Intelligence, executive function, attention, visual perception, and short-term memory were assessed in two groups of children who underwent surgery and subsequent radiotherapy and chemotherapy for cerebellar medulloblastoma at the Carlo Besta National Neurologic Institute, Milan, Italy. All 21 patients selected received the same combined radiotherapy-chemotherapy, but only one group (11 patients) was treated with intrathecal methotrexate (MTX) in addition. Both groups performed worse on cognitive tests than matched controls (cousins and siblings). Children younger than 10 years receiving MTX had significantly lower scores in all tests, and particularly executive function. Their impaired performance on arithmetic, comprehension, and block design was directly correlated with the extent of periventriculat leukomalacia observed on MRI. Only short-term memory was impaired in the MTX patients older than 10 years. In the group not receiving MTX, the 3 to 10 year old patients did significantly worse than controls in three tests only, whereas patients older than 10 showed no impairment in test performance compared to controls. The use of intrathecal methotrexate in the treatment of medulloblastoma should be reassessed. [1]

COMMENT. Intrathecal methotrexate therapy in children with medulloblastoma may worsen the cognitive deficits induced by chemotherapy and radiotherapy. Children younger than 10 years are especially at risk of impaired cognitive function following methotrexate.

The increase in survival rate of children with brain tumors over the past 20 years has been accompanied by a decrease in intellectual functioning and other complications. (see Progress in Pediatric Neurology II. PNB Publ, 1994;pp339-341) [2]. The omission of methotrexate may avoid the complications of leukoencephalopathy and dementia. Complications of cranial irradiation are reviewed in Progress in Pediatric Neurology III, 1997;pp423-430.