The Challenge of Viral Encephalitis in the Indian ICU: A Practical Approach for Critical Care Physicians

Dr Neeraj Manikath , claude.ai

Abstract

Viral encephalitis represents a significant neurological emergency in Indian intensive care units, with Japanese encephalitis and acute encephalitis syndrome continuing to pose substantial morbidity and mortality despite vaccination programs. The Indian ICU physician faces unique challenges including limited diagnostic resources, overlapping clinical presentations with autoimmune encephalitis, and the need for time-sensitive therapeutic decisions. This review synthesizes current evidence with practical approaches to diagnosis, management of complications, and rehabilitation strategies tailored to the Indian critical care setting.

Introduction

Encephalitis remains a major public health challenge in India, with an estimated annual incidence of 5.9-7.3 per 100,000 population—significantly higher than Western nations (1). The Indian ICU landscape is characterized by late presentations, resource constraints, and a predominance of infectious etiologies rather than autoimmune causes seen in developed countries. Viral encephalitis accounts for approximately 60-70% of acute encephalitis syndrome (AES) cases in India, with Japanese encephalitis virus (JEV) historically responsible for 20-60% of cases in endemic regions (2,3).

Pearl: The epidemiological profile of encephalitis in India differs markedly from Western countries—infectious causes predominate over autoimmune, and delayed presentations with established complications are the norm rather than the exception.

Japanese Encephalitis and Acute Encephalitis Syndrome (AES) Outbreaks

Epidemiological Landscape

Japanese encephalitis remains endemic in 24 Indian states, with recurrent outbreaks particularly affecting Uttar Pradesh, Assam, Bihar, and West Bengal (4). The monsoon and post-monsoon periods (June-October) see peak transmission, coinciding with rice cultivation and vector proliferation. However, the landscape has evolved—while JE vaccination has reduced JEV burden in some regions, other pathogens including scrub typhus, dengue, Chandipura virus, Nipah virus, and enteroviruses have emerged as significant contributors to AES (5,6).

The clinical presentation of JE typically includes acute fever, altered sensorium, seizures (seen in 85-90% of pediatric cases), and characteristic extrapyramidal features including mask-like facies, tremors, and cogwheel rigidity (7). The case fatality rate ranges from 20-30%, with 30-50% of survivors experiencing long-term neurological sequelae (8).

Oyster: Not all AES is Japanese encephalitis! In recent outbreaks in Bihar and Uttar Pradesh, hypoglycemic encephalopathy related to litchi consumption (hypoglycin A toxicity) and scrub typhus have been identified as major contributors, responding to entirely different management strategies (9,10).

Diagnostic Challenges

The gold standard for JE diagnosis—detection of IgM antibodies in CSF or a four-fold rise in paired serum samples—is often unavailable or delayed in resource-limited settings. Serum JE IgM enzyme-linked immunosorbent assay (ELISA) becomes positive only by day 3-5 of illness, and cross-reactivity with other flaviviruses (dengue, West Nile) complicates interpretation (11).

Hack: In endemic areas during outbreak periods, implement a syndromic approach: acute fever + altered consciousness + seizures in monsoon/post-monsoon = presumptive AES management. Simultaneously investigate for treatable mimics (hypoglycemia, electrolyte disturbances, bacterial meningitis, scrub typhus) while awaiting confirmatory tests.

Outbreak Management Considerations

During AES outbreaks, ICU capacity is rapidly overwhelmed. Triage becomes critical:

High-priority ICU admission: GCS ≤8, refractory seizures, respiratory failure, hemodynamic instability
Intermediate monitoring: GCS 9-12, single seizure episode, stable vitals
Ward-based care with monitoring: GCS 13-15, no seizures, stable neurological examination

Mass casualties require surge protocols including designated AES wards with enhanced monitoring, trained nursing staff in seizure management, and clear escalation criteria (12).

Differentiating Viral from Autoimmune Encephalitis with Limited Diagnostics

The Diagnostic Dilemma

The clinical overlap between viral and autoimmune encephalitis creates substantial diagnostic uncertainty, particularly when advanced neuroimaging and antibody testing are unavailable. Autoimmune encephalitis—particularly anti-NMDA receptor encephalitis—is increasingly recognized in India, accounting for 5-15% of encephalitis cases in tertiary centers (13,14).

Clinical Clues for Differentiation

Favoring Autoimmune Encephalitis:

Subacute onset over days to weeks (vs. acute in viral)
Prominent psychiatric features, personality changes, behavioral disturbances
Orofacial dyskinesias, autonomic instability, central hypoventilation
Normal or mildly elevated CSF protein (<100 mg/dL)
Absence of fever or fever that resolves early
Medial temporal lobe involvement on MRI (though seen in HSV too)
Younger women (anti-NMDA receptor) or older men with malignancy (paraneoplastic)

Favoring Viral Encephalitis:

Acute onset with prominent fever
Rapid progression to coma
Brainstem involvement (cranial nerve palsies, respiratory dysfunction)
CSF protein >100 mg/dL, polymorphonuclear predominance early
Seasonal clustering (JE, dengue) or geographic factors
Hemorrhagic changes on imaging (HSV)

Pearl: The presence of movement disorders (dystonia, chorea, orofacial dyskinesias) strongly suggests autoimmune etiology. These are rare in viral encephalitis except for the parkinsonian features of JE (15).

Practical Diagnostic Approach with Limited Resources

Step 1: CSF Analysis Interpretation Even basic CSF analysis provides valuable information:

Lymphocytic pleocytosis + elevated protein: Supports viral or autoimmune
Neutrophilic pleocytosis: Bacterial, early viral, or Listeria
Normal CSF: Does not exclude encephalitis (10-15% have normal initial CSF)
RBCs + xanthochromia: Consider HSV with hemorrhagic necrosis

Step 2: MRI Brain (if available) Characteristic patterns guide diagnosis:

Bilateral thalamic/basal ganglia: JE, Nipah, West Nile virus
Medial temporal lobes: HSV, limbic encephalitis
Bilateral cortical/subcortical FLAIR hyperintensities: Autoimmune
Hemorrhagic changes: HSV, hemorrhagic dengue
Brainstem involvement: Listeria, enterovirus 71, rabies

Hack: When MRI is unavailable, use CT brain despite lower sensitivity. Though CT misses many cases of encephalitis, the presence of temporal lobe hypodensities (HSV) or thalamic hypodensities (JE) provides valuable diagnostic information. Normal CT doesn't exclude encephalitis but helps rule out mass lesions and guides lumbar puncture safety.

Step 3: Empiric Treatment Decision Create a probability-based treatment matrix:

Clinical Scenario	Empiric Coverage
Acute fever + seizures + endemic area/season	Acyclovir + doxycycline (scrub typhus)
Subacute + psychiatric + dyskinesias	Acyclovir + immunotherapy trial
Temporal lobe findings on imaging	Acyclovir (HSV until excluded)
CSF >100 WBC with neutrophils	Add ceftriaxone + ampicillin

Managing Refractory Seizures and Raised ICP

Seizure Management

Seizures occur in 50-80% of viral encephalitis cases and are refractory in approximately 20-30% (16). The challenge in Indian ICUs includes limited availability of continuous EEG monitoring, making non-convulsive status epilepticus (NCSE) a hidden contributor to poor outcomes.

First-Line Management:

Lorazepam 0.1 mg/kg IV (4 mg in adults) or midazolam 0.2 mg/kg IM if no IV access
Levetiracetam 60 mg/kg IV loading (maximum 4500 mg) followed by 500-1500 mg BD
- Preferred over phenytoin due to better safety profile, no loading-related hypotension, and efficacy in encephalitis-related seizures (17)
Sodium valproate 20-40 mg/kg IV loading followed by 10-15 mg/kg TID as alternative

Refractory Seizures (continuing after two appropriate AEDs):

Midazolam infusion: 0.2 mg/kg bolus, then 0.05-0.4 mg/kg/hr titrated to seizure cessation
Propofol infusion: 1-2 mg/kg bolus, then 2-10 mg/kg/hr (monitor for propofol infusion syndrome if >4 mg/kg/hr for >48 hours)
Thiopentone infusion: 3-5 mg/kg bolus, then 1-5 mg/kg/hr (requires invasive BP monitoring)

Oyster: Phenytoin, while widely available and inexpensive, causes hypotension during loading, has multiple drug interactions, and shows inferior efficacy in acute symptomatic seizures compared to levetiracetam (18). Reserve it for when alternatives are unavailable.

Hack for Resource-Limited Settings: When continuous infusions and ventilatory support aren't available, consider high-dose midazolam via nasogastric tube (0.3-0.5 mg/kg loading, then 0.1-0.3 mg/kg Q4-6H) or rectal diazepam (0.5 mg/kg Q8-12H) for seizure cluster management in intermediate care areas (19).

Raised Intracranial Pressure Management

Cerebral edema with raised ICP contributes significantly to mortality in viral encephalitis, particularly JE (seen in 30-40% of cases) and HSV encephalitis (20).

Clinical Indicators of Raised ICP:

Deteriorating GCS, especially with flexor or extensor posturing
Cushing's triad (hypertension, bradycardia, irregular respirations)
Asymmetric or dilated pupils
Fundoscopy showing papilledema (though often absent acutely)

Management Protocol:

Tier 1 (All patients with suspected raised ICP):

Head elevation to 30 degrees, midline head position
Maintain euvolemia with isotonic saline
Avoid hypotonic fluids and dextrose-containing solutions
Target normothermia (fever increases ICP by 7-10 mmHg per degree Celsius)
Maintain PaCO2 35-40 mmHg if ventilated
Prevent hypertonic stimuli (adequate sedation, analgesia)

Tier 2 (Clinical deterioration or herniation signs):

Hypertonic saline 3% bolus: 5 mL/kg (250-500 mL) over 15-30 minutes, then infusion at 0.5-1 mL/kg/hr targeting sodium 145-155 mmol/L
- Superior to mannitol in most studies, longer duration of action, less rebound (21)
Mannitol 20% bolus: 0.5-1 g/kg (100-200 mL) over 15 minutes Q6-8H (if hypertonic saline unavailable)
- Monitor osmolar gap (target <320 mOsm/L), urine output

Tier 3 (Refractory raised ICP):

Induced hypothermia (target 32-34°C for 24-72 hours) - requires specialized equipment
Barbiturate coma (thiopentone) - requires hemodynamic monitoring
Decompressive craniectomy - controversial in encephalitis, consider only in focal hemispheric swelling with impending herniation (22)

Pearl: Osmotherapy should be guided by serial sodium and serum osmolality measurements. In resource-limited settings without osmolality testing, maintain serum sodium between 145-155 mmol/L as a surrogate marker during hypertonic saline therapy.

The Role of Empiric Acyclovir and Other Antivirals

Acyclovir: The Cornerstone of Empiric Therapy

Acyclovir remains the only antiviral with proven efficacy in encephalitis (HSV), yet its empiric use in all suspected encephalitis cases—including JE where it has no proven benefit—is justified by the devastating consequences of untreated HSV encephalitis (23).

Dosing and Administration:

Acyclovir 10 mg/kg IV Q8H (30 mg/kg/day) for 14-21 days
Adjust for renal function: CrCl 25-50: 10 mg/kg Q12H; CrCl 10-25: 10 mg/kg Q24H
Administer over 1 hour in 100-250 mL normal saline to prevent nephrotoxicity
Ensure adequate hydration (2.5-3 L/day maintenance)

Pearl: Early acyclovir administration (within 48 hours) in HSV encephalitis reduces mortality from 70% to 20-30% and improves neurological outcomes (24). The adage "treat first, diagnose later" is paramount in suspected encephalitis.

Monitoring for Acyclovir Toxicity:

Nephrotoxicity (most common): Monitor creatinine, maintain hydration
Neurotoxicity (confusion, hallucinations, tremors, seizures): Particularly with renal impairment
Thrombophlebitis: Use central line for prolonged therapy
Crystalluria: Maintain adequate urine output

When to Stop Acyclovir

Continue Full Course if:

HSV PCR positive (continue 21 days total)
HSV PCR unavailable and clinical/imaging suggestive
Uncertain diagnosis with concern for HSV

Consider Stopping After 5-7 Days if:

Negative HSV PCR on CSF obtained before acyclovir initiation
Alternative confirmed diagnosis (bacterial meningitis, autoimmune encephalitis)
JE confirmed with no HSV risk factors and no hemorrhagic/temporal lobe changes

Hack: In endemic areas during JE outbreaks with resource constraints, risk-stratify acyclovir use: Continue full course for patients with temporal lobe involvement, hemorrhagic features, or atypical presentations. Consider stopping after 5-7 days in classic JE presentations (bilateral thalamic involvement, extrapyramidal features, epidemic period) once HSV is reasonably excluded.

Other Antiviral Considerations

Ganciclovir/Valganciclovir:

Consider for CMV encephalitis (immunocompromised hosts)
Dosing: Ganciclovir 5 mg/kg IV Q12H for 14-21 days

Ribavirin:

Used in Nipah virus encephalitis (outbreaks in Kerala, West Bengal)
Dosing: 30 mg/kg loading, then 15 mg/kg Q6H for 4 days, then 7.5 mg/kg Q8H for 6 days
Evidence limited but used during outbreaks (25)

Oseltamivir:

No proven benefit in influenza-associated encephalopathy, but consider in confirmed influenza

Oyster: There is no proven antiviral therapy for JE, dengue, or most arboviruses. Supportive care and complication management drive outcomes. Avoid the temptation to add unproven antivirals—focus resources on proven interventions.

Neurological Rehabilitation and Long-Term Disability

Scope of the Problem

The burden of post-encephalitic sequelae in India is substantial. Studies show 30-65% of survivors experience persistent neurological deficits including cognitive impairment (40-50%), motor deficits (20-40%), behavioral disturbances (25-35%), and epilepsy (15-25%) (26,27). In children surviving JE, school performance and quality of life are significantly impaired.

Predictors of Poor Neurological Outcome:

GCS ≤8 at presentation
Refractory seizures or status epilepticus
Prolonged ICU stay (>7 days)
Delayed presentation (>5 days of symptoms)
Need for mechanical ventilation
Brainstem involvement on imaging
Young age (<5 years) or elderly (>60 years)

Early ICU-Based Rehabilitation

Neurological recovery begins in the ICU, not after discharge. Early mobilization and rehabilitation prevent complications and improve outcomes (28).

ICU Rehabilitation Protocol:

Week 1 (Acute Phase):

Passive range-of-motion exercises to all limbs TDS
Proper positioning to prevent contractures (ankle splints, hand rolls)
Oral care and swallowing assessment before oral intake
Bowel and bladder management protocols

Week 2 Onward (Stabilization Phase):

Active-assisted exercises as consciousness improves
Sitting balance training when extubated and hemodynamically stable
Speech and language therapy assessment
Cognitive stimulation (orientation cues, family interaction)

Oyster: Tracheostomy timing is critical in encephalitis. Early tracheostomy (day 7-10) in patients with GCS ≤8 and anticipated prolonged ventilation facilitates rehabilitation, improves secretion management, and reduces sedation requirements (29).

Post-ICU and Long-Term Rehabilitation

The continuum of care extends beyond ICU survival. Comprehensive rehabilitation requires multidisciplinary coordination often lacking in resource-constrained settings.

Structured Rehabilitation Plan:

Motor Rehabilitation:

Physiotherapy: 5 days/week minimum, focused on strength, balance, ambulation
Occupational therapy: Activities of daily living, fine motor skills
Orthoses for foot drop, wrist contractures as needed

Cognitive Rehabilitation:

Neuropsychological assessment at 3 months post-discharge
Memory training, attention exercises, executive function tasks
School reintegration plans for children

Seizure Management:

Continue antiepileptic drugs for minimum 2 years if seizures occurred during acute illness
Prolonged therapy if structural brain injury evident on MRI
Monitor for late-onset epilepsy (occurs in 15-20% within 2 years)

Behavioral and Psychiatric Support:

Screen for depression, anxiety, post-traumatic stress
Behavioral modification for personality changes
Family counseling and support groups

Hack for Resource-Limited Settings: Develop "Encephalitis Survivor Clinics" as dedicated follow-up pathways with scheduled multidisciplinary assessments at 1, 3, 6, and 12 months. Use standardized outcome measures (Modified Rankin Scale, Pediatric Cerebral Performance Category) to track progress and allocate limited rehabilitation resources to those most likely to benefit (30).

Social Reintegration and Support Systems

In the Indian context, family education and community support are vital. The financial burden of encephalitis—acute care costs, lost wages, ongoing rehabilitation—is catastrophic for many families.

Key Components:

Disability certification for government benefit schemes
School accommodation plans (special education needs, exam modifications)
Vocational rehabilitation for working-age adults
Caregiver training and respite care options
Connection with NGOs and support groups (e.g., Encephalitis Society India chapters)

Pearl: Recovery continues for 12-24 months post-encephalitis. Serial assessments capture ongoing improvements. Premature discharge from rehabilitation services underestimates recovery potential and abandons patients during the critical recovery window.

Conclusion

Viral encephalitis in the Indian ICU represents a convergence of epidemiological burden, diagnostic challenges, therapeutic complexities, and rehabilitation needs. Success requires a syndrome-based approach that acknowledges resource limitations while maximizing evidence-based interventions. Early empiric acyclovir, aggressive seizure control, meticulous ICP management, and commitment to comprehensive rehabilitation form the cornerstones of modern encephalitis care.

As the epidemiology evolves with vaccination programs, climate change, and emerging pathogens, Indian intensivists must remain vigilant, adaptable, and committed to both acute life-saving interventions and long-term outcome optimization. The challenge is substantial, but so too is the opportunity to impact survival and quality of life for thousands of patients annually.

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Final Pearl: The battle against viral encephalitis in India is won not by sophisticated diagnostics or expensive therapeutics alone, but by timely recognition, evidence-based empiric treatment, meticulous supportive care, and unwavering commitment to rehabilitation. Every intensivist treating encephalitis should remember: survival is the beginning, not the end, of our responsibility to these patients.

learningmedicine

Wednesday, November 5, 2025