Meningitis, Other CNS Infections and Sepsis

Janet Wong, M.D.

1
 Mediators of Meningeal Inflammation Cell wall components and cell membrane components are released
naturally by bacteria and accelerated by antibiotic therapy and give rise to
the two sentinel cytokines, TNF and IL-1 which then will set off a cascade
of the cytokines, both proto-inflammatory and anti-inflammatory. IL-1 has
anti-inflammatory side effects. It regulates its own production of TNF and
• Tumor necrosis factor alpha • Prostaglandins IL-1. These and the rise and colonization of white cells give rise to the
endothelial damage, which is one of the critical areas in the pathogenesis
• Interleukin - 1 • Interleukin gamma
of both cells. Because not only does it lead to alteration of the blood-brain
• Interleukin - 6 • Platelet-activating factor barrier, but you get alterations in the endothelium, which gives rise to
• Interleukin -8 • Nitric Oxide altered blood flow, because of thrombosis and edema. The bottom line to
all of this is that you eventually get ischemia and reperfusion injury and
• Interleukin - 10 • White blood cell products
neuronal damage, both by the cytokines and the thrombosis and the oxygen
radicals that are toxic.
• Macrophage inflammatory proteins 1 & 2
The mediators of meningeal inflammation appear to be the same as they
are for suppurative arthritis and sepsis. And I’ve shown here, remember the
TNF IL-1 are inflammatory agents, IL-10, TNF receptor, IL-1 receptor are
anti-inflammatory and will modulate the inflammatory response. Of course,
these factors are very critical because they cause neuronal damage.

CSF inflammation has been shown to be affected by cytokines. With TNF,

the IL-1, the IL-6 and for PGE-2, there has been a direct correlation with a
concentration of these cytokines in spinal fluid and outcome for meningitis.

Adjunctive therapies have been tried for meningitis. For meningitis, these
agents have been evaluated as anti-inflammatory substances. But only
dexamethasone has been studied in both animals and in a large number
of clinical trials.

2
 SIRS and Sepsis: a Continuum
• SIRS-- Presence of two or more of the following: altered temperature,
tachypnea, tachycardia and abnormal WBC
• SEPSIS --SIRS with proven/suspected microbial etiology
• SEVERE SEPSIS --Sepsis with signs of organ dysfunction
• SEPTIC SHOCK-- SEPSIS with hypotension and multiple organ dysfunction
(may become refractory)
Sepsis. SIRS, systemic inflammatory response syndrome, to sepsis,
severe sepsis and septic shock are the terms now that most people will
use. They are a hierarchical categorization of sepsis with regard to
outcome. If you just look at sepsis, severe sepsis and septic shock, the
case fatality rate is significantly higher as you go towards the more severe
disease, septic shock. You can look at severe sepsis or septic shock and
with or without multiple organ dysfunction. And of course, with multiple
organ dysfunction, mortality is higher. With severe sepsis, 40% overall, you
look at it without multiple organ dysfunction it’s 32%. With multiple organ
dysfunction it’s 66%.
3
Bacteriology and Outcome of Pediatric Sepsis
Meningococcemia portends a very poor prognosis. Meningococcemia is
probably associated with a mortality rate of 15-30%. 73% would be rather
Organism % % Deaths high. You also have a very high case mortality rate in Pseudomonas, but it’s
S. aureus 31 23 pretty much true in many centers, this Pseudomonas is the problem.

N. meningitidis 19 29
Kleb-Enterob. sp. 12 10
C-N Staph. 10 3
H. influenzae 9 2
E. coli 9 7
P. aeruginosa 6 9
S. pneumoniae 2 1

4
 Outcome of Pediatric Sepsis
If appropriate antibiotics are given initially, empirically, the outcome is far
better statistically than if an inappropriate weapon is chosen.

Variable % Deaths
Culture-positive 40
Culture-negative 39
Appropriate antibiotics 34
Inappropriate antibiotics 53

5
Complications of Severe Meningococcemia
In addition to the neurologic abnormalities, is one of the most devastating
aspects of meningococcemia is the amputations that result from infarcts of
DIC 68%
skin and bone in the extremities. So this is a really severe complication.
ARDS 34%
Renal failure 9%
Pancreatitis 7%
Myocarditis 7%
Adrenal hemorrhage 5%
Myocardial infarction 2%

6
 Initial Empiric Therapy for Sepsis
Initial empiric therapy for sepsis varies. In newborns ampicillin and
aminoglycoside, cefotaxime. There are no data that show that with
Community-acquired
ampicillin and aminoglycoside, the outcome with that regimen is any
Newborns Amp + aminoglycoside or Cefotaxime different than with ampicillin and cefotaxime. Cefotaxime is better, but

Infants Ceftriaxone, Cefotaxime there’s no data to show that it actually is better than the other regimen. I do
not like cefotaxime used routinely in nurseries where every child is
Children Ceftriaxone, Cefotaxime
suspected of something because of the potential for resistance. In infants
Hospital-acquired and children, ceftriaxone and cefotaxime you are not going to use that

Anti-staph + aminoglycoside, or cephalosporin routinely.

Immunocompromised
Many possibilities: Anti-staphylococcal penicillin + Aminoglycoside or
cephalosporin; cephalosporin + Aminoglycside; cephalosporin alone;
meropenem alone. Anaerobe coverage for intraabdominal or pelvic origin
With hospital acquired infections, nosocomial diseases, we usually use an
anti-staphylococcal with an aminoglycoside or a cephalosporin, depending
on what you encountered and what the predisposing factors are. If MRSA
is a problem, then we use vancomycin.

For the anaerobic coverage, the physician would want to use this for
intraabdominal and pelvic origins, probably metronidazole is the most
appropriate of the anaerobic agents and the most effective. Clindamycin is
okay for intraabdominal. Meropenem has aerobic coverage.

7
Etiologic Agents of Neonatal Bacterial Menin-
gitis Meningitis. In the United States and many other developed countries,
Hemophilus has disappeared as a cause of meningitis.

The etiologic agents of neonatal bacterial meningitis. Group B strep by far

the most common, with a case fatality rate of 15%. Other organisms
Organism % Death % include E. Coli, Klebsiella and Enterobacter species.

Gram-positive pathogens
Group B Streptococcus 52 15
Enterococcus 5 25
Group D Streptococcus 3 0
Staphylococcus aureus 8 50
Others 2 0
Gram-negative pathogens
Escherichia coil 9 28
Klebsiella pneumoniae 3 0
Enterobacter cloacae 3 0
Serratia marcescens 3 0
Other gram-negative rods 8 25
Fungi
Candida albicans 1 0

8
 Meningococcal Meningitis
• Incidence is sporadic; recent small outbreaks in many U.S. cities.
• Prognosis with meningococcemia worse (fatality rate=12-30%) than with
meningitis (fatality rate=4-5%).
• May relate to endotoxin concentration in different body fluids
• Limb amputation and skin grafting is common in meningococcemia
with shock
• Long-term sequelae in 5 - 10%, hearing alterations
Meningococcal disease is very sporadic in the United States. There are
small outbreaks in many areas. 90% are either meningo group B or C. The
prognosis of meningococcemia is considerably worse than that for
meningitis. It may be linked to endotoxin concentrations because in
meningitis there is very little circulating endotoxin in the blood stream. Thus
you are not prone to DIC and shock. Of course, shock coupled with
meningitis is devastating in terms of cerebral blood flow.
9
 Pneumococcal Meningitis
• Incidence varies; no evidence of increased virulence
• Case-fatality rates approx. 10% in children. The virulence of pneumococci
has not changed in recent years.
• Long-term morbidity >30.%; hearing impairment common and occurs
early in disease (reversible, it not severe/profound).
• Multidrug resistance increasing worldwide
Long-term sequelae. The case fatality rate in meningitis is probably 4 or
5%. Long-term sequelae are also relatively low, 5 - 10%. Hearing alteration
probably being the single most common abnormality. Pneumococcal
meningitis is by far more severe than meningococcal or Hemophilus. This
incidence varies considerably. The case fatality rate in children is about
10%. In adults, considerably higher. About 30%.
Long term morbidity is high in meningococcal and it varies from probably
15 - 30%, a little more than 30%. Hearing impairment is common. It occurs
early in the disease. Possibly reversible but not if the child has severe or
profound hearing abnormality at the outset, they will not reverse and be
normal. They become a little less profound or less severe, but they will not
be reversed. And of course multi-drug resistance is a major problem in
many areas of the world. And of course in the United States there are
maybe 20-25% resistants.
10
 Factors Influencing Effectiveness of Antibi-
otic Therapy for Bacterial Meningitis
• Absent specific antibody and functional complement in CSF
- Inefficient phagocytosis of pathogen
- High conc. of bacteria in CSF
• Poor penetration into CSF
• Bactericidal versus static activity
• Drug in CSF: peak conc. vs persistent conc. in relation to MIC
Factors influencing the effectiveness of antibiotic therapy. Absence of
specific antibody and functional complement in CSF allow bacteria to
multiply to fairly high concentrations. So that the initial concentration of
bacteria in CSF at the time of diagnosis is around 107 organisms. That is
why with Hemophilus, Pneumococcus and usually Meningococcus, if they
are not pretreated, can be seen readily on the gram stain smear of CSF.
Remembering that the cut- off is about 105 organisms. So if you have more
than 105 organisms, or more, you are able to see one or several organisms
per high power field. If you see myriads of organisms at the outset, that’s
a very poor prognostic sign. So it also relates to concentrations of 108 or 109
organisms, the prognosis is poor. It is very difficult to see Listeria in the
CSF of babies with meningitis because they have on average 103 organ-
isms, and that is below the cut-off point of what can be seen on gram stain.
Poor penetration into the CSF. We know that the blood-brain barrier is very
efficient and that antibiotics do not penetrate very well. In meningitis they
penetrate better because there is alteration of the blood-brain barrier. We
prefer bactericidal agents, whether they are concentration dependent or
independent.
11
Treatment of Neonatal Meningitis--Initial Em-
piric Regimens Initial treatment: Empiric regimens in the neonate included ampicillin and
aminoglycoside or cefotaxime. Again, there is no evidence that one is better
than the other. Once we know that it’s, let’s say E. coli, we will usually with
cefotaxime alone. You don’t have to monitor concentrations of the
Early onset: Ampicillin + aminoglycoside or cefotaxime
glycosides and we usually do not keep a combination going for coliforms.
Late onset: Term infant same as above Maybe initially, but we’ll use cefotaxime alone once we know the organism

LBW/preterm: Vancomycin + amikacin or cephalosporin
When Etiology Known
Group B strep: Ampicillin +/- aminoglycoside
Coliforms: Cefotaxime +/- aminoglycoside
Pseudomonas: Ceftazidime +/- aminoglycoside
Listeria: Ampicillin +/- aminoglycoside
and we know that the child is clearly responding to it. Late onset, low birth
weight, premature term infant who is in the hospital usually has a
nosocomial pathogen. But we will usually use either vancomycin or another
anti-staphylococcal agent. Once we know the etiology of group B strep,
usually we’ll treat alone with ampicillin. Others prefer to continue the
combination for the entire period. With coliforms, usually we’ll treat with
cefotaxime once we know the susceptibilities and the clinical responses.
Pseudomonas: we almost always use a combination. Listeria: we use
ampicillin alone. We don’t see much Listeria. One of the few cases of
meningitis that has a good outcome in the neonate is Listeria. We use
ampicillin. Some prefer to keep the combination up for much of the period
of therapy.

12
 Management of Non-neonatal Meningitis
Modifications of the Initial Empiric Regimen
• Larger dosage of cefotaxime (75 mg/kg Q 6h) or one extra 80-100 mg/kg
dose of ceftriaxone at 12 hr
• Addition of vancomycin (15 mg/kg Q 6h), in all age groups, until results
of cultures and susceptibility testing are available
Non-neonatal meningitis: Ceftriaxone or cefotaxime is recommended in an
area where there is pneumococcal penicillin resistance is a problem, alter
the cephalosporin regimen, increasing the dosage of cefotaxime to 75 mg
/kg every 6 hours. This maintains the concentrations during the dosing
interval of six hours in the CSF over the MIC of the organism for at least
four of those six hours. Or add one extra dosage, one extra dose of
ceftriaxone at 12 hours. We’ve based that on our animal studies and we’ve
shown that one extra dose of very highly cephalosporin-resistant
pneumococcus with a MIC/MBC of 4 to ceftriaxone, if you just add one extra
dose at 12 hours the sterilization occurs at 24 hours.
Vancomycin. In most centers we now do add vancomycin initially and we’ll
wait until the results of susceptibility testing from the oxacillin disk to
determine whether to continue this or not. Toxicity does not occur at this
high dosage. Peak value is usually in the range of 20 - 25 µ per million. I
have no hesitation to go up to 40 µ per million. Toxicity concerns about
vancomycin are really based on the studies in the 70’s and the early 80’s.
The preparation has changed, has been cleaned up, and we have just not
seen toxicity, unless it gets up over 60, which we do not like.
13
Duration of Treatment for Uncomplicated
Bacterial Meningitis
• NEONATES
GBS and other strep. 10-14 d
Duration of treatment: Group B strep, 10 - 14 days. Most times they get 14
days. These are for uncomplicated disease. Obviously for the child with
complications, this does not apply. A gram negative enteric, a minimum of
21 days. For Listeria, treat for just 10 days. For meningococcus 4-7 days.
There are some very beautiful studies in adults and 4 days is totally
effective. 4-7 days is adequate. Hemophilus: 7-10 days. Pneumococcus:

Gram neg. enterics 21 d 10 days for the child who has an uncomplicated course.

Listeria 10 d
• INFANTS AND CHILDREN
Meningococcus 4-7 d
Haemophilus 7-10 d
Pneumococcus 10 d

14
New Antimicrobial Agents for Treatment of Men-
New agents: the only one approved so far is meropenem. The dosage for
ingitis meningitis is 40 mg/kg every 8 eight hours. It’s a good drug. The only
question that remains is how effective it will be against resistant
pneumococci. There is really not enough experience with the drug yet to
* Meropenem (Merrem)
know whether it will be effective alone as therapy for cephalosporin-
* Cefepime (Maxipime) resistant pneumococcus. MIC’s are usually in the range of 0.5. Maybe
slightly higher. We had one at 1 µ per mil. That’s the highly resistant
ceftriaxone-resistant strain. Cefepime has not been approved for pediatric
Cefpirome
use, but it has been studied in children. It should be effective. How it affects
Trovafloxacin the pneumococcus that are resistant is unknown. Trovafloxacin is a
fluoroquinolone is going to undergo studies very soon in meningitis world
wide.

15
 Dexamethasone Therapy for Meningitis
Dexamethasone therapy: If you choose to use it, the dosage is 0.6 - 0.8 mg
per kilo daily, 2-3 times daily, in two or three doses is fine. And I’d do it for
€ Regimen: 0.6 - 0.8 mg/kg daily in 2, 3 or 4 divided doses for 2 - 4
two days.
days
€ First dose should be given before or at the time of the first parenteral The first dose of dexamethasone should be given before or at the same
time as the first parenteral dose. Remember the effects of dexamethasone
antibiotic dose
is only on what the first dose of the antibiotic does to the organs, in the
€ lt is doubtful that dexamethasone will be effective if given more than 30 to releasing more of the antitoxin or cell wall products and it’s subsequent
60 min after the first parenteral antibiotic dose enhancement of inflammation TNF and IL-1. So you have to give it right
away or it doesn’t have that effect.

16
 Changes in Body Water in Meningitis
Ninety percent of children with bacterial meningitis had increased body
water, mainly extracellular fluid. SIADH was found in 50% and that varies
€ Approximately 90% of children with bacterial meningitis had Increased
from study to study.
body water, related to increased extracellular water
• Ave. excess ECW = 33 + 32 ml/kg
• Varied directly with severity of illness and complications
• SIADH in + 50%; all had >45 ml/kg excess ECW and hyponatremia
€ Restriction of fluid is reasonable if systemic blood pressure maintained in
normal or high normal range

17
 Fluid Restriction Did Not Improve Outcome
from Bacterial Meningitis
• 50 children with meningitis divided according to presence of, decreased
Na and randomized to receive maintenance or restricted fluid.
Restriction of fluid is reasonable and the way that I look at it is that
restriction is fine but the critical point is to maintain the blood pressure at
either in the middle of the normal range or in the high normal range,
because the only thing driving cerebral blood flow in meningitis is systemic
blood pressure. If these babies are kept too dry and their blood pressure is
in the low range, you are losing the only significant drive for the child who

• Restricted fluid assoc, with decreased mean TBW and ECW; these were has a lot of cerebral edema. You don’t want to do that.

unchanged in those given maintenance fluid.

• Analysis revealed poor outcome associated significantly with age, coma
score, serum sodium Na + plasma osmolarity (PO) at Admission and PO,
TBW + ECW at 48 hr.

18
 Second Lumbar Puncture in Meningitis
Second lumbar puncture in meningitis. We do a second lumbar puncture
in meningitis in all neonates in about 24 - 48 hours. You can not look at the
€ Indications child and know exactly what’s going on. It’s very difficult. The second
- All neonates at 24 - 36 hrs lumbar puncture should be done when there is a lack of clinical improve-
ment in the first 48 hours. You anticipate for a child with meningococcemia
- Lack of clinical improvement within 24 - 36 hrs of starting treatment
that in 48 hours that child is going to show improvement. If that child
- Resistant pneumococcal meningitis
doesn’t show improvement, something’s wrong. Either the wrong dose or
- Prolonged or secondary fever something happened, and that must be evaluated. A normal child, the child

€ Not indicated at completion of therapy in uncomplicated patients, except
for neonates at end of treatment
who responds routinely with meningococcemia, does not need a second
tap. Resistant pneumococcal meningitis, I think that’s important. Once you
know that the organism is resistant I believe a second tap to document,
bacteriologically, a cure is important. And of course, children with
prolonged or secondary fever, something else that is suspicious that you
are not sure that your pressure is under control, a tap is indicated. It is not
indicated at completion of therapy in the uncomplicated patient, with the
exception of the newborn. We still believe that a newborn should be tapped
at the end of therapy. We have been fooled so many times when the baby
looks fine, we tap them and sure enough they had three, four, five hundred
cells, 60% polys and that’s not acceptable. So treatment was extended and
of course we did some CT scans on the children.

19
 Prolonged Fever in Meningitis
• Be familiar with usual fever patterns
• Check details of antibiotic regimen
• Examine for focal neurologic signs, phlebitis, arthritis, URI and UTI
• Consider CRP, LP, imaging studies
• If above is unrevealing, drug fever is possible
What about prolonged fever in meningitis? Prolonged fever in meningitis -
the first thing to know about fever is what is the expected pattern? With
Hemophilus it came down slowly, so in five days you still had 20% of
children who had some fever. Their temperature was coming down but they
were not afebrile. With meningococcus, if they are still febrile after four or
five days, something is wrong. Pneumococcus, something is wrong. So you
must know the fever pattern. And of course in a newborn, all these indices
do not apply because the newborn may or may not even have fever. If a
child has prolonged fever, then you should check the antibiotic regimen and
be sure that it’s being given they way you thought it was being given. Look
at the charts to see if there is a decimal point error. And then look for
nosocomial infection, line infection, urinary tract infection before you start
to do a lot of other things. But with meningococcemia, if there’s a second-
ary fever on day five, look to see if there’s any jaundice. Because secondary
with immune-mediated arthropathy occurs after four days and you get fever
and it’s a simple thing to manage.
You can consider a C-reactive protein, which can be very useful in both
sepsis and meningitis to tell you whether there is ongoing infection or, if
this is a newborn, using this as a index of when one would stop therapy. If
a child has prolonged fever and the CRP is normal, that’s reassuring. A LP
might be indicated in the prolonged fever if you can’t explain it otherwise.
Drug fever is a diagnosis of last resort.
20
 Indications for CT or MRI
When is a CT or MRI indicated? It is always indicated when the usual
course of disease is halted. When the child is not responding as you would
• When usual course of disease is altered: anticipate, such as with prolonged obtundation, seizures after 72 hours of
-Prolonged obtundation therapy, excessive irritability; often excessive irritability and meningeal

-Seizures >72 hr after diagnosis signs that continue may be a sign of subdural empyema; focal neurologic
findings, enlarging head circumference. All children with neonatal
-Excessive irritability
meningitis, especially those with Citrobacter diversus should have a CT
• Focal neurologic findings scan. We do a CT scan in all children with bacterial meningitis sometime
• Enlarging head circumference into the first week. The only exception being Listeria. It is not important in
Listeria because they all do well in Listeria. Not in the
• Neonatal meningitis, especially caused by Citrobacter diversus
immunocompromised Listeria patient but in the newborn with Listeria
• Persistently abnormal CSF value(s) meningitis. Otherwise we think all newborns should have it. But with C.
• Relapse or recurrence diversus it should be done right at the outset because 75% of those
patients have brain abscess. With persistently abnormal CSF values, a CT
or an MRI may reveal an abscess.

21
 Predisposing Factors Associated with Brain
Abscesses Brain abscess: The predisposing factors associated with brain abscess in
almost 60% were otitis, mastoiditis and sinusitis, congenital heart disease.
The next most common category is unknown.

Otitis/Mastoiditis and Sinusitis 38%

Congenital heart disease 20%
Unknown 14%
Trauma 7%
Meningitis 7%
Pulmonary infections 3%
Neurosurgery 2%
Miscellaneous 10%

22
 Bacteria Recovered from Brain Abscesses
Cultures positive/Done 82%
Etiologic agents of bacterial meningitis: Gram positive aerobes are the
most common and these are streptococci, more common than staphylo-
cocci. Twice as common. Streptococci, mainly the alpha Streptococci,
gram negative aerobes, mostly Enterobacteriaceae, followed by

Gram positive aerobes 68% Hemophilus followed by Pseudomonas. If you have a Pseudomonas brain
abscess, think of chronic otitis. Anaerobes are most common, where alpha
Gram negative aerobes 28%
Streptococci followed by Bacteroides and then some other gram-negatives.
Anaerobes 27% There are some miscellaneous ones. Then of course it is not infrequent to
Miscellaneous 7% have more than one organism as a cause of the abscess.

Multiple isolates 27%

23
 Therapy of Brain Abscess
• Initial empiric regimen can include anti-staphylococcal agent (nafcillin
or vancomycin), cefotaxime and metronidazole
• Specific therapy based on identification and susceptibility of organ-
ism(s)
• Duration dependent on surgical procedure (incision or excision), results
of follow-up imaging studies and clinical condition.
Therapy for brain abscess: the initial empiric therapy is variable but I think
it should include an anti-staphylococcal agent, even nafcillin or vancomycin.
And nafcillin is fine. So nafcillin, cefotaxime and metronidazole. I prefer
metronidazole for brain abscess for anaerobes. Specific therapy is based
on the identification of the organism, if you find the organism. That’s maybe
more difficult now than ever. Duration is totally dependent on what is done
with the patient. If a surgical procedure is done and it’s an excision of the
abscess, which they used to do more frequently than they do now, then only
about 7 - 10 days of therapy after complete excision is indicated. If it’s
incision or needle aspiration or nothing is done, than you must follow the
course of the child and the MRI’s or the CT’s to see how it’s responding.
Often therapy will be extended 4-6 weeks or longer.
24
 Aseptic Meningitis

• Total number: 14,526

• Cases by month: peaks in June to December

• Cases by age:
< 1 yr 22%
1 - 4 yrs 7.6%
5 - 9 yrs 10%
10 - 14 yrs 7%

25
 Etiology of Aseptic Meningitis
Etiologic agents of viral encephalitis: Herpes simplex is a common cause
of encephalitis. Herpes simplex type II is the one that the newborn most
Group B Coxsackieviruses 93 cases
frequently with - about 75% of the cases in causing meningitis and
Echoviruses 64 cases encephalitis - but it also causes a “aseptic meningitis” in older patients and

Polioviruses 7 cases is a sexually transmitted infection. And then the other causes: enterovirus
we think of as an aseptic meningitis but it also causes a
Group A Coxsackieviruses 3 cases
meningoencephalitis as well, adenoviruses as well plus the others.
Un-typable enterovirus 1 case
Adenovirus 1 case

26
SYMPTOMS IN PEDIATRIC PATIENTS WITH ASEPTIC MENINGITIS*
Patient Groups (%) <3 mos 3 mos-70 yrs
Fever 91 70
Irritability 43 66
Vomiting 7 57
Diarrhea 10 18
Coryza 22 13
Rash 17 2
In those > 5 yrs old: headache (95%), photophobia (56%).
and myalgia (15%)

27
CSF Findings in Patients <24 Mos of Age with
Aseptic Meningitis

INDEX
WBC (CELLS/MM3) 0-4050>1000: 7%
PMN(%) 0-100 > 75:16%
PROTEIN (MG/DL) 6-550 > 120:10%
CSF/SERUM GLUCOSE 27-130 < 40: 7%

28
PCR for Diagnosis of Aseptic Meningitis

• Sensitivity >95%; specificity 90-95%

• Pos. predictive value 76%

Neg. predictive value 96%

• Results in 5-6 hours

• Advantages: shorter antibiotic course, avoid steroid Rx and
reduced length of hospitalization.

29
 Acute Neurologic Complications of Aseptic
Meningitis

Age of Patients
< 12 Weeks > 12 Weeks
Finding
Complex seizures 0.9% 6.3%
Full fontanelle 3.3% 15.9%
Increased Head Circumference 0.9% 0
Diminished consciousness 0 3.2%

30
 Sequelae of Aseptic Meningitis

• 6 mos - 2 yrs. of age

• Headache, altered school performance, convulsions for 6 mos - 2 yrs in
21%
• Transient abnormalities not correlated with age, CSF findings or etiology
• No permanent sequelae

31
 Long-term Sequelae in Infants Who Had
Aseptic Meningitis at < 2 Years of Age

• Using age appropriate neurodevelopmental tests, the scores did not

differ between cases and controls
• No short or long term neurologic developmental sequelae

32
 Etiologic Agents of Viral Encephalitis

Herpes simplex viruses Tickborne viruses

Herpes simplex virus type t Powassan virus
Herpes simplex virus type 2 Colorado tick fever
(neonates)
Mosquito borne viruses Enteroviruses
LaCrosse Adenoviruses
St. Louis
Japanese Immunocompromised
Eastern equine Varicella-zoster
Western equine Epstein-Barr
Venezuelan equine Cytomegalovirus
Human herpesvirus type 6

33
 Neurocysticercosis
€ Most prevalent parasitic disease of CNS in United States
€ Uncomplicated neurocysticercosis is most common in non-endemic areas
after single exposure
€ Suspected in those with afebrile seizure(s).
€ Diagnosis: CT and MRI equivalent for detection of cysts and granuloma
in parenchyma. CT better for calcification and MRI for edema and
presence of cysts in VF and subarachnoid space.
€ Treatment: Albendazole (15 mg/kg daily x 8 days) preferred over
praziquantel (50 mg/kg daily x 15 days)
Neurocysticercosis: If you are in a state bordering Mexico we see this quite
frequently but it is not limited to those states. It is the most prevalent
parasitic disease of the central nervous system. Uncomplicated
neurocysticercosis is most common in non-endemic areas after a single
exposure, such as in the United States and you usually only have one cyst.
And that’s the vast majority of our patients. Although a few children may
have over 100 cysts. Suspect this diagnosis in those with afebrile seizures.
CT or MRI are useful for detecting the cyst in the CNS parenchyma. CT is
better for calcification, as you know, and MRI is for edema and the
presence of cysts in the ventricular fluid.
34
 Primary Amebic Meningoencephalitis
• Caused by Naegleria fowleri. Found in lakes, rivers and occasionally
heated pools.
• Inoculated during swimming/diving; 2-3 day incubation; acute and severe
signs of meningitis; unusual tastes and smells
• Diagnosis: Purulent CSF. Wet mount of unspun CSF reveals motile
amebae. Can be cultured on non-nutrient agar seeded with E. coli.
• Treatment: Not usually effective. Amphotericin (IV + IT) possibly
combined with miconazole, sulfadiazine and/or rifampin.
Treatment: The treatment of choice is albendazole, 15 mg/kg daily for 8
days. I think it’s preferred over praziquantel, 50 mg/kg daily for 10 days. A
single cyst and they have seizures doesn’t mean treatment because it has
already died. We normally do not treat a single cyst child and they do quite
well.
Primary amebic meningoencephalitis: this is a problem in summer time
caused by the acute suppurative disease caused by Naegleria fowleri.
Found in lakes, rivers and occasionally heated pools. It’s inoculated during
swimming, diving where it gets into the cribriform plate. One of the rare
permutations is unusual smell or taste because the cribriform plate is
involved in the process, but that’s pretty unusual. It is suspected in a child
who is acutely ill with purulent spinal fluid and in the summer months, and
no organisms are seen on gram stain smear. That should trigger you to ask
the lab to do a wet mount for the motile amebae. So It’s indicated in a child
who is very ill, with very purulent spinal fluid, nothing seen on gram stain
smear, in the summer. Treatment: not very effective. There have only been
several survivors. Amphotericin certainly intravenously, maybe intrathecally
and possibly combined with miconazole, sometimes given intrathecally and
rifampin. There are one or two survivors. It’s not a very good regimen. The
only other form of primary amebic meningoencephalitis that occurs
occasionally, but it’s more chronic, is Acanthamoeba. That’s very uncom-
mon but it does occur. The treatment of choice is ketoconazole, flucytosine,
with or without flucytosine.
35