Definition
A.Inflammation of the brain parenchyma.
B.Viral encephalitis: An acute viral infection of the brain parenchyma, characterized by a moderate elevation of white blood cells in the cerebrospinal fluid (CSF) and focal neurological deficits. These include but are not limited to altered mental status, cognitive impairments, aphasia, hemiparesis, paresthesias, and behavioral changes.
C.Bacterial or fungal encephalitis: Rare.
D.Paraneoplastic and autoimmune encephalitis: Beyond the scope of this text but should be considered in the setting of known history of or concern for cancer and a sterile CSF analysis. Etiology of disease is related to an inflammation of the brain parenchyma secondary to an antibody attack of the neuronal surface cells and/or synaptic proteins.
Incidence
A.Despite its rarity in contrast to bacterial meningitis, encephalitis remains a significant health concern associated with a high rate of morbidity and mortality.
B.Incidence is related to global distribution patterns of viral infections with the herpes virus and arthropod-borne viruses.
Pathogenesis
A.Encephalitis is characterized as an inflammation of the brain parenchyma due to infectious, postinfectious, or noninfectious etiology with symptoms of altered mental status, focal neurological deficits, and seizures.
B.Viral infection is the most common cause of encephalitis in adults. Herpes simplex virus (HSV) is the leading cause of encephalitis worldwide.
C.In addition to HSV, common causes of infectious encephalitis are varicella herpes zoster virus (VZV), cytomegalovirus (CMV), West Nile Virus, influenza, HIV, mumps, rabies, and measles. Also, more than a dozen species of arthropod-borne viruses are known to cause encephalitis.
Predisposing Factors
A.Recent viral illness.
B.Mosquito bites.
C.Tick bites.
D.Exposure to pig, bat, duck, and rodent feces.
E.Rabid animal bites.
F.Travel to areas with known infective vectors.
G.Immunocompromised state.
H.Immunosuppressive therapy.
I.Organ transplantation.
Subjective Data
A.Common complaints/symptoms.
1.Presentation varies from mild confusion and inappropriate behavior to comatose state.
2.Affected patients present with cortical findings as viruses gravitate toward the brain parenchyma.
3.Cortical symptoms include but are not limited to altered mental status, cognitive impairment, aphasias, hemiparesis, paresthesias, and behavioral changes.
4.Meningeal irritation should not be a symptom. However, it may be seen in patients with meningoencephalitis.
B.Family and social history.
1.Familial history is often noncontributory.
2.Social history may reveal recent viral illness and travel abroad, particularly to sub-Saharan Africa and exposure to rodents, ticks, and mosquitoes.
3.History of cancer or concern for cancer diagnosis may be a factor.
C.Review of systems.
1.General: Fatigue, weakness, fever, or chills.
2.Head, ear, eyes, nose, and throat (HEENT): Headaches.
3.Neurological: Lethargy, syncope, seizures, muscle weakness, altered sensation, altered speech, or disorientation.
Physical Examination
A.Altered mental status: Presence or absence of normal brain function. This is the important distinguishing feature between encephalopathy and meningitis.
B.Focal neurological deficits: Including, but not limited to, cognitive impairments, aphasia, hemiparesis, paresthesias, and behavioral changes.
C.Seizure activity.
D.Nuchal rigidity (unlikely): Including tenderness to palpation and pain with flexion and extension.
Diagnostic Tests
A.A noncontrast CT of the head: Required.
1.Patients will likely have altered mental status, focal neurological deficits, and new onset seizures, which raise concern for elevated intracranial pressure; this allows for ruling out a space occupying lesion.
2.CT scan of the head with temporal lobe edema that does not follow a vascular pattern is the classic presentation of HSV encephalitis.
B.MRI: Shows demyelination, which may be present in other clinical states with similar presentation.
C.Lumbar puncture: Gold standard for a diagnosis of viral encephalitis.
1.CSF analysis.
a.Cell count/differential, glucose, protein and gram stain, and bacterial culture.
b.Abnormal CSF suggestive of viral encephalitis.
i.Elevated opening pressure.
ii.CSF white blood cell (WBC) count elevated but less than 250/μL and lymphocyte dominant.
iii.CSF red blood cell (RBC) count may be present in HSV encephalitis.
iv.CSF glucose greater than 60 mg/dL and CSF/serum ratio of greater than 0.6.
v.CSF protein elevated but less than 150 mg/dL.
vi.Culture and polymerase chain reaction (PCR) test for virus.
1)If culture is negative but strong clinical and radiological suspicion for HSV/VZV encephalitis remains, repeat lumbar puncture in 3 to 5 days and continue treatment.
2.Contraindications to lumbar puncture.
a.Systemic anticoagulation.
b.Thrombocytopenia.
c.Coagulopathy.
d.Open sacral wound at level L3 to L5.
e.CT head with evidence of increased intracranial pressure and/or mass lesion.
D.EEG: Often abnormal in acute encephalitis.
E.Relevant blood work: CBC, basal metabolic profile (BMP), partial thromboplastin time (PTT)/prothrombin time (PT)/international normalized ratio (INR), lactate, and arterial blood gas.
F.Blood cultures.
Differential Diagnosis
A.Viral encephalitis.
B.Bacterial meningitis.
C.Epidural abscess.
D.Nonconvulsive status epilepticus.
E.Subarachnoid hemorrhage.
Evaluation and Management Plan
A.General plan: Viral encephalitis.
1.Rule out bacterial meningitis due to high risk of morbidity and mortality.
2.Patient presentation suggestive of central nervous system (CNS) infection.
3.Follow SEPSIS 3.0 guidelines for fluid resuscitation management of septic shock.
4.Begin broad-spectrum antibiotics as well as antiviral therapy and glucocorticoids if appropriate.
5.Obtain a Stat
CT head without contrast to rule out alternative diagnoses.
6.Use lumbar puncture with CSF analysis for definitive treatment, and if available meningitis/encephalitis PCR for rapid identification of causative pathogen.
7.Arrange for hemodynamic management and supportive care.
8.Admit to ICU for appropriate level of care.
9.Consider MRI of the brain in patients who fail to improve despite treatment to evaluate alternative diagnoses.
10.Consider EEG brain for patients with fluctuating neurological examination or a suppressed level of consciousness.
B.Patient/family teaching points.
1.Worsening neurological examination may lead to acute respiratory failure requiring intubation and mechanical ventilation.
2.Seizures may require treatment with anti-epileptics and in severe cases intubation and mechanical ventilation for treatment with potent sedatives.
3.Evidence of cerebral edema on head CT may prompt aggressive medical management with mannitol and hypertonic saline, including surgical decompression.
4.Evidence of hydrocephalus on head CT may prompt neurosurgical evaluation and intervention.
5.Long-term neurological sequelae are likely with encephalitis.
C.Pharmacotherapy.
1.Definitive diagnosis of encephalitis: Based on CSF analysis and culture data.
2.HSV/VZV encephalitis: Acyclovir 10 mg/kg IV q8 hours for a duration of 21 days.
a.Kidney function should be assessed because acyclovir is nephrotoxic.
3.CMV encephalitis: Ganciclovir 5 mg/kg IV q12 hours + Foscarnet 60 mg/kg q8 hours until symptoms improve.
4.HIV encephalitis.
a.Highly Active Antiretroviral Therapy (HAART): Resume or initiate.
b.Patient-specific treatment plan: Refer to infectious disease guidelines for treatment of HIV/AIDS.
5.De-escalation of antimicrobial therapy based on negative cultures or preferably definitive meningitis/encephalitis PCR test.
6.Patients presenting with seizure activity: Prompt initiation of antiepileptics and discontinuation of medications known to reduce seizure potential.
D.Discharge instructions.
1.Patients should be instructed to seek emergency care if they experience signs and symptoms of fever, headache, neck pain, confusion, and muscle weakness.
Follow-Up
A.Patients with neurological sequelae on discharge are to obtain follow-up with a neurologist.
Consultation/Referral
A.Consider infectious disease consult for atypical pathogens or patients who do not respond to traditional therapy.
B.Consult neurology for patients with neurological sequelae.
Special/Geriatric Considerations
A.Viral encephalitis in elderly patients may often present with mild confusion, lethargy, and nonspecific neurological findings. The provider must be vigilant to recognize patients at high risk for CNS infection and promptly initiate treatment.
Bibliography
Dalmau, J., & Rosenfeld, M. R. (2018, December 10). Paraneoplastic and autoimmune encephalitis. In A. F. Eichler (Ed.), UpToDate. Retrieved from https://www.uptodate.com/contents/paraneoplastic-and-autoimmune-encephalitis
Gaieski, D. F., Nathan, B. R., & O’Brien, N. F. (2015). Emergency neurological life support: Meningitis and encephalitis. New York, NY: Springer Science+Business Media.
Gluckman, S. J. (2017, October 15). Viral encephalitis in adults. In J. Mitty (Ed.), UpToDate. Retrieved from https://www.uptodate.com/contents/viral-encephalitis-in-adults
Wijdicks, E. F. M., & Rabinstein, A. A. (2012). Neurocritical care. (pp. 27–43). New York, NY: Oxford University Press.