Parkinson disease and hypoxic-ischemic encephalopathy.
PSP-like clinical manifestations of this patient: supranuclear gaze palsy, rigidity and dorsiflexion of the neck, dopa-unresponsive parkinsonism, and subcortical dementia are compatible with its clinical diagnostic criteria (8). Neuropathological examination showed predominantly Lewy body pathology and scattered hypoxic ischemic foci.
Because clinical picture of this patient was compatible with PSP, we screened the entire brain with Gallyas-silver impregnation method (11). Gallyas-positive structures were found in the substanita nigra, subthalamic nucleus, putamen, dentate gyrus and CA4 of hippocampus, cerebral cortex, and Purkinje cells. Because these findings are partly overlapping with those observed with neurofibrillary tangles in PSP (4), our initial histological diagnosis included PSP, in addition to Lewy body disease and hypoxic-ischemic encephalopathy, which shared among several leading neuropathologist in this area. Because this diagnosis of PSP was based on the assumption that these Gallyas-positive structures are NFTs of PSP (Figure 13), one may ask whether these Gallyas-positive structures are NFTs of PSP? On further examination, however, these Gallyas-positive structures were found to be 1) negative for AT8, 2) granular in cytoplasm without fibrillary structure, 3) abundant around ischemic foci. These features are different from NFTs but rather compatible with those recently reported in ischemic lesions (5). Moreover, typical tuft-shaped astrocytes were absent. We, therefore, declined our initial histological diagnosis of PSP. Because trivial ischemic lesions are one of the most frequent findings in human autopsy brains, it is worth paying attention to possible induction of Gallyas-postive structures around ischemic foci for correct interpretation. Cytopathological differentiation from NFTs is possible based on the absence of AT8 immunoreactivity and fibrillary structures.
One may wonder how PSP-like features were dominant in this patient with Lewy pathology even without authentic PSP lesions. It has been reported that Lewy body pathology is possibly related to clinical features mimicking PSP (1-3, 9) even without concomitant lesions characteristic of PSP. Copresence of PSP lesions (6) or argyrophilic grains (10) may feature clinical manifestations. Anyway, it remains still unanswered how Lewy pathology leads to PSP-like manifestations.
Contributed by Naoki Kasahata, MD; Toshiki Uchihara, MD, PhD; Ayako Nakamura; Yoshio Miyazawa, MD; Tetsumasa Kamei, MD