Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal CNS infection related to the John Cunningham (JC) virus. While classically associated with immunocompromised states, there is increasing recognition of PML presentations among seemingly immunocompetent patient cohorts.

We present the case of a 67 year old male who presented with a 4 week history of worsening left upper limb ataxia. He did not have any significant background medical history and did not use any regular medications. There was no history of malignancy or prior immunosuppression. Examination demonstrated mild dysarthria, left upper limb dysmetria and a left upper limb postural tremor. Magnetic resonance imaging revealed a left cerebellar lesion located at the middle cerebellar peduncle, with sparing of the dentate nucleus. Despite corticosteroid therapy for a presumed inflammatory or neoplastic lesion, the patient continued to clinically decline over the following weeks, becoming markedly dysarthric and becoming bed bound due to severe ataxia.

Extensive investigations including cerebrospinal fluid analysis, computed tomography and PET imaging did not show an underlying explanation for the cerebellar pathology. Ultimately a targeted cerebellar biopsy demonstrated features consistent with a diagnosis of PML, later confirmed on cerebrospinal fluid JC virus PCR. Following this, extended cytokine studies demonstrated reduced induction of interferon gamma (IFNγ), indicating an acquired anti interferon gamma immunodeficiency syndrome. Treatment with a single dose of pembrolizumab resulted in transient plateau of symptoms but no meaningful improvement. The patient passed away 4 months after initial presentation.

This case demonstrates the under recognised entity of PML without clear history of immunocompromise. It highlights the potential role of relative immunodeficiency secondary to reduced IFNγ production and stresses the importance of thorough immunological workup for occult immunodeficiency in otherwise immunocompetent patients. This case also demonstrated a case of PML treated with pembrolizumab, an increasingly recognised potential treatment for PML.