Progressive multifocal leukoencephalopathy: the challenge of opportunistic infections in patients with human immunodeficiency virus infection

A 78-year-old man was admitted to the emergency department because of disorientation, gait imbalance, and dysarthria for 3 weeks. Brain magnetic resonance imaging (MRI) on admission revealed frontal subcortical lesions, with hypointense signals in T1-weighted images and hyperintense signals in T2-weighted images, and some round lesions with peripheral restriction of diffusion and slight vasogenic edema (Figure 1). Laboratory tests on admission showed a positive human immunodeficiency virus (HIV) serology, with a viral load of 971,000 copies and a CD4⁺T-lymphocyte count of 111 cells/mm³. Under suspected cerebral toxoplasmosis, the patient underwent therapy with sulfadiazine, pyrimethamine, and folinic acid, which was interrupted after 3 weeks considering the lack of clinical improvement and negative polymerase chain reaction for Toxoplasma in cerebrospinal fluid with a concomitant negative serum serology. The cerebrospinal fluid analysis also revealed positivity for both John Cunningham (33,000 copies/mL) and Epstein-Barr (5,000 copies/mL) viruses, raising the hypothesis of progressive multifocal leukoencephalopathy (PML) and primary lymphoma of the central nervous system. A new MRI examination showed a persistent lack of enhancement and involvement of U-fibers (Figure 2). Based on all available data, the patient was diagnosed with PML secondary to an initial HIV infection. The patient progressed with clinical worsening with an unfavorable outcome, despite having started combined antiretroviral therapy. PML is a rare, progressive, and often fatal disease that should be included in the differential diagnosis of immunocompromised patients who present with progressive neurological symptoms¹.The diagnosis is challenging and is usually made based on MRI findings² and high suspicion.

FIGURE 1:
MRI scan on admission. Axial T2-weighted fluid-attenuated inversion recovery. Bilateral frontal subcortical lesional areas with peripheral restriction on difusion and slight vasogenic edema.

FIGURE 2:
MRI scan 2 weeks after admission. Axial diffusion-weighted imaging and T2-weighted fluid-attenuated inversion recovery showing a persistent peripheral restriction and lack of enhancement with involvement of U-fibers.

REFERENCES

• ¹
  Cortese I, Reich DS, Nath A. Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease. Nat Rev Neurol. 2021;17(1):37-51. Available from: https://doi.org/10.1038/s41582-020-00427-y
  » https://doi.org/10.1038/s41582-020-00427-y
• ²
  Berger JR, Aksamit AJ, Clifford DB, Davis L, Koralnik IJ, Sejvar JJ, et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013;80(15):1430-8. Available from: https://doi.org/10.1212/WNL.0b013e31828c2fa1
  » https://doi.org/10.1212/WNL.0b013e31828c2fa1

• Financial Support: No funding to declare.

Publication Dates

• Publication in this collection
  16 Dec 2022
• Date of issue
  2022

History

• Received
  14 Oct 2022
• Accepted
  09 Nov 2022