ENCEPHALITIS 

Encephalitis = inflammation of brain parenchyma associated with neurological dysfunction

 Distinguished from:

  • Meningitis → meningeal inflammation
  • Meningoencephalitis → overlap


 EPIDEMIOLOGY 

  • Incidence: ~5–10 per 100,000/year
  • High mortality: HSV encephalitis ~20–30% even with treatment
  • Seasonal patterns:
    • Summer/monsoon (India) → arboviruses (JE, dengue, chikungunya)
    • Winter → viral respiratory-related encephalitis
  • Age groups:
    • Neonates → HSV, enterovirus
    • Children → JE, autoimmune
    • Adults → HSV, autoimmune, TB


ETIOLOGY 

 INFECTIOUS CAUSES

 Viral (MOST COMMON)

  • Herpes simplex encephalitis ( MOST IMPORTANT)
  • Japanese encephalitis
  • Rabies
  • Varicella zoster encephalitis
  • Enteroviruses (Coxsackie, Echo)
  • Arboviruses (West Nile, dengue)
  • COVID-19

 Bacterial

  • Tuberculous encephalitis
  • Listeria monocytogenes infection
  • Neurosyphilis
  • Brain abscess-related inflammation

Parasitic / Fungal

  • Cerebral malaria
  • Toxoplasmosis
  • Cryptococcosis

 AUTOIMMUNE ENCEPHALITIS

  • Anti-NMDA receptor encephalitis 
  • LGI1, CASPR2
  • Paraneoplastic (small cell lung cancer)


 POST-INFECTIOUS / PARA-INFECTIOUS

  • Acute disseminated encephalomyelitis

 PATHOPHYSIOLOGY

 Mechanisms

  1. Direct viral invasion
    • HSV → temporal lobe necrosis
  1. Immune-mediated injury
    • Autoantibodies against neuronal receptors
  1. Cytokine storm
    • BBB disruption
  1. Cerebral edema → raised ICP

 HSV ENCEPHALITIS 

  • Temporal lobe involvement
  • Hemorrhagic necrosis
  • Personality changes + seizures

 CLINICAL FEATURES

 CLASSIC TRIAD

  • Fever
  • Altered mental status
  • Seizures

Category

Features

General

Fever, headache

Neurological

Confusion, coma

Seizures

Focal or generalized

Focal deficits

Aphasia, hemiparesis

Behavioral

Psychosis (NMDA)

Raised ICP

Vomiting, papilledema

Movement disorders

Dyskinesia (NMDA)


Virus

When to Suspect 

Herpes simplex virus type 1

Most common; acute fever + altered behavior + seizures; temporal lobe signs (aphasia, personality change); MRI: temporal hyperintensity; CSF RBCs present (hemorrhagic necrosis)

Herpes simplex virus type 2

Neonates, immunocompromised; meningitis > encephalitis; genital herpes history

Varicella zoster virus

Recent shingles (dermatomal rash); stroke-like deficits (vasculopathy); elderly/immunocompromised

Japanese encephalitis virus

Rural Asia/India; mosquito exposure; movement disorders (parkinsonism); MRI: bilateral thalamic lesions

West Nile virus

Fever + encephalitis + acute flaccid paralysis (anterior horn cell); elderly; mosquito exposure

Dengue virus

Dengue features: thrombocytopenia, rash, plasma leakage; encephalopathy ± encephalitis

Chikungunya virus

Severe polyarthralgia + fever + neuro symptoms

Rabies virus

Animal bite history; hydrophobia, aerophobia, agitation; fatal once symptomatic

Cytomegalovirus

AIDS/transplant; periventricular lesions; retinitis association

Epstein-Barr virus

Infectious mononucleosis features; lymphadenopathy; mild encephalitis

Human herpesvirus 6

Post-transplant; limbic encephalitis (memory loss, seizures)

Enteroviruses

Children; summer outbreaks; aseptic meningitis ± encephalitis

Influenza virus

Recent flu illness; encephalopathy more common than true encephalitis


Organism / Disease

When to Suspect 

Streptococcus pneumoniae

Most common adult meningitis; acute fever + altered sensorium; CSF: neutrophils↑, protein↑, glucose↓; may follow pneumonia/otitis

Neisseria meningitidis

Young adults + outbreaks; petechial rash, septic shock (Waterhouse–Friderichsen)

Listeria monocytogenes

Elderly, pregnancy, immunocompromised; brainstem signs; ampicillin needed (resistant to cephalosporins)

Haemophilus influenzae

Unvaccinated children; respiratory infection history

Mycobacterium tuberculosis

Subacute (weeks); fever + headache + cranial nerve palsy; basal meningitis, hydrocephalus; CSF: lymphocytes↑, protein very high, glucose very low

Staphylococcus aureus

Post-neurosurgery/trauma; brain abscess (ring lesion)

Streptococcus milleri group

Dental/sinus infection → brain abscess

Nocardia species

Immunocompromised; multiple brain abscesses

Brucella species

Endemic areas (India); chronic meningitis + neuropsychiatric features

Leptospira interrogans

Exposure to contaminated water; fever + jaundice + aseptic meningitis


Parasite 

When to Suspect 

Taenia solium

Most common parasitic CNS infection in India; seizures; multiple ring lesions with scolex(“hole-with-dot”)

Plasmodium falciparum

Fever + coma + seizures; malaria endemic area; retinal hemorrhages, severe anemia

Toxoplasma gondii

AIDS (CD4 <100); multiple ring-enhancing lesions (basal ganglia); responds to pyrimethamine + sulfadiazine

Naegleria fowleri

Freshwater exposure; rapidly fatal, resembles bacterial meningitis; neutrophils in CSF but no bacteria

Acanthamoeba species

Subacute in immunocompromised; focal deficits + encephalopathy

Echinococcus granulosus

Large cystic brain lesion; raised ICP; endemic livestock exposure

Trypanosoma brucei

Sleep disturbance, neuropsychiatric symptoms (“sleeping sickness”)

Angiostrongylus cantonensis

Eosinophils in CSF; snail/raw food exposure

 DIFFERENTIAL DIAGNOSIS

  • Meningitis
  • Brain abscess
  • Stroke
  • Status epilepticus
  • Metabolic encephalopathy

 DIAGNOSIS 

International Encephalitis Consortium criteria

Encephalitis = inflammation of brain parenchyma with:

  • Altered mental status ≥24 hours (mandatory)
    PLUS ≥2 of:
  • Fever ≥38°C
  • Seizures
  • New focal neurological deficit
  • CSF pleocytosis
  • EEG abnormalities
  • Neuroimaging suggestive

  INITIAL  WORKUP 

BEFORE LP (if needed)

  • ABC stabilization
  • Blood glucose
  • Electrolytes
  • Sepsis workup

IMMEDIATE TESTS

  • CBC, CRP, ESR
  • LFT, RFT
  • Blood cultures ×2
  • HIV testing
  • Malaria, dengue (India-specific)


  LUMBAR PUNCTURE 

 Contraindications BEFORE LP

  • Papilledema
  • Focal deficit
  • Immunocompromised
  • GCS < 10
     Do CT/MRI first

A. CSF ANALYSIS (About 10% of patients will have normal CSF studies.)

Parameter

Viral

Bacterial

TB

Fungal

Autoimmune

Opening pressure

Normal/↑

↑↑

↑

↑

Normal

Cells

Lymphocytes

Neutrophils

Lymphocytes

Lymphocytes

Mild

Protein

Mild ↑

↑↑

↑↑

↑

Mild ↑

Glucose

Normal

↓

↓

↓

Normal

B. CSF-SPECIFIC TESTS

Gold Standard Tests

  • PCR (MOST IMPORTANT)
    • HSV-1, HSV-2
    • VZV
    • Enterovirus
    • CMV (immunocompromised)

 HSV PCR = gold standard for Herpes Simplex Encephalitis


 Additional CSF Tests

  • CSF culture (bacterial)
  • CSF ADA (TB)
  • Cryptococcal antigen
  • GeneXpert (TB)

C. Autoimmune Encephalitis Workup

  • Anti-NMDA receptor antibodies
  • Anti-LGI1, CASPR2
  • GABA-B antibodies

 Classic: Anti-NMDA receptor encephalitis


  NEUROIMAGING 

A. CT Brain (Initial)

  • Rule out:
    • Mass lesion
    • Hemorrhage
    • Raised ICP

 Often normal early


B. MRI Brain (GOLD STANDARD)

Typical MRI Findings

Etiology

MRI Findings

HSV

Temporal lobe hyperintensity(usually appear 3-5 day after the infection.)

Autoimmune

Limbic system involvement

Japanese encephalitis

Thalamus

Rabies

Brainstem

EEG 

Pattern

Suggests

Periodic lateralized epileptiform discharges (PLEDs)

HSV encephalitis

Diffuse slowing

Encephalopathy

Seizure activity

Nonconvulsive status

EEG helps in:

  • Detecting subclinical seizures
  • Supporting HSV diagnosis

MANAGEMENT 

1. INITIAL APPROACH (FIRST GOLDEN HOURS)

A. ABC + NEUROCRITICAL CARE PRIORITIES

  • Airway
    • Intubate if:
      • GCS ≤ 8
      • Refractory seizures
      • Severe agitation
      • Raised ICP with risk of herniation
  • Breathing
    • Target SpO₂ > 94%
    • Avoid hypercapnia (↑ ICP)
  • Circulation
    • Maintain MAP ≥ 65 mmHg
    • Avoid hypotension (↓ cerebral perfusion pressure)


B. IMMEDIATE EMPIRICAL THERAPY (DO NOT WAIT FOR CSF)

 Start within 1 hour of suspicion

1. ANTIVIRAL (MANDATORY)

  • Acyclovir
    • Dose: 10 mg/kg IV q8h
    • Duration:
      • HSV: 14–21 days
    • Adjust for renal function

2. ANTIBIOTICS (IF MENINGOENCEPHALITIS NOT EXCLUDED)

  • Ceftriaxone 2 g IV q12h
  • Vancomycin (trough-based dosing)
  • Add:
    • Ampicillin (if >50 yrs / immunocompromised → cover Listeria)

3. CONSIDER ADDITIONAL ANTIVIRALS

  • Ganciclovir ± foscarnet
    • If CMV suspected (immunocompromised)


 2. TARGETED ETIOLOGY-SPECIFIC THERAPY

A. VIRAL ENCEPHALITIS

1. HSV encephalitis (MOST IMPORTANT EXAM POINT)

  • Drug: Acyclovir
  • Duration:
    • 14–21 days
  • Repeat CSF PCR if:
    • No improvement

2. Varicella Zoster Virus (VZV)

  • Acyclovir 10–15 mg/kg IV q8h
  • ± steroids (controversial, for vasculopathy)

3. Japanese Encephalitis (common in India)

  • No specific antiviral
  • Pure supportive ICU care

4. CMV Encephalitis

  • Ganciclovir 5 mg/kg IV every 12 hours + Foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 21 days.

5. Arboviruses (Dengue, West Nile)

  • Supportive only

 B. BACTERIAL (MENINGOENCEPHALITIS)

  • Treat as meningitis initially
  • Modify after CSF culture

 C. TUBERCULAR ENCEPHALITIS

  • ATT (HRZE regimen) + steroids

 D. FUNGAL ENCEPHALITIS

  • Amphotericin B
  • Followed by:
    • Fluconazole

 E. AUTOIMMUNE ENCEPHALITIS 

Examples:

  • Anti-NMDA receptor
  • LGI1, CASPR2

Treatment:

  1. First line
    • IV methylprednisolone (1 g/day × 5 days)
    • IVIG OR plasmapheresis
  1. Second line
    • Rituximab
    • Cyclophosphamide

 3. MANAGEMENT OF COMPLICATIONS 

 A. SEIZURE MANAGEMENT

  • 1st line: Lorazepam
  • 2nd line:
    • Levetiracetam
    • Phenytoin

Refractory seizures:

  • Midazolam infusion
  • Propofol infusion

B. RAISED ICP MANAGEMENT

General Measures:

  • Head elevation: 30°
  • Neutral neck
  • Avoid fever, hypoxia, hypercapnia

Osmotherapy:

  • Mannitol
    • 0.25–1 g/kg IV bolus
  • OR hypertonic saline

Advanced:

  • Sedation (propofol)
  • Controlled ventilation (PaCO₂ 35 mmHg)
  • Barbiturate coma (last resort)