Progressive Supranuclear Palsy (Steele-Richardson-Olszewski syndrome)


What is PSP (SRO syndrome)?

First described by Steel, Richardson, and Olszewski (1964)

Supranuclear refers to being located above the level of the motor neurons of the spinal or cranial nerves. The term is used to indicate disorders of movement caused by destruction or functional impairment of brain structures such as the motor cortex, pyramidal tract, or corpus striatum.

PSP is a progressive disorder with onset typically being after the age of 40 years, consisting of an akinetic-rigid syndrome and a supranuclear gaze palsy associated variably with dysarthria, dysphagia, axial rigidity, and evidence of pyramidal tract dysfunction (Walton, 1993)

Anatomical and Functional Review of PSP


Progressive Supranuclear Palsy is most commonly described as the degeneration of several areas of the basal ganglia, cerebellum, and brain stem. Not only is there degeneration in each of the following areas, but PSP is also characterized by irregular accumulations of tau protein causing neurofibrillary tangles within the: pallidum, subthalamic nucleus, red nucleus, oculomotor nucleus, dentate nucleus, medulla, ventral tegmentum and neostriatum (caudate and especially putamen) (Looi et al. 2011).
Subcortical atrophy in PSP affects the midbrain (particularly the ventral tegmentum), neostriatum, mamillary bodies and the superior cerebellar peduncle, with the neostriatum and midbrain involved in frontostriatal circuits. Hence, there is evidence that frontostriatal pathways may be disrupted by PSP. (Looi et al. 2011)
Neurofibrillary tau protein tangles are especially prominent in the primary motor cortex, which affects the ability to initiate voluntary movements. In addition to tau protein tangles, there is also an increase in glial tangle pathology in tufted astrocytes, thorn-shaped astrocytes, coiled bodies, and interfascicular threads.Screen shot 2013-11-22 at 4.22.05 PM.png

In addition degeneration and tangles within specific brain structures, neurochemically, there is evidence of damage to the nigrostriatal dopaminergic pathway and striatal cholinergic interneurons.

PSP exhibits remarkable neurological and clinical heterogeneity (the quality of being diverse and not comparable in kind) however crosses often with Alzheimer's disease (AD), Parkinson's disease (PD), and Corticobasal Degeneration (CBD). Lewy bodies, another type of protein aggregation typical of Parkinson's disease, in the brain stem and cortex have been noted in PSP.




Pathways Affected in PSP


FrontalMotorPathways.jpg
The corticospinal tract conducts impulses from the brain to the spinal cord, controlling primarily conscious movements of distal musculature (lateral tract) and of axial and girdle muscles (anterior tract). It contains primarily axons originating from the motor cortex. The corticospinal tract is concerned specifically with discrete voluntary skilled movements, such as precise movement of the fingers and toes. The lateral tract decussates in the medulla, where the anterior tract bifurcates at the medulla. In one particular study using diffusion tensor imaging to assess white matter tract degeneration, compared with controls, abnormal diffusivity was observed predominantly in the superior cerebellar peduncles, body of the corpus callosum, inferior longitudinal fasciculus, and superior longitudinal fasciculus in patients with PSP (Whitwell et al., 2011).

The corticobulbar tract consists of the upper motor neurons of the cranial nerves. The muscles of the face, head and neck are controlled by the corticobulbar system, terminating on motor neurons within brainstem motor nuclei. This contrasts the corticospinal tract, where the cerebral cortex connects to spinal motor neurons, and thereby controls movement of the torso, upper and lower limbs. Because these nerves control the muscles of the face and neck, they are involved in facial expression, mastication, swallowing, and other functions.


Clinical Symptoms


The first and most prominent symptom that becomes apparent in PSP is balance issues, followed by inability to perform voluntary vertical saccades (primarily downward). The balance issues include gait disturbances and backwards falls.


Once seen by a physician, a major determinant of PSP would be any sign of Supranuclear Opthalmoplegia, which is when the brain is sending
faulty information to cranial nerves involved in eye movement. Square wave jerks are commonly seen, which are inappropriate saccades that take the eye off target and are followed by another saccade to attempt to bring the focus back to target. These issues may be due to degenerative changes to the superior colliculus. Experimental studies in monkeys have demonstrated that injection of gamma-aminobutyric acid (GABA) agonists into the superior colliculus restricts saccadic eye movements, while injection of GABA antagonists leads to square-wave jerks (Traccis et al., 1997). This study allows us to understand that degeneration of the superior colliculus may lead to the inability to process GABA (simulated by the GABA antagonist in the above study) and therefore cause these square wave jerks.

Note that in the video to the right, the patient has little trouble making horizontal saccades. However, when asked to look up or down, the process is very slow and involves partial horizontal saccades in order to make the vertical saccade. If you look closely, there appear to be square wave jerks occuring during vertical saccade attempts.

Another common set of symptoms of PSP involves pseudobulbar palsy, which is the result of damage of motor fibers traveling from the cerebral cortex to the lower brain stem. Damage to the corticobulbar tract, as mentioned above, can lead to problems in chewing and swallowing. Trouble swallowing (in conjunction with the other symptoms mentioned) is an early sign that PSP may be developing.

Summary


Progressive Supranuclear Palsy is a degenerative disease that develops in adults typically over the age of 40. It currently does not have a cure and there are very little treatments for the symptoms of the disease. Consisting of degeneration and tangling of neurons in several brain structures including the basal ganglia, brain stem and cerebellum as well as atrophy of the nigrostriatal dopaminergic system, the disease manifests primarily as the inability to initiate muscle movements as well as maintain proper posture and gait. Common symptoms of PSP, due to the previously mentioned atrophy and tangling, include gait disturbances and falling backwards, inability to make downward vertical saccades, and inability to control facial muscles or swallow. Although easily confused with Parkinson's disease or Corticobasal degeneration, PSP maintains a very distinct set of characteristics and symptoms that make it difficult to confuse with other diseases once progressed. With the life expectancy being only 8 years after onset of symptoms, PSP is a debilitating and terminal disease.

Glossary


atrophy:
(of body tissue or an organ) to waste away, typically due to the degeneration of cells, or become vestigial during evolution

dysarthria:
difficult or unclear articulation of speech that is otherwise linguistically normal

dysphagia:
difficulty or discomfort in swallowing, as a symptom of disease

axial rigidity:
rigidity of the neck and trunk

pyramidal tract dysfunction:
The pyramidal tracts refers to both the corticospinal and corticobulbar tracts

saccade:
a rapid movement of the eye between fixation points

Quiz


1. True or False; PSP involves neurofibrillary tangles, but no degeneration.

2. True or False; A common characteristic of PSP gait disturbance involves falling forward.

3. True or False; Supranuclear gaze palsy causes patients with PSP to have difficulty making vertical saccades.

4. True or False; The tau protein tangles are especially prominent in the primary motor cortex.

5. True or False; Pseudobulbar palsy creates the inability to use one's hands for fine motor movements.

6. List the three diseases that, in the early stages, PSP may be misdiagnosed as because of their similar features.

7. How are the superior colliculi affected by PSP and what major symptom does this lead to and why?

8. Which neurochemical pathway is affected in PSP?

9. What are the differences between the corticospinal and corticobulbar tracts? How are the affected by PSP and what it the result?

10. What type of chemical was injected into the superior colliculi of monkeys that caused square wave jerks? Why did this cause square wave jerks?

Further Reading


CurePSP (2012). Foundation for PSP, CBD and related brain diseases. http://www.psp.org.
  • This is the national website for PSP and other related brain diseases. It discusses what PSP is, current research taking place on PSP, and discusses and compares PSP to other brain diseases and what we can do as a nation to help find a cure.

National Institute of Neurological Disorders and Stroke (2011). Progressive Supranuclear Palsy fact sheet. Retrieved from: http://www.ninds.nih.gov/disorders/psp/detail_psp.htm
  • This is a "fact sheet" for PSP, listing statistics, causes, symptoms, and prognosis information about Progressive Supranuclear Palsy

References

Looi, J.C.L., Macfarlane, M.D., Walterfang, M., Styner, M., Velakoulis, D., Latt, J., Van Westen, D., & Nilsson, C. (2011). Morphometric analysis of subcortical structures in Progressive Supranuclear Palsy: in vivo evidence of neostriatal and mesencephalic atrophy. Psychiatry Res., 2, 163-175.

Kent, A. (2013). Progressive supranuclear palsy. Nursing Standard, (27) 51, 48-57.

Traccis, S., Marras, M.A., Puliga, M.V., Ruiu, M.C., Masala, P.G., Carboni, A., Aiello, I., Pugliatti, M., & Rosati, G. (1997). Square-wave jerks and square-wave oscillations: Treatment with valproic acid. Clinica Neurologica, (18) 2, 51-58.

Walton, J. (Ed.). (1993). Brain's diseases of the nervous system. Oxford, UK: Oxford University Press.

Watts, R.L. & Koller, W.C. (1997). Movement disorders: Neurologic principles and practice. New York, NY: McGraw-Hill Health Professions Division.

Whitwell, J.L., Master, A.V., Avula, R., Kantarci, K., Eggers, S.D., Edmonson, H.A., Jack Jr., C.R., & Josephs, K.A. (2011). Clinical correlates of white matter tract degeneration in Progressive Supranuclear Palsy. JAMA Neurology. Retrieved from: http://archneur.jamanetwork.com/article.aspx?articleid=803290