DESCRIPTION

• Acute inflammation of the brain
• 20,000 cases in US 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
  • Autoimmune, paraneoplastic, collagen vascular disease
• 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 US:
    • 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

[Outline]

• DESCRIPTION
• ETIOLOGY

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)

DIAGNOSIS 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

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

PRE-HOSPITAL

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
• Run IV saline at KVO or half maintenance to avoid cerebral edema

ED TREATMENT/PROCEDURES

• Seizure control:
  • Abort with lorazepam or diazepam
  • Initiate antiseizure medication (fosphenytoin or phenobarbital) if more than 1 seizure has occurred
• 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: 20 mg/kg IV div. q8h up to age 12 yr)
• 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
• Ganciclovir: 5 mg/kg IV div. q12h
• Foscarent: 90 mg/kg IV div. q12h or 60 mg/kg IV q8h
• 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

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

All patients

Empiric treatment for HSV-1 infection with acyclovir should always be initiated as soon as possible if the patient has encephalitis without apparent explanation to decrease morbidity/mortality

ICD9

• 049.9 Unspecified non-arthropod-borne viral diseases of central nervous system
• 058.29 Other human herpesvirus encephalitis
• 323.9 Unspecified causes of encephalitis, myelitis, and encephalomyelitis

ICD10

• A86 Unspecified viral encephalitis
• B00.4 Herpesviral encephalitis
• G04.90 Encephalitis and encephalomyelitis, unspecified

[Outline]

• ICD9
• ICD10

• Fitch MT, Abrahamian FM, Moran GJ, et al. Emergency department management of meningitis and encephalitis. Infect Dis Clin North Am. 2008;22(1):33–52.
• Long SS. Encephalitis diagnosis and management in the real world. Adv Exp Med Biol. 2011;697:153–173.
• Mandell G. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010.
• Wingfield T, McHugh C, Vas A, et al. Autoimmune encephalitis: A case series and comprehensive review of the literature. QJM. 2011;104:921–931.
• Ziai WC, Lewin JJ 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

Mary Saunders