95

Central Nervous System Infections

Benjamin H. Schnapp and Corlin Jewell

parenchyma itself, then it is termed encephalitis. However, these dis-

KEY CONCEPTS
ease states are not mutually exclusive and exist on a continuum of
• CNS infection should be considered in all patients with headache, nuchal meningoencephalitis. Generally, greater degrees of encephalitis portend
rigidity, fever, altered sensorium, or diffuse or focal neurologic findings. a worse prognosis, as more tissue is involved.
• Patients with suspected CNS infection should be asked about history
focused on risk factors for CNS disease and infection and receive a full Bacterial Meningitis
neurologic examination. Bacterial meningitis has a high mortality rate despite treatment, with
• CSF testing is the most reliable method of assessing the presence of men- rates variable depending on the organism, time to appropriate treat-
ingitis and should be obtained in all patients in which there is a suspicion ment, and patient factors. Streptococcus pneumoniae remains the pre-
for CNS infection. dominant pathogen in adult patients, accounting for over half of cases
• Early initiation of empirical antimicrobial therapy is recommended in cases despite a recent decline in incidence.1 Other common causes in adults
of suspected acute CNS infection. This should occur before imaging or lum- include Neisseria meningitidis, Haemophilus influenzae, and Listeria
bar puncture. monocytogenes. N. meningitidis is the predominant organism in chil-
• Patients without focal neurologic symptoms, altered level of consciousness dren. Listeria is more commonly seen in elderly adults and infants. In
or signs of increased intracranial pressure do not require imaging prior to the first six weeks of life, Group B streptococcus species as well as Esch-
lumbar puncture. erichia coli also represent common causes of bacterial meningitis. Bac-
• We recommend steroid treatment before or alongside treatment with anti- terial meningitis caused by H. influenzae was previously responsible
biotics in all cases of suspected meningoencephalitis. for a much larger proportion of cases, but the incidence has declined
• First-line treatment for healthy adults with suspected bacterial meningitis sharply since the introduction of the vaccine for type B (HiB).
is ceftriaxone or cefotaxime plus vancomycin in most countries given high Meningococcal disease refers to meningitis caused by N. meningit-
antibiotic resistance. idis, and is most common in younger individuals, particularly those
• Acyclovir is recommended for patients with suspected encephalitis because living in very close proximity to others such as in military barracks or
HSV is a common pathogen. college dormitories. A, B, and C represent the major groups. Group B
• Clinical course and risk factors, such as immunosuppression, dictate the is particularly prevalent in Europe, while group C is commonly isolated
need to test and treat for fungal and tuberculous meningoencephalitis. in the United States. A conjugate vaccine containing serogroups A, C,
• In the absence of a clear clinical picture of viral meningitis, patients should Y, and W-135 has been developed, as well as a separate vaccine for sero-
generally be empirically covered for bacterial meningitis and admitted to group B. These vaccines are highly effective in children, but have yet to
the hospital. be broadly distributed to developing countries.
• Antibiotic chemoprophylaxis should be given for close contacts of patients The infection process in bacterial meningitis generally begins with
with meningitis resulting from N. meningitidis and contacts of patients with nasopharyngeal colonization and invasion of the mucosa. The vary-
H. influenzae living with immunocompromised or unvaccinated individuals. ing capsular properties of each organism protect the bacteria. Once
• CT or MRI can be used in patients with a suspected brain abscess. bacteria cross the blood-brain barrier to enter the CSF, host defense
• MRI with gadolinium contrast of the entire spine is the definitive imaging mechanisms within the CSF are often ineffective. Bacteria then prolif-
test for patients with suspected spinal epidural abscess. erate, which causes the body to signal for leukocytes to enter the CSF.
Meningeal and subarachnoid space inflammation is associated with
the release of cytokines into the CSF, inciting an inflammatory cas-
FOUNDATIONS cade that promotes increased permeability of the blood-brain barrier,
cerebral vasculitis, edema, and increased intracranial pressure (ICP).
Background and Pathophysiology A subsequent decrease in cerebral blood flow can then lead to cerebral
The etiology of CNS infections continues to change as a result of new hypoxia.
therapeutic interventions, vaccines, and the growing number of immu- Meningeal infection may also occur in association with a dural leak
nosuppressed patients. Despite advances, however, the morbidity and secondary to neurosurgery or trauma to the CNS. Skin flora, includ-
mortality from a CNS infection remains high; good outcomes can be ing coagulase-negative staphylococcus species, Staphylococcus aureus,
maximized with early recognition and treatment. and Cutibacterium acnes are seen most commonly in this population,
The two most common CNS infections, meningitis and encephali- though infections caused by Pseudomonas aeruginosa also occur.
tis, are delineated by the tissue that is infected. Meningitis refers to an Mortality from bacterial meningitis is highest in patients with
infection of the meningeal layers lying between the bony covering of advanced presentations, serious underlying disease or advanced age.
the CNS and the brain tissue. If the infection is present in the brain The fatality rate is highest with Listeria meningitis with a mortality rate

1322
 CHAPTER 95 Central Nervous System Infections 1323

up to 27%.2 Overall, many survivors have some degree of residual neu- Tuberculous Meningitis
rologic deficit, with the highest rates found in those with pneumococ- Mycobacteria typically gain access to the CNS via hematogenous
cal meningitis.3 spread, and once present will begin to form granulomas. These can
Meningitis from Lyme disease (Borrelia burgdorferi) presents sim- rupture, inciting an inflammatory response from the host. This can
ilarly to other causes of bacterial meningitis, but can also cause other have the side effect of causing vasculitis and potentially a stroke. Tuber-
neurologic symptoms, including facial palsies and radiculopathies. culous meningitis is also frequently complicated by hydrocephalus
Late Lyme infection, occurring in some cases years after initial infec- requiring neurosurgical intervention; in advanced disease, up to 25%
tion, can cause encephalopathy which can manifest as migraines, psy- of patients may require some neurosurgical procedure for obstruction
chosis, and somatoform disorders. (ventriculoperitoneal shunt or drainage). Tuberculous meningitis leads
to severe disability or death in roughly half of the cases, and, as with
Viral Meningitis bacterial meningitis, depends on the patient’s age, comorbidities, time
Given the decrease in the incidence of bacterial meningitis, largely sec- to diagnosis, and the progression of their disease.
ondary to vaccination efforts, viral infections are now the most com-
mon cause of meningitis. Enteroviruses and herpesviruses are the most Fungal Meningitis
common causes,4 often occurring in those with risk factors such as a CNS infections caused by fungal species are most commonly caused
suppressed immune system. The overall prognosis for the majority of by Cryptococcus (typically C. neoformans and C. gattii) and have been
cases of viral meningitis is excellent. increasing in recent years. Other common causes of fungal meningitis
include Aspergillus species and Coccidioides immitis. Diabetic patients
Viral Encephalitis are at high risk of developing cerebral mucormycosis via direct inva-
The same organisms responsible for viral meningitis may also be asso- sion of the sinuses, and CNS invasion by Histoplasma capsulatum is
ciated with encephalitis. A common mechanism of viral transmission also commonly seen in AIDS patients.
is through the skin via insect vectors (e.g., Zika virus or West Nile Over a million cases of fungal CNS infections are estimated to
virus), although clinical disease develops in only a small percentage of occur annually, likely via similar mechanisms as bacterial meningi-
the people bitten. Tick-borne viral encephalitis is endemic to parts of tis. Because these infections typically affect those with compromised
Europe and Russia and is an important consideration for residents and immune systems, this increase is likely secondary to an increasing
recent travelers to those regions; a vaccine is available. Transmission number of people living with iatrogenic chronic immunosuppression
of viral encephalitis often occurs by hematogenous spread from infec- and HIV infection. Pulmonary exposure, followed by hematogenous
tions of the respiratory, gastrointestinal, or urogenital tracts. Other spread, is the primary pathogenic mechanism in most cases of cryp-
mechanisms include retrograde transmission along neuronal axons, as tococcal meningitis. Infection with C. neoformans is considered an
seen in the herpes virus, and direct invasion of the subarachnoid space acquired immunodeficiency syndrome (AIDS)-defining illness but can
after infection of the olfactory submucosa, as seen in rabies or herpes. occur in those with immunocompromised states arising from other
The outcomes in viral encephalitis, including permanent neuro- causes. Infection with C. gatti can occur even in immunocompetent
logic sequelae, are dependent on both the host and the infecting agent. patients. Candida species are also a major cause of fungal meningitis.
Acyclovir treatment has reduced the mortality from HSV encephalitis These infections typically occur in those with candidemia or via the
from up to 70% down to 9%, but with 34% of surviving patients hav- implantation of neurosurgical hardware (such as CNS shunts).
ing moderate to severe neurologic disability.5 Common complications Common CNS complications of fungal meningitis include
include seizures, motor deficits, and impaired cognition. Encephalitis abscesses, increased ICP, neurologic deficits, seizures, bone invasion,
caused by Japanese encephalitis virus, Eastern equine virus, and St. fluid collections, and ocular abnormalities (seen in up to 40% of patients
Louis encephalitis virus is severe, with high mortality rates and high with cryptococcal meningitis). The mortality rate of fungal meningo-
rates of neurologic sequelae among survivors. West Nile virus pro- encephalitis is usually around 20% to 30%, but may be up to 97% in
duces encephalitis in less than 1% of those infected but has resulted untreated Candida meningitis, and varies with the severity of illness,
in 2000 deaths in the United States as of 2016.6 Western equine virus timeliness of diagnosis, and administration of appropriate treatment.
and California encephalitis virus cause milder infections, and death is
rare. Zika virus has been associated with the development of Guillain- Central Nervous System Abscess
Barré syndrome (GBS) as well as severe encephalitis in developing CNS abscesses occur due to both local contiguous invasion as well as
fetuses of infected mothers, resulting in devastating neurologic defects. hematogenous spread from remote infections. They are also associ-
It is not entirely clear if the virus also causes neuroinvasive disease in ated with intravenous (IV) drug use, neurologic surgery, and cranial
adults. Powassan virus, another tick-borne cause of CNS infection in trauma. In cases of contiguous spread, the location of the abscess
North America, is known to cause severe encephalitis with a mortal- within the brain is typically dictated by the source of invasive infection
ity of approximately 10% and a high rate of neurologic disability in or the surgical procedure (Fig. 95.1). Brain abscesses secondary to oti-
survivors. CMV can also cause encephalitis, particularly in patients tis media are most often found within the temporal lobe or cerebellum,
who are infected with HIV or are otherwise immunocompromised. whereas cases arising from sinusitis usually result in abscesses in the
Influenza virus, well-known for its respiratory effects, is another rare frontal or temporal lobes. Hematogenous spread of microorganisms
cause of high-mortality encephalitis in adults. Encephalitis second- (most commonly from the pulmonary system) often results in mul-
ary to measles and mumps has almost disappeared in the developed tiple brain abscesses, although solitary lesions may also occur. Rarely,
world due to widespread vaccination, but still can occur, particularly patients present without a clear source or the presence of risk factors.
in those who are immunocompromised. Primary measles encephalitis Antibiotic prophylaxis in the immunosuppressed, improved diagnostic
is typically self-limited but carries a mortality of approximately 10% imaging, and neurosurgical interventions have all contributed to more
to 15%. Patients with this disease can go on to develop both subacute favorable outcomes.7
and chronic encephalitis (sometimes occurring years later) which is The spinal epidural space also represents a common site of CNS
universally fatal. abscesses. Increasing numbers of spinal surgeries, immunosuppressed
1324 PART III Emergency Medicine by System

Because meningitis can result from both contiguous and hematog-

enous spread, the physical examination should include a search for
an inciting infection, such as a skin abscess, sinusitis, endocarditis, or
osteomyelitis. Manifestations of endocarditis may be present, partic-
ularly in cases found to be due to S. aureus. Petechiae and cutaneous
hemorrhages are widely reported with meningococcemia, typically on
the extremities although they can occur anywhere on the body. Endo-
toxic shock with vascular collapse and DIC often develops in severe
meningococcal disease, but shock may be present in the advanced
stages of any bacterial meningitis. A finding of a systemic infection in
a patient with signs of potential meningeal irritation should encourage
rather than dissuade the clinician from considering the possibility of a
concomitant CNS infection.
Cerebral venous thrombosis occurs in approximately 1% of patients
with meningitis, likely due to coagulopathy induced by the robust CNS
immune response; this rare complication can manifest as new-onset
seizures, altered sensorium, and new focal neurologic deficits. Menin-
Fig. 95.1 A brain abscess which has developed adjacent to the site gococcemia may cause Waterhouse-Friderichsen syndrome, or bilat-
of a CSF shunt, as seen on MRI. CNS abscesses commonly develop eral adrenal hemorrhage, often accompanied by other signs of severe
adjacent to surgical sites, as this is one way bacteria can bypass the systemic infection such as DIC and purpura.
blood-brain barrier. The presentation of fungal meningitis can sometimes be subtle even
in the healthy adult population. Headache, low-grade fever, malaise,
patients, and high rates of intravenous drug use are contributing fac- and weight loss may be present but often to such a mild degree that
tors to an increase in the incidence of these abscesses, which are asso- CNS infection is not initially considered. Tuberculous meningitis,
ciated with high rates of permanent neurologic morbidity. Infection in contrast to other types of meningitis, can have a subacute or even
typically enters the epidural space via the blood but can also arise from chronic presentation, with symptoms developing months after onset
contiguous spread from nearby infections (e.g., psoas abscess, vertebral of infection. Cases can be vague and nonspecific, including fever,
osteomyelitis). weight loss, night sweats, and malaise, with or without headache and
meningismus. In some cases, CNS involvement may be the only mani-
CLINICAL FEATURES festation of tuberculosis, but CNS infection can also present alongside
pulmonary tuberculosis or disseminated (miliary) infection.
Meningitis
The clinical picture of bacterial and viral meningitis is classically Encephalitis
defined by fever, headache, photophobia, and nuchal rigidity. Unfortu- Encephalitis can occur from a viral, bacterial or fungal cause; it is not
nately, subtle presentations lacking these classic features are common. possible to definitively distinguish the etiology of the infection based
In immunosuppressed or geriatric patients, alteration in mental status on clinical features, although certain presentations can be suggestive.
may be the only finding, and therefore requires a lower threshold for Viral encephalitis can occur secondary to primary viral invasion of the
ruling out meningitis in these special populations. Clinical presenta- CNS, such as West Nile or rabies virus. Alternatively, it can be caused
tions in neonates may include a bulging fontanelle, but are often subtle, by reactivation of a previously dormant viral illness, such as varicella-
such as changes in behavior, decreased tone, or weakness as noticed zoster virus (VZV).
by parents; consequently, guidelines universally recommend a lum- The diagnosis of encephalitis requires an alteration of conscious-
bar puncture as part of the evaluation of a neonate with a suspected ness or behavior without another known cause. Fever, headache, sei-
infection. zures, and disorientation can be present. The symptoms exhibited
The physical findings in meningitis are variable depending on by the patient are representative of the affected area of the brain. For
patient factors (e.g., age, comorbidities), pathogen, and time course of example, HSV has a predilection for the temporal lobes and therefore,
the disease (early vs. late). Two classic exam maneuvers, the Kernig patients with HSV encephalitis can present with psychosis, personality
sign (inability to straighten leg to a position of full knee extension when or behavior changes, or hallucinations, occasionally prompting an ini-
patient is lying supine with hip flexed to a right angle) and Brudzinski tial diagnosis of a psychiatric disorder. A thorough skin and mucosal
sign (attempts to flex the neck passively are accompanied by flexion of examination may reveal the presence of herpetic lesions, as enceph-
the hips), have a low sensitivity of less than 12%; however, they have alitis can be associated with cutaneous outbreak in some cases. West
a high specificity and strongly suggest meningitis if they are present Nile virus can result in neuroinvasive disease resulting in a wide range
(Table 95.1).1 of symptoms, including muscle weakness, memory loss, behavioral
Patients with suspected meningitis should first be examined for changes, and difficulty concentrating. In cases of rabies encephalitis,
evidence of a structural lesion precipitating their symptoms, as these patients also present with agitation, extreme hydrophobia, and mus-
patients may require CT imaging to rule out other causes of their cular spasms.
symptoms. Signs of mass lesions can include papilledema, decreased
venous pulsations, new-onset seizures, abnormal level of conscious- Central Nervous System Abscess
ness, or focal neurologic deficits. An accurate fundoscopic exam can The most common finding in patients with an intracranial abscess is
be challenging to obtain and bedside ultrasound offers an alternative headache. Findings seen consistently in other CNS infections, such as
tool for assessing intracranial pressure.8 Patients without abnormal fever and altered mental status, may not be present. Most patients with
findings on neurologic examination may proceed to lumbar puncture intraparenchymal abscess have a subacute clinical course with symp-
without CT.9 toms progressing over 1 or more weeks. Just as with encephalitis, the
 CHAPTER 95 Central Nervous System Infections 1325

considerations are viral meningitis, acute subarachnoid hemorrhage

TABLE 95.1 Approximate Sensitivity,
(SAH), acute arterial dissection, and the noninfectious causes of men-
Specificity, Positive and Negative Likelihood ingitis including drugs, malignancy, or autoimmune conditions.
Ratios of Clinical Findings and Examination Distinguishing between viral and bacterial meningitis is described
Maneuvers for CSF Pleocytosis in Patients in the Diagnostic Testing section. Because subarachnoid blood is irri-
With Suspected Meningitis tating to the meninges, it will cause neck pain similar to meningitis,
Sensitivity Specificity LR+ LR-
but can be distinguished using CT imaging and LP. Generally, patients
with SAH and cervical artery dissection will lack associated infectious
Headache 91% 16% 1.1 0.5 symptoms and signs, such as a prodrome or fever.
Fever 30% 58% 0.7 1.2 In subacute meningitis, symptoms develop over a period of 1 to 7
Jolt accentuation 21% 82% 1.2 1.0 days. Although this time course makes viral meningitis most likely,
Kernig sign 2% 97% 0.8 1.0 bacterial and fungal etiologies remain possible. Brain tumor, spinal
abscess, infections outside the CNS such as osteomyelitis, and drug
Brudzinski sign 2% 98% 1.0 1.0
effects are potential diagnoses. Other considerations that may mimic
Nuchal rigidity 13% 80% 0.6 1.1
subacute meningitis include CNS malignancy, intracranial hemor-
Focal neurologic 2% 96% 0.5 1.0 rhage, brain abscess and nonconvulsive status epilepticus. CNS abscess
deficit should be considered especially if fever is minimal or absent or if there
Vomiting 4% 85% 0.3 1.1 are focal neurologic findings. Nonconvulsive status epilepticus is a con-
Rash 2% 96% 0.6 1.0 sideration in patients with altered mental status, especially if there is a
Physician suspicion 44% 40% 0.8 1.4 seizure history or a known structural brain lesion.
The spectrum of chronic meningitis includes the viral meningiti-
Adapted from Nakao JH, Jafri FN, Shah K, Newman DH. Jolt des, as well as meningitis caused by tuberculosis, syphilis, and fungi.
accentuation of headache and other clinical signs: poor predictors of Symptoms have generally been present in this group for at least 1
meningitis in adults. Am J Emerg Med. 2014;32(1):24–28. week and generally have a prolonged, indolent course. The potential
causes of culture-negative meningitis symptoms are broad and var-
symptoms exhibited by patients depends on the site affected by the ied, including rheumatologic, neoplastic, and medication-induced
abscess. For example, those with abscesses near the frontal lobe may symptoms. Generally, these atypical causes will present during the
present with disinhibited behavior, and abscesses near the motor cor- timeframe for chronic meningitis but may occasionally be seen with
tex may demonstrate focal weakness. Seizures occur in approximately a subacute course.
25% of patients. Abrupt neurologic deterioration and death can result Spinal epidural abscess should be suspected in patients with back
from abscesses that rupture into the ventricular system. pain accompanied by fever, back pain with neurologic deficits on exam,
Abscesses can also present in the epidural space in the spine, most or relatively rapid onset atraumatic back pain, though patients may not
commonly in the lumbar region.10 However, multiple areas may be always present with classic signs and symptoms. Patients with spinal
affected which can be discontiguous.11 Like brain abscesses however, surgery and instrumentation, IV drug abuse, and immunosuppres-
presentations can be nonspecific and mimic more benign causes of sion are at higher risk, and benefit from a lower threshold for testing.
back pain. The most common presenting symptom of an abscess within Epidural hematoma, osteomyelitis, discitis, aortic aneurysm rupture,
the epidural space is midline pain, which is present in the majority of aortic dissection, and pulmonary embolism are other considerations.
patients. Conversely, fever is only present in approximately half of
cases, particularly early in the course. Complications of a spinal abscess DIAGNOSTIC TESTING
primarily result from cord compression, including paralysis, motor
and sensory deficits, and bowel and bladder dysfunction. These defi- Blood Testing
cits may be permanent once they develop, even with prompt treatment, Currently, no test can substitute for cerebrospinal fluid analysis. The
making prompt diagnosis critical to avoid serious morbidity. complete blood count (CBC) with differential is a nonspecific adjunct
in the diagnostic evaluation of a patient suspected to have a CNS infec-
CSF Shunt Infection tion. However, a normal leukocyte count and differential does not rule
These infections typically manifest with signs of increased intracranial out the diagnosis of a CNS infection.
pressure and hydrocephalus such as headache, altered mental status, Procalcitonin has been shown in multiple studies to have some
nausea, and vomiting. They most often occur within 6 months of shunt value in the discrimination between bacterial and viral etiologies of
placement and are typically the result of skin flora being introduced meningitis. With an estimated sensitivity of 90% and specificity of 98%
into the CSF space. for bacterial infection, it may be useful as an adjunct when the clinical
picture is unclear, but it is currently not considered definitive to rule
out bacterial meningitis.12 In addition, elevation in serum erythrocyte
DIFFERENTIAL DIAGNOSES
sedimentation rate (ESR) and C-reactive protein (CRP) are potentially
The diagnoses of acute, subacute, and chronic meningitis and the other useful but not diagnostic in the differentiation of bacterial and viral
potential pathologies that must be considered vary based on the time meningitis.13
course of the presenting symptoms. Acute meningitis encompasses A serum glucose level is needed to interpret the CSF glucose level.
patients with clear signs and symptoms of meningitis who are eval- Although most patients do not require coagulation studies, patients
uated within 24 hours of the onset of their symptoms. While other who are taking warfarin should have their INR checked. Patients on
diagnoses can be considered during the initial evaluation, antibiotic direct oral anticoagulants can be checked for anti-Xa levels, if available,
therapy should be initiated as soon as possible in these patients to cover to assess for current anticoagulant activity. Coagulation status should
for the possibility of bacterial meningitis. In this group of patients with be considered in patients on anticoagulants prior to attempting a lum-
rapid onset of symptoms, the most important differential diagnostic bar puncture given the risk of bleeding complications.
1326 PART III Emergency Medicine by System

A B
Fig. 95.2 CT image of multiple brain metastases with surrounding edema. When evaluating for CNS infec-
tion, findings such as this may suggest that LP is unnecessary or unwise.

Blood cultures should be obtained for all patients who are being Lumbar Puncture
evaluated for a CNS infection, ideally on arrival. However, they may A lumbar puncture (LP) for CSF analysis is indicated whenever
still have benefit later in the patient’s course even if antimicrobial ther- meningitis or encephalitis is suspected unless the skin overlying the
apy has already been administered, because pneumococcal and menin- puncture site is infected or there is potential for brain herniation. In
gococcal infections may be identified in the blood of patients with the majority of patients with suspected meningitis who have no focal
these CNS infections. neurologic findings (including no altered mental status), LP can be
safely performed without delay and without preceding neuroimag-
Neuroimaging ing studies. Coagulation studies do not need to be routinely obtained
A CT scan without contrast of the head or magnetic resonance imaging prior to LP, but should be considered in those with personal or family
(MRI) scan of the brain is indicated in any patient with a suspected history of coagulopathy, use of anticoagulation medications, organ
CNS infection in which an intracranial hemorrhage or mass lesion is failure, or evidence of DIC. A platelet count below 40,000 should also
suggested by history or examination. Contrast studies are more sensi- prompt consideration for delaying an LP. An INR greater than 1.4 in
tive if a mass lesion is high on the differential (Fig. 95.2). A CT scan patients on warfarin is a relative contraindication to LP. The guide-
may show hypodense lesions in the temporal lobes in patients with lines for DOACs depend on the agent being used; ideally these should
HSV encephalitis, although an MRI scan reveals enhancement with be held at least 24 hours prior to an LP.15 The need for a LP cannot
greater sensitivity (Fig. 95.3). Neuroimaging should not delay antimi- be anticipated in most cases in the ED, however, and the emergent
crobial therapy, which can be initiated prior to imaging, and LP should need for the procedure must be weighed against the increased risk
still be obtained expeditiously. of bleeding.
A contrast-enhanced cranial CT or MRI scan is diagnostic for a Herniation has been described in patients following LP, hence the
CNS abscess, though the MRI is more sensitive. Large lesions are gen- recommendation to avoid a LP in patients with evidence of increased
erally visible on non–contrast-head CTs, although again, MRI is more intracranial pressure. A recent study showed the risk of herniation to be
sensitive and can show smaller lesions that may be mimicking menin- only 0.1% in the first hour following LP, suggesting that some reported
gitis or encephalitis. When evaluating for spinal abscess, CT imaging cases of herniation may be due to the infectious process itself.9 Regard-
of the spine is insufficiently sensitive. MRI of the entire spine is the less, at the present time, we recommend that LP be avoided in those
test of choice (Fig. 95.4), as lesions may be multiple and discontin- patients with the presence of papilledema, increased optic nerve sheath
uous, and can be difficult to localize by exam alone. In patients with diameter on ultrasound, mass lesions on CT imaging or other signs of
contraindications to MRI, a CT myelogram of the spine is an alter- increased ICP. Early initiation of antimicrobial therapy should not be
native, although definitive testing is preferred if possible due to the delayed pending LP for patients with high clinical suspicion for CNS
high morbidity associated with missed spinal abscess. Transfer to an infections. However, the CSF can be sterilized within as little as one hour
MRI-capable center may be appropriate if imaging is not available in post-antibiotics, so LPs should proceed as expeditiously as is feasible.
a timely manner. If the physician is unable to obtain CSF during the LP, consider-
Bedside ultrasound of the optic nerve sheath diameter is a rapid ation should be given to a prompt radiology-guided LP. If no LP can be
and accurate way to evaluate for increased intracranial pressure. This is performed, the blood cultures obtained on presentation may still be of
performed using a high-frequency probe placed over a closed eye. The assistance in identifying the causative microbe.
optic nerve can be assessed in either longitudinal or transverse planes
and measured 3 mm behind the globe of the eye;14 the upper limit of Opening Pressure
normal for optic nerve sheath dilation is 5 mm (Fig. 95.5). A diameter The normal upper limit of CSF pressure in an adult is 20 cm H2O. The
greater than 5 mm suggests increased intracranial pressure but does opening pressure is only valid for patients in the lateral recumbent
not distinguish among potential causes. position, because it may increase substantially when the patient is in
 CHAPTER 95 Central Nervous System Infections 1327

A B
Fig. 95.3 Temporal lobe enhancement on brain MRI. This is a common imaging finding in patients with HSV
encephalitis.

A B

C D
Fig. 95.4 Epidural abscess as seen on lumbar spine MRI. CT imaging may miss smaller spinal cord lesions
such as these.
1328 PART III Emergency Medicine by System

LOGIQ
E9

1+

+ + +2

LT ONSD
Fig. 95.5 The optic nerve sheath diameter using ultrasound is mea-
sured 3 mm behind the optic disc. This method can be used by the
clinician at bedside to quickly assess patients for increased intracranial
pressure. Fig. 95.6 CSF specimens after collection. The clear appearance, indis-
tinguishable from water, is a normal finding; any degree of cloudiness
can suggest CNS infection.
the sitting position. It may also be falsely elevated when the patient
is tense, has marked muscle contraction, or is obese. The pressure is
often elevated in bacterial, tuberculous, and fungal meningitides and a 1000 cells/mm3 with a neutrophil predominance (Table 95.2). How-
variety of noninfectious processes, and often normal in viral meningi- ever, the initial CSF analysis exhibits lymphocytosis (lymphocyte count
tis. There is little data however on the sensitivity and specificity of this greater than 50%) in approximately 10% of cases of bacterial meningi-
marker. As such, obtaining an opening pressure when possible prior tis. In some cases of L. monocytogenes meningitis, CSF analysis shows a
to collecting CSF provides an additional data point to support a viral cell count of less than 1000 cells/mm3 with lymphocyte predominance
or bacterial clinical picture but cannot be used in isolation. If CSF col- but near-normal CSF glucose levels. In viral meningitis, encephalitis,
lection requires the patient to sit up for mechanical reasons or patient tuberculous meningitis, or fungal meningitis, counts are typically less
comfort, opening pressure may be safely omitted. than 1000 cells/mm3 with lymphocyte predominance. However, early
(within 48 hours) viral presentations may reveal neutrophils and be
Cerebrospinal Spinal Fluid Analysis indistinguishable from presentations of bacterial meningitis. Treat-
When possible, at least three sterile tubes each containing 1 to 1.5 mL ment with antibiotics before the LP will decrease the yield of Gram
of CSF should be obtained and numbered in sequence. A fourth tube stain and cultures but likely does not affect the CSF cell counts or total
is desirable in case additional studies are later necessary. The fluid CSF protein in meningitis.
should then be sent to the laboratory for immediate analysis of turbid- A traumatic LP is suggested by the presence of 10,000 or more red
ity, xanthochromia, glucose, protein, cell count and differential, Gram blood cells (RBCs)/mm3 or fewer RBCs in the final tube than in the
stain, and bacterial culture. When only a small amount of fluid can initial tube. In the presence of a traumatic LP, the CSF white blood cell
be obtained, the most important studies are the cell count with dif- (WBC) pleocytosis can be estimated by subtracting one leukocyte for
ferential, the Gram stain, and culture. Depending on the clinical sce- every 500 to 1000 RBCs.
nario and patient risk factors, such as HIV, immunosuppression, travel Normal CSF cell counts, although reassuring, do not completely
history, or exposures, additional testing can be valuable as well. These exclude bacterial meningitis, especially in immunocompromised
studies can include cryptococcal antigens, acid-fast bacilli stain, or the patients. Lumbar puncture for brain abscess is unlikely to offer diag-
Venereal Disease Research Laboratory (VDRL) test for neurosyphilis. nostic yield except in cases of abscess rupture into the ventricular
Ideally, a cell count should be performed on both the first and last tubes space. Although abnormalities can be seen, the CSF can also be entirely
collected to help differentiate true CSF pleocytosis from contamination normal. Lumbar puncture is generally contraindicated in cases of spi-
of the specimen by peripheral blood from a traumatic LP. nal epidural abscess due to concern for seeding the infection.
The CSF should be assessed immediately for turbidity or cloudi-
ness by the person performing the LP. Normal CSF is completely clear,
Gram Stain
colorless, and indistinguishable from water (Fig. 95.6); any degree of A Gram stain of a CSF specimen may identify the causative organism
turbidity is pathologic. Changes in CSF clarity can generally be seen up to 75% of the time in cases of bacterial meningitis, however this
when leukocyte counts are greater than 200 to 500 cells/mm3. is highly dependent on the concentration of the bacteria present. The
yield is diminished to 40% to 60% when there has been prior treatment
Cerebrospinal Spinal Fluid Cell Count with antibiotics.16 Gram-stain appearance of the CSF of a patient with
Normal adult CSF contains no more than 5 leukocytes/mm3 with at N. meningitidis is shown in Figure 95.7.
most one granulocyte (polymorphonuclear [PMN] leukocyte); the
presence of more than one PMN or a total cell count of more than 5 Xanthochromia
cells/mm3 is evidence of CNS infection. The presence of any eosino- Xanthochromia is the yellowish discoloration of the supernatant of
phil in the CSF is abnormal; occasionally basophils may be seen in the centrifuged CSF specimens, detectable by visual inspection or spectro-
absence of disease. The cell counts in bacterial meningitis often exceed photometry. Xanthochromia is an abnormal finding and is concerning
 CHAPTER 95 Central Nervous System Infections 1329

TABLE 95.2 Typical CSF Findings for Various Etiologies of Meningitis and Encephalitis
Normal Bacterial Viral Fungal/TB
Pressure (cm H20) 5–20 >30 Normal or increased Increased
Protein (mg/dL) 18–45 Increased Normal or increased Normal or increased
Glucose 2/3 serum glucose Decreased Normal Normal or decreased
Gram stain Negative 60–90% positive Negative Negative
White blood cells <5 Usually >1000 100–1000 50–500
WBC differential predominance None Neutrophils Lymphocytes Lymphocytes or monocytes

viral encephalitis, neoplasms, and demyelination syndromes. HSV and

VZV can have higher CSF protein values than are typically seen in viral
CNS infection (>100 mg/dL).

Other Stains
Historically, an India ink staining of the CSF was performed to diagnose
cryptococcal meningitis. Though it is a rapid means of diagnosis, it has
poor sensitivity (as low as 30% in non-AIDS patients). Cryptococcal
antigen testing is now the gold standard for investigating cryptococcal
infection, with baseline serum and CSF antigen titers providing a good
estimate of fungal burden and prognosis but not response to therapy.
Latex agglutination and enzyme immunoassay techniques have high
sensitivity for cryptococcus as well but are inferior to antigen testing.
Acid-fast bacilli (AFB) staining has been used for diagnosis of tubercu-
Fig. 95.7 The Gram stain appearance of a CSF sample infected with N. lous meningitis but has poor sensitivity (typically <60%).
meningitidis, a gram-negative coccus. Magnification 1000x.
Lactic Acid
for SAH when detected. It results from the lysis of RBCs with the The normal reference range for CSF lactate is between 0.88 to 2.7 mmol/L.
release of the breakdown pigments oxyhemoglobin, bilirubin, and met- Although nonspecific, elevations in CSF lactic acid concentrations are sus-
hemoglobin into the CSF. This process takes hours to occur, though in picious for bacterial meningitis, while normal lactate levels (<2.7 mmol/L)
patients presenting between 12 hours and 2 weeks of symptom onset, are usually seen in patients with viral causes of meningitis. Recent studies
the sensitivity is close to 100% if analyzed using spectrophotometry. have shown CSF lactate to have excellent predictive value in differentiat-
Visual inspection of the centrifuged specimen has been found to be ing bacterial from viral meningitis,17 and CSF lactate may be useful as an
much lower (47%). If a traumatic tap has introduced enough plasma to adjunct in the workup of suspected meningitis. We recommend its use,
raise the CSF protein level to 150 mg/dL or more, blood pigments may when available, to aid in determining the cause of CNS infection.
cause xanthochromia. If the CSF protein level is less than 150 mg/dL,
however, xanthochromia of a centrifuged CSF specimen almost always Antigen Detection
indicates that a SAH has occurred. Nucleic acid amplification tests such as PCR have sensitivities of 67%
to 100% for H. influenza, 79% to 100% for S. pneumoniae, and 91%
Glucose to 100% for N. meningitides; specificities are nearly 100% for all three
The CSF glucose level is normally two-thirds of the serum glucose; organisms.1 The value of antigen testing has been demonstrated in mul-
when the serum glucose is within normal range, the CSF glucose is tiple studies in which acute bacterial meningitis was confirmed only by
usually between 50 and 80 mg/dL. In the first 4 hours after food intake PCR.1 The sensitivity of bacterial culture is much lower and varies con-
or parenteral glucose administration, however, the ratio is decreased, siderably based on the specific causative microorganism; under ideal
and the results are difficult to interpret with certainty. A CSF-to-serum conditions, cultures may miss a third of organisms, and sensitivity can
glucose ratio of less than 0.5 in normoglycemic subjects is abnormal be even lower if the patient has been treated with antibiotics. PCR test-
and may represent the impaired glucose transport mechanisms and ing has been demonstrated to have a sensitivity of 70% despite antibi-
increased CNS glucose use associated with bacterial meningitis. Mild otic therapy up to 1 week following initiation of treatment.18
decreases in the CSF glucose level may occur in viral, fungal, or tuber- Antigen and antibody testing have particular utility in HSV enceph-
culous meningitis. However, bacterial meningitis should be presumed alitis. Although enzyme-linked immunosorbent assays (ELISAs) can
to be the cause of low CSF glucose until it is clearly excluded. detect HSV antibody production, the appearance of antibodies in CSF
occurs too late to aid in any therapeutic decision analysis. PCR ampli-
Protein fication and the identification of HSV DNA have a sensitivity of 96%
The normal CSF protein level in adults is typically below 45 mg/dL. An and a specificity of 99% early in the disease, such that brain biopsy is
elevated CSF protein (higher than 100 mg/dL) commonly occurs with no longer needed to make this diagnosis. PCR testing is sensitive for
acute bacterial meningitis. When a traumatic LP has occurred, the CSF other viral infections as well, including VZV and enterovirus, though
protein can be corrected for the presence of blood by subtracting 1 mg/ identification of the exact virus usually does not affect management.
dL of protein for each 1000 RBCs. Elevated CSF protein concentrations Diagnosis of VZV encephalitis is further improved by testing for IgG
can result from any cause of meningitis, SAH, CNS vasculitis, syphilis, and IgM antibodies in the CSF.
1330 PART III Emergency Medicine by System

TABLE 95.3 Common Bacterial Pathogens and Initial Antibiotic Regimens for Suspected
Bacterial Meningoencephalitis,a Listed by Age Group and Risk Factors
Patient Subgroup Most Common Bacterial Pathogen Most Common Intravenous Therapy
Neonates (up to 4 weeks) S. agalactiae, E. coli, L. monocytogenes, S. agalactiae, Ampicillin (100 mg/kg/dose q8h for 0-7 days and 75 mg/kg/dose for
gram-negative bacilli 8-28 days) AND Cefotaxime (50 mg/kg every 8 hrs; may increase to
50 mg/kg q6h for 8-28 days)
Infants and children S. pneumoniae, N. meningiditis Ceftriaxone (100 mg/kg every day) OR Cefotaxime (75 mg/kg every
6 hrs)
Adults S. pneumoniae, N. meningiditis Ceftriaxone (2 g every 12 hrs) OR Cefotaxime (2 g q4–6h) AND
Vancomycin (loading dose: 20–35 mg/kg actual body weight [not to
exceed 3000 mg] or 20–25 mg/kg actual body weight not to exceed
3000 mg in patients with obesity, then 15–20 mg/kg actual body
weight every 8–12 hrs)
Elderly S. pneumoniae, N. meningiditis, L. monocytogenes Ceftriaxone (2 g every 12 hrs) OR Cefotaxime (3 g every 6 hrs) AND
Vancomycin (loading dose: 20–35 mg/kg actual body weight [not to
exceed 3000 mg] or 20–25 mg/kg actual body weight not to exceed
3000 mg in patients with obesity, then 15–20 mg/kg actual body
weight every 8–12 hrs) AND Ampicillin (2 g every 4 hrs)
Immunocompromised S. pneumoniae, N. meningiditis, H. influenzae Ceftriaxone (2 g every 12 hrs) OR Cefotaxime (3 g every 6 hrs) AND
Vancomycin (loading dose: 20–35 mg/kg actual body weight [not to
exceed 3000 mg] or 20–25 mg/kg actual body weight not to exceed
3000 mg in patients with obesity, then 15–20 mg/kg actual body
weight every 8–12 hrs) AND Ampicillin (2 g every 4 hrs)
Suspected hospital-acquired S. aureus, S. epidermidis, aerobic gram-negative bacilli Vancomycin (15–20 mg/kg every 8 hrs) AND Cefepime (2 g every 8
organism hrs) OR Meropenem (2 g every 8 hrs)
Adapted from Dorsett M, Liang SY. Diagnosis and treatment of central nervous system infections in the emergency department. Emerg Med Clin
North Am. 2016;34(4):917-942.25
aIn addition to dexamethasone (adults 0.4 mg/kg IV, up to 10 mg; infants and children 0.15 mg/kg, up to 10 mg

PCR has improved the diagnosis of tuberculous meningitis as well MANAGEMENT

and newer assays continue to show improved performance character-
istics. One of the latest assays, Xpert Ultra, was recently shown to have Initial management of the patient with suspected CNS infection focuses
a sensitivity of 95% (compared to previous assays and culture with a on ensuring CNS oxygenation and perfusion. In cases of severely ele-
45% sensitivity) and has been endorsed as the initial diagnostic test of vated ICP, management is with endotracheal intubation, mannitol,
choice by the World Health Organization.19 hypertonic saline, and maintenance of eucapnia on the ventilator.

Bacterial Cultures Bacterial Meningitis

Bacterial cultures of CSF should be performed despite some organisms, such Treatment of bacterial meningitis requires bactericidal antibiotics
as mycobacterium, being difficult to culture. Although results of cultures will that penetrate the blood-brain barrier and achieve therapeutic CSF
not be available in the ED, they can be helpful to the subsequent treatment concentrations. Until the causative organism is identified, broad-
team for guiding antimicrobial therapy if positive. Bacterial culture yields spectrum coverage of the most common pathogens is indicated (Table
can be decreased in patients pretreated with antibiotics, depending on the 95.3). Ceftriaxone (2 g every 12 hours) or cefotaxime (3 g every 6
timing of the antibiotics and the cultures. Although antigen testing holds hours) are the most commonly used agents, with vancomycin (15–20
promise, it alone cannot replace bacterial cultures at this time. mg/kg every 8 hours) added to cover potentially resistant organ-
isms. In neonates, especially those with hyperbilirubinemia, ceftri-
Additional Investigations axone should be avoided, because it displaces bilirubin from albumin
Other ancillary investigations such as echocardiography, body fluid binding sites and can further increase bilirubin levels in the blood.
cultures, chest X-ray, CT of the maxillary region, and urinalysis may be Cefotaxime is instead recommended in this population. We recom-
undertaken as necessary to evaluate suspected coexistent disease, such mend high-dose ampicillin (2 g every 4 hours) be added in adults
as a distant infection that may be seeding the CNS. over 50 years old and infants younger than 1 month old (100 mg/kg/
Characteristic EEG abnormalities have been associated with HSV dose q8h for 0–7 days and 75 mg/kg/dose for 8–28 days) because they
type 1 encephalitis, including diffuse high-amplitude slow waves, tem- are at risk for Listeria. If Listeria meningitis is suspected, gentamicin
poral lobe spike-and-wave activity, and periodic lateralized epilep- may also have a mortality benefit if added to ampicillin, though this
tiform discharges, although these changes are not specific enough to should be used cautiously in patients with renal dysfunction.
make them diagnostic. More than half of patients with viral encephali- Patients who have had a recent hospitalization, especially for sur-
tis may have an abnormal EEG, most commonly in patients with HSV; gery, may be at risk for hospital-acquired antibiotic-resistant organ-
it is not routine however to obtain an EEG emergently in the ED and isms and may benefit from broader coverage with cefepime (2 g every
EEG is unlikely to acutely change management unless nonconvulsive 8 hours) instead of ceftriaxone. In patients allergic to cephalosporins,
status epilepticus is diagnosed. meropenem or chloramphenicol is recommended. Linezolid (600 mg
 CHAPTER 95 Central Nervous System Infections 1331

every 12 hours) or moxifloxacin (400 mg once daily) with vancomycin two common causes of this disease. Patients with CMV encephalitis
can be used in cephalosporin-resistant strains of pneumococcus. can be treated with ganciclovir (5 mg/kg every 12 hours), although this
Treatment with corticosteroids (0.15 mg/kg up to 10 mg IV dexa- diagnosis is unlikely to be made in the ED. Otherwise, patients should
methasone every 6 hours for 4 days) decreases mortality in patients largely be treated supportively.
with pneumococcal meningitis and decreases the incidence of hearing
loss in patients with H. influenzae meningitis. Interestingly, this benefit Central Nervous System Abscess
has only been shown in high-income countries and not in low-income The location, size, and number of abscesses influences the choice of
countries, likely secondary to better access to medications and special- medical management, surgical excision, or aspiration. Consideration
ist care in the former.20 Though some data suggest benefit persists if of empiric antimicrobial therapy is ideally accomplished in consul-
started within 12 hours of antibiotic initiation, the first dose of steroids tation with neurosurgical providers, as it is reasonable to withhold
should be given with or 20 minutes before initiation of antibiotics in antimicrobial therapy prior to aspiration or surgical excision if an
suspected adult bacterial meningitis. However, a recent large, prospec- urgent neurosurgical intervention is planned. If neurosurgery is
tive study showed an increased incidence of adverse outcomes related delayed, however, we recommend initiating empiric treatment, as
to dexamethasone in cases of Listeria CNS infections and therefore ste- prolonged time without antibiotics has been associated with adverse
roids should be discontinued if this organism is identified.21 outcomes.
Abscesses originating from sinus or ear infections are treated with
Tuberculous Meningitis cefotaxime (2 g IV every 4-6 hours) or ceftriaxone (2 g IV every 12
Early antimicrobial intervention in acute tuberculous meningitis hours) plus metronidazole (500 mg IV every 6 to 8 hours). Abscesses
improves the patient’s prognosis and a strong clinical suggestion of this related to trauma or neurosurgical procedures require vancomycin for
disease is an appropriate indication to begin antituberculous therapy. A S. aureus or methicillin-resistant S. aureus coverage. Patients at high
standard treatment regimen consists of 4-drug therapy with isoniazid (5 risk for tuberculous, fungal, or parasitic abscess may also receive cov-
mg/kg once daily; max dose 300 mg), rifampin (20 to 30 mg/kg once erage for the suspected etiologic agent. Corticosteroids may mitigate
daily; max dose 600 mg), pyrazinamide (<40 kg: 35 mg/kg/dose; 40 to 55 superimposed cerebral edema and a recent meta-analysis did not show
kg: 1000 mg daily; 56 to 75 kg: 1500 mg daily; 76 to 90 kg: 2000 mg daily), an increase in mortality with their use.22 We therefore recommend
and ethambutol (<40 kg: 25 mg/kg/dose; 40 to 55 kg: 800 mg daily; 56 10 mg IV dexamethasone for CNS abscesses associated with cerebral
to 75 kg: 1200 mg daily; 76 to 90 kg: 1600 mg daily). Alternative dosing edema.
strategies exist that involve less-frequent dosing and can be considered Spinal epidural abscesses should also be managed with a combined
with infectious disease consultation. Neurosurgical consultation may be medical and surgical approach. Neurosurgical consultation should be
required in cases of hydrocephalus or mass lesions. Corticosteroids have obtained as soon as possible to evaluate the need for emergent inter-
also been shown to decrease secondary complications, and we recom- vention, particularly if neurologic deficits are present. Additionally, we
mend an initial dose of 0.15 mg/kg of IV dexamethasone. recommend empiric vancomycin (loading dose: 20 to 35 mg/kg actual
body weight [not to exceed 3000 mg] or 20 to 25 mg/kg actual body
Fungal Meningitis weight not to exceed 3000 mg in patients with obesity, then 15 to 20
Because fungal meningitis most often has a prolonged course and can mg/kg actual body weight every 8 to 12 hrs) and ceftriaxone (2 g IV
be difficult to diagnose in the ED, the initiation of antifungal treat- every 12 hours) for antimicrobial treatment. When atypical organisms
ment is rarely required in the ED unless clinical suspicion is high. Four such as Pseudomonas are present or suspected, broader coverage is rec-
agents are commonly used to treat fungal meningitis: amphotericin B, ommended with a fourth-generation cephalosporin (e.g., cefepime 2 g
flucytosine, miconazole, and fluconazole. Of these, amphotericin B, IV every 8 hours).
either alone or in combination with flucytosine, is the most common
regimen. Fluconazole can be used if flucytosine is not available and can CSF Shunt Infection
be used as monotherapy if amphotericin B is not available, though it is After obtaining neuroimaging (either CT or rapid MRI protocol), man-
associated with higher rates of treatment failure. agement generally includes neurosurgical consultation and empiric
antibiotics directed at skin flora, including S. aureus and Streptococ-
Viral Meningitis cus as well as MRSA and Pseudomonas. We recommend vancomycin
The majority of viral meningitis cases have a short, relatively benign (loading dose: 20 to 35 mg/kg actual body weight [not to exceed 3000
and self-limited course followed by a complete recovery. Acyclovir (10 mg] or 20 to 25 mg/kg actual body weight not to exceed 3000 mg in
mg/kg IV every 8 hours) is recommended in immunocompromised patients with obesity, then 15 to 20 mg/kg actual body weight every 8
patients with HSV meningitis and should be considered based on the to 12 hrs) and an anti-pseudomonal beta-lactam, such as cefepime (2
theoretical benefit in immunocompromised patients with VZV men- g every 8 hours).
ingitis. Benefit has not been shown in HSV or VZV meningitis in
immunocompetent patients. In these cases, as with most types of viral Chemoprophylaxis
meningitis, care is mainly supportive, because no treatments have been The risk for developing meningococcal meningitis is increased 400
shown to be effective for relieving symptoms, shortening the course of to 800 times in individuals with close contact with an infected per-
disease, or preventing disease progression. son. Close contacts at risk include health care workers exposed to the
Early cases of viral meningitis may be indistinguishable from bacte- patient’s secretions (as might occur during endotracheal intubation
rial meningitis, and diagnostic certainty may not be provided by initial or nasotracheal suctioning), those exposed for a prolonged period
CSF analysis. When doubt exists about the veracity of the diagnosis, it (e.g., spending more than 8 hours less than three feet away from
is reasonable to initiate workup and empiric antibiotics and admit the the patient such as roommates, intimate partners, daycare atten-
patient to the hospital. dants) or those exposed to an infected person’s oral excretions. At
risk contacts should be treated with four doses of oral rifampin (600
Viral Encephalitis mg every 12 hours) or a single dose of oral ciprofloxacin (500 mg).
In cases of suspected viral encephalitis, empiric IV acyclovir (10 mg/ Pregnant women can receive a single intramuscular (IM) dose of cef-
kg IV every 8 hours) is recommended as it targets both HSV and VZV, triaxone (250 mg). In addition, close contacts should be advised to
1332 PART III Emergency Medicine by System

TABLE 95.4 Recommended Population for Prophylaxis and Antibiotic Dosing Regimens,
Listed by Exposure Type
Population Medication Dose Frequency
N. meningitidis Close contacts (roommates, partners, daycare workers), Ciprofloxacin 500 mg Once
health care workers exposed to secretions Rifampin 600 mg Every 12 hours for 2 days
Ceftriaxone 250 mg Once (preferred in pregnancy)
H. influenzae Immunocompromised children (including unvaccinated), Rifampin 20 mg/kg Daily for four days
contacts with unvaccinated children <4 years old
All others (bacterial, viral, fungal) All None None None

watch for fever, sore throat, rash, or any symptoms of meningitis. The development of a highly effective pneumococcal vaccine has
If there are signs of active meningococcal disease, the close contact been hampered by the large number of serotypes of the organism.
should be hospitalized for IV antibiotics as presented above, because Despite this, a single dose of the vaccine should be considered for
rifampin is not recommended as therapy against invasive meningo- elderly or debilitated patients, especially those with pulmonary disease,
coccal disease. and for patients with impaired splenic function, splenectomy, or sickle
Rifampin prophylaxis (20 mg/kg once daily; max dose 600 mg for cell anemia. Vaccination against pneumococcus is recommended in
four days) is currently recommended by the Centers for Disease Con- patients who have been treated for an episode of pneumococcal pneu-
trol (CDC) for contacts of patients with H. influenzae meningitis in monia to prevent recurrent infection. A heptavalent conjugated pneu-
households with members aged younger than 4 years who have not mococcal vaccine has also been developed and is recommended for
completed their vaccination schedule or immunocompromised chil- universal childhood immunization by the ACIP.
dren (<18 years old), regardless of their vaccination status. It is only A conjugate vaccine effective against Hib has been developed for
recommended in childcare facilities caring for immunocompromised use in the pediatric population and is recommended for all infants
or unvaccinated children in instances where two confirmed cases have starting at 2 months.
occurred. There is no current recommendation for chemoprophylaxis
in pneumococcal meningitis. See Table 95.4 for a summary of the
guidelines.
DISPOSITION
With the exception of obvious presentations of viral meningitis, the
Immunoprophylaxis majority of CNS infections require inpatient evaluation and treatment
Although vaccinations against pathogens implicated in CNS infection for IV antimicrobials, monitoring for acute decompensation, follow-
are not routinely administered in the ED, it is useful to be aware of ing of cultures, specialist input, and potential surgical intervention,
currently available vaccinations so that patients and family members depending on the infection. Because normal CSF cell counts do not
may be queried regarding their risk for vaccine-preventable diseases. completely exclude bacterial meningitis, patients with a high likeli-
A quadrivalent meningococcal vaccine based on the polysaccharide hood of meningitis require hospitalization with frequent reevaluation,
capsule and conferring protection against group A, C, Y, and W-135 antimicrobial therapy, and possible repeat LP.
meningococci has been in routine use since it was approved in 1978. It Some patients with suspected viral meningitis should be consid-
is currently recommended for routine use in children and adolescents ered for hospitalization. These include patients who are immunocom-
aged 11 to 21 years old. People living in close quarters with other indi- promised, patients with more severe disease or refractory symptoms,
viduals (e.g., college students, military recruits), travelers to endemic patients who are unable to tolerate oral intake, and those in whom the
areas, as well as asplenic individuals are at increased risk of meningo- diagnosis is unclear.
coccal disease and should receive the vaccine. Two vaccines targeting The references for this chapter can be found online at ExpertConsult.
serogroup B also have been approved for use in the United States since com.
2014 but have yet to be routinely administered. The capsular polysac-
charide vaccines used to immunize adults are not protective in children
younger than 2 years old because of poor antibody response.
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Infect. 2016;22(suppl 3):S37–S62. 14. Millington SJ, Silva Restrepo M, Koenig S. Better with ultrasound: lumbar
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2006-2015. J Infect. 2019;78(3):208–214. antithrombotic management for lumbar puncture: Association of British
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2019;25(2):325–327. MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a
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outcome of brain abscess: systematic review and meta-analysis. Neurology. 20. Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids
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diagnosing increased intracranial pressure: a systematic review and meta- 21. Charlier C, Perrodeau É, Leclercq A, et al. Clinical features and prognostic
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A, de Beek DV. [Cranial computed tomography, lumbar puncture and 22. Simjian T, Muskens IS, Lamba N, et al. Dexamethasone administration
clinical deterioration in bacterial meningitis: a nationwide cohort study]. and mortality in patients with brain abscess: a systematic review and
Ned Tijdschr Geneeskd. 2019:163. meta-analysis. World Neurosurg. 2018;115:257–263.
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CHAPTER 95: QUESTIONS AND ANSWERS

1. Which of the following presentations should receive a lumbar infection. Treatment should not be delayed obtaining neuroimaging
puncture to rule out CNS infection: first (if necessary), or until the lumbar puncture is completed. How-
a. 23-year-old healthy female with fever and stiff neck but minimal ever, lumbar puncture should still be obtained expeditiously, because
headache. culture yields begin to decrease after 1 hour.
b. 32-year-old male with diabetes and unexplained altered mental 3. Which of the following antimicrobial regimens would be appropri-
status. ate coverage for suspected meningitis in a 40-year-old patient with
c. 67-year-old male with fever and new right arm weakness. no comorbidities in a country with high antibiotic use?
d. All of the above a. Ceftriaxone
Answer: D. All patients with fever, headache, altered mental status or b. Ceftriaxone and vancomycin
new neurologic deficits should be considered for possible meningitis c. Acyclovir and ceftriaxone
or encephalitis. Lumbar puncture and CSF analysis is the most reliable d. Cefotaxime, vancomycin, and ampicillin
method for assessing for CNS infection; imaging and blood tests are Answer: B. Ceftriaxone and vancomycin are the appropriate initial
inadequate alone. antibiotics for suspected meningitis or encephalitis in an adult patient.
2. Patients with suspected bacterial meningitis should receive which Ceftriaxone alone may be appropriate in lower income countries with
of the following interventions FIRST? less antibiotic use and resistance. Ampicillin is added for patients older
a. Non-contrast CT of the head than 50 years and neonates due to risk of Listeria. Acyclovir should
b. MRI with contrast of the head be added for immunocompromised patients with suspected HSV or
c. Lumbar puncture to evaluate for bacterial cause VZV infections. Cefepime should be used instead of ceftriaxone in
d. Steroids and antibiotics for presumed bacterial infection patients at his risk for pseudomonas infections (e.g., recent surgical
Answer: D. Patients with suspected bacterial meningitis should receive procedures).
steroids and antibiotics first to cover for the possibility of bacterial

1332.e1
1332.e2 References

CHAPTER 95: QUESTIONS AND ANSWERS—cont’d.

4. What is the most appropriate imaging test for a patient with low 5. Contacts with exposure to which of the following types of meningo-
back pain, low-grade fever, and a history of IV drug use? encephalitis should receive prophylactic antibiotics?
a. CT lumbar spine without contrast a. Pneumococcal
b. CT myelogram of the lumbar spine b. Tuberculous
c. MRI of the lumbar spine with contrast c. Meningococcal
d. MRI of the cervical, thoracic and lumbar spine with contrast d. West Nile
Answer: D. Because exam findings can be inaccurate, patients with Answer: C. Close contacts with exposure to patients diagnosed with
suspected epidural abscess should receive an MRI with contrast of their meningococcal meningitis or encephalitis should receive chemopro-
entire spine. Presentations can be subtle and may not include all of the phylaxis, most commonly with oral rifampin. Chemoprophylaxis is
classical features such as fever and back pain; patients must be que- also recommended for immunocompromised close contacts of patients
ried for potential risk factors. CT myelogram of the entire spine is an with H. influenzae CNS meningitis.
acceptable alternative for patients unable to undergo an MRI.