Cyclosporin A (CsA) induces neurological side effects in up to 40% of patients. A reversible posterior leukoencephalopathy syndrome is the most serious complication. Symptoms include headache, altered mental functioning, seizures, cortical blindness, and other visual disturbances, with hypertension. Neuroimaging studies show white matter changes in the posterior regions of the brain. Other neurological side effects of CsA include tremor, diffuse encephalopathy, cerebellar syndrome, extrapyramidal syndrome, pyramidal weakness, and peripheral neuropathy. Hypertension, hypomagnesemia, hypocholesteremia, and the vasoactive agent endothelin may all play a role in the pathogenesis of CsA neurotoxicty. Neurotoxicity is more frequent with high CsA blood levels, but levels may be within the therapeutic range. Dose reduction or withdrawal of CsA usually results in resolution of clinical symptoms and of neuroimaging abnormalities.

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The purpose of this study was to determine whether lower doses of dexamethasone for treatment of brain tumor edema are as effective as the conventional dose of 16 mg/d. We consecutively executed two double-blind randomized trials in patients with CT-proven brain metastasis and Karnofsky scores of 80 or less. In the first series, we compared 8 mg dexamethasone per day versus 16 mg/d; in the second series, 4 mg/d versus 16 mg/d. Standardized evaluation of quality of life and side effects took place at days 0, 7, 28, and 56. We randomized a total of 96 patients and evaluated eighty-nine. The Karnofsky score improved in the 8-mg group, which had improvement of 8.0 +/- 10.1 (mean +/- SD) points at day 7 versus 7.3 +/- 14.2 points in the 16-mg group. In the second series, the 4-mg group had improvement of 6.7 +/- 11.3 points at day 7 and 7.1 +/- 18.2 points at day 28 versus 9.1 +/- 12.4 and 5.6 +/- 18.5 points in the 16-mg group. Toxic effects occurred more frequently in the 16-mg group (p < 0.03). We conclude that administration of 4 mg dexamethasone per day for treatment of brain tumor edema results in the same degree of improvement as does administration of 16 mg/d after 1 week of treatment in patients who have no signs of impending herniation. Toxic effects are dose-dependent and, during a 4-week period, occurred more frequently in patients using 16 mg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

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Diagnostic decision making in the case of patients suspected of having leptomeningeal metastasis (LM) can be very difficult. The results of cerebrospinal fluid (CSF) cytology can be repeatedly negative, and the predictive value of gadolinium-enhanced magnetic resonance imaging (MRI) is not well known. We report the results of CSF cytology and Gd MRI in 61 patients with known cancer, suspected of having LM. We combined our data with those from a similar study and calculated the sensitivity and specificity of CSF and Gd MRI, in the absence of a "gold standard diagnosis." CSF cytology was positive for LM in 35 patients and MRI in 38. With CSF cytology sensitivity 75% and specificity 100%, with Gd MRI sensitivity was 76% but specificity only 77%. We conclude that Gd MRI provides strong support in the diagnosis of LM in patients with cancer who have negative results on CSF cytology.