Spectrum Of White Matter Changes In Ischemic Lesions

Morphological studies on cerebral ischemia concentrate mainly on the grey matter and white matter changes are regarded as secondary or overlapping injuries. Immunohistochemical (IHC) studies to highlight the combination of various cellular changes in ischemic white matter but have not well documented. We selected 11 archival cases of 3 different ischemic processes (i.e. large vessel occlusion, small vessel occlusion, and hypoperfusion) with survival period range 2-35 days from the ischemic event. The white matter was examined using HE-LFB histochemistry, APP, GFAP, and HLA-DR immunostains focusing on myelin, axonal, astrocytic and microglial changes respectively. The various white matter changes are probably reflective of the different mechanism, duration, severity and extent of ischemia. The APP-IHC shows patchy axonal expression, swelling, and finally complete axonal loss. HLADR-IHC highlights early microglial injuries (fragmentation of processes), complete cell loss, and subsequent replacement by cells of macrophage phenotype. Surrounding the ischemic areas are reactive microglia. Astrocytic changes range from fragmentation of processes (clasmatodendrosis) to different stages of cell loss. Astrocytic swelling tends to occur with cerebral edema. Large vessel occlusion results in complete tissue loss while in small vessel disease the damage is more selective. The injury is generally more subtle in hypoperfusion but can be pronounced focally. Our study has documented the spectrum of white matter injury in different scenarios of cerebral ischemia.