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Klaus Fliessbach; Horst Urbach, MD; Christoph Helmstaedter, PhD; Hendrik Pels, MD; Axel Glasmacher, MD; Jürgen A. Kraus, MD; Thomas Klockgether, MD; Ingo Schmidt-Wolf, MD; Uwe Schlegel, MD

Arch Neurol. 2003;60:563-568.

Background  Long-term neurotoxicity is a frequent complication of combined radiotherapy and chemotherapy in patients with primary central nervous system lymphoma. Treatment protocols without radiotherapy have been implemented to avoid this; however, little detailed neuropsychologic and neuroradiologic data exist to assess the frequency of long-term treatment sequelae in this patient group.

Objective  To determine whether a polychemotherapy regimen based on high-dose methotrexate results in cognitive impairment and/or changes detectable by magnetic resonance imaging of the brain during long-term follow-up.

Patients and Methods  Twenty patients with histologically proven primary central nervous system lymphoma were treated with a novel chemotherapy protocol that included systemic and intraventricular administration of methotrexate and cytarabine (ara-C). Standardized neuropsychologic testing and magnetic resonance imaging investigations were performed prior to therapy and prospectively during a median follow-up period of 36 months (range, 21-69 months).

Results  Ten patients achieved durable remissions without relapse for more than 1 year after completion of chemotherapy. There was no gross cognitive decline in any of these patients during the follow-up period. In contrast, magnetic resonance imaging revealed therapy-induced white matter changes in 5 of these patients.

Conclusions  We conclude that chemotherapy alone is associated with a low risk of long-term neurotoxicity in primary central nervous system lymphoma. Methotrexate-induced white matter lesions detectable on magnetic resonance imaging are not inevitably associated with significant cognitive decline.

From the Departments of Neurology (Mr Fliessbach, and Drs Pels, Kraus, Klockgether, and Schlegel), Radiology (Dr Urbach), Internal Medicine (Drs Glasmacher and Schmidt-Wolf), and Epileptology (Neuropsychological Section) (Dr Helmstaedter), University of Bonn, Bonn, Germany.

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