What is the appropriate management for transient confusion following a high fever, potentially indicating acute febrile encephalopathy?

Management of Transient Confusion After High Fever

Transient confusion following high fever should not automatically be labeled as acute febrile encephalopathy; instead, it requires systematic evaluation to distinguish true encephalitis from other causes of encephalopathy, with metabolic, toxic, autoimmune, and non-CNS sepsis sources being considered early in the diagnostic workup. 1

Key Diagnostic Distinction

The critical first step is differentiating true encephalitis from other encephalopathies:

• Features suggesting non-encephalitic encephalopathy include past history of similar episodes, symmetrical neurological findings, myoclonus, asterixis, lack of fever, acidosis, or unexplained negative base excess 1

• Features suggesting true encephalitis include the constellation of current or recent febrile illness with altered behavior, personality, cognition or consciousness, new onset seizures, or new focal neurological signs 1

• Metabolic, toxic, autoimmune and non-CNS sources of sepsis must be considered early as causes for encephalopathy, especially when features suggest a non-encephalitic process 1

Clinical Assessment Algorithm

History Elements to Obtain

• Duration and pattern of fever (high fever vs. low-grade pyrexia) 1
• Timing of confusion relative to fever (during fever vs. persisting beyond 24 hours after defervescence) 1
• Presence of headache, vomiting, or seizures 1
• Travel history, animal contacts, insect bites, recent vaccination 1
• Rash (varicella zoster, enterovirus, rickettsial disease) 1
• Known immunocompromise or HIV risk factors 1

Examination Findings That Matter

• Glasgow Coma Score and mini-mental state (though GCS is crude for detecting subtle behavioral changes) 1
• Focal neurological signs (present in 78% of pediatric encephalitis cases vs. typically absent in simple febrile encephalopathy) 1
• Meningism, papilloedema, movement disorders 1
• Symmetrical vs. asymmetrical findings (symmetrical suggests metabolic/toxic cause) 1
• Asterixis or myoclonus (suggests metabolic encephalopathy) 1

Immediate Management Priorities

Temperature Control

• Aggressively treat fever to normal levels with antipyretic medications (acetaminophen or NSAIDs as first-line agents), as fever is independently associated with poor neurological outcomes 2, 3
• Target temperature of 36.0-37.5°C 2
• Do not delay antipyretic treatment while searching for fever source, as fever duration correlates with worse outcomes 2

Diagnostic Workup

If altered consciousness or focal neurologic signs are unexplained:

• Lumbar puncture should be considered unless contraindicated 1
• For new focal neurologic findings suggesting disease above the foramen magnum, obtain imaging (non-contrast CT adequate to exclude mass lesions) before lumbar puncture 1
• If bacterial meningitis suspected and lumbar puncture delayed, start empirical antibiotics after blood cultures obtained 1

CSF analysis should include:

• Bacterial cultures, viral PCR panel (HSV, enterovirus, JE), cell count, protein, glucose 3, 4
• HSV PCR is critical as more subtle presentations are now recognized (low-grade pyrexia, speech disturbances, behavioral changes) 1

Imaging:

• MRI within 48 hours is the imaging modality of choice, detecting early cerebral changes in approximately 90% of cases versus only 25% for CT 3
• CT brain is adequate initially to exclude mass lesions or obstructive hydrocephalus 1

Additional investigations:

• At least two sets of blood cultures (60 mL total) 2
• Chest radiograph for all ICU patients with new fever 2
• Blood glucose, electrolytes, liver function, ammonia levels (to exclude metabolic causes) 4, 5

Common Etiologies in Acute Febrile Encephalopathy

Based on prospective studies from tertiary centers:

• Pyogenic meningitis (most common: 25.7-36.7%) 4, 5
• Viral encephalitis (11.4-28.3%): HSV, Japanese encephalitis, dengue, enteroviruses 4, 5
• Tuberculous meningitis (4.2-25.7%) 4, 5
• Cerebral malaria (21.7%) 5
• Septic encephalopathy (9.17%) 5
• Scrub typhus and leptospirosis (emerging causes) 4

Critical Pitfalls to Avoid

• Neurogenic fever occurs in approximately 25% of neurocritical patients; always investigate all potential infectious sources before attributing fever to central causes 3

• Febrile convulsions are distinct from encephalopathy: febrile seizures generally occur with onset of fever, while seizures as part of encephalopathy typically occur beyond 24 hours or with persistent altered consciousness 1

• Influenza-associated encephalopathy can present with rapid and severe clinical course, thought to be due to brain edema mediated by cytokines rather than direct brain invasion; steroids should be considered 1

• Avoid aspirin in children due to association with Reye's syndrome (acute encephalopathy with liver dysfunction following viral illness, particularly influenza B) 1

• Low GCS (<7) and undiagnosed cases of acute febrile encephalopathy are the strongest predictors of mortality 4

Disposition and Monitoring

• Patients with falling level of consciousness require urgent ICU assessment for airway protection, ventilatory support, and management of raised intracranial pressure 3

• Continuous oxygen saturation monitoring with target ≥92% 3

• Central temperature monitoring when available (bladder catheter, esophageal thermistor, or pulmonary artery catheter) for accurate temperature measurement 2

• Do not discharge without either a definite or suspected diagnosis, with arrangements for outpatient follow-up 3