Encephalitis¶
Chapter 142 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Encephalitis is defined as inflammation of the brain caused by infection (commonly viral) or autoimmune processes.
- Common viral causes include herpes simplex virus (HSV), West Nile virus (WNV), and enteroviruses; arboviruses cause epidemics.
- Diagnostic workup includes CSF PCR, MRI, EEG, and serologic testing, with HSV encephalitis requiring urgent antiviral therapy.
- Management involves acyclovir, supportive care, and monitoring for complications like seizures and neurologic sequelae.
- Prognosis varies widely, with severe outcomes in cases of rabies, progressive multifocal leukoencephalopathy (PML), and subacute sclerosing panencephalitis (SSPE).
1. DEFINITION & OVERVIEW¶
Encephalitis is an inflammation of the brain caused by infection (most commonly viral) or autoimmune processes. It often presents with acute febrile illness, altered consciousness, and focal neurologic signs. Viral encephalitis may involve the spinal cord (encephalomyelitis) or cause meningoencephalitis. Autoimmune encephalitis may present with atypical features like NMDA receptor antibodies.
Table 142-1 Viruses Causing Acute Encephalitis in North America¶
| COMMON | LESS COMMON |
|---|---|
| Herpesviruses | Rabies |
| Cytomegalovirusa | Eastern equine encephalitis virus |
| Herpes simplex virus 1b | Powassan virus |
| Herpes simplex virus 2 | Cytomegalovirusa |
| Human herpesvirus 6 | Colorado tick fever virus |
| Varicella-zoster virus | Mumps |
| Epstein-Barr virus | Jamestown Canyon virus |
| Arthropod-borne viruses | |
| La Crosse virus | |
| West Nile virusc | |
| St. Louis encephalitis virus | |
| Zika | |
| Enteroviruses |
1.1 Viral vs. Autoimmune Causes¶
Viral encephalitis is caused by pathogens like HSV, WNV, and arboviruses. Autoimmune encephalitis may involve antibodies against NMDA receptors, LGI-1, or CASPR2, mimicking viral infections.
1.2 Clinical Spectrum¶
Ranges from mild (e.g., HSV encephalitis with focal symptoms) to severe (e.g., rabies, PML). May present with altered consciousness, seizures, or focal deficits.
2. EPIDEMIOLOGY¶
Approximately 20,000 cases/year in the U.S., though actual numbers may be higher. WNV is the most common arbovirus cause, with epidemics in August-September. HSV encephalitis is more common in adults, while enteroviruses affect infants. Rabies is rare in the U.S. but linked to bat exposure.
2.1 Risk Factors¶
Travel to endemic regions, exposure to ticks/rodents, immunocompromise, and recent STI history. WNV risk is highest in elderly and immunocompromised.
2.2 Demographics¶
HSV encephalitis peaks in adults 20-40 years old; WNV affects older adults. PML is more common in HIV/AIDS patients on immunosuppressive therapies.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Viral causes include HSV, WNV, arboviruses, and enteroviruses. Autoimmune encephalitis involves antibodies against NMDA receptors or other proteins. Rabies virus causes rapid CNS invasion. PML results from JC virus reactivation in immunocompromised hosts.
3.1 Viral Mechanisms¶
HSV causes necrotizing encephalitis; WNV induces inflammation in the brainstem and cortex. Arboviruses (e.g., WNV) cause vascular damage and neuronal injury.
3.2 Autoimmune Pathogenesis¶
Antibodies against NMDA receptors or LGI-1 disrupt synaptic function, leading to seizures and cognitive dysfunction. Autoimmune encephalitis may mimic viral infections.
4. CLINICAL FEATURES¶
Altered consciousness (confusion, coma), seizures, focal deficits (e.g., aphasia, ataxia), and behavioral changes. HSV encephalitis often presents with temporal lobe involvement. Rabies may show hydrophobia and paralysis.
4.1 Neuroimaging Findings¶
MRI shows temporal lobe abnormalities in HSV encephalitis. WNV may present with thalamic/brainstem lesions. PML shows multifocal demyelination.
4.2 CSF Findings¶
Lymphocytic pleocytosis, elevated protein, normal glucose. HSV CSF PCR is diagnostic. PML shows JCV DNA in CSF.
5. DIFFERENTIAL DIAGNOSIS¶
Rabies, neurosyphilis, bacterial meningitis, autoimmune encephalitis, and tumors. Distinguish from viral meningitis (mild CSF pleocytosis vs. severe encephalitis).
5.1 Mimicking Viral Encephalitis¶
Mycobacterial infections, Listeria, neurosyphilis, and autoimmune conditions (e.g., NMDA receptor encephalitis).
5.2 Specific Differentiation¶
Rabies presents with hydrophobia and paralysis; PML shows multifocal demyelination on MRI.
6. INVESTIGATIONS & DIAGNOSIS¶
CSF PCR for HSV, WNV, and EBV; MRI for focal lesions; EEG for periodic sharp waves. Serologic testing for arboviruses and autoimmune markers.
Table 142-2 Use of Diagnostic Tests in Encephalitis¶
| Test | Clinical Utility |
|---|---|
| CSF HSV PCR | Diagnostic for HSV encephalitis |
| MRI with FLAIR/DWI | Detects temporal lobe involvement |
| EEG | Identifies periodic sharp waves |
| JCV PCR | Confirms PML |
| Metagenomic sequencing | Detects rare pathogens |
6.1 Diagnostic Algorithms¶
CSF PCR is first-line for HSV/EBV. MRI with FLAIR/DWI sequences identifies temporal lobe involvement. EEG detects periodic complexes in HSV encephalitis.
6.2 Special Tests¶
Metagenomic sequencing for rare pathogens. JCV PCR for PML. Autoantibody testing for autoimmune encephalitis.
7. MANAGEMENT & TREATMENT¶
Acyclovir (10 mg/kg IV q8h for 21 days) is first-line for HSV. Ganciclovir/foscarnet for CMV. PML requires immune reconstitution. Supportive care includes anticonvulsants, ICP monitoring, and ICU management.
7.1 Antiviral Therapy¶
Acyclovir for HSV, ganciclovir/foscarnet for CMV, and intravenous immunoglobulin for rabies. PML requires discontinuation of immunosuppressants.
7.2 Supportive Care¶
Manage seizures, ICP, and infections. Hydration and renal monitoring for acyclovir. Glucocorticoids may reduce IRIS in PML.
8. PROGNOSIS & COMPLICATIONS¶
Mortality 20-30% for HSV encephalitis; 80% for rabies. PML has 50% 1-year survival with severe sequelae. SSPE is progressive and fatal. Long-term sequelae include cognitive deficits, motor dysfunction, and epilepsy.
8.1 Outcome Factors¶
Early treatment improves HSV outcomes. PML prognosis depends on immune reconstitution. SSPE is uniformly fatal.
8.2 Complications¶
Seizures, neurologic deficits, IRIS in PML, and secondary infections. WNV may cause chronic cognitive impairment.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Acyclovir safe; avoid live vaccines. Pediatrics: Neonatal HSV requires high-dose acyclovir. Elderly: Higher WNV risk. Immunocompromised: PML and CMV encephalitis risks.
9.1 Pregnancy¶
Acyclovir is safe; avoid live vaccines. Monitor for HSV transmission to neonates.
9.2 Immunocompromised Patients¶
Higher risk for PML, CMV, and opportunistic infections. Immune reconstitution is critical for PML management.
10. KEY POINTS & CLINICAL PEARLS¶
- HSV encephalitis requires urgent acyclovir. 2. MRI with FLAIR/DWI is critical for diagnosis. 3. PML is a complication of immunosuppressive therapies. 4. WNV encephalitis peaks in summer. 5. Autoimmune encephalitis may mimic viral infections.