What is the initial evaluation and management for an adult with new‑onset encephalopathy?

Initial Evaluation and Management of New-Onset Encephalopathy in Adults

Immediate Stabilization and Airway Assessment

The first priority is to distinguish true encephalitis from encephalopathy, as this fundamentally determines management: encephalitis requires immediate empiric IV acyclovir and lumbar puncture, while encephalopathy demands identification and correction of underlying precipitating factors. 1

• Assess airway protection immediately: Patients with altered consciousness who cannot protect their airway require intubation, particularly if Glasgow Coma Scale is deteriorating or aspiration risk exists 2
• Transfer patients with declining consciousness to intensive care for airway management, ventilatory support, and cerebral perfusion optimization 2, 3
• Higher grades of encephalopathy necessitate ICU monitoring 2, 1

Critical Decision Point: Encephalitis vs. Encephalopathy

Features Suggesting Encephalitis (Requires Immediate Acyclovir)

Start IV acyclovir 10 mg/kg every 8 hours immediately if ANY of the following are present, before diagnostic results return: 1, 4

• Fever with altered mental status (present in 91% of HSV encephalitis cases) 2
• Seizures (present in one-third of encephalitis patients) 2
• Focal neurological deficits (speech disturbances, behavioral changes, focal weakness) 2
• Severe headache with nausea/vomiting 2
• CSF pleocytosis (even if glucose is low, which can occur in HSV) 4

Critical pitfall: Never delay acyclovir while awaiting lumbar puncture or imaging if encephalitis is suspected—mortality is high without treatment 1, 4

Features Suggesting Encephalopathy (Non-Inflammatory)

• Symmetrical neurological findings without focal deficits 2
• Extracranial sepsis source (urinary tract infection, pneumonia) 2, 3
• Known precipitating factors: hepatic disease, renal failure, metabolic derangements, medications, alcohol 5, 6
• Absence of fever or low-grade pyrexia only 2

Initial Diagnostic Workup

Neuroimaging (Perform Before Lumbar Puncture)

• MRI is superior to CT for evaluating encephalopathy and should be obtained when available 2
• CT brain is acceptable if MRI unavailable, primarily to exclude contraindications to lumbar puncture (mass effect, hemorrhage) and alternative diagnoses 2
• Neuroimaging is "usually appropriate" for new-onset altered mental status, delirium, or psychosis 2

Lumbar Puncture (If Encephalitis Suspected)

Collect at least 20 cc CSF if possible; freeze 5-10 cc for additional testing: 2

• Opening pressure, cell count with differential, protein, glucose 2
• HSV-1/2 PCR (mandatory—but note: can be negative in 5-10% if obtained <72 hours after symptom onset) 2, 4
• VZV PCR 2
• Enterovirus PCR 2
• Gram stain and bacterial culture 2
• Cryptococcal antigen, VDRL 2
• Oligoclonal bands and IgG index 2

Critical pitfall: A single negative HSV PCR should NOT prompt discontinuation of acyclovir if clinical suspicion remains high and the sample was obtained early 4

Blood Tests

• Routine blood cultures before antibiotics 2, 3
• Complete blood count, comprehensive metabolic panel (sodium, glucose, calcium, renal function, liver function) 2, 6
• Thiamine level and empiric IV thiamine 500 mg TID if any risk factors for Wernicke's encephalopathy (alcohol use, malnutrition, vomiting) 7
• HIV serology, syphilis testing (RPR and specific treponemal test) 2
• Hold acute serum for paired antibody testing (collect convalescent sample 10-14 days later) 2
• Ammonia level if hepatic encephalopathy suspected (though do not rely on this alone for diagnosis) 1

Electroencephalography (EEG)

• Obtain EEG in all patients with unexplained encephalopathy to detect non-convulsive status epilepticus, which occurs in up to 8% of comatose patients 3, 8
• EEG may show distinctive patterns: temporal lobe sharp waves in HSV-1, generalized slowing in metabolic encephalopathy 2, 8
• EEG is particularly critical if subtle motor movements or fluctuating consciousness off sedation 3

Additional Testing Based on Clinical Context

• Chest imaging (X-ray or CT) to identify pneumonia as sepsis source 2, 3
• Urine dipstick for blood to detect rhabdomyolysis 2
• Blood glucose monitoring in every patient; maintain >70 mg/dL 3

Management Algorithm for Confirmed/Suspected Encephalitis

Empiric Acyclovir Therapy

• Start IV acyclovir 10 mg/kg every 8 hours immediately (adjust for renal function) 1, 4
• Continue for 14-21 days if HSV confirmed 1, 4
• Acyclovir can be safely discontinued if: HSV PCR negative >72 hours after symptom onset, consciousness unaltered, normal MRI (performed >72 hours after symptoms), and CSF WBC <5×10⁶/L 4

Seizure Management

• Administer appropriate antiepileptics alongside acyclovir 4
• For refractory seizures: IV valproate 20-30 mg/kg loading dose or levetiracetam 30-60 mg/kg/day 4
• Treat with rectal/IV diazepam or IV lorazepam for acute seizures 3

Specialist Consultation

• Obtain immediate neurological specialist consultation with clinical review within 24 hours 4

Management Algorithm for Encephalopathy (Non-Inflammatory)

Identify and Correct Precipitating Factors (Resolves 90% of Cases)

The cornerstone of encephalopathy management is identifying and treating the underlying cause: 1

Septic Encephalopathy

• Initiate broad-spectrum IV antimicrobials within 1 hour of recognizing sepsis 3
• Obtain blood cultures before antibiotics but never delay antimicrobials for culture collection 3
• Target adequate tissue perfusion (capillary refill <2-3 seconds, warm extremities, baseline mental status, urine output >0.5 mL/kg/hour) 3
• Administer crystalloid boluses 10-20 mL/kg up to 40-60 mL/kg in first hour, titrated to perfusion markers 3
• Start norepinephrine if hypoperfusion persists despite fluids; target MAP ≥65 mmHg 3
• Apply supplemental oxygen to maintain saturation >90% 3

Hepatic Encephalopathy

• Lactulose 30-45 mL (20-30 g) orally three to four times daily, titrated to produce 2-3 soft stools per day 1
• Add rifaximin 550 mg twice daily to reduce recurrence risk by 58% 1
• Identify precipitating factors: infection, GI bleeding, constipation, medications, electrolyte disturbances 1
• Initiate liver transplant evaluation after first episode or if recurrent/intractable 1

Metabolic Encephalopathy

• Hyponatremia (most common metabolic cause—45% of cases): correct slowly to avoid osmotic demyelination 6
• Hypoglycemia (second most common—30% of cases): provide glucose source immediately 3, 6
• Correct electrolyte abnormalities (potassium, phosphate, calcium) promptly 3

Wernicke's Encephalopathy

• IV thiamine 500 mg three times daily if any risk factors (alcohol use, malnutrition, vomiting) 7
• Administer before glucose to prevent precipitation 7

Uremic Encephalopathy

• Arrange urgent dialysis if indicated 5

Supportive Care

• Minimize sedation; when required, titrate to predefined endpoints 3
• Maintain continuous observation with structured neurological examinations several times daily 3
• Position semi-recumbent with head of bed elevated 30-45° 3
• Encourage early mobilization once stable to prevent delirium and weakness 3

Common Pitfalls to Avoid

• Never delay acyclovir while awaiting confirmatory testing if encephalitis is possible 1, 4
• Do not stop acyclovir based solely on a single negative CSF PCR obtained early in illness 4
• Do not rely on ammonia levels alone for diagnosis or monitoring of hepatic encephalopathy 1
• Do not use corticosteroids as monotherapy or first-line treatment in encephalitis 4
• Do not aggressively fluid-load patients with predominant meningitis, as this may worsen cerebral edema 3
• Do not leave septic patients unattended; perform frequent structured neurological assessments 3

Prognostic Factors

• Early presentation (<6 hours from symptom onset) improves outcomes 6
• Higher Glasgow Coma Scale at presentation predicts better prognosis 6
• Septic encephalopathy has the worst prognosis among encephalopathy subtypes 6
• Mortality rate for encephalopathy in elderly is approximately 19%, with 79% of deaths occurring in patients with comorbidities 6