Review Article

Fungal Meningitis Due to

Contaminated Epidural
Steroid Injections

* 2012, American Academy

of Neurology.

Karen Roos, MD, FAAN

In the fall of 2012, as we finalized this

, an unpreceissue of
dented outbreak of fungal meningitis
occurred that was caused by contaminated preservative-free methylprednisolone acetate solution from the New
England Compounding Center used in
epidural steroid injections in thousands
of patients. The predominant pathogen
was found to be Exserohilum rostratum
(a black mold). Aspergillus fumigatus
and Cladosporium were identified, as
well. At the time of writing, all of the patients who have become sick received
epidural steroid injections with methylprednisolone from one of three contaminated methylprednisolone lots.
Seventeen thousand five hundred vials
of methylprednisolone from these
contaminated lots were distributed to
75 facilities in 23 states.1
Neurologists are knowledgeable
about the treatment and complications
of fungal meningitis. In this issue of
, Drs Zunt and Baldwin
review the diagnosis and treatment of
meningitis due to Cryptococcus neoformans, Histoplasma capsulatum,
Coccidioides immitis, and Aspergillus
fumigatus in the article Chronic and
Subacute Meningitis. The complications of fungal meningitisVmost notably
hydrocephalus, increased intracranial
pressure, and strokeVare difficult to
manage. Shunt obstructions in CNS
mold infections are common, requiring multiple shunt revisions and associated morbidity.
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Fungal meningitis causes subacute

meningitis, which by definition is headache and low-grade fever of 4 weeks or
greater duration caused by inflammation that evolves over weeks to months.
As of November 5, 2012, the US
Centers for Disease Control and Prevention (CDC) has not recommended
antifungal prophylaxis or lumbar puncture for asymptomatic patients who
received epidural steroid injections.
The CDC has recommended the initiation of IV voriconazole, 6 mg/kg every
12 hours, for symptomatic patients with
meningitis or parameningeal infections
who received contaminated epidural
steroid injections until the etiology of
the meningitis or parameningeal infection can be determined. In addition,
the CDC has recommended consideration of IV liposomal amphotericin B,
7.5 mg/kg/day, in addition to voriconazole, in patients with severe disease
and in those who do not improve or
have progressive disease with voriconazole monotherapy.2
As the number of deaths continues
to rise, both neurologists and their
patients hope for the ability to identify
CNS infection or parameningeal infection prior to the onset of symptoms.
The index case of Exserohilum rostratum, reported by Lyons and colleagues,3 had abnormal enhancement
on MRI in cervical paraspinal muscles
at the epidural steroid injection site
suggestive of possible infected fluid
collection. Two serologic tests are
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Fungal Meningitis

available for invasive fungal disease.

The Aspergillus galactomannan assay is
sensitive and specific for invasive infection due to Aspergillus species,
while the $-D-glucan assay is sensitive
for invasive fungal disease.4 CSF analysis is either normal or abnormal. In
meningitis caused by a fungus or mold,
there is a CSF pleocytosis, a decreased
glucose concentration, and an increased protein concentration. In a
parameningeal infection, CSF pleocytosis and an increased protein concentration are characteristic. CSF should
also be sent for fungal smear and
culture, the $-D- glucan assay, and the
Aspergillus galactomannan assay. CSF
should not be obtained at the level of
the neuroaxis where the epidural
steroid injections were given because
of the risk of spinal osteomyelitis or
epidural abscess at the site of injection.
If serology or CSF analysis is abnormal,
imaging of the level of the spine where
the epidural injection was performed is
indicated. These recommendations
may not lead to early detection, but
the only alternative is watchful waiting,

e2

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and as the number of deaths continues

to increase, a more proactive approach
may be indicated.
REFERENCES
1. Centers for Disease Control and Prevention
(CDC). Multistate outbreak of fungal
infection associated with injection of
methylprednisolone acetate solution from a
single compounding pharmacyVUnited
States, 2012. MMWR Morb Mortal Wkly Rep
2012;61(41):839Y842.
2. Centers for Disease Control and Prevention
(CDC). Multistate fungal meningitis outbreak
investigation interim treatment guidance for
central nervous system and/or parameningeal
infections associated with injection of
potentially contaminated steroid products.
www.cdc.gov/hai/outbreaks/clinicians/index.
html#Guidance. Accessed November 7, 2012.
3. Lyons JL, Gireesh ED, Trivedi JB, et al. Fatal
Exserohilum meningitis and central nervous
system vasculitis after cervical epidural
methylprednisolone injection [published
online ahead of print October 17, 2012].
Ann Intern Med. In press.
4. Cuetara MS, Alhambra A, Moragues MD,
et al. Detection of (1Y3)-$-D-glucan as an
adjunct to diagnosis in a mixed population
with uncommon proven invasive fungal
diseases or with an unusual clinical
presentation. Clin Vaccine Immunol
2009;16(3):423Y426.

December 2012

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.