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Leptomeningeal carcinomatosis is defined as malignant infiltration of the pia matter and arachnoid membrane. Leukaemias and lymphomas, lung, breast cancer and melanoma are the primary tumours commonly associated with leptomeningeal carcinomatosis. Diagnosis is based on compatible symptoms and signs, cytological evidence of malignancy in the cerebrospinal fluid, and neuroimaging studies. Treatment is largely palliative (median survival 2-4 months). Patients with lympomatous or leukaemic meningitis, chemosensitive tumours such as breast cancer, low tumour burden, minimal neurological deficits, good performance status and controllable systemic disease survive longer with occasional long-term responses. Available treatment options include focal radiation therapy to CNS sites of bulky, symptomatic or obstructive meningeal deposits, intrathecal cytotoxic therapy and systemic chemotherapy. No evidence of superiority of intrathecal treatment compared with best palliative care (including radiation therapy and systemic treatment) is available from clinical trials. Novel treatment approaches include intrathecal liposomal Ara-C, the development of new cytotoxic compounds, signal transduction inhibitors and monoclonal antibodies for intrathecal or systemic use. Until data from multi-centre randomised trials are available, rationalisation of therapy should be done by stratifying patients to prognostic groups. High-risk patients will only survive for a few weeks and are better managed with supportive measures, whereas low-risk patients justify vigorous cerebrospinal fluid-directed treatment combined with radiation therapy and systemic chemotherapy.

The purpose of this research is to clarify the feasibility and to determine the extent of transnasal drug delivery to the brain through the cerebrospinal fluid (CSF) in the rat, using 3H-5-fluorouracil (5FU) as a model drug. It was confirmed first that the concentration of 5FU in the CSF was significantly higher following nasal administration compared with intravenous injection, indicating direct transport of 5FU from the nasal cavity to the CSF. Concentration-time profiles of 5FU in the plasma and in the cerebral cortex were determined following intravenous infusion, nasal instillation and nasal perfusion. In order to evaluate the extent of drug transport from the nasal cavity to the cerebral cortex by way of the CSF, the apparent brain uptake clearances were calculated. The uptake clearance following nasal perfusion (8.65 microl/min/g tissue) was significantly large (p < 0.001) in comparison with that following intravenous infusion (6.20 microl/min/g tissue), while that following nasal instillation (6.94 microl/min/g tissue) was not. Consequently, significant amount of 5FU is transported from the nasal cavity to the brain through the CSF and thus, the delivery of the hydrophilic drug to the brain is augmented by nasal drug application.