Abstract
Intrathecal chemotherapy has been determined to cause transient or permanent paraparesis due to myelopathy in patients with leukemia or other malignancies. To systematically evaluate the effect of methotrexate on spinal cord function, somatosensory evoked potentials (SEP) were measured in children with acute lymphoblastic leukemia (ALL). A prospective evaluation was performed in 38 consecutive children aged 1.4-15.3 years with newly diagnosed ALL during treatment. Intrathecal methotrexate therapy was included in the therapy schedule of all patients as central nervous system (CNS) therapy in addition to intravenous chemotherapy in 19 standard risk patients and intravenous chemotherapy with cranial irradiation in 19 intermediate or high-risk patients. The measured conduction times were compared with those of 38 control children matched for age, height, and sex. A significant increase in the conduction time of the tibial nerve SEP was found between the Th12 level and the cortex in children with ALL after receiving intrathecal methotrexate therapy during the induction and CNS therapy phases when compared with their controls. The difference of the mean latencies was 1.45 ms (95% CI 0.39-2.51; P < 0.01). There was no significant delay in the median nerve SEP from the brain stem to the cortex, indicating that the conduction delay was in the area of the spinal cord exposed to intrathecal methotrexate. Moreover, the cortical amplitudes of the median nerve SEPs were significantly reduced when measured immediately after intravenous and intrathecal methotrexate and compared to the amplitudes measured after induction therapy in standard risk patients (P = 0.001). Intrathecal methotrexate with systemic chemotherapy causes a deterioration in the somatosensory pathways within the CNS, suggesting also spinal cord dysfunction in children with ALL in addition to the cerebral dysfunction described earlier.
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