What is the treatment for Brainstem Encephalitis?

Treatment of Brainstem Encephalitis

Immediately initiate empirical therapy with intravenous acyclovir (10 mg/kg every 8 hours) plus ampicillin (2g every 4 hours) within the first hour of clinical suspicion, as this combination covers the two most common treatable causes—HSV and Listeria monocytogenes—and significantly reduces mortality and morbidity. 1, 2, 3

Immediate Empirical Treatment Protocol

Core Antimicrobial Therapy

• Start acyclovir 10 mg/kg IV every 8 hours immediately for all suspected brainstem encephalitis cases, as HSV (particularly HSV-1) accounts for approximately 80% of viral brainstem encephalitis and early treatment reduces mortality from 70% to 8-30% 1, 2, 4, 3

• Add ampicillin 2g IV every 4 hours to cover Listeria monocytogenes, which is the most common bacterial cause of infectious brainstem encephalitis, particularly in healthy young adults 1, 3

• Do not delay treatment for lumbar puncture or neuroimaging results—treatment must begin within 1 hour of clinical suspicion, as delays beyond 2-4 hours significantly worsen outcomes 1, 5, 2

Pathogen-Specific Considerations

Listeria monocytogenes (most common bacterial cause):

• Presents with biphasic illness: flu-like prodrome followed by brainstem dysfunction with autonomic dysfunction, myoclonus, and cranial neuropathies 1, 3
• 75% have CSF pleocytosis and nearly 100% have abnormal brain MRI 3
• Ampicillin plus gentamicin is the recommended combination; trimethoprim-sulfamethoxazole is the alternative in penicillin-allergic patients 1
• Critical pitfall: Cephalosporins do NOT cover Listeria—never use third-generation cephalosporins alone in patients ≥50 years or with risk factors 5

Herpes Simplex Virus (third most common infectious cause):

• HSV-1 causes 80% of HSV brainstem encephalitis cases, HSV-2 causes 20% 3
• 50% have isolated brainstem involvement; 50% also have supratentorial (temporal/frontal) involvement 3
• Mortality with acyclovir is 22% versus 75% without treatment 3
• Continue acyclovir for 14-21 days in confirmed cases 1, 2

Varicella-Zoster Virus:

• Can cause brainstem encephalitis associated with Ramsay Hunt syndrome, often without rash, fever, or CSF pleocytosis 1
• Acyclovir is recommended; ganciclovir is an alternative; adjunctive corticosteroids can be considered 1

Additional Empirical Coverage Based on Clinical Context

If bacterial meningitis cannot be excluded:

• Add ceftriaxone (2g IV every 12 hours) or cefotaxime to the ampicillin regimen 5
• This provides coverage for S. pneumoniae and N. meningitidis while maintaining Listeria coverage 5

If rickettsial or ehrlichial infection suspected (based on exposure history, rash):

• Add doxycycline to the empirical regimen 1

If tuberculosis or brucellosis suspected (based on epidemiology, subacute presentation):

• These can also cause brainstem encephalitis with autonomic dysfunction and cranial neuropathies 1

Diagnostic Workup (Performed Concurrently with Treatment)

Neuroimaging

• MRI is preferred over CT for brainstem encephalitis, as it has superior sensitivity for brainstem lesions 1, 6, 7
• Perform imaging as soon as possible, but do not delay treatment 1
• Nearly 100% of Listeria brainstem encephalitis cases show abnormal MRI 3

Lumbar Puncture

• Perform LP as soon as possible after admission unless contraindicated by signs of raised intracranial pressure or brain shift 1
• If CT shows significant brain shift, tight basal cisterns, or raised ICP, consider LP on case-by-case basis 1

CSF Analysis

• HSV PCR on all CSF specimens—if negative but clinical suspicion remains high, repeat LP in 3-7 days 1, 2
• CSF cultures for bacteria (including Listeria) and blood cultures 3
• CSF protein, glucose, cell count, and differential 6, 7
• Consider VZV PCR, enterovirus PCR, and other viral studies based on clinical context 1

Treatment Duration and Monitoring

• Acyclovir for HSV: 14-21 days for confirmed HSV encephalitis 1, 2
• Ampicillin for Listeria: 21 days for confirmed Listeria infection 1, 5
• Monitor renal function throughout acyclovir treatment, as nephropathy occurs in up to 20% of patients, typically after 4 days of IV therapy 2, 4
• Ensure adequate hydration during acyclovir administration to prevent crystalluria and obstructive nephropathy 2, 4

Dose Adjustments

• Neonates: Acyclovir 20 mg/kg IV every 8 hours 5, 2, 4
• Renal impairment: Reduce acyclovir dose based on creatinine clearance 2, 4
• Elderly patients: Consider dose reduction due to age-related renal function decline 4

Autoimmune and Paraneoplastic Causes

If infectious workup is negative and patient fails to improve on antimicrobials:

• Consider autoimmune brainstem encephalitis, particularly Behçet disease (most common autoimmune cause) 3, 8

• Over 90% of Behçet brainstem encephalitis cases have abnormal MRI and 94% have CSF pleocytosis 3

• High-dose IV corticosteroids (methylprednisolone 1g IV daily for 3-5 days) are recommended for autoimmune causes 1, 8

• Consider plasma exchange if poor response to corticosteroids 1

• Paraneoplastic brainstem encephalitis typically has normal MRI, CSF pleocytosis with normal protein, and detectable anti-neuronal antibodies 3, 8

• Prognosis is poor; treatment with immunosuppression is only partially beneficial 3

Critical Pitfalls to Avoid

• Never delay acyclovir while awaiting diagnostic confirmation—early treatment is the single most important factor in reducing mortality 1, 2
• Never use cephalosporins alone in patients ≥50 years or with immunocompromise, as they do not cover Listeria 1, 5
• Never assume labial herpes indicates HSV encephalitis—it is merely a marker of critical illness with no diagnostic specificity 1
• Do not stop empirical therapy prematurely even if initial CSF studies are negative—HSV PCR can be falsely negative early in disease 1, 2
• Do not overlook VZV as a cause, especially in elderly or immunocompromised patients, as it can present without rash 1

Supportive Care

• All patients require hospitalization with access to intensive care units 6, 7
• Monitor for increased intracranial pressure and impending herniation 6, 7
• Surgical decompression may be indicated for refractory increased ICP or impending uncal herniation 6, 7
• Intensive supportive and rehabilitative care is essential, as some patients show slow improvement over weeks to months even without specific diagnosis 9