Parenchymatous degeneration of the central nervous system in childhood leukemia

Abstract

A 7‐year‐old boy with acute lymphocytic leukemia suffered increasing dementia, seizures, ataxia, and spasticity. The neuropathologic findings appeared unique, and included extensive fibrillary gliosis, with lesser degrees of myelin loss and axonal dystrophy. Similar though less severe findings were observed on re‐examination of CNS tissues from 23 other children who died of leukemia. Subcortical fibrillary gliosis was particularly prominent in 22 of 23 cases, and occurred symmetrically in the subependymal and subpial regions, inferior olives, cerebellar roof nuclei, substantia nigra, internal and external capsules, subventricular nuclei, basis pontis, and ventral horns of the spinal cord. The subcortical fibrillary gliosis was out of proportion to the myelin pallor and was not associated with leukemic infiltration. Alzheimer Type II glia were also present diffusely in 22 of 24 cases. No clear etiologic association could be established between the severity of the neuropathologic alterations and the following actors: age at death, duration of illness, elevated intracranial pressure, or treatment regimens. However, the reported case demonstrated the most severe parenchymatous changes at autopsy and received the most intensive treatment of the CNS. This association suggests that the neurologic deterioration may be the consequence of antileukemic treatment. Additional studies to define the frequency of such CNS abnormalities and the factors leading to their development are needed.

Brain lesions following combined treatment with methotrexate and craniospinal irradiation

“…The pathogenetic mechanism behind the cerebral lesions remains obscure; a number of factors may be involved such as the CSF concentration of MTX [19]; the nature of the diluent [20,21]; folate deficiency, the combination of MTX treatment with CNS irradiation [9,22] and a particular idiosincrasy to MTX [21]. Our findings indicate that whenever both the i.v.…”

“…Less frequent is an encephalopathy characterized by confusion, somnolence, ataxia, spasticity and ultimately by brain failure. Some neuropathological reports have underlined that there may be demyelination, foci of micronecrosis with astrocytosis and loss of oligodendroglial cells throughout the white matter [9][10][11].…”

Neurological complications of childhood leukaemia.

“…The syndrome of methotrexate-radiation toxicity was first described in children with treated CNS leukaemia (Kay et al, 1972;Hendin et al, 1974;Rubinstein et al, 1975), but has recently been recorded in those who receive prophylactic irradiation and subsequent parenteral methotrexate in fairly high dosage (Price and Jamieson, 1975;McIntosh et al, 1976). We have not encountered permanent neurological impairment in children receiving prophylactic irradiation, possibly because the Medical Research Council protocols involve neither high-dose parenteral nor long-continued intrathecal methotrexate.…”

Measles inclusion-body encephalitis in a child with treated acute lymphoblastic leukaemia.

“…(2) the damaging effects of chemotherapy and/or radiotherapy (Kay et al, 1972;Hendin et al, 1974;Rubinstein et al, 1975;Price and Jamieson, 1975;Weiss et al, 1974); (3) haemorrhages due to leukaemia or thrombocytopenia (Pitner and Johnson, 1973); and (4) infection to which these patients are abnormally susceptible (Levine et al, 1972;Simone et al, 1972). In the present case we found no signs of recurrent leukaemia, of radionecrosis, of toxic encephalopathy, or of intracranial haemorrhage, but there was clear evidence of an atypical infection of the brain.…”