Chronic neurologic disturbance in childhood leukemia

Abstract

Twenty-three leukemic children were studied prospectively to detect chronic effects of therapy. All patients received CNS prophylaxis, including 2400 R cranial irradiation, and intermittent maintenance therapy with intravenous methotrexate, cyclophosphamide and cytosine arabinoside. Neurologic symptoms were observed in 12 patients, all of whom had intermittent limping and mild incoordination, between the 10th and 18th month of maintenance therapy. Five of the 12 sustained seizures and four of these had subsequent abnormalities in motor, perceptual, behavioral or language development. Three school-aged children have learning disability and perceptual-motor defects. Studies of CSF folate and MTX content are presented but not helpful in delineating the etiology of these neurologic symptoms.

MRI morphometric and neuropsychological correlates of long‐term memory in survivors of childhood leukemia

“…Since the early 1980s, alternative protocols have been developed involving a combination of chemo‐agents including neurotoxic methotrexate 4. Early computed tomography (CT) and magnetic resonance imaging (MRI) studies with populations of children who received both chemotherapy and irradiation reported ventricular dilation, cortical calcification, and atrophy 5–7 that were more severe compared to children who received chemotherapy only 1. Neuroimaging findings varied, however, from no significant brain abnormalities 8, to transient white matter changes in a small percentage of ALL survivors 9, and to significant widening of the sulci and ventricle in children receiving exclusively chemotherapy 10.…”

Total body irradiation: a neuropsychological risk factor in pediatric bone marrow transplant recipients

“…Pediatric patients subjected to a combination of these therapeutic modalities may be at risk of neurological and neuropsychological impairment. Studies of long-term survivors of childhood acute lymphoblastic leukemia (ALL) have shown that central nervous system (CNS) preventive therapy is associated with transient as well as permanent neurological disturbances, including neuropsychological deficits of varying degrees (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Methotrexate Accumulation and Folate Depletion in Cells as a Possible Mechanism of Chronic Toxicity to the Drug

“…The neurological impairments include transient incoordination and paraplegia, seizures, learning disorders and fatal leucoencephalopathy (Meadows & Evans, 1976;Bleyer et al, 1973;McIntosh et al, 1976). Other less frequent toxic effects of methotrexate include bone pain, osteoporosis and pulmonary fibrosis.…”