What causes microglial nodules and multinucleated giant cells in the white matter of the brain?

From the Guidelines

Microglial nodules and multinucleated giant cells in the white matter of the brain are primarily caused by viral encephalitis, particularly HIV encephalitis, as well as other conditions such as progressive multifocal leukoencephalopathy (PML) caused by JC virus, as evidenced by the most recent study 1. The formation of these cellular abnormalities represents the brain's inflammatory response to infection or injury, with microglia acting as the primary immune defense cells in the central nervous system. Some key points to consider include:

• The presence of microglial nodules and multinucleated giant cells is a hallmark of viral encephalitis, particularly HIV encephalitis, and can also be seen in other conditions such as PML caused by JC virus 1.
• Other viral infections that can cause similar findings include cytomegalovirus (CMV), herpes simplex virus, and JC virus (causing progressive multifocal leukoencephalopathy) 1.
• Additionally, these pathological changes may be seen in some autoimmune conditions affecting the central nervous system, certain fungal infections, and rarely in response to some parasitic infections 1.
• The diagnosis of the underlying cause of microglial nodules and multinucleated giant cells can be challenging and requires a combination of clinical, radiological, and laboratory findings, including MRI and CSF analysis 1.
• It is essential to consider the clinical context and radiological findings, such as the presence of white matter lesions, callosal thinning, and foci of restricted diffusion, to aid in the differential diagnosis 1.

From the Research

Causes of Microglial Nodules and Multinucleated Giant Cells

• Microglial nodules and multinucleated giant cells in the white matter of the brain are associated with various opportunistic infections and HIV-related lesions, as observed in AIDS patients 2.
• The presence of multinucleated giant cells is a hallmark of HIV infection, and they are often found in microglial nodules (MGNs) of cases with HIV-related lesions 2.
• Productive HIV infection was observed in 55.1% of cases with microglial nodules, with 85 out of 110 cases showing multinucleated giant cells in the MGNs 2.
• Other opportunistic pathogens, such as Toxoplasma gondii, cytomegalovirus, and JC virus, can also cause microglial nodules and multinucleated giant cells in the white matter 2, 3.
• JC virus infection can lead to progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain that affects oligodendrocytes and astrocytes in the white matter 4, 5.
• PML can present with multiple asymmetric subcortical and deep white-matter lesions on magnetic resonance imaging (MRI) 5.
• Measurement of viral sequences in cerebrospinal fluid (CSF) using polymerase chain reaction (PCR) can help diagnose CNS white-matter lesions, including PML and HIV-1 encephalitis 3.

Opportunistic Infections

• Toxoplasma gondii encephalitis and cytomegalovirus encephalitis are common opportunistic infections that can cause microglial nodules and multinucleated giant cells in the white matter 2.
• JC virus infection is a rare opportunistic infection that can lead to PML, a lytic infection of oligodendrocytes 5.
• HIV-1 encephalitis is another condition that can cause microglial nodules and multinucleated giant cells in the white matter, particularly in AIDS patients 3.

Diagnostic Approaches

• Immunohistochemistry and PCR can be used to diagnose microglial nodules and multinucleated giant cells in the white matter, and to identify the underlying opportunistic infection or HIV-related lesion 2, 3.
• MRI can help identify white-matter lesions, but may not be diagnostic on its own 5.
• Measurement of viral sequences in CSF using PCR can support the diagnosis of CNS white-matter lesions, including PML and HIV-1 encephalitis 3.