Changes in Brain Volumes Are Relevant during Natalizumab-Associated Progressive Multifocal Leukoencephalopathy:...

Area of Science:

• Neurology
• Immunology
• Radiology

Background:

• Progressive Multifocal Leukoencephalopathy (PML) is a serious opportunistic infection.
• Natalizumab treatment increases PML risk, particularly in multiple sclerosis patients.
• Understanding brain volume changes during PML and its associated Immune Reconstitution Inflammatory Syndrome (IRIS) is crucial.

Observation:

• A case of Natalizumab-associated PML with cerebellar involvement and consciousness disturbances was observed.
• Clinical improvement coincided with the onset of mild IRIS, which co-localized with the PML lesion.
• Brain magnetic resonance imaging (MRI) was used to analyze volumetric changes during the infection and IRIS.

Findings:

• During IRIS, white matter volume increased, while grey matter volume decreased.
• Cerebrospinal fluid volume consistently increased throughout the PML duration, suggesting a remote effect.
• A significant decrease in brain parenchymal fraction was noted, while total brain volume remained stable.

Implications:

• Neurodegeneration appears to be the primary driver of persistent disability in Natalizumab-associated PML.
• The neurodegenerative process is likely widespread and inflammatory.
• IRIS and humoral factors from the PML lesion may sustain this neurodegeneration.