Methotrexate-induced subacute myelopathy: a serious but treatable complication.

Subacute myelopathy is a rare but serious complication of methotrexate (MTX) that may cause paraplegia. Although its underlying mechanisms have not been fully elucidated, homocysteine is thought to play a role in the pathogenesis of this adverse effect. Herein, we report the case of a 34-years old female patient with diffuse large B-cell lymphoma who developed progressive paraplegia accompanied by dysfunctional bladder and bowel movements after treatment with a modified CODOX-M/IVAC regimen, including high-dose intravenous MTX and intrathecal (IT-) MTX. Neurological symptoms gradually improved to almost normal levels within 4.5 months of onset following treatment with a combination of S-adenosylmethionine, methionine, cyanocobalamin, and folate. During chemotherapy, including high-dose MTX and IT-MTX for hematological malignancies, MTX-induced subacute neuronal damage should be carefully evaluated, and appropriate treatment should be initiated as early as possible.

Paraplegia and paraparesis from intrathecal methotrexate and cytarabine contaminated with trace amounts of vincristine in China during 2007.

PURPOSE: The production and administration of drugs used intrathecally requires special care to prevent contamination with neurotoxic agents. In 2007, we investigated a widespread outbreak of paraplegia and paraparesis among Chinese patients who received intrathecal drugs to identify the presumed contaminant and its source to prevent further cases. PATIENTS AND METHODS: We defined a case as onset from January 1 to October 31, 2007, of bilateral flaccid paraparesis or paraplegia or retention and incontinence of stool or urine, in a patient receiving intrathecal drugs. Using a retrospective cohort approach, we selected 12 hospitals from all hospitals that had reported cases. In these hospitals, we identified all 448 patients (including 107 cases) who received intrathecal chemotherapy or chemoprophylaxis in 2007. We calculated attack rates and Mantel-Haenszel adjusted risk ratios for intrathecal drug type and lot. RESULTS: All 12 hospitals used intrathecal methotrexate or cytarabine produced by one pharmaceutical plant. Only two lots of each drug were associated with cases. Lot-specific attack rates ranged from 42% to 100% (risk ratio, ∞; lower confidence bounds, 1.8 to 7.3). Vincristine production had immediately preceded production of the implicated lots on the same equipment. By using ultra performance liquid chromatography, we detected vincristine (0.28 to 18 µg) in unused vials from implicated lots of methotrexate and cytarabine. CONCLUSION: Trace amounts of vincristine that contaminated intrathecal drugs caused a large outbreak of severe neurologic damage. Vincristine and other neurotoxic drugs should not be produced on any equipment that is also used for producing drugs that are to be administered intrathecally.

Update on chymopapain.

Chemonucleolysis with chymopapain is accepted by many surgeons as a reasonable alternative to lumbar diskectomy for the treatment of lumbar disk disease. Approximately 70 to 75 per cent of carefully selected patients are successfully treated following this therapy, but extreme care must be exercised for precise needle placement and prompt and vigorous management of major allergic reactions. Methods to avoid major complications and their management, should they occur, are discussed.

Central necrosis of the spinal cord induced by hyperbaric oxygen exposure.

Seventy-six adult rats were exposed to 60 psig of oxygen on consecutive days until death. At autopsy, 17 of the animals segmental foci of central necrosis of the spinal cord gray matter, often associated with small ball- and flame-shaped hemorrhages in either the cervical and/or lumbosacral enlargements. Paraplegia or quadriplegia were clinically observed prior to death. The oxygen-induced spinal cord lesions are similar though not identical to those observed in experimental and human spinal cord trauma. These observations indicate that the therapeutic use of hyperbaric oxygen in patients with spinal cord injury has a potential danger of causing central spinal cord necrosis.