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• Paragonimus

westermani• Schistosomiasis• Fascioliasis

Ectopic CNS

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– 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

• 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 serologyAm 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– 17 years of age or older and– Cloudy CSF or– Bacteria on gram stain or– CSF leukocyte count > 1000 cells/mm3

• Exclusion Criteria– 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

• 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

• 2/26 WBC 1,822 g <10 p 413 GNR

• 2/27 WBC 192,000 g 20 p 368 GNR

• 2/28 WBC 4,380 g 20 p 280 GNR

• 3/2 WBC 2,725 g 34 p 290 GNR

• 3/3 WBC 1,765 g 40 p 230 GNR

• 3/5 WBC 125 g 35 p 169 neg

• 3/6 WBC 970 culture negative

• 3/7 WBC 100 culture negative

• 3/12 WBC 293 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