Meningitis and Encephalitis Table of Contents

Emergency Neurological Life Support

Meningitis and Encephalitis Protocol
Version 5.0

Authors
Vikram Dhawan, MD
Jennifer McGuire, MD
Katharina M. Busl, MD, MS

Last updated: May 2022

2
 Meningitis and Encephalitis Table of Contents

Meningitis and Encephalitis Algorithm

[Grab your
reader’s
attention
with a great
quote from
the
document or
use this
space to
emphasize a
key point.
To place
this text box
anywhere
on the page,
just drag it.]

3
 Meningitis and Encephalitis Table of Contents
Meningitis and Encephalitis Algorithm ........................................................................................3
Checklist ......................................................................................................................................5
Communication ...........................................................................................................................5
Suspicion of Meningitis or Encephalitis .......................................................................................6
Fever, headache, altered mental status, stiff neck ..................................................................6
Begin Resuscitation, Start Antibiotics .........................................................................................8
Empirical treatment ..................................................................................................................8
Head CT if Indicated .................................................................................................................18
Lumbar Puncture .......................................................................................................................20
Rapid assessment of spinal fluid ...........................................................................................20
Normal LP .................................................................................................................................21
Rules out meningitis and encephalitis ...................................................................................21
Evaluate for Other Diagnoses ...............................................................................................21
Very High WBCs .......................................................................................................................22
WBCs > 100-1000 .................................................................................................................22
Suspicion of Bacterial Meningitis ...........................................................................................22
Elevated WBCs and no RBCs ...................................................................................................23
Probably viral meningitis ........................................................................................................23
Viral meningitis or viral (non-herpes) encephalitis treatment .................................................23
Elevated WBCs and RBCs ........................................................................................................24
Consider herpes encephalitis ................................................................................................24
Empirical treatment and diagnosis of herpes encephalitis ....................................................24
Elevated WBCs and Very High Total Protein ............................................................................25
Fungal or TB Meningitis .........................................................................................................25
Elevated RBCs, Xanthochromia ................................................................................................26
Likely Subarachnoid Hemorrhage .........................................................................................26
Management of SAH .............................................................................................................26

4
 Meningitis and Encephalitis Protocol

Checklist
☐ Vital signs, history, examination
☐ Contact and droplet precautions (until pathogen classified)
☐ IV access
☐ Labs: CBC, PT/PTT, chemistries, glucose, blood cultures, lactate
☐ IV fluids, treat shock
☐ Immediate administration of dexamethasone followed by appropriate antibiotics for
presumptive bacterial meningitis
☐ Consider acyclovir (if herpes simplex virus is a concern)
☐ Head CT, if patient neurological exam abnormal
☐ Lumbar puncture (LP), if CT results available
☐ If meningococcus remember exposure prophylaxis for contacts

Communication
☐ Presenting signs, symptoms, vital signs on admission and relevant past medical history
☐ Relevant laboratory results including white blood cell count, bicarbonate level, lactate level,
and renal function
☐ Head CT and results if obtained
☐ IV fluid administered, input/output
☐ Antibiotics administered and time started; dexamethasone if given
☐ Results of LP (if able to be performed), including opening pressure
☐ Current vital signs, pretransfer physical and neurological exam
☐ Ongoing concerns, active issues, outstanding studies/tests
☐ Infectious precautions applied/required

5
 Meningitis and Encephalitis Protocol
Suspicion of Meningitis or Encephalitis
Fever, headache, altered mental status, stiff neck
Patients that have a hyper-acute (hours) and acute (hours to days) onset of headache and
altered mental status should be considered to have meningitis or encephalitis. Additional signs
of meningismus, fever, new rash, focal neurological findings or new onset seizure significantly
increase the suspicion of CNS infection.

Infants often have non-specific manifestations of CNS infection such as fever, hypothermia,
lethargy, irritability, respiratory distress, poor feeding, vomiting, or seizures. In older children,
clinical manifestations include fever, headache, photophobia, nausea, vomiting, and decreased
mental status.

As with all acute medical and neurological events, the basics of ABC (airway, breathing and
circulation) should be evaluated early in the Emergency Department course. Patients with
altered mental status are at high risk for airway compromise and should be monitored closely
for needing intubation. Likewise, patients with bacterial meningitis are at risk for lung or
bloodstream infections with the same pathogen, and as such, vital signs and hemodynamics
need to be monitored closely to diagnose sepsis.

Meningitis is defined as inflammation of the meninges (and will have an abnormal LP) while
encephalitis is defined as inflammation of the brain (and the LP is usually normal). If both are
inflamed, the patient has meningoencephalitis. Meningitis causes fever, meningismus (flexion
limitation of neck when fully supine), and pain (head and/or neck) but other than depressing a
patient’s mental status, does not affect any cortical function. Encephalitis on the other hand
typically causes cortical disturbances (seizures, aphasia, hemiparesis, etc.). In pure
encephalitis, the spinal fluid is free of white cells, but protein may be elevated. Once white
cells are found in the spinal fluid, some form of meningitis is also present.

The two conditions that are most important to recognize in the first hour are bacterial
meningitis and herpes encephalitis as these diseases have specific treatments that can
improve patient outcome if administered quickly.

Fever
Measuring oral temperature is adequate. Both fever (temperature > 38°C) or hypothermia
(temperature < 35°C) are compatible with CNS infection. If the patient is euthermic, the pretest
probability of bacterial meningitis or HSV encephalitis is decreased. However, newly
immunocompromised patients, patients with viral meningitis, and even a rare patient with
bacterial meningitis may present euthermic. Depending on other signs and symptoms, it may
be appropriate to stop here and work-up other causes of headache.

Headache
The presence of a new, never experienced headache is a significant symptom that needs
work-up on its own merits. If the headache is sudden in onset (i.e. a thunderclap headache
within seconds) this suggests subarachnoid hemorrhage (SAH). Patients with SAH can have
fever because blood in the meninges causes a chemical meningitis. If the headache is typical

6
 Meningitis and Encephalitis Protocol
of the patient’s usual headache, one should not completely dismiss this symptom’s importance
as meningitis and encephalitis will cause exacerbation of a pre-existing headache disorder.
Lastly, it is quite uncommon to have meningitis without headache or neck pain, but less
uncommon in encephalitis.

Altered Mental Status

CNS infections typically depress the level of consciousness (see the ENLS protocol Coma).
Neonates may be lethargic, stop eating, and become irritable, have pale or marble skin and
hypo or hypertonia. As an individual ages, children may have symptoms more defined than a
neonate such as headache, nausea, vomiting, seizures. Adults typically become somnolent
then stuporous. Adults may also have more specific signs such as neck stiffness and fever.
Delirium is common with the chief objective sign of inattentiveness (can’t repeat back serial
digits). Sepsis can compound the mental status if significant hypotension is present. Elderly
patients or patients with pre-existing neurological conditions may become agitated and
combative.

Stiff Neck/Meningismus
Meningitis causes reflex contraction of the erector spinae muscles causing limitation in passive
neck flexion (meningismus). Patient may complain of neck stiffness or pain, but many do not,
so this symptom has poor negative predictive value. To test for the sign of meningismus,
place the patient fully supine (completely flatten the bed and remove the pillow), then rotate the
head on neck. You should feel no resistance to rotation if the patient is fully relaxed. Then,
ask the patient to not resist, place you hand under their head, and slowly flex the head on the
neck and see if you can fully flex the neck so that the chin touches the manubrium. If it does,
meningismus is absent. If there is a limitation, it typically occurs at a specific degree of flexion
and beyond. Measure the distance from the chin to the chest with your fingers and report the
degree of flexion limitation as the number of finger breadths you can place in-between. If the
patient resists flexion to all degrees, especially if there is resistance to head rotation,
meningismus may be present but this finding is less specific. Do not test for neck flexion
limitation if the patient is standing or sitting as this produces false negatives; the patient must
be fully supine.

7
 Meningitis and Encephalitis Protocol
Begin Resuscitation, Start Antibiotics
Empirical treatment
If the patient meets SIRS criteria (hypotension, fever), an initial fluid bolus of 30 ml/kg of
crystalloid solution should be immediately infused over 20-30 minutes, and the patient’s vital
signs, mental status, and airway should be reassessed every 5 min during this phase of
treatment. If IV access cannot be obtained within a few minutes of presentation, interosseous
access should be placed. Antibiotics should be given concomitantly with IV fluids, or
immediately after starting IV fluids, and should never be delayed.

Select the appropriate antibiotics/antivirals based on a) the course of the suspected CNS
infection, b) age of the patient, and c) other infectious risk factors

• Children < 2 months are at risk for group B streptococci (GBS), Escherichia coli,
Listeria monocytogenes, Streptococcus pneumonia, Haemophilus influenzae and
Neisseria meningitidis. Use IV ampicillin, gentamycin, and cefotaxime.
• In older infants (2 to 23 months), children, and adolescents, the causes are typically
Streptococcus pneumoniae (which may be penicillin resistant), Neisseria
meningitides, and Haemophilus influenzae. In the younger patients in this group,
GBS may still occur. Administer vancomycin plus either cefotaxime or ceftriaxone.
The empiric antibiotic regimen should be broadened in infants and children with
immune deficiency, recent neurosurgery, penetrating head trauma, or other
anatomic defects.
• Young adults with suspected bacterial meningitis are at risk for Haemophilus
influenzae (if not vaccinated), Neisseria meningitidis, and Streptococcus
pneumoniae. As such, they should be started on a 3rd generation cephalosporin
and vancomycin at doses appropriate for CNS penetration.
• Middle-aged adults are at highest risk for Streptococcus pneumoniae. As such, they
should be started on a 3rd generation cephalosporin and vancomycin at doses
appropriate for CNS penetration. Vancomycin can be used alone in patients with a
severe penicillin allergy. (Vancomycin plus Moxifloxacin or levofloxacin or
Meropenem can be used in case of penicillin allergy or resistance.
• The elderly and immunosuppressed are at risk for Streptococcus pneumoniae and
Listeria monocytogenes. As such, they should be started on ampicillin, a 3rd
generation cephalosporin and vancomycin at doses appropriate for CNS
penetration. Vancomycin for S. pneumoniae, and trimethoprim-sulfamethoxazole for
Listeria, can be used in patients with a severe penicillin allergy.
• For suspected CNS infections that evolve over days, consider viral encephalitis,
particularly herpes simplex encephalitis. Treatment should begin with acyclovir at
10mg/kg every 8 hours. IV hydration should be sufficient to achieve euvolemia.
This avoids the complication of acyclovir-associated renal failure.
• For suspected CNS infections that evolve over days in an immunosuppressed
patient, consider fungal meningitis. If there is a high index of suspicion for fungal
meningitis, such as prior history of fungal CNS disease or systemic fungal infections,
and rapid disease progression, empiric amphotericin B can be considered.

8
 Meningitis and Encephalitis Protocol
• TB meningitis is another CNS infection to be considered in the early differential
diagnosis, especially if there has been a subacute and more protracted course of
onset of illness: In a patient presenting with a symptom duration of more than 5
days, particularly if the patient is immunocompromised, the diagnosis of TB
meningitis should be considered. Tuberculosis is more prevalent in high-risk groups,
including the homeless, nursing home residents, ethnic minorities, and persons
infected with HIV. Empiric treatment regimens are largely based on those for
pulmonary TB.

There is evidence supporting the use of dexamethasone in bacterial meningitis, particularly in

CNS infections caused by Streptococcus pneumoniae, and Haemophilus influenzae. In a
Cochrane systematic review and meta-analysis, it was found that corticosteroids overall
reduced the rate of any hearing loss, severe hearing loss, and neurological sequelae.
Subgroup analyses showed that corticosteroids a) prevented hearing loss in children with
bacterial meningitis b) reduced severe hearing loss only in children with meningitis due to H.
influenzae, c) reduced mortality in Streptococcus pneumoniae but not for other bacteria and d)
protected against severe hearing loss and short-term sequelae for children in high-income
countries, but not for those in low-income countries. Adjunctive corticosteroids are also
recommended for TB meningitis regardless of disease severity.

Give dexamethasone 10 mg IV, ideally given 10 to 20 minutes before antibiotics, or with the
first dose of antibiotics, until up to 4 hours after the first antibiotic dose. Corticosteroid
administration should not delay the administration of IV antibiotics. Other corticosteroids can
be used in equivalent doses if dexamethasone is not available. Dexamethasone is the
preferred corticosteroid, when these agents are used, due to superior penetration into the
cerebrospinal fluid (CSF) and a longer half-life. There is insufficient data to recommend
starting corticosteroids in neonates.

9
 Meningitis and Encephalitis Protocol

TARGET AGENT CHILDREN ADULTS

BACTERIAL
Group B Streptococci Ampicillin 0 to 7 days: 100 2 g IV every 4 h
Listeria mg/kg/dose IV every
Gram-negative bacteria 8-12 h
(E. coli)
8 to 28 days: 75
mg/kg/dose IV every
6h
> 28 days: 100
mg/kg/dose IV every
6 h (MAX: 2 g/dose)
H. influenzae Ceftazidime 0 to 7 days: 50 2 g IV every 8 h
N. meningitidis mg/kg/dose IV every
P. aeruginosa 8-12 h
S. pneumoniae 8-28 days: 50
mg/kg/dose IV every
8h
≥28 days: 50
mg/kg/dose IV every
6-8 h (Maximum
dose: 6g/day)

H. influenzae Cefotaxime 0-7 days: 50 2 g IV every 4-6 h

N. meningitides mg/kg/dose IV every
P. aeruginosa 8-12 h
S. pneumoniae 8-28 days: 50
mg/kg/dose IV every
6-8 h
>28 days: 75
mg/kg/dose IV every
6-8 h (maximum
dose: 12 g/day)
H. influenzae Ceftriaxone* Neonatal: 2 g IV every 12h
N. meningitidis < 14 days: 50 mg/kg
S. pneumoniae IM once daily
14-28 days: 100
mg/kg x1, then 80-
100 mg/kg/day IV
once daily
Infants/children:

10
 Meningitis and Encephalitis Protocol
80-100 mg/kg/day
divided every 12-24
hours
(Maximum dose: 4
g/day)
S. aureus Vancomycin 0-7 days: 10 15-20 mg/kg/dose IV
S. pneumoniae mg/kg/dose IV every every 8 -12 h
8-12 h
8-28 days:
10mg/kg/dose IV
every 6-8 h
>28 days:
15mg/kg/dose IV
every 6 h
Enterococcus species Gentamicin 0-7 days: 4 5 mg/kg/day IV in divided
Listeria mg/kg/dose IV every doses every 8 h
monocytogenes 24 h
S. agalactiae
P. aeruginosa 8-60 days: 5
mg/kg/dose IV every
24h
60 days-10 years: 2.5
mg/kg/dose IV every
8h

>10 years: 5
mg/kg/day IV
divided every 8 h
H. influenzae Meropenem 40 mg/kg/dose IV 2 g IV every 8 h
N. meningitidis every 8 h
S. pneumoniae (maximum dose: 2
g/dose)
Alternative in penicillin Aztreonam 0-7 days: 30 2 g IV every 6-8 h
allergy mg/kg/dose IV
- component of empiric every 8 h
therapy
- H. influenzae ≥8 days: 30
Enterobacteriaceae mg/kg/dose IV every
P. aeruginosa 6-8 h (MAX: 8 g/day)

11
 Meningitis and Encephalitis Protocol

TARGET AGENT CHILDREN ADULTS

VIRAL
Herpes simplex virus Acyclovir 0-90 days: 20 10 mg/kg/dose IV every 8
mg/kg/dose IV every h
8h
90 days-12 years: 10-
15 mg/kg/dose IV
every 8 h
≥12 years: 10
mg/kg/dose IV
every 8 h (Maximum
dose 8 g/day)
Varicella-Zoster virus Acyclovir Acyclovir dosing: see 10 mg/kg/dose IV every 8
above h
Ganciclovir dosing:
see
Or below

Ganciclovir 5 mg/kg/dose IV every 12

h

Cytomegalovirus (in Ganciclovir 0-3 months: 6 5 mg/kg/dose every 12 h

HIV-infected) mg/kg/dose every 12 plus foscarnet until
h symptoms improve*
≥3 months:5
mg/kg/dose every 12
h. Add foscarnet until
symptoms improve
*off-label

12
 Meningitis and Encephalitis Protocol

TARGET AGENT CHILDREN ADULTS

FUNGAL
Candida species Amphotericin B <28 days: use Use lipid complex
Aspergillus species conventional formulation:5 mg/kg/dose
Mucorales formulation: IV daily
Mycoses 1mg/kg/dose IV (may premedicate with
Molds once daily acetaminophen +
Leishmania species antihistamine to prevent
Histoplasmosis ≥28 days: use infusion reactions)
Coccidiomycoses liposomal
formulation:5
mg/kg/dose IV daily
(may premedicate
with acetaminophen +
antihistamine to
prevent infusion
reactions)
Cryptococcus Liposomal dosing as above 3-6 mg/kg/day IV daily
Empiric in febrile amphotericin B (may premedicate with
neutropenic patients acetaminophen +
diphenhydramine to
prevent infusion
reactions)

13
 Meningitis and Encephalitis Protocol

TARGET AGENT CHILDREN ADULTS

MYCOBACTERIAL (Initial intensive phase)
Empiric for strong Ethambutol Weight-based:
suspicion of
tuberculous meningitis: <15 years or ≤ 40kg: <15 years or ≤40 kg: 15
combination regimen (4 15 to 25 mg/kg/dose to 25 mg/kg/day
drugs) PO once daily
(maximum dose:
1g/dose)

40- 55 kg: 800 mg PO 40-55 kg: 800 mg PO

once daily daily
56-75 kg: 1200 mg 56-75 kg: 1200 mg PO
PO once daily daily
76-90 kg: 1600 mg 76-90 kg: 1600 mg PO
PO once daily daily
Isoniazid <15 years and ≤40 5 mg/kg/dose
kg: 10-15 PO once daily
mg/kg/dose PO once
daily
(Maximum dose: 300
mg/dose)

<15 years and >40

kg, or ≥15
years: 5mg/kg/day
Pyrazinamide <40 kg: 35 mg/kg/day 40-55 kg: 1000 mg PO
once daily
40-55 kg: 1000 mg 56-75kg: 1500 mg PO
daily once daily
56-75 kg: 1500 mg 76-90kg: 2000 mg PO
daily once daily
76-90 kg: 2000 mg
daily

14
 Meningitis and Encephalitis Protocol
Rifampin/rifampicin <28 days: 2.5- 10 to 20 mg/kg once
10mg/kg/dose daily
IV every 12 h (maximum: 600 mg/dose)

<15 years and ≤40kg:

10-20
mg/kg/dose IV once
daily

<15 years and >40kg,

or ≥15 years: 10
mg/kg once daily
(maximum: 600
mg/dose)

* Neonates should only receive intramuscular formulations of ceftriaxone. Intravenous formulations have potential for fatal lung and kidney
damage in preterm and term neonates.

15
 Meningitis and Encephalitis Protocol
Table 4

Neonate (<28 Infants/Children Adults - Adults - Healthcare

days) (≥28 days) immunocompetent immunocompromised associated
Ampicillin (0-7 Ceftriaxone (80- Ceftriaxone (2 g IV Cefepime (2 g IV every Cefepime (2
d: 100 100 mg/kg/day IV every 12 h) 8 h) g IV every 8
mg/kg/dose IV divided every 12- h)
every 8 h; 8- 24 hours;
28 d: 75 maximum dose:
mg/kg/dose IV 4 g/day)
every 6 h)
Or Or Or Or
°Cefotaxime (75 Cefotaxime (2 g IV Meropenem (2 g IV Ceftazidime
mg/kg/dose IV every 4-6 h) every 8 h) (2 g IV every
q6-8h) 8 h)
Plus Plus Plus Plus Or
Gentamicin Vancomycin (15 Vancomycin (15-20 Vancomycin (15-20 Meropenem
(0-7 d: 4 mg/kg/dose IV mg/kg/dose IV mg/kg IV every 8-12 h) (2 g IV every
mg/kg/dose IV q6h) every 8-12 h 8 h)
every 24 h; 8-
28 d: 5
mg/kg/dose IV
every 24 h)
Or Plus (if >50 yrs) Plus Plus
o
Cefotaxime Ampicillin (2 g IV Ampicillin (2 g IV Vancomycin
(0-7 d: 50 every 4 h) every 4 h) (15-20
mg/kg/dose IV mg/kg IV
every 8-12 h; every 8-12
8-28 d: 50
h)
mg/kg/dose IV
every 6-8 h)
Or
Ceftazidime
(0-7 d:
50mg/kg/dose
IV every
8-12 h; 7-28 d:
50mg/kg/dose
IV every
8 h)
*Dexamethasone *Dexamethasone
(0.15mg/kg IV (10mg IV every 6 h)
q6h) – give –
before or with give before or with
first dose of first
antibiotic dose of antibiotic

16
 Meningitis and Encephalitis Protocol

Notes on Table 4
*in patients with certain risk factors (e.g., unimmunized patients, young children [age
≥ 6 weeks to 5 years], children with sickle cell disease, asplenic patients) or if there is
known or suspected Haemophilus influenzae or S. pneumoniae infection (e.g., based
on Gram stain results).
¶Dexamethasone, if given, should be administered before or immediately after the
first
dose of antibiotics. Duration of treatment: 2-4 days for adults and children
◦Cefotaxime: currently on shortage in U.S.
Vancomycin: not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose
to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL

If Beta lactam allergic:

For Listeria: trimethoprim-sulfamethoxazole - 5mg/kg (based on the trimethoprim
component) IV every 6 to 12h
For S. Pneumoniae, N. Meningitidis, H. influenzae: replace the Beta lactam with
moxifloxacin 400mg po daily or levofloxacin 750mg IV daily
Suspected healthcare associated meningitis: replace Beta lactam with Aztreonam
(2g IV every 6 to 8h) or Ciprofloxacin (400mg IV every 8 to 12h)

17
 Meningitis and Encephalitis Protocol
Head CT if Indicated
In patients where there is a moderate to high suspicion of CNS infection and the lumbar
puncture has not yet been done, parenteral anti-infectives SHOULD NOT BE DELAYED while
waiting for a CT scan. CSF sterilization occurs only after 4-6 hours in the most sensitive
organisms, and patient outcomes are linked to earlier antibiotic treatment. Therefore,
presumptive treatment in a patient who later has a normal LP is far better than waiting to give
antibiotics for the CT, then LP results confirm bacterial meningitis.

A head CT is NOT always required prior to an LP. The logic of performing a head CT prior to
LP is to prevent cerebral herniation from an intracranial mass lesion. In this setting, lowering
lumbar pressure could cause downward herniation of the brain.

Indications for neuroimaging prior to lumbar puncture:

✓ Patient is ≥ 60 years
✓ History of CNS disease
✓ Immunocompromised state
✓ History of seizure (within one week of presentation)
✓ Abnormal neurologic exam findings
o Impaired level of consciousness
o Abnormal language
o Cranial nerve findings
o Motor findings
o Papilledema or loss of venous pulsations on fundoscopic examination

A normal head CT does not necessarily protect the patient form a herniation syndrome. Brain
herniation after LP occurs in approximately 5% of cases or less. CT scan can detect brain shift
and findings of impending herniation, contraindicating an LP. However, CSF pressure may be
elevated, even to levels where herniation may occur, in absence of abnormalities on CT.
Meningitis can be fulminant and characterized by progressive inflammation of the meninges
and brain swelling. Patients can herniate after LP because of disease progression, or due to
the inflammatory response to bacterial proinflammatory substances liberated after antibiotic
administration (especially if steroids are not given around the time of first antibiotic
administration), and not necessarily as a result of the LP. Vice versa, CSF pressure can be
normal in patients with space occupying lesions causing brain shift seen on CT scan, even in
the stage of herniation, and the LP may lead to herniation even with the CSF having normal
pressure.

In a patient with none of the above indications, doing an LP prior to head imaging is likely safe.
However, in most patients who have a clinical presentation consistent with meningitis or
encephalitis, there will be enough diagnostic uncertainty that CT may be advisable prior to LP
to rule out other etiologies. Although MRI is preferable for encephalitis but CT with and without
contrast can be performed.

18
 Meningitis and Encephalitis Protocol
If the head CT shows a mass lesion or other condition that adequately explains the patient's
mental status, then that cause should be diagnostically evaluated and LP avoided.

19
 Meningitis and Encephalitis Protocol
Lumbar Puncture
Rapid assessment of spinal fluid
An LP is essential for both establishing a diagnosis and tailoring therapy.

The opening pressure should be measured with a manometer prior to the collection of CSF in
the left lateral decubitus position. CSF should be collected in (at least) 4 tubes.
• Send tube 1 and tube 4 for RBCs and WBC count and differential (if tube 1 was
turbid, and tube 4 is clear, this suggests a traumatic tap)
• Send tube 2 for protein, glucose, and lactic acid
• Send tube 3 for gram stain and culture; India ink if fungal infection is suspected;
antigens, PCR (For viruses, especially herpes viruses. May also be sent in tube 2),
IgM for viruses, viral culture

Some laboratories perform bacterial antigen assays which may be useful. Additional
laboratory tests that may be performed by some centers include bacterial PCR (particularly for
Mycobacterium), enterovirus PCR, fungal antigens and viral culture.

20
 Meningitis and Encephalitis Protocol
Normal LP
Rules out meningitis and encephalitis
An LP is considered normal if:

• No RBCs/HPF or up to ≤ 5
• WBCs ≤ 5/HPF
• CSF glucose/serum glucose ratio >0.6
• Protein < 50 mg/dl
• No organisms seen on gram stain

If all of the above are true, meningitis is ruled out. However, a normal LP may be consistent
with non-herpetic encephalitis, but other than medical support there is no emergency
intervention that is necessary. Evaluation for systemic infection should also ensue.

Evaluate for Other Diagnoses

A normal LP is highly predictive of absent bacterial infection of the meninges. Pure
encephalitis, and perhaps early herpes simplex encephalitis, can have a normal lumbar
puncture since the inflammation is within the brain parenchyma and may not communicate with
the subarachnoid space. However, given the constellation of fever, leukocytosis and altered
mental status, it is likely the patient is suffering a depressed mental status from systemic
inflammation rather than direct involvement of the central nervous system itself.

This is termed “metabolic encephalopathy” and is common in patients with preexisting brain
disorders or atrophy. Once the true infection is found and treated (urinary tract, lungs, sepsis),
the patient’s mental status improves to baseline. Prolonged poor mental status after systemic
signs of treatment appears (defervescence, falling WBC count) may prompt additional
investigation as to cause.

21
 Meningitis and Encephalitis Protocol
Very High WBCs
WBCs > 100-1000
Marked elevation in WBCs without RBCs is highly suggestive of bacterial meningitis. So, if the
following is true:

• No RBC
• WBCs 100-1000/HPF or higher
• CSF glucose/serum glucose ratio <0.6, but rarely normal
• Protein > 50 mg/dl
• Organisms seen on gram stain in approximately 70% of cases

Then, the patient likely has bacterial meningitis.

Suspicion of Bacterial Meningitis

• Continue antibiotics
• Stop acyclovir
• Continue dexamethasone
• Adjust antibiotics, and either continue or stop dexamethasone based on final culture
results, and sensitivities

In addition to antibiotics and dexamethasone, supportive care and management of other

systems is important in patients with bacterial meningitis. Some patients may have a
concomitant bloodstream infection with the offending pathogen and may require early goal
directed therapy for sepsis. If the LP demonstrates an elevated OP, ICP monitoring and
treatment of intracranial hypertension may be required. Details of management of intracranial
hypertension can be found in the ENLS manuscript on the same topic and in the 2019
Neurocritical Care Society Guidelines for Cerebral Edema Management. Risks, including the
potential of a superinfection with the foreign body, must be weighed with the potential benefits.

If the OP is found to be greatly elevated (e.g., > 400 mm H2O), expert opinion recommends
that the needle stylet should be left in place and mannitol administered. It may be prudent to
recheck the pressure after a few minutes to confirm that the CSF pressure has declined,
before removing the needle. Hyperventilation should probably be avoided as these patients
already may suffer from some degree of decreased cerebral vessel diameter due to
vasculopathy. Mannitol or hypertonic saline may be reasonable considerations.

22
 Meningitis and Encephalitis Protocol
Elevated WBCs and no RBCs
Probably viral meningitis
Mild elevation in WBCs without RBCs is suggestive of viral meningitis or viral (not herpes)
encephalitis. If the following is true:

• No RBC per HPF

• WBCs 10-100s
• Normal CSF glucose/serum glucose ratio (>0.6)
• Protein < 50 mg/dl (if elevated, it is usually <100 mg/dL)
• No organisms seen on gram stain

Then the patient likely has a non-herpes viral meningitis or encephalitis.

Seroconversion of HIV should also be considered.

Viral meningitis or viral (non-herpes) encephalitis treatment

Treatment of viral meningitis or viral (non-herpes) encephalitis:
• Discontinue acyclovir and antibiotics
• Discontinue dexamethasone
• Treat headache
• For West Nile Virus, there is risk of respiratory decompensation from spinal cord
involvement so admission to the ICU for observation may be appropriate

23
 Meningitis and Encephalitis Protocol
Elevated WBCs and RBCs
Consider herpes encephalitis
If the following is true:

• Elevated RBC (10–100/HPF or higher),

• WBCs in the hundreds/HPF, typically with lymphocytic predominance,
• CSF glucose/serum glucose ratio >0.6, or sometimes lower,
• Protein < 50 mg/dL or mildly elevated usually <100 mg/dL, and
• No organisms on gram stain,

then the patient may have herpes encephalitis. The presence of seizures and findings of uni-
or bilateral hypodensities with or without hemorrhage in the temporal lobes on brain MRI, and
rarely on brain CT scans, are also compatible with this diagnosis.

Empirical treatment and diagnosis of herpes encephalitis

• Continue acyclovir 10 mg/kg every 8 hours IV
• Send CSF for HSV PCR
• Continue other antibiotics until cultures/PCR results back
• MRI of the brain
• Achieve and maintain euvolemia to prevent acyclovir associated renal failure

24
 Meningitis and Encephalitis Protocol
Elevated WBCs and Very High Total Protein
Fungal or TB Meningitis
Fungal CNS infections are highly variable in clinical presentation and need to be considered in
suspected CNS infections that evolve over days in an immunosuppressed patient. Prior
history of CNS disease or systemic fungal infections and rapid disease progression should
raise the index of suspicion for fungal meningitis.

As with other CNS infections, fast identification and treatment initiation significantly affects the
odds of a better outcome. Typical CSF findings include lymphocytic pleocytosis (few to
several hundred per HPF) and for certain organisms also with eosinophilic predominance. CSF
glucose is decreased, and CSF protein is generally elevated (up to 250 mg/dl or beyond). If
CSF acquisition via LP is difficult or impossible, it can be an indicator of very high (>1 gm/dL)
CSF protein and obstructive hydrocephalus. Empiric amphotericin B should be administered
during diagnostic testing.

25
 Meningitis and Encephalitis Protocol
Elevated RBCs, Xanthochromia
Likely Subarachnoid Hemorrhage
If the following is true:

• Elevated RBC (100 to 1,000/HPF or higher),

• WBC < 5/HPF or fewer than 1 WBC/500 RBC,
• CSF glucose/serum glucose ratio >0.6,
• Protein < 50 mg/dl,
• No organisms on gram stain, and
• Xanthochromia,

then the patient likely has a subarachnoid hemorrhage that was not detected on the CT scan.
Xanthochromia may be absent if the LP was done within the first few hours of headache onset
(and so one typically only sees RBCs).

Management of SAH
Review the head CT to look for subarachnoid blood (this can be absent after SAH
approximately 5% of the time, particularly with small hemorrhages and imaging obtained long
after symptom onset).

See the ENLS protocol Subarachnoid Hemorrhage.

Pediatric considerations

Bacterial meningitis is a true medical emergency. Pediatric patients should be resuscitated

similarly using the ABC approach with securing airway, breathing and circulation. Shock may
also be a presentation in pediatric patients. IV access with rapid isotonic fluid resuscitation of
20-60 mL/kg in the first hour should be administered with a goal to restore normal peripheral
perfusion, heart rate and blood pressure for age. For fluid refractory shock, epinephrine for
cold shock and norepinephrine for warm shock should be started. Initiation of antibiotics
should not be delayed for investigations such as imaging and LP. Age-appropriate use of
antibiotics and use of dexamethasone have been discussed above.
Other conditions to keep in mind include Acute Flaccid Myelitis (AFM), which is a rare but
feared problem with children presenting as acute paralysis. Decreasing vaccine coverage has also
led to measles encephalitis and mumps-associated meningitis in pediatric population

26