What is the management approach for a patient with necrotizing post-infectious encephalitis, presenting with fever, headache, confusion, and seizures, following a recent viral infection?

Management of Necrotizing Post-Infectious Encephalitis

Initiate immediate high-dose intravenous methylprednisolone (1 gram daily for 3-5 days) as first-line therapy for necrotizing post-infectious encephalitis, with early consideration of plasma exchange or tocilizumab for severe or steroid-refractory cases, as aggressive early immunotherapy significantly improves neurological outcomes in this life-threatening condition. 1, 2

Immediate Critical Care Actions

Airway and ICU Management:

• Assess airway protection urgently in patients with declining consciousness, as necrotizing encephalitis causes rapid deterioration requiring ICU-level management of raised intracranial pressure and cerebral perfusion optimization 3, 4
• Transfer to intensive care unit for ventilatory support, intracranial pressure monitoring, and correction of electrolyte imbalances 5, 3
• Obtain neurological specialist assessment within 24 hours of presentation 3, 4

Empiric Antiviral Coverage:

• Start acyclovir 10 mg/kg IV every 8 hours immediately while awaiting diagnostic confirmation, particularly in patients with seizures or altered consciousness, as HSV encephalitis remains a critical differential diagnosis 3, 6
• Continue acyclovir for 14-21 days if HSV is confirmed; immunocompromised patients require at least 21 days 5, 3

Diagnostic Workup

Neuroimaging:

• Obtain MRI brain within 48 hours as the imaging modality of choice, which detects early cerebral changes in approximately 90% of cases versus only 25% sensitivity for CT 3, 4
• Look specifically for bilateral symmetrical thalamic lesions with central necrosis and hemorrhage, along with lesions in cerebral white matter, brainstem, and cerebellum—the characteristic pattern of acute necrotizing encephalopathy 7

Laboratory Studies:

• Perform lumbar puncture with CSF PCR assays for HSV and other viral pathogens, with results ideally available within 24-48 hours 3, 4
• Obtain EEG when distinguishing psychiatric versus organic causes or when subtle motor or non-convulsive seizures are suspected (abnormal in >80% of encephalitis cases) 3, 4
• For returning travelers from malaria-endemic areas, obtain rapid blood malaria antigen tests and three thick and thin blood films 5, 4

Immunotherapy Protocol

First-Line Treatment:

• Administer high-dose intravenous methylprednisolone as first-line therapy for acute disseminated encephalomyelitis (ADEM) and necrotizing encephalitis 3, 4
• Recent case reports demonstrate excellent outcomes with high-dose methylprednisolone combined with tocilizumab, with patients improving from Glasgow Coma Scale of 6 to 12 within three weeks 1

Second-Line and Combination Therapy:

• Consider plasma exchange (5-10 sessions every other day) for severe or steroid-refractory cases, as it is particularly effective in refractory encephalitis 3, 8
• Tocilizumab should be considered early in severe cases, particularly when cytokine storm is suspected as the underlying mechanism 1, 2
• Intravenous immunoglobulin may be of value in ADEM with peripheral nerve involvement or when corticosteroid therapy is contraindicated 8

Critical Timing Consideration: A common pitfall is delaying immunotherapy while awaiting definitive diagnosis. The evidence strongly suggests that early aggressive immunosuppression (within 24-48 hours) minimizes brain damage and systemic inflammation, with significantly better outcomes compared to delayed treatment 1, 9, 2. One case series showed dramatically different outcomes based on timing and aggressiveness of anti-inflammatory approach 9.

Seizure Management

Antiepileptic Drug Selection:

• IV valproate 20-30 mg/kg loading dose achieves 88% seizure cessation within 20 minutes without associated hypotension 3
• Levetiracetam 30-60 mg/kg/day demonstrates 73% seizure cessation rate 3
• Avoid phenytoin as first-line (only 56% efficacy and causes hypotension in 12% of cases) 3

Etiology-Specific Considerations

Post-Infectious Triggers:

• Necrotizing encephalitis has been reported following influenza A/H1N1, SARS-CoV-2, Chikungunya virus, and other viral infections 1, 9, 2, 7
• The mechanism involves cytokine storm and blood-brain barrier disruption rather than direct viral invasion 2
• Treatment focuses on immunosuppression rather than prolonged antiviral therapy once viral etiology is confirmed 8, 7

Exclude Treatable Mimics:

• Rule out cerebral malaria in returning travelers (treat with quinine, quinidine, or artemether if suspected) 4
• Exclude Toxoplasma gondii (treat with pyrimethamine plus sulfadiazine or clindamycin) 4

Multidisciplinary Team Involvement

The management requires input from neurologists, infectious disease physicians, virologists, neurophysiologists, neuroradiologists, neurosurgeons, and intensive care staff 5, 3

Discharge Planning and Rehabilitation

Mandatory Follow-Up:

• Do not discharge patients without either definite or suspected diagnosis and formulated rehabilitation plans 5, 3, 4
• All patients require comprehensive rehabilitation assessment before discharge, as 30-50% develop long-term neurological or psychiatric sequelae 10

Expected Sequelae:

• Monitor for anxiety, depression, obsessive behaviors, and cognitive deficits, which often become evident after discharge rather than during acute illness 5, 3
• Arrange neuropsychology, neuropsychiatry, speech and language therapy, neuro-physiotherapy, and occupational therapy assessments 5
• One study found 96% of encephalitis patients reported ongoing complications, yet 33% were discharged without outpatient follow-up—a critical gap to avoid 5

Prognosis: Recent case reports demonstrate that with early aggressive immunotherapy (high-dose steroids plus tocilizumab or plasma exchange), patients can achieve almost full neurological function with minimally dependent activities of daily living within 8 weeks post-treatment 1, 2. However, delayed treatment is associated with high morbidity and mortality 8, 7.