What is the management of acute encephalitic syndrome?

Management of Acute Encephalitic Syndrome

Patients with suspected acute encephalitis require immediate empiric acyclovir treatment (10 mg/kg IV every 8 hours) while simultaneously pursuing urgent diagnostic workup, with management in a setting that provides neurological specialist review within 24 hours and immediate ICU access for deteriorating patients. 1, 2

Immediate Initial Management

Empiric Treatment

• Start acyclovir immediately (10 mg/kg IV every 8 hours in adults with normal renal function) for all suspected encephalitis cases, as HSV encephalitis is the most treatable cause and delays in treatment significantly worsen outcomes 2, 3
• Continue acyclovir for 14-21 days if HSV is confirmed; neonates require higher dosing (20 mg/kg IV every 8 hours for 21 days) 2
• Do not wait for diagnostic confirmation before starting acyclovir—the risk-benefit ratio strongly favors empiric treatment 3, 4

Critical Care Assessment

• Patients with declining consciousness require urgent ICU evaluation for airway protection, ventilatory support, management of raised intracranial pressure, optimization of cerebral perfusion pressure, and correction of electrolyte imbalances 1, 5
• Transfer to neurological ward, high dependency unit, or ICU based on severity of presentation 1
• Implement continuous monitoring for seizures, as both convulsive and non-convulsive seizures are common complications 6, 2

Diagnostic Workup (Performed Simultaneously with Treatment)

Neuroimaging

• MRI is the imaging modality of choice and should be obtained within 48 hours, as it detects early cerebral changes in approximately 90% of cases versus only 25% sensitivity for CT 6, 1
• MRI findings guide etiology: frontotemporal involvement suggests HSV; thalamic and basal ganglia lesions suggest Japanese encephalitis 2, 7
• If MRI is impractical due to patient instability or unavailability, urgent CT can exclude structural causes and raised intracranial pressure, but should not delay lumbar puncture if no contraindications exist 6, 3

Cerebrospinal Fluid Analysis

• Lumbar puncture is critical for diagnosis and should not be delayed unless strict contraindications exist (signs of herniation, focal mass lesion with mass effect) 1, 3
• CSF PCR results should ideally be available within 24-48 hours of collection 1
• CSF pleocytosis generally favors infectious etiology; normal CSF suggests encephalopathy or non-infectious causes 7

Electroencephalography

• EEG is abnormal in >80% of encephalitis cases but need not be performed routinely in all patients 6
• Obtain EEG when: distinguishing psychiatric versus organic causes in patients with mildly altered behavior, or when subtle motor or non-convulsive seizures are suspected 6, 2

Etiology-Specific Treatment Modifications

Viral Causes

• HSV encephalitis: Continue acyclovir 10 mg/kg IV every 8 hours for 14-21 days (mortality reduced to 5% with treatment) 2
• VZV encephalitis: Acyclovir 10-15 mg/kg IV three times daily; consider short course of corticosteroids if vasculitic component is present 2
• CMV encephalitis: Combination therapy with ganciclovir (5 mg/kg IV every 12 hours) plus foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours) for 3 weeks 2

Parasitic Causes

• Cerebral malaria (Plasmodium falciparum): Quinine, quinidine, or artemether; exchange transfusion for ≥10% parasitemia; corticosteroids are NOT recommended 6, 1
• Obtain rapid blood malaria antigen tests and three thick/thin blood films for patients from endemic areas; if cerebral malaria is likely and results delayed, initiate anti-malarial treatment immediately 1
• Toxoplasma gondii: Pyrimethamine plus either sulfadiazine or clindamycin 6, 1

Autoimmune/Postinfectious Causes

• Acute Disseminated Encephalomyelitis (ADEM): High-dose corticosteroids are first-line; alternatives include plasma exchange or intravenous immunoglobulin 6, 1
• Distinguishing ADEM from acute infectious encephalitis is critical as management differs fundamentally 6

Syndromic Approach for Resource-Limited Settings

• Neurological AES pattern (frontotemporal MRI lesions): Treat as HSV with acyclovir pending confirmation 7
• Systemic AES pattern (fever, hepatosplenomegaly, thrombocytopenia, normal/minimal MRI changes): Test for malaria first; if positive, give antimalarials; if negative, start doxycycline and ceftriaxone for scrub typhus/leptospirosis pending serology 7

Seizure Management

• Treat seizures with appropriate antiepileptic medications alongside acyclovir 2
• For refractory status epilepticus, consider continuous EEG monitoring and escalation to anesthetic agents under ICU care 2
• Monitor for drug interactions between antimicrobials and antiepileptic medications 2

Adjunctive Therapies and Controversies

Corticosteroids

• Corticosteroids are NOT generally recommended for acute viral encephalitis and remain controversial 3
• One retrospective study showed better outcomes in HSV encephalitis patients treated with corticosteroids, but this lacks prospective validation 2
• Corticosteroids ARE indicated for ADEM, VZV with vasculitis, and Baylisascaris procyonis 6, 2

Surgical Intervention

• Surgical decompression is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management 3

Discharge Planning and Rehabilitation

• Do not discharge patients without either a definite or suspected diagnosis and formulated follow-up plans 1
• All patients require access to rehabilitation assessment, as sequelae (anxiety, depression, cognitive deficits) may not be immediately apparent at discharge 1, 5
• Arrange outpatient follow-up and ongoing therapy plans at a discharge meeting 1
• Many patients experience long-term neuropsychological deficits requiring multidisciplinary management 4, 8

Critical Pitfalls to Avoid

• Never delay acyclovir while awaiting diagnostic confirmation—HSV encephalitis outcomes are time-dependent 2, 3, 4
• Do not rely on CT alone; MRI is far more sensitive for early changes 6
• Do not withhold lumbar puncture unnecessarily; it can be performed after neuroimaging if immediately available, but strict contraindications are rare 3
• Do not discharge without rehabilitation assessment and follow-up planning 1
• Consider geographic and seasonal epidemiology when determining likely pathogens (e.g., malaria in endemic areas, Japanese encephalitis in Asia) 1, 7