Fever with Altered Sensorium: Etiology, Evaluation, and Management

Etiology

1. CNS Infections (Most common and time-critical)

• Organisms vary by age. Streptococcus pneumoniae predominates in adults (>50% of cases). Neisseria meningitidis is most common in children/adolescents. Listeria monocytogenes affects neonates, elderly, and immunocompromised patients. Group B Streptococcus and E. coli are seen in the first 6 weeks of life.
• Pathogenesis: nasopharyngeal colonization → mucosal invasion → bacteremia → BBB crossing → CSF pleocytosis → cytokine cascade → cerebral edema → raised ICP → altered consciousness.
• Classic triad: fever + neck stiffness + altered sensorium (only present in ~45% of cases).

• Herpes simplex virus (HSV-1) is the most treatable cause and must be assumed until proven otherwise. Arboviruses (Japanese encephalitis, West Nile, Dengue) are important in endemic regions. Enteroviruses are common in children.
• Presentation: fever + behavioral change + seizures + focal neurological deficits. HSV classically involves temporal lobes (personality change, olfactory hallucinations, dysphasia).

• Subacute-to-chronic course (weeks to months). Fever + headache + meningism + cranial nerve palsies (CN VI, III most common). Basilar exudate on imaging. High suspicion in HIV, malnutrition, immunocompromised.

• Almost exclusively in immunocompromised (HIV, transplant). Can present subtly with low-grade fever, headache, minimal meningismus.

• Plasmodium falciparum (rarely P. vivax). Mechanism: infected red cell adhesion to cerebral endothelium → obstruction of microvascular flow + inflammatory cytokine release → encephalopathy. Untreated, nearly 100% fatal; with treatment, mortality is 15-20%. Common in endemic areas; peripheral smear and RDT are bedside tests.

• Fever + raised ICP + focal deficits. Sources: sinusitis, otitis media, dental infection, endocarditis, post-neurosurgical. Altered sensorium indicates significant mass effect or rupture.

2. Systemic Causes (Secondary CNS dysfunction)

Evaluation

Step 1: Initial Rapid Assessment (First 5-10 minutes)

• ABCs: Airway patency (GCS <8 → intubate), breathing, circulation (BP, HR, SpO2)
• Vital signs: Temperature, HR, BP, RR, SpO2, blood glucose (POCT immediately)
• Rapid neurological assessment: GCS, pupillary size/response, focal deficits, signs of herniation (Cushing's reflex = bradycardia + hypertension + irregular breathing)
• Do not delay empirical treatment for investigations in critically ill patients

Step 2: Focused History

• Onset and tempo (acute = bacterial/viral; subacute = TB/fungal/autoimmune)
• Travel history (malaria-endemic regions, AES areas)
• Immunocompromised state (HIV, steroids, transplant, diabetes)
• Animal contacts (rabies, Nipah)
• Seizure activity (witnessed, focal or generalized)
• Drug history, alcohol use
• Recent trauma, ear/sinus infection, dental procedure
• Vaccination history (meningococcal, HiB, JE)
• Contact with similar illness (meningococcal, enterovirus)

Step 3: Physical Examination

Step 4: Investigations

• Blood glucose (hypoglycemia is immediately reversible)
• CBC with differential
• Renal function, LFT, electrolytes
• Blood cultures x 2 (before antibiotics if possible, but do NOT delay treatment)
• Peripheral smear (malaria) + RDT
• Widal test / Typhidot if clinical suspicion
• HIV rapid test
• Urine routine + culture
• Arterial blood gas / VBG
• 12-lead ECG

• HSV PCR on CSF (sensitivity ~98%, specificity ~99%)
• JE IgM ELISA on CSF/serum (AES workup)
• CSF VDRL for neurosyphilis
• Cryptococcal antigen in immunocompromised
• EEG: periodic lateralized epileptiform discharges (PLEDs) in HSV encephalitis; useful if non-convulsive status suspected
• MRI brain with contrast: superior to CT for encephalitis (temporal lobe T2/FLAIR changes in HSV), brain abscess, CVT, TB meningitis (basilar enhancement)
• NMDA-R and other autoimmune antibody panels if initial workup negative

Management

Immediate Stabilization

1. IV access x2, oxygen (maintain SpO2 >94%), monitor
2. Correct hypoglycemia: 50 mL of 50% dextrose IV (after thiamine 100 mg if alcohol/malnutrition suspected)
3. Do not delay antibiotics while arranging CT or LP - if CT is needed, draw blood cultures first, then start empirical treatment, then image, then LP

Raised ICP Management (if signs present)

• Head of bed 30 degrees
• Endotracheal intubation + ventilation (target PaCO2 35-40 mmHg; brief hyperventilation to 30-35 only as temporizing measure)
• Mannitol 0.5-1 g/kg IV over 20-30 min, or hypertonic saline (3%)
• Neurosurgical consultation

Empirical Antimicrobial Therapy

• Ceftriaxone 2 g IV q12h (or cefotaxime 3 g IV q6h) + Vancomycin 15-20 mg/kg q8h
• Add Dexamethasone 0.15 mg/kg (up to 10 mg) IV q6h x 4 days, given WITH or 20 minutes BEFORE first antibiotic dose (proven mortality benefit in pneumococcal meningitis; reduces hearing loss in H. influenzae)

• Above regimen + Ampicillin 2 g IV q4h (adult); for neonates: 100 mg/kg/dose q8h

• Replace ceftriaxone with Cefepime 2 g IV q8h (covers Pseudomonas + resistant organisms)

• Meropenem or Chloramphenicol

• Acyclovir 10 mg/kg IV q8h x 14-21 days; confirm with CSF HSV PCR; do NOT wait for result before starting

• 4-drug regimen: HRZE (isoniazid + rifampicin + pyrazinamide + ethambutol) x 2 months, then HR x 7-10 months
• Add Dexamethasone 0.4 mg/kg/day tapered over 6-8 weeks

• IV Artesunate 2.4 mg/kg at 0, 12, 24h then once daily (preferred over quinine)
• Supportive: manage hypoglycemia, seizures (benzodiazepines), anemia

• Treat the underlying sepsis (source control + broad-spectrum antibiotics per focus)
• Avoid benzodiazepines where possible
• Optimize hemodynamics and oxygenation

Anticonvulsant Management

• Active seizures: Lorazepam 0.1 mg/kg IV (or diazepam 0.15 mg/kg IV) as first line
• Refractory: Phenytoin/Levetiracetam loading
• Prophylactic anticonvulsants are not routinely indicated in meningitis (unless specific encephalitis with seizure risk)

Supportive Care

• Fluid balance: avoid hypo-osmolar fluids (worsen cerebral edema); use isotonic crystalloids
• Fever control: paracetamol (NSAIDs with caution in sepsis/bleeding risk)
• Nutrition: early enteral if intubated
• Nursing: 30-degree head elevation, aspiration precautions, pressure area care, Foley catheter monitoring

Chemoprophylaxis for Contacts (Meningococcal)

• Rifampicin 600 mg oral q12h x 4 doses, OR
• Ciprofloxacin 500 mg oral single dose (preferred in adults)
• Pregnant women: Ceftriaxone 250 mg IM single dose

Summary Algorithm

Fever + Altered Sensorium
        │
        ├── ABC, POCT glucose, IV access, O2
        │
        ├── Signs of raised ICP?
        │    YES → CT head first → LP when safe
        │    NO  → LP without delay
        │
        ├── Draw blood cultures → Start empirical Rx:
        │    Ceftriaxone + Vancomycin + Dexamethasone
        │    + Acyclovir (if encephalitis suspected)
        │    + Ampicillin (if age >50 / neonate)
        │
        ├── Parallel workup:
        │    CBC, CMP, coags, smear (malaria), LFT, RFT, ABG
        │    CXR, blood cultures, urine cultures
        │
        ├── CSF Analysis → Tailor therapy
        │
        └── Specific causes:
             Cerebral malaria → IV Artesunate
             TB meningitis   → HRZE + Steroids
             Viral AES/JE    → Supportive + Acyclovir (empirical)
             Septic enceph.  → Treat source
             Autoimmune      → Steroids/IVIG/Plasmapheresis

• ROSEN's Emergency Medicine, Chapter 95 (CNS Infections) - ROSEN's Emergency medicine Concepts and clinical practice
• Harrison's Principles of Internal Medicine 22E (2025) - Encephalitis section
• Park's Textbook of Preventive & Social Medicine - AES/JE guidelines (NVBDCP 2014)
• Park's Textbook of Preventive & Social Medicine - Fever with altered sensorium referral criteria