Clinically Isolated Brainstem Progressive Multifocal Leukoencephalopathy: Diagnostic Challenges

BACKGROUND Acute brainstem syndrome (ABS), as the initial manifestation of progressive multifocal leukoencephalopathy (PML), is rarely reported. Appropriate history and neurodiagnostic testing are essential to encompass the extended spectrum of clinical and radiological differentials of ABS. CASE REPORT A 47-year-old woman presented to the emergency department with slurred speech, dizziness, right-sided facial droop, and numbness. Brain magnetic resonance imaging (MRI) revealed non-enhancing hyperintensities in the right lateral pons and brachium pontis, eventually extending to the bilateral middle cerebellar peduncle, pons, left>right cerebellar hemisphere, right thalamocapsular region, and midbrain region. Lumbar puncture revealed 3 cerebrospinal fluid-specific oligoclonal bands. Initial diagnosis of multiple sclerosis led to high-dose intravenous steroid treatment. The patient continued to deteriorate, leading to multiple emergency department visits and hospital admissions. Additional history revealing previously diagnosed, treatment-naive HIV prompted a repeat lumbar puncture. Cerebrospinal fluid polymerase chain reaction (PCR) for JC polyomavirus (JCV) was positive, leading to the diagnosis of clinically isolated brainstem PML. Unfortunately, the patient developed pneumonia and hypoxic respiratory failure, which ultimately led to her death. CONCLUSIONS This case highlights the need for considering isolated brainstem PML, as a diagnostic possibility, in patients presenting with acute-subacute brainstem symptoms and compatible neuroimaging findings. Clinicians need to be aware of varying PML presentations with brainstem or diencephalic variants, as well as monofocal lesions. The prognosis for PML has improved somewhat, secondary to immune reconstitution by highly active antiretroviral therapy, risk stratification in drug-induced PML, and other emerging treatments, such as pembrolizumab.