Abstract
Cerebral infarction-induced cessation of function in areas of the brain remote from, but connected to, the primary site of damage was termed “diaschisis” by von Monakow.1 Initially, the concept of diaschisis did not include morphological changes. However, accumulating evidence has shown that histopathologic changes also occur in nonischemic remote brain regions that have synaptic connections with the primary lesion site. For example, after cerebral infarction in the middle cerebral artery (MCA) territory, neuronal death, gliosis, and axonal degeneration have been found in the ipsilateral thalamus, substantia nigra (SN), and distal pyramidal tract, all of which lie outside the MCA territory.2–7 This kind of secondary neurodegeneration occurs selectively in such areas several days or weeks after stroke onset, and this can be detected by neuroimaging techniques.8 For quite a long time, the role of secondary degeneration in stroke recovery has not been well understood. Recently, emerging studies suggest that secondary degeneration is associated with neurological deficits and can predict motor outcome after stroke.9–15 In this review, we aimed to summarize the pathological and neuroimaging evidence of secondary neurodegeneration in the ipsilateral thalamus, SN, and pyramidal tract after MCA infarction and described its potential significance for stroke management. We searched PubMed from 1980 to September 2011, using the terms “cerebral infarction,” “middle cerebral artery,” “Wallerian degeneration,” “anterograde degeneration,” “retrograde degeneration,” and “transneuronal degeneration.” Further articles were identified from the references cited in those articles and through searches of our personal files. The final list of references was selected on the basis of originality and relevance to the topics covered in this review. ### Postmortem Studies Data from postmortem studies provide direct evidence of secondary neurodegeneration after focal cerebral infarction (Figure 1). Histopathologic examination at 4 months after MCA infarction revealed a delayed and selective decrease in the …
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