A 68-year-old woman was admitted with gradual onset of bilateral weakness of the upper and lower limbs. She had been experiencing involuntary trunk movement, dizziness, and ataxia for six weeks, but was still able to perform her daily activities independently. Her symptoms progressed to include frequent headaches, bradykinesia, and postural tremor over her right hand and right arm, and tingling pain localizing to her right posterior auricular area. No skin rash, papullae, bullae, or ulcers were noted on her face, trunk, or limbs. The tremor in her hands progressed, such that she could no longer grasp objects, put on clothes, comb her hair, or stand on one leg. A visit to the neurologic outpatient clinic confirmed that muscle power in all four limbs was normal. However, her trunk and limbs were numb, and she reported pruritus over her entire trunk.
One week before admission, she underwent magnetic resonance imaging of the brain, which revealed multiple small hyperintense spots in her basal ganglia, indicating lacuna infarcts, demyelinating lesions, and arteriosclerosis with tortuosity of the arteries. However, her symptoms and signs were not compatible with these findings, so continued observation was suggested. Four days later, she was noted to have urinary frequency, difficulty voiding, and a residual urine volume of 856 mL, all of which were indicative of a neurogenic bladder, so a Foley tube was inserted. No diplopia, slurred speech, loss of consciousness, dyspnea, or obvious weight loss was observed throughout the course of her admission. Her limb weakness became severe, and physical and neurologic examination revealed that the muscle power in her right upper and lower limbs had decreased from 5 to 4 and 5 to 3, respectively, and in the left lower limb had decreased from 5 to 4. Further, diminished sensation of pinprick and light touch was noted to be below T4.
On admission, laboratory data showed mildly increased white cells and neutrophils. Electrolytes, renal and hepatic function, vitamin B12, and folate were normal. A lumbar puncture was performed, and showed lymphocyte-predominant pleocytosis and elevation of microproteins and glucose, but her white cell count was normal. No specific laboratory findings indicating tuberculosis, or bacterial or fungal infection were noted, and polymerase chain reaction results were negative for cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. No malignant cells were apparent, and no positive findings of antibodies such as SS-A, SS-B, RA, C3, C4, or antinuclear antibody were noted. T2 weighted axial images on spinal magnetic resonance imaging revealed a patchy diffuse area of hyperintensity extending from C3 to T5, so the patient was diagnosed with transverse myelitis (Figure 1). Given that neuromyelitis optica and optic neuritis should also be suspected even if the visual field is normal, we arranged for visual evoked potentials, which were negative. Her right upper limb and bilateral lower limb weakness and incontinence of urine and stool was unresponsive to treatment.
One month after admission, the patient complained of a cold sensation extending from her bilateral legs to her chest, with abnormal tremor and night sweats. She was treated with clonazepam 0.5 mg twice daily and imipramine 10 mg at bedtime to relieve her discomfort. However, two days later, she suffered from intermittent coldness, numbness, tightness, and a cramping sensation ascending from her leg to her chest, severe tingling pain with duration of 10-15 minutes, and a period of 5-10 minutes. These symptoms lasted throughout the day, with a visual analog pain score >9. Physical examination showed no limitation in range of motion, joint tenderness, hotness, or swelling, so the clinical impression was that of neuropathic pain. Rest did not relieve her pain, and she experienced difficulty sleeping. She was then treated with gabapentin 300 mg at bedtime, clonazepam 0.5 mg twice daily, and tramadol 100 mg three times daily. The patient reported that her pain was intractable, so the tramadol was gradually increased. Half an ampoule of pethidine was also given as needed. On the advice of an anesthesiologist skilled in pain management, 2 mL of patient-controlled analgesia (dihydroxyacetone phosphate and morphine 160 mg infused at a rate 0.2 mL per hour, with a loading dose of 2 mL, a dose ceiling of 10 mL over four hours, and a lockout interval of eight minutes) was arranged for two weeks. Given the potential problem of lethargy as a side effect of morphine, her pain medication was augmented by increasing the dose of her fentanyl patch to 24 mug per hour, along with administration of clonazepam 0.5 mg three times daily, gabapentin 300 mg three times daily, and a combination of acetaminophen 325 mg + tramadol 37.5 mg four times daily. We also added nonsteroidal anti-inflammatories, an antidepressant (sertra-line), anticonvulsants (tizanidine, baclofen), and acupuncture, to no avail. Her visual analog pain score remained at 7-8. The dose of gabapentin was gradually escalated from 100 mg to 300 mg three times daily, and titrated by 100-300 mg every 3-7 days to the usually effective daily dose range of 1800-3600 mg. Her pain became unbearably severe during rehabilitation, to the extent that she cried throughout the day. Morphine 10 mg was given via injection as needed, but caused general weakness, dizziness, dry mouth, and hallucinations, which prevented any further rehabilitation.
Six weeks after starting the patient on medical treatment for her neuropathic pain, we resorted to an intrathecal morphine pump to maintain the lowest dose of morphine able to keep the therapeutic effects and side effects in balance. A catheter was inserted into the dural sac via the L4/5 space, with the morphine dosage maintained at 0.2 mL (0.5 mg) per hour. Her pain was relieved immediately during a preimplantation trial, so an intrathecal pump (Figure 2) was implanted and set to deliver a morphine dosage of 1.3 mL (3.25 mg) per hour during the day and 1.0 mL (2.5 mg) per hour at night. Her visual analog score decreased to 2-3, and the muscle cramps ascending from the leg to the chest became mild, lasting for about 10-15 seconds and appearing at intervals of about 30-60 minutes. Previous medication was stopped, with only tizanidine 4 mg three times daily being administered after implantation of the pump. Her pain, numbness and tingling, and cold, burning, and cramping sensations were relieved significantly and she was able to return to her rehabilitation program.
After rehabilitation, muscle power in her lower limb improved markedly from 2 to 4. Her neurologic deficit also improved at this point, such that her training program of intermittent catheterization four times daily was discontinued in favor of spontaneous voiding. Functional status, such as ability to sit, improved from poor to fair. Her functional status improved from complete dependence to being able to perform activities of daily living with moderate assistance. Her functional independence score increased from 48 prior to implantation to 74 at the time of discharge, and further to 87 seven months after admission. Her Barthel index increased from 10 to 25 after four months of an aggressive rehabilitation program.