CNS TISSUE DAMAGE &COGNITIVE DEFICITS--NURSING MODEL

DESCRIPTION: The overall goal of this
project is to test and refine a preliminary nursing model of Central
Nervous System (CNS) Tissue Damage and Cognitive Impairments following
whole brain radiation (RTX) and intrathecal Chemotherapy (IT CTX) in
children. Whole brain RTX and IT CTX have contributed to the dramatic
improvement in the long-term survival of children with acute lymphoblastic
leukemia, brain tumors and those requiring bone marrow transplant for
oncologic or immunologic disorders. As more children achieve long-term
disease remission, knowledge about damage to CNS tissue and the resulting
cognitive impairments associated with whole brain RTX and IT CTX will
become increasingly important. The specific aims of this study are to: 1)
study early CNS tissue damage following whole brain RTX and IT CTX; 2)
study delayed CNS tissue damage following whole brain RTX and IT CTX; 3)
investigate the cognitive impairments that occur following delayed CNS
tissue damage; 4) investigate the relationship between delayed CNS tissue
damage and cognitive impairments. A longitudinal, repeated measures design
will be used to study 96 children between the ages of 12-months and
12-years. Three different doses of whole brain RTX (2400, 1800 and 1000
centigray) and two different IT CTX regimens (methotrexate (MTX) alone; and
MTX, cytosine arabinoside and hydrocortisone) will be studied.
Cerebrospinal fluid and serum will be collected prior to and at specific
intervals following whole brain RTX and IT CTX to measure membrane damage
to the 1) vascular endothelial cells forming the blood brain barrier; 2)
myelin (while matter); and 3) brain cells (neural, glial). Cognitive
evaluations of general intelligence, visual spatial skills, language and
memory will also be conducted. This study will advance nursing knowledge
by testing and refining integrated model of CNS tissue damage and Cognitive
Impairments. Knowledge about the relationships between tissue damage and
cognitive impairments can be used for early identification of children at
risk for cognitive impairments so that interventions can be initiated. The
findings of this research will be of value to nurses and other health
professionals who care for children with whole brain RTX and IT CTX, and
may also be applicable to adults who receive similar types of CNS therapy.
years have resulted in cure or markedly extended life span for many
children. The long-term effects of these treatments, however, have only
recent begun to be documented. Cognitive impairment, beginning several
years following treatment with whole brain irradiation (RTX) and
intrathecal chemotherapy (IT CTX), has been reported, but the mechanisms
and pathogenesis of damage are poorly understood. To the extent that it is
possible to predict later cognitive impairment on the basis of early CNS
damage, and to the extent that damage is found to be dose-related, the
proposed investigation will have considerable clinical significance and
could lay important groundwork for minimizing CNS effects through radiation
dosage adjustments. In addition, the prospective design will facilitate
tracking specific cellular and cognitive changes over time to better
explain the underlying mechanisms of the impairment.