Brain Pathology Case of the Month - July 2000


FINAL DIAGNOSIS:

PROGRESSIVE SUPRANUCLEAR PALSY, TYPICAL.

DISCUSSION:

Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski syndrome, is characterized by postural instability and falls, symmetric bradykinesia and axial rigidity, pseudobulbar palsy, and ophthalmoplegia (1). Dementia is observed in some cases. Autonomic dysfunction in the form of hypertension has also been reported (2). The extrapyramidal symptoms are typically unresponsive to levodopa. The presentation of PSP can be atypical, which often confuses clinical diagnosis (3). Pathologically, PSP is characterized by the abnormal accumulation of tau protein in neurons and, less commonly, in astrocytes. Tau containing globose neurofibrillary tangles are frequently seen, accompanied by neuronal loss and gliosis. The pathologic diagnosis is established based upon semiquantative assessment of the density and location of tangles (4,5). In typical cases, the pallidum, subthalamic nucleus, substantia nigra, and pontine tegmentum have the highest density of tangles, followed by the oculomotor nucleus, pontine nuclei, striatum, medulla and dentate nucleus. Tangles are occasionally seen in the cortex and hippocampus (4,5). In atypical cases, the density of tangles is lower than typical cases, with most of the neurofibrillary tangles detected in the brain stem and basal ganglia. Although the cortex in PSP may have neurofibrillary tangles, the morphology and molecular phenotype of the abnormal tau in the cortex is to be different from that found in the brain stem (6). Several other neurodegenerative diseases including corticobasal degeneration, Pick's disease and multiple system atrophy must be differentiated pathologically from PSP. Corticobasal degeneration is characterized by a large number of ballooned neurons in the cortex (7). In Pick's disease, Pick's bodies are typically found in the cortex with the brain stem spared(8). Glial inclusion bodies are found in multiple system atrophy but not in PSP (9).

REFERENCES:

  1. Litvan I, Mangone CA, McKee A et al. Natural history of progressive supranuclear aplsy (Steele-Richardson-Olszewski syndrome) and clinical predicators of survival: a clinicopathological study. J Neurol Neurosurg Psych 1996; 60:615-620.
  2. Ghika J, Bogousslavsky J. Presymptomatic hypertension is a major feature in the diagnosis of progressive supranuclear palsy. Archives of Neurol 1997; 54:1104-1108.
  3. Collins SJ, Ahlskog JE, Parisi JE, Maraganore DM. Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria. J Neurol Neurosurg Psych 1995; 58:167-173.
  4. Litvan I, Hauw JJ, Bartko JJ et al. Validity and reliability of the preliminary NINDS Neuropathologic criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol 1996; 55:97-105.
  5. Hauw JJ, Daniel SE, Dickson D et al. Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy) Neurol 1994; 44:2015-2019.
  6. Schmidt ML. Huang R. Martin JA. et al. Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer's disease PHFtau. Neuropathol Exp Neurol 1996; 55:534-9
  7. Bergeron C. Davis A. Lang AE. Corticobasal ganglionic degeneration and progressive supranuclear palsy presenting with cognitive decline. Brain Pathol 1998; 8:355-65.
  8. Feany MB. Mattiace LA. Dickson DW. Neuropathologic overlap of progressive supranuclear palsy, Pick's disease and corticobasal degeneration. . J Neuropathol Exp Neurol. 1996; 55:53-67.
  9. Nishima M, Namba Y, Ikeda K, et al. Glial fibrillary tangles with straight tubules in the brains of patients with progressive supranuclear palsy. Neurosci Lett 1992; 143:35-38.

Contributed by Kar-Ming Fung, MD, PhD, Mark S Forman, MD, PhD, Brett Cucchiara, MD, Elizabeth ZuLinska MD, Maria Wallis-Crespo, MD, Ehud Lavi, MD




International Society of Neuropathology