Atypical presentation of progressive multifocal leukoencephalopathy in a patient with progressive ataxic syndrome: a case report

Abstract

Case Presentation: A 38-year-old female patient, diagnosed with human immunodeficiency virus infection in 2015 and who initiated antiretroviral therapy only in 2018, presented in June 2019 with paresthesia in the lower limbs associated with progressive gait impairment. Over the following two months, the clinical course progressed to dysphagia, dysarthria, and a marked decline in functional independence. By September 2019, the patient required a wheelchair for mobility. Neurological examination revealed bidirectional horizontal nystagmus, scanning speech, cervical dystonic tremor, global ataxia, impairment of deep sensation, and a scissoring gait. Initial investigations for metabolic and nutritional causes of ataxia showed no abnormalities in copper, vitamin E, or vitamin B12 levels. Brain magnetic resonance imaging demonstrated atrophy of the cerebellar hemispheres and vermis, associated with extensive T2/FLAIR hyperintensity involving the cerebellum and bilateral middle cerebellar peduncles, without supratentorial involvement. Cerebrospinal fluid analysis revealed mild hyperproteinorrhachia, and polymerase chain reaction testing for John Cunningham virus was positive. Discussion: Progressive multifocal leukoencephalopathy is classically characterized by supratentorial white matter involvement. However, exclusively infratentorial disease, as observed in this case, represents a rare and likely underrecognized presentation, particularly in patients presenting with a progressive ataxic syndrome. This atypical clinical and radiological pattern may mimic degenerative, inflammatory, or metabolic disorders, potentially delaying the correct diagnosis. Despite regular use of antiretroviral therapy in the months preceding symptom onset, the prolonged period of prior immunosuppression likely associated with persistent viremia and chronically reduced CD4 lymphocyte levels constitutes a key factor for the development of this opportunistic infection. Recognition of this presentation broadens the known clinical and radiological spectrum of progressive multifocal leukoencephalopathy and underscores the need for a high index of diagnostic suspicion in immunosuppressed individuals. Final Comments: In immunosuppressed patients presenting with subacute or progressive acquired ataxia, progressive multifocal leukoencephalopathy should be considered even in the absence of supratentorial lesions. Awareness of isolated infratentorial presentations is essential to prevent diagnostic delays and to enable appropriate clinical management, with direct implications for functional prognosis and quality of life.