What is the management and treatment approach for acute febrile encephalopathy?

Management of Acute Febrile Encephalopathy

Patients with acute febrile encephalopathy require immediate empiric acyclovir 10 mg/kg IV every 8 hours while pursuing urgent diagnostic workup, with management in a setting where neurological specialist review is available within 24 hours. 1, 2, 3

Immediate Assessment and Stabilization

Critical Initial Actions

• Initiate acyclovir immediately for all patients with suspected encephalitis presenting with fever and altered mental status, at 10 mg/kg IV every 8 hours in adults and children with normal renal function (20 mg/kg IV every 8 hours in neonates), before diagnostic confirmation 2, 3
• Patients with Glasgow Coma Scale <7 or falling level of consciousness require immediate ICU assessment for airway protection, ventilatory support, management of raised intracranial pressure, optimization of cerebral perfusion pressure, and correction of electrolyte imbalances 2, 3
• Administer appropriate antiepileptic medications immediately if seizures are present, as seizures occur in approximately one-third of encephalitis cases 1, 2

Key Clinical Features to Assess

• Look specifically for fever (present in 80-91% of cases), altered mental status ranging from confusion to coma, disorientation (76%), speech disturbances (59%), behavioral changes (41%), and new-onset seizures (29-33%) 1, 4, 5
• Examine for focal neurological signs, neck stiffness, and document Glasgow Coma Score, as GCS <7 is the strongest predictor of mortality 1, 5
• Consider antibody-mediated encephalitis if subacute presentation (weeks-months), orofacial dyskinesia, choreoathetosis, faciobrachial dystonia, intractable seizures, or hyponatraemia are present 1, 2

Diagnostic Workup

Essential Investigations

• 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 3
• Perform lumbar puncture for CSF analysis including cell count, protein, glucose, Gram stain, bacterial culture, and PCR for HSV, enterovirus, and mycobacterium tuberculosis, with results ideally available within 24-48 hours 1, 3
• Obtain EEG when distinguishing psychiatric versus organic causes in patients with mildly altered behavior, or when subtle motor or non-convulsive seizures are suspected (abnormal in >80% of encephalitis cases) 3

Differential Diagnosis Considerations

• Exclude metabolic, toxic, autoimmune, and non-CNS sources of sepsis early, especially if there are features such as past history of similar episodes, symmetrical neurological findings, myoclonus, asterixis, lack of fever, or acidosis 1
• For patients returning from malaria-endemic areas, perform rapid blood malaria antigen tests and three thick and thin blood films, initiating anti-malarial treatment if cerebral malaria seems likely and there will be delay in obtaining results 3

Etiology-Specific Treatment

Viral Encephalitis

• Continue acyclovir 10 mg/kg IV every 8 hours for 14-21 days for confirmed HSV encephalitis in adults and children, which has decreased mortality to 5% 2
• For varicella-zoster virus encephalitis, administer acyclovir 10-15 mg/kg IV three times daily, with consideration of a short course of corticosteroids if a vasculitic component is present 2
• For cytomegalovirus encephalitis, use 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

Bacterial Meningitis

• Tuberculous meningitis is the predominant cause of acute febrile encephalopathy in developing countries (25.7% in recent studies), requiring anti-tuberculous therapy 5, 6
• Acute pyogenic meningitis accounts for 17-37% of cases, with Streptococcus pneumoniae and Haemophilus influenzae as major pathogens requiring appropriate antibiotics 5, 6, 7

Other Infectious Causes

• For cerebral malaria (Plasmodium falciparum), administer quinine, quinidine, or artemether, with exchange transfusion recommended for ≥10% parasitemia; corticosteroids are not recommended 3
• For Toxoplasma gondii, treat with pyrimethamine plus either sulfadiazine or clindamycin 3
• Consider emerging causes including scrub typhus and dengue encephalitis, which occur predominantly in post-monsoon seasons 5

Autoimmune/Inflammatory Encephalitis

• For Acute Disseminated Encephalomyelitis (ADEM), administer high-dose intravenous methylprednisolone as first-line treatment, followed by oral corticosteroid taper over 4-6 weeks 4, 3
• For antibody-mediated encephalitis (VGKC-complex or NMDA receptor), initiate early immunosuppression with high-dose steroids, IVIg, or plasma exchange, as early immune suppression results in improved outcomes 2, 8
• Screen for neoplasm in all patients with VGKC complex or NMDA receptor antibody-associated encephalitis 2

Management of Seizures

First-Line Antiepileptic Therapy

• Administer benzodiazepines as first-line treatment for acute seizures 2
• For refractory seizures, IV valproate at 20-30 mg/kg loading dose achieves 88% seizure cessation within 20 minutes without associated hypotension 2
• Levetiracetam 30-60 mg/kg/day is equally effective to valproate, with 73% seizure cessation rate in refractory status epilepticus 2

Refractory Status Epilepticus

• Consider continuous EEG monitoring and escalation to anesthetic agents under ICU care for refractory status epilepticus 2
• Phenytoin 18-20 mg/kg IV or fosphenytoin equivalent can be used, though efficacy is only 56% when following benzodiazepines and is associated with hypotension in 12% of cases 2

Special Populations and Considerations

Pediatric Patients

• Children may present with non-specific symptoms including feeding and respiratory difficulties, confusion, irritability, or behavior changes (up to 76% of cases) 4
• Patients with prolonged febrile seizures ≥30 minutes or requiring ≥2 intravenous anticonvulsants have 25-67% risk of acute encephalitis and require hospital admission 9

Prognostic Factors

• The strongest predictors of mortality are female gender, fever >38°C at admission, GCS <7, and undiagnosed cases of acute febrile encephalopathy 5
• MRI showing disease-related findings (such as altered signal intensity in bilateral medial temporal and insular areas in HSV encephalitis) predicts increased mortality 5

Discharge Planning and Follow-up

• Do not discharge patients without either a definite or suspected diagnosis, and formulate arrangements for outpatient follow-up and plans for ongoing therapy and rehabilitation at a discharge meeting 3
• All patients should have access to assessment for rehabilitation, as sequelae of encephalitis (including anxiety, depression, and cognitive deficits) may not be immediately apparent at discharge 2, 3
• Monitor for drug interactions between antimicrobials and antiepileptic medications 2