Abstract 849 Poster Session II, Sunday, 5/2 (poster 145)

Background. So far little is known about changes in cerebral hemodynamics during chemo-therapy. Methods to increase drug delivery to the CNS include circumvention of the blood-brain barrier by direct injection of chemotherapeutic agents into the CSF. Attempts to increase drug delivery to the CNS as well as accidental overdose have caused serious side effects and warrant investigation.

Patients and Methods. Six patients with medulloblastoma, and supratentorial primitive neuroectodermal tumor as well as a patient with craniopharyngeoma underwent intrathecal and intralesional administration of chemotherapy. Ages ranged from 5 months to 16 years. We examined cerebral blood flow velocities (CBFV) during intrathecal administration of etoposide, mafosfamid, methotrexate and bleomycin. Measurements were performed with transcranial Doppler sonography (DWL, Multidop X) in the MCA before and after administration of the chemotherapeutic agent. CBFV was measured continuously in the MCA during administration.

Results. CBFV in the MCA remained constant during administration of etoposide, mafosfamide and bleomycin. An increase following administration was observed with methotrexate. The two patients who received methotrexate both showed transient increases up to 188% of baseline value. The increase ocurred 1-3 minutes after intrathecal administration of methotrexate and lasted up to 2 minutes.

Conclusion. An increase in CBFV following intrathecal administration has so far not been observed and the mechanism for this reaction is unknown. We speculate that this increase may involve inhibition of biosynthetic pathways for dopamine and serotonine as has been observed in the past. Another proposed mechanism may be due to arteriolar vasodilatation following transient acidemia.

study supported by the Children's Cancer Research Institute / St. Anna Kinderspital Vienna, Austria