What is the appropriate diagnostic and therapeutic approach for a patient with suspected viral encephalitis?

Management of Suspected Viral Encephalitis

All patients with suspected viral encephalitis require immediate empirical intravenous acyclovir at 10 mg/kg every 8 hours without waiting for diagnostic confirmation, as this dramatically reduces mortality from herpes simplex encephalitis—the most treatable cause—from 70% to approximately 25%. 1, 2

Immediate Empirical Treatment (Within First Hour)

• Start IV acyclovir 10 mg/kg every 8 hours immediately upon clinical suspicion, before any diagnostic testing is completed 1, 2
• Continue empirical acyclovir for minimum 14-21 days for confirmed HSV encephalitis; immunocompromised patients require at least 21 days 1, 2
• Do not delay acyclovir while awaiting lumbar puncture, neuroimaging, or PCR results—treatment must begin within the first hour of presentation 1, 3, 4
• Consider adding empirical antibiotics (ceftriaxone plus vancomycin) if bacterial meningitis cannot be excluded, and doxycycline if rickettsial or ehrlichial infection is possible based on exposure history 1

Diagnostic Workup (Parallel to Treatment Initiation)

Lumbar Puncture Timing and Contraindications

• Perform LP as soon as possible after hospital admission unless specific contraindications exist 1
• Contraindications requiring CT head first: focal neurological deficits suggesting mass effect, papilledema, Glasgow Coma Scale <12, new-onset seizures, severe immunocompromise, or anticoagulation 1
• If CT shows significant brain shift, tight basal cisterns, or raised intracranial pressure, consider LP on case-by-case basis 1
• For anticoagulated patients: reverse warfarin with vitamin K plus prothrombin complex concentrate or fresh frozen plasma; stop heparin and reverse with protamine before LP 1
• If LP initially contraindicated, reassess every 24 hours and perform when safe 1

Essential CSF Studies

• HSV-1/2, VZV, and enterovirus PCR (highest priority—HSV PCR has >95% sensitivity and specificity for HSE) 1, 3, 4
• Cell count with differential, protein, glucose 3, 4
• Bacterial culture and Gram stain 1
• Additional PCR for immunocompromised: EBV, CMV, HHV-6 1
• Consider: Cryptococcal antigen, acid-fast bacilli staining/culture, VDRL, Toxoplasma antibodies in immunocompromised patients 1

Neuroimaging

• MRI brain with and without contrast is preferred over CT—detects early HSE changes in 90% versus only 25% for CT 1, 5, 3
• Perform MRI as soon as possible, ideally within 24-48 hours 1, 5
• If MRI unavailable, obtain CT head, but recognize its significant limitations 1, 3
• Classic HSE findings: temporal lobe involvement with hemorrhagic changes 3, 4

Additional Investigations

• EEG: shows epileptiform activity in 50% early, generalized slowing in 80% later 1
• Serum studies: HSV serology (less useful acutely), autoimmune encephalitis antibodies (NMDA receptor, VGKC-complex), paraneoplastic antibodies 1, 5
• Blood cultures, HIV testing, complete metabolic panel 1

Special Populations

Immunocompromised Patients

• Broader empirical coverage required: continue acyclovir 10 mg/kg every 8 hours for minimum 21 days, then reassess with repeat CSF PCR 1
• Consider long-term oral suppressive therapy until CD4 >200 cells/μL in HIV patients 1
• Expanded diagnostic workup must include: CMV, EBV, VZV, JC virus, Toxoplasma, Cryptococcus, Mycobacterium tuberculosis, Listeria 1
• CT before LP should be strongly considered even without focal signs 1

Elderly Patients

• HSV encephalitis is more common in elderly than younger adults, making prompt diagnosis especially critical 1
• Higher likelihood of alternative diagnoses (stroke, systemic sepsis causing encephalopathy), but do not withhold empirical acyclovir 1
• Acyclovir dose adjustment required for renal impairment (common in elderly): creatinine clearance 50-80 mL/min requires dose reduction 2

Travelers/Geographic Considerations

• Consider arboviral causes (West Nile, Japanese encephalitis, dengue), rabies, malaria based on travel history 1, 6
• If cerebral malaria suspected and film results delayed, start antimalarials empirically 1
• No proven specific therapy exists for most arboviral encephalitides—supportive care is critical 1, 6

Autoimmune Encephalitis Considerations

• If viral workup negative after 48-72 hours and patient not improving, strongly consider autoimmune encephalitis 1, 5
• NMDA receptor antibody encephalitis: send serum and CSF antibodies (CSF more sensitive), initiate high-dose IV methylprednisolone 1g daily for 3-5 days plus either IVIG or plasma exchange 1, 5
• Screen for underlying malignancy: CT or PET chest/abdomen/pelvis, especially ovarian teratoma in young women 1, 5
• Second-line immunotherapy (rituximab, cyclophosphamide) if poor response to first-line 1, 5

Critical Care Management

• ICU admission indicated for: declining consciousness requiring airway protection, seizures, dysautonomia, signs of increased intracranial pressure 1, 7, 6
• Seizure management: IV levetiracetam 30-60 mg/kg/day or IV valproate 20-30 mg/kg loading dose; avoid phenytoin as first-line 5
• Monitor and correct electrolyte abnormalities, particularly hyponatremia 7
• Surgical decompression reserved for impending uncal herniation or refractory increased intracranial pressure 3, 4

Common Pitfalls to Avoid

• Never delay acyclovir while awaiting PCR confirmation—HSV PCR can be negative in first 72 hours or with delayed LP 1, 8
• Do not rely on CT brain alone—MRI is vastly superior for detecting early encephalitic changes 5, 3
• Do not discharge patients without definite or suspected diagnosis and confirmed outpatient follow-up 1
• Do not assume normal CSF excludes encephalitis in immunocompromised patients 1
• Corticosteroids are not routinely recommended for viral encephalitis and may worsen HSV outcomes; reserve for confirmed autoimmune or ADEM cases 1, 6, 3

Prognosis and Follow-up

• HSV encephalitis mortality: 70% untreated, reduced to 25% with acyclovir; only 32% achieve normal function or mild sequelae even with treatment 2, 8
• All patients require comprehensive rehabilitation assessment before discharge—30-50% develop long-term neurological or psychiatric sequelae including anxiety, depression, obsessive behaviors, and cognitive deficits 1, 6, 5
• Arrange outpatient follow-up with neurology, neuropsychology, and rehabilitation services at discharge—never discharge without scheduled appointments 1, 5
• Sequelae may not be immediately apparent at hospital discharge but emerge weeks to months later 1, 6

Outcome Measures

• Acyclovir must be administered at appropriate dosing (10 mg/kg every 8 hours, adjusted for renal function) 1, 2
• Once etiologic agent identified, target therapy specifically or discontinue if no specific treatment available 1
• Medical record must document specific reasons if neuroimaging not performed 1