To describe an atypical presentation of progressive multifocal leukoencephalopathy with brainstem involvement and its evolution to locked-in syndrome, highlighting the clinico-radiological correlation and its diagnostic value.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection of the central nervous system caused by reactivation of the JC virus in immunocompromised patients, especially those with HIV infection. Although its typical presentation involves the supratentorial white matter, forms affecting the brainstem or cerebellum are rare and are associated with rapid clinical progression and a poorer prognosis. Recognition of these atypical patterns is essential for early diagnosis and accurate clinico-radiological correlation.

Not applicable (N/A).

A 20-year-old male with a recent diagnosis of HIV infection (CD4 count: 16 cells/µL; viral load: 779,668 copies/mL), not on antiretroviral therapy, presented with two months of asthenia, intermittent fever, and diarrhea, followed by dysarthria, right hemiparesis, and truncal ataxia. Neurological examination revealed resting nystagmus and severe left-sided dysmetria. Brain MRI showed T2/FLAIR hyperintense lesions involving the medulla, pons, middle cerebellar peduncle, and left cerebellar hemisphere, without contrast enhancement. Cerebrospinal fluid analysis showed a positive PCR for JC polyomavirus (1,395,000 copies/mL), confirming the diagnosis of progressive multifocal leukoencephalopathy. During hospitalization, the patient developed locked-in syndrome with preservation of vertical eye movements and later experienced aspiration pneumonia, sepsis, and dependence on tracheostomy and gastrostomy.

Infratentorial involvement in progressive multifocal leukoencephalopathy is rare and represents a diagnostic challenge. Brainstem involvement, particularly at the bulbar level, may lead to the development of locked-in syndrome, characterized by tetraplegia and anarthria with preserved consciousness and vertical eye movements, allowing minimal interaction with the environment. This case highlights the importance of recognizing atypical presentations of the disease and correlating clinical and imaging findings for timely diagnosis.