Progressive Supranuclear Palsy

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PSP is an atypical parkinsonian disorder associated with progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia first described by Steele-Richard-son-Olszewski (35). Frontal lobe syndrome and subcortical dementia are present in some cases. In contrast to PD, gross examination of the brain often has distinctive features. Most cases have varying degrees of frontal atrophy that may involve the precentral gyrus. The midbrain, especially the midbrain tectum, and to a lesser extent the pons, shows atrophy. The third ventricle and aqueduct of Sylvius may be dilated. The substantia nigra shows loss of pigment, whereas the locus ceruleus is often better preserved. The subthalamic nucleus is smaller than expected and may have a gray discoloration. The superior cerebellar peduncle and the hilus of the cere-bellar dentate nucleus are usually atrophic and have a gray color due to myelinated fiber loss (36).

Microscopic findings include neuronal loss, gliosis and NFTs affecting the basal ganglia, diencephalons, and brainstem (Fig. 4). The nuclei most affected are the globus pallidus, subthalamic nucleus, and substantia nigra. The cerebral cortex is relatively spared, but lesions are common in the peri-Rolandic region. Recent studies suggest that cortical pathology may be more widespread in cases of PSP with atypical features, such as dementia (37). The limbic lobe is preserved in PSP.

The striatum and thalamus often have some degree of neuronal loss and gliosis, especially the ventral anterior and lateral thalamic nuclei. The basal nucleus of Meyn-

FIGURE 4 Progressive supranuclear palsy: The basal ganglia have neurofibrillary tangles (NFTs) and threads (A) and tufted astrocytes (B) with tau immunostains. There is severe neuronal loss and gliosis in the subthalamic nucleus (C) and many NFTs and glial lesions in the subthalamic nucleus (D). The substantia nigra has neuronal loss and NFTs in pigmented neurons (arrow) (E). The neurons in the substantia nigra have tau-immunoreactive NFTs (F).

ert usually has mild cell loss. The brainstem regions that are affected include the superior colliculus, periaqueductal gray matter, oculomotor nuclei, locus ceruleus, pontine nuclei, pontine tegmentum, vestibular nuclei, medullary tegmentum, and inferior olives. The cerebellar dentate nucleus is frequently affected and may show grumose degeneration, a type of neuronal degeneration associated with clusters of degenerating presynaptic terminals around dentate neurons (38). The dentatorubrothalamic pathway consistently shows fiber loss. The cerebellar cortex is preserved, but there may be mild Purkinje loss with scattered axonal torpedoes. The spinal cord is often affected, where neuronal inclusions can be found in anterior horn and intermediolateral cells.

Silver stains (e.g., Gallyas stain) or immunostaining for tau reveal NFTs in residual neurons in the basal ganglia, diencephalon, brainstem, and spinal cord. In addition to NFTs, special stains demonstrate argyrophilic, tau-positive inclusions in both astrocytes and oligodendrocytes. Tufted astrocytes are increasingly recognized as a characteristic feature of PSP (39) and are commonly found in the motor cortex and striatum (40) (Fig. 4). They are fibrillary lesions within astrocytes based upon double immunolabeling of tau and glial fibrillary acidic protein. Oligodendroglial lesions appear as argyrophilic and tau-positive perinuclear fibers or "coiled bodies," and they are often accompanied by thread-like processes in the white matter, especially in the diencephalon and cerebellar white matter.

NFTs in PSP are composed of 15-nm straight filaments (41). The abnormal filaments in glial cells in PSP also contain straight filaments. Biochemical studies also show differences between tau in AD and PSP. In AD, the abnormal insoluble tau migrates as three major bands (68, 64, and 60 kDa) on Western blots, whereas in PSP, it migrates as two bands (68 and 64 kDa) (42).

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