Essential tremor followed by progressive supranuclear palsy: postmortem reports of 11 patients

Abstract

For many years, clinicians have commented on the development of signs of parkinsonism among their essential tremor (ET) patients, but the links between ET and parkinsonism are not well understood. We report 11 (12.4%) of 89 ET patients who were prospectively collected at the Essential Tremor Centralized Brain Repository during the course of its first 9 years. All patients had long-standing ET (median duration, 38 years); there was a 5- to 49-year latency from the onset of ET to the development of either parkinsonism or dementia.Despite the presence of parkinsonism or dementia during life, none had been diagnosed clinically with progressive supranuclear palsy(PSP). All 11 received the postmortem diagnosis of PSP. The prevalence of PSP in this ET sample (12.4%) is clearly larger than the population prevalence of PSP (0.001%-0.0065%). It is also 2 to 5 times the proportion of normal cases with incidental PSP in 2 previous autopsy series. This case series raises the questions of an association between ET and PSP, whether ET patients are at an increased risk of developing PSP, and what the proportion of ET patients who develop presumed Parkinson disease or Alzheimer disease in life actually have PSP (i.e. ET + PSP).

Figure 1

Archimedes spirals drawn with the right hand in cases 2 (A), 6 (B), 7 (C), and 8 (D). There is moderate or greater tremor (rating ≥2) in each case.

Figure 2

Immunostaining for hyperphosphorylated tau (AT8) in case 1. (A) There are 3 neurofibrillary tangles ([NFTs], arrows) in the ventral arm of the dentate nucleus. (B) There are 4 NFTs (arrows) and normal pigmented neurons in the caudal substantia nigra pars compacta. (C) This is a glial cytoplasmic inclusion (open arrow) in the anterior limb of internal capsule (630x). Magnifications: A, B, 200x; C, 630x.

Figure 3

Immunostaining for hyperphosphorylated tau (AT8) in case 3. (A) There are 2 neurofibrillary tangles ([NFTs], arrows) and a glial cytoplasmic inclusion (GCI) (open arrow) in the subthalamic nucleus. (B) There are 2 NFTs (arrows) and scattered neuropil threads in the dorsal arm of the inferior olivary nucleus. (C) There are 3 NFTs (arrows) in the pontine nuclei. (D) There is an NFT (arrow) and a tufted astrocyte (arrowhead) in the red nucleus. (E) There is an NFT (arrows), a tufted astrocyte (arrowhead), and a GCI (open arrow) in the superior parietal lobe. Magnifications: A, D, E, 400x; B, C, 200x.

Figure 4

Immunostaining for hyperphosphorylated tau (AT8) in case 5. (A) There is a neurofibrillary tangle ([NFT], arrow) in the pontine nuclei. (B) There is a tufted astrocyte (arrowhead) in the motor cortex. (C) There is a glial cytoplasmic inclusion (open arrow) in the subthalamic nucleus. (D) There is an NFT with labeled processes (arrow) in the internal segment of the globus pallidus. Magnifications: A, C, D, 400x; B, 630x.

Figure 5

Immunostaining for hyperphosphorylated tau (AT8) in case 8. (A) There are 2 tufted astrocytes (arrowheads) and a glial cytoplasmic inclusion (GCI) (open arrow) in the prefrontal cortex. (B) There are 5 tufted astrocytes (arrowheads), a neurofibrillary tangle ([NFT], arrow) and a GCI (open arrow) in the precuneus. (C) A tufted astrocyte (arrowhead) in the motor cortex. (D) A tufted astrocyte (arrowhead) and an NFT (arrow) in the head of the caudate nucleus. Magnifications: A, B, D, 200x; C, 630x.