There is paucity of studies analyzing DWI in MRI sequences when imaging cytomegalovirus (CMV) meningoencephalitis. The main objective of this study is to demonstrate that DWI sequence is mandatory when imaging immunocompromised patients presenting with encephalitic symptoms, as this sequence can reveal very peculiar lesions in the setting of CMV encephalitis.

Three CSF PCR CMV positive cases were identified in a 13-year retrospective study with MRI scans including T1, FLAIR, DWI with automated ADC calculation, and T1 with contrast injection, and were reviewed by a senior neuroradiologist.

Our three cases presented multiple high-signal intensity punctiform lesions in DWI, which uniformly were in restricted diffusion. Each patient had multiple lesions (mean 19.3, range 12–30): 96.5% were supratentorial and 3.5% were infratentorial. Among supratentorial lesions, 62.5% were subependymal, 28.6% were periventricular and 8.9% were subcortical. Some lesions remained in a long lasting restricted diffusion state. All cases had FLAIR curvilinear periventricular high signal intensities. No contrast uptake was found.

Punctiform DWI lesions had a clear ventricle wall tropism, consistent with classical autopsy findings. The classical histological knowledge-compatible explanation for long lasting diffusion restriction is non-lethal cytotoxic edema owing to CMV inclusions.

Subependymal and periventricular punctiform restricted diffusion lesions in the setting of meningoencephalitis in immunocompromised patients seem highly evocative of CMV encephalitis. The diffusion sequence probably reveals focal lesions constitutive of cellular viral inclusions.