Encephalitis

• Altered state of consciousness
• Seizures
• Personality changes
• Cranial nerve palsies
• Speech disturbances
• Motor and sensory deficits
  
  

Infectious Causes

• Herpesviruses: Herpes simplex virus (HSV)-1, HSV-2 (more common in neonates), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6, herpes B virus.
• Flaviviruses: West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, Saint Louis encephalitis virus, Powassan virus, dengue virus.
• Other Viruses: Measles virus, mumps virus, rabies virus, HIV, Zika virus, influenza virus, coronaviruses, and adenoviruses.

• Common Pathogens: Neisseria meningitidis (particularly in children and elderly), Listeria monocytogenes, Treponema pallidum (syphilis), and Mycoplasma species.
• Vector-borne Diseases: Rickettsia (e.g., Rocky Mountain spotted fever) and Borrelia burgdorferi (Lyme disease).
  
  

• Cryptococcus, Histoplasma, Blastomyces, and Candida species.
  
  

• Toxoplasma gondii, Naegleria fowleri, Balamuthia mandrillaris, and Plasmodium falciparum.
  
  

• Direct person-to-person spread (e.g., HSV, EBV).
• Vector-borne transmission through mosquitoes and ticks (e.g., arboviruses, Lyme disease).
• Rarely through blood transfusion or organ transplantation, as seen with West Nile virus.
  
  

Non-Infectious Causes

• Represents up to one-third of cases with a defined cause.
• Common antibodies involved:
  • Anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibodies, often associated with ovarian teratomas.
  • Antibodies targeting leucine-rich glioma-inactivated 1 (LGI1) or CASPR2.
• Often follows infections or co-occurs with malignancies.

• Acute disseminated encephalomyelitis (ADEM) is frequently observed in children as a post-infectious phenomenon.

• Creutzfeldt-Jakob disease involves progressive neurodegeneration due to abnormal prion proteins.

• Caused by antibodies linked to underlying malignancies, such as anti-Hu or anti-Yo antibodies.
  
  

Pathogen Entry and Dissemination

• Portals of Entry:
  • Viruses often replicate in peripheral tissues such as the gastrointestinal tract, respiratory system, or skin before dissemination.
  • Pathogens reach the central nervous system (CNS) through:
    • Hematogenous Spread: Seen with viruses like enteroviruses, arboviruses, herpes simplex virus (HSV), mumps virus, and HIV.
    • Retrograde Axonal Transport: Utilized by pathogens like rabies virus, HSV, and certain prion diseases.
• Specific Transmission Modes:
  • HSV encephalitis is often due to reactivation of latent virus in the trigeminal ganglia.
  • Arboviruses are introduced via insect vectors such as mosquitoes or ticks.
  • Rabies virus spreads through bites or exposure to infected animal secretions.
    
    

Viral Mechanisms and Inflammatory Response

1. Cell Entry and Infection:
   • After breaching the blood-brain barrier, viruses infect neural cells, leading to cellular dysfunction.
   • Perivascular congestion and hemorrhage accompany a diffuse inflammatory response, predominantly affecting gray matter due to regional neuronal tropism.
2. Focal Involvement:
   • Some viruses exhibit specific regional preferences, such as HSV, which primarily targets the inferior and medial temporal lobes.
3. Host Immune Response:
   • The interplay between viral neurotropism and the host immune system (e.g., humoral antibodies, cytotoxic T cells, cytokines) governs the extent and pattern of brain inflammation.
     
     

Autoimmune Mechanisms

• In autoimmune encephalitis, antibodies or T-cells mistakenly target brain antigens, leading to inflammatory damage.
• Anti-NMDA receptor encephalitis and other paraneoplastic syndromes exemplify such immune-mediated conditions. These are typically responsive to immunosuppressive therapies, reflecting their immune-based pathogenesis.
  
  

Pathophysiological Differences in Specific Conditions

1. Direct Viral Invasion:
   • Viral infections like HSV and VZV cause direct cytotoxic effects in gray matter.
   • Measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML) represent slow virus infections, with pathophysiology that remains incompletely understood.
2. Immune-Mediated Damage:
   • Acute disseminated encephalomyelitis (ADEM) and postinfectious encephalomyelitis (PIE) involve immune-mediated demyelination of perivenous white matter, often triggered by infections such as measles, Epstein-Barr virus (EBV), or cytomegalovirus (CMV).
     
     

Key Pathological Features

• Disruption of neural cell functioning
• Perivascular inflammation and congestion
• Predominant involvement of gray matter
• Multifocal demyelination in immune-mediated conditions
  
  

Global Incidence

• The global incidence of encephalitis ranges from 1.5 to 14 cases per 100,000 population annually.
• Approximately 20,000 cases of encephalitis occur annually in the United States, with viral causes being the most common.
• Data suggest underreporting due to variations in clinical presentations, diagnostic criteria, and hospital discharge policies.
  
  

United States Statistics

• Viral encephalitis accounts for several thousand cases reported annually to the CDC, with an additional ~100 cases attributed to post-infection encephalitis (PIE).
• Herpes simplex encephalitis (HSE) is the most common cause of sporadic encephalitis in Western countries, with an incidence of 0.2 per 100,000.
• Arboviruses are a significant cause of episodic encephalitis. However, <10% of individuals bitten by arbovirus-infected insects develop overt encephalitis. Key examples include:
  • St. Louis encephalitis: Predominantly affects urban areas near the Mississippi River.
  • California virus encephalitis (LaCrosse virus): More common in children in rural Midwest and Northeast regions.
  • Eastern equine encephalitis (EEE): Rare but often fatal, primarily seen in New England and surrounding areas.
  • Western equine encephalitis (WEE): Common in rural areas west of the Mississippi River.
  • Powassan virus: Tick-borne arbovirus associated with sporadic encephalitis cases.
• Rare forms include rabies encephalitis (0–3 cases/year), typically linked to exposure during immigration.

International Statistics

• Japanese encephalitis (JE) is the most common viral encephalitis outside the U.S., occurring in Japan, Southeast Asia, China, and India.
• Tick-borne encephalitis (TBE) is increasing in Europe due to expanded endemic areas and prolonged tick activity seasons. In 2021, there were 3027 reported cases across 25 European Union/EEA countries.
  
  

Age-Related and Demographic Trends

• Age Extremes: Neonates and elderly individuals are at the highest risk:
  • Neonatal HSE is a manifestation of disseminated infection, with 2–3 per 10,000 live births affected.
  • Older children and adults tend to develop localised central nervous system (CNS) infections.
• Arboviral infections vary by age:
  • St. Louis encephalitis and West Nile encephalitis are more severe in individuals >60 years.
  • LaCrosse encephalitis disproportionately affects children <16 years.
  • Eastern and Western equine encephalitis are particularly severe in infants.
    
    

Seasonal and Geographical Variations

• Seasonal patterns in the U.S. reveal a peak in arbovirus cases during summer and early autumn (July–October).
• Endemic areas for TBE in Europe include forested regions of Central, Eastern, and Northern Europe, with cases steadily rising in countries like Czechia, Sweden, and Germany.
  
  

Trends in Specific Populations

• The incidence of encephalitis associated with HIV has decreased due to advancements in antiretroviral therapy.
• Autoimmune encephalitis has shown a rising incidence due to improved diagnostic capabilities. Anti-NMDAR encephalitis is the most commonly identified autoimmune form, with a female predominance.
• Acute disseminated encephalomyelitis (ADEM) is rare (0.2–0.4 per 100,000 children annually), typically presenting between ages 3 and 7 years.

Key Diagnostic Factors

• Age Extremes: Neonates (<1 year) and elderly individuals (>65 years) are at higher risk due to underdeveloped or weakened immune responses, respectively.
• Immunosuppression: Conditions such as HIV infection, chemotherapy, or immunosuppressive medications predispose to infections like Cytomegalovirus (CMV), Toxoplasma gondii, and Epstein-Barr Virus (EBV).
• Vector Exposure and Animal Bites:
  • Mosquitoes transmit arboviruses such as West Nile, Japanese encephalitis, and equine encephalitis viruses.
  • Tick exposure is associated with Powassan virus and tick-borne encephalitis.
  • Rabies results from animal bites or exposure to infected secretions.
• Geography and Seasonal Variations:
  • Arboviruses peak in summer and early autumn.
  • Regional distribution includes tick-borne encephalitis in Europe and Japanese encephalitis in Asia.
    
    

Common Symptoms and Clinical Findings

• A frequent symptom in infectious causes, except in immunocompromised individuals and some conditions like subacute sclerosing panencephalitis (SSPE).
  
  

• Rash types can help identify the etiology:
  • Vesicular: Herpes simplex virus (HSV), varicella-zoster virus (VZV).
  • Petechial: Rickettsial infections.
  • Erythema Migrans: Lyme disease.
  • Kaposi Sarcoma: Seen in HIV/AIDS.
    
    

• A hallmark of encephalitis presenting as lethargy, confusion, or psychosis. Severe forms include amnesia, hallucinations, and disorientation.
  
  

• Common presentations include hemiparesis, ataxia, cranial nerve deficits, or tremors. Tremors are frequently seen in arbovirus infections, and paraesthesias in rabies or tick-borne encephalitis.
  
  

• Common in HSV, human herpesvirus-6, and other viral encephalitis.
• Limbic encephalitis may involve faciobrachial dystonic seizures.
  
  

• Presents with headache, photophobia, and neck stiffness, especially in meningoencephalitis.
  
  

Historical and Clinical Clues

• Prodrome: Symptoms such as fever, headache, and myalgia often precede neurologic manifestations.
• Specific Exposure History: Travel to endemic areas, vector bites, or exposure to infected animals is critical for identifying causes like arboviruses or rabies.
• Unique Presentations:
  • Severe lethargy in West Nile encephalitis.
  • Localised skin or eye lesions in neonatal HSV infection.
  • Subacute headaches in HIV-positive individuals with Toxoplasma gondii.
    
    

High-Risk Activities and Occupations

• Activities like trekking, spelunking, or exposure to bats and livestock increase zoonotic infection risk.
• Occupational risks include farm workers (Nipah virus), forestry workers (Lyme disease), and healthcare workers (tuberculosis).
  
  

Other Diagnostic Features

• Parotitis: Seen in mumps-related encephalitis.
• Gastrointestinal Symptoms: Common in enterovirus infections.
• Movement Disorders: Orofacial dyskinesias in anti-NMDA receptor encephalitis, myoclonus in Creutzfeldt-Jakob disease.
  
  

Neurological Signs

• Altered Mental Status:
  • Personality changes, confusion, lethargy, or decreased alertness are hallmark signs.
• Focal Neurological Deficits:
  • Hemiparesis, ataxia, aphasia, cranial nerve deficits, and Babinski's sign.
  • Tremors (often linked to arboviruses) and paraesthesias (e.g., rabies, tick-borne encephalitis).
• Seizures:
  • Generalised tonic-clonic or focal seizures are common.
  • Faciobrachial dystonic seizures may indicate limbic encephalitis.
    
    

Meningeal Signs

• Meningismus:
  • Headache, photophobia, and neck stiffness may occur, though less pronounced than in meningitis.
    
    

Systemic Signs

• Rash:
  • Vesicular (HSV, VZV), petechial (rickettsial fever), or erythema migrans (Lyme disease).
• Autonomic and Hypothalamic Dysfunction:
  • Dysphagia (notably in rabies) and loss of temperature regulation or vasomotor control.
    
    

Movement Disorders

• Myoclonus (e.g., Creutzfeldt-Jakob disease) and orofacial dyskinesias (anti-NMDA receptor encephalitis).
  
  

Neonatal Findings

• Neonates with HSV Encephalitis:
  • Seizures, irritability, poor feeding, bulging fontanelles, and possible herpetic skin lesions.
    
    

Uncommon Findings

• Acute Flaccid Paralysis:
  • Associated with West Nile virus or other arboviruses.
• Parotitis:
  • Seen in mumps-related encephalitis.
• Ataxia:
  • Linked to arboviruses like St. Louis encephalitis.
    
    

First-Line Investigations

Blood Tests

1. Full Blood Count (FBC):
   • Elevated white blood cell (WBC) count in infectious causes.
   • Relative lymphocytosis in viral encephalitis; leukopenia and thrombocytopenia in rickettsial and viral fevers.
   • Eosinophilia in parasitic infections (Baylisascaris procyonis).
2. Serum Electrolytes:
   • Hyponatremia in anti-voltage-gated potassium channel encephalitis, rickettsial infections, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
3. Liver Function Tests:
   • Elevated in infections like Coxiella burnetii, Rickettsia, and Epstein-Barr virus (EBV).
4. Blood Cultures:
   • Obtain two sets to detect systemic bacterial or fungal infections.
     
     

Imaging

1. Computed Tomography (CT):
   • Screening tool for mass effects, intracranial pressure, or hemorrhages.
   • Findings:
     • Herpes simplex virus (HSV): Hypodense lesions in the temporal lobe.
     • HIV: White matter hypodensities.
     • West Nile virus: Deep brain hyperintensities.
2. Magnetic Resonance Imaging (MRI):
   • Highly sensitive and specific for encephalitis.
   • Findings:
     • HSV: T2 hyperintensities in the temporal lobes and cingulate gyrus.
     • Japanese encephalitis: Hyperintensities in bilateral thalami and brainstem.
     • Varicella zoster virus: Gray and white matter hyperintensities.
       
       

Lumbar Puncture and Cerebrospinal Fluid (CSF) Analysis

1. Opening Pressure:
   • Elevated in bacterial, fungal, and tubercular infections.
2. Cell Counts:
   • Pleocytosis in viral encephalitis (initial polymorphonuclear dominance, later lymphocytosis).
   • RBCs in HSV-related hemorrhagic encephalitis.
3. Protein and Glucose:
   • Elevated protein in bacterial and autoimmune causes; normal or mildly elevated in viral infections.
   • Glucose decreased in bacterial, fungal, and parasitic infections.
4. CSF Polymerase Chain Reaction (PCR):
   • Essential for identifying viral causes (e.g., HSV, enterovirus, Mycoplasma pneumoniae).
     
     

Additional Investigations

1. Electroencephalogram (EEG):
   • Background slowing common.
   • HSV: Periodic lateralising epileptiform discharges (PLEDs).
   • Anti-NMDA receptor encephalitis: Delta brush patterns.
2. Paraneoplastic Antibodies:
   • Anti-NMDA receptor, anti-LGI1, anti-CASPR2 antibodies to identify paraneoplastic encephalitis.
3. Brain Biopsy:
   • Reserved for undiagnosed cases.
   • Diagnostic for infections like rabies (Negri bodies) or HSV (Cowdry type A inclusions).
4. Advanced Imaging and Biomarkers:
   • Whole-body CT or PET for malignancy screening.
   • Real-time quaking-induced conversion (RT-QuIC) for prion diseases.
     
     

Viral Meningitis

• Features:
  • Presents with fever, headache, and neck stiffness but typically lacks altered mental status or focal deficits.
  • Can coexist with encephalitis (meningoencephalitis).
• Investigations:
  • CSF: Elevated WBC (lymphocytic predominance), normal glucose, slightly elevated protein.
  • MRI: Meningeal enhancement without parenchymal involvement.
    
    

Metabolic/Toxic Encephalopathy

• Features:
  • Altered mental status without structural brain abnormalities.
  • Often related to metabolic disturbances or systemic infections.
• Investigations:
  • Normal CSF and MRI findings.
  • EEG: Generalised slowing or triphasic waves.
    
    

Status Epilepticus

• Features:
  • Recurrent or continuous seizures can mimic encephalitis symptoms.
  • May occur in patients with pre-existing seizure disorders, often due to subtherapeutic drug levels.
• Investigations:
  • EEG: Ongoing seizure activity.
  • MRI and CSF: Typically normal unless an underlying cause is present.
    
    

Central Nervous System Vasculitis

• Features:
  • Focal neurological signs, headaches, and possible confusion.
• Investigations:
  • MRI: Multiple small cortical strokes.
  • Angiography: Beading or segmental narrowing of vessels.
  • Biopsy: Lymphocytic infiltration in vessel walls.
    
    

Posterior Reversible Encephalopathy Syndrome (PRES)

• Features:
  • Headache, confusion, seizures, and visual disturbances; often associated with hypertension, renal failure, or eclampsia.
• Investigations:
  • MRI: T2/FLAIR hyperintensities, typically in the posterior brain regions.
    
    

Intracranial Neoplasms

• Features:
  • Headache (worse in the morning), altered mental status, focal deficits, or seizures.
• Investigations:
  • MRI: Mass lesions or cystic changes.
  • Biopsy: Confirms diagnosis in unclear cases.
    
    

Neurosarcoidosis

• Features:
  • Cranial nerve involvement (e.g., CN II, VII), hypothalamic dysfunction, and peripheral neuropathy.
  • Systemic signs include erythema nodosum, lymphadenopathy, and arthralgia.
• Investigations:
  • MRI: Meningeal enhancement.
  • CSF: Elevated lymphocytes and protein.
  • Biopsy: Non-caseating granulomas.
    
    

Systemic Lupus Erythematosus (SLE)

• Features:
  • Neuropsychiatric symptoms, seizures, and systemic signs such as arthritis, rash, or renal disease.
• Investigations:
  • Serology: Positive ANA, anti-dsDNA, or anti-Smith antibodies.
    
    

Intracranial Hemorrhage

• Features:
  • Headache, altered mental status, and focal neurological deficits.
• Investigations:
  • CT: Detects acute hemorrhage.
  • Lumbar puncture: Xanthochromia in subarachnoid hemorrhage.
    
    

Ischemic Stroke

• Features:
  • Sudden onset of focal neurological deficits with altered mental status or seizures.
• Investigations:
  • MRI: Restricted diffusion on diffusion-weighted imaging (DWI).

  • 
    

Mitochondrial Disorders (e.g., MELAS)

• Features:
  • Hearing loss, seizures, stroke-like episodes, lactic acidosis.
• Investigations:
  • Genetic testing: Mitochondrial DNA mutations.
  • MRI: T2 hyperintensities in atypical territories.

Bacterial and Fungal Meningitis

• Features:
  • Fever, neck stiffness, and altered consciousness.
• Investigations:
  • CSF: Elevated WBC with neutrophil predominance, high protein, and low glucose.
  • Cultures: Identify causative organisms.
    
    

Prehospital Care

• Assess and manage for shock or hypotension:
  • Initiate crystalloid infusion in patients with circulatory compromise.
• Protect the airway in patients with altered mental status; administer oxygen.
• Implement seizure precautions:
  • Treat seizures with lorazepam (0.1 mg/kg IV).
• Establish IV access during transport to facilitate rapid treatment upon ED arrival.
  
  

Emergency Department Care

• Initial Priorities:
  • Begin empirical treatment with acyclovir (10 mg/kg IV q8h) for suspected herpes simplex encephalitis (HSE) or varicella-zoster encephalitis (VZV).
  • Draw blood cultures and collect laboratory samples before initiating IV therapy.
  • Perform MRI (preferred) or contrast-enhanced CT before lumbar puncture (LP), unless contraindicated.
• Supportive Care:
  • Address complications such as hypoxemia, hypotension, or electrolyte disturbances.
  • Monitor for raised intracranial pressure (ICP) or systemic issues like hyponatremia.
• Empiric Therapy for Common Pathogens:
  • HSV/VZV: Acyclovir.
  • Cytomegalovirus (CMV): Ganciclovir + foscarnet for immunocompromised patients.
  • Other pathogens: Tailored treatment depending on clinical suspicion and laboratory results.
    
    

Management of Increased Intracranial Pressure (ICP)

• General Measures:
  • Elevate the head of the bed to 30°–45°.
  • Manage fever, pain, and prevent systemic hypotension or seizures.
• Pharmacologic Interventions:
  • Diuretics: Furosemide (20 mg IV) or mannitol (1 g/kg IV) for severe cases.
  • Corticosteroids: Dexamethasone (10 mg IV q6h) for edema surrounding lesions.
  • Hypertonic saline for osmotherapy if mannitol is ineffective.
• Advanced Monitoring:
  • Consider intraventricular monitoring in select cases, though its utility is debated.
    
    

Antiviral Therapy

• Start empiric antiviral treatment immediately for suspected viral encephalitis:
  • Acyclovir: First-line for HSV and VZV.
  • Ganciclovir and Foscarnet: For CMV, particularly in immunocompromised individuals.
  • Human herpesvirus 6 (HHV-6): Consider ganciclovir or foscarnet for immunocompromised hosts.
• Adjust therapy based on PCR results and clinical findings.
  
  

Corticosteroids

• Indications:
  • High-dose corticosteroids are the first-line treatment for acute disseminated encephalomyelitis (ADEM) and autoimmune encephalitis.
  • Use cautiously in viral encephalitis due to limited evidence of benefit.
• Recommended Protocol:
  • Administer for 3–7 days to minimise side effects like gastrointestinal bleeding and secondary infections.
    
    

Treatment of Autoimmune Encephalitis

• Immunotherapy:
  • First-line: High-dose corticosteroids, intravenous immunoglobulin (IVIG), or plasma exchange.
  • Second-line: Rituximab (preferred for antibody-mediated cases) or cyclophosphamide.
• Paraneoplastic Encephalitis:
  • Treat underlying malignancies promptly (e.g., ovarian teratoma resection for anti-NMDAR encephalitis).
    
    

Systemic Complications

• Address systemic manifestations such as:
  • Hypotension, seizures, respiratory failure, or exacerbation of chronic conditions.
  • Implement thromboprophylaxis and gastrointestinal ulcer prevention in prolonged cases.
    
    

Rehabilitation

• Post-Infectious Recovery:
  • Cognitive therapy, physiotherapy, and behavioral therapy improve functionality after encephalitis.
  • Non-pharmacological treatments such as music therapy may alleviate neuropsychiatric symptoms like apathy or cognitive decline.
    
    

Surgical Interventions

• Reserved for refractory cases of elevated ICP:
  • Options include shunting, decompressive craniectomy, or ICP monitoring devices.
  • Surgical decompression may benefit select patients with severe HSV encephalitis.
    
    

General Prognostic Factors

• Mortality rates vary widely:
  • 6–9% in the U.S.
  • ~12% in England for infectious encephalitis.
• Poor prognostic indicators include:
  • Age >65 years.
  • Immunosuppression (e.g., HIV, immunosuppressive therapy).
  • Coma, mechanical ventilation, or status epilepticus during illness.
  • Elevated cerebrospinal fluid (CSF) polymorphonuclear count or acute thrombocytopenia.
  • Cerebral edema or diffuse brain involvement.
• Late sequelae:
  • Severe disability in over 50% of survivors.
  • In children, cognitive impairments, motor deficits, ataxia, epilepsy, and personality changes occur in up to two-thirds of cases.
    
    

Infectious Encephalitis

• Untreated mortality: 50–75%.
• Mortality with acyclovir: ~20%.
• Prognostic factors:
  • Delay in initiating acyclovir or absence of treatment leads to worse outcomes.
  • Poor outcomes are associated with older age, decreased consciousness, diffuse cerebral edema, and intractable seizures.
• Sequelae:
  • Memory impairment, personality changes, anosmia, and psychiatric issues.
    
    

• Japanese Encephalitis (JE) and Eastern Equine Encephalitis (EEE):
  • Mortality rates: 20–70%.
  • Long-term sequelae include intellectual disabilities, hemiplegia, and epilepsy.
• West Nile and St. Louis Encephalitis:
  • Mortality: 2–20%, higher in those >60 years.
  • Sequelae: Behavioral changes, memory loss, seizures.
• Western Equine Encephalitis (WEE):
  • Mortality: <5%.
  • Long-term outcomes include developmental delays, seizures, and occasional paralysis in children.
• La Crosse Virus (LAC):
  • Most cases recover fully; severe disease leads to neurological dysfunction in 25%.
    
    

• VZV:
  • Mortality: 15% in immunocompetent patients; nearly 100% in immunocompromised individuals.
• EBV:
  • Mortality: ~8%.
  • 12% of survivors have lasting neurological deficits.
    
    

• Mortality is nearly 100% in symptomatic cases, with only rare survivors.
  
  

Autoimmune Encephalitis

• Mortality rates are generally lower compared to infectious causes.
• Anti-NMDA Receptor Encephalitis:
  • Mortality: Up to 6%.
  • Relapse rate: 12–25%.
  • Early immunotherapy improves outcomes, but cognitive and behavioral impairments may persist.
• Anti-LGI1 Encephalitis:
  • Lower mortality than anti-NMDA, but higher relapse rates.
• Long-term management challenges include relapse prevention and addressing residual neurological symptoms.
  
  

Post-Infectious Syndromes

• Post-Infectious Encephalitis (PIE):
  • Often associated with measles or other viral infections.
  • Mortality can reach 40%, with high rates of neurological sequelae.
• Subacute Sclerosing Panencephalitis (SSPE):
  • Uniformly fatal, with disease progression over weeks to years.
    
    

Prognostic Considerations for Specific Factors

• Seizures:
  • Occur in ~60% of cases; strong predictor of post-encephalitic epilepsy.
  • 10% of survivors develop epilepsy within 5 years; 20% within 20 years.
• Age and Severity:
  • Extremes of age (<1 year or >55 years) and pre-existing neurological conditions are associated with poorer outcomes.
• Immunocompromised Status:
  • HIV, chemotherapy, or immunosuppressive therapy increases mortality risk and worsens outcomes.
    
    

Rehabilitation and Recovery

• Rehabilitation therapies:
  • Cognitive and behavioral interventions, along with physiotherapy, improve functionality in survivors.
• Long-term follow-up:
  • Monitoring for epilepsy, motor impairments, and neuropsychiatric sequelae is essential.
    
    

Short-Term Complications

1. Death:
   • Mortality rates depend on the underlying etiology.
   • Untreated herpes simplex virus (HSV) encephalitis mortality: ~70%; reduced to ~10% with acyclovir.
   • Rabies and amoebic encephalitis are nearly universally fatal.
   • High mortality is also observed in eastern equine encephalitis, Japanese encephalitis, and viral hemorrhagic fevers.
2. Hypothalamic and Autonomic Dysfunction:
   • Includes SIADH, diabetes insipidus (DI), hyperthermia, and vasomotor instability.
   • Management:
     • SIADH: Fluid restriction and avoidance of hypotonic fluids.
     • DI: Desmopressin and normovolemia maintenance.
     • Hyperthermia: Cooling devices and antipyretics.
3. Ischemic Stroke:
   • Worsens outcomes based on severity.
   • Antiplatelet or anticoagulant therapy may be considered if safe.
4. Seizures and Status Epilepticus:
   • Ongoing convulsive activity is common.
   • Treatment:
     • IV lorazepam or diazepam for acute seizures.
     • IV fosphenytoin as a maintenance therapy.
     • Persistent seizures require intubation and general anesthesia.
       
       

Long-Term Complications

1. Neurological:
   • Includes cognitive impairments, ADHD, amnesia, neuropsychiatric disorders, motor deficits, and speech issues.
   • Rehabilitation with neuropsychiatric services, speech therapy, and physical therapy is critical.
2. Post-Encephalitic Epilepsy:
   • Occurs in 10% within 5 years and 20% within 20 years.
   • Strongly associated with seizures during the acute phase and abnormal brain MRI findings.
3. Autoimmune Encephalitis:
   • Commonly triggered post-HSV encephalitis, occurring in 23–27% of cases.
   • Presents with age-dependent neurological decline and responds to immunotherapy.
4. Hypersomnolence and Sleep Disorders:
   • Includes parasomnia, insomnia, and hypersomnia.
   • These disorders may persist beyond the acute phase and hinder recovery.
5. Chronic Fatigue Syndrome:
   • Seen post-viral encephalitis, with symptoms such as persistent fatigue, myalgia, and cognitive difficulties.
   • Managed through a multidisciplinary approach.
6. Movement and Sensory Deficits:
   • Includes motor weakness, ataxia, and sensory disturbances.
   • May necessitate assistive devices and ongoing physiotherapy.
     
     

Other Variable Complications

1. Hydrocephalus:
   • Seen in bacterial, fungal, or parasitic encephalitis due to impaired CSF absorption.
   • Treatment: Ventriculoperitoneal shunting.
2. Cerebral Hemorrhage:
   • Managed conservatively with blood pressure control or surgically for larger bleeds.
3. Cerebral Vasculitis:
   • Common in varicella-zoster virus (VZV) encephalitis.
   • Management: High-dose corticosteroids in selected cases.
4. Cerebral Vein Thrombosis:
   • Treatment is challenging due to the risk of bleeding from anticoagulants.
5. Encephalitis Lethargica (Von Economo's Disease):
   • Rarely seen post-viral encephalitis; characterised by somnolence, fatigue, and ophthalmoplegia.
     
     

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