Rashless varicella-zoster virus encephalitis in two patients: diagnostic challenges and delayed neurological complications, a case report

Background Varicella-zoster virus (VZV) can cause a wide spectrum of central nervous system infections, but early diagnosis is challenging in the absence of a typical rash. Rashless VZV encephalitis often presents with non-specific clinical and neuroimaging findings and may mimic autoimmune encephalitis or primary central nervous system lymphoma. We report two patients with rashless VZV encephalitis confirmed by cerebrospinal fluid metagenomic next-generation sequencing (mNGS), highlighting diagnostic challenges and delayed neurological complications. Case presentation Patient 1 was a 68-year-old man who presented with fever, seizures, and impaired consciousness. Brain magnetic resonance imaging (MRI) showed multiple abnormal lesions, and cerebrospinal fluid analysis revealed marked pleocytosis and elevated protein levels. Cerebrospinal fluid cytology showed mitotic figures and suspicious atypical lymphoid cells, and serum GABAB antibody was weakly positive whereas the cerebrospinal fluid autoimmune encephalitis antibody panel was negative, raising concern for autoimmune encephalitis or primary central nervous system lymphoma. Cerebrospinal fluid mNGS detected VZV, confirming the diagnosis. He improved after acyclovir plus short-course dexamethasone, but developed a new acute ischemic lesion approximately 6 weeks later, together with recurrent cerebrospinal fluid inflammation, suggesting probable VZV-associated vasculopathy. Patient 2 was a 74-year-old man who presented with fever, low back pain, vomiting, and impaired consciousness. Brain MRI showed multifocal lesions involving the frontal lobe, brainstem, cerebellum, and bilateral temporal lobes. Cerebrospinal fluid mNGS confirmed VZV infection. He improved after antiviral treatment and dexamethasone, but later developed urinary retention, impaired defecation sensation, and bilateral lower-limb weakness, raising suspicion of VZV-related Elsberg syndrome. Conclusions Rashless VZV encephalitis may pose substantial diagnostic difficulty because routine clinical, imaging, and laboratory findings are often non-specific. Cerebrospinal fluid mNGS is a valuable adjunct for etiological diagnosis. Clinicians should also remain alert to delayed neurological complications during follow-up, particularly probable VZV-associated vasculopathy and lumbosacral nerve root involvement.