Neuroinfeccion en Urgencias

D i a g n o s i s an d Tre a t m e n t
of Central Nervous System

Infections in the Emergency
Department
a a,b,
Maia Dorsett, MD, PhD , Stephen Y. Liang, MD, MPHS *
KEYWORDS
Meningitis Encephalitis Brain abscess Emergency department Diagnosis
Treatment
KEY POINTS
The classic triad of fever, neck stiffness, and altered mental status is present in only a mi-
nority of patients with meningitis.
Kernig’s and Brudzinski’s signs are poorly sensitive but relatively specific physical exam-
ination maneuvers for identifying meningitis.
Imaging tests and lumbar puncture should not delay initiation of empiric antibiotic therapy
in patients suspected to have bacterial meningitis.
Although certain cerebrospinal fluid (CSF) profiles are highly suggestive of viral or bacterial
meningitis infection, emergency physicians should not be not falsely reassured by a
benign CSF fluid profile supporting a viral cause.
Encephalitis should be considered in any patient presenting with new-onset seizure or
focal neurologic deficit accompanied by fever, headache, altered mental status, or behav-
ioral changes.
Disclosures: The authors report no conflicts of interest in this work. S.Y. Liang is the recipient of
a KM1 Comparative Effectiveness Research Career Development Award (KM1CA156708-01) and
received support through the Clinical and Translational Science Award (CTSA) program
(UL1RR024992) of the National Center for Advancing Translational Sciences (NCATS) as well
as the Barnes-Jewish Patient Safety & Quality Career Development Program, which is funded
by the Foundation for Barnes-Jewish Hospital.
a
Division of Emergency Medicine, Washington University School of Medicine, 660 South Euclid
Avenue, Campus Box 8072, St Louis, MO 64110, USA; b Division of Infectious Diseases, Washing-
ton University School of Medicine, 660 South Euclid Avenue, Campus Box 8051, St Louis, MO
63110, USA
* Corresponding author. Division of Infectious Diseases, Washington University School of Med-
icine, 660 South Euclid Avenue, Campus Box 8051, St Louis, MO 63110.
E-mail address: sliang@dom.wustl.edu
Emerg Med Clin N Am 34 (2016) 917–942

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918 Dorsett & Liang
INTRODUCTION
A key clinical responsibility of the emergency physician is to consider the “worst case
scenario” for a given chief complaint. When it comes to infections of the central ner-
vous system (CNS), the greatest challenge is identifying patients that have a rare life-
threatening diagnosis amid the multitude of patients presenting with nonspecific
symptoms. Alone or in combination, fever, headache, altered mental status, and
behavior changes encompass a broad differential diagnosis. A diagnosis not consid-
ered is a diagnosis never made. In this vein, this review discusses the clinical signs and
symptoms that should lead emergency physicians to consider CNS infection, paying
particular attention to the sensitivity and specificity of different clinical findings at the
bedside. Subsequently, the diagnostic workup and management of patients for whom
there is high clinical suspicion for CNS infection is discussed.
MENINGITIS
The term “meningitis” applies broadly to inflammation of the meninges. While menin-
gitis can arise from a wide variety of pathologies, infectious and non-infectious, for the
purpose of this review we specifically refer to acute infections of the meninges of bac-
terial, viral, or fungal origin. Bacterial meningitis occurs when organisms gain access
to the subarachnoid space either through bacteremia (usually from an upper airway
source), contiguous spread from dental or sinus infections, traumatic or congenital
communications with the exterior, or a neurosurgical procedure.1 The severe inflam-
mation associated with bacterial meningitis results in edema of the brain and
meninges, and eventually increased intracranial pressure once the compensatory
mechanisms for cerebrospinal fluid (CSF) displacement have been overwhelmed.1
Bacterial meningitis is associated with significant morbidity with mortality rates
ranging from 13 to 27%.2
In contrast to bacterial infection, meningitis caused by viral infection is usually
less severe. The most common causes are enteroviruses (eg, Coxsackie A and B,
echovirus). Herpes simplex virus (HSV, types 1 and 2), cytomegalovirus (CMV),
Epstein-Barr virus (EBV), varicella zoster virus (VZV), mumps virus, and human immu-
nodeficiency virus (HIV) may also cause viral meningitis.3 Fungal meningitis is usually
secondary to systemic mycoses (eg, Cryptococcus neoformans, Coccidioides immi-
tis, Histoplasma capsulatum) originating elsewhere in the body, usually from a pulmo-
nary focus of infection in an immunocompromised patient.4 Rare fungal infections
have also been associated with contaminated glucocorticoid injections to treat
chronic pain.5
Meningitis is a poster child for the success of childhood vaccination in reducing the
incidence of many life-threatening infectious diseases. Before the introduction of an
effective vaccine in 1988, Haemophilus influenzae type B (Hib) was the leading cause
of bacterial meningitis in the United States. After the recommendation that all infants
receive the Hib vaccination starting at age 2 months, the incidence of Hib meningitis
among children less than 5 years of age declined by greater than 99%.6 Similarly, the
advent of the pneumococcal seven-valent conjugate vaccine and the meningococcal
conjugate vaccine significantly decreased the incidence and mortality of pneumo-
coccal and meningococcal meningitis in the United States.7 Meningitis due to noso-
comial pathogens, including Gram-negative bacteria and Staphylococcus, have
now surpassed Neisseria meningitidis and H influenzae in incidence.7 With changing
pathogen demographics, the average age of a patient with meningitis has increased
from 15 months of age in 1986 to 35 years in the present day.8

Diagnosis and Treatment of CNS Infections 919
Meningitis is a relatively rare diagnosis in US emergency departments (ED). Be-

tween 1993 and 2008, approximately 66,000 US ED patients were diagnosed with
meningitis annually, with an incidence of 62 per 100,000 visits.9 With regards to the
cause of meningitis, ED diagnoses include unspecified (60%), viral (31%), bacterial
(8%), and fungal (1%) causes. Bacterial meningitis is much more prevalent in devel-
oping countries, where the average incidence approaches 50 cases per 100,000
and 1 in 250 children are affected within the first year of life.8
Clinical Presentation
The number of patients presenting to the ED with symptoms suggestive of meningitis
far exceeds the number of patients who actually have the disease. The classic symp-
tom triad of fever, neck stiffness, and altered mental status is present in only a minority
of patients.10 Other associated symptoms may include nausea and vomiting, cranial
nerve abnormalities, rash, and seizure. Infants can also present with nonspecific
symptoms such as lethargy and irritability. With regards to the accuracy of the clinical
history and physical examination in diagnosing meningitis in adults, low sensitivity
plagues common complaints and findings, including headache (27%–81%), nausea
and vomiting (29%–32%), and neck pain (28%).11 Sensitivity varies for individual com-
ponents of the “classic triad” of fever (42%–97%), neck stiffness (15%–92%), and
altered mental status (32%–89%). In some cases, 99% to 100% of patients found
to have meningitis had at least one component of the classic triad. Therefore, if the pa-
tient presenting with acute headache does not have neck stiffness or fever and is men-
tating normally, it is extremely unlikely that they have meningitis.12,13 A prospective
study of children ages 2 months to 16 years from Israel also demonstrated the nondis-
criminatory value of symptoms in diagnosing meningitis.14
Classic physical examination maneuvers for the evaluation of meningitis have
been taught to generations of physicians. Kernig’s sign, first described in 1882, con-
sists of flexing the patient’s neck and then extending the patient’s knees. It is consid-
ered positive when the maneuver elicits pain at an angle of less than 135 .15 First
reported in 1909, Brudzinski’s sign, where the neck is passively flexed with the pa-
tient in supine position, is considered positive if it results in flexion of the hips and
knees. The sensitivities of Kernig’s and Brudzinski’s signs reported in Brudzinski’s
original paper were 42% and 97%, respectively. However, most of Kernig’s and
Brudzinski’s patients were children with meningitis due to Mycobacterium tubercu-
losis and Streptococcus pneumoniae, both of which are associated with severe
meningeal inflammation.15 Several recent studies have examined the usefulness of
these classic signs in contemporary patient populations. These studies collectively
demonstrate that these signs have low sensitivity in predicting CSF pleocytosis
(Table 1).10,16,17 The absence of these clinical signs, therefore, cannot adequately
rule out of the presence of meningitis or obviate the need for a lumbar puncture
(LP). However, Kernig’s and Brudzinski’s signs are quite specific (92%–98%) for pre-
dicting CSF pleocytosis, and therefore, their presence should increase clinical sus-
picion for meningitis.
An additional maneuver to elicit meningeal irritation is the “head-jolt” test. The pa-
tient is asked to move their head back and forth in the horizontal plane at a rate of 2
to 3 turns per second. It is considered positive if the patient’s headache worsens. It
was initially tested in a cohort of patients with both fever and headache and had a re-
ported sensitivity of 97% for CSF pleocytosis.18 Two subsequent studies in US ED pa-
tients and intensive care unit patients in India demonstrated much lower sensitivity
(6%–21%), suggesting that the absence of a positive head jolt does not effectively
rule out meningitis.10,16

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Dorsett & Liang
Table 1
Sensitivities, specificities, and likelihood ratios for classic meningeal signs in predicting cerebrospinal fluid pleocytosis
Sensitivity (95% CI) Specificity (95% CI) LRD LRL Reference

Nuchal rigidity 30 68 0.94 1.02 Thomas et al,17 2002
39.4 (29.7, 49.7) 70.3 (59.8, 79.5) 1.33 (0.89, 1.98) 0.86 (0.7, 1.06) Waghdhare et al,10 2010
13 (8, 17) 80 (74, 85) 0.6 1.1 Nakao et al,16 2014
Kernig’s sign 5 95 0.97 1.0 Thomas et al,17 2002
14.1 (7.95, 22.6) 92.3 (84.8, 96.9) 1.84 (0.77, 4.35) 1.0 Waghdhare et al,10 2010
2 (0, 4) 97 (95, 99) 0.8 0.93 (0.84, 1.03) Nakao et al,16 2014
Brudzinski’s sign 5 95 0.97 1.0 Thomas et al,17 2002
11.1 (5.68, 19) 93.4 (86.2, 97.5) 1.69 (0.65, 4.35) 1.0 Waghdhare et al,10 2010
2 (0, 4) 98 (96, 100) 1.0 0.95 (0.87, 1.04) Nakao et al,16 2014
Head jolt 6.06 (2.26, 12.7) 98.9 (94, 100) 5.52 (0.67, 44.9) 0.95 (0.89, 1.0) Waghdhare et al,10 2010
21 (15, 27) 82 (76, 87) 1.2 1.0 Nakao et al,16 2014
Abbreviation: LR, likelihood ratio.

Given the poor performance of clinical signs and the physical examination in ruling
out meningitis, overall clinical gestalt remains an important part of making the diag-
nosis. In a prospective cohort, Nakao and colleagues16 found that physician suspicion
had a sensitivity of only 44% in predicting pleocytosis. However, in 3 patients where
the CSF culture grew an infective organism (N meningitidis, C. neoformans, and
Enterovirus), clinicians suspected bacterial meningitis before performing the LP, sug-
gesting that physician judgment may be the best current diagnostic tool.
Diagnostic Workup
In the absence of clear contraindications, patients suspected of having meningitis
should undergo LP. If the clinical suspicion for bacterial meningitis is high, empiric an-
tibiotics should be started immediately when the LP cannot be performed right
away.19–21 Although the sensitivity of the CSF culture decreases with antibiotic admin-
istration, cultures can remain positive for up to 4 hours afterward.22
In patients at risk for an intracranial mass or midline shift, it is recommended that
computed tomography (CT) of the head be obtained before LP given the potential
for brain herniation.23 Current guidelines from the Infectious Disease Society of Amer-
ica recommend obtaining a head CT before LP in patients who are immunocompro-
mised, have a history of CNS disease, have had a new-onset seizure within 1 week
of presentation, or have examination findings consistent with papilledema, abnormal
level of consciousness, or focal neurologic deficit.24 In patients in whom head CT is
thought to be necessary, the correct sequence of actions are first, immediate admin-
istration of antibiotics, then CT, followed by LP as soon as possible.
In Sweden, it was found that adoption of guidelines recommending head CT before
LP in patients with altered mental status led to increased CT use even in patients who
did not meet criteria. Far worse, adherence to guidelines for early empiric antibiotics in
suspected bacterial meningitis was poor.25 This undesirable practice pattern has been
replicated in other environments as well.22 In 2009, moderate-to-severe impairment of
mental status and new onset seizures were removed from the list of indications for
head CT before LP in the Swedish guidelines, leading to significantly earlier treatment
of bacterial meningitis and a decrease in overall mortality.25
Once the LP has been completed, ideally with an opening-pressure performed, CSF
fluid analysis can help predict a bacterial, viral, or fungal cause for meningitis
(Table 2).1,2 In addition to cell count, glucose, and protein, CSF should be sent for cul-
ture. Molecular studies such as polymerase chain reaction (PCR) assays for HSV
Table 2
Typical cerebrospinal fluid profiles for bacterial, viral, and fungal meningitis
Parameter Normal Bacterial Virala Fungala

CSF opening pressure <170 mm Elevated Normal Normal or elevated
Cell count <5 cells/mm3 >1000/mm3 <1000 mm3 <500/mm3
Cell predominance — Neutrophils Lymphocytes Lymphocytes
CSF glucose >0.66 serum Low Normal Low
CSF protein <45 mg/dL Elevated Normal Elevated
a
CSF consistent with these profiles are not sufficient to rule out bacterial meningitis.
Data from 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; and Tintinalli JE, Stapczyn-
ski JS. Tintinalli’s emergency medicine: a comprehensive study guide. 7th edition. New York:
McGraw-Hill; 2011.

922 Dorsett & Liang
should be considered in immunocompetent individuals. Special CSF testing for fungal

(eg, cryptococcal antigen, fungal culture) and mycobacterial infection (eg, acid fast
bacteria stain and mycobacterial culture) can be sent in cases where there is higher
clinical suspicion for an atypical infection, particularly in immunocompromised
patients.
Although certain CSF profiles are highly suggestive of viral or bacterial infection,
emergency physicians should not be falsely reassured by CSF profiles suggestive
that a patient has viral rather than bacterial meningitis. In a prospective study of 696
patients with culture-proven bacterial meningitis, only 88% of patients had one or
more CSF findings predictive of bacterial meningitis.26 A fifth had a negative CSF
Gram stain. Two studies have assessed the discriminatory value of CSF laboratory
tests in distinguishing viral versus bacterial meningitis in the setting of a negative
Gram stain.27,28 Both studies found low discriminatory value for classic CSF parame-
ters, including significantly elevated neutrophil count, high protein, or low glucose in
distinguishing bacterial from viral meningitis.28 For example, 50% of patients with bac-
terial meningitis had a neutrophil count less than 440/mm3 and greater than 10% of the
patients with viral meningitis had a neutrophil count of greater than 500/mm3.
Several studies have assessed the discriminatory value of CSF lactate in distin-
guishing viral from bacterial meningitis. CSF lactate, produced by bacterial anaerobic
metabolism or ischemic brain tissue, is not affected by blood lactate concentration.29
A meta-analysis assessing the diagnostic accuracy of CSF lactate for differentiating
bacterial from viral meningitis found that in both pediatric and adult patients with
Gram stain–positive or culture-proven bacterial meningitis, a CSF lactate level of
greater than 3.9 mmol/L had a sensitivity of 96% (95% confidence interval [CI]
93%–98%) and specificity of 97% (95% CI 96%–99%) for differentiating bacterial
meningitis.30 The sensitivity of the test dropped dramatically to 29% (95% CI 23%–
75%) in the subset of patients pretreated with antibiotics.
Apart from CSF analysis, procalcitonin is a serum marker that has shown promise in
distinguishing bacterial from viral meningitis. In general, serum procalcitonin is an in-
flammatory marker that increases disproportionately in patients with underlying
bacterial infection.31,32 It has been used in a wide variety of clinical settings to assess
likelihood of underlying bacterial infection.32 In the setting of suspected meningitis but
a negative CSF Gram stain, a serum procalcitonin level of greater than 0.98 ng/mL was
found to have a sensitivity of 87%, specificity of 100%, positive predictive value of
100%, and negative predictive value of 99% for identifying bacterial meningitis.27
Generally, in patients with CSF pleocytosis or with moderate-to-high clinical suspi-
cion for bacterial meningitis, empiric antibiotics should be continued pending finaliza-
tion of CSF cultures and other diagnostic tests when indicated. In the pediatric
population, the bacterial meningitis score is a validated clinical prediction tool that
identifies children with CSF pleocytosis at very low risk for bacterial meningitis. Pa-
tients are considered “very low risk” for bacterial meningitis if they lack all of the
following criteria: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of
at least 1000 cell/mL, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least
10,000 cells/mL, and a history of seizure before or at time of presentation.33–35 As the
bacterial meningitis score was developed to assist clinicians in deciding which pa-
tients warrant admission for parental antibiotics in the presence of CSF pleocytosis,
patients warranting admission regardless were excluded from the derivation and vali-
dation cohorts. Thus, the score does not apply to patients less than 29 days of age or
those with critical illness, a ventricular shunt device, recent neurosurgery, immunosup-
pression, or other bacterial infection necessitating inpatient antibiotic therapy. Pa-
tients who were pretreated with antibiotics were also excluded. In a meta-analysis

of 8 independent validation studies, the bacterial meningitis score was 99.3% (95% CI
98.7% to 99.7%) sensitive for bacterial meningitis, with a negative predictive value of
99.7% (95% CI 99.3% to 99.9%). Of 4896 patients with CSF pleocytosis, the bacterial
meningitis score misclassified 9 as having aseptic rather than bacterial meningitis. As
7 of these children were either less than 2 months of age or had petechiae or purpura
on examination, the authors recommended that the score only be applied to non-ill-
appearing children older than 2 months of age who do not have petechiae or purpura
on examination and have not been pretreated with antibiotics.
Treatment
Bacterial meningitis
Common pathogens responsible for bacterial meningitis vary with age, degree of
immunocompromise, and clinical history (Table 3).8 For example, in neonates, the
most common causative organisms in the first week of life, Streptococcus galactiae,
Escherichia coli, and Listeria monocytogenes, are replaced by S pneumoniae and N
meningitidis by the sixth week. Antibacterial therapy should be geared toward the
most likely pathogen (see Table 2).8 With the exception of the very young, patients
who have recently undergone a neurosurgical procedure, or those who have suffered
penetrating head trauma, S pneumoniae remains the most common bacterial path-
ogen. Meningitis due to S pneumoniae is treated intravenously with a combination
of a high-dose third-generation cephalosporin (eg, ceftriaxone) and vancomycin in
light of worldwide emergence of resistant S pneumoniae.8
Table 3
Etiologic and recommended antimicrobial therapy by age and clinical context
Most Common Bacterial

Patient Subgroup Pathogen Initial Intravenous Therapy
Neonates, <1 wk S agalactiae, E coli, Ampicillin (50 mg/kg every 8 h) AND
L monocytogenes Cefotaxime (50 mg/kg every 8 h)
Neonates, >1 wk L monocytogenes, S agalactiae, Ampicillin (50 mg/kg every 6 h) AND
and <6 wk Gram-negative bacilli Cefotaxime (50 mg/kg every 6 h)
Infants and children S pneumoniae, N meningiditis Cefriaxone (80–100 mg daily) OR
Cefotaxime (75 mg/kg every 6 h)
AND Vancomycin (15–20 mg/kg
every 8 h)
Adults S pneumoniae, N meningiditis Ceftriaxone (2 g every 12 h) OR
Cefotaxime (3 g every 6 h) AND
Vancomycin (15–20 mg/kg
every 8 h)
Elderly S pneumoniae, N meningiditis, Ceftriaxone (2 g every 12 h) OR
L monocytogenes Cefotaxime (3 g every 6 h) AND
Vancomycin (15–20 mg/kg every
8 h) AND Ampicillin (2 g every 4 h)
Immunocompromised S pneumoniae, N meningiditis, Vancomycin (15–20 mg/kg every 8 h)
H influenzae, aerobic AND Ceftazidime (2 g every 8 h)
Gram-negative bacilli OR Cefepime (2 g every 8 h) OR
Meropenem (2 g every 8 h) AND
Ampicillin (2 g every 4 h)
Nosocomial S aureus, S epidermidis, aerobic Vancomycin (15–20 mg/kg every 8 h)
Gram-negative bacilli AND Ceftazidime (2 g every 8 h)
OR Cefepime (2 g every 8 h) OR
Meropenem (2 g every 8 h)

924 Dorsett & Liang
In addition to prompt antibiotic therapy, corticosteroids should be considered as

adjunctive therapy in some cases of suspected bacterial meningitis. The use of cortico-
steroids for the treatment of meningitis was prompted by the finding in animal models
that meningitis outcomes were worse with increasing severity of the inflammatory pro-
cess in the subarachnoid space.36 There have been conflicting results as to their benefit
in bacterial meningitis ever since the first clinical trials examining their use were pub-
lished in the 1960s. A 2013 Cochrane Review analyzed 25 randomized control trials
spanning patients of all ages and types of bacterial meningitis to determine the benefit
of corticosteroids in reducing overall mortality, deafness, and other neurologic
sequelae.37 Overall, there was a nonsignificant reduction in mortality (17.7% vs
19.9%; risk ratio [RR] 0.90, 95% CI 0.80–1.01) with corticosteroid use. However, in sub-
group analysis, corticosteroids reduced mortality in patients with bacterial meningitis
due to S pneumoniae (RR 0.84, 95% CI 0.72–0.98) but not H influenzae or N meningi-
tidis. There was a significant reduction in hearing loss (RR 0.74, 95% CI 0.63–0.87)
and subsequent neurologic sequelae (RR 0.83, 95% CI 0.69–1). There was no benefit
found for patients treated with corticosteroids in low-income countries. With regards
to the timing of corticosteroid administration, it is traditionally thought that they should
be administered before or at the time of antibiotic infusion. However, the results of the
Cochrane Review suggest that there is no significant difference in mortality reduction if
corticosteroids are administered before, with, or after antibiotics are given. There was a
slightly more favorable effect on reducing hearing loss and short-term neurologic
sequelae if corticosteroids were administered before or with antibiotics.
Viral meningitis
There is no specific antiviral therapy for most viral causes of meningitis, and treatment
is largely supportive with spontaneous recovery anticipated in most cases. HSV-1 and
HSV-2 cause different CNS diseases in adults. Although HSV-1 is associated with
devastating encephalitis, HSV-2 causes a benign viral meningitis with meningeal signs
and CSF pleocytosis, usually in the concurrent setting of primary genital infection.38 If
HSV-2 meningitis is suspected or confirmed in an adult, treatment with acyclovir can
be initiated but is of unclear benefit. In stark contrast, HSV-2 infection in an infant can
lead to life-threatening encephalitis.
Fungal meningitis
Fungal meningitis is almost always a disease of the immunocompromised. If the clin-
ical suspicion for fungal meningitis is high, empiric antifungal therapy with amphoter-
icin B is appropriate pending isolation of a specific fungus to tailor antifungal therapy.
ENCEPHALITIS
Encephalitis is inflammation of the brain parenchyma. It is technically a pathologic

diagnosis, but the term is commonly used to describe a clinical syndrome of brain
inflammation.39 The differential diagnosis for encephalitis is broad, with infectious
(viral, bacterial, or parasitic), postinfectious, and noninfectious (metabolic, toxic, auto-
immune, paraneoplastic) causes possible. Viral infections are associated with 2
distinct forms of encephalitis. The first is a direct infection of the brain parenchyma
due to viremia (eg, West Nile virus) or viral reactivation in neuronal tissue (eg, HSV,
VZV).40 The second is a postinfectious encephalomyelitis (also known as acute
disseminated encephalomyelitis), likely an autoimmune phenomenon more often
seen in children and young adults following a disseminated viral illness or vaccina-
tion.40,41 This review focuses on viral encephalitis due to direct infection because it
is responsible for the majority of acute encephalitis encountered in emergency care.

In the Western world, encephalitis is an uncommon disorder. The reported inci-

dence of encephalitis from all causes ranges from 0.7 to 12.6 per 100,000 adults
and 10.5 to 13.8 per 100,000 children.39 Worldwide, the causes of encephalitis remain
unidentified in up to 85% of cases, due in part to limited diagnostic capabilities as well
as emerging pathogens.42 Even in a British study in which 203 patient samples under-
went exhaustive testing for infectious and noninfectious causes of encephalitis, 37%
of causes were unknown.42 HSV encephalitis (HSV-1) remains the most common
cause of sporadic viral encephalitis in industrialized nations, accounting for 10% to
15% of cases with an annual incidence of 1 in 250,000 to 500,000, and a bimodal
age distribution primarily affecting the very young and the elderly.43,44 VZV comes in
at a close second and is actually more common than HSV in immunocompromised in-
dividuals, accounting for 19% to 29% of encephalitis cases.42,45,46
The first step in approaching a patient with suspected CNS infection is to determine if
bacterial meningitis is present, necessitating emergent empiric antibiotic therapy.
However, when there is also evidence of brain parenchymal involvement in the form
of focal neurologic findings or seizures, one must consider encephalitis as well. The
clinical presentation of encephalitis correlates with the underlying function of the brain
parenchyma involved (Table 4). For example, because HSV encephalitis is classically
associated with the temporal lobes, it can present with personality changes, psycho-
sis, olfactory or gustatory hallucinations, or acute episodes of terror that may initially
be misdiagnosed as a psychiatric disorder.40,47 Inferior frontal and temporal lobe
involvement may also present with upper-quadrant visual field deficits, difficulty stor-
ing or recalling new information, hemiparesis with greater involvement of the face and
arm, or aphasia when the dominant hemisphere is involved.40 Certain viruses, such as
West Nile virus and Eastern equine encephalitis virus, have a predilection for basal
ganglia and thalamus and are associated with tremors or other movement disor-
ders.48–50 Several bacterial and viral causes, including Bartonella henselae, M tuber-
culosis, Enterovirus-71, flaviviruses (eg, West Nile virus, Japanese encephalitis
virus), and alphaviruses (eg, Eastern equine encephalitis virus), can cause brainstem
encephalitis manifesting as autonomic dysfunction, lower cranial nerve involvement,
and respiratory drive disturbance.39,42 Despite these classic associations, no present-
ing sign, symptom, or CSF finding alone or in combination with another can accurately
distinguish one cause of encephalitis from another.42
Diagnosis
Because antibiotic therapy should be initiated rapidly in a patient with suspected
CNS infection, the most urgent question to ask when you suspect encephalitis is
whether a patient requires antiviral coverage in addition to standard antibiotics.
The initial approach to diagnosis parallels that of meningitis (Fig. 1). All patients
should have an LP, unless there is a clear clinical contraindication such as a
coagulation abnormality, local infection at the LP site, or evidence of significant
mass effect on imaging studies. Head CT should be performed before LP if the pa-
tient has moderate-to-severe impairment of consciousness, focal neurologic deficit,
posturing, papilledema, seizures, relative bradycardia with hypertension, or immu-
nocompromise.39 In addition to a standard laboratory evaluation, all patients with
suspected encephalitis should be tested for HIV infection because this may change
the scope of subsequent diagnostic testing and empiric treatment. CSF findings in
HSV encephalitis vary along a spectrum from normal to lymphocytic pleocytosis to
hemorrhagic. However, no general CSF findings can reliably distinguish HSV from

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Dorsett & Liang
Table 4
Demographics, clinical presentation, and treatment of select causes of viral encephalitis
Neurologic Symptoms
(in Addition to
Headache, Fever, Non-neurologic Treatment (Adult
Pathogen Demographics Altered Mental Status) Symptoms Diagnostic Test Dosing)
HSV Usually young and Seizures, olfactory/ Rash HSV-1, HSV-2PCR (CSF) Acyclovir
elderly; no seasonal gustatory 10 mg/kg every 8 h
predilection hallucinations, (adjust for renal
aphasia, personality function)
changes, hemiparesis
(face/arm > leg),
upper visual field cut
VZV Most common in Cranial nerve palsies, Shingles VZV PCR (CSF) Acyclovir
immunocompromised cerebellitis 10 mg/kg every 8 h
(adjust for renal
function)
CMV Immunocompromised Behavior changes, coma Pneumonitis, retinitis, CMV PCR (CSF) Ganciclovir
myelitis 5 mg/kg every 12 h
Enterovirus Usually young Rhombencephalitis Hand-foot-mouth Enterovirus PCR (CSF) Supportive care
(myoclonus, tremors, disease, rash,
ataxia, cranial nerve myocarditis,
palsies), poliolike pericarditis,
acute flaccid paralysis, conjunctivitis,
neurogenic shock pulmonary edema
Arboviruses Summer months IgG and IgM (CSF and Supportive care
serum)
Flaviviridae
West Nile virus US, Africa, Europe, Tremors, parkinsonism, Insect bite, myalgias,
(80% infections Middle East, Asia asymmetric flaccid hepatitis,
asymptomatic) paralysis pancreatitis,
myocarditis,
rhabdomyolysis,
orchitis, rash
St. Louis Widespread in US; Vomiting, confusion, Insect bite, malaise,
encephalitis virus adults (>50 y) disorientation, myalgias, syndrome
stupor, coma of inappropriate
antidiuretic hormone
secretion
Togaviridae
Eastern equine Eastern and gulf coasts Seizures Myalgias, malaise
encephalitis virus of US, Caribbean, and
South America;
Diagnosis and Treatment of CNS Infections

children and adults
Western equine West, Midwest US, and Seizures Myalgias, malaise
encephalitis virus Canada; infants and
adults
Rabies virus Exposure to infected Agitation, bizarre Hydrophobia, fever, Rabies virus RNA by Postexposure
animal behavior, coma, malaise, anxiety, pain, rtPCR (saliva) vaccination; once
stupor or itching at site of infected, supportive
the bite wound care but universally
fatal
927
928 Dorsett & Liang
Fig. 1. Algorithm for diagnostic workup of encephalitis in the ED setting blood count. CMP,
complete metabolic panel; IV, intravenous; PT/PTT, prothrombin time/partial thromboplastin.
other causes of viral encephalitis.43,47 As a consequence, molecular (eg, PCR) and

serologic testing are important for establishing a specific diagnosis (see Table 4).
During early infection, initial diagnostic tests may be negative. Approximately 5%
to 10% of adults with HSV encephalitis will initially have a normal CSF profile and
a negative HSV PCR. In patients in whom the diagnosis is strongly suspected, a
repeat LP at 24 to 48 hours is recommended.39 From the perspective of emergency

medicine, treatable causes of viral encephalitis are limited predominantly to HSV and
VZV, and it is unlikely that sending a diverse battery of expensive diagnostic molec-
ular tests will influence immediate care. However, it can be helpful to have the micro-
biology laboratory save CSF so that other clinicians can expand the initial diagnostic
workup as needed without repeating the LP.
MRI is significantly more sensitive than CT in detecting early cerebral changes in
viral encephalitis. In HSV encephalitis, CT is abnormal in approximately a quarter of
patients. MRI is abnormal in approximately 90% of patients, with the most character-
istic findings being edematous changes in the orbital surfaces of the frontal lobes and
medial temporal lobe.39 MRI also offers the advantage of identifying alternative causes
of encephalitis, and thus, should be performed on all patients with suspected enceph-
alitis in whom the diagnosis remains uncertain.39,51
An electroencephalogram (EEG) does not need to be performed routinely in all pa-
tients with suspected encephalitis. However, it is a potentially useful adjunct in
several situations. First, in patients who are comatose or poorly responsive, EEG
may reveal non-convulsive status epilepticus requiring antiepileptic management.
In a subset of patients presenting with psychiatric symptoms, an abnormal EEG
can point to an organic cause. For instance, HSV encephalitis is associated
with characteristic non-specific diffuse high-amplitude slow waves, sometimes
with temporal lobe spike-and-wave activity and periodic lateralized epileptiform
discharges.39
Treatment
The management of encephalitis should be directed toward the underlying cause.
Because no clinical sign, symptom, or CSF finding can reliably differentiate HSV
from other viral causes of encephalitis, the initiation of empiric treatment with intrave-
nous acyclovir is indicated in any patient suspected to have viral encephalitis until a
definitive diagnosis can be achieved. The most significant factor determining outcome
in HSV encephalitis is starting antiviral treatment as early as possible, ideally within
6 hours of presentation.52,53 A multicenter observational study of 93 patients found
that the only 2 factors significantly associated with poor outcome were how sick the
patient was at presentation (Simplified Acute Physiology score >27) and the initiation
of acyclovir more than 2 days after initial presentation.54
In the study mentioned above, 41% of patients did not have acyclovir initiated until
after 2 days of presentation.54 This proportion of patients was similar to a second
retrospective study of 184 patients in which acyclovir was initiated more than
1 day after hospital admission in 37% of patients eventually diagnosed with HSV en-
cephalitis.55 These data suggest that HSV encephalitis can be difficult to diagnose
and requires a high degree of initial clinical suspicion. In a retrospective study,
several patient characteristics were significantly associated with delay of acyclovir
initiation, including severe underlying disease (odds ratio [OR] 4.1; 95% CI 1.5–
11.7), alcohol abuse (OR 3.4; 95% CI 1.3–8.9), delay of greater than 1 day from
admission to first brain imaging (OR 8.4; 95% CI 3.9–18.0), and a finding of less
than 10 leukocytes/mm3 in CSF at admission (OR 2.5; 95% CI 0.7–5.8).
Acyclovir is dosed according to weight and age. The ideal body weight (IBW) should
be used to calculate the acyclovir dose (males: IBW [kg] 5 50 kg 1 2.3 kg for each inch
over 5 feet; females: IBW [kg] 5 45.5 kg 1 2.3 kg for each inch over 5 feet).56 The dose
should be reduced in patients with pre-existing renal impairment because acyclovir is
renally excreted. In order to help prevent acyclovir-induced crystalluria and nephro-
toxicity, patients should be well hydrated to maintain adequate urine output. Concur-
rent administration of nephrotoxic drugs should be minimized.

930 Dorsett & Liang
BRAIN ABSCESS
A brain abscess is a collection of purulent material resulting from infection within the
brain parenchyma. Focal inflammation and edema (early cerebritis) expand and prog-
ress over days to a wider inflammatory response in the white matter, surrounding an
increasingly necrotic core (late cerebritis). In the course of a few weeks, a collagenous
capsule surrounds and walls off the core, although surrounding inflammation and
edema may persist. A predisposing contiguous focus of infection is present in more
than half of all cases of bacterial (pyogenic) abscess, with otitis, mastoiditis, sinusitis,
meningitis, and odontogenic infections being the most common.57 Metastatic or he-
matogenous seeding of the brain parenchyma from a distant source of infection (eg,
bacterial endocarditis, congenital heart disease with right-to-left shunt, pulmonary
infection) accounts for up to a third of cases. Traumatic inoculation through gunshot
wounds and other penetrating injuries can likewise predispose to brain abscess for-
mation, as can open neurosurgical procedures.
Streptococcus and Staphylococcus species are implicated in the vast majority of
bacterial brain abscesses, although Gram-negative bacteria (Proteus spp, Klebsiella
spp, E coli, and Enterobacteriae) have been found in up to 15% of cases, particularly
in Europe, Asia, and Africa.57 Nearly a quarter of all brain abscesses are polymicrobial
in nature. Nocardia, fungal (eg, Aspergillus spp, Candida spp, C neoformans), and
parasitic (eg, Toxoplasma gondii) brain abscesses are most likely to be encountered
in the setting of severe immunocompromise (eg, HIV infection, transplantation).
The reported incidence of brain abscess ranges from 0.4 to 0.9 cases per 100,000
persons, with higher incidence reported in immunocompromised populations.58,59
Most patients present in the third or fourth decade of life, and brain abscess is
more commonly diagnosed in men.57,59 Mortality from brain abscess has historically
run as high as 40%, but has decreased to 10% since 2000, owing much to advances
in diagnostic imaging and management strategies.57
The classic triad of headache, fever, and focal neurologic deficits associated with
brain abscess is present in only 20% of patients.57 Fever is only present in half of
the cases.57 Onset of neurologic symptoms can be subtle and indolent, spanning
days to weeks, manifesting as hemiparesis, cranial nerve palsy, gait disorders, or
signs and symptoms of increased intracranial pressure (eg, nausea, vomiting, papille-
dema, altered mental status).60 Up to a quarter of cases may be accompanied by focal
or generalized seizures.57 Frontal lobe abscess may present as headache and behav-
ioral changes. An occipital lobe abscess, cerebellar abscess, or abscess with
concomitant meningitis or intraventricular rupture can present with neck stiffness. In
many cases, headache alone may be the only initial symptom of a brain abscess,
particularly in its earliest stages. In the absence of associated neurologic findings, a
heightened clinical suspicion for brain abscess, particularly in immunocompromised
patients, is necessary to carry the evaluation forward.
Diagnosis
Imaging is paramount to diagnosing brain abscess. Emergent CT with contrast can
reveal ring-enhancing lesions characteristic of abscess in the late stages of cerebritis
and as the lesion encapsulates.61 MRI with gadolinium remains the most sensitive mo-
dality to look for and characterize the extent of brain abscess, particularly in early cer-
ebritis as well as in the posterior fossa (eg, brainstem) where visualization by CT may
be limited. Given the hematogenous nature of many brain abscesses, blood cultures

can aid with identifying a causative organism in a quarter of cases.57 In most cases,
the CSF is sterile; however, if there is suspicion for concomitant meningitis or abscess
rupture into a ventricle, LP may be useful in obtaining CSF for culture. In this situation,
contraindications to LP, including the risk for brain herniation due to mass effect, must
be carefully weighed against any potential benefit, particularly if neurosurgical aspira-
tion, drainage, or excision of the abscess is already anticipated.
Treatment
A multidisciplinary approach combining surgical and medical therapy to treat brain ab-
scess optimizes clinical outcomes. Neurosurgical consultation should be sought to
determine whether an invasive procedure is necessary to obtain a culture from the ab-
scess to guide antibiotic therapy and definitively drain its contents. Stereotactic nee-
dle abscess aspiration under CT or other imaging guidance is preferred in most
situations, although surgical excision may be needed in others (eg, patients at high
risk for brain herniation due to mass effect or with multiloculated abscess).
If surgical intervention is planned within hours and the patient is clinically stable,
empiric antibiotic therapy may be withheld to optimize the yield of bacterial cultures
obtained from the abscess, but this decision is best made in conjunction with the
neurosurgeon. Empiric broad-spectrum antibiotic therapy targeted against Staphylo-
coccus, Streptococcus, Gram-negative organisms, and anaerobes can be achieved
through a combination of intravenous vancomycin, a third- or fourth-generation ceph-
alosporin (eg, ceftriaxone, cefepime), and metronidazole. Long-term intravenous anti-
biotic therapy, tailored to causative organisms identified on culture, is favored and
traditionally averages 6 to 8 weeks.57
SPECIAL SITUATIONS
The Febrile Neonate
In infants less than 48 hours old, CNS infection can present as temperature instability,
spells of apnea and bradycardia, feeding difficulty, and irritability alternating with leth-
argy. At greater than 48 hours of age, infants with CNS infection are more likely to present
with neurologic symptoms, including seizures, a bulging anterior fontanel, extensor
posturing, focal cerebral signs, or cranial nerve palsies. Although the workup and man-
agement of an ill-appearing infant are relatively clear-cut (blood, urine, and CSF cultures
accompanied by timely initiation of empiric antibiotics), the more common clinical
conundrum encountered is the diagnostic workup and management of the well-
appearing febrile infant younger than 90 days. Many febrile infants in this age group
will have no focus of infection on physical examination, but w10% will have an underly-
ing serious bacterial infection (SBI).62 Most of these are urinary tract infections (7%–9%
overall), whereas meningitis represents less than 0.5%. The low prevalence of meningitis
in this population opens the door to a wide variety of practice patterns when it comes to
deciding when it is appropriate to perform an LP.62–64 As infants less than 28 days are at
greater risk for SBI (overall prevalence of 11%–25%), the general consensus favors per-
forming an LP in all cases and admitting to the hospital pending culture results.62 Well-
appearing febrile infants 28 to 90 days old present more of a management dilemma.
Several criteria (Rochester, Boston, Philadelphia, and subsequent derivations) have
been developed to determine which patients should undergo LP in the first place and
who should be admitted for empiric antibiotics pending culture results.65–67
Only the Rochester criteria do not include a mandatory CSF analysis (Box 1). In the
original study, 1% of the low-risk infants had an SBI, which included urinary tract
infections and one case of N meningitidis bacteremia.67 Procalcitonin is a promising

932 Dorsett & Liang
Box 1
The Rochester criteria for identifying the febrile neonate at low risk for serious bacterial
infection
Rochester Criteria
Infant appears generally well
Infant has been previously healthy
Born at 37 weeks’ gestation
Did not receive perinatal antimicrobial therapy
Was not treated for unexplained hyperbilirubinemia
Had not yet received antimicrobial agents
Had not been previously hospitalized
Had no chronic or underlying illness
Was not hospitalized longer than the mother
No evidence of skin, soft tissue, bone, joint, or ear infection
Laboratory values
WBC between greater than 5000 and less than 15,000/mm3
Absolute band count less than or equal to 1500/mm3
Less than or equal to 10 WBC per high-power field on urine microscopic examination
Less than or equal to 5 WBC per high-power field in microscopic examination of stool
smear for infants presenting with diarrhea
Abbreviation: WBC, white blood cell.

Data from Pantell RH, Newman TB, Bernzweig J, et al. Management and outcomes of care of
fever in early infancy. JAMA 2004;291(10):1203–12.
marker of SBI (including meningitis) in the pediatric population, but may not be widely
available as a rapid diagnostic test.68 In general, in low-risk infants less than 90 days
of age, empiric antibiotics should not be administered without performing an LP.
In addition to SBI, neonates, especially between days 9 and 17 days of life, are at
significant risk for HSV-2 infection. Apart from the typical features of infection in neo-
nates, HSV should be suspected if a neonate presents with seizures, hepatic failure, or
characteristic skin lesions (present in 35% of neonates with HSV), or if there is a
maternal history of HSV-2 genital infection.69 Empiric antibiotic coverage for the
neonate (see Table 3) generally consists of a third-generation cephalosporin in com-
bination with ampicillin. Acyclovir should be added if there is sufficient suspicion for
HSV infection.
The Elderly Patient

At the opposite end of life’s continuum, clinical signs and symptoms of CNS infection
vary, and atypical presentations abound. Fever, headache, and neck stiffness are less
common features in older patients with bacterial meningitis than non-specific symp-
toms such as altered mental status, stupor, or coma.70–73 Kernig’s and Brudzinski’s
signs are also less likely to be present or reliable. In light of this, performing an LP
as part of the evaluation of mental status change, even in the absence of fever, should
be strongly considered in this population. In contrast to younger adults where bacterial
meningitis due to N meningitidis is common, patients 65 years and older are more
likely to develop meningitis due to S pneumoniae, L monocytogenes or gram-
negative bacteria, or of an unknown origin.70,71 Empiric antibiotic therapy in the elderly
patient should therefore include expanded coverage for L monocytogenes with intra-
venous ampicillin in addition to vancomycin and a third-generation cephalosporin.

Although the differential diagnoses for mental status change and behavioral
changes in the elderly patient can be wide ranging, HSV encephalitis should always
be considered. In a Swedish national retrospective study, HSV encephalitis was
more commonly seen in those greater than the age of 60 years and was associated
with significantly greater mortality in those older than 70 years.74 If the clinical suspi-
cion for HSV encephalitis is high, an LP should be performed and empiric acyclovir
started pending molecular testing of the CSF for HSV.
Patients with Exposure to Arthropod Vectors

Arthropod vectors, including ticks and mosquitoes, can transmit a range of pathogens
capable of causing CNS infection. Lyme disease, a tick-borne infection associated
predominantly with the spirochete Borrelia burgdorferi and the most common
vector-borne illness in the United States, can lead to neurologic disease in up to
12% of untreated patients.75 Lymphocytic meningitis and encephalitis associated
with Lyme disease are acute in onset and can be hard to distinguish from viral CNS
infections. Lyme meningitis is often associated with cranial neuropathies, particularly
involving the seventh cranial nerve (facial nerve palsy) as well as radiculoneuritis lead-
ing to pain in peripheral nerve distributions. In patients with suspected CNS infection
due to B burgdorferi, CSF should be sent to assess for presence of antibodies to this
pathogen. Antibiotic therapy should consist of intravenous ceftriaxone, cefotaxime, or
penicillin G. Rocky Mountain Spotted Fever (RMSF), an infection caused by Rickettsia
rickettsii, is classically associated with a constellation of fever, headache, and a diffuse
macular and/or petechial rash that is inclusive of the palms and soles. In some cases,
a lymphocytic meningitis and encephalitis can also be seen with RMSF. Doxycycline is
the preferred antibiotic for treating RMSF. Human monocytic ehrlichiosis (HME) due to
Ehrlichia chaffeensis and human granulocytic anaplasmosis (HGA) due to Anaplasma
phagocytophilum are likewise tick-borne and can manifest with CSF lymphocytic
pleocytosis; both are also treated with doxycycline. Apart from ticks, mosquito vectors
can carry arboviruses (eg, West Nile virus, St. Louis encephalitis virus, Eastern and
Western equine encephalitis virus) responsible for causing meningitis and/or enceph-
alitis as already discussed before.
Arthropod-borne infections follow seasonal and geographic patterns centered on
the life cycle and distribution of the vectors. Infections generally peak in the warm,
summer months (June, July, and August) when vectors are active and patients are
most likely to come into contact with them. Vectors such as the Ixodes tick that trans-
mits Lyme disease are found primarily in the eastern United States, whereas the Der-
macentor tick responsible for RMSF has a wider distribution across southeastern and
south-central states. Infections associated with these ticks tend to fall along similar
geographic lines. The same can be said of HME and HGA. Therefore, knowledge of
the geographic distribution of potential arthropod vectors and careful assessment of
other epidemiologic risk factors in combination with a recent history of arthropod
exposure and/or bite are important when considering the diagnosis of an
arthropod-borne CNS infection.
Human Immunodeficiency Virus and Other Immunocompromised States

HIV infection preferentially impairs cell-mediated immunity, predisposing patients to
viral, fungal, and parasitic diseases. In addition to the common CNS infections seen
in the general population, HIV-related CNS infections are frequently opportunistic,
stemming from the reactivation of latent pathogens such as JC virus, EBV, CMV,
and T gondii.76,77 Disseminated histoplasmosis with CNS involvement can result
from either acute infection or reactivation. Susceptibility to such infections occurs

934 Dorsett & Liang
when the CD41 count falls to less than 200 cells per microliter, and many are consid-
ered AIDS-defining illnesses.
Opportunistic CNS infection should always be considered in patients with advanced
HIV who present with signs or symptoms of CNS infection, including altered mental
status, fever, headache, seizures, or focal neurologic signs. The underlying cause
hinges on the overall clinical presentation, time course of disease, CSF analysis,
and radiographic features (Table 5). Chronic headache with indolent symptoms (eg,
low-grade fever) can be characteristic of CNS tuberculosis as well as fungal meningitis
due to C neoformans, C immitis, or H capsulatum. Multiple brain abscesses on imag-
ing and a history of a positive T gondii serum immunoglobulin G (IgG) should trigger
concern for toxoplasmosis. Coinfections may be present in up to 15% of patients.76
The initial diagnostic workup for patients with HIV infection and presumed CNS oppor-
tunistic infection is outlined in Fig. 2. Treatment depends on the most likely cause and
should be initially broad pending the results of this workup. In addition to empiric anti-
biotic therapy, treatment may consist of initiating or continuing antiretroviral therapy
(ART). Paradoxic worsening of the infection following initiation of ART therapy can
occur as a result of immune reconstitution inflammatory syndrome, a consequence
of exaggerated activation of the recovering immune system classically encountered
in patients with tuberculosis, cryptococcal meningitis, or progressive multifocal
leukoencephalopathy.78
Although syphilis can cause CNS infections in immunocompetent patients,
neurosyphilis has become closely associated with coexisting HIV infection in the
post-penicillin era.79–81 In general, the neurologic manifestations of syphilis are
classified as either early or late neurosyphilis. Early symptomatic neurosyphilis
(also known as acute syphilitic meningitis) usually occurs within the first 12 months
of infection and involves diffuse inflammation of the meninges, resulting in head-
ache, photophobia, nausea, vomiting, and cranial nerve palsies.79 Ocular findings,
most commonly uveitis, can also be observed.81 Acute syphilitic meningitis, with
and without ocular manifestations, has become the most common neurologic infec-
tion in HIV patients and can occur even after the patient received initial treatment of
primary or secondary syphilis.81 Late neurosyphilis can take upwards of 15 to
20 years to develop and includes manifestations such as meningovascular syphilis,
tabes dorsalis, and CNS gummas. A low CD41 count (<350 cells/mL) is an indepen-
dent risk factor for developing neurosyphilis.80 For patients suspected of having
neurosyphilis, a serum nontreponemal test, usually a rapid plasma reagin or
Venereal Disease Research Laboratory (VDRL), should be sent but may be non-
reactive in late disease. In such cases, a serum treponemal test, such as fluorescent
treponemal antibody absorption (FTA-ABS), should also be sent because these
tests remain reactive lifelong after infection with syphilis. The diagnosis of neurosy-
philis is usually established by the presence of a reactive CSF-VDRL but cannot be
excluded if the test is nonreactive.81 Treatment with penicillin G is the standard for
neurosyphilis.
Apart from HIV, other immunocompromised patients, particularly those receiving
immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation
or those with hematologic malignancy, are not only at increased risk for bacterial CNS
infection but opportunistic infections as well.82–84 Solid-organ transplant recipients are
at heightened susceptibility for developing brain abscess due to Nocardia as well as
fungi (eg, Aspergillus spp, Candida spp). In addition to empiric antibiotic therapy
directed against usual bacteria, appropriate therapy targeted toward these organisms
may be warranted. Consultation with an infectious disease specialist can be beneficial
in optimizing empiric therapy in these complex patient populations.

Table 5
Clinical presentation, diagnosis, and treatment of opportunistic infections in HIV disease
Typical CD4D
Cell Count at Treatment 5
Presentation Temporal Special CSF Tests Typical Radiographic Antiretroviral
Infection (Cells/mL) Clinical Presentation Evolution (Sensitivity/Specificity) Appearance Therapy AND
CMV encephalitis <50 Altered mental status, Days CMV PCR (>90%/>90%) Usually normal; may have Ganciclovir
seizures evidence of ventriculitis with

ventriculomegaly and
periventricular
enhancement on MRI
Cryptococcal meningitis <50 (rarely Fever, headache, altered Days Elevated opening May be normal; “Punched- Amphotericin B and
up to 200) mental status, vomiting pressure; cryptococcal out” cystic lesions on MRI if flucytosine
antigen cryptococcocomas develop
Progressive multifocal <100 Altered mental status, focal Weeks to JC virus PCR (50%–90%/ Hyperintense areas in white —
leukoencephalopathy neurologic deficits months 90%–100%) matter on T2-FLAIR imaging
CNS lymphoma <100 Altered mental status, focal Weeks to EBV PCR (100%/50% Usually solitary, —
neurologic deficits, months specific) heterogeneously enhancing
headache lesions with mass effect
Toxoplasma <200 Fever, headache, altered Days T gondii PCR Multiple ring-enhancing Pyrimethamine, folinic
encephalitis mental status (50%–80%/100%) lesions with mass effect acid, and sulfadiazine
OR trimethoprim-
sulfamethoxazole
Tuberculous meningitis <200 Altered mental status, Days to weeks Culture and acid-fast Rarely basilar enhancement; Rifampin, isoniazid,
cranial neuropathies bacilli stain (>80%) possibly abscesses or pyrazinamide,
tuberculomas ethambutol
Acute syphilitic <350 Headache, photophobia, Within 12 mo CSF VDRL (CSF FTA-ABS No pathognomonic findings Pencillin-G 3–4 million
meningitis emesis. Ocular (chronic more sensitive but units every 4 h
manifestations (CN neurosyphilis less specific) 10–14 d
palsies, uveitis, optic 5–20 y)
neuritis) commonly
associated
Abbreviation: FLAIR, fluid-attenuated inversion recovery.
935
936
Dorsett & Liang
Fig. 2. Workup for presumed CNS infection in a patient with advanced HIV disease. (Modified from Tan IL, Smith BR, von Geldern G, et al.
HIV-associated opportunistic infections of the CNS. Lancet Neurol 2012;11(7):605–17.)
Cerebrospinal Fluid Shunt Infections

CSF shunt infection can be a cause for shunt failure and manifests with signs of
increased intracranial pressure and hydrocephalus (eg, depressed level of conscious-
ness, nausea, vomiting, headache, irritability in young children). It is the most common
complication of CSF shunt surgery (>11% in one multicenter prospective study) and
most often seen within 6 months of shunt placement due to intraoperative contamina-
tion with skin flora.85,86 As far as clinical presentation, there are several factors that in-
crease the likelihood that shunt infection is the underlying cause of shunt malfunction.
These factors include a history of recent shunt revision (adjusted odds ratio [aOR] 2.4;
95% CI 1.3–4.4), presence of fever (aOR 8.4; 95% CI 4.3–16.3), and white blood
cell greater than 15,000/mL (aOR 3.2; 95% CI 1.5–6.6).87,88 For patients with ventricu-
loperitoneal shunts, abdominal pain and peritonitis are less commonly seen, but are
highly predictive of shunt infection.89 Evaluation of patients with suspected CSF shunt
infection includes imaging to evaluate for shunt malfunction with either a head CT
(sensitivity of 53%–92%) or rapid cranial MRI (sensitivity of 51%–59%), shunt series
radiographs, and sampling of CSF through LP or shunt aspiration, and should involve
neurosurgical consultation.90 Empiric antibiotic therapy should be directed primarily
against skin flora and nosocomial pathogens, including Streptococcus aureus and
Pseudomonas aeruginosa.
SUMMARY
Despite the broad range of causative organisms and clinical presentations possible in
CNS infection, the initial ED evaluation is fundamentally the same. First, a high index of
clinical suspicion is necessary. The diagnosis should be considered in patients pre-
senting with headache, fever, altered mental status, or behavior change, especially
in the young, the elderly, or the immunocompromised. Second, the clinical history
and physical examination must be viewed as a whole when deciding whether further
evaluation for CNS infection is warranted. If a patient has focal neurologic deficits,
signs of increased intracranial pressure, a history of neurosurgical procedure or immu-
nocompromise, or is obtunded, neuroimaging should be performed to rule out asym-
metric mass effect before LP. As time is of the essence, empiric antibiotic coverage
tailored to the patient’s age and clinical risk factors should be initiated as soon as
possible if bacterial meningitis or HSV encephalitis is suspected. Finally, benign imag-
ing and CSF analysis can be falsely reassuring early on in disease, and an aggressive
course of action is always prudent in cases where a strong clinical suspicion for
serious CNS infection exists.
REFERENCES
1. Tintinalli JE, Stapczynski JS. Tintinalli’s emergency medicine: a comprehensive

study guide. 7th edition. New York: McGraw-Hill; 2011.
2. 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.
3. Logan SAE, MacMahon E. Viral meningitis. BMJ 2008;336(7634):36–40.
4. Gottfredsson M, Perfect JR. Fungal meningitis. Semin Neurol 2000;20(3):307–22.
5. Smith RM, Schaefer MK, Kainer MA, et al. Fungal infections associated with
contaminated methylprednisolone injections. N Engl J Med 2013;369(17):
1598–609.
6. Centers for Disease Control and Prevention (CDC). Progress toward elimination
of Haemophilus influenzae type b invasive disease among infants and

938 Dorsett & Liang
children–United States, 1998-2000. MMWR Morb Mortal Wkly Rep 2002;51(11):

234–7.
7. Castelblanco RL, Lee M, Hasbun R. Epidemiology of bacterial meningitis in the
USA from 1997 to 2010: a population-based observational study. Lancet Infect
Dis 2014;14(9):813–9.
8. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicro-
bial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23(3):
467–92.
9. Takhar SS, Ting SA, Camargo CA, et al. U.S. emergency department visits for
meningitis, 1993–2008. Acad Emerg Med 2012;19(6):632–9.
10. Waghdhare S, Kalantri A, Joshi R, et al. Accuracy of physical signs for detecting
meningitis: a hospital-based diagnostic accuracy study. Clin Neurol Neurosurg
2010;112(9):752–7.
11. Attia J, Hatala R, Cook DJ, et al. The rational clinical examination. Does this adult
patient have acute meningitis? JAMA 1999;282(2):175–81.
12. Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults.
A review of 493 episodes. N Engl J Med 1993;328(1):21–8.
13. Sigurdardóttir B, Björnsson OM, Jónsdóttir KE, et al. Acute bacterial meningitis in
adults. A 20-year overview. Arch Intern Med 1997;157(4):425–30.
14. Amarilyo G, Alper A, Ben-Tov A, et al. Diagnostic accuracy of clinical symptoms
and signs in children with meningitis. Pediatr Emerg Care 2011;27(3):196–9.
15. Ward MA, Greenwood TM, Kumar DR, et al. Josef Brudzinski and Vladimir Mikhai-
lovich Kernig: signs for diagnosing meningitis. Clin Med Res 2010;8(1):13–7.
16. Nakao JH, Jafri FN, Shah K, et al. Jolt accentuation of headache and other clinical
signs: poor predictors of meningitis in adults. Am J Emerg Med 2014;32(1):24–8.
17. Thomas KE, Hasbun R, Jekel J, et al. The diagnostic accuracy of Kernig’s sign,
Brudzinski’s sign, and nuchal rigidity in adults with suspected meningitis. Clin
Infect Dis 2002;35(1):46–52.
18. Uchihara T, Tsukagoshi H. Jolt accentuation of headache: the most sensitive sign
of CSF pleocytosis. Headache 1991;31(3):167–71.
19. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis:
risk stratification for adverse clinical outcome and effect of antibiotic timing.
Ann Intern Med 1998;129(11):862–9.
20. Proulx N, Fréchette D, Toye B, et al. Delays in the administration of antibiotics are
associated with mortality from adult acute bacterial meningitis. QJM 2005;98(4):
291–8.
21. Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic
administration and penicillin-nonsusceptible strains in adult intensive care unit
patients with pneumococcal meningitis: the PNEUMOREA prospective multi-
center study. Crit Care Med 2006;34(11):2758–65.
22. Michael B, Menezes BF, Cunniffe J, et al. Effect of delayed lumbar punctures on
the diagnosis of acute bacterial meningitis in adults. Emerg Med J 2010;27(6):
433–8.
23. van Crevel H, Hijdra A, de Gans J. Lumbar puncture and the risk of herniation:
when should we first perform CT? J Neurol 2002;249(2):129–37.
24. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management
of bacterial meningitis. Clin Infect Dis 2004;39(9):1267–84.
25. Glimaker M, Johansson B, Grindborg O, et al. Adult bacterial meningitis: earlier
treatment and improved outcome following guideline revision promoting prompt
lumbar puncture. Clin Infect Dis 2015;60(8):1162–9.

26. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic
factors in adults with bacterial meningitis. N Engl J Med 2004;351(18):1849–59.
27. Ray P, Badarou-Acossi G, Viallon A, et al. Accuracy of the cerebrospinal fluid re-
sults to differentiate bacterial from non bacterial meningitis, in case of negative
gram-stained smear. Am J Emerg Med 2007;25(2):179–84.
28. Viallon A, Desseigne N, Marjollet O, et al. Meningitis in adult patients with a nega-
tive direct cerebrospinal fluid examination: value of cytochemical markers for dif-
ferential diagnosis. Crit Care 2011;15(3):R136.
29. Posner JB, Plum F. Independence of blood and cerebrospinal fluid lactate. Arch
Neurol 1967;16(5):492–6.
30. Sakushima K, Hayashino Y, Kawaguchi T, et al. Diagnostic accuracy of cerebro-
spinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis:
a meta-analysis. J Infect 2011;62(4):255–62.
31. Assicot M, Gendrel D, Carsin H, et al. High serum procalcitonin concentrations in
patients with sepsis and infection. Lancet 1993;341(8844):515–8.
32. Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue
antibiotics in acute respiratory tract infections. Evid Based Child Health 2013;
8(4):1297–371.
33. Nigrovic LE, Kuppermann N, Malley R. Development and validation of a multivari-
able predictive model to distinguish bacterial from aseptic meningitis in children
in the post-Haemophilus influenzae era. Pediatrics 2002;110(4):712–9.
34. Nigrovic LE, Kuppermann N, Macias CG, et al. Clinical prediction rule for identi-
fying children with cerebrospinal fluid pleocytosis at very low risk of bacterial
meningitis. JAMA 2007;297(1):52–60.
35. Nigrovic LE, Malley R, Kuppermann N. Meta-analysis of bacterial meningitis
score validation studies. Arch Dis Child 2012;97(9):799–805.
36. Tauber MG, Khayam-Bashi H, Sande MA. Effects of ampicillin and corticosteroids
on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid
lactate levels in experimental pneumococcal meningitis. J Infect Dis 1985;
151(3):528–34.
37. Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial men-
ingitis. Cochrane Database Syst Rev 2013;(6):CD004405.
38. Steiner I, Benninger F. Update on herpes virus infections of the nervous system.
Curr Neurol Neurosci Rep 2013;13(12):414.
39. Solomon T, Michael BD, Smith PE, et al. Management of suspected viral enceph-
alitis in adults—Association of British Neurologists and British Infection Associa-
tion National Guidelines. J Infect 2012;64(4):347–73.
40. Johnson RT. Acute encephalitis. Clin Infect Dis 1996;23(2):219–24.
41. Murthy SNK, Faden HS, Cohen ME, et al. Acute disseminated encephalomyelitis
in children. Pediatrics 2002;110(2 Pt 1):e21.
42. Granerod J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differ-
ences in their clinical presentations in England: a multicentre, population-
based prospective study. Lancet Infect Dis 2010;10(12):835–44.
43. Greenlee JE. Encephalitis and postinfectious encephalitis. Continuum (Minneap
Minn) 2012;18:1271–89.
44. Whitley RJ, Lakeman F. Herpes simplex virus infections of the central nervous
system: therapeutic and diagnostic considerations. Clin Infect Dis 1995;20(2):
414–20.
45. Grahn A, Studahl M. Varicella-zoster virus infections of the central nervous sys-
tem—prognosis, diagnostics and treatment. J Infect 2015;71(3):281–93.

940 Dorsett & Liang
46. Koskiniemi M, Rantalaiho T, Piiparinen H, et al. Infections of the central nervous

system of suspected viral origin: a collaborative study from Finland. J Neurovirol
2001;7(5):400–8.
47. Whitley RJ. Herpes simplex encephalitis: clinical assessment. JAMA 1982;
247(3):317.
48. Deresiewicz RL, Thaler SJ, Hsu L, et al. Clinical and neuroradiographic manifes-
tations of eastern equine encephalitis. N Engl J Med 1997;336(26):1867–74.
49. Hayes EB, Sejvar JJ, Zaki SR, et al. Virology, pathology, and clinical manifesta-
tions of West Nile virus disease. Emerg Infect Dis 2005;11(8):1174–9.
50. Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging path-
ogens. Lancet 2002;359(9305):507–13.
51. Domingues R, Fink MC, Tsanaclis AM, et al. Diagnosis of herpes simplex enceph-
alitis by magnetic resonance imaging and polymerase chain reaction assay of
cerebrospinal fluid. J Neurol Sci 1998;157(2):148–53.
52. Ibitoye RT, Sarkar P, Rajbhandari S. Pitfalls in the management of herpes simplex
virus encephalitis. BMJ Case Rep 2012;2012.
53. Sili U, Kaya A, Mert A, et al. Herpes simplex virus encephalitis: clinical manifes-
tations, diagnosis and outcome in 106 adult patients. J Clin Virol 2014;60(2):
112–8.
54. Raschilas F, Wolff M, Delatour F, et al. Outcome of and prognostic factors for her-
pes simplex encephalitis in adult patients: results of a multicenter study. Clin
Infect Dis 2002;35(3):254–60.
55. Poissy J, Wolff M, Dewilde A, et al. Factors associated with delay to acyclovir
administration in 184 patients with herpes simplex virus encephalitis. Clin Micro-
biol Infect 2009;15(6):560–4.
56. Stehman CR, Buckley RG, DosSantos FL, et al. Bedside estimation of patient
height for calculating ideal body weight in the emergency department.
J Emerg Med 2011;41(1):97–101.
57. Brouwer MC, Coutinho JM, van de Beek D. Clinical characteristics and outcome
of brain abscess: systematic review and meta-analysis. Neurology 2014;82(9):
806–13.
58. Nicolosi A, Hauser WA, Musicco M, et al. Incidence and prognosis of brain ab-
scess in a defined population: Olmsted County, Minnesota, 1935-1981. Neuroe-
pidemiology 1991;10(3):122–31.
59. Helweg-Larsen J, Astradsson A, Richhall H, et al. Pyogenic brain abscess, a 15
year survey. BMC Infect Dis 2012;12:332.
60. Brouwer MC, Tunkel AR, McKhann GM, et al. Brain abscess. N Engl J Med 2014;
371(5):447–56.
61. Rath TJ, Hughes M, Arabi M, et al. Imaging of cerebritis, encephalitis, and brain
abscess. Neuroimaging Clin N Am 2012;22(4):585–607.
62. Biondi EA, Byington CL. Evaluation and management of febrile, well-appearing
young infants. Infect Dis Clin North Am 2015;29(3):575–85.
63. Aronson PL, Thurm C, Alpern ER, et al. Variation in care of the febrile young infant
<90 days in US pediatric emergency departments. Pediatrics 2014;134(4):
667–77.
64. Pantell RH, Newman TB, Bernzweig J, et al. Management and outcomes of care
of fever in early infancy. JAMA 2004;291(10):1203–12.
65. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever
in selected infants. N Engl J Med 1993;329(20):1437–41.

66. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to
89 days of age with intramuscular administration of ceftriaxone. J Pediatr 1992;
120(1):22–7.
67. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low risk for
serious bacterial infection–an appraisal of the Rochester criteria and implications
for management. Febrile Infant Collaborative Study Group. Pediatrics 1994;94(3):
390–6.
68. van Rossum AMC, Wulkan RW, Oudesluys-Murphy AM. Procalcitonin as an early
marker of infection in neonates and children. Lancet Infect Dis 2004;4(10):
620–30.
69. James SH, Kimberlin DW. Neonatal herpes simplex virus infection: epidemiology
and treatment. Clin Perinatol 2015;42(1):47–59, viii.
70. Domingo P, Pomar V, de Benito N, et al. The spectrum of acute bacterial menin-
gitis in elderly patients. BMC Infect Dis 2013;13:108.
71. Wang AY, Machicado JD, Khoury NT, et al. Community-acquired meningitis in
older adults: clinical features, etiology, and prognostic factors. J Am Geriatr
Soc 2014;62(11):2064–70.
72. Magazzini S, Nazerian P, Vanni S, et al. Clinical picture of meningitis in the adult
patient and its relationship with age. Intern Emerg Med 2012;7(4):359–64.
73. Lai W-A, Chen S-F, Tsai N-W, et al. Clinical characteristics and prognosis of acute
bacterial meningitis in elderly patients over 65: a hospital-based study. BMC Ger-
iatr 2011;11:91.
74. Hjalmarsson A, Blomqvist P, Sköldenberg B. Herpes simplex encephalitis in
Sweden, 1990-2001: incidence, morbidity, and mortality. Clin Infect Dis 2007;
45(7):875–80.
75. Bacon RM, Kugeler KJ, Mead PS, et al. Surveillance for Lyme disease–United
States, 1992-2006. MMWR Surveill Summ 2008;57(10):1–9.
76. Tan IL, Smith BR, von Geldern G, et al. HIV-associated opportunistic infections of
the CNS. Lancet Neurol 2012;11(7):605–17.
77. Arribas JR. Cytomegalovirus encephalitis. Ann Intern Med 1996;125(7):577.
78. Müller M, Wandel S, Colebunders R, et al. Immune reconstitution inflammatory
syndrome in patients starting antiretroviral therapy for HIV infection: a systematic
review and meta-analysis. Lancet Infect Dis 2010;10(4):251–61.
79. Ghanem KG. REVIEW: Neurosyphilis: a historical perspective and review. CNS
Neurosci Ther 2010;16(5):e157–68.
80. Ghanem KG, Moore RD, Rompalo AM, et al. Neurosyphilis in a clinical cohort of
HIV-1-infected patients. AIDS 2008;22(10):1145–51.
81. González-Duarte A, López ZM. Neurological findings in early syphilis: a compar-
ison between HIV positive and negative patients. Neurol Int 2013;5(4):e19.
82. Davis JA, Horn DL, Marr KA, et al. Central nervous system involvement in cryp-
tococcal infection in individuals after solid organ transplantation or with AIDS.
Transpl Infect Dis 2009;11(5):432–7.
83. Ohara H, Kataoka H, Nakamichi K, et al. Favorable outcome after withdrawal of
immunosuppressant therapy in progressive multifocal leukoencephalopathy after
renal transplantation: case report and literature review. J Neurol Sci 2014;
341(1–2):144–6.
84. Yehia BR, Blumberg EA. Mycobacterium tuberculosis infection in liver transplan-
tation. Liver Transpl 2010;16(10):1129–35.
85. Simon TD, Hall M, Riva-Cambrin J, et al. Infection rates following initial cerebro-
spinal fluid shunt placement across pediatric hospitals in the United States. Clin-
ical article. J Neurosurg Pediatr 2009;4(2):156–65.

942 Dorsett & Liang
86. Wallace AN, McConathy J, Menias CO, et al. Imaging evaluation of CSF shunts.
AJR Am J Roentgenol 2014;202(1):38–53.
87. Garton HJ, Kestle JR, Drake JM. Predicting shunt failure on the basis of clinical
symptoms and signs in children. J Neurosurg 2001;94(2):202–10.
88. Rogers EA, Kimia A, Madsen JR, et al. Predictors of ventricular shunt infection
among children presenting to a pediatric emergency department. Pediatr Emerg
Care 2012;28(5):405–9.
89. Piatt JH, Garton HJL. Clinical diagnosis of ventriculoperitoneal shunt failure
among children with hydrocephalus. Pediatr Emerg Care 2008;24(4):201–10.
90. Boyle TP, Nigrovic LE. Radiographic evaluation of pediatric cerebrospinal fluid
shunt malfunction in the emergency setting. Pediatr Emerg Care 2015;31(6):
435–40.


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D i a g n o s i s an d Tre a t m e n t

of Central Nervous System

Emerg Med Clin N Am 34 (2016) 917–942

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

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Meningitis is a relatively rare diagnosis in US emergency departments (ED). Be-

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Sensitivity (95% CI) Specificity (95% CI) LRD LRL Reference

Abbreviation: LR, likelihood ratio.

Parameter Normal Bacterial Virala Fungala

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should be considered in immunocompetent individuals. Special CSF testing for fungal

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Most Common Bacterial

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In addition to prompt antibiotic therapy, corticosteroids should be considered as

Encephalitis is inflammation of the brain parenchyma. It is technically a pathologic

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In the Western world, encephalitis is an uncommon disorder. The reported inci-

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Diagnosis and Treatment of CNS Infections

other causes of viral encephalitis.43,47 As a consequence, molecular (eg, PCR) and

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Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

Abbreviation: WBC, white blood cell.

The Elderly Patient

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Patients with Exposure to Arthropod Vectors

Human Immunodeficiency Virus and Other Immunocompromised States

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seizures evidence of ventriculitis with

Abbreviation: FLAIR, fluid-attenuated inversion recovery.

Cerebrospinal Fluid Shunt Infections

1. Tintinalli JE, Stapczynski JS. Tintinalli’s emergency medicine: a comprehensive

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

children–United States, 1998-2000. MMWR Morb Mortal Wkly Rep 2002;51(11):

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

46. Koskiniemi M, Rantalaiho T, Piiparinen H, et al. Infections of the central nervous

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

Downloaded from ClinicalKey.com at Universidad Ces November 01, 2016.

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