Encephalitis

Encephalitis describes brain parenchymal inflammation caused by infection or from a primary autoimmune process. It can be linked with meningitis (meningoencephalitis) or with spinal cord (encephalomyelitis) or nerve root involvement (encephalomyeloradiculitis).

Clinical Manifestations

Characterized by altered level of consciousness (confusion, behavioural abnormalities) or depressed level of consciousness (coma, lethargy), and with evidence of focal or diffuse neurologic injury that can practically have any manifestation:

• Hallucinations, agitation, personality change, behavioural disorders, frank psychosis
• Focal or generalized seizures
• Aphasia, ataxia, upper or lower motor neuron weakness
• Involuntary movements (myoclonus, tremor)
• Cranial nerve deficits
• HPA abnormalities (temperature dysregulation, diabetes insipidus, SIADH)

Etiology

• Viruses (hundreds of possible culprits)
  • HSV
  • VZV
  • EBV
  • Alphaviruses (eastern equine encephalitis)
  • Flaviviruses (WNV, St Louis encephalitis virus, Japanese encephalitis virus, Powassan virus)
  • Bunyaviruses (California encephalitis virus, La Crosse virus)
  • Zika virus
  • Chikungunya virus
  • Rabies
• Non-viral infectious encephalitis
  • Mycobacteria
  • Bartonella
  • Fungal
  • Rickettsiae
  • Listeria
  • Mycoplasma
  • Naegleria fowleri, Acanthamoeba, Balamuthia
• Paraneoplastic and autoimmune encephalitis
  • Anti-NMDA
  • Anti-VGKC
  • Anti-AMPA
  • Anti-GABA
  • Anti-GAD65
  • Hashimoto's encephalopathy (Anti-TG, Anti-TPO)

Diagnosis

• CSF via LP
  • at least 20 mL should be collected
  • contraindications: increased ICP
  • viral meningoencephalitis: lymphocytic pleocytosis, elevated protein, normal glucose concentration
  • A CSF pleocytosis (>5 cells/μL) occurs in >95% of immunocompetent patients with documented viral encephalitis. In rare cases, a pleocytosis may be absent on the initial lumbar puncture (LP) but present on subsequent LPs. Patients who are severely immunocompromised by HIV infection, glucocorticoid or other immunosuppressant drugs, chemotherapy, or lymphoreticular malignancies may fail to mount a CSF inflammatory response.
  • persisting CSF neutrophilia should prompt consideration of bacterial infection, leptospirosis, amebic infection, and noninfectious processes such as acute hemorrhagic leukoencephalitis
  • decreased CSF glucose concentration is distinctly unusual in viral encephalitis and should suggest the possibility of bacterial, fungal, tuberculous, parasitic, leptospiral, syphilitic, sarcoid, or neoplastic meningitis
• MRI/CT/EEG
  • Focal findings in a patient with encephalitis should always raise the possibility of HSV encephalitis
  • EEG abnormalities occur in >75% of PCR-documented cases of HSV encephalitis; they typically involve the temporal lobes but are often nonspecific

Treatment

Best supportive care: avoid hypotonic fluids, consider ICU admission, ICP monitoring, neurovitals, fluid restriction, fever treatment and suppression.

Treat seizures if they develop, and consider prophylaxis in severe cases.

Acyclovir for HSV encephalitis -- start empirically in all cases of suspected viral encephalitis particularly if focal features are present. The course is acyclovir 10 mg/kg IV q8H x 21 days. Complications of therapy include elevations in blood urea nitrogen and creatinine levels (5%), thrombocytopenia (6%), gastrointestinal toxicity (nausea, vomiting, diarrhea) (7%), and neurotoxicity (lethargy or obtundation, disorientation, confusion, agitation, hallucinations, tremors, seizures) (1%). To date, acyclovir-resistant isolates have not been a significant clinical problem in immunocompetent individuals.

Ganciclovir and foscarnet, either alone or in combination, are often used in the treatment of CMV-related CNS infections, although their efficacy remains unproven. Cidofovir (see below) may provide an alternative in patients who fail to respond to ganciclovir and foscarnet, although data concerning its use in CMV CNS infections are extremely limited.

Intravenous ribavirin (15–25 mg/kg per day in divided doses given every 8 h) has been reported to be of benefit in isolated cases of severe encephalitis due to California encephalitis (La Crosse) virus.

No specific antiviral therapy of proven efficacy is currently available for treatment of WNV encephalitis.

References

1. Harrison's Chapter 132, 20E
2. Paraneoplastic and autoimmune encephalitis - UpToDate
3. Autoimmune encephalitis: clinical spectrum and management | Practical Neurology