ENCEPHALITIS/MENINGITIS
Marianne Gausche-Hill, MD, Professor of Clinical Medicine, David Geffen School of Medicine at the University
of California, Los Angeles, Director, Emergency Medical Services Fellowship, and Director, Pediatric Emergency
Medicine Fellowship, Department of Emergency Medicine, Harbor-UCLA Medical Center, Los Angeles
| Epidemiology: most cases occur in late summer and early fall; epidemic pattern related to viral (arbovirus) etiology;
agents—West Nile virus (WNV); herpes simplex virus (HSV); others; incidence—19,000 hospitalizations
each year in United States; etiologic agent unknown in ≈60% of cases; risk—infants and elderly patients at highest
risk
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| Relevant patient history: recent travel; exposure to ticks and animals; recent infections or vaccinations (eg, measles,
mumps, pertussis); drug use or exposure to toxins (part of differential diagnosis); signs and symptoms; time
course of disease
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| Signs and symptoms: fever (present in 70%-90% of cases); malaise; headache; altered level of consciousness or
uncharacteristic behavior (consider encephalitis or meningitis even in absence of fever); focal neurologic changes
(especially cranial nerve defects); new-onset seizure (especially if followed by altered level of consciousness);
ataxia; pneumonitis may occur with HSV- or cytomegalovirus-associated encephalitis
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| Evaluation: imaging—chest radiograph; computed tomography (CT) of head; magnetic resonance imaging (MRI)
or angiography appropriate in some cases (eg, suspicion of HSV-associated encephalitis); laboratory—liver
function tests (LFTs); complete blood cell count, prothrombin time, and partial thromboplastin time (screening
for associated complications); toxic screen and cultures from blood and urine (for differential diagnosis)
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 | Cerebrospinal fluid (CSF): classic panel includes cell count, protein and glucose levels, and culture and sensitivity;
note—hold extra tube for additional studies; profile—protein somewhat elevated (≈60 mg/dL); glucose often
normal; white blood cell (WBC) count usually <500 cells/µL (sometimes ≤10 cells/µL); tests—polymerase
chain reaction (PCR) gold standard for diagnosing HSV-associated encephalitis but not always immediately
available (treat empirically until HSV ruled out); viral studies, including cultures from throat swabs or stool
specimens; enzyme-linked immunosorbent assay (ELISA) identifies arboviruses (eg, WNV)
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| Differential diagnosis: Reye’s syndrome (LFTs and serum ammonia elevated; bilirubin relatively normal); parameningeal
infections; partially treated meningitis (eg, drug-resistant tuberculosis-associated meningitis); brain abscess
or tumor; metabolic disease (suspect in afebrile children presenting with lethargy or altered level of
consciousness; check levels of lactate, ammonia, and glucose; screen for inborn errors of metabolism); hepatic encephalopathy
(elevated ammonia)
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| West Nile virus: primarily infects birds; causes encephalitides in humans, horses, and other mammals; transmitted
by mosquitos; prevalence—identified in all states except Washington, Alaska, and Hawaii; sentinal cases
in chickens predict outbreaks in humans; signs and symptoms—1 of 150 infected individuals develop malaise,
rash, gastrointestinal symptoms; if untreated, progression to altered mental status and acute flaccid paralysis syndrome
may occur; testing—CSF culture (need ≥10 mL); prevention—avoid outdoor activity during dawn or
dusk; put screens on windows; wear long-sleeve shirts; use N,N-diethyl-m-toluamide (DEET; safe for children
\>6 mo of age)
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| Herpes encephalitis: most common sporadic encephalitis, may result in bizarre behavior patterns including uncharacteristic
violence; highest risk during neonatal period; second peak occurs in adults \>50 yr of age; signs and
symptoms—fever; headache; altered mental status; CSF findings—pleocytosis; red blood cells (RBCs) or xanthochromia
may be present
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| Ancillary studies: electroencephalography—classic pattern shows paroxysmal lateralized eliptiform discharges;
appropriate for patients presenting with altered mental status; imaging—CT shows hypodensity and sometimes
hemorrhage in temporal lobe; contrast enhancement generally occurs as disease progresses; MRI shows bright
signal in temporal lobe
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| Management: acyclovir in neonates—empiric treatment appropriate when mother has history of herpes or when neonate
has focal seizure or neurologic findings, dermal manifestations, or high fever; some clinicians propose use in
all neonates with pleocytosis and gram-negative culture results; maternal infection—≥2% of pregnant women
seroconvert (HSV-1 or HSV-2) during pregnancy; encephalitis generally associated with HSV-2 but may occur
with HSV-1; complications—hypoventilation; hyperpyrexia; disseminated intravascular coagulation; syndrome of
inappropriate antidiuretic hormone secretion
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| Incidence: marked decline since introduction of vaccine against Haemophilus influenzae
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| Pathology: pathogenesis—primarily spread hematogenously, but local extension (eg, from otitis media, sinusitis,
or mastoiditis) may occur; pathophysiology—bacteremia, followed by meningeal invasion and bacterial replication;
sequelae primarily caused by resultant inflammation
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| Etiology: bacterial—group B streptococcus, Escherichia coli, Listeria monocytogenes, and Klebsiella in neonates;
group B streptococcus and E coli most common agents in infants 1 to 3 mo of age; Streptococcus pneumoniae
and Neisseria responsible for 85% of cases in individuals \>3 mo of age; viral—enteroviruses most common
viral agents (may cause encephalitis or meningitis); arboviruses usually associated with encephalitis, but may cause
meningitis; HSV-6, HSV-7, and HSV-2
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| Signs and symptoms: clinical manifestations vary with age; behavioral anomalies, fever, and headache increase
index of suspicion; viral meningitis often subacute presentation, whereas bacterial meningitis typically acute presentation;
fever frequent in all age groups; headache (assess infants by “bouncing”); vomiting in all age groups;
bulging fontanelle (late finding in infants); meningeal signs (especially in patients \>2 yr of age)
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| Classic signs: nuchal rigidity—patient cannot place chin on chest; in some cases, patient cannot bring head to
midline; spinal rigidity—may manifest as opisthotonos, when severe; Kernig’s sign—patient lies supine with
knees and hips flexed; pain occurs in hamstrings when legs extended; Brudzinski’s sign—patient flexes hips
and knees in response to flexion of neck (less accurate in elderly patients); reliability—meningeal signs present
in 93% of infants \>12 mo of age with bacterial meningitis; ≈66% of adults present with classic triad (fever, headache,
stiff neck); Dutch study found 99% of patients with bacterial meningitis present with fever, headache, or altered
mental status (all 3 signs present in 50%-80% of adult cases); Kernig’s and Brudzinski’s signs less reliable;
meningeal signs have relatively low sensitivity (absence does not rule out meningitis; presence requires lumbar
puncture [LP] or explanation)
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| Ancillary studies: laboratory studies (eg, serum glucose, especially in patients with altered mental status); testing
for cryptococcal antigen and syphilis
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| Computed tomography: guidelines by Infectious Diseases Society of America (IDSA) advise CT before LP for
patients with altered mental status, focal neurologic deficits, papilledema, seizure within 1 wk, immunocompromise,
or history of central nervous system (CNS) disease; study suggested value in patients \>60 yr of age (identified
tumors, but performing LP in patients with unrecognized tumors did not appear to cause harm)
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| CSF findings: WBCs—broad ranges complicate distinction between bacterial and viral meningitis; 75% of patients
with bacterial meningitis have \>1000 cells/µL (ie, assume bacterial etiology and manage appropriately);
most patients with viral meningitis have <300 cells/µL; corrections possible if traumatic tap results in blood in
CSF; protein—mildly elevated in patients with viral meningitis; markedly elevated in patients with bacterial meningitis;
protein levels also increase with tumors of brain and spinal cord, stroke, degenerative diseases (eg, multiple
sclerosis), and lead intoxication; glucose—low levels associated with bacterial, but not typically viral, meningitis;
glucose level in CSF usually 50% to 66% of level in serum; xanthochromia—lysis of RBCs occurs in patients with
meningitis and HSV-associated encephalitis (sometimes associated with elevated bilirubin and high intake of dietary
carotenoids); Gram stain—specificity almost 100%; gram-negative results suggestive of HSV-associated
encephalitis; >80% of adults with pneumococcal meningitis have gram-positive results
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| Management: prehospital—assessment of airway, breathing, and circulation (ABCs); rapid transport; rapid glucose
for patients with altered mental status; universal precautions; emergency department (ED)—
cardiorespiratory monitoring; rapid attainment of cultures; early initiation of antibiotic therapy when bacterial etiology
suspected (delay associated with increased morbidity and mortality); rapid testing for HIV when appropriate;
patients with bacterial meningitis transferred to intensive care unit (ICU)
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| Suspected bacterial meningitis: rates of pneumococcal resistance to penicillin and cephalosporins vary widely (global
average, 35%); vancomycin added when resistance suspected; ampicillin and gentamycin indicated in patients
<2 mo (ceftriaxone contraindicated because it may uncouple bilirubin); ceftriaxone indicated in patients \>2 mo,
unless markedly jaundiced; vancomycin appropriate if Gram-stain results delayed; otherwise healthy adults
treated with ceftriaxone and vancomycin; ampicillin or penicillin added to regimen in immunocompromised
adults to cover Listeria; special cases—vancomycin added to regimen in patients with intravenous drug abuse or
ventriculoperitoneal (VP) shunt and after neurosurgery; timing of administration—initiating antibiotics may
sterilize CSF within 1 to 4 hr, but antibiotic therapy should not be delayed because of diagnostic testing
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| Ruling out bacterial meningitis: CSF findings include negative Gram-stain results, absolute neutrophil count
(ANC) <1000 cells/µL, and protein levels <80 mg/dL; in addition, patients have peripheral ANC <10,000 cells/
µL and no history of seizure before, or at time of, presentation; if above criteria met, patient has only 0.1% risk
for bacterial meningitis
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| Timing of antibiotic administration: initiation must begin in ED (within 1-1.5 hr of presentation); delay in antibiotic
administration by \>3 hr associated with increased rates in 3-mo mortality
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| Corticosteroids: insufficient data to recommend use in neonates; some evidence of harm associated with use in patients
with viral etiology or gram-negative meningitis; most authors recommend avoiding dexamethasone in infants
≤6 wk of age; evidence supports use in older infants and children with Haemophilus influenzae-associated meningitis;
administration must begin before, or concomitant with, first dose of antibiotics; dosing—0.15 mg/kg q6h for
2 to 4 days; controversy—data insufficient to demonstrate clear benefit with adjunctive use in children with pneumococcal
meningitis
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| Management algorithms: infants and children—assess need for CT in children with suspected bacterial meningitis;
perform CT before LP in patients with immunocompromise, history of trauma, VP shunt, hydrocephalus,
papilledema, or focal neurologic deficits; obtain blood for culture and initiate dexamethasone and empiric antibiotic
therapy; perform LP if no findings on CT (or if CT not indicated); continue therapy in patients with CSF findings
consistent with bacterial meningitis; adults—assess need for CT (indicated in patients with
immunocompromise, history of CNS disease, new-onset seizure, papilledema, altered consciousness, or focal neurologic
deficits); initiate antibiotics and dexamethasone (0.15 mg/kg q6h for 2-4 days, initiated before, or concomitant
with, first dose of antibiotic); continue therapy if CSF culture gram-negative or if patient has pneumococcal
disease
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| Complications: deafness common in children (often occurs at presentation); seizures occur in 30% of patients
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| Admission: patients with probable bacterial meningitis require monitoring (ICU or step-down); conservative approach
includes admission for all patients with meningitis (exceptions may occur during outbreaks of viral meningitis); alternate
option for patients with uncertain diagnosis—observe for 6 to 12 hr; perform second LP; administer ceftriaxone
and follow up
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| Other management issues: LP preparation—applying topical lidocaine before local anesthesia eases LP in children;
exposure to Neisseria—chemoprophylaxis recommended only for individuals exposed to secretions from
infected patients (acceptable for those in direct care of patient)
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| Case 1: infant, 3 wk of age, with history of low-grade fever and poor feeding; mother has no history of HSV infection
or recent fever; examination normal for age; treatment—ampicillin and gentamicin or cefotaxime; acyclovir
not indicated unless LP reveals cloudy CSF; imaging—CT not indicated
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| Case 2: boy, 5 yr of age, with 2 days of fever and 1 day of lethargy; examination findings include lethargy and
nuchal rigidity; imaging—CT indicated before performing LP, due to altered level of consciousness; treatment—
dexamethasone and ceftriaxone; vancomycin or acyclovir may be added, depending on CSF findings
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| Case 3: boy, 13 yr of age, with 2-day history of headache and vomiting; febrile; no meningismus or focal neurologic
findings; imaging—CT not indicated; admission—recommended (conservative approach)
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| Case 4: woman, 47 yr of age, presents with altered mental status, low-grade fever, and history of headache; LP—
important part of diagnostic evaluation; treatment—initiate antibiotics and corticosteroids only if CSF positive for
S pneumoniae; initiate acyclovir and avoid corticosteroids if encephalitis suspected
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| Reporting: all cases of acute encephalitis and meningitis reportable in California; reporting details available at
www.cdc.gov
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Suggested Reading
Afonso N et al: Appropriate use of polymerase chain reaction for detection of herpes simplex virus 2 in cerebrospinal
fluid of patients at an inner-city hospital. Diagn Microbiol Infect Dis 57:309, 2007; Bloch KC, Glaser C: Diagnostic
approaches for patients with suspected encephalitis. Curr Infect Dis Rep 9:315, 2007; Leaman J:
Meningitis in an infant: all that’s aseptic is not viral. JAAPA 20:26, 2007; Leep Hunderfund AN et al: 73-year-
old woman with fever and mental status changes. Mayo Clinic Proc 82:874, 2007; Lepur D, Barsic B: Community-acquired
bacterial meningitis in adults: antibiotic timing in disease course and outcome. Infection Jul 23, 2007
[Epub ahead of print]; Listernick R: A 10-day-old infant with seizures. Pediatr Ann 36:78, 2007; Marco de Lucas
E et al: Computed tomography perfusion usefulness in early imaging diagnosis of herpes simplex virus encephalitis.
Acta Radiol 47:878, 2006; Seupaul RA: Evidence-based emergency medicine/rational clinical examination
abstract. How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis? Ann Emerg
Med 50:85, 2007; Stephens DS et al: Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet
369:2196, 2007; Weisfelt M et al: Bacterial meningitis: a review of effective pharmacotherapy. Expert Opin Pharmacother
8:1493, 2007; Welinder-Olsson C et al: Comparison of broad-range bacterial PCR and culture of cerebrospinal
fluid for diagnosis of community-acquired bacterial meningitis. Clin Microbiol Infect Jun 30, 2007 [Epub
ahead of print]; Wyer PC: Bacterial meningitis score accurately predicts which children are at low risk. J Peditr
151:99, 2007.
Educational Objectives
| The goal of this program is to improve the management of patients with suspected encephalitis or meningitis. After
hearing and assimilating this program, the clinician will be better able to:
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| Recognize the classic signs and symptoms associated with encephalitis and meningitis.
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| Discuss the management of herpes simplex virus–associated encephalitis, including the appropriate use of acyclovir.
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| Identify those patients for whom computed tomography is indicated before a lumbar puncture is performed.
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| Distinguish bacterial from viral meningitis based on history, clinical presentation, and laboratory values.
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| Implement management algorithms for children and adults with suspected bacterial meningitis.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Dr. Gausche-Hill was recorded at 36th Annual Scientific Assembly, sponsored by the American College of Emergency
Physicians, State Chapter of California, and held May 31 to June 2, 2007, in Newport Beach, CA.. The Audio-
Digest Foundation thanks Dr. Gausche-Hill and the American College of Emergency Physicians, State Chapter of
California for their cooperation in the production of this program.
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