What is the most likely cause and recommended management of acute encephalopathy in a patient with active herpes zoster (shingles)?

Encephalopathy with Shingles

Most Likely Cause

In a patient with active shingles presenting with encephalopathy, the most likely cause is VZV encephalitis due to viral reactivation with CNS invasion, typically manifesting as a vasculopathy affecting cerebral vessels. 1

VZV is one of the most commonly identified causes of acute encephalitis in adults, and critically, CNS reactivation may occur even in the absence of visible skin lesions. 1 The pathophysiology involves viral reactivation leading to CNS vasculopathy, particularly affecting small vessels in immunocompromised patients (multifocal leukoencephalopathy) and large vessels in immunocompetent hosts. 1, 2

Key Diagnostic Considerations

• Proximity matters: The closer the dermatomal herpes zoster is to the CNS (head/neck shingles), the higher the likelihood of symptomatic CNS involvement including encephalitis. 3
• Immunocompromised patients are at particularly high risk for VZV encephalitis and multifocal leukoencephalopathy. 1, 2
• Temporal relationship: Encephalopathy developing during or shortly after shingles onset strongly suggests VZV encephalitis rather than other etiologies. 4, 3

Immediate Management Algorithm

Step 1: Initiate Empiric Antiviral Therapy Immediately

Start intravenous acyclovir 10 mg/kg every 8 hours immediately upon clinical suspicion, without waiting for virological confirmation. 1, 5 Treatment delays beyond 48 hours after hospital admission are associated with significantly worse prognosis and increased mortality. 1, 6

• For VZV encephalitis, some experts recommend 15 mg/kg three times daily if renal function is normal, though most clinicians use 10 mg/kg due to renal toxicity concerns. 1
• Treatment duration should be at least 7-14 days depending on clinical response. 1, 5
• Aggressive hydration (2.5-3 liters/m²/day) is essential to prevent acyclovir-induced renal complications. 5

Step 2: Obtain Diagnostic Studies

Perform MRI (preferred over CT), EEG, and lumbar puncture unless contraindicated. 1

CSF Analysis Priority:

• Send both VZV PCR AND VZV antibody testing - antibody detection in CSF has greater sensitivity than viral DNA detection alone. 1
• VZV PCR sensitivity is only 80-95% in immunocompromised patients, so negative PCR does not exclude the diagnosis. 5
• Look for CSF atypical lymphocytes (17-26% range), which are a rare but important diagnostic clue for VZV encephalitis. 3
• Typical CSF profile shows lymphocytic pleocytosis with normal glucose and variably elevated protein. 3

Neuroimaging:

• MRI with T2-weighted or FLAIR sequences is the gold standard, showing hyperintensities in affected brain regions. 7
• CT has limited sensitivity (may be normal in up to 37% of cases) but is useful to exclude intracranial hemorrhage. 7

EEG:

• General background slowing bilaterally is typical of viral encephalitis. 3
• Absence of unilateral focal frontotemporal/parietal focus argues against HSV encephalitis. 3

Step 3: Monitor for Acyclovir Neurotoxicity

Critical pitfall: Acyclovir itself can cause encephalopathy, particularly in patients with renal impairment, elderly patients, or immunocompromised individuals. 8, 9, 10

• Monitor renal function closely - acyclovir plasma concentrations are higher in geriatric patients due to age-related renal changes. 8
• Dose reduction is required in patients with underlying renal impairment. 8
• If encephalopathy worsens or fails to improve despite acyclovir therapy, consider acyclovir neurotoxicity as a complicating factor. 9, 10
• In cases where acyclovir neurotoxicity is suspected and VZV PCR is positive, the management dilemma requires careful risk-benefit assessment. 10

Step 4: Adjunctive Therapies

Consider corticosteroids (60-80 mg prednisolone daily for 3-5 days), particularly if there is evidence of vasculitic component. 1

• The inflammatory nature of VZV encephalitis provides rationale for steroid use. 1
• Stronger indication exists when vasculopathy is documented on imaging. 1

Implement seizure management:

• Administer antiepileptic treatment for patients who develop seizures. 7
• Consider prophylactic anticonvulsants in high-risk patients with significant neurological deficits. 7

Step 5: Supportive Care

• Elevate head of bed to 30 degrees to reduce intracranial pressure. 7
• Implement aspiration precautions and IV hydration for altered consciousness. 7
• Avoid medications causing CNS depression. 7
• Correct electrolyte imbalances and monitor renal function closely. 1

Special Populations

Immunocompromised Patients:

• Higher risk for multifocal leukoencephalopathy and visceral dissemination. 1, 5, 2
• May require prolonged courses of IV acyclovir. 1
• Require immediate hospitalization. 5

Dialysis Patients:

• Particularly vulnerable to both VZV encephalitis and acyclovir neurotoxicity. 4
• Encephalopathy may develop despite oral acyclovir treatment for preceding herpes zoster. 4
• Rapid response to IV acyclovir is expected if VZV encephalitis is the cause. 4

Common Pitfalls to Avoid

1. Waiting for diagnostic confirmation before starting acyclovir - this delay significantly worsens outcomes. 1, 5
2. Assuming visible rash is required - CNS reactivation can occur without skin lesions. 1
3. Relying solely on VZV PCR - antibody testing increases diagnostic sensitivity. 1
4. Inadequate hydration - failure to provide aggressive IV fluids increases risk of acyclovir-induced renal failure. 5
5. Missing acyclovir neurotoxicity - worsening encephalopathy on treatment may indicate drug toxicity rather than treatment failure. 9, 10
6. Underdosing in renal impairment - requires careful dose adjustment, not complete avoidance. 8

Prognosis

Most cases of VZV encephalitis respond well to prompt acyclovir therapy, with complete recovery expected if treatment is initiated early. 1, 4, 3 However, delays in treatment beyond 48 hours significantly worsen outcomes. 1 Elderly patients (>63 years) have higher mortality risk. 6