What is the recommended treatment for shingles with central nervous system (CNS) involvement?

Treatment of Shingles with Central Nervous System Involvement

For shingles with central nervous system involvement, intravenous acyclovir at a dose of 10 mg/kg every 8 hours for 14-21 days is the recommended treatment. 1, 2

Diagnosis and Clinical Presentation

• Herpes zoster affecting the CNS typically presents as meningitis with headache, photophobia, fever, and meningismus, or as encephalitis with altered mental status 1
• CSF analysis usually shows lymphocytic pleocytosis, mildly elevated protein, and normal glucose levels 1
• CSF PCR for VZV should be obtained to confirm the diagnosis, as it has high sensitivity and specificity 2, 1
• It's critical to distinguish between VZV meningitis and encephalitis, as encephalitis represents a more severe condition with higher risk of neurologic morbidity and mortality 1, 3

Treatment Protocol

First-Line Treatment

• Intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days in adults with normal renal function 1, 2
• Higher doses (20 mg/kg every 8 hours) are recommended for neonates 1, 3
• Treatment should be initiated as soon as possible after symptom onset, as earlier treatment is associated with better outcomes 1, 2

Management of Complications

• If CSF pressure is ≥25 cm of CSF and there are symptoms of increased intracranial pressure, perform CSF drainage via lumbar puncture 1
• For persistent pressure elevation, repeat lumbar puncture daily until pressure and symptoms stabilize 1
• Consider temporary percutaneous lumbar drains or ventriculostomy for patients requiring repeated daily lumbar punctures 1

Special Populations

• Pregnant or lactating patients may be treated in a fashion identical to nonpregnant patients with the same disease manifestation, except that doxycycline should be avoided 2
• Immunocompromised patients may have more severe disease with risk of cutaneous dissemination and visceral involvement including viral pneumonia, encephalitis, and hepatitis 4
• Patients with HIV infection are at increased risk for shingles with CNS involvement, and may have more severe or prolonged disease course 2, 4

Monitoring and Follow-up

• Monitor renal function throughout treatment, as acyclovir can cause nephrotoxicity 3
• Consider obtaining a repeat CSF specimen for PCR at the end of therapy in patients who have not had appropriate clinical response 3
• If PCR remains positive for VZV at the end of treatment, antiviral therapy should be continued 3
• Follow patients clinically after completion of therapy to monitor for potential neurological sequelae 1

Important Considerations and Pitfalls

• Failure to distinguish between meningitis and encephalitis can lead to inadequate treatment duration 1
• Delayed initiation of antiviral therapy is associated with worse outcomes, so treatment should begin as soon as possible, even before confirmatory test results are available 2, 1
• Relapse can occur after completion of therapy, requiring vigilant follow-up 1, 3
• Among patients with inflammatory bowel disease on immunomodulators who develop shingles with CNS involvement, immunomodulator therapy should be discontinued in severe cases if possible 2
• Immunomodulator therapy can be reintroduced after all vesicles have crusted over and fever has resolved 2

Alternative Treatments

• For patients with acyclovir allergy or resistance, foscarnet (40 mg/kg IV every 8 hours) may be considered 3
• Famciclovir and valacyclovir, while effective for uncomplicated herpes zoster, have not been adequately studied for CNS involvement and are not recommended as first-line therapy for this indication 5, 6

By promptly initiating intravenous acyclovir at appropriate doses and duration, monitoring for complications, and providing supportive care, the morbidity and mortality associated with CNS involvement in herpes zoster can be significantly reduced.