Author:
Roger M.Barkin
MarySaunders
Description
- Acute inflammation of the brain
- 20,000 cases in the U.S. annually
- Mortality: 10%
- Inflammatory reaction occurs within brain parenchyma with destruction of neurons, parenchymal edema, and petechial hemorrhages
- Route of CNS infection usually hematogenous:
- Respiratory or GI tract
- Blood transfusion
- Organ transplant
- Neural migration occurs with rabies, herpes simplex virus (HSV), and varicella zoster virus (VZV) encephalitis
Etiology
- Viral is most common
- Noninfectious
- 50% of cases have no identifiable cause
Specific Viruses
- HSV:
- 10-20% of all encephalitides
- Primary or reactivation
- Early treatment improves prognosis
- Arbovirus:
- 10-15% of all encephalitides
- Zoonotic transmission (mosquitoes, ticks) in warm months
- Eastern equine causes fulminant encephalitis:
- Tropism for the hippocampus
- Abrupt onset of headache, fever, vomiting progressing to coma
- Western equine occurs mostly in the western 2/3 of the U.S.:
- Often preceded by nonspecific upper respiratory/GI tract symptoms
- Japanese - most prevalent arboviral encephalitis worldwide:
- Indolent course of fever, headache, myalgias, and fatigue followed by confusion, delirium, masklike facies, and parkinsonism, seizures, brainstem dysfunction, coma, and death
- Flavivirus:
- West Nile virus - increased incidence in North America:
- Found in mosquitoes and birds
- Febrile illness, often with rash
- Headache
- Lymphadenopathy
- Polyarthropathy
- Increased morbidity/mortality in elderly patients
- Flaccid paralysis can lead to respiratory failure with 50% mortality
- Enteroviral:
- Occurs mainly in children <10 yr old
- Relatively benign course with little or no long-term sequelae
- Measles encephalitis:
- Occurs several days to 2-3 wk after primary infection and rash, or after years of latent infection
- Abrupt onset and rapid progression to coma
- Seizures common (50-60%)
- Postimmunization incidence of 1 per 1 million vaccinated
- HIV encephalitis:
- Lower CD4 counts predispose to encephalitis
- Typical features include motor spasticity and dementia
- Involvement of white matter with extensive neural degeneration
- Rhabdovirus: Rabies
- CNS infection in the absence of systemic infection
Nonviral
- Mycoplasma pneumoniae
- Toxoplasma gondii
- Rickettsia rickettsii
- Mycobacterium tuberculosis
- Borrelia burgdorferi
- Bartonella henselae
Immunocompromised/HIV Patients
- Histoplasma
- Cryptococcus neoformans
- VZV
- Listeria monocytogenes
- Cytomegalovirus (CMV)
- T. gondii
- Human herpesvirus type 6 (HHV-6)
Autoimmune
- Anti-LGI1 encephalitis
- Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis
Signs and Symptoms
- Often begins with a preceding flulike illness over a few days:
- Mild headache, fever, sore throat, reduced appetite, myalgias
- Altered level of consciousness, drowsiness, coma
- Impaired cognitive ability and personality change, hallucinations, psychosis
- Restlessness, agitation, irritability, delirium
- Rash:
- Lyme disease
- Rocky Mountain spotted fever
- Varicella
- HSV
- Seizures
- Fever, headache, vomiting, possible meningismus
- Focal neurologic deficits, tremor, ataxia, cranial nerve palsies (more common than meningitis)
- Papilledema on funduscopy:
- Autonomic dysfunction can lead to hypotension and cardiac arrhythmias
- Clinical picture varies from mild headache and mild cognitive/emotional lability to severe agitation, seizures, coma, permanent neurologic sequelae, and death
- Clinical course of symptoms may be slow moving or rapidly progressive
History
Arboviruses (eastern equine, western equine, St. Louis, and West Nile virus) cause disease when mosquitoes are active, whereas HSV can occur at any time
Physical Exam
- Patients with encephalitis have an altered mental status ranging from subtle deficits to complete unresponsiveness
- Other findings reflect neurologic involvement
Essential Workup
- Lumbar puncture
- Cell count/chemistry:
- Elevated WBC, predominantly lymphocytes
- Elevated protein
- Glucose (normal in viral disease)
- Gram stain with or without India ink for suspected/confirmed HIV
- Viral and bacterial cultures (fungi if indicated by history)
- Antigen assays for:
- HSV
- Cryptococcus
- Toxoplasmosis
- Other viral antigen and antibody assays if available (enterovirus, adenovirus, CMV, mumps, varicella zoster)
Diagnostic Tests & Interpretation
Lab
- CBC:
- WBC usually elevated; however, a normal WBC does not exclude infection
- Electrolytes, glucose, BUN, creatinine
- Bacterial and viral blood cultures
- Liver function tests, ammonia level if hepatic failure suspected
- Carboxyhemoglobin level if CO poisoning suspected
- Toxicology screen if ingestion suspected in differential
- Polymerase chain reaction (PCR):
- Confirm viral nucleic acids in CSF
- HSV, varicella, enteroviruses, others
- West Nile virus IgM serology
Imaging
- CT scan:
- To rule out trauma, hemorrhagic conditions, and mass lesions
- Cerebral edema may be the only finding consistent with encephalitis
- HSV may show parenchymal hemorrhagic areas of the frontal and temporal lobes, along with edema
- MRI:
- Hypodense temporal lobes in HSV
Diagnostic Procedures/Surgery
EEG may be useful in the presence of proven or suspected seizures
Differential Diagnosis
- Meningitis
- Brain abscess
- Sepsis
- Stroke (hemorrhagic or ischemic)
- Head injury
- Subarachnoid hemorrhage
- Encephalopathy (hepatic, uremic)
- Epilepsy
- Acute disseminated encephalomyelitis (ADEM)
- Metabolic:
- Electrolyte abnormalities (Na+, K+, Cl−, Ca2+, Mg2+, phosphate)
- Hypoglycemia
- Hyperglycemic nonketotic coma
- Neoplastic
- Drugs/toxins
- Carbon monoxide (CO) inhalation
Prehospital
Stabilize. Treat seizures
Initial Stabilization/Therapy
- ABCs:
- Intubate patients who are obtunded/comatose/absent gag reflex
- Naloxone, thiamine, glucose (or Accu-Chek) for altered mental status
- For signs of raised intracranial pressure on funduscopy or CT:
- Hyperventilate to PCO2 of 25-30 mm Hg
- Administer mannitol
- Neurosurgical consult for suspected hydrocephalus and intracranial monitoring
- Run IV saline at KVO or half maintenance to avoid cerebral edema
ED Treatment/Procedures
- Seizure control:
- No specific treatment for most viral encephalitides:
- Steroid use controversial
- Treat HSV encephalitis with acyclovir IV:
- Initiate if considered likely based on clinical grounds, CT, and CSF findings.
- Initiate ganciclovir and foscarnet for suspected immunocompromised-related infections (CMV, HHV-6)
- Administer antibiotic to cover for meningitis if diagnosis uncertain, especially when rash present (e.g., meningococcemia, rickettsia)
Medication
- Acyclovir: 10 mg/kg IV div q8h, max 30 mg/kg/d (peds: 10-15 mg/kg IV q8h up to age 12 yr) for 14-21 d:
- Alternatives to acyclovir (adults):
- Ganciclovir 5 mg/kg IV q12h
- Foscarnet 90 mg/kg IV q12h or 60 mg/kg IV q12h
- Lorazepam: 2-4 mg per dose slow IV (peds: 0.05-0.1 mg/kg) per dose
- Diazepam: 5 mg IV per dose (peds: 0.1-0.2 mg/kg IV or 0.2-0.5 mg/kg per rectum)
- Fosphenytoin: Loading dose 20 mg/kg IV to a max 1 g
- Mannitol: 0.5-1 g/kg of a 20% solution to run IV over 20-30 min
- Phenobarbital: Load 15-20 mg/kg to 300-800 mg IV at 25 mg/min. Monitor respirations
- FitchMT, AbrahamianFM, MoranGJ, et al. Emergency department management of meningitis and encephalitis . Infect Dis Clin North Am. 2008;22(1):33-52.
- LongSS. Encephalitis diagnosis and management in the real world . Adv Exp Med Biol. 2011;697:153-173.
- MaillesA, DeBrouckerT, CostanzoP, et al. Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France . Clin Infect Dis. 2012;54:1455-1464.
- WingfieldT, McHughC, VasA, et al. Autoimmune encephalitis: A case series and comprehensive review of the literature . QJM. 2011;104:921-931.
- ZiaiWC, LewinJJ 3rd. Update in the diagnosis and management of central nervous system infections . Neurol Clin. 2008;26(2):427-468.
See Also (Topic, Algorithm, Electronic Media Element)
Meningitis