Unique Intradural Inflammatory Mass Containing Precipitated Morphine: Confirmatory Analysis by LESA‐MS and MALDI‐MS

Abstract

Opioids are often used for analgesia via continuous intrathecal delivery by implantable devices. A higher concentration and daily dose of opioid have been postulated as risk factors for intrathecal granuloma formation. We present a 42-year-old female patient with chronic abdominal pain from refractory pancreatitis, with an intrathecal drug delivery device implanted 21 years prior, delivering continuous intrathecal morphine. After many years without concerning physical signs or complaints, with gradual increases in daily morphine dose, she presented with rapidly progressive neurologic deficits, including lower extremity, bladder, and bowel symptoms. These symptoms were determined to be secondary to mass effect and local inflammation related to an intrathecal catheter tip granuloma, detected on magnetic resonance imaging of the spine. The mass was urgently resected. On histopathologic examination, this granuloma was found to be unique, in that in addition to the expected inflammatory components, it appeared to contain precipitated nonpolarizable crystals. These were identified as precipitated morphine using liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) and matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MALDI-FTICR-MSI). In addition to the unique finding of precipitated morphine crystals, the long-term follow-up of both morphine concentration and daily dose increases provides insight into the formation of intrathecal granulomas.

Letter to Editor re: “Unique Intradural Inflammatory Mass Containing Precipitated Morphine” by Kim et al.

“…These effects are concentration dependent . The present report of Kim et al . suggests the possibility that other issues secondary to the formation of precipitates may also contribute.…”

“…I read with interest the excellent report by Kim et al . on a spinal mass resected from a patient 50 mg/mL morphine intrathecally.…”

The Management of Unresectable Intrathecal Catheter-Tip-Associated Granuloma Using Morphine Therapy Cessation and Spinal Cord Stimulation

“…Even non-opiate drugs such as baclofen may cause the formation of catheter-tip-associated inflammatory masses [12]. Kim et al have reported a case of a patient who had a catheter-tip-associated lesion that was histologically confirmed to be precipitated by morphine after 21 years of intrathecal therapy [13]. The etiopathogenesis of CTG needs further investigation in order to reduce the complication rate of IADP therapy and develop an optimized treatment strategy.…”

“…SCS has become a promising therapy option for FBSS [14]; however, its use in acute pain syndromes caused by conditions that cannot be surgically addressed is rarely discussed in the literature. In this case study of an unresectable CTG, the SCS system provided the patient with long-term pain relief and allowed for the discontinuation of all opioid pain medications [13].…”

Characterization of Effect of Repeated Bolus or Continuous Intrathecal Infusion of Morphine on Spinal Mass Formation in the Dog

“…In recent studies in the guinea pig, we found that two mu agonists, DMT-DALDA and PZM21, that are not activators of MRGP-r produce little or no mast cell degranulation, do not activate fibroblasts and when infused intrathecally do not produce intrathecal masses (30). Of note, it was recently reported that a spinal mass resected from a patient receiving 50 mg/mL morphine displayed particulates of morphine, in a loculated fluid-filled sac at the catheter tip, suggesting that at concentrations close to solubility in a buffered water environment with restricted diffusion access, particulate formation may occur, and may contribute to the local reaction (31).…”