Contributed by Naoki Kasahata, MD1,2,3; Toshiki Uchihara, MD, PhD3; Ayako Nakamura3, Yoshio Miyazawa, MD 4; Tetsumasa Kamei, MD1
1 Department of Neurology, Chigasaki Tokushukai General Hospital
2 Division of Neurology, Department of Internal Medicine, Tokyo Metropolitan Ohtsuka Hospital
3 Department of Neurology, Tokyo Metropolitan Institute of Neuroscience
4 Department of Pathology, Chigasaki Tokushukai General Hospital
A 71-year-old female had been well until approximately 2 years before admission, when a neurologist noted muscle rigidity, decreased arm swing while walking, mask-like face, pill rolling tremor and some difficulty in writing. Levodopa/carbidopa (up to 200mg/day) was not effective and was withheld because of exacerbation of tingling sensation of the lower extremities. Four months before admission, she complained of visual hallucinations of children or objects. Endoscopic examination identified a gastric ulcer as a cause of melena and anemia, which lead her to this admission.
General physical examination showed anemia and inspiratory stridor. Neurological findings suggestive of progressive supranuclear palsy (PSP) were as follows: 1) (subcortical) dementia (she showed forgetfulness, slow thinking, apathy, and depression, on the other hand, apparent aphasia, apraxia, or agnosia were absent), 2) supranuclear gaze palsy, 3) pseudobulbar palsy, 4) dorsiflexion of neck, rigidity of neck, absence of tremor and no cog-wheel rigidity of extremities, and 5) postural reflex disturbance.
Laboratory examination showed BUN 32.9 mg/dl and Hb 10.7 mg/dl, but was otherwise unremarkable. During this admission levodopa/carbidopa up to 400mg/day was tried without clinical improvement. Sudden cardiopulmonary arrest on the 24th hospital day was followed by repeated respiratory tract infections until she died on the 58th hospital day. The final clinical diagnosis was 1) dopa-unresponsive parkinsonism compatible with PSP, 2) hypoxic-ischemic encephalopathy, 3) pneumonia, and 4) gastric ulcer.
An MRI showed no apparent atrophy of the midbrain tegmentum (Figure 1) but small T2 and FLAIR high intensities were present (Figure 2). GROSS AND MICROSCOPIC PATHOLOGY
The autopsy was performed about four hours after death and showed aspiration pneumonia with organization, gastric ulcer (scar), gastrointestinal tract hemorrhage, atrophy of organs, and malnutrition.
Brain weight was 985g. Cortical atrophy was mild in frontal and parietal lobes and moderate in temporal tips. Cerebral cortices became thin and brown especially from the central region to occipital lobes (Figure 3). Cerebral white matter showed swelling and discoloration (Figure 3). Dentate nucleus showed mild discoloration (Figure 4). The substantia nigra were thin and depigmented (Figure 5). The locus ceruleus was depigmented (Figure 5).
Ischemic changes, such as loss of neurons, sponginess, marked gemistocytic astrocytosis with some ischemic neurons, were scattered through the entire cerebral cortices, putamen, globus pallidus externa, substantia nigra, pontine nuclei, and cerebellum. The dentate nucleus showed spongy changes and neuronal loss. Loss of pigmented neurons of the substantia nigra was accentuated in the ventrolateral tier. Lewy bodies were detected in the substantia nigra (Figure 6), the oculomotor nucleus, the loci cerulei, and the dorsal motor nucleus of the Vagus (Figure 7) but were not apparent in cerebral cortices or in the amygdala. Plaque pathology was Braak A and tangle pathology was Braak III. There was also axonal depletion in epicardial nerve fascicles of left ventricle as shown by SMI-31 immunostains (Figure 8) and this was more easily appreciated with immunostains for tyrosine hydroxylase (TH)-positive axons (Figure 9). These sometimes contained alpha-synuclein deposits (Figure 10).
Gallyas-silver impregnation demonstrated argyrophilic structures around hypoxic ischemic foci (Figure 11: Gallyas positive structures are abundant in the putamen, Figure 12: same part as C. Neuronal loss, sponginess, and gemistocytic astrocytosis in the putamen, hematoxylin and eosin). These Gallyas-positive structures were granular in appearance and never exhibited fibrillary structures like NFTs (Figure 13, higher magnification of Figure 11. Gallyas-Braak). They were not stained with AT8 (Figure 14 Same section as Figure 13, AT8), isoform-specific antibodies (RD3, RD4), Bodian and Campbell-Switzer staining. They were abundant in the putamen (Figure 11) and dentate gyrus of hippocampus, frequent in cerebral cortices and Purkinje cells, but infrequently in substantia nigra and subthalamic nucleus. Typical tuft shaped astrocytes were absent throughout the brain.