A Rare Case of Multiple Ring-Enhancing Lesions on Magnetic Resonance Imaging of the Brain in Varicella-Zoster Virus Encephalitis with Human Immunodeficiency Virus

Case

A 50-year-old male with human immunodeficiency virus (HIV) infection, on highly active antiretroviral therapy, presented with new-onset generalized tonic-clonic seizures and right hemiparesis. On physical examination, no skin rash was noted, and the patient denied any prior history of skin lesions or rashes. The neurological examination demonstrated right upper and lower extremity weakness (Medical Research Council grade 3/5) but was otherwise unremarkable. Laboratory work revealed pancytopenia, C-reactive protein of 14 mg/L, CD4+ of 8, and a viral load of 102,491. The magnetic resonance imaging (MRI) of the brain with and without contrast demonstrated multiple ring-enhancing lesions in the bilateral cerebral hemispheres (right > left) on the T1 post-contrast sequence (Figure 1). The findings on the diffusion weighted imaging and the apparent diffusion coefficient sequences were not consistent with ischemic strokes. The gradient echo sequence did not demonstrate any hemorrhagic strokes. The computed tomography angiography was unremarkable with no segmental stenosis or occlusions. Serum Toxoplasma gondii IgM and IgG were negative. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 1, red blood cell count of 8, glucose of 51, protein of 68, and oligoclonal bands of 0. CSF polymerase chain reaction was positive for varicella-zoster virus (VZV) and negative for herpes simplex virus 1/2, Epstein-Barr virus, John Cunningham virus, Cryptococcus neoformans, Toxoplasma gondii, Enterococcus faecalis, and Mycobacterium tuberculosis. Intravenous acyclovir therapy was initiated. Repeat CSF analysis and MRI of the brain after intravenous acyclovir therapy revealed clearance of the VZV infection and an interval decrease in the multiple ring-enhancing lesions (Figure 1), respectively. A biopsy of the ring-enhancing lesion was offered to the patient for a definitive diagnosis; however, the patient refused. The patient was discharged on maintenance acyclovir therapy with no further reported recurrences.

Figure 1.

Magnetic resonance imaging of the brain: On the axial T1 post-contrast sequence, multiple ring-enhancing lesions were noted in the bilateral cerebral hemispheres (right > left) prior to intravenous acyclovir therapy. After completion of therapy, repeat imaging demonstrated a significant interval decrease in the multiple ring-enhancing lesions as noted on the axial T1 post-contrast sequence. Note the lesions on the corresponding axial T2 fluid-attenuated inversion recovery (FLAIR) sequence both prior to and after completion of acyclovir therapy.

Discussion

Multiple ring-enhancing lesions on MRI of the brain in VZV encephalitis have rarely been reported in literature. They are commonly seen in toxoplasmosis, tuberculomas, and primary central nervous system lymphoma in patients with HIV infection. ¹ VZV encephalitis is typically a vasculopathy with MRI of the brain showing ischemic and hemorrhagic strokes at the cortical-subcortical junction. ²

Patients with VZV encephalitis often present with focal neurological deficits on physical examination. A typical rash several months prior to the development of the focal neurological symptoms may be a subtle clue to the diagnosis but may not always be present. In addition, seizures may frequently occur in patients with VZV encephalitis. Nevertheless, VZV encephalitis should be considered in the differential diagnosis in HIV patients presenting with focal neurological deficits.

Multiple ring-enhancing lesions in VZV encephalitis is an atypical radiographic finding, which can be misdiagnosed for toxoplasmosis or tuberculomas due to a framing effect. A clinician may frame their judgment on the “multiple ring-enhancing lesions” rather than explore the other accompanying clinical manifestations. This case provides a broader radiological spectrum of findings that may be seen in patients with VZV encephalitis. It is important to be cognizant of the atypical radiographic findings and the subtle clinical manifestations of VZV encephalitis as it can lead to a timely diagnosis, early therapy, and improved neurological outcomes.

ORCID iD

Tasneem F. Hasan, MD, MPH, CPH https://orcid.org/0000-0001-7477-9502