Comparison of clinical, radiological and outcome parameters in patients with progressive multifocal leukoencephalopathy (PML) with and without HIV infection: a cohort study

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the central nervous system (CNS) caused by reactivation of the John Cunningham (JC) polyomavirus, commonly occurring in immunosuppressed individuals. Comparative data on the clinical and neuroimaging features of PML in human immunodeficiency virus (HIV)-positive and HIV-negative patients from India remain scarce. To compare clinical profiles, neuroimaging characteristics, and outcomes of HIV-positive and HIV-negative PML patients with cerebrospinal fluid (CSF) JC virus polymerase chain reaction (PCR) or brain biopsy PCR confirmation. This single-centre ambispective cohort study included adults (age ≥ 18 years) presenting to a tertiary care hospital in India between January 2019 - July 2025, who were diagnosed with PML. Demographic, clinical, laboratory, imaging and outcome data were collected. These were thereafter compared between the HIV-positive and HIV-negative PML cohorts. We recruited 41 PML patients out of 100 who were screened during the study period. Of these, 29 (70.7%) were HIV-positive and 12 (29.3%) were HIV-negative. HIV positive PML patients were younger [Mean age: (42 ± 10.5 vs 50 ± 13.4 years, p-value = 0.05)] and presented with a shorter symptom duration [4.2 ± 2.2 months vs 7.1 ± 5.3 months (p-value = 0.02)] compared to the HIV-negative cohort. Cognitive impairment (53.6% overall) was the most common symptom overall, with altered sensorium [27.6% vs 16.7% (p = 0.694)] and cerebellar ataxia [41.4% vs 25% (p = 0.480)] observed more commonly in HIV-positive patients and hemiparesis [66.7% vs 44.8% (p = 0.306)] manifesting more frequently in HIV-negative cases. However, these were not statistically significant. Radiologically, multifocal lesions (56.1%) were most commonly seen. Infratentorial involvement [72.3% vs 50% (p-value = 0.491)] and multifocal/diffuse lesions [86.2% vs 75% (p-value = 0.491)] were more common in HIV-positive, although these did not attain statistical significance. The shrimp sign was more common in patients with HIV [37.9% vs 25% (p = 0.003)]. Twenty-six patients (63.4%) showed symptomatic improvement with treatment, while six (14.6%) worsened and nine (22%) succumbed to their illness. Adult HIV-positive PML patients present earlier and tend to have diffuse, infratentorial and deep grey matter involvement. Adult HIV-negative PML patients frequently exhibit focal or punctate lesions. Certain imaging features, such as the shrimp sign in HIV-positive patients and the milky way sign in HIV-negative patients, may provide valuable diagnostic clues, but are not definitive and require confirmation in larger studies. PML patients may show clinical improvement if early therapy for the etiology of PML is provided.