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 Volume 59, Number 1, July 09, 2002
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Neurology 2002;59:48-53
© 2002 American Academy of Neurology

Intrathecal methotrexate affects cognitive function in children with medulloblastoma

D. Riva, MD, C. Giorgi, MD, F. Nichelli, DN, S. Bulgheroni, DN, M. Massimino, MD, G. Cefalo, MD, L. Gandola, MD, M. Giannotta, MD, I. Bagnasco, MD, V. Saletti, MD and C. Pantaleoni, MD

From the Developmental Neurology Unit (Drs. Riva, Giannotta, Bagnasco, Saletti, and Pantaleoni, and F. Nichelli, and S. Bulgheroni) and Functional and Stereotactic Neurosurgery Unit (Dr. Giorgi), Istituto Nazionale Neurologico C. Besta; and Oncologic Pediatric Unit (Drs. Massimino and Cefalo) and Radiotherapy Unit (Dr. Gandola), Istituto Nazionale per la Cura dei Tumori, Milano, Italy.

Address correspondence and reprint requests to Dr. Daria Riva, Divisione di Neurologia dello Sviluppo, Istituto Nazionale Neurologico, Via Celoria, 11, 20133 Milano, Italy; e-mail: driva{at}istituto-besta.it

Background: Cognitive impairment occurs after malignant brain tumor treatment in children, following brain radiotherapy and systemic and intrathecal chemotherapy.

Objectives: 1) To compare two groups of children who underwent surgery for cerebellar medulloblastoma with their cousins and siblings, assessing intelligence, executive function, attention, visual perception, and short-term memory. Both groups were treated with the same combined radiotherapy–chemotherapy, but differed in that only one group received intrathecal methotrexate (MTX+). 2) To relate these measures to MRI findings (leukomalacia).

Results: The two groups performed worse than their control subjects in all tests. The MTX+ group younger than 10 years performed significantly worse in all tests, particularly executive ones. The group older than 10 years performed significantly worse only in short-term memory. Younger patients without MTX performed significantly worse than controls only in some neuropsychological measures; there were no differences between older patients and control subjects. Only in the MTX+ group was there a direct correlation between extent of leukomalacia and performance in some tests.

Conclusions: The administration of intrathecal methotrexate to children with medulloblastoma worsens the cognitive deficits induced by chemotherapy and radiotherapy. The use of intrathecal methotrexate in the treatment of medulloblastoma and other malignancies should be reassessed.




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