revealed 1 WBC, 3 Red blood cells,protein 28mg/dL, glucose 68mg/dL. Rest of studies including cryptococcal antigen, Encephalitis paneland toxoplasma immunoglobulin were negative. However CSF was positive for HIV RNA 6508 copies/mLand 524,000 copies of JC virus. Patient was started on anti-retroviral therapy (ART) which resulted insignificant improvement of his mental status upon post discharge follow up.

Discussion: JC virus is carried by majority of people and is usually benign but may cause potentially life threatening infections in immunocompromised patients such as HIV positive individuals and patients undergoing immunosuppressive therapy. Recently PML cases have been reported in patient undergoing treatment with immunomodulatory agents such as natalizumab, rituximab. Clinical presentation is variable andmay include visual deficits, mental impairment, weakness, ataxia and seizures. Our patient presented with insomnia which has not been reported in literature. Diagnosis depends on clinical presentation,neuroimaging characteristics and detection of JC virus in CSF. Brain biopsy is gold standard but rarely performed.
Conclusions : ART (Anti-retroviral therapy) is the mainstay of treatment. Recently a small clinical trial have shown that pemrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against JC virus. Prognosis is poor and 1- year survival is approximately 50%. Up to 80% of survivors may have significant neurologic sequelae. Immune reconstitution inflammatory syndrome (IRIS) after initiation of ART is yet another complication and may result in paradoxical worsening of neurological symptoms and may require addition of glucocorticoids.

References
1.Koralnik IJ. Progressive multifocal leukoencephalopathy revisited: Has the disease outgrown its name?Ann Neurol. 2006;60(2):162-173.
2.Cinque P, Koralnik IJ, Gerevini S, Miro JM, Price RW. Progressive multifocal leukoencephalopathy in HIV-1 infection. Lancet Infect Dis. 2009;9(10):625-636.
3.Petito CK, Cho ES, Lemann W, Navia BA, Price RW. Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review. J Neuropathol Exp Neurol. 1986;45(6):635-646.
4.Cortese I, Muranski P, Enose-Akahata Y, et al. Pembrolizumab treatment for progressive multifocal leukoencephalopathy. N Engl J Med 2019;380:1597-1605.

A RARE CASE REPORT OF PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY PRESENTING WITH INSOMNIA