Eosinophilic meningitis
Mary Naguit
Eosinophilic meningitis is a rare entity. The key criteria is that the cerebrospinal fluid
shows the presence of an increased number of eosinophil in a patient with clinical manifestations
of meningitis. The most common causes of eosinophilic meningitis worldwide are the parasitic
infections caused by nematodes.
Etiologies
Eosinophilic meningitis due to parasites is most often seen as sporadic cases in Southeast
Asia, South Pacific and the Caribbean. The most widely reported cause is Angiostrongylus
cantonensis. The larvae of this rat lung nematode are ingested in undercooked seafood such as
crabs, prawns and snails. Gnasthoma spinigerum is an intestinal nematode of cats and dogs,
which is acquired by eating undercooked fish. The increase in world travel and ship-borne
dispersal of infected rats leads to more cases being reported outside Southeast Asia. In the United
States, Baylisascaris procyonis is the most common parasitic cause of eosinophilic meningitis;
this infection is acquired by accidental ingestion of raccoon feces.
Coccidiodes immitis is often cited as the most common nonparasitic infectious cause of
eosinophilic meningitis, but such an occurrence is still uncommon. A case report by Almoujahed
et al(2001) showed occasional eosinophils in the CSF with a 55 year old African-American male
with a history of VP shunt placement. It turned out that the patient had a history of travel to
California and developed pulmonary Coccidioidomyosis which disseminated to the central
nervous system complicated by hydrocephalus. The disease remained indolent after the VP shunt
placement and was diagnosed incidentally 3 years after during a shunt malfunction.
Myeloproliferative disease in the form of hematologic malignancies or metastatic cancer
should be ruled out if an infectious etiology is not found. Procedures involving the spinal cord
including contrast myelography and ventriculoperitoneal shunts can also cause an increase in
eosinophilia in the CSF. In the pediatric age group, eosinophilic meningitis is most commonly
caused by a ventriculoperitoneal shunt. A study by Fulkerson et al in 2008 described the risk
factors, relationship to infection, and clinical significance of CSF eosinophilia in a large group of
shunt-treated pediatric patients. Eosinophils were recognized during a follow-up shunt evaluation
in 31% of 300 patients after preliminary placement. They concluded that cerebrospinal fluid
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eosinophilia is a common occurrence in the pediatric age group with shunts. Patients with CSF
eosinophilia leads to more shunt malfunction. Patients with Propionibacterium acnes-induced
shunt infections have higher eosinophil percentages than are found in infections associated with
other organisms. The researchers suggested anaerobic culture studies to be performed in
suspected cases of eosinophilic meningitis in patients with shunts.
An interesting case of allergic Aspergillus sinusitis causing eosinophilic meningitis was
reported in the National University Hospital in Singapore. The patient presented with cavernous
sinus thrombosis leading to abducens nerve palsy and CSF eosinophilia. The latter was deemed
not a consequence of a concomitant CSF infection caused by Angiostrongylus or other parasites
because of the negative epidemiologic risk factors. Clinical features noted are the products of the
inflammatory contents of the sinus eroding through the sinus wall with leakage into the venous
sinuses and subarachnoid space. Erosion through the intraethmoid septae, the lamina papyracea,
through the cribriform plate or posterior wall of the frontal sinus into the epidural space was
noted. The process is thought to be caused by bone resorption secondary to the expanding
allergic mucin mass.
Another interesting but rare case is CSF eosinophils in an infant. A report in University
of Virginia Health Sciences Center by Hewett and Hendley. There were noted two cases of
rapidly occurring CSF eosinophilia caused by GBS meningitis in 2-week-old infants, they
concluded that the influx of white blood cells in response to GBS in the subarachnoid space may
be particularly likely to proceed along the humoral or antibody mediated pathway in infants two
weeks of age and less.
Clinical Manifestations
Severe headache is the most common complaint and has been attributed to intracranial
pressure. Nausea, vomiting and neck stiffness are frequent. Paresthesias of the thorax and
extremities are seen. Altered consciousness and generalized weakness are rare. Fever is not a
prominent symptom even in infection. Other nonspecific symptoms include visual disturbances,
photophobia, vomiting, arthralgias, myalgias, GI and respiratory symptoms.
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Laboratory Diagnosis
The definition of eosinophilic meningitis is presence of eosinophilia in the CSF, either
greater than 10 eosinophils/mm3 or greater than 10% of the total CSF leukocytes, in a patient
with symptoms of meningitis. The CSF shows leukocyte counts in the range of 20-5000 cells
(usually 150-2000). Wrights solution or Giemsa stain is commonly used to visualize the CSF
eosinophilia. Peripheral blood eosinophilia does not correlate with CSF eosinophilia.
CSF
eosinophilia is usually 20 – 70% with normal or minimally low glucose and slightly elevated
CSF Protein.
In eosinophilic meningitis due to parasites, eosinophila pleocytosis peaks at weeks 1-2
and then gradually resolves over several months. To note,
invasion by helminths
of the central
nervous system is the most recurrent cause of eosinophilic pleocytosis in the CSF.
CSF opening pressure is variable and should be performed to determine if measures to
decrease intracranial pressure are warranted.
For Angiostrongylus cantonensis, CSF ELISA and Serum ELISA have the highest
accuracy. Monoclonal antibody against CSF antigens is useful, if available.
CNS imaging should be performed to exclude other potential causes of meningitis. Focal
lesions are not expected on CT or MRI. Ophthalmologic evaluation should be performed to
screen for the presence of elevated intracranial pressure. In patients with parasites, larvae may
be seen in the eye.
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Therapy
The disease is usually self-limiting if the cause is infectious or due to spinal cord
manipulation, although some symptoms including headache may persist for > 4 weeks.
Most of the patients affected with eosinophilic meningitis can be adequately managed
with supportive therapy with analgesics plus rehydration. NSAIDs should be avoided since they
are occasionally the direct cause of CSF pleocytosis and headache. In patients with increased
intracranial pressure, serial lumbar punctures may produce major clinical improvement.
Antihelminthic agents are commonly prescribed for parasitic infections although
neurological symptoms often worsen because of larvae death within the CSF.
Corticosteroid therapy provides symptomatic relief of headaches. In a double-blind
placebo controlled trial of 129 adult (> 15 years old) patients with eosinophilic meningitis and
who were admitted in a Thai hospital were studied. A 2 week course of prednisolone was
efficacious in treating headaches refractory to supportive therapy. The dose used was 60mg
prednisolone/day (Chotmongkol V, CID 2000). Albendazole or mebendazole was also thought
to be effective in the pediatric age groups but should be used with caution as it may exacerbate
neurologic symptoms especially if the larvae has matured in the
Conclusion
Eosinophilic meningitis is a manifestation of an underlying illness. It is a syndrome with
varied etiologies, including parasitic infections. While rare, the worldwide incidence of these
organisms should make a clinician have a high index of suspicion.
Presence of persistent headache and eosinophilia in travelers coming from developing
countries or residents of Asia should raise the index of suspicion for eosinophilic meningitis due
to parasites (Leone 2007, Kirsh 2008). A thorough travel and food history is thus should be
performed on all patients with eosinophilic meningitis.
After infectious diseases, especially parasitic diseases have been ruled out, a search for an
underlying hematological disease by examination of peripheral blood smear and bone marrow
aspiration is indicated if infection cannot be confirmed and if no evidence of spinal cord or CSF
manipulation has occurred.
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If eosinophilic meningitis was found to be caused by a parasite, there is currently no
vaccine is available to prevent this infection. As with any other form of parasitic disease, people
exposed to sources of these infections should watch out for fresh produce that have been
contaminated by snails, slugs or raccoon feces. Thorough cleaning however does not eliminate
the larvae so caution in intake of these foods is important. Undercooked mollusks, prawns, fish
and crabs should also be avoided.
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Reading List
1. Almoujahed MO, et al. Coccidioidal meningitis: incidental diagnosis 3 y after ventriculoperitoneal shunt placement for hydrocephalus. Scand J Infect Dis. 2002;34(2):142-3.
2. Barry M, Thanassi W. Meningitis, Eosinophilic. Encyclopedia of the Neurological Sciences.
p102-105.
3. Chan YC et al. Eosinophilic meningitis secondary to allergic Aspergillus sinusitis. J Allergy
Clin Immunol - 01-JUL-2004; 114(1): 194-5
4. Chotmongkol V, Sawanyawisuth K, Thavornpitak Y. Corticosteroid for eosinophilic
meningitis. Clin Infect Dis. 2000;31:660–2.
5. Chotmongkol V, Sawanpanitch K, Sawanyawisuth K, Louhawilai S, Limpawattana P.
Treatment of eosinophilic meningitis with a combination of prednisolone and mebendazole. Am
J Trop Med Hyg 2006;74:1122-1124.
6. Chotmongkol. V et al. SE Asian J Trop Med Pub Health. 2004; 35:172-174.
7. Eosinophilic meningitis in a neonate. Clin Pediatr Eosinophilic Meningitis. Infectious
Disease Epidemiology Section. Office of Public Health, Louisiana Dept of Health & Hospitals.
8. Fulkerson DH et al. Cerebrospinal fluid eosinophilia in children with ventricular shunts. J
Neurosurg Pediatr. 2008 Apr;1(4):288-95.
9. Hewett FA 2nd and Hendley JO. (Phila). 2002 May;41(4):269-71. Department of Pediatrics,
University of Virginia Health Sciences Center, Charlottesville 22901, USA.
10. Kirsch S, Dekumyoy P, Loescher T, Roman L, Haberl. A Case of Eosinophilic Meningitis in
Germany. J Neurol (2008) 255:1102–1103. DOI 10.1007/s00415-008-0846-2.
11. Sebastiano Leone S, De Marco M, Ghirga P, Nicastri E, Esposito M, Narciso P. Eosinophilic
Meningitis in a Returned Traveler From Santo Domingo: Case Report and Review. Journal of
Travel Medicine. Vol 14 Is 6, p407 – 410.
12. Slom TJ et al. An outbreak of eosinophilic meningitis caused by Angiostrongylus
cantonensis in travelers returning from the Caribbean. N Engl J Med. 2002;346(9):668-75.
13. Weller P, "Chapter 209. Trichinella and Other Tissue Nematodes" (Chapter). Fauci AS,
Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles
of Internal Medicine, 17th Edition: http://www.accessmedicine.com/content.aspx?aID=2896618.
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Table: Causes of Eosinophilic Meningitis( Barry and Thanassi, 2003)
Parasites:
Common
-
Angiostrongylus cantonensis
-
Gnasthoma spinigerum
-
Baylisascaris procyonis
Less Common
-
Taenia solium(neurocysticercosis)
-
Schistosomiasis(ectopic CNS/spinal)
-
Paragonimiasis(ectopic CNS/spinal)
-
Toxocariasis(migrating larvae)
-
Strongyloidiasis(migrating larvae)
-
Onchocerciasis
-
Ascariasis(migrating larvae)
-
Echinococcosis(ectopic CNS cysts)
-
Trichinosis
-
Fascioliasis
-
Coenurosis(ectopic CNS cysts)
Nonparasitic infectious etiologies
-
Coccidiomycosis
-
Cryptococcosis(rare)
-
Myiasis (ectopic CNS penetration)
-
Other bacterial, rickettsial, or viral meningitis (very rare with low-level CSF
eosinophilia)
-
Meningeal tuberculosis (rare)
Drugs
-
Antimicrobials: Ciprofloxacin, Cotrimoxazole
-
Intraventricular Gentamicin/Vancomycin
-
NSAIDS, Ibuprofen
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Myeloproliferative diseases
-
Hypereosinophilic syndrome
-
Hodgkin’s disease
-
Leukemia
-
Lymphoma
-
Disseminated glioblastoma
-
Paraneoplastic syndrome associated with lung cancer
Procedures involving the spinal cord and CSF
-
Contrast myelography
-
Ventriculoperitoneal shunts
Miscellaneous conditions
-
Sarcoidosis
-
Eosinophilic granuloma
-
Multiple sclerosis
-
Allergic Aspergillus Sinusitis(Chan et al 2004)
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