Letters to the Editor: Letters & Announcements
To the Editor:
We are grateful to Murphy et al. (1) for reporting their case of a patient who developed a suspected catheter tip obstruction and subsequent loss of therapeutic effects after having received intrathecal baclofen. We compared their report with the collective clinical and preclinical experience regarding inflammatory masses, and offer two observations.
First, our previous laboratory studies, published analyses of medical-device reports, consensus-panel reports, and the information presented in this case lead us to believe that Murphy et al.’s patient most likely did not have a catheter tip inflammatory mass lesion, at least, not the type we have seen in preclinical studies and physician reports. Her symptoms of fluctuating ITB efficacy may have been catheter-related, but we do not see a strong case for those symptoms being related to the MR image in the case report.
Specifically, the irregularity around the catheter tip is not typical of the opioid-induced inflammatory mass lesions reported to arise at the tip of intrathecal drug administering catheters in human patients and animal models. Catheter tip inflammatory masses usually are distinct, globular- or spheroid-shaped lesions best visualized on T1 MR image sequences with gadolinium contrast (2,3) (Fig. 1). Imaging diagnosis based on other criteria can be misleading. For example, precipitated drug can mimic a tumor or inflammatory mass lesion in patients with implanted spinal drug-delivery systems (4). Murphy et al.’s published noncontrast image reveals an ill-defined irregularity that does not appear large enough to occlude all or most of the drug-administration apertures, as these extend circumferentially to 15-mm proximal to the catheter tip. The loss of efficacy most likely was due to catheter problems unrelated to the MRI findings, especially because the second contrast injection confirmed patency. As the catheter was patent, the MRI findings were incidental to the loss of efficacy.
Second, the case report attributes the MRI findings and a clinical complication to intrathecal baclofen but provided no information on drug concentration, pump flow rate, or whether the drug administered to this patient was the approved, preservative-free formulation of Novartis Lioresal Intrathecal® (baclofen injection). Murphy et al. cited our previous work and referred to our statement in 2002 that “No masses were reported in patients who received baclofen as the only intrathecal medication” (5,6). We emphasize that animal studies (7) and hundreds of thousands of patient-years of clinical experience with Novartis Lioresal Intrathecal have not identified a single case of a catheter tip mass lesion.
Preliminary experimental evidence suggests that dural mast cell activation and subsequent release of inflammatory mediators (such as cytokines, and histamine) are responsible for catheter tip inflammatory mass lesions (8,9). To our knowledge, there are no reports of baclofen producing mast cell activation. These findings dovetail with clinical reports of inflammatory mass lesions and direct spinal cord toxicity that appear to have been caused by compounded and/or impure drugs, or the long-term administration of drug formulations not specifically tested and approved for chronic intrathecal use (10–12). We emphasize the importance of limiting intrathecal drug delivery to drugs that are tested and approved for this route of administration.
Robert J. Coffey, MD
Jeffrey W. Allen, PhD
1. Murphy PM, Skouvaklis DE, Amadeo RJJ, et al. Intrathecal catheter granuloma associated with isolated baclofen infusion. Anesth Analg 2006;102:848–52.
2. Hassenbusch S, Burchiel K, Coffey RJ, et al. Management of intrathecal catheter-tip inflammatory masses: a consensus statement. Pain Med 2002;3:313–23.
3. Allen JW, Horais KA, Tozier NA, et al. Time course and role of morphine dose and concentration in intrathecal granuloma formation in dog: a combined magnetic resonance imaging and histopathology investigation. Anesthesiology 2006;105:581–89.
4. Wadhwa RK, Shaya MR, Nanda A. Spinal cord compression in a patient with a pain pump for failed back syndrome: a chalk-like precipitate mimicking a spinal cord neoplasm—case report. Neurosurgery 2006;58:E387.
5. Coffey RJ, Burchiel K. Inflammatory mass lesions associated with intrathecal drug catheters: report and observations on 41 patients. Neurosurgery 2002;50:78–87.
6. Yaksh TL, Hassenbusch S, Burchiel K, et al. Inflammatory masses associated with intrathecal drug infusion: a review of preclinical evidence and human data. Pain Med 2002;3:300–12.
7. Sabbe MB, Grafe MR, Pfeifer BL, et al. Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog. Neurotoxicology 1993;14:397–410.
8. Allen JW, Horais KA, Tozier NA, Yaksh TL. Opiate pharmacology of intrathecal inflammatory masses. Anesthesiology 2006;105:590–98.
9. Allen JW, Zielinksa W, Cizkova D, Yaksh TL. Degranulation of dural mast cells by in vivo and ex vivo opiate exposure. Toxicol Sci 2004;78:S-1 (The Toxicologist). Abstract 427.
10. Jones TF, Feler CA, Simmons BP, et al. Neurological complications including paralysis after a medication error involving implanted intrathecal catheters. Am J Med 2002;112:31–6.
11. Levin GZ, Tabor DR. Paraplegia secondary to progressive necrotic myelopathy in a patient with an implantable morphine pump. Am J Phys Med Rehabil 2005;84:193–6.
12. Knox S, Atkinson RP, Stephens R, et al. Myelopathy as a complication of intrathecal drug infusion systems. Arch Neurol 2007;64:286–7.