Download All of Meningitis in One Hour

Meningitis:
Eosinophilic
Postneurosurgical
Steroids in Acute Bacterial Meningitis
You are consulted on this 33 yo male returning from Thailand
with peripheral blood and CSF eosinophilia, HA, neck stiffness,
and paresthesias across his chest and face…
Eosinophilic Meningitis
Nematodes
• Angiostrongylus
cantonensis
• Gnathostoma
spinigerum
• Baylisascaris
procyonis
• Toxocara canis
Cestodes
• Taenia solium
Trematodes Ectopic CNS
• Paragonimus
westermani
• Schistosomiasis
• Fascioliasis
Eosinophilic Meningitis
Nonparasitic
• Coccidiomycosis
• Cryptococcosis
• Myiasis
Noninfectious
• Foreign material in CNS
• Idiopathic
hypereosinophilic
syndrome
• Leukemia/lymphoma
• Cipro/Bactrim
• Intraventricular
gentamicin/vanc
• NSAIDS
• Myelography contrast
Angiostrongylus cantonensis
• Adults reside in
pulmonary arteries of
rats
• Eggs hatch in the
lungs, the larvae are
swallowed, expelled in
feces and seek an
appropriate molluscan
intermediate host
• Develops into infective
larvae in:
– Slugs, land snails
– Freshwater prawns,
land and coconut
crabs, frogs
Coconut Crabs
• Humans
are
incidental
hosts
• Larvae
migrate to
brain and
die
Angiostrongylus cantonensis
• Epidemics and sporadic infections reported in
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South Pacific
Southeast Asia
Tawain
Jamaica, Cuba, Egypt
• Recognized sources of human infection
– Raw or undercooked snails, prawns, crabs
– Contamination of leafy vegetables by larvae
deposited by slugs or snails
– Caesar salad recognized in one epidemic
NEJM 2002 246:668
• 12 cases
• 9 hospitalized
• Median #days until
HA – 11 days (6-31)
• CSF eosinophilia in
5/9 patients
• Peripheral blood
eosinophilia in 9/9
however only 4/9 at
admission
• 3 pts with severe HA
requiring repeat LPs
and steroids
All patients ate Caesar salad in
Jamaica on April 8
• Romaine lettuce was
imported from U.S.
• Canned, salted
anchovies
• Unknown if Jamaican
parsley garnish
present
Figure 1. Adult Angiostrongylus cantonensis recovered from rat lungs. A. Adult female
worm with characteristic barber-pole appearance (anterior end of worm is to the top).
Scale bar = 1 mm. B. Tail of adult male, showing copulatory bursa and long spicules
(arrows). Scale bar = 85 µm.
Infection in New Orleans
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11 yo boy
Children’s Hospital June 1993
7 days of HA, myalgias
5 days of low-grade fever and stiff neck
WBC 10.6 N51L36E6
CSF WBC 215 68% lymphs 16% eos
Admitted to eating a raw snail off the street
after a dare
Angiostrongylus infection
• Disease self-limited
• Rare fatal cases (massive inoculum)
• Incubation period 1-6 days after ingestion
of infected snails
• HA, stiff neck, fever, rash, pruritus,
abdominal pain, nausea, vomiting
• Paresthesias – chest wall, face, limbs
• Cranial nerve palsies (fourth and sixth
most common)
Angiostrongylus infection
• Occasionally larva seen on CSF
• MRI may show meningeal enhancement
or tracts in the brain, subcortical lesions
• Heavy worm burden increases probability
of brain involvement
• Serology to 31 kD Angiostrongylus
cantonensis antigen
Angiostrongylus treatment
• Supportive care
• Killing larvae in and around the brain may
be detrimental
• Repeated lumbar punctures helpful in
treating headaches
• Recovery usually complete by 2 months
• Corticosteroids decrease duration of
headaches
CID 2000; 31: 660-2
Steroids in Angiostrongylus
infection
• Prednisone 60 mg po qd for 2 weeks
decreases duration of headache from 13
days to 5 days
• No data on mortality or using steroids in
large worm burden patients but this makes
pathophysiologic sense
You are consulted on a 20 yo traveler returning from Korea
(after eating the pickled fish and kimchi) with high peripheral
eosinophilia and eosinophilic meningitis…
Gnathostoma spinigerum
• Adult worms reside in stomachs of cats,
dogs, opposums, raccoons
• Eggs shed in feces and hatch in one week
• Subsequently ingested by small
crustaceans called Cyclops
• These crustaceans are then ingested by
fishes, frogs, snakes where they encyst in
the muscle as infectious larvae
Gnathostoma spinigerum
• Most infections occur
after eating undercooked
or pickled freshwater fish,
chicken or pork
• Infectious larvae can also
burrow through the skin
• Infections may occur after
ingesting Cyclops in
contaminated water
Kimchi preparation
Cyclops
Gnathostomiasis
• Nausea, vomiting, gastrointestinal pain
and fever shortly after ingestion
• 3-4 weeks after ingestion, intermittent
migratory subcutaneous swellings
• Usually nonpitting, often erythematous,
and occasionally pruritic and painful
• May resemble classic cutaneous larva
migrans
• Eosinophilia may be extreme
Gnathostomiasis
• Migrating larvae may invade any tissue
• Although gnathostomiasis is a less
frequent cause of encephalomyelitis
compared to A. cantonensis it tends to
result in permanent neurologic deficits and
death because there is more invasion of
the brain
• Ivermectin and albendazole give cure
rates >90%
You are consulted on a 32 yo man who cleaned raccoon feces
off of his house then rubbed his eye…
Baylisascaris procyonis
• Ascarid of raccoons
• Visceral larval migrans in humans
• Severe and commonly fatal eosinophilic
meningoencephalitis occurs in more than half
the cases
• Eye involvement is common
• Diagnosed by detecting larvae in tissue
• Experimental serology
• Albendazole and steroids are commonly tried
“Raccoon Roundworm”
Encephalitis
LATIN
Procyon lotor
– Pro – before
– Kyon – dog
– Lotor -- washer
Procyon lotor
CID 2004: 39 (15 November) p 1484
Risk Factors for Baylisascariasis
• Exposure to raccoon latrines
• PICA/geophagia
• Age < 4 yrs
• Male sex
Asymptomatic infections?
• 389 children in Chicago
• Ages 1-4 yrs
• 8% seropositive for Baylisascaris
procyonis
• Previously, only 2 cases of severe CNS
baylisascariasis in children in Chicago
suburbs
Pediatr Infect Dis J. 2002 Oct;21(10):971-5.
Bayliscariasis
• Once shed in raccoon feces, the
Baylisascaris procyonis eggs become
infective in 2-4 weeks
• After ingestion of eggs, infective larvae
emerge, penetrate gut and migrate
through liver and lung and are distributed
by bloodstream to somatic tissues
• Only 5-7% of ingested larvae penetrate
CNS and eye
Bayliscariasis
• Severity of disease
– Number of eggs ingested
– Extent/location of larval migration
– Severity of ensuing inflammation and necrosis
Diagnosis
• Clinical findings and exposure
• Stool O&P on patient not useful (no adult in
intestines)
• Peripheral and CNS eosinophilia
• Deep white matter lesions on MRI
• Serology
– Dept of Veterinary Pathology at Purdue
• (765) 494-7558
• Exclusion of other causes of visceral, ocular or
neural larval migrans
– ELISA for Toxocara at CDC
Treatment
• Laser photocoagulation in ocular dz
• No cure for clinical disease
• Albendazole and dexamethasone used with
good CNS and ocular penetration
• Prophylaxis with albendazole on days 1-10 or
days 3-10 after exposure offers 95-100%
protection
• No children receiving albendazole after eating
raccoon feces have developed baylisascariasis
CID 2004: 39 (15 November)
Toxocara canis
• Rarely visceral larval migrans of
toxocariasis can involve the CNS
• Several case reports of albendazole and
corticosteroids with good outcome
• Definitive diagnosis by demonstration of
larvae in tissue
• ELISA serology
Am J Trop Med Hyg. 2003 Sep;69(3):341-3.
Board Review
Steroids in Adults with Bacterial
Meningitis
• 5 published trials
– 3 randomized placebo controlled
– 1 randomized but no placebo
– 1 systemic sampling open cohort study
• In 4 of 5 studies results inconclusive
• However de Gans and van de Beek study
rather influential on current practice
• Inclusion Criteria
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17 years of age or older and
Cloudy CSF or
Bacteria on gram stain or
CSF leukocyte count > 1000 cells/mm3
• Exclusion Criteria
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Betalactam allergy
Pregnant
Cerebrospinal shunt
Antibiotics in previous 48 hrs
Recent head trauma or neurosurgery
PUD, active TB, fungal infection
Treatment
• Dexamethasone 10 mg IV q6 for 4 days or
placebo
• Amoxicillin 2 g IV q4h for 7-10 days
• Regimen based on available data on
susceptibility to antibiotics of CSF isolates
in Netherlands
Conclusions
• Is adjunctive dexamethasone detrimental in
patients with meningitis caused by S.
pneumoniae that are resistant to PCN or
cephalosporins?
• A diminished inflammatory response may
reduce CSF vancomycin concentrations
• 78 of 108 CSF cultures positive for S.
pneumoniae (72%) were submitted for
susceptibility testing – all sensitive to PCN
• That’s a perfect world
Conclusions
• What about the delay in inclusion of
patients only with CSF findings?
• Will we see more gain from treating even
earlier than in this study?
• Did we not see a difference in neurologic
deficits because dexamethasone kept
sicker patients alive?
• What would we see with formal
neurocognitive testing?
Conclusions
• Routine use of dexamethasone is
warranted in most adults with suspected
pneumococcal meningitis
• If the meningitis is found not to be caused
by S. pneumoniae, dexamethasone should
be discontinued
• If the strain is highly resistant to PCN or
cephalosporins “careful observation and
follow-up are critical”
Case Presentation
• 35 yo WM OIF
• IED blast 26 December
• Bilateral frontal and posterior fossa
hemicraniectomies and right partial
lobectomy and ventriculostomy
• Calvarium salvage into abdomen
• January 14 ventriculostomy removed
• February 26th pt becomes febrile/obtunded
Case Presentation
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Temperature to 104, pupils dilated
Tracheostomy/ PICC line
Blood cultures drawn, PICC line DC’d
CT – mild hydrocephalus, right frontal lobe
remnant blood without rim enhancement
• Lumbar drain placed by Neurosurgery with
purulent CSF returned
• Blood and CSF cultures E. coli
• Sensitive to Cefepime/Ceftaz/Ceftriaxone/
Cipro/Gent/Imipenem/Zosyn/
Amikacin
Resistant to Ampicillin/Unasyn/Bactrim
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2/26
2/27
2/28
3/2
3/3
3/5
3/6
3/7
3/12
WBC 1,822
WBC 192,000
WBC 4,380
WBC 2,725
WBC 1,765
WBC 125
WBC 970
WBC 100
WBC 293
g <10 p 413 GNR
g 20 p 368 GNR
g 20 p 280 GNR
g 34 p 290 GNR
g 40 p 230 GNR
g 35 p 169 neg
culture negative
culture negative
culture negative
• Imipenem/Gent and intrathecal polymyxin
50,000 units qd via lumbar drain
• Meropenem/Amikacin and intrathecal
amikacin 10 mg qd
• Meropenem/Amikacin and intrathecal
polymyxin
• Due to lack of sterilization of CSF cultures,
ventriculostomy placed and polymyxin
instilled directly into ventricles
Aminoglycosides in CSF
• Aminoglycosides are hydrophilic and cross
blood-brain barrier poorly
• Lumbar sac administration yields high local CSF
drug levels but poor intraventricular levels
• Intraventricular administration yields high
concentrations in both ventricular and spinal
fluid
• In newborns intraventricular aminoglycoside is
no more effective and may be more toxic than
given intravenously
NEJM 1975; 293:1215-1220
J Neurosurg 1979; 50:95-99
Lancet 1980; 1:787-791