title: Imaging changes and cognitive outcome in primary CNS lymphoma after enhanced chemotherapy delivery.
abstract: OBJECTIVE
  In children, MR imaging abnormalities consistent with leukoencephalopathy after treatment for hematologic malignancy do not correlate with neurologic dysfunction and are often overinterpreted with regard to clinical significance. We hypothesized that this would also be true in primary CNS lymphoma (PCNSL) patients who attained a complete response (CR) after treatment with chemotherapy and osmotic blood-brain barrier disruption (BBBD). We hypothesized that cognitive function loss measured after tissue diagnosis but before BBBD-enhanced chemotherapy could be correlated with brain changes visualized by imaging, whereas a correlation would not be present after therapy if the patient attained a complete tumor response, analogous to the findings in children.
  
  
  METHODS
  Sixteen primary CNS lymphoma patients were followed after CR (no enhancing tumor) by using a methotrexate-based regimen. Neuropsychological (NP) cognitive testing and MR imaging or CT (when MR imaging was not available) were performed before treatment and at completion of the 12-month treatment for each patient. Thereafter, the same studies were available for nine of these 16 CR patients, who were followed for a median of 55 months. Zone I was defined as enhancing tumor, and zone II as surrounding abnormal MR T2 signal intensity or low-attenuation CT. The cognitive scores were converted to Z scores and the MR T2 signal intensity or CT low-attenuated changes were converted to a summary zone II abnormality score.
  
  
  RESULTS
  A significant association between neurocognitive data and zone II abnormality was found at baseline after tissue diagnosis but before chemotherapy (r = -.55; P < .028), but no correlation existed at end of treatment. Imaging studies showed that seven patients developed a new T2 or low-attenuation abnormality by the end of treatment, whereas 15 patients showed a decrease, stable appearance, or complete resolution of their baseline zone II abnormality by end of treatment. Although cognitive loss compared with age-matched control subjects was common before starting therapy, by the end of treatment all patients' cognitive function improved significantly (P < .005).
  
  
  CONCLUSIONS
  The current data suggest that neither enhanced chemotherapy delivery nor changes in MR imaging T2 signal intensity or CT low attenuation, in PCNSL patients who attained a CR, were associated with a decrease in cognitive function.
authors.affiliation: Department of Neurology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. neuwelte@ohsu.edu
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
authors.forename: Paul E
authors.initials: PE
authors.lastname: Guastadisegni
authors.forename: Péter
authors.initials: P
authors.lastname: Várallyay
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Doolittle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D002648:Child; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis* / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009483:Neuropsychological Tests; D012074:Remission Induction; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D008727:Methotrexate