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Neuropsychological outcome after chemotherapy for primary CNS lymphoma

A prospective study

From the Departments of Neurology (Dr. Fliessbach, A. Althaus, Dr. Pels, Dr. Linnebank, A. Juergens, Dr. Klockgether, Dr. Schlegel), Epileptology (Drs. Fliessbach and Helmstaedter), Radiology (Dr. Urbach), and Internal Medicine (Drs. Glasmacher and Schmidt-Wolf), University Hospital Bonn, Germany.

Address correspondence and reprint requests to Dr. Klaus Fliessbach, Klinik für Epileptologie, Sigmund-Freud-Str. 25, 53105 Bonn, Germany; e-mail: klaus.fliessbach{at}ukb.uni-bonn.de

Background: Combined radio- and chemotherapy for primary CNS lymphoma (PCNSL) is associated with a considerable risk of long-term neurotoxicity. The impact of high-dose methotrexate (MTX)-based chemotherapy alone on cognition and quality of life (QOL) is controversial.

Objective: To assess the impact of the tumor itself and its treatment with high-dose MTX-based chemotherapy on long-term cognition and QOL in patients with PCNSL.

Methods: Prospective neuropsychological examinations and MRI were performed in patients with PCNSL who were in complete remission for more than 12 months after completion of chemotherapy. A QOL assessment was performed at long-term follow-up.

Results: Twenty-three patients were eligible. The median follow-up period was 44 months after diagnosis. In long-term follow-up, 22 (95%) of 23 patients showed either preserved or improved cognitive functions as compared with pretreatment and immediate posttreatment baseline assessment. One patient showed an isolated decline in psychomotor speed. Eleven (48%) of 23 patients displayed at least mild cognitive deficits at long-term follow-up not related to therapy. Nineteen (83%) of 23 patients reported a good QOL. MRI revealed confluent white matter abnormalities in eight patients that were not associated with cognitive decline.

Conclusion: In patients with primary CNS lymphoma (PCNSL) treated with a methotrexate (MTX)-based chemotherapy, no gross cognitive decline has to be expected as a long-term treatment effect. MTX-induced white matter changes apparent on MRI are not inevitably associated with cognitive impairment. Nevertheless, a substantial fraction of patients with PCNSL retain cognitive deficits as a residual symptom of the tumor.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 12 issue to find the title link for this article.

Received July 28, 2004. Accepted in final form December 13, 2004.

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