CASE REPORT
Effectively Managing Intractable Neuropathic Pain in an Acute Transverse Myelitis Patient via Intrathecal Morphing Pumping: A Case Report
Wei-Ting Wu1, Yu-Hui Huang2,3, Der-Cherng Chen4, Yu-Hsuan Huang1, Li-Wei
Chou1,5
¹Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung 40447, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung
40201, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chung Shan Medical
University Hospital, Taichung 40201, Taiwan; 4Center of Neuropsychiatry, Department of
Neurosurgery, China Medical University Hospital, Taichung 40402, Taiwan; 5School of
Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Correspondence to: Li-Wei Chou, M.D., MS
Department of Physical Medicine and Rehabilitation, China Medical University Hospital Address: No 2 Yuh-Der Road, Taichung, 40447, Taiwan, ROC.
TEL: 886-4-22052121-2381 Fax: 886-4-22026041
Disclosures:
No commercial party having a direct financial interest in the results of the research
supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated.
Abstract
Transverse myelitis is a rare inflammatory myelopathy characterized by motor and sensory function loss below the affected level of the spinal cord and causes neurogenic bowel and bladder. It also causes a relatively rare neuropathic pain accompanied with spasticity. Traditional therapies for neuropathic pain are multiple treatments such as multimodal
analgesic regimens, antiepileptic or antidepressant medications, opioids, sympathetic blocks, and spinal cord stimulation. Persistent neuropathic pain can distress a person’s life by
affecting sleep, work, recreation and emotional well-being. A patient reported to have suffered from intractable neuropathic pain after an acute transverse myelitis was not relieved despite combined therapies of medication with nonsteroidal anti-inflammatory drug,
antiepileptic, antidepressant, opioids, and acupuncture. Intrathecal morphine pumping implantation controlled the pain without side effects and the patient became ready for aggressive rehabilitation. The patient’s muscle power improved significantly and may soon be able to walk with the aid of a walker under minimal assistance.
Key words: Intrathecal morphing pump; Neuropathic pain; Rehabilitation; Transverse
Introduction
Acute transverse myelitis (ATM) is a rare inflammatory myelopathy. It manifests inflammatory cerebrospinal fluid (CSF) by either pleocytosis or increased immunoglobulin G index. The specific cause of inflammatory transverse myelitis is unknown but it has been noted to relate to multiple sclerosis (MS), neuromyelitis optica (NMO), acute disseminated encephalomyelitis, and connective tissue disease.1,2 Spinal lesions of MS are usually less than
two vertebral segments in length, asymmetric symptoms and signs with previous episodes of neurological dysfunction. And a relapsing demyelination affecting predominantly the optic nerves and spinal cord with more than three vertebral segments will be suspected NMO. The others would be suspected ATM, and viral infection is known to be a potential etiology. So ATM is a different diagnosis with infections such as herpes zoster virus or herpes simplex virus, as well as autoimmune diseases such as systemic lupus erythematosus or Sjögren's syndrome. It involves the entire cross section and is longitudinally extensive along three vertebral body segments rostrocaudally. It causes complete motor and sensory function loss below the affected level of the spinal cord and causes neurogenic bowel, neurogenic bladder, and sexual dysfunction. Although several people suffer from neuropathic pain, Laffey et al. has suggested that neuropathic pain is relatively rare in transverse myelitis.3 However,
chronic neuropathic pain below the lesion level is a late complication.3
Neuropathic pain arises from damage or pathological change in the peripheral or central nervous system. Neuropathic pain may affect the level of spine lesion or below or above it
because of de-innervation. Neuropathic pain, which is accompanied with spasticity or rigidity, is mediated by the activation of nociceptive afferents from muscles, or pain from excessive vasoconstriction that result in tissue hypoxia and the activation of chemosensitive nociceptors.4 It may be a burning, pricking, or an aching sensation. If the pain is not well
managed, joints contracture, muscle atrophy, pressure ulcers, pneumonia, cardiovascular problems, and decreased functional status occur in a bedridden or immobilized state. The treatment options of neuropathic pain include antiepileptic or antidepressant medications, sympathetic blocks, spinal cord stimulation, and intrathecal baclofen or opioids.5
A patient reported to have suffered from intractable neuropathic pain after ATM was not relieved despite combined therapies of medication with nonsteroidal anti-inflammatory drugs (NSAID), antiepileptic, antidepressant, opioids, and acupuncture. Intrathecal morphine (ITM) pumping implantation controlled the pain without side effects and the patient became ready for aggressive rehabilitation.
Case report
A 68-year-old woman was admitted because of a gradual onset of bilateral upper and lower limbs weakness. She had been suffering from trunk involuntary movement, dizziness, and ataxia for a month and a half, but was still able to conduct her daily activities independently. She then reported to have felt frequent headaches, bradykinesia, and postural tremor over her right hand and right upper limb, and tingling pain that shifted to her right posterior auricular area. No skin rash, papullae, bulla, or ulcer was noted on her face, trunk or limbs. The tremor on her hands progressed; thus, she could no longer grasp objects, wear clothes, comb her hair, or stand on one leg. She visited the neurologic out-patient department while the muscle power on her four limbs was still at normal level. However, her trunk and limbs were numb and itching all over her whole trunk.
One week before her admission, she underwent a brain magnetic resonance imaging (MRI). The MRI revealed multiple small hyperintensity spots in her basal ganglia, which indicate lacuna infarctions, demyelination lesions, and arteriosclerosis with tortuosity of arteries. However, the symptoms and signs were not compatible with these findings; thus, continuous observations were suggested. Four days later, urinary frequency and voiding difficulty with residual urine of about 856 cc were noted, which were indicative of a
neurogenic bladder. Thus, a foley tube was inserted. No diplopia, slurred speech, conscious loss, dyspnea, or obvious weight loss was observed throughout the whole course. The weakness in the limbs became severe, and a physical and neurologic examination revealed
that the muscle power of the right upper and lower limb decreased from 5 to 4 and 5 to 3, respectively, and the left lower limb decreased from 5 to 4. Besides, the sensation of pinprick and light touch below the T4 spinal level was also noted.
After admission, laboratory data showed a mild increase of white blood count (WBC) and neutrophilic segment. The level of electrolyte, renal function, liver function, vitamin B12, and folic acid were normal. Lumbar puncture was then performed, and the CSF findings showed lymphocyte-predominant pleocytosis, elevation of microprotein and glucose, but the WBC count was normal. No specific findings of bacteria, tuberculosis, or fungus were noted in the culture, and the polymerase chain reaction result was negative for viruses such as cytomegalovirus, herpes simplex viruses, and Epstein-Barr virus. No malignant cell was apparent, and no positive findings of antibiotics such as SS-A, SS-B, RA, C3, C4, and ANA were noted. Spinal MRI T2 weight axial images revealed a patchy diffuse area of
hyperintensity from C3 to T5 vertebral segments; thus, the patient was diagnosed with transverse myelitis (Figure 1). Since the NMO and optic neuritis should also be suspected even the visual field was normal, we arranged VEP and it showed negative finding. Although she received treatment, right upper limb and bilateral lower limb weakness and urine and stool incontinence persisted without any improvement during the course.
One month after admission, the patient complained of coldness from her leg to chest with abnormal tremor and night sweating. She was administered with 0.5 mg of clonazepam twice a day and 10 mg of imipramine at bedtime to relieve the discomfort. However, two
days later, she suffered from intermittent coldness, numbness, tightness, and a cramping sensation ascending from her leg to chest with severe tingling pain lasting for about 10 to 15 minutes for a period of about 5 to 10 minutes. These symptoms manifested the whole day with a visual analogic scale (VAS) of more than 9. The physical examination showed no range of motion limitation, joint tenderness, hotness, or swelling, thus neuropathic pain was impressed. Rest did not relieve the pain, and the patient experienced difficulty sleeping. She was then administered with 300 mg of gabapentin at bedtime, 0.5 mg of clonazepam twice a day, 100 mg of tramadol three times a day. Tramadol was gradually increased because the patient reported that the pain was intractable. She was also given 0.5 amp of pethidine as needed. With the advice of an anesthesiologist for pain management, 2 mL of patient-controlled analgesia (dihydroxyacetone phosphate, 160 mg of morphine, an infusion of 0.2 mL/hour, a loading dose of 2 mL, limit of 4 h for 10 mL, and lockout interval of 8 minutes) were arranged for two weeks. Given its lethargic side effect, the medicines were continued by increasing the patchy morphine (fentanyl) amount to 24 mcg per hour, 0.5 mg of clonazepam three times a day, 300 mg of gabapentin three times a day, and ultracet (325 mg of
acetaminophen / 37.5 mg of tramadol) four times a day. We added treatments such as NSAID, antidepressants such as sertraline, anticonvulsant such as tizanidine, baclofen, and acupuncture, but did not have significant effects. VAS remained at 7 to 8. The dose of gabapentin was gradually adjusted with initiation doses of 100 to 300 mg three times daily. The dose was titrated by 100 to 300 mg every 3 to 7 days to the usual effective dose from
1800 mg to 3600 mg per day.6 The pain became severe after rehabilitation and was
unbearable to the extent that she cried the whole day. About 10 mg of morphine had to be given through injection to the patient as needed. However, morphine causes side effects of general weakness, dizziness, dried mouth, and hallucinations; thus, follow up rehabilitation could not be performed on the patient.
One and half month after medical treatment for the neuropathic pain, we then resorted to ITM pumping for maintaining the lowest dose of morphine to keep the effects and side effects in balance. A catheter was inserted into a dura sac through the L4/5 space with the morphine dosage kept at 0.2 mL (0.5 mg) per hour. The pain was immediately relieved during the pre-implant trial. Thus, ITM pumping (Figure 2) was implanted for treatment with a dosage of 1.3 mL (3.25 mg) per hour during the day and 1.0 mL (2.5mg) per hour at night. VAS decreased to 2 to 3, and the muscle cramp ascending from the leg to chest went mild with a duration of about 10 to 15 seconds and an interval of about 30 min to 1 hour. The previous medications were terminated and only 4 mg of tinazidine was administered three times a day after the implantation of ITM pumping. The tingling pain, numbness, coldness, burning, and cramping sensation were significantly relieved and she was able to return to her rehabilitation course.
After rehabilitation, the muscle power of the lower limb greatly improved from 2 to 4. Neurological deficiency was also relieved at this point, and the intermittent catherization program training was discontinued from four times a day to total spontaneous voiding.
Functional status such as sitting was improved from poor to fair. Her daily living improved from complete dependence to moderate assistance. The functional independence measure increased from 48 prior to implantation to 74 when she was discharged, and increased to 87 seven months after admission. The Barthel index also increased from 10 to 25 after four months of aggressive rehabilitation programs.
Discussion
The patient once suffered from common cold one week before the initial symptoms. Although all CSF finding were negative, virus infection will be more suspected. Besides, no past history or family history of autoimmune disease were mentioned among the patient’s family. We once surveried, with VEP and other tests, for any possibilities of different diagnosis like NMO and optic neuritis. Idiopathic transverse myelitis had been the final diagnosis due to all tests were negative finding.
The prognosis of ATM is poor. Less than half of the number of cases significantly recover, and most of the patients remain completely paralyzed after the initial attack.7 The
first treatment is to overcome the inflammatory process with high-dose intravenous
corticosteroid therapy leading to rapid clinical improvement.8 However, long-term follow-up
data on patients with ATM reveal about one-third of severe disabilities, recovering with little to no sequelae, and moderate degree of permanent disability.9,10 Aggressive rehabilitation
could increase the activity of daily living and functional status, and decrease complications such as cardiovascular, respiratory problems, muscle atrophy, and pressure ulcers because the nervous system is dynamic and continually changing. Moreover, maintaining optimal activity is essential for neural regeneration and restoration.11
If severe pain and spasticity are noted during the treatment course and are not treated well, the prognosis will be poor. Persistent neuropathic pain can distress a person’s life by affecting sleep, work, recreation and emotional well-being.12 The treatment for neuropathic
pain is difficult; thus, multiple treatments or multimodal analgesic regimens should be used. Available therapies such as antiepileptic drugs, tricyclic antidepressant drugs, opioids, topical lidocaine, antidepressant drugs like serotonin-norepinephrine reuptake inhibitors such as duloxetine, and analgesic agents are effective in managing neuropathic pain.13, 14 Other
treatments such as acupuncture were studied, and Sonia A Vagela et al.15 reported a case of
TM with a constant deep dull pain despite multiple medicines. After acupuncture, the pain was totally relieved.
In these treatments, the Canadian Pain Society recommends the use of tricyclic antidepressants (TCAs) such as imipramine as first-line treatment for neuropathic pain.16
However, the side effects are anticholinergic such as dry mouth, dry eyes, urinary retention, excess sedation, orthostatic hypotension, constipation, and blurry vision. Patients with a history of cardiovascular disease must avoid TCAs because cases of tachycardia, myocardial infarction, and sudden cardiac death have been reported. 17 For the elderly, the risk of falling
increases because of cognitive problems. 17 Recently, serotonin-norepinephrine reuptake
inhibitors such as duloxetine were suggested as second-line treatment options, but the common side effect is nausea, and it may cause hepatotoxicity. 18 Antiepileptic drugs such as
gabapentin are a first-line treatment option for painful polyneuropathies, postherpetic neuralgia, partial onset seizures, and central neuropathic pain. 18 However, sedation,
somnolence, dizziness, increased risk of falls, and cognitive impairment are the side effects among the elderly, 17 and maybe affect the rehabilitation.Our patient showed no sign of
improvement when treated with the combined therapy mentioned above.
In our patient, the opioids really worked, but not well controlled the pain during the course of therapy. Not only the other forms of dose giving for opioids could not maintain the concentration in the blood, but also we didn’t know that how much opioids were exactly absorbed into the body. When we added more dose for our patient through oral or patch forms, the side effect such as nausea, transient confusion, hallucinations, and constipation became severe and even bothered the rehabilitation and activity of daily living. Since the ITM pump was implanting into the thecal, it gave a lower incidence of dependence, tolerance, and side effects when compared with systemic administration.19
Studies on the use of continued morphine infusion through thecal for pain control are currently being performed. Genni Duse et al. 20 reported that the impact of ITM infusions on
perception and psychosocial functionality for chronic nonmalignant pain, and failed to respond to multimodal analgesic regimens. The study reported statistical improvement at each testing interval compared with the baseline (P < 0.005). 20 Programmable intrathecal
pump is a continuous and controlled drug delivery system that directly delivers drugs into the cerebrospinal fluid around the spinal cord.21, 22 The drug dosage can be adjusted and refilled
with minimal invasive procedure. The dosage of morphine through this type is more effective but much lower than others; thus, cases of systemic side effects are lessened.
The basis of the dose used for ITM pumping is in accordance with the patient’s
by 0.2 mL (0.5 mg) per hour according to the suggestions of Alı’ Shaladi et al.23, the
following days before implanting showed rebounding pain sensation. So we adjusted the dose until it came to an excellent dose. Besides, much medicine was terminated except tinazidine after ITM pumping implanting, so the dosage of ITM pumping would be increased to relieve the neuropathic pain. Beside, the dosages were set as 1.3 mL (3.25 mg) per hour during the day and 1.0 mL (2.5mg) per hour at night because the patient’s symptoms got more severe in the daytime during the rehabilitation programs, and released in the nighttime after resting.
Four months after ITM pumping implantation, the morphine infusion rate did not increase and even decreased when the dosage was balanced. With the pain managed well without side effects, the patient was able to return to her rehabilitation course. Her muscle power improved four months after implantation, and we look forward to her being able to walk with a walker device under minimal assistance.
The side effects of ITM pumping implantation were also reported, like nausea, vomiting, constipation, urinary retention, pruritus, mental status change, and respiratory depression.24
Besides, the incidence of intrathecal catheter tip inflammatory mass, and infection were also reported. Fortunately, the side effects were not noted in our patient.
Conclusion
We reported a case of neuropathic pain caused by transverse myelitis and managed with ITM pumping. The treatment of neuropathic pain is not yet fully developed, and a poor response to combined therapy causes severe complications such as immobilization, muscular-skeletal system, respiratory system, and cardiovascular system problems. Combined therapy causes side effects no matter how well it is administered. Therefore, ITM pumping is an effective treatment for severe neuropathic pain.
Reference:
1. Kaplin AI, Krishnan C, Deshpande DM, Pardo CA, Kerr DA. Diagnosis and management of acute myelopathies. Neurologist. 2005;11(1):2–18.
2. Krishnan C, Kerr DA. Idiopathic transverse myelitis. Arch Neurol. 2005; 62(6) : 1011 – 1013.
3. Laffey JG, Murphy D, Regan J, O'Kecffc D. Efficacy of spinal cord stimulation for neuropathic pain following idiopathic acute transverse myelilis: a case report. Clinical
Neurology and Neurosurgery. 1999;101 (2): 125-7.
4. Christian Geber, Ulf Baumgärtner, Rainer Schwab, et al. Revised Definition of
Neuropathic Pain and Its Grading System: An Open Case Series Illustrating Its Use in Clinical Practice. The American Journal of Medicine. 2009; 122, S3–S12. 5. Krishnan C, Kaplin AI, Deshpande DM, Pardo CA, Kerr DA, Transverse myelitis:
pathogenesis, diagnosis and treatmenl. Front Biosci. 2004;9:1483-99.
6. Kristen Jefferies, Treatment of neuropathic pain. Semin Neurol. 2010;30:425–432. 7. Lee Goldman, MD, Dennis Ausiello, MD. Cecil Medicine. 23rd ed. Philadelphia:
Saunders Elsevier; 2007.
8. Kennedy PG, Weir AI. Rapid recovery of acute transverse myelitis treated with steroids. Postgrad Med J. 1988;64:384–5.
9. Christensen PB, Wermuth L, Hinge HH, Bomers K. Clinical course and long-term prognosis of acute transverse myelopathy. Acta Neurol Scand. 1990;81(5):431–435. 10. Defresne P, Hollenberg H, Husson B, et al. Acute transverse myelitis in children: clinical
11. Cristina L. Sadowsky, Daniel Becker, Glendaliz Bosques, et al.. Rehabilitation in Transverse Myelitis. Continuum Lifelong Learning Neurol. 2011;17(4):816–830. 12. Srinivasa N. Raja, and Jennifer A. Haythornthwaite. Combination Therapy for
Neuropathic Pain — Which Drugs, Which Combination, Which Patients? N Engl J Med. 2005; 352; 13.
13. Chen H, Lamer TJ, Rho RH, et al. Contemporary management of neuropathic pain for the primary care physician. Mayo Clin Proc. 2004;79:1533-45.
14. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60:1524-34. 15. Sonia A Vagela, Clare P Donnellan. Acupuncture for back pain, knee pain and insomnia
in transverse myelitis- a case report. Acunpuncture In Medicine. 2008;26(3):188-192. 16. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent
guidelines. Am J Med. 2009; 122(10, Suppl):S22–S32. 17. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of
neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237–251. 18. Moulin DE, Clark AJ, Gilron I, et al. Canadian Pain Society. Pharmacological
management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007;12(1):13–21.
19. Anderson CA, Burchiel KJ. A prospective study of long-term intrathecal morphine in the management of chronic non-malignant pain. Neurosurgery. 1999;44:289–301.
20. Genni Duse; Giorgio Davia; Paul F. White. Improvement in psychosocial outcomes in chronic pain patients receiving intrathecal morphine infusions. Anesth Analg.
2009;109:1981–6.
21. Lee KS, Chu KS, Chung CL, Lin CL, Hwang SL, Howng SL. Intrathecaldrug delivery system with programmable morphine pump for pain of terminally Ill cancer patients.
J Chinese Oncol. 2009;25:159–66.
22. Stearns L, Boortz-Marx R, Du Pen S, et al. Intrathecal Drug Delivery for the management of Cancer Pain. A Multidisciplinary Consensus of Best Clinical Practices. J Support
Oncol. 2005;3:399–408.
23. Alı’ Shaladi, Maria Rita Saltari, Bruno Piva, et al. Continuous intrathecal morphine infusion in patients with vertebral fractures due to osteoporosis. Clin J Pain.
2007;23:511–517.
24. Xiulu Ruan. Drug-related side effects of long-term intrathecal morphine therapy. Pain
Figure Legends
Figure 1. A. Sagittal T2-weighted axial images reveal a patchy diffuse area of hyperintensity
from the C3 to T5 vertebral segments. B. Sagittal T1-weighted image obtained after the intravenous administration of gadolinium reveals minimal enhancement.
Figure 2. ITM pumping was set in the subcutaneous site and the tube was inserted into dura
