DOI:10.2214/AJR.07.2225
AJR 2007; 189:W375-W381
© American Roentgen Ray Society
Imaging Appearance of Intrathecal Catheter Tip Granulomas: Report of Three Cases and Review of the Literature
Jinnah A. Phillips1,
Edward J. Escott2,
John J. Moossy3 and
Harry C. Kellermier4
1 Department of Radiology, University of Pittsburgh Medical Center, UPMC
Presbyterian, 200 Lothrop St., Pittsburgh, PA 15213.
2 Division of Neuroradiology, Department of Radiology, University of Pittsburgh
Medical Center, UPMC Presbyterian, Pittsburgh, PA.
3 Department of Neurological Surgery, University of Pittsburgh Medical Center,
UPMC Presbyterian, Pittsburgh, PA.
4 Division of Neuropathology, Department of Pathology, University of Pittsburgh
Medical Center, UPMC Presbyterian, Pittsburgh, PA.
Received February 19, 2007;
accepted after revision July 10, 2007.
WEB This is a Web exclusive article.
Address correspondence to J. A. Phillips
(phillipsja{at}upmc.edu).
Abstract
OBJECTIVE. The purpose of this article is to discuss the clinical,
radiologic, and pathologic features of intrathecal catheter tip inflammatory
masses and to review the literature regarding this phenomenon.
CONCLUSION. Formation of inflammatory masses at catheter tips can
complicate chronic intrathecal opioid administration and have devastating
neurologic sequelae. It is critical that radiologists recognize this entity
and prompt immediate neurosurgical evaluation.
Keywords: catheter tip • complications • granuloma • inflammatory mass • intrathecal • opioid
Introduction
Inflammatory masses at the catheter tip as a complication of long-term
infusion of intrathecal analgesic medications were first reported in the
neurosurgical literature by North et al.
[1] in 1991 but have been only
cursorily documented in the radiology literature. Although uncommon, this
complication of intrathecal drug delivery can have devastating neurologic
sequelae but is not always clinically suspected in patients with chronic lower
back pain who report increasing back pain or development of neurologic
symptoms. Imaging studies often are requested for these patients, and it
becomes the responsibility of the radiologist to actively search for a cause
of the symptoms, including evidence of formation of inflammatory masses. The
radiologist may not be made aware of the presence of the catheter; therefore,
knowledge of the characteristic imaging appearance of these lesions can lead
the radiologist to search carefully for the catheter and subsequently suggest
the correct diagnosis. We present three cases of inflammatory masses at the
tips of intrathecal catheters, describe the radiologic and pathologic
features, and review the literature regarding this phenomenon.
Materials and Methods
Within 1 year at our institution, three patients (two men, one woman) with
a mean age of 60 years (range, 43-70 years) came to the attention of our
neurosurgical department as a result of increasing back pain and progressive
neurologic decline. Each patient had a spinal catheter for intrathecal
administration of opioids, and all underwent surgery for removal of
inflammatory masses at the intrathecal catheter tip that were identified after
imaging evaluation. We informally polled the principal spinal surgeons at our
institution, but no additional cases of inflammatory masses at intrathecal
catheter tips were found. The electronic medical record of each patient was
reviewed, including the operative and pathology reports. The pathology slides
from the original specimens were retrospectively reviewed by a
fellowship-trained neuropathologist.
Two of the patients underwent CT myelography after fluoroscopically guided
intrathecal injection of iohexol (Omnipaque, GE Healthcare), one by lumbar
puncture and one by injection through the intrathecal catheter. Helical axial
images from T1-S2 were acquired (LightSpeed QX/i scanner, GE Healthcare) at
2.5-mm intervals and reformatted in the sagittal and coronal planes. All three
patients underwent presurgical MRI on a 1.5-T system (Signa, GE Healthcare).
Unenhanced images included sagittal and axial T1- and T2-weighted sequences
through the thoracic and lumbar portions of the spine. Sagittal and axial
T1-weighted images were obtained after uneventful IV administration of
gadobenate dimeglumine (MultiHance, Bracco).
The cases were reviewed with a neuroradiologist who had a certificate of
added qualification and were deemed of diagnostic quality. In all instances,
the finding of a mass at or near the tip of the intrathecal catheter with
enhancement on MR images or appearing as an intrathecal mass or filling defect
on CT myelograms was considered suggestive of an inflammatory mass at the
catheter tip. Correlation between CT myelographic and MRI findings were made
wherever possible.
Results
Case 1
A 70-year-old man with chronic lower back pain and multiple previous spinal
operations presented after experiencing 6 months of worsening back pain
refractory to increasing doses of morphine, progressive leg weakness, and 2
days of urinary retention. At admission, the intrathecal pump was delivering
28 mg of morphine daily. Findings on CT myelography 4 months previously had
suggested severe spinal stenosis at the T11-L1 level, which was poorly
evaluated owing to insufficient intrathecal contrast enhancement at this level
caused by a near complete myelographic block. However, the distal aspect of
the intrathecal catheter was found to extend through the level of the block
with the catheter tip immediately cephalic to it. MRI of the lumbar spine at
the time of hospitalization showed a 1.5 x 2.7 cm nodular soft-tissue
mass with rim enhancement at the T12-L1 level, corresponding to the location
of the intrathecal catheter (Figs.
1A-1E).
This mass was causing severe compression and displacement of the conus
medullaris. The findings raised concern about an inflammatory granuloma of the
catheter tip, and neurosurgical consultation was recommended.
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Fig. 1A —70-year-old man with progressive back pain and neurologic decline.
Axial CT myelogram depicts nearly complete myelographic block. Spinal cord
(asterisk) is compressed and displaced to right of canal by mass
(arrowhead) near catheter tip (arrow).
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Fig. 1E —70-year-old man with progressive back pain and neurologic decline.
Axial T2-weighted image though mass depicts lamellated appearance of lesion
with central hyperintensity (arrow) and peripheral hypointensity
(arrowhead). Arrowhead indicates inner of two hypointense rings,
better depicted in D. Punctuate area of hypointensity at tip of arrow
is catheter. Asterisk indicates compressed and displaced spinal cord.
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At surgery, T12 and L1 laminotomies were needed to access the lesion. After
the dura and the arachnoid were opened, a slightly rubbery hypervascular
encapsulated yellowish mass was identified at the catheter tip. Exudative
fluid was expressed from the lesion when the catheter tip was removed from its
central core. The mass was adherent to local nerve roots, necessitating gentle
microsurgical dissection. Histopathologic examination of the tissue fragments
revealed devitalized fibrous tissue with focal mild inflammation
(Fig. 1F). Results of bacterial
and fungal cultures of the tissue were negative. On discharge to the
rehabilitation facility, the patient remained weak in the lower extremities,
but the back pain was substantially relieved. At follow-up, however, the
weakness had progressed to the point of nearly complete absence of motor
strength in the lower extremities.
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Fig. 1F —70-year-old man with progressive back pain and neurologic decline.
Photograph shows area of devitalized fibrous tissue (thin arrow)
adjacent to somewhat lamellated collagen with admixed chronic inflammatory
cells (thick arrow). (H and E, x100)
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Case 2
In 2004 a 66-year-old woman with failed back syndrome underwent placement
of an intrathecal morphine pump for pain control. In August 2005, a myelogram
showed abnormal pooling of contrast material immediately proximal to the
catheter tip, raising concern about an area of loculation or adhesions.
Looping of the distal end of the catheter within the thecal sac also was found
(Figs. 2A and
2B). After discussion with the
patient and her husband, observation was recommended. In December 2005, the
patient fell and fractured her ankle. In January 2006, the patient began to
notice difficulty controlling her legs. Within a month she was admitted to the
hospital with a 0 of 5 motor strength score in the lower extremities and
clinical findings of a T10 motor level, decreased rectal tone, and lack of
bladder control. Sensation was preserved. Contrast-enhanced MRI revealed a
rim-enhancing lesion ventral to the spinal cord at the T10 level, where the
myelographic abnormality had been previously identified. The distal aspect of
the intrathecal catheter was found to course along the periphery of the lesion
(Figs.
2A-2E).
Decompressive laminectomy, intradural exploration, and resection of the mass
were recommended.
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Fig. 2A —66-year-old woman with 0 of 5 lower extremity motor strength score
and loss of bowel and bladder control. Coronal reconstruction from CT
myelogram performed with injection by pump. Catheter is looped within thecal
sac, extending superiorly along left side of spinal canal and inferiorly along
right side (arrowheads). Contrast material is pooled near catheter
tip (arrow).
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Fig. 2B —66-year-old woman with 0 of 5 lower extremity motor strength score
and loss of bowel and bladder control. Axial CT myelogram at T10 level after
intrathecal contrast injection with intrathecal pump. Contrast material
(arrow) is pooled near catheter tip, and spinal cord is mildly
displaced posteriorly and toward left, causing concern about area of
loculation or adhesions, which can correspond to area of chronically increased
concentration of opioid. Arrowhead indicates catheter where it loops near
inflammatory mass.
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Fig. 2E —66-year-old woman with 0 of 5 lower extremity motor strength score
and loss of bowel and bladder control. Axial T2-weighted MR image through
lesion in C and D shows lesion is centrally hyperintense, rim is
hypointense, and spinal cord (asterisk) is displaced posteriorly
toward left and compressed by lesion. Low signal intensity of catheter
(arrowhead) is evident along periphery of mass. Mass (arrow)
has formed in area of contrast pooling present in A and B.
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Laminectomies from T8 to T11 were performed and followed by opening of the
dura and arachnoid. A grayish-green lesion directly ventral and slightly
eccentric to the right of the spinal cord was identified. The catheter was
identified and dissected out of the mass. Fragments of tissue were submitted
for histopathologic and microbiologic analysis. The microscopic findings were
consistent with chronic inflammation with necrosis and fibrosis
(Fig. 2F). Results of Gram and
Grocott stains were negative for bacterial and fungal organisms. On discharge
to a rehabilitation facility, the patient remained paraplegic, with neurogenic
bladder and bowel. Four months later she had little improvement, needing a
wheelchair for mobility, chronic indwelling bladder catheterization, and
assistance with her bowel regimen. In addition, stage 1-2 decubitus ulcers had
developed on the patient's buttocks.
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Fig. 2F —66-year-old woman with 0 of 5 lower extremity motor strength score
and loss of bowel and bladder control. Photograph shows necrotic material
(thin arrow) with adjacent chronically inflamed fibrous tissue
(thick arrow), imparting appearance similar to necrobiotic granuloma.
(H and E, x100)
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Case 3
A 43-year-old man with a history of spinal trauma, numerous lumbar surgical
procedures, and chronic lower back pain underwent insertion of a pump system
for intrathecal delivery of hydromorphone. He arrived in the emergency
department with increasing back pain, new-onset difficulty urinating, and
severe constipation and reported no increasing lower extremity weakness or
paresthesias. The findings at neurologic examination were unremarkable.
Contrast-enhanced MRI of the thoracic and lumbar spine revealed an
approximately 8-mm peripherally enhancing mass in the right side of the thecal
sac at the inferior aspect of T12. The mass was intimately associated with the
intrathecal catheter but located approximately 1.5 cm proximal to the catheter
tip (Figs.
3A-3C).
The findings were discussed with the patient's neurosurgeon, and operative
intervention was pursued.
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Fig. 3A —43-year-old man with increasing back pain, new-onset difficulty
urinating, and severe constipation. T1-weighted sagittal MR image of lumbar
spine depicts small mass (arrow) of intermediate signal intensity
within thecal sac at T12-L1 level.
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Fig. 3C —43-year-old man with increasing back pain, new-onset difficulty
urinating, and severe constipation. Sagittal T2-weighted MR image shows lesion
(arrow) has central hyperintensity and peripheral hypointensity. Low
signal intensity with associated susceptibility artifact of catheter tip above
lesion (arrowhead) is evident.
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At surgery, a T12-L1 granuloma was found densely adherent to the arachnoid
and lateral dura and local nerve roots. This finding necessitated partial
excision of several nerve roots in addition to dissection of the mass away
from the meninges. The mass and a portion of the distal part of the catheter
were submitted for pathologic review. H and E staining revealed a catheter
with a cuff of dense connective tissue surrounded by multiple necrobiotic-like
granulomas with mild lymphocytic inflammatory infiltrates. Although
polarizable suture material was found in adjacent, noninflammatory soft
tissue, no polarizable material such as talc was present within the
granulomas. Granulomatous tissue was seen to protrude into a catheter
fenestration with only minimal occlusion of the lumen (Figs.
3D and
3E). All stains for infectious
organisms had negative results.
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Fig. 3D —43-year-old man with increasing back pain, new-onset difficulty
urinating, and severe constipation. Photograph shows one area of specimen
appears to consist of three zones arranged in layers: area of devitalized and
necrotic fibrous tissue (thin arrow), intervening layer of fibrosis
and chronic inflammation (thick arrow), and third layer of prominent
vascularity (medium arrow). (H and E, x40)
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Fig. 3E —43-year-old man with increasing back pain, new-onset difficulty
urinating, and severe constipation. Photograph of section through mass shows
intrathecal catheter embedded in chronically inflamed fibrous matrix. Fibrous
tissue (thick arrow) surrounds catheter. Necrotic and
necrobiotic-like areas are present (thin arrow), and fibrin and
devitalized material extend into catheter fenestration (medium
arrow). (H and E, x40)
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The patient tolerated surgery well, but the postoperative course was
complicated by pseudomeningocele formation necessitating operative repair. Two
weeks after discharge after repair of the pseudomeningocele, the patient again
arrived in the emergency department with swelling and pain at the operative
site and new onset of paresthesias in the right leg. He was hospitalized for
further evaluation.
Discussion
Development of an inflammatory mass at a catheter tip is a rare but
potentially devastating complication of long-term intrathecal administration
of analgesic medications. It is well documented in the anesthesiology and
neurosurgical literature but little discussed in the radiologic literature.
The complication was first reported in 1991 by North et al.
[1], and by 2002, 41 cases had
been identified either in the literature or in reports to the U.S. Food and
Drug Administration [2]. By
2003 more than 90 cases were known
[3]. Reporting of this
complication is voluntary, but data indicate the incidence of granuloma
formation is approximately 0.04% after 1 year of therapy and 1.15% after 6
years of therapy [3].
The typical characteristics of patients with inflammatory masses at
catheter tips are exemplified by the cases of our three patients. Most
patients have been receiving intrathecal medications for the management of
chronic pain, the mean duration of therapy being 24.5 months
[2]. Early clues to the
diagnosis include diminishing analgesic coverage, often despite marked
increases in drug dosage, and subtle but progressive neurologic decline. With
growth of the mass, increased spinal cord compromise can result in paralysis,
decreased sensation, and loss of bowel and bladder control
[2-7],
all of which may persist despite resection of the lesion. These catheters are
increasingly being placed with their tips in the lumbar region below the conus
in an attempt to eliminate the risk of neurologic sequelae of granuloma
formation, but neurologic dys-function can still occur
[4,
8].
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Fig. 1B —70-year-old man with progressive back pain and neurologic decline.
Sagittal T1-weighted image without contrast enhancement performed 4 months
after myelogram shows lamellated-appearing lesion (arrow) at T12-L1
level with components of intermediate and high signal intensity. Artifact is
from previous posterior fusion.
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Fig. 1C —70-year-old man with progressive back pain and neurologic decline.
Contrast-enhanced sagittal T1-weighted image shows rim enhancement of lesion
(arrowhead) with inner hypointense nonenhancing ring
(arrow), which may represent lamellated collagen or devitalized
fibrous tissue.
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Fig. 1D —70-year-old man with progressive back pain and neurologic decline.
Sagittal T2-weighted image shows central hyperintensity (arrow) and
peripheral hypointensity (arrowhead). These regions may correspond to
central necrotic debris and lamellated collagen or devitalized fibrous tissue,
respectively. Second, outer hypointense rim of unknown causation also is
evident.
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Fig. 2C —66-year-old woman with 0 of 5 lower extremity motor strength score
and loss of bowel and bladder control. Sagittal T1-weighted contrast-enhanced
MR image of thoracic spine performed 6 months after myelogram shows rim
enhancement of lesion (arrow) at T10.
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Fig. 2D —66-year-old woman with 0 of 5 lower extremity motor strength score
and loss of bowel and bladder control. Sagittal T2-weighted MR image of
thoracic spine shows lesion has central hyperintensity (arrow) and
peripheral hypointense rim (arrowhead).
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Clinical suspicion of this complication should prompt early imaging. MRI is
considered the study of choice in patients for whom it is not contraindicated
because not only is the lesion well depicted on MRI but also MRI can show to
best advantage the degree of cord and nerve root compromise by the lesion.
Intrathecal catheters can be difficult to identify with MRI alone, however,
and the radiologist may not be given the history of the presence of a
catheter. Therefore, if an enhancing intradural extramedullary mass is
identified on MRI of the thora-columbar or lumbar region, a catheter-based
lesion should be in the differential diagnosis, and a history of intrathecal
analgesic administration should be sought. In patients for whom MRI is
contraindicated, CT myelography can aid in the detection of catheter tip
masses [4].
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Fig. 3B —43-year-old man with increasing back pain, new-onset difficulty
urinating, and severe constipation. Sagittal T1-weighted contrast-enhanced MR
image of lumbar spine shows lesion (arrow) undergoing brisk
peripheral enhancement.
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Although many cases have been reported in the clinical literature, the
imaging appearance of catheter-related lesions has been only cursorily
discussed (Table 1). All of the
masses are described as occurring at catheter tips
[2,
3,
5,
8,
9], but we propose that
catheters with side fenestrations can cause inflammatory masses proximal to
the catheter tip, as occurred in all three of our cases. Older models of
intrathecal pumps had catheters with end holes, but current models are
available only with closed-end side-fenestration construction.
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Fig. 4A —57-year-old woman with intrathecal catheter. Sagittal T2-weighted
image with fat saturation of lumbar spine. Metallic tip (arrow) at
distal aspect of closed-end catheter can be mistaken for inflammatory mass at
catheter tip on MRI. However, recognition of associated susceptibility
artifact (arrowhead) enables correct identification of catheter
tip.
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Fig. 4B —57-year-old woman with intrathecal catheter. Sagittal reformatted CT
scan of lumbar spine shows CT with or without myelography can easily depict
nature of catheter tip (arrow) and better delineate catheter itself
(arrowheads). CT myelography has additional advantage of more clearly
identifying presence or absence of catheter tip mass than CT without
intrathecal contrast enhancement.
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On MRI, contrast-enhanced T1-weighted imaging typically reveals enhancement
of the lesion [2,
4,
5], frequently in a ringlike
pattern [10], as in our three
cases. On unenhanced T1-weighted images, the masses varied in appearance and
had either intermediate to mildly low signal intensity. One mass had
T1-weighted hyperintense material within it that caused a lamellated
appearance. Variable signal intensity characteristics on T2-weighted images
have been reported [5,
8], but our cases exemplify the
T2-weighted hypointense peripheral rim and central hyperintensity described by
Blount et al. [10].
Imaging pitfalls exist and should be recognized by the interpreting
radiologist. For instance, some closed-end catheters have a metallic marker at
the tip, which can cause artifacts on MRI that can be mistaken for a catheter
tip lesion [4]. For this
reason, contrast-enhanced imaging is critical. If confusion remains, CT
myelography can aid in correct identification of the catheter tip itself and
the presence of an unusual mass at or near the catheter tip (Fig.
4A,
4B).
Histologic examination of catheter tip lesions frequently reveals central
necrotic debris with a peripheral margin of fibrotic and inflammatory cells
derived from the arachnoid layer and evidence of increased vascularity
[3,
5,
7]. The presence of central
necrosis within a mass of inflammatory hypervascular tissue likely explains
the imaging appearance of rim enhancement on T1-weighted contrast-enhanced
images and may contribute to the central area of high signal intensity on
T2-weighted images. The peripheral fibrotic component may explain the rim of
peripheral low or intermediate signal intensity seen on T2-weighted images.
Despite their designation as granulomas in much of the literature, the masses
do not meet histopathologic criteria for true granulomas but represent an
accumulation of granulation tissue without giant cells
[9]. The over-whelming majority
of cases have no evidence of bacterial or fungal infection.
The origin of inflammatory masses at intrathecal catheter tips is not known
with certainty, but the preponderance of evidence from human and animal
investigations points to opioids as the causative agents. Morphine sulfate in
particular has been implicated in inflammatory mass formation with a greater
likelihood of development of masses at high local concentrations of the drug
[6,
7,
9]. We postulate that in case 2
the pooling of contrast material at the catheter tip may correspond to an area
of increased concentration of opioid, which may have predisposed the patient
to granuloma formation in this region. It is uncertain why the contrast agent
pooled in this location, but adhesions might have caused partial loculations
or another alteration of normal CSF flow, possibly even looping of the
catheter. Trials with animal models have shown that hydromorphone,
D/L-methadone, D-methadone,
L-methadone, and the opiate antagonist naloxone are capable of
inducing catheter tip masses
[11]. A single case report
[12] suggests the presence of
a small inflammatory mass at the tip of an intrathecal catheter used for
baclofen infusion, but it is unclear whether this is the same entity that
occurred in the animal trials, and fibrous scars have been reported over
baclofen catheter tips.
More than 95,000 intrathecal drug delivery systems have been implanted in
the United States since the introduction of the technology in the 1980s
[5]. Many of these devices are
used for long-term administration of analgesic medications such as morphine
sulfate. Although uncommon, formation of inflammatory masses at the tips of
intrathecal catheters is a known complication of this therapy and can have
devastating and potentially permanent neurologic consequences. This lesion
should be suspected if a mass with the characteristic appearance of
hyperintensity with a hypointense rim on T2-weighted images and peripheral
enhancement is detected. When called on to image a patient with progressive
pain refractory to increasing doses of intrathecal medications or with new
neurologic deficits, the radiologist must maintain a high index of suspicion
for this lesion.
Acknowledgments
We thank Eric Jablonowski for assistance with the figures.
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Abstract
Introduction
