Neuropathologic correlates of white matter hyperintensities

Area of Science:

• Neuropathology
• Neuroimaging
• Vascular Neurology

Background:

• White matter hyperintensities (WMH) are frequently observed in elderly individuals on neuroimaging.
• The precise histopathologic basis of WMH remains incompletely understood.
• Previous studies have not definitively linked specific pathological features to WMH severity.

Purpose of the Study:

• To determine the histopathologic correlates of white matter hyperintensities (WMH) in elderly individuals.
• To investigate the relationship between in vivo WMH severity and underlying white matter pathology.
• To compare the histopathology of lesioned WMH areas with non-lesioned white matter.

Main Methods:

• Two studies were conducted on postmortem human brains.
• Study 1 correlated in vivo WMH severity (Scheltens scale) with regional white matter pathology using histologic and immunohistochemical stains.
• Study 2 directly compared the histology of WMH lesions with normal white matter identified by postmortem MRI.

Main Results:

• No single histopathologic variable fully explained WMH severity.
• Reduced vascular integrity was significantly associated with increased WMH severity (beta = -0.53, p = 0.01).
• Both vascular integrity and blood-brain barrier integrity were significantly reduced in WMH compared to normal white matter.

Conclusions:

• White matter hyperintensities (WMH) are characterized by a loss of vascular integrity.
• The findings confirm the vascular origin of WMH.
• Impaired vascular and blood-brain barrier integrity are key mechanisms in the evolution of WMH.