Chemical-Induced Aseptic Meningitis as a Result of Intrathecal
Hydromorphone Therapy: Case Report
Sydney Willhite and Sangeeta Juloori, MD
INTRODUCTION
Chemical meningitis, a specific type of drug-induced aseptic meningitis
resulting from intrathecal injection, is a rare outcome that may be the
result of drug solutions or other equipment utilized in neurosurgical
procedures.1 It has been theorized to be caused by a
hypersensitivity reaction or by direct meningeal
irritation.2,3,4 It is characterized by lack of
infectious etiology and by improvement in a few days without use of
antibiotics. CSF (cerebrospinal fluid) analysis reveals pleocytosis
typically of polymorphonuclear predominance but may be of lymphocytic or
eosinophilic predominance as well; additionally, the CSF protein is
usually elevated while the glucose level remains within normal
limits.1
This report is of a patient diagnosed with chemical meningitis as a
result of hydromorphone via an intrathecal pain pump who was diagnosed
by process of exclusion based on CSF findings and cultures.
CASE REPORT
An 81-year-old male with history of failed back syndrome warranting an
intrathecal pain pump presented with sudden onset altered mental status
(AMS) and fever reaching 38.3°C of three days duration. He reported
confusion one week prior lasting three days as well. Other complaints
included difficultly initiating urination, chronic arthralgia, and an
intermittent headache. Initial exam was notable for an exquisitely
tender prostate, yet urinalysis showed no signs of infection. A complete
blood count (CBC) at this time was within normal limits except for mild
anemia, noted to be chronic, and for increased absolute eosinophils,
which were attributed to seasonal allergies and were not a new finding.
Ceftriaxone and acetaminophen were started while awaiting results of
urine and blood cultures.
The following day, the patient was afebrile and his AMS had resolved.
Additionally, neurology was consulted and had no concerns. The plan was
to continue ceftriaxone while awaiting urine and blood cultures and to
de-escalate antibiotic treatment if no further signs of infection arose.
On day three, the patient reported acute on chronic back pain and exam
was notable for diffuse tenderness of the lower thoracic spine. A lumbar
and thoracic MRI revealed meningeal enhancement of the mid to lower
thoracic spine. With concern for intrathecal pump catheter infection or
chemical meningitis, a lumbar puncture was ordered, ceftriaxone was
continued, and vancomycin and ampicillin were started. CSF results are
shown in Table 1.
The CSF studies were most significant for eosinophilia and elevated CSF
protein, making chemical meningitis caused by the hydromorphone via the
intrathecal pump the most likely cause. No viral, bacterial, or fungal
cause was found. The patient was started on dexamethasone and began
improving. He was discharged after six days with no further symptoms. A
dexamethasone taper began, and the patient followed up with his
neurosurgeon. The hydromorphone was changed to fentanyl to prevent
future chemical meningitis. This was the medication of choice as he had
been intolerant of morphine via his intrathecal pump previously.
DISCUSSION
We diagnosed this patient with chemical meningitis after CSF analysis
ruled out infectious etiology and instead revealed pleocytosis of
eosinophilic predominance, protein three times the upper limit of
normal, and glucose within the normal range.
As true chemical meningitis is rare, there are a limited number of
reported cases due to direct intrathecal injection. Yet, it is believed
that direct injection of any substance into the CSF could result in
chemical meningitis.2 Such reactions have occurred
with intrathecal use of baclofen,2morphine,5 radiographic agents,2anesthetic agents,6aminoglycosides,7 and
corticosteroids.8
Hydromorphone is a morphine derivative with a hydrogenated ketone that
has an identical chemical formula and molecular weight as
morphine.9,10 As morphine and hydromorphone are very
similar small molecules, it is likely that both can be the culprit of
chemical meningitis; this has been previously demonstrated with
intrathecal morphine.5 Additionally, as previously
mentioned, it is believed that any molecule injected into the CSF can
cause chemical meningitis likely via meningeal irritation.
Lastly, case reports have shown that intrathecal morphine can result in
granuloma formation leading to spinal cord
compression11 and experiments conducted in dogs
resulted in similar granuloma formation with intrathecal morphine,
hydromorphone, and fentanyl.12 It is suspected that
histamine release occurs via mast cell degranulation and inflammatory
cells subsequently exit the vasculature and form
granulomas.12 This worrisome complication warrants
imaging in cases of suspected chemical meningitis to ensure granuloma
formation is not the direct cause of neurologic symptoms.
CONCLUSION
Chemical meningitis is a diagnosis of exclusion that must be considered
in patients experiencing fever and neurologic symptoms who have had
direct intrathecal injection. As it is believed that any molecule can be
the cause, chemical meningitis must remain in the differential in a
multitude of scenarios. This is of particular importance as pain pumps
continue to be implanted for the large number of patients experiencing
chronic pain.
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CONFLICT OF INTEREST
None
AUTHOR CONTRIBUTION
SW: Assisted in treatment of the patient and described the manuscript.
SJ: Treated the patient and revised the manuscript.