E043 Progressive multifocal leukoencephalopathy: a rare neurological complication of mycophenolate therapy in antisynthetase syndrome

Background/Aims Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating infection of the central nervous system caused by reactivation of the John Cunningham (JC) virus in immunocompromised individuals. The incidence density of PML among mycophenolate mofetil (MMF) users is estimated at 14.4 cases per 100,000 person-years. While monoclonal antibody therapies such as natalizumab and efalizumab are the most frequent culprits, PML has also been reported in patients receiving conventional immunosuppressants, including MMF. The disease carries a poor prognosis, with mortality rates reaching 50-65 % within the first year despite cessation of immunosuppressive therapy. Mirtazapine, a 5-HT2A receptor antagonist, has been explored as a potential adjunct as it may inhibit JC virus entry into glial cells. Methods We report the case of a 57-year-old woman with antisynthetase syndrome (Jo-1 and Ro-52 antibody positive) who presented to the stroke unit at Maidstone Hospital with a two-week history of progressive neurological symptoms, including memory impairment, motor dysphasia, left-sided weakness, and intermittent kaleidoscopic visual disturbance. She had interstitial lung involvement but was otherwise amyopathic and functionally independent. She was on MMF and a low maintenance dose of prednisolone, with no prior rituximab exposure. On examination, she was cognitively intact with normal gait and subtle left pronator drift. Power was 4-/5 in the left upper limb and 5/5 elsewhere, with preserved sensation. Inflammatory markers were mildly elevated (CRP 14 mg/L, ESR 6 mm/h). MRI brain showed extensive multifocal right-sided subcortical white-matter lesions. The stroke team referred her to rheumatology to evaluate for cerebral involvement of antisynthetase syndrome. However, neuroradiology review suggested an infective aetiology, raising suspicion for PML. Results HIV testing was negative. Cerebrospinal fluid JC-virus PCR was initially negative, recognising that false negatives occur in up to 30% of early cases. As symptoms progressed, she was referred to a tertiary centre in London, where a stereotactic brain biopsy revealed focal macrophage-rich inflammation with enlarged oligodendroglial nuclei displaying a ground-glass appearance. Luxol-fast blue staining highlighted multifocal demyelination, and immunohistochemistry for SV40 confirmed oligodendroglial intranuclear viral inclusions, consistent with PML. Following multidisciplinary discussion, all immunosuppressive therapy was withdrawn. She was commenced on intravenous immunoglobulin (IVIG) for her antisynthetase syndrome. Mirtazapine was considered but declined. Her neurological status improved after discontinuation of immunosuppression, and she remains clinically stable on IVIG alone. Conclusion This case underscores the diagnostic challenge of PML in autoimmune disease treated with MMF. Even in the absence of monoclonal antibody therapy, clinicians should maintain a high index of suspicion for PML when new focal or cognitive deficits occur. Early neuroimaging, CSF analysis, and tissue confirmation are essential to guide management. Given the high mortality rate, prompt discontinuation of immunosuppression, multidisciplinary collaboration, and patient education on PML risk before initiating MMF therapy are vital.