Encephalitis

Introduction

Encephalitis is an inflammatory disorder of the brain parenchyma, most commonly caused by viral infections, but it can also be immune-mediated, bacterial, fungal, or parasitic in origin. The inflammation leads to cerebral dysfunction manifested by altered mental status, seizures, focal neurological deficits, and behavioral changes.

It is a neurological emergency, as delayed diagnosis or treatment can result in permanent neurological damage or death.

---

Epidemiology

• Incidence: Varies geographically; estimated at 5–10 cases per 100,000 population annually in developed countries.

• Age groups: Can affect all ages; higher incidence in children, the elderly, and immunocompromised individuals.

• Seasonality: Arboviral encephalitis is more common in summer and fall in temperate climates.

---

Etiology

1. Infectious Causes

Viral (Most Common)

• Herpes simplex virus (HSV) – most common sporadic cause in developed countries; HSV-1 in adults, HSV-2 in neonates.

• Varicella-zoster virus (VZV)

• Enteroviruses (coxsackievirus, echovirus)

• Arboviruses (West Nile virus, Japanese encephalitis virus, Zika virus)

• Rabies virus

• Measles virus (acute or subacute sclerosing panencephalitis)

• Mumps virus

• Cytomegalovirus (CMV) – mainly in immunocompromised patients

• Epstein-Barr virus (EBV)

• Human herpesvirus-6 (HHV-6)

Bacterial

• Mycoplasma pneumoniae

• Treponema pallidum (neurosyphilis)

• Borrelia burgdorferi (neuroborreliosis)

Fungal

• Cryptococcus neoformans

• Aspergillus spp.

Parasitic

• Toxoplasma gondii

• Naegleria fowleri

---

2. Autoimmune and Parainfectious Causes

• Autoimmune encephalitis (e.g., anti-NMDA receptor encephalitis, anti-LGI1 encephalitis)

• Acute disseminated encephalomyelitis (ADEM) – post-infectious or post-vaccination

---

Pathophysiology

Infectious encephalitis typically results from:

• Direct viral invasion of the CNS.

• Immune-mediated neuronal damage due to inflammatory cytokines and immune cell infiltration.

• Disruption of the blood–brain barrier, allowing entry of pathogens and immune cells.

• In autoimmune encephalitis, neuronal antigens are targeted by autoantibodies, leading to synaptic dysfunction without necessarily causing direct neuronal death.

---

Risk Factors

• Extremes of age (infants, elderly)

• Immunosuppression (HIV, post-transplant, chemotherapy)

• Recent infection or vaccination

• Exposure to vectors (mosquitoes, ticks)

• Travel to endemic regions

• Lack of vaccination against measles, mumps, rubella, or Japanese encephalitis

---

Clinical Features

Core Triad

1. Fever

2. Headache

3. Altered mental status (confusion, disorientation, personality change)

Other Symptoms

• Seizures (focal or generalized)

• Focal neurological deficits (aphasia, hemiparesis, cranial nerve palsies)

• Photophobia, neck stiffness (meningitic features)

• Behavioral disturbances, hallucinations

• Movement disorders (chorea, ataxia)

• In autoimmune forms: psychiatric symptoms, autonomic instability

---

Complications

• Increased intracranial pressure (ICP)

• Brain herniation

• Status epilepticus

• Persistent neurological deficits

• Death

---

Diagnosis

History and Examination

• Onset, progression, exposure history, travel, vaccination status

• Complete neurological assessment

Laboratory Investigations

• Complete blood count, electrolytes, liver and renal function tests

• Inflammatory markers: ESR, CRP

CSF Analysis (via lumbar puncture unless contraindicated)

• Lymphocytic pleocytosis (10–500 cells/μL)

• Normal or mildly elevated protein

• Normal glucose (may be low in bacterial or TB encephalitis)

• PCR for viral DNA/RNA (HSV, VZV, enteroviruses, etc.)

Neuroimaging

• MRI brain: Preferred; may show temporal lobe hyperintensity in HSV encephalitis, thalamic involvement in Japanese encephalitis.

• CT scan: Useful if MRI not available or to rule out contraindications for lumbar puncture.

Electroencephalography (EEG)

• May show periodic lateralized epileptiform discharges (PLEDs) in HSV encephalitis.

---

Management

Management involves urgent empiric therapy while awaiting diagnostic confirmation, supportive care, and treatment of the underlying cause.

---

1. Supportive Measures

• Hospital admission, often ICU monitoring for severe cases

• Maintenance of airway, breathing, and circulation

• Control of fever

• Fluid and electrolyte balance

• Nutritional support

---

2. Empiric Antiviral Therapy

• Acyclovir (for suspected HSV or VZV encephalitis):

  • Dose: 10 mg/kg IV every 8 hours for 14–21 days

  • Initiate promptly without waiting for PCR results, as delay worsens outcomes.

---

3. Adjunctive Antimicrobial Therapy

If bacterial meningoencephalitis is a possibility:

• Empiric broad-spectrum antibiotics (e.g., ceftriaxone 2 g IV every 12 hours + vancomycin) until bacterial causes are excluded.

---

4. Anticonvulsant Therapy

• Levetiracetam: Start 500–1000 mg IV/PO twice daily; adjust for seizures.

• Alternatives: Phenytoin, valproate.

---

5. Corticosteroids

• May be considered in autoimmune encephalitis or ADEM.

• Example: Methylprednisolone 1 g IV daily for 3–5 days.

---

6. Immunotherapy (Autoimmune Encephalitis)

• High-dose corticosteroids, IV immunoglobulin (IVIG), or plasma exchange.

• Second-line: Rituximab or cyclophosphamide.

---

Prognosis

• Mortality varies by cause: untreated HSV encephalitis mortality ~70%, reduced to 20–30% with prompt acyclovir.

• Arboviral encephalitis often has high morbidity.

• Many survivors experience residual neurological deficits (memory loss, personality changes, epilepsy).

---

Prevention

• Vaccination (MMR, Japanese encephalitis, varicella, rabies).

• Vector control measures.

• Post-exposure prophylaxis for rabies.

• Safe food and water practices to avoid enteroviral infections.