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Transverse myelitis associated with Acinetobacter baumanii intrathecal pump catheter-related infection
Case Reports
Transverse Myelitis Associated With Acinetobacter baumanii Intrathecal Pump Catheter-Related Infection Eroboghene E. Ubogu, M.D., Judah R. Lindenberg, M.D., and Mary Ann Werz, M.D., Ph.D. Objective: To describe a late neurologic complication of intrathecal pump implantation and show the methods used for the diagnosis and successful treatment of transverse myelitis in this setting. Case Report: A 32-year-old man with a chronic abdominal pain syndrome presented with right lowerextremity numbness 2 months after the placement of an intrathecal morphine pump. This progressed to bilateral lower extremity and ascending sensory loss to T12-L1 dermatome, significant lower-extremity weakness, constipation with overflow incontinence, and detrusor instability causing urinary incontinence in discrete episodes over the following 2 months consistent with a myelopathy. Magnetic resonance imaging (MRI) of the thoracic spine and cerebrospinal fluid (CSF) analysis were consistent with transverse myelitis. The intrathecal pump was removed and an Acinetobacter baumanii catheter-tip infection was diagnosed. Clinical course improved with the co-administration of intravenous corticosteroids and antibiotics, with significant clinical improvement within 30 days. Conclusions: Clinicians should recognize transverse myelitis as a possible late complication of intrathecal pump placement. Early medical intervention and removal of the intrathecal pump may be necessary to prevent irreversible spinal cord damage and may support good recovery. Reg Anesth Pain Med 2003;28:470-474. Key Words:
Acinetobacter baumanii, Catheter-related infection, Intrathecal pump, Transverse myelitis.
T
he presence of opioid receptors in the spinal cord serves as the basis for intrathecal morphine therapy for chronic nonneuropathic pain.1 Complications of intrathecal pump implantation include peri-operative bleeding (including epidural hemorrhage), cerebrospinal fluid (CSF) leak, pump pocket seroma,2 pump or catheter malfunction,3 and infection.4 Spinal cord compression from an inflammatory mass at the catheter tip, catheter-tip granuloma,2,5-7 as well as sexual dysfunction8 also has been described. Transverse myelitis as a consequence of catheter-related infection is rare and is
Case Report
From the Department of Neurology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH. Accepted for publication May 21, 2003. Reprint requests: Dr. Mary Ann Werz, Department of Neurology, University Hospitals of Cleveland, Hanna House 5th Floor, 11100 Euclid Ave, Cleveland, OH 44106-5040. E-mail: maryann. [email protected] or [email protected] © 2003 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/03/2805-0019$30.00/0 doi:10.1016/S1098-7339(03)00222-0
A 32-year-old right-handed man with a presumptive diagnosis of chronic abdominal pain caused by sclerosing cholangitis presented to the emergency room (June, 2002) with a subacute progressive bilateral leg weakness associated with bowel and bladder incontinence. Over the preceding 6 years, he had undergone extensive diagnostic and therapeutic procedures at other institutions for chronic abdominal pain refractory to tinzanadine 4 to 8 mg orally at bedtime and controlled-release morphine sulfate 30 mg orally every 8 hours. Bilat-
470
not widely considered as a potential complication of microbial colonization of a catheter tip. Unrecognized myelitis is a potentially dangerous condition that may result in irreversible paralysis. We report a case of transverse myelitis associated with Acinetobacter baumanii intrathecal pump catheter–related infection occurring as a late complication of intrathecal pump placement, with resolution after pump removal and combined intravenous steroid and antibiotic therapy.
Regional Anesthesia and Pain Medicine, Vol 28, No 5 (September–October), 2003: pp 470 –474
Transverse Myelitis and Catheter Infection
eral radiofrequency neurolysis of the T11 and T12 spinal nerves was performed with the addition of 3% phenol and 0.25% bupivacaine in November and December, 2001, after an earlier celiac plexus nerve block yielded transient but significant pain relief. The chronic abdominal pain was refractory to these procedures. As a consequence, an intrathecal morphine pump was implanted through the L3-L4 intervertebral space in February, 2002, without immediate complications. There was a 90% improvement in abdominal pain with increased functional status after intrathecal morphine titration coupled to decreased but continued dependence on oral tinzanadine and controlled-release morphine sulfate 30 mg orally every 12 hours. Two months later, he awoke with right lowerextremity parasthesias, extending from the lateral aspects of the proximal thigh to the foot, with medial sparing. Clinical examination confirmed the sensory loss without muscle weakness on confrontation testing. A magnetic resonance image (MRI) of the lumbar spine showed subtle effacement of the L4 neural foramen. Neurologic consultation at another facility 2 weeks later revealed no further findings. Of note, there were no cutaneous lesions to suggest varicella zoster infection. Electromyography and nerve conduction studies were performed, which showed absent right tibial H-responses and active denervation and reinnervation in right L5 and S1 muscles, consistent with a right L5-S1 radiculopathy or lower lumbar plexopathy. A 6-day course of low-dose oral methylprednisolone was instituted with minimal abatement of the parasthesias. One month later, he awoke with left leg weakness without sensory loss. Clinical examination revealed the prior abnormalities with a Medical Research Council (MRC) grade 3/5 left lower-extremity weakness and left ankle clonus. Emergent MRI of the thoracic and lumbar spine performed at another institution was reported to show a hyperintense signal at T9-T10 that was interpreted as an artifact possibly caused by metal within the catheter tip, or mass-like impingement into the left ventral surface of the thoracic cord. Intravenous steroids were started. A computed tomography of the lumbar spine showed the intrathecal catheter tip located at T9T10 without evidence of cord compression or thecal sac compromise. This is contrary to what may be seen with an epidural abscess or extradural mass originating from bony tissue as an alternative cause for the symptoms. CSF analysis showed a lymphocytic pleocytosis (white blood cell ⫽ 45/L with 97% lymphocytes), protein ⫽ 28 mg/dL (15-45), glucose ⫽ 83 mg/dL (40-80), and an elevated myelin basic protein of 4.6 ng/mL (0-1.49). Oligoclonal
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bands and IgG index and synthetic rate were normal. A normal brain MRI coupled with the earlier listed results excluded a demyelinating disease. The clinical presentation was hypothesized to result from mechanical trauma of the thoracic cord by the intrathecal catheter tip. Surgical withdrawal to the mid-T12 level was performed at the patient’s request, complicated by a persistent CSF leak at L3-L4 requiring fluoroscopy-guided blood patching and surgical oversew symptom stabilization. Cutaneous fixation of the catheter was performed with intravenous vancomycin for infection prophylaxis. In June 2002, 2 months after the initial symptoms, he presented to the emergency room at University Hospitals of Cleveland for the first time with a 5-day history of increased left lower-extremity weakness accompanied by constipation with overflow incontinence and bladder incontinence owing to detrusor instability. The parasthesias were present up to the level of his waist bilaterally, with worse intensity on the left. There was no history of trauma, infectious exposure, or foreign travel. The patient was afebrile. Neurologic examination was significant for a dense T12-L1 sensory level with spastic paraparesis (MRC grade 4/5 proximally, 4⫹/5 distally on the right, and 3/5 proximally, and 2/5 distally on the left), hyperreflexia of lowerextremity deep tendon reflexes, with sustained left patellar and ankle clonus. There were extensor plantar responses bilaterally. Laboratory evaluation was significant for a white cell count of 6,900/L with 3% immature band neutrophils. CSF analysis was not performed because of the recent lumbar procedures and the patient’s complaint of lower back discomfort. A 2.7-g dose (30 mg/kg) of intravenous methylprednisolone was administered emergently. An emergent lumbar spine MRI with gadolinium contrast showed abnormal T2-weighted intramedullary hyperintense signal in the posterior cord at the T10-T11 intervertebral level consistent with a diagnosis of transverse myelitis (Fig 1). A catheter tip granuloma was excluded. The patient was admitted to the neurology service and methylprednisolone was instituted at 250 mg intravenously every 6 hours for 72 hours. The intrathecal pump was removed within 24 hours of admission and intravenous gentamicin 450 mg (5 mg/kg) every 24 hours and ceftriaxone 2 g intravenously every 12 hours was administered. Over the next 2 to 3 days, there was gradual reduction of the sensory level with concurrent improvement of left leg strength. Laboratory evaluation and review of old gastrointestinal biopsy specimens were not consistent with sclerosing cholangitis. An opiate detoxification regimen was commenced that resulted in a successful weaning without signs of withdrawal
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Discussion
Fig 1. Initial MRI of the lower thoracic spine. An axial T2-weighted MRI of the thoracic spine with gadolinium contrast showed an intradural, intramedullary hyperintense signal of the posterior spinal cord at the T10-T11 intervertebral level consistent with transverse myelitis (see arrow).
and no recurrence of pain after psychologic counseling. The intrathecal pump catheter tip cultures grew greater than 50 colonies of pan-sensitive Acinetobacter baumanii. Gentamicin was discontinued. On day 4 of admission, oral prednisone taper was initiated for 15 days. Within a week of admission, motor strength had improved to MRC grade 4/5 proximally and MRC grade 3/5 distally in the left lower limb. The right side was normal. Bowel and urinary incontinence had resolved completely. There was an improvement in the left patella and ankle clonus with a combination of oral baclofen and tinzanadine. He was discharged on day 12 of admission to a skilled rehabilitation facility for acute rehabilitation, psychologic counseling, and completion of a 2-week course of intravenous ceftriaxone. Routine follow-up evaluation after 1 month of in-patient rehabilitation showed continued improvement in lower-extremity strength with residual spasticity, cautious independent ambulation, and parasthesias limited only to the right foot. The repeat MRI of the thoracic spine performed 3 months later showed complete resolution of the T2-weighted hyperintense signal at T10-11 (Fig 2) consistent with resolution of the transverse myelitis. His chronic abdominal pain was controlled without analgesia and he began to pursue full employment with some functional limitations affecting mobility.
Intrathecal opiate analgesia is indicated in patients with intra-abdominal pain refractory to other conservative pharmacologic and nonpharmacologic measures. It has been shown to be beneficial in the treatment of pain secondary to malignancy and has been used increasingly for nonmalignant pain.9 The clinician should be aware that spinal cord disease could occur as a late complication that warrants aggressive therapy to prevent irreversible sequelae. Our patient had progressive symptoms and signs occurring acutely or subacutely and CSF evidence of myelitis in the context of an intrathecal catheter tip infected with Acinetobacter baumanii. The symptoms persisted and progressed despite the withdrawal to a lower spinal level, making traumatic thoracic cord injury or catheter tip granuloma less likely explanations. Clinical improvement and subsequent radiologic resolution occurred only after the removal of the intrathecal pump and co-administration of intravenous corticosteroids and antibiotics, as evidenced by significant although incomplete neurologic and functional recovery. In retrospect, a diagnosis of a functional pain syndrome was made in this patient. A psychologic evaluation was not performed before intrathecal pump implantation. Initial psychologic evaluation may provide a means of instituting behavioral therapy for individuals with functional pain syndromes. The onset of myelopathic symptoms should be a
Fig 2. Follow-up MRI of the lower thoracic spine. The repeat axial T2-weighted thoracic spine MRI with gadolinium contrast performed 3 months after treatment shows absence of the hyperintense signal at the T10-T11 intervertebral level suggestive of radiologic resolution (see arrow).
Transverse Myelitis and Catheter Infection
strong indication for intrathecal pump removal if referable to the catheter site. The initial presentation and electromyography/nerve conduction studies in this case may have suggested a radiculopathy or plexopathy; however, the results also were consistent with anterior horn cell damage of the right L5-S1 spinal cord level. The subsequent progression with a suggestive MRI and CSF analysis should prompt the clinician to the diagnosis. If traumatic spinal cord injury secondary to catheter placement were considered, it would be expected that myelopathy could occur as an early complication. A course of combined intravenous/oral corticosteroids for 10 to 14 days and an MRI of thoracic spine with gadolinium 4 to 6 weeks afterward would be prudent after withdrawal of the catheter tip distally in such cases. One should be cautious of a radiologic diagnosis of spinal cord artifactual changes in an individual with myelopathic complaints. The progression of clinical and radiologic features of myelopathy should alert the clinician to the potential for an intrathecal pump catheter–related infection or catheter tip granuloma as being responsible for the myelopathy. In this case, a further CSF leak complicating the catheter withdrawal to a lower spinal level could have been a route for polymicrobial spinal cord infection. Although this was performed to meet the patient’s request, it could have resulted in potentially devastating consequences. Catheter tip granulomas are a well-established complication of intrathecal infusions of high concentration or doses of morphine or hydromorphine, but not baclofen.5 These may occur after an average of 24.5 months and may cause spinal cord or cauda equina compression, not transverse myelitis.5-7 Neurologic progression is usually slowly progressive with increasing granuloma size. Surgical specimens revealed noninfectious chronic inflammation, granuloma formation, and fibrosis or necrosis.5-7 This is not consistent with the findings in this case. Management of catheter tip granulomas includes surgical removal of the intrathecal pump with/without laminectomy, depending on the size of the granuloma and severity of compression.5-7 Transverse myelitis is a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic dysfunction, which develops acutely or subacutely. It is characterized clinically by the presence of bilateral signs and/or symptoms that need not be symmetric, the presence of a clear sensory level, and evidence of spinal cord inflammation (CSF pleocytosis, elevated immunoglobulin G index, or gadolinium enhancement on MRI).10 Common etiologies include viral infection (hepatitis viruses, herpes viruses, human T-cell lymphotro-
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phic-1 virus, enteroviruses), bacterial infections (mycoplasma, mycobacterium tuberculosis), Lyme disease, connective tissue diseases (systemic lupus erythematosus, Sjo¨ grens syndrome, sarcoidosis, antiphospholipid antibody syndrome), parainfectious, multiple sclerosis, and idiopathic etiology.10 The clinical presentation, prior CSF analysis, and MRI evaluation in this case meets the diagnostic criteria for transverse myelitis. Infection of the central nervous system is a rare complication of intrathecal pump placement. Catheter tips may become colonized without clinical consequence. The most likely organisms include Staphylococcus aureus, coagulase-negative staphylococcus, Streptococcus viridans, Neisseria spp., Corynebacterium spp., Enterobacter spp., Klebsiella spp., and yeasts.11 Cases of meningitis and cerebritis have been associated with Staphylococcus spp., Enterobacter aerogenes, and Klebsiella pneumoniae.12-14 Transverse myelitis has been described rarely, and occurred in association with a paravertebral abscess, osteomyelitis, epidural abscess, and phlegmonous duritis in an individual with Staphylococcus epidermidis peridural catheter infection.15 Acinetobacter is an aerobic nonfermentive gramnegative coccobacillus that is a significant cause of nosocomial infections, especially in neurosurgical patients.16 Most central nervous system infections reported were cases of adult meningitis, almost exclusively caused by baumanii species (previously known as Herellea vaginocola).17 Acinetobacter infection occurs opportunistically, but with enhanced virulence in patients undergoing invasive procedures (arterial or venous catheterization, mechanical ventilation, nasogastric tube placement, or thoracic drainage).17 Suri showed that after undergoing both emergent and elective cranial surgery, 24.7% of patients with infections were infected with Acinetobacter spp.18 Most infections were responsive to fluoroquinolone antibiotics, although higher rates of multidrug resistance occurred among intensive care unit patients, with uniform fatality in resistant meningitis cases.18 To our knowledge, this is the first reported case of an isolated transverse myelitis associated with an Acinetobacter intrathecal pump catheter-related infection. The management of this disease was based on the general principles of treating the underlying microbial cause with intravenous antibiotics, reducing cord inflammation with high-dose intravenous corticosteroids, and removal of the intrathecal pump. The use of fluoroquinolones as initial therapy for Acinetobacter myelitis may be adequate, however, broad antibiotic coverage for gram-negative organisms with a third-generation cephalosporin and aminoglycoside, as undertaken in this case,
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may ensure better coverage for polymicrobial infections and resistant strains. This case report shows transverse myelitis as a rare late complication of intrathecal pump implantation successfully treated by a combination of pump removal, antibiotics, and corticosteroids with good recovery. The Transverse Myelitis Consortium Working Group10 suggests that the clinical signs and symptoms of myelopathy should be followed by an MRI of the appropriate spinal level with gadolinium administration within 4 hours to confirm the absence of structural abnormality causing spinal cord compression. Spinal cord inflammation should be confirmed by gadolinium MRI enhancement, CSF pleocytosis, or elevated immunoglobulin G index. MRI with gadolinium should be performed to exclude brain demyelination. Early recognition and therapy of transverse myelitis are paramount in preventing irreversible spinal cord damage. We advocate that the development of neurologic complications after intrathecal pump implantation requires prompt specialist evaluation and suggest cooperation between anesthesiologists and neurologists in the early management of this potentially devastating complication.
References 1. Wang JF, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979;50:149-151. 2. North RB, Cutchis PN, Epstein JA, Long DM. Spinal cord compression complicating subarachnoid infusion of morphine: Case report and laboratory experience. Neurosurgery 1991;29:778-794. 3. Brazenor G. Long-term intrathecal administration of morphine: A comparison of bolus injection via reservoir with continuous infusion by implanted pump. Neurosurgery 1987;21:484-491. 4. Auld AW, Maki-Jokela A, Murdoch DM. Intraspinal narcotic analgesia in the treatment of chronic pain. Spine 1985;10:777-781. 5. Coffey RJ, Burchiel K. Inflammatory mass lesions associated with intrathecal drug infusion catheters: Report and observations on 41 patients. Neurosurgery 2002;50:78-86. 6. Bejjani GK, Karim NO, Tzortzidis F. Intrathecal granuloma after implantation of a morphine pump: Case report and review of the literature. Surg Neurol 1997; 48:288-91.
7. Cabbell KL, Taren JA, Sagher O. Spinal cord compression by catheter granulomas in high-dose intrathecal morphine therapy: Case report. Neurosurgery 1998;42:1176-80. 8. Doleys DM, Dinoff BL, Page L, Tutak U, Willis KD, Coleton M. Sexual dysfunction and other side effects of intraspinal opiate use in the management of chronic non-cancer pain. Am J Pain Manage 1998;8: 5-11. 9. Zenz M, Strumpf M, Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 1992;7:69-77. 10. Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002;59:499-505. 11. Nitescu P, Hultman E, Appelgren L, Linder LE, Curelaru I. Bacteriology, drug stability and exchange of percutaneous delivery systems and antibacterial filters in long-term intrathecal infusion of opioid drugs and bupivacaine in “refractory” pain. Clin J Pain 1992;8:324-337. 12. Bennett MI, Tai YM, Symonds JM. Staphylococcal meningitis following synchromed intrathecal pump implant: A case report. Pain 1994;56:243-244. 13. de Champs C, Guelon D, Joyon D, Sirot D, Chanal M, Sirot J. Treatment of a meningitis due to an enterobacter aerogenes producing a derepressed cephalosporinase and a klebsiella pneumoniae producing an extended-spectrum beta-lactamase. Infection 1991;19: 181-183. 14. Hakim A, Rossi C, Kabanda A, Deplano A, De Gheldre Y, Strelens MJ. Ommaya-catheter-related staphylococcus epidermidis cerebritis and recurrent bacteremia documented by molecular typing. Eur J Clin Microbiol Infect Dis 2000;19:875-877. 15. Konig HJ, Schleep J, Krahling KH. A case of transverse spinal cord syndrome following contamination of a peridural catheter. Reg Anaesthesie 1985;8:60-62. 16. Bergogne-Berezin E, Towner KJ. Acinetobacter spp. as nosocomial pathogens: Microbiological, clinical and epidemiological features. Clin Microbiol Rev 1996; 9:148-165. 17. Garcia-Garmendia JL, Ortiz-Leyba C, GernachoMontero J, Jimenez-Jimenez FJ, Perez-Paredes C, Barrero-Almodovar AE, Gili-Miner M. Risk factors for Acinetobacter baumanii nosocomial bacteremia in critically ill patients: A cohort study. Clin Infect Dis 2001;33:939-946. 18. Suri A, Mahapatra AK, Kapil A. Acinetobacter infection in neurosurgical intensive care patients. Natl Med J India 2000;13:296-300.
Transverse Myelitis Associated With Acinetobacter baumanii Intrathecal Pump Catheter-Related Infection Eroboghene E. Ubogu, M.D., Judah R. Lindenberg, M.D., and Mary Ann Werz, M.D., Ph.D. Objective: To describe a late neurologic complication of intrathecal pump implantation and show the methods used for the diagnosis and successful treatment of transverse myelitis in this setting. Case Report: A 32-year-old man with a chronic abdominal pain syndrome presented with right lowerextremity numbness 2 months after the placement of an intrathecal morphine pump. This progressed to bilateral lower extremity and ascending sensory loss to T12-L1 dermatome, significant lower-extremity weakness, constipation with overflow incontinence, and detrusor instability causing urinary incontinence in discrete episodes over the following 2 months consistent with a myelopathy. Magnetic resonance imaging (MRI) of the thoracic spine and cerebrospinal fluid (CSF) analysis were consistent with transverse myelitis. The intrathecal pump was removed and an Acinetobacter baumanii catheter-tip infection was diagnosed. Clinical course improved with the co-administration of intravenous corticosteroids and antibiotics, with significant clinical improvement within 30 days. Conclusions: Clinicians should recognize transverse myelitis as a possible late complication of intrathecal pump placement. Early medical intervention and removal of the intrathecal pump may be necessary to prevent irreversible spinal cord damage and may support good recovery. Reg Anesth Pain Med 2003;28:470-474. Key Words:
Acinetobacter baumanii, Catheter-related infection, Intrathecal pump, Transverse myelitis.
T
he presence of opioid receptors in the spinal cord serves as the basis for intrathecal morphine therapy for chronic nonneuropathic pain.1 Complications of intrathecal pump implantation include peri-operative bleeding (including epidural hemorrhage), cerebrospinal fluid (CSF) leak, pump pocket seroma,2 pump or catheter malfunction,3 and infection.4 Spinal cord compression from an inflammatory mass at the catheter tip, catheter-tip granuloma,2,5-7 as well as sexual dysfunction8 also has been described. Transverse myelitis as a consequence of catheter-related infection is rare and is
Case Report
From the Department of Neurology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH. Accepted for publication May 21, 2003. Reprint requests: Dr. Mary Ann Werz, Department of Neurology, University Hospitals of Cleveland, Hanna House 5th Floor, 11100 Euclid Ave, Cleveland, OH 44106-5040. E-mail: maryann. [email protected] or [email protected] © 2003 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/03/2805-0019$30.00/0 doi:10.1016/S1098-7339(03)00222-0
A 32-year-old right-handed man with a presumptive diagnosis of chronic abdominal pain caused by sclerosing cholangitis presented to the emergency room (June, 2002) with a subacute progressive bilateral leg weakness associated with bowel and bladder incontinence. Over the preceding 6 years, he had undergone extensive diagnostic and therapeutic procedures at other institutions for chronic abdominal pain refractory to tinzanadine 4 to 8 mg orally at bedtime and controlled-release morphine sulfate 30 mg orally every 8 hours. Bilat-
470
not widely considered as a potential complication of microbial colonization of a catheter tip. Unrecognized myelitis is a potentially dangerous condition that may result in irreversible paralysis. We report a case of transverse myelitis associated with Acinetobacter baumanii intrathecal pump catheter–related infection occurring as a late complication of intrathecal pump placement, with resolution after pump removal and combined intravenous steroid and antibiotic therapy.
Regional Anesthesia and Pain Medicine, Vol 28, No 5 (September–October), 2003: pp 470 –474
Transverse Myelitis and Catheter Infection
eral radiofrequency neurolysis of the T11 and T12 spinal nerves was performed with the addition of 3% phenol and 0.25% bupivacaine in November and December, 2001, after an earlier celiac plexus nerve block yielded transient but significant pain relief. The chronic abdominal pain was refractory to these procedures. As a consequence, an intrathecal morphine pump was implanted through the L3-L4 intervertebral space in February, 2002, without immediate complications. There was a 90% improvement in abdominal pain with increased functional status after intrathecal morphine titration coupled to decreased but continued dependence on oral tinzanadine and controlled-release morphine sulfate 30 mg orally every 12 hours. Two months later, he awoke with right lowerextremity parasthesias, extending from the lateral aspects of the proximal thigh to the foot, with medial sparing. Clinical examination confirmed the sensory loss without muscle weakness on confrontation testing. A magnetic resonance image (MRI) of the lumbar spine showed subtle effacement of the L4 neural foramen. Neurologic consultation at another facility 2 weeks later revealed no further findings. Of note, there were no cutaneous lesions to suggest varicella zoster infection. Electromyography and nerve conduction studies were performed, which showed absent right tibial H-responses and active denervation and reinnervation in right L5 and S1 muscles, consistent with a right L5-S1 radiculopathy or lower lumbar plexopathy. A 6-day course of low-dose oral methylprednisolone was instituted with minimal abatement of the parasthesias. One month later, he awoke with left leg weakness without sensory loss. Clinical examination revealed the prior abnormalities with a Medical Research Council (MRC) grade 3/5 left lower-extremity weakness and left ankle clonus. Emergent MRI of the thoracic and lumbar spine performed at another institution was reported to show a hyperintense signal at T9-T10 that was interpreted as an artifact possibly caused by metal within the catheter tip, or mass-like impingement into the left ventral surface of the thoracic cord. Intravenous steroids were started. A computed tomography of the lumbar spine showed the intrathecal catheter tip located at T9T10 without evidence of cord compression or thecal sac compromise. This is contrary to what may be seen with an epidural abscess or extradural mass originating from bony tissue as an alternative cause for the symptoms. CSF analysis showed a lymphocytic pleocytosis (white blood cell ⫽ 45/L with 97% lymphocytes), protein ⫽ 28 mg/dL (15-45), glucose ⫽ 83 mg/dL (40-80), and an elevated myelin basic protein of 4.6 ng/mL (0-1.49). Oligoclonal
•
Ubogu et al.
471
bands and IgG index and synthetic rate were normal. A normal brain MRI coupled with the earlier listed results excluded a demyelinating disease. The clinical presentation was hypothesized to result from mechanical trauma of the thoracic cord by the intrathecal catheter tip. Surgical withdrawal to the mid-T12 level was performed at the patient’s request, complicated by a persistent CSF leak at L3-L4 requiring fluoroscopy-guided blood patching and surgical oversew symptom stabilization. Cutaneous fixation of the catheter was performed with intravenous vancomycin for infection prophylaxis. In June 2002, 2 months after the initial symptoms, he presented to the emergency room at University Hospitals of Cleveland for the first time with a 5-day history of increased left lower-extremity weakness accompanied by constipation with overflow incontinence and bladder incontinence owing to detrusor instability. The parasthesias were present up to the level of his waist bilaterally, with worse intensity on the left. There was no history of trauma, infectious exposure, or foreign travel. The patient was afebrile. Neurologic examination was significant for a dense T12-L1 sensory level with spastic paraparesis (MRC grade 4/5 proximally, 4⫹/5 distally on the right, and 3/5 proximally, and 2/5 distally on the left), hyperreflexia of lowerextremity deep tendon reflexes, with sustained left patellar and ankle clonus. There were extensor plantar responses bilaterally. Laboratory evaluation was significant for a white cell count of 6,900/L with 3% immature band neutrophils. CSF analysis was not performed because of the recent lumbar procedures and the patient’s complaint of lower back discomfort. A 2.7-g dose (30 mg/kg) of intravenous methylprednisolone was administered emergently. An emergent lumbar spine MRI with gadolinium contrast showed abnormal T2-weighted intramedullary hyperintense signal in the posterior cord at the T10-T11 intervertebral level consistent with a diagnosis of transverse myelitis (Fig 1). A catheter tip granuloma was excluded. The patient was admitted to the neurology service and methylprednisolone was instituted at 250 mg intravenously every 6 hours for 72 hours. The intrathecal pump was removed within 24 hours of admission and intravenous gentamicin 450 mg (5 mg/kg) every 24 hours and ceftriaxone 2 g intravenously every 12 hours was administered. Over the next 2 to 3 days, there was gradual reduction of the sensory level with concurrent improvement of left leg strength. Laboratory evaluation and review of old gastrointestinal biopsy specimens were not consistent with sclerosing cholangitis. An opiate detoxification regimen was commenced that resulted in a successful weaning without signs of withdrawal
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Discussion
Fig 1. Initial MRI of the lower thoracic spine. An axial T2-weighted MRI of the thoracic spine with gadolinium contrast showed an intradural, intramedullary hyperintense signal of the posterior spinal cord at the T10-T11 intervertebral level consistent with transverse myelitis (see arrow).
and no recurrence of pain after psychologic counseling. The intrathecal pump catheter tip cultures grew greater than 50 colonies of pan-sensitive Acinetobacter baumanii. Gentamicin was discontinued. On day 4 of admission, oral prednisone taper was initiated for 15 days. Within a week of admission, motor strength had improved to MRC grade 4/5 proximally and MRC grade 3/5 distally in the left lower limb. The right side was normal. Bowel and urinary incontinence had resolved completely. There was an improvement in the left patella and ankle clonus with a combination of oral baclofen and tinzanadine. He was discharged on day 12 of admission to a skilled rehabilitation facility for acute rehabilitation, psychologic counseling, and completion of a 2-week course of intravenous ceftriaxone. Routine follow-up evaluation after 1 month of in-patient rehabilitation showed continued improvement in lower-extremity strength with residual spasticity, cautious independent ambulation, and parasthesias limited only to the right foot. The repeat MRI of the thoracic spine performed 3 months later showed complete resolution of the T2-weighted hyperintense signal at T10-11 (Fig 2) consistent with resolution of the transverse myelitis. His chronic abdominal pain was controlled without analgesia and he began to pursue full employment with some functional limitations affecting mobility.
Intrathecal opiate analgesia is indicated in patients with intra-abdominal pain refractory to other conservative pharmacologic and nonpharmacologic measures. It has been shown to be beneficial in the treatment of pain secondary to malignancy and has been used increasingly for nonmalignant pain.9 The clinician should be aware that spinal cord disease could occur as a late complication that warrants aggressive therapy to prevent irreversible sequelae. Our patient had progressive symptoms and signs occurring acutely or subacutely and CSF evidence of myelitis in the context of an intrathecal catheter tip infected with Acinetobacter baumanii. The symptoms persisted and progressed despite the withdrawal to a lower spinal level, making traumatic thoracic cord injury or catheter tip granuloma less likely explanations. Clinical improvement and subsequent radiologic resolution occurred only after the removal of the intrathecal pump and co-administration of intravenous corticosteroids and antibiotics, as evidenced by significant although incomplete neurologic and functional recovery. In retrospect, a diagnosis of a functional pain syndrome was made in this patient. A psychologic evaluation was not performed before intrathecal pump implantation. Initial psychologic evaluation may provide a means of instituting behavioral therapy for individuals with functional pain syndromes. The onset of myelopathic symptoms should be a
Fig 2. Follow-up MRI of the lower thoracic spine. The repeat axial T2-weighted thoracic spine MRI with gadolinium contrast performed 3 months after treatment shows absence of the hyperintense signal at the T10-T11 intervertebral level suggestive of radiologic resolution (see arrow).
Transverse Myelitis and Catheter Infection
strong indication for intrathecal pump removal if referable to the catheter site. The initial presentation and electromyography/nerve conduction studies in this case may have suggested a radiculopathy or plexopathy; however, the results also were consistent with anterior horn cell damage of the right L5-S1 spinal cord level. The subsequent progression with a suggestive MRI and CSF analysis should prompt the clinician to the diagnosis. If traumatic spinal cord injury secondary to catheter placement were considered, it would be expected that myelopathy could occur as an early complication. A course of combined intravenous/oral corticosteroids for 10 to 14 days and an MRI of thoracic spine with gadolinium 4 to 6 weeks afterward would be prudent after withdrawal of the catheter tip distally in such cases. One should be cautious of a radiologic diagnosis of spinal cord artifactual changes in an individual with myelopathic complaints. The progression of clinical and radiologic features of myelopathy should alert the clinician to the potential for an intrathecal pump catheter–related infection or catheter tip granuloma as being responsible for the myelopathy. In this case, a further CSF leak complicating the catheter withdrawal to a lower spinal level could have been a route for polymicrobial spinal cord infection. Although this was performed to meet the patient’s request, it could have resulted in potentially devastating consequences. Catheter tip granulomas are a well-established complication of intrathecal infusions of high concentration or doses of morphine or hydromorphine, but not baclofen.5 These may occur after an average of 24.5 months and may cause spinal cord or cauda equina compression, not transverse myelitis.5-7 Neurologic progression is usually slowly progressive with increasing granuloma size. Surgical specimens revealed noninfectious chronic inflammation, granuloma formation, and fibrosis or necrosis.5-7 This is not consistent with the findings in this case. Management of catheter tip granulomas includes surgical removal of the intrathecal pump with/without laminectomy, depending on the size of the granuloma and severity of compression.5-7 Transverse myelitis is a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic dysfunction, which develops acutely or subacutely. It is characterized clinically by the presence of bilateral signs and/or symptoms that need not be symmetric, the presence of a clear sensory level, and evidence of spinal cord inflammation (CSF pleocytosis, elevated immunoglobulin G index, or gadolinium enhancement on MRI).10 Common etiologies include viral infection (hepatitis viruses, herpes viruses, human T-cell lymphotro-
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phic-1 virus, enteroviruses), bacterial infections (mycoplasma, mycobacterium tuberculosis), Lyme disease, connective tissue diseases (systemic lupus erythematosus, Sjo¨ grens syndrome, sarcoidosis, antiphospholipid antibody syndrome), parainfectious, multiple sclerosis, and idiopathic etiology.10 The clinical presentation, prior CSF analysis, and MRI evaluation in this case meets the diagnostic criteria for transverse myelitis. Infection of the central nervous system is a rare complication of intrathecal pump placement. Catheter tips may become colonized without clinical consequence. The most likely organisms include Staphylococcus aureus, coagulase-negative staphylococcus, Streptococcus viridans, Neisseria spp., Corynebacterium spp., Enterobacter spp., Klebsiella spp., and yeasts.11 Cases of meningitis and cerebritis have been associated with Staphylococcus spp., Enterobacter aerogenes, and Klebsiella pneumoniae.12-14 Transverse myelitis has been described rarely, and occurred in association with a paravertebral abscess, osteomyelitis, epidural abscess, and phlegmonous duritis in an individual with Staphylococcus epidermidis peridural catheter infection.15 Acinetobacter is an aerobic nonfermentive gramnegative coccobacillus that is a significant cause of nosocomial infections, especially in neurosurgical patients.16 Most central nervous system infections reported were cases of adult meningitis, almost exclusively caused by baumanii species (previously known as Herellea vaginocola).17 Acinetobacter infection occurs opportunistically, but with enhanced virulence in patients undergoing invasive procedures (arterial or venous catheterization, mechanical ventilation, nasogastric tube placement, or thoracic drainage).17 Suri showed that after undergoing both emergent and elective cranial surgery, 24.7% of patients with infections were infected with Acinetobacter spp.18 Most infections were responsive to fluoroquinolone antibiotics, although higher rates of multidrug resistance occurred among intensive care unit patients, with uniform fatality in resistant meningitis cases.18 To our knowledge, this is the first reported case of an isolated transverse myelitis associated with an Acinetobacter intrathecal pump catheter-related infection. The management of this disease was based on the general principles of treating the underlying microbial cause with intravenous antibiotics, reducing cord inflammation with high-dose intravenous corticosteroids, and removal of the intrathecal pump. The use of fluoroquinolones as initial therapy for Acinetobacter myelitis may be adequate, however, broad antibiotic coverage for gram-negative organisms with a third-generation cephalosporin and aminoglycoside, as undertaken in this case,
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may ensure better coverage for polymicrobial infections and resistant strains. This case report shows transverse myelitis as a rare late complication of intrathecal pump implantation successfully treated by a combination of pump removal, antibiotics, and corticosteroids with good recovery. The Transverse Myelitis Consortium Working Group10 suggests that the clinical signs and symptoms of myelopathy should be followed by an MRI of the appropriate spinal level with gadolinium administration within 4 hours to confirm the absence of structural abnormality causing spinal cord compression. Spinal cord inflammation should be confirmed by gadolinium MRI enhancement, CSF pleocytosis, or elevated immunoglobulin G index. MRI with gadolinium should be performed to exclude brain demyelination. Early recognition and therapy of transverse myelitis are paramount in preventing irreversible spinal cord damage. We advocate that the development of neurologic complications after intrathecal pump implantation requires prompt specialist evaluation and suggest cooperation between anesthesiologists and neurologists in the early management of this potentially devastating complication.
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