Causes of Vasogenic Edema in Immunosuppressed Patients
In immunosuppressed patients, vasogenic edema results primarily from infectious encephalitis (particularly viral pathogens like CMV, VZV, HSV, EBV, and JC virus causing PML), fungal infections (cryptococcus), parasitic infections (toxoplasmosis), and non-infectious causes including primary CNS lymphomas and cerebral amyloid angiopathy-related inflammation. 1
Infectious Causes
Viral Pathogens
Cytomegalovirus (CMV) is the most frequently identified herpesvirus in HIV-positive immunosuppressed patients (13% prevalence), particularly when CD4 counts fall below 50 cells/μL. 1 MRI characteristically reveals subependymal gadolinium enhancement with nonspecific white matter abnormalities on T2-weighted images. 1
Varicella-Zoster Virus (VZV) causes severe meningoencephalitis in immunocompromised patients with reactivation disease, producing vasogenic edema that can appear as diffuse T2 hyperintensity covering the brain surface with elevated apparent diffusion coefficient values. 1, 2 CSF PCR has 80-95% sensitivity and 95% specificity in immunocompromised persons. 1
Herpes Simplex Virus (HSV-1 and HSV-2) produces temporal and inferior frontal lobe edema with high signal intensity on FLAIR and T2-weighted images. 1, 3 HSV-2, EBV, and VZV were detected in 11 HIV-negative immunocompromised patients in one study. 1
Epstein-Barr Virus (EBV) occurs in 10.6% of HIV-positive patients and can drive primary CNS lymphomas in immunosuppressed individuals. 1 T2-weighted MRI may reveal hyperintensities in cortical white and gray matter. 1
JC Virus (Progressive Multifocal Leukoencephalopathy) affects patients with cell-mediated immunodeficiencies, particularly AIDS and hematologic malignancies. 1 MRI shows nonenhancing, confluent subcortical white matter hyperintensity on T2 or FLAIR sequences. 1
Human Herpesvirus 6 (HHV-6) causes reactivation disease particularly in transplant recipients, with MRI revealing hyperintense T2-weighted signal in white matter of frontal and parietal lobes extending to edema of temporal lobes and limbic system. 1
Fungal and Parasitic Infections
Cryptococcus is a critical fungal pathogen causing meningoencephalitis in immunocompromised patients. 1
Toxoplasma gondii represents an important parasitic cause of brain lesions with associated vasogenic edema in immunosuppressed individuals. 1
Bacterial Causes
Listeria monocytogenes and tuberculous meningitis should be considered as bacterial causes of encephalitis with potential vasogenic edema in immunocompromised hosts. 1
Non-Infectious Causes
Primary CNS lymphomas are usually EBV-driven and occur in severely immunosuppressed patients, particularly those with advanced HIV. 1
Cerebral amyloid angiopathy-related inflammation can present with vasogenic edema and numerous microhemorrhages in immunosuppressed patients. 4
Pathophysiological Mechanism
Vasogenic edema results from alterations in the blood-brain barrier through direct actions on cerebrovascular endothelial cells or mediated through the neurovascular unit, causing extracellular fluid accumulation. 1, 5 This contrasts with cytotoxic edema, which involves intracellular water accumulation from failed ion transport. 1, 5
In immunocompromised patients, impaired inflammatory and immune responses mean that severely immunosuppressed patients may have brain lesions on CT not associated with focal neurological presentations or papilledema. 1 MRI is therefore the imaging modality of choice in immunocompromised patients. 1
Critical Clinical Pitfalls
Immunocompromised patients are more likely to have subtle and sub-acute presentations of viruses that cause acute encephalitis in immunocompetent hosts. 1
CSF may be acellular in immunocompromised patients with encephalitis despite increased risk of CNS infection, so CSF investigations for microbial pathogens should be performed irrespective of CSF cell count. 1
Less common pathogens to consider include Coccidioides species, Histoplasma capsulatum, and West Nile virus, depending on geographic exposure and clinical circumstances. 1