Meningitis Cns Infections Sepsis

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

• Interleukin - 1

• Interleukin gamma

endothelial damage, which is one of the critical areas in the pathogenesis

• 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

• Interleukin - 10

• White blood cell products

all of this is that you eventually get ischemia and reperfusion injury and

of both cells. Because not only does it lead to alteration of the blood-brain

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 Sepsis. SIRS, systemic inflammatory response syndrome, to sepsis,

• SIRS--

Presence of two or more of the following: altered temperature, tachypnea, tachycardia and abnormal WBC

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

• SEPSIS --SIRS with proven/suspected microbial etiology

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

• SEVERE SEPSIS --Sepsis with signs of organ dysfunction

look at it without multiple organ dysfunction it’s 32%. With multiple organ dysfunction it’s 66%.

• SEPTIC SHOCK-- SEPSIS with hypotension and multiple organ dysfunction (may become refractory)

3

Bacteriology and Outcome of Pediatric Sepsis Meningococcemia portends a very poor prognosis. Meningococcemia is

Organism

%

% Deaths

S. aureus

31

23

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

probably associated with a mortality rate of 15-30%. 73% would be rather high. You also have a very high case mortality rate in Pseudomonas, but it’s pretty much true in many centers, this Pseudomonas is the problem.

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

DIC

68%

ARDS

34%

Renal failure

9%

Pancreatitis

7%

Myocarditis

7%

Adrenal hemorrhage

5%

Myocardial infarction

2%

aspects of meningococcemia is the amputations that result from infarcts of skin and bone in the extremities. So this is a really severe complication.

6

Initial Empiric Therapy for Sepsis Initial empiric therapy for sepsis varies. In newborns ampicillin and

Community-acquired

aminoglycoside, cefotaxime. There are no data that show that with 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

Children

Ceftriaxone, Cefotaxime

Hospital-acquired Anti-staph + aminoglycoside, or cephalosporin Immunocompromised

not like cefotaxime used routinely in nurseries where every child is suspected of something because of the potential for resistance. In infants and children, ceftriaxone and cefotaxime you are not going to use that routinely.

With hospital acquired infections, nosocomial diseases, we usually use an

Many possibilities: Anti-staphylococcal penicillin + Aminoglycoside or

anti-staphylococcal with an aminoglycoside or a cephalosporin, depending

cephalosporin; cephalosporin + Aminoglycside; cephalosporin alone;

on what you encountered and what the predisposing factors are. If MRSA

meropenem alone. Anaerobe coverage for intraabdominal or pelvic origin

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 Meningitis

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 %

Group B Streptococcus

52

15

Enterococcus

5

25

Group D Streptococcus

3

0

Staphylococcus aureus

8

50

Others

2

0

Escherichia coil

9

28

Klebsiella pneumoniae

3

0

Enterobacter cloacae

3

0

Serratia marcescens

3

0

Other gram-negative rods

8

25

1

0

include E. Coli, Klebsiella and Enterobacter species.

Gram-positive pathogens

Gram-negative pathogens

Fungi Candida albicans

8

Meningococcal Meningitis 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

•

Incidence is sporadic; recent small outbreaks in many U.S. cities.

•

Prognosis with meningococcemia worse (fatality rate=12-30%) than with

meningitis. It may be linked to endotoxin concentrations because in

meningitis (fatality rate=4-5%).

meningitis there is very little circulating endotoxin in the blood stream. Thus

•

May relate to endotoxin concentration in different body fluids

•

Limb amputation and skin grafting is common in meningococcemia

prognosis of meningococcemia is considerably worse than that for

you are not prone to DIC and shock. Of course, shock coupled with meningitis is devastating in terms of cerebral blood flow.

with shock •

Long-term sequelae in 5 - 10%, hearing alterations

9

Pneumococcal Meningitis 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

•

Incidence varies; no evidence of increased virulence

•

Case-fatality rates approx. 10% in children. The virulence of pneumococci

meningitis is by far more severe than meningococcal or Hemophilus. This

has not changed in recent years.

incidence varies considerably. The case fatality rate in children is about

•

•

Long-term morbidity >30.%; hearing impairment common and occurs

probably being the single most common abnormality. Pneumococcal

10%. In adults, considerably higher. About 30%.

early in disease (reversible, it not severe/profound).

Long term morbidity is high in meningococcal and it varies from probably

Multidrug resistance increasing worldwide

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 Antibiotic Therapy for Bacterial Meningitis

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

•

Absent specific antibody and functional complement in CSF

bacteria in CSF at the time of diagnosis is around 107 organisms. That is why with Hemophilus, Pneumococcus and usually Meningococcus, if they

-

Inefficient phagocytosis of pathogen

are not pretreated, can be seen readily on the gram stain smear of CSF.

-

High conc. of bacteria in 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

•

Poor penetration into CSF

•

Bactericidal versus static activity

a very poor prognostic sign. So it also relates to concentrations of 108 or 109

•

Drug in CSF: peak conc. vs persistent conc. in relation to MIC

organisms, the prognosis is poor. It is very difficult to see Listeria in the

per high power field. If you see myriads of organisms at the outset, that’s

CSF of babies with meningitis because they have on average 103 organisms, 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 Empiric 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

Late onset:

Term infant same as above

Maybe initially, but we’ll use cefotaxime alone once we know the organism

Vancomycin + amikacin or cephalosporin

and we know that the child is clearly responding to it. Late onset, low birth

LBW/preterm:

glycosides and we usually do not keep a combination going for coliforms.

weight, premature term infant who is in the hospital usually has a

When Etiology Known Group B strep: Ampicillin +/- aminoglycoside Coliforms:

Cefotaxime +/- aminoglycoside

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: Ceftazidime +/- aminoglycoside

Pseudomonas: we almost always use a combination. Listeria: we use

Listeria:

ampicillin alone. We don’t see much Listeria. One of the few cases of

Ampicillin +/- aminoglycoside

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 Non-neonatal meningitis: Ceftriaxone or cefotaxime is recommended in an

Modifications of the Initial Empiric Regimen •

•

area where there is pneumococcal penicillin resistance is a problem, alter the cephalosporin regimen, increasing the dosage of cefotaxime to 75 mg

Larger dosage of cefotaxime (75 mg/kg Q 6h) or one extra 80-100 mg/kg

/kg every 6 hours. This maintains the concentrations during the dosing

dose of ceftriaxone at 12 hr

interval of six hours in the CSF over the MIC of the organism for at least

Addition of vancomycin (15 mg/kg Q 6h), in all age groups, until results of cultures and susceptibility testing are available

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

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.

• NEONATES GBS and other strep.

There are some very beautiful studies in adults and 4 days is totally

10-14 d

Gram neg. enterics

21 d

Listeria

10 d

effective. 4-7 days is adequate. Hemophilus: 7-10 days. Pneumococcus: 10 days for the child who has an uncomplicated course.

• INFANTS AND CHILDREN Meningococcus Haemophilus Pneumococcus

4-7 d 7-10 d 10 d

14

New Antimicrobial Agents for Treatment of Meningitis

New agents: the only one approved so far is meropenem. The dosage for 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

*

Meropenem (Merrem)

*

Cefepime (Maxipime)

pneumococci. There is really not enough experience with the drug yet to know whether it will be effective alone as therapy for cephalosporinresistant 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

Cefpirome

ceftriaxone-resistant strain. Cefepime has not been approved for pediatric 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

€ Regimen: 0.6 - 0.8 mg/kg daily in 2, 3

or 4 divided doses for 2 - 4

per kilo daily, 2-3 times daily, in two or three doses is fine. And I’d do it for two days.

days € First dose should be given before or at the time of the first parenteral antibiotic dose € lt is doubtful that dexamethasone will be effective if given more than 30 to 60 min after the first parenteral antibiotic dose

The first dose of dexamethasone should be given before or at the same time as the first parenteral dose. Remember the effects of dexamethasone is only on what the first dose of the antibiotic does to the organs, in the releasing more of the antitoxin or cell wall products and it’s subsequent 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

€ Approximately 90% of children with bacterial meningitis had Increased

water, mainly extracellular fluid. SIADH was found in 50% and that varies 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

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,

•

•

50 children with meningitis divided according to presence of, decreased

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

Na and randomized to receive maintenance or restricted fluid.

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

€ Indications

in meningitis in all neonates in about 24 - 48 hours. You can not look at the 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-

- Lack of clinical improvement within 24 - 36 hrs of starting treatment

ment in the first 48 hours. You anticipate for a child with meningococcemia

- Resistant pneumococcal meningitis - Prolonged or secondary fever € Not indicated at completion of therapy in uncomplicated patients, except for neonates at end of treatment

that in 48 hours that child is going to show improvement. If that child doesn’t show improvement, something’s wrong. Either the wrong dose or something happened, and that must be evaluated. A normal child, the child 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 What about prolonged fever in meningitis? Prolonged fever in meningitis the first thing to know about fever is what is the expected pattern? With

•

Be familiar with usual fever patterns

•

Check details of antibiotic regimen

children who had some fever. Their temperature was coming down but they

•

Examine for focal neurologic signs, phlebitis, arthritis, URI and UTI

were not afebrile. With meningococcus, if they are still febrile after four or

•

Consider CRP, LP, imaging studies

•

If above is unrevealing, drug fever is possible

Hemophilus it came down slowly, so in five days you still had 20% of

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 secondary 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

•

When usual course of disease is altered:

course of disease is halted. When the child is not responding as you would 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

-Excessive irritability

findings, enlarging head circumference. All children with neonatal 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

•

Neonatal meningitis, especially caused by Citrobacter diversus

Listeria

because

they

all

do

well

in

Listeria.

Not

in

the

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 Etiologic agents of bacterial meningitis: Gram positive aerobes are the most common and these are streptococci, more common than staphylococci. Twice as common. Streptococci, mainly the alpha Streptococci,

Cultures positive/Done

82%

gram negative aerobes,

Gram positive aerobes

68%

Hemophilus followed by Pseudomonas. If you have a Pseudomonas brain

Gram negative aerobes

28%

Anaerobes

27%

Miscellaneous Multiple isolates

7%

mostly Enterobacteriaceae, followed by

abscess, think of chronic otitis. Anaerobes are most common, where alpha Streptococci followed by Bacteroides and then some other gram-negatives. There are some miscellaneous ones. Then of course it is not infrequent to have more than one organism as a cause of the abscess.

27%

23

Therapy of Brain Abscess Therapy for brain abscess: the initial empiric therapy is variable but I think

•

•

Initial empiric regimen can include anti-staphylococcal agent (nafcillin

And nafcillin is fine. So nafcillin, cefotaxime and metronidazole. I prefer

or vancomycin), cefotaxime and metronidazole

metronidazole for brain abscess for anaerobes. Specific therapy is based

Specific therapy based on identification and susceptibility of organ-

on the identification of the organism, if you find the organism. That’s maybe

ism(s) •

it should include an anti-staphylococcal agent, even nafcillin or vancomycin.

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

Duration dependent on surgical procedure (incision or excision), results

abscess, which they used to do more frequently than they do now, then only

of follow-up imaging studies and clinical condition.

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

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

Group A Coxsackieviruses

3 cases

Un-typable enterovirus

1 case

Adenovirus

1 case

frequently with - about 75% of the cases in causing meningitis and

we think of as an aseptic meningitis but it also causes a meningoencephalitis as well, adenoviruses as well plus the others.

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) PMN(%)

0-4050>1000: 7% 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 LaCrosse

Enteroviruses Adenoviruses

St. Louis Japanese

Immunocompromised

Eastern equine

Varicella-zoster

Western equine

Epstein-Barr

Venezuelan equine

Cytomegalovirus Human herpesvirus type 6

33

Neurocysticercosis Neurocysticercosis: If you are in a state bordering Mexico we see this quite

€ 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

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

in parenchyma. CT better for calcification and MRI for edema and

better for calcification, as you know, and MRI is for edema and the

presence of cysts in VF and subarachnoid space.

presence of cysts in the ventricular fluid.

€ Treatment: Albendazole (15 mg/kg daily x 8 days) preferred over praziquantel (50 mg/kg daily x 15 days)

34

Primary Amebic Meningoencephalitis Treatment: The treatment of choice is albendazole, 15 mg/kg daily for 8

• Caused by Naegleria fowleri. Found in lakes, rivers and occasionally heated pools.

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

• 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.

days. I think it’s preferred over praziquantel, 50 mg/kg daily for 10 days. A

Amphotericin (IV + IT) possibly

combined with miconazole, sulfadiazine and/or rifampin.

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 uncommon but it does occur. The treatment of choice is ketoconazole, flucytosine, with or without flucytosine.

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