A prospective evaluation of changes in brain structure and cognitive functions in adult stem cell transplant recipients

Abstract

Hematopoietic stem cell transplantation (HSCT) is an efficacious treatment for many hematologic malignancies. However, the conditioning regimen of high-dose (HD) chemotherapy with or without total body irradiation (TBI) can be associated with neurotoxicity. In this prospective study, we used quantitative neuroimaging techniques to examine regional gray matter and ventricular volumes, and standardized neuropsychological tests to assess cognitive function before and one year after HSCT in twenty-eight patients with hematologic malignancies and in ten healthy controls evaluated at similar intervals. Nineteen patients received conditioning treatment with HD chemotherapy alone and nine had both TBI and HD chemotherapy. There was a significant reduction in gray matter volume in the middle frontal gyrus bilaterally and in the left caudate nucleus in the patient group (all patients combined) but not among healthy controls over the one-year follow-up period. There was a significant increase in left lateral ventricle volume and in total ventricle volume in the patient group, relative to healthy controls. Similar brain structural changes were seen for patients treated with HD chemotherapy alone. The neuropsychological results showed that 21% of patients could be classified as impaired at baseline. The Reliable Change Index suggested no significantly different rates of cognitive decline between patients and healthy controls. The findings suggest that HSCT patients may be at an increased risk for developing regional brain volume loss, and that subgroups may experience cognitive dysfunction prior to and one year following the transplant.

Brain damage following prophylactic cranial irradiation in lung cancer survivors

“…Chemotherapy has previously been associated with cognitive and structural brain changes in many cancer survivors and could therefore appear to be a contributing factor to the identified deficits in this study (Simo et al 2013). However, most of the previous chemotherapy-related studies performed in long-term breast cancer survivors found subtle cognitive deficits and structural brain changes predominantly in frontal regions (Correa et al 2013;Deprez et al 2011;Inagaki et al 2007;McDonald et al 2013). Indeed, our research group also conducted a neuropsychological and neuroimaging study on SCLC patients following a platinum-based chemotherapy prior to PCI.…”

Structural connectivity abnormality in children with acute mild traumatic brain injury using graph theoretical analysis

“…Our analysis demonstrated evidence of abnormalities in nodal degree, nodal clustering coefficient, or nodal betweeness centrality in certain hubs including superior frontal gyrus, middle frontal gyrus, superior parietal gyrus, precuneus, supplementary motor area, and calcarine. Some of these hub areas have been reported to be associated with TBI outcomes based on structural or functional neuroimaging findings [Correa et al, 2013; Kohl et al, 2009; Leunissen et al, 2013; Lipszyc et al, 2014; Max et al, 2006; Sanchez-Carrion et al, 2008; Scheibel et al, 2007; Tuner and Levine, 2008; Wilde et al, 2012]. For example, the superior parietal gyrus was found to have significant changes in cortical thickness [Wilde et al, 2012] and functional activation [Kohl et al, 2009] in patients with TBI.…”

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT

“…112 They noted grey matter loss and a concomitant increase in ventricular volume in patients 1-year following HCT, and no corresponding changes in healthy participants in the control group. Despite the noted changes in neuroimaging, statistically significant differences in rates of neurocognitive dysfunction were not found.…”