Can herpes zoster (varicella‑zoster virus reactivation) cause encephalopathy in older or immunocompromised patients?

Can Herpes Zoster Cause Encephalopathy?

Yes, herpes zoster (varicella-zoster virus reactivation) definitively causes encephalopathy and encephalitis, particularly in older adults and immunocompromised patients, and requires immediate empiric intravenous acyclovir treatment. 1

Epidemiology and Risk

VZV encephalitis ranks among the most common identified etiologies of acute encephalitis in adults, and CNS reactivation can occur even when cutaneous lesions are absent. 1 The mechanism involves:

• Small-vessel vasculopathy (multifocal leukoencephalopathy) that predominates in immunocompromised hosts 1
• Large-vessel disease that is more typical in immunocompetent individuals 1
• Direct CNS invasion following viral reactivation from dorsal-root and cranial-nerve ganglia 1

The probability of VZV reactivation rises progressively with age, reaching approximately 50% in individuals older than 85 years. 1 Encephalitis affects only 0.1–0.2% of herpes zoster patients overall but occurs more frequently in disseminated cases. 2

High-Risk Populations

Immunocompromised patients have markedly higher risk for VZV encephalitis and multifocal leukoencephalopathy. 1 Specific high-risk conditions include:

• HIV/AIDS infection 1
• Hematologic malignancies (lymphoma, leukemia) 1
• Solid-organ or hematopoietic stem-cell transplantation 1
• Chronic systemic corticosteroid therapy 1
• Immunosuppressive regimens for autoimmune diseases 1

Importantly, VZV encephalitis can occur in immunocompetent children and adults, though this is rare. 3, 4

Clinical Presentation

VZV encephalitis is the most likely cause of encephalopathy in patients with active shingles. 1 Key features include:

• Fever, headache, altered consciousness, ataxia, and seizures 1
• Onset may be insidious in elderly or immunocompromised individuals, often lacking fever or CSF pleocytosis 1
• Cutaneous lesions may be completely absent (zoster sine herpete), complicating diagnosis 1, 4
• Delirium is common in VZV encephalitis 1

Diagnostic Approach

Neuroimaging

Perform MRI as the preferred modality (over CT) to detect characteristic hyperintensities; MRI is the gold standard for identifying VZV-related lesions. 1

Cerebrospinal Fluid Analysis

Conduct lumbar puncture unless contraindicated. Send both VZV PCR and VZV antibody assays, because CSF antibody detection offers greater sensitivity than PCR alone. 1, 5 VZV PCR has 80–95% sensitivity and 95% specificity in immunocompromised patients. 1

Electroencephalography

Obtain EEG to assess for diffuse background slowing typical of viral encephalitis. 1

Treatment Protocol

Initiate empiric intravenous acyclovir 10 mg/kg every 8 hours immediately upon clinical suspicion, without awaiting virologic confirmation. 1, 5 This recommendation is critical because:

• Delaying antiviral treatment beyond 48 hours after hospital admission is linked to significantly poorer prognosis and higher mortality 1
• Continue therapy for a minimum of 7–14 days, adjusting duration according to clinical response 1, 5
• Some experts advocate 15 mg/kg three times daily in patients with normal renal function, but the majority use 10 mg/kg to limit renal toxicity 1

Adjunctive Therapy

Corticosteroids (e.g., prednisolone 60–80 mg daily for 3–5 days) may be considered, particularly when imaging demonstrates a vasculitic component, because VZV encephalitis has an inflammatory pathogenesis. 1, 5 The encephalitic process is mainly driven by immune-mediated inflammation rather than direct cytopathic injury. 1

Supportive Care

Maintain vigilant supportive care, including correction of electrolyte disturbances and close monitoring of renal function throughout treatment. 1 Aggressive hydration (2.5–3 liters/m²/day) is necessary to prevent renal complications of acyclovir. 1

Special Considerations for Immunocompromised Hosts

Immunocompromised patients require heightened vigilance for multifocal leukoencephalopathy and possible visceral dissemination; prolonged courses of intravenous acyclovir are often necessary. 1 Deep tissue invasion can lead to myelitis and hepatitis among other visceral complications. 1

Prognosis

When acyclovir is started promptly, most patients achieve complete recovery; however, treatment initiation after 48 hours markedly increases the risk of adverse outcomes. 1 Near-complete neurological recovery is possible with timely acyclovir and corticosteroid therapy. 3

Critical Pitfalls to Avoid

• Do not wait for virologic confirmation before starting IV acyclovir—treatment must be initiated immediately upon clinical suspicion 1, 5
• Do not dismiss the diagnosis based on absence of rash—CNS reactivation frequently occurs without cutaneous lesions 1, 4
• Do not rely on a single negative CSF PCR—VZV antibody testing in CSF may be more sensitive 1
• Do not delay treatment beyond 48 hours—this is the critical window that determines prognosis 1