Intrathecal Methotrexate Causing Paraplegia in a Middle-Aged Woman

Intrathecal Methotrexate Causing Paraplegia in a MiddleAged Woman S. Weiss S. Weiss and Y. Kahn, ‘Rokach’ Hospital, Tel Aviv (Israel) To the Editor The treatment and prophylactic therapy of meningeal leukemia with intrathecal (IT) methotrexate (MTX) in acute lymphoblastic leukemia is a well-established procedure. However, attention must be paid to the increasing number of reports of serious complications due to IT MTX (1). The present work describes a 46-year-old woman suffering from acute lymphoblastic leukemia, who slowly developed progressive permanent flaccid paraplegia post MTX treatment and a rise in CSF protein level during that therapy. Case Report A 46-year-old woman with acute lymphoblastic leukemia received treatment with prednison, 6 MP, cytosin-arabinoside and later vincristine. Complete hemato-logical and clinical remission was achieved. Half a year later, the patient complained of severe headache, but neurological examination revealed no pathology. A lumbar puncture showed the presence of lymphoblasts in CSF. Five IT injections of 20 mg MTX with parabens preservative in 20 ml of normal saline were administered over a 2-week period. The lymphoblasts in CSF disappeared and the protein level rose from 80, 65, 135, to 400 mg/dl while the white blood cells changed from 58, 12, 113 to 60/wl. The patient received cranial irradiation of 2,400 rad. 1 day after the last IT MTX injection the patient began complaining of weakness and pains in both legs. Over a 3-week period she developed flaccid paraplegia with a sensory level at D10, accompanied by stool and urinary incontinence, and finally right arm weakness. Partial remission of the neurological disturbances was observed in the next 6 months. 60 Weiss/Kahn The patient died from septicemia, after the reappearance of the leukemia. Permission for autopsy was denied. Discussion Paraplegia complicating IT MTX treatment has been reported mainly in children and teenagers and in a few adults [1J. The toxic neurological reaction to MTX therapy can be classified into three groups according to the clinical manifestations [2]: Chemical arachnoiditis, encephalopathy and myelopathy. In myelopathy direct damage to the spinal cord or root nerves may cause serious consequences; such as paralysis, transient or permanent paraplegia, quadriplegia and even death. This complication may perhaps be partially preventable. Different predisposing factors were suggested to be responsible for the development of these neurological complications [1]. These include the chemical preservatives, diluents, and contaminants of MTX. Comparison of 5 patients with severe neurotoxic manifestations post-IT MTX with 20 asymptomatic patients receiving the same therapy, showed that the toxic patients