Study Design: Case report. Patient Sample: A 42- year-old Caucasian male. Results: Catheter-tip granuloma formation is possible despite a normal catheter access study in patients with intrathecal (IT) infu- sion systems and its recurrence is possible after surgical excision. Increasing concentrations of hydromorphone from 50 mg/ml to 100 mg/ml without altering the daily dosage may have precipitated granuloma formation. Conclusions: In patients with previously implanted spinal catheters for intrathecal drug delivery, catheter access studies cannot be relied upon to rule out catheter-tip granulomas, which should be included in the differential diagnosis in patients with worsening clinical conditions or new onset neurologic symptoms. Caution should be exercised when increasing concentrations of intrathecal opioids while monitoring for signs or symptoms of intrathecal catheter- tip granuloma formation. Removal of previously implanted catheters and/or reductions in opioid concentrations may be necessary to prevent recurrent granuloma formations, which can occur quickly after surgical excision.
Intrathecal drug infusion systems have been utilized since the 1980s to manage a variety of chronic pain conditions and spasticity. Thus far, over 150,000 pumps have been implanted worldwide [
Although often associated with high concentrations of opioid therapy, most commonly morphine, other medications such as hydromorphone may result in catheter granulomas near the tip of the subarachnoid catheter [1,4]. For example, according to a case review of 41 patients, 31 patients receiving morphine and 9 patients receiving hydromorphone intrathecally were found to have inflammatory mass lesions at the catheter tip [
In the current case we report a 42-year-old male who presented to our pain clinic in 2009 with chronic low back pain, which began after he was rear-ended in a motor vehicle accident in 1993 while at work. He eventually went on to have a lumbar laminectomy in 1994 followed by an L4-5, L5-S1 fusion in 1995. However, due to ongoing chronic low back pain, the patient then went on to have a spinal cord stimulator implanted which was later removed within one year due to lack of efficacy. Subsequently an intrathecal pump and subarachnoid catheter was placed in August 1997 by an another pain management physician which provided good relief of pain. His pump was replaced in 2001 for normal end of life battery and pump site revision one year later due to pump discomfort after losing over 100 lbs of weight due to respiratory illness and development of skin excoriation over the pump site. The patient also underwent catheter removal and replacement at that time with the catheter tip placed to approximately T5 spinal level. However, the patient still continued to have difficulty ambulating and decreased sensation in his lower extremities, thus leading him to utilize a wheel-chair for next 7 years.
At the initial visit in our clinic in 2009, the patient complained of 10/10 low back pain, right greater than left, radiating down bilateral lower extremities described as sharp, stabbing, burning, aching and constant. In addition, the patient reported weakness and numbness in his bilateral lower extremities, but no bowel or bladder incontinence. On physical exam, the patient had mild tenderness of bilateral iliolumbar ligaments, sciatic notch and SI joint as well as mild limitation of flexion, extension and bilateral lateral flexion with pain. In addition, the patient had a positive straight leg raise bilaterally as well as hyperesthesia on the left L4, L5 and S1 and motor strength of 4+/5 for the bilateral lower extremities. Reflexes were intact with negative clonus and Babinski.
Examination of available pump telemetry printouts indicate that the patient was receiving intrathecal hydromorphone 50 mg/ml at a daily rate of 19.00 mg/day as early as March 2000, prior to revision of his original pump. Prior to this, the patient was receiving intrathecal morphine 50 mg/ml with clonidine 30 mcg/ml at a dose of 32 mg/day morphine. His most recent pump was replaced in August 2006 from which time he had been maintained on a stable dose of intrathecal hydromorphone 50 mg/ml at a rate of 17.59 mg/day from 2006 until presenting to our clinic in September 2009. In February 2010, we changed the patient’s hydromorphone from 50 mg/ml to 100 mg/ml in an effort to reduce refill intervals and maintained the same daily dose of 17.59 mg/day. However, approximately 16 months after increasing the concentration of the intrathecal hydromorphone, the patient developed increasing pain followed by new onset of numbness in his feet. A catheter access study was undertaken which failed to reveal catheter occlusion (Figures 1 and 2) and thus the patient was maintained on his daily dose of hydromorphone 17.59 mg/day at a concentration of 100 mg/ml. Over the next two months the patient continued to complain of increasing pain and was treated with a variety of oral opioid medications. In addition, he began complaining of a gradually progressive ascending numbness from the feet up to his waist and a more pronounced “heaviness” sensation in his legs which had not been present previously. At that point an MRI was obtained (two months after catheter access study) (Figures 3-5). Films were not available for review but concern of a catheter-tip granuloma was raised with the interpreting radiologist. However, the report was read as, “likely [a] hemorrhagic focus abutting the posterior aspect of the spinal cord at T5/6” [with] “a diffusely increased T2 signal intensity
involving the thoracic cord from T2-T9”. Thus, the initial MRI interpretation unfortunately did not appreciate catheter-tip granuloma but rather spinal cord hematoma of uncertain chronicity (Figures 3(a)-(c) and 4). The patient continued to have numbness below the waist with perineal anesthesia and presented to another hospital six days later. On this admission a subsequent MRI revealed a large catheter-tip granuloma which enhanced with contrast, as well as extensive T2 signal prolongation within the spinal cord from T5 - T7 (Figures 6 and 7). The patient underwent semi-urgent surgical exploration, catheter tip removal and excision of the granuloma. However, a portion of the granuloma could not be resected due to tenacious adherence to the spinal cord (Figures 8(a) and (b)). At three months post-operative the patient showed no change in neurologic function with persistent sensory gait ataxia, and hypoesthesia below T6. After approximately five months, repeat MR imaging was obtained revealing recurrent catheter-tip granuloma just inferior to the original granuloma location and, just proximal to the newly trimmed catheter tip (Figures 9(a)-(c)). No changes in the patient’s dose or concentration of hydromorphone were made after the first surgery and he continued to receive a daily medication infusion of 17.59 mg/day of hydromorphone 100 mg/ml, in addition to taking Percocet 10/325 mg every 4 - 6 hours orally. Repeat laminectomy and resection of his recurrent granuloma was performed, as well as removal of his catheter and pump system. No significant changes in his clinical condition or neurologic function were observed post-operatively.
Catheter-tip granulomas remain a rare but potentially devastating complication from intrathecal (IT) infusion therapy [
Although the majority of cases have been with morphine, hydromorphone may also result in granuloma formation as seen in our case. Thus far, baclofen and diamorphine (heroin) have also been associated with IT granulomas [
Our case supports the notion that the concentration of medication, rather than the daily dose as originally once thought, was the primary causative agent which precipitated granuloma formation [
The location of the catheter-tip has also been suggested to play a role in granuloma formation [5,7,14]. Initially this patient had a granuloma form at T5 and then again at T6 after catheter-tip trimming. Given the relatively small space of cerebrospinal fluid (CSF) at such rostral thoracic locations, some authors have postulated higher catheter-tip placement may predispose to higher local concentrations of drugs at the catheter-tips thus inducing the cellular inflammatory cascade [5,15]. Indeed, granulomas that form at catheter-tips placed inferior to the conus medularis generally result in less severe neurological deficits as well as a more complete recovery should they develop a compressive granuloma [
Although the true yearly incidence of granuloma formation for all pain patients may be dependent on several factors such as the drug, concentration, cathetertip location, daily dose, or patient sensitivity as discussed, the estimated cumulative risk of developing an inflammatory mass was 0.04% over one year, 0.12% over two years, but 1.15% over 6 years [
It is important to note that the majority of radiographically diagnosed granulomas are asymptomatic [
Catheter-tip granulomas, although well reported in the neurosurgical and pain medicine literature are less well described in the radiological literature [
Treatment of catheter-tip masses should take into account the patient’s clinical condition, as well as the physician’s experience [
In summary, benefits of IT therapy include localized and improved analgesia, decreased side effects compared with systemic medications and more alert, less hypersomnolent patients when compared to oral opioids [
The authors would like to gratefully acknowledge Ashley Zimmerman, PA-C for her editorial assistance in preparation of this manuscript.