Encephalitis

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

Infectious Causes

Viral Agents

• 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
• West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, Saint Louis encephalitis virus, Powassan virus, dengue virus
• Measles virus, mumps virus, rabies virus, HIV, Zika virus, influenza virus, coronaviruses, and adenoviruses

Bacterial Causes

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

Fungal Agents

• Cryptococcus, Histoplasma, Blastomyces, and Candida species

Parasitic Causes

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

Transmission

• 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

Immune-mediated and Autoimmune Encephalitis

• Represents up to one-third of cases with a defined cause
• 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

Para-Infectious Syndromes

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

Prion Diseases

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

Paraneplastic Syndromes

• 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: Utilised 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

Cell Entry and Infection

• After breaching the blood-brain barrier, viruses infect neural cells, leading to cellular dysfunction
• Perivascular congestion and haemorrhage accompany a diffuse inflammatory response, predominantly affecting grey matter due to regional neuronal tropism

Focal Involvement

• Some viruses exhibit specific regional preferences, such as HSV, which primarily targets the inferior and medial temporal lobes

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

Direct Viral Invasion

• Viral infections like HSV and VZV cause direct cytotoxic effects in grey matter
• Measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML) represent slow virus infections, with pathophysiology that remains incompletely understood

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 grey 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
• Cases are 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

Presence of Risk 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

 Fever

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

Rash

• 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

Altered Mental State

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

Focal Neurological Deficits

• 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

Seizures

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

Meningismus

• 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

• Seen in Creutzfeldt-Jakob disease

Orofacial Dyskinesias

• Seen in 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

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)

Serum Electrolytes

• Hyponatremia in anti-voltage-gated potassium channel encephalitis, rickettsial infections, and syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Liver Function Tests

• Elevated in infections like Coxiella burnetii, Rickettsia, and Epstein-Barr virus (EBV)

Blood Cultures

• Obtain two sets to detect systemic bacterial or fungal infections

Imaging

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

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

Opening Pressure

• Elevated in bacterial, fungal, and tubercular infections

Cell Counts

• Pleocytosis in viral encephalitis (initial polymorphonuclear dominance, later lymphocytosis)
• RBCs in HSV-related hemorrhagic encephalitis

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

CSF Polymerase Chain Reaction (PCR)

• Essential for identifying viral causes (e.g., HSV, enterovirus, Mycoplasma pneumoniae)

Additional Investigations

Electroencephalogram (EEG)

• Background slowing common
• HSV: Periodic lateralising epileptiform discharges (PLEDs)
• Anti-NMDA receptor encephalitis: Delta brush patterns

Paraneoplastic Antibodies

• Anti-NMDA receptor, anti-LGI1, anti-CASPR2 antibodies to identify paraneoplastic encephalitis

Brain Biopsy

• Reserved for undiagnosed cases
• Diagnostic for infections like rabies (Negri bodies) or HSV (Cowdry type A inclusions)

Advanced Imaging and Biomarkers

• Whole-body CT or PET for malignancy screening
• Real-time quaking-induced conversion (RT-QuIC) for prion diseases

Viral Meningitis

• 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

• 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

• 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

• 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)

• 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

Herpes Simplex Virus (HSV) 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.

Arboviral Encephalitis

• 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%.

Varicella-Zoster Virus (VZV) and Epstein-Barr Virus (EBV)

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

Rabies Encephalitis

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

Autoimmune Encephalitis

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 therpies

• 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

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.

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.

Ischemic Stroke

• Worsens outcomes based on severity.
• Antiplatelet or anticoagulant therapy may be considered if safe.

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

Neurological

• Includes cognitive impairments, ADHD, amnesia, neuropsychiatric disorders, motor deficits, and speech issues.
• Rehabilitation with neuropsychiatric services, speech therapy, and physical therapy is critical.

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.

Autoimmune Encephalitis

• Commonly triggered post-HSV encephalitis, occurring in 23–27% of cases.
• Presents with age-dependent neurological decline and responds to immunotherapy.

Hypersomnolence and Sleep Disorders

• Includes parasomnia, insomnia, and hypersomnia.
• These disorders may persist beyond the acute phase and hinder recovery.

Chronic Fatigue Syndrome

• Seen post-viral encephalitis, with symptoms such as persistent fatigue, myalgia, and cognitive difficulties.
• Managed through a multidisciplinary approach.

Movement and Sensory Deficits

• Includes motor weakness, ataxia, and sensory disturbances.
• May necessitate assistive devices and ongoing physiotherapy.

Other Variable Complications

Hydrocephalus

• Seen in bacterial, fungal, or parasitic encephalitis due to impaired CSF absorption.
• Treatment: Ventriculoperitoneal shunting.

Cerebral Hemorrhage

• Managed conservatively with blood pressure control or surgically for larger bleeds.

Cerebral Vasculitis

• Common in varicella-zoster virus (VZV) encephalitis.
• Management: High-dose corticosteroids in selected cases.

Cerebral Vein Thrombosis

• Treatment is challenging due to the risk of bleeding from anticoagulants.

Encephalitis Lethargica (Von Economo's Disease)

• Rarely seen post-viral encephalitis; characterised by somnolence, fatigue, and ophthalmoplegia.

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