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Hypoplasia of the Cerebellar Vermis and Cognitive Deficits in Survivors of Childhood Leukemia
K. T. Ciesielski, PhD;
R. Yanofsky, MD;
R. N. Ludwig, MD;
D. E. Hill, MS;
B. L. Hart, MD;
R. S. Astur, MS;
T. Snyder, PhD
Arch Neurol. 1994;51(10):985-993.
Abstract
Background
Neurodevelopmental evidence of the cerebellum's protracted course of postnatal development suggests that it is particularly sensitive to early toxic insult from cancer therapy. If this is the case, one would expect that there is a relationship between the pattern of neuropsychological and magnetic resonance imaging deficits and that both may indicate cerebellar abnormalities.
Objective
To investigate the profiles of neuropsychological functions and the morphologic features of the cerebellum, using in vivo magnetic resonance imaging planimetry in survivors of acute lymphoblastic leukemia (ALL) treated with radiation and chemotherapy.
Design
Thirteen survivors of childhood ALL with onset at age 2 to 5 years and a uniform protocol of treatment involving cranial radiation of 24 Gy and five doses of intrathecal methotrexate sodium participated in the study. Ten controls matched the patients in age and socioeconomic status. Each child was assessed with a comprehensive battery of neuropsychological tests and with magnetic resonance imaging of the brain.
Measurements
The neuropsychological scores were transformed into z scores and clustered into right and left hemisphere measures. Planimetric measures of the cerebellar vermis and pons were collected in the midsagittal plane.
Results
Consistently observed in survivors of ALL were the following: (1) significant cognitive deficits in visualspatial-motor coordination and figural memory, functions commonly related to the right side of the brain; and (2) hypoplasia of the cerebellar vermis, lobuli I through V and particularly VI to VII. Lateralization of the neurobehavioral deficits was not reflected in structural brain abnormalities.
Conclusions
Coexistence of the cerebellar hypoplasia and visual-motor coordination and memory deficits supports the neurodevelopmental approach to brain sequelae in survivors of ALL; it also suggests significance of the cerebellum for both motor and complex nonmotor cognitive processing.
Author Affiliations
From the Clinical Neuroscience Laboratory, Department of Psychology, University of New Mexico, Albuquerque (Dr Ciesielski and Messrs Hill and Astur); Manitoba Cancer Treatment and Research Foundation, Winnipeg (Dr Yanofsky); the Department of Oncologic Imaging, Cross Cancer Institute, Edmonton, Alberta (Dr Ludwig); the Department of Radiology, University of New Mexico, Albuquerque (Dr Hart); and the Department of Psychiatry, Neuropsychology, University of Alberta Hospitals, Edmonton (Dr Snyder).
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