Is White Matter Involved in Patients Entered into Typical Trials of Neuroprotection?

Abstract

Background and Purpose— One of the reasons for the failure of trials of neuroprotection in stroke may be the lack of white matter (WM) protection. However, whether patients entered into typical neuroprotection trials have WM involved in the ischemic process is unknown. We studied patients who were enrolled in neuroprotection trials at our center and used a neuroimaging coregistration approach to determine whether final infarcts involved WM and, if so, in what proportion. We also aimed to provide the first in vivo volume distribution of gray matter (GM) and WM in normal stroke-aged brains. Methods— Patients enrolled in trials of neuroprotection had late computed tomography or magnetic resonance scans coregistered in standard stereotaxic coordinate space after segmentation of symptomatic cerebral infarcts. These were then superimposed on a probabilistic map of GM and WM, which was developed from age-matched normal controls in whom GM and WM volumes were assessed. Results— Forty-two patients (mean age, 73.7±10.5 years) were studied from 6 trials of neuroprotection. WM formed 41.7% of the brain volume in 37 control subjects (mean age, 73.5±8.4 years). In the segmented infarcts, WM comprised a median of 49% (interquartile range, 36.5 to 77.9) of the infarct volume. Ninety-five percent of infarcts had some involvement of WM tracts. Conclusions— WM occupies ≈42% by volume of the normal stroke-aged brain. Patients entered into typical trials of neuroprotection may have significant WM volumes involved in the ischemic process, thus providing a rationale for the development of neuroprotectants for this compartment.