Relationship between lobar intracerebral hemorrhage and leukoencephalopathy associated with cerebral amyloid angiopathy: clinicopathological study of 64 Japanese patients

Cerebral amyloid angiopathy (CAA) has two major clinical manifestations: intracerebral hemorrhages and ischemic lesions. Among these, the lobar type of intracerebral hemorrhage (ICH) is a well-known clinical manifestation, while the CAA-related diffuse deep white matter degeneration known as leukoencephalopathy is thought to be rare. The characteristics of CAA-related leukoencephalopathy are still incompletely understood, and the relationship between lobar ICH and leukoencephalopathy in patients with CAA has not been properly clarified. The main purpose of this study is to elucidate the clinical and histopathological features of CAA-related lobar ICH and leukoencephalopathy in order to determine whether the degree of deep white matter degeneration parallels the severity of CAA-associated vasculopathies that lead to vascular wall rupture. We studied 64 Japanese patients with histopathologically proven amyloid beta protein (Abeta) type CAA presenting with lobar ICH (52 biopsy and 12 autopsy). In this study, a total of 106 hematomas were observed. CAA-related cerebral hemorrhages tend to occur recurrently and multifocally. Multiple simultaneous lobar hemorrhages occasionally developed (9.4%). CAA -related ICH in the sixth decade was not rare (14.1%). Although most patients suffered relapsing and/or multiple severe ICH, no patient in our series presented with diffuse leukoencephalopathy. In conclusion, Abeta type cerebrovascular amyloid deposition causes recurrent, multifocal, and often multiple simultaneous ICH even in relatively younger elderly patients, but rarely produces diffuse leukoencephalopathy. This suggests that CAA-associated vasculopathies that cause vascular wall rupture do not always lead to ischemic deep white matter degeneration, and that there may be another unknown pathogenetic mechanism producing the latter CAA-related white matter lesion.