Progressive Supranuclear Palsy


Overview or introductory paragraph

Progressive Supranuclear Palsy (PSP), also known as Steele-Richardson-Olzsewski syndrome (SRO), is a neurodegenerative brain disorder that affects cognition, vision, and movement. The disease usually develops during a person’s sixth decade of life and most patients only survive for five to nine years after onset. Characteristics include axial rigidity, vertical gaze palsy, dysarthria, and dysphagia. There is also a behavioral shift in patients, with many of them becoming apathetic.







Functional anatomical review (including structure(s), location…)


Neurofibrillary tangles
Neurofibrillary tangles

One of the underlying disruptions of PSP is tau maintenance. Tau is important in maintaining neuronal morphology through microtubule binding and is usually soluble. Tau is a naturally occurring protein in the brain that is usually regulated and disposed of before reaching higher levels. PSP forms as a result of neurons in certain areas of the brain becoming damaged due to the buildup of this protein, which is referred to as neurofibrillary tangles. Tau is present in all neurons, and it plays important roles in the structure and function (metabolism) of normal neuron function. Because of the accumulation of tau, PSP is said to be a tauopathy (Eggenberger).
Those with PSP show neuronal loss and neurofibrillary tangles in the basal ganglia (epsecially in the globus pallidus), diencephalon, and brainstem. Along with damage to the basal ganglia, there is also damage done to the subthalamic nuclei and the dentate nucleus of the cerebellum. The midbrain - the portion of the brain responsible for balance and coordinating eye movements – is also said to be damaged and atrophied (Hain).






Hummingbird sign shows up in the mid-sagital view of the brain in an MRI and is typical for patients with PSP. This sign is caused by atrophy of the midbrain tegmentum and a relative increase in the length of the interpeduncular fossa over the anteroposterior diameter of the midbrain tegmentum (Poh):


Hummingbird atrophy (left), normal (right)
Hummingbird atrophy (left), normal (right)



Mickey mouse sign is referring to the axial MRI view of the brainstem, showing a selective atrophy of the midbrain tegmentum, with relative sparing of the midbrain tectum and cerebral peduncles, hence giving you the Mickey Mouse symbol (Poh):


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Mickey Mouse atrophy (left), normal (right)
Mickey Mouse atrophy (left), normal (right)

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Input & Output pathways (e.g., neuronal connections)

external image bg_circuits.jpg
In the brain there is a tract called the dentatorubrothalamic tract. It connects the dentate nucleus to the thalamus while sending collaterals to the red nucleus. In a study to assess if functional neural connectivity is disrupted along the dentatorubrothalamic tract and in the premotor cortex, there were some interesting implications. The study found that there was a reduction in functional connectivity between the thalamus and gray matter regions (notably the premotor cortex and prefrontal cortex). There was also white matter loss observed in the cerebellum and the brainstem and both gray and white matter loss in premotor cortex extending into prefrontal cortex and striatum. The premotor cortex is intricately connected with the prefrontal cortex and accounts for reasoning and executive function (Whitwell et al).

With white matter, and therefore integrity, loss in the cerebellum there will be far-reaching consequences in someone affected with PSP. Depending on where the white matter loss takes place, the patient can expect to experience loss in motor control, motor learning, and cognitive functions such as attention, language, and regulating fear and pleasure responses. Along with the loss of intregrity to the white matter of the cerebellum, the matter degeneration of the other brain structures will further cause loss of motor control and cognition (Wolf et al).

There was also motor control dysfunction due to disruption of basal ganglia influence on motor control via projections to thalamus. Atrophy, neuronal lass, gliosis, and the build-up of tau affect thalamocortical motor pathways in those with PSP. There was also degeneration of superior longitudinal fasciculus which projects between the frontal and parietal lobes, thereby affecting the long-range fibers that connect the two segments. There were also correlations between the functional connectivity of the supplementary motor cortex and deficits in motor and cognition tests. This further suggests that PSP's disruptions of thalamocortical connections is contributing to motor control deficits (Whitwell et al).

Summary or concluding paragraph:



With Progressive Supranuclear Palsy there is currently no cure and will get worse over time for those who have it. The course of the disease runs from five to nine years on average from onset to death. Quality of life will be deteriorate along with the progression of the PSP. Dysphagia and the risk from falls will also present some difficulty. There are some medicinal options available such as Epithilone D: a chemotherapy drug that would be given at small dosages that can potentially untangle tau clumps. non-medicinal treaments can include walking aids (canes, walkers, etc.), physical therapy (to alleviate symptoms somewhat), and bifocals or prisms (aid with sight).

One symptom for the disease include a loss of balance with a tendency to fall backwards. Another is an inability to aim the eyes properly with particular difficulty in gazing downward, or vertical gaze palsy. PSP has Parkinsonian and dementia-like symptoms that can make differentiation difficult upon first glance. These symptoms include: stiffness and awkward movements, rigid facial muscles, depression and anxiety, loss of vitality, and impuslive behavior. Difficulties with memory, decision-making, problem-solving, and reasoning are also present.



Glossary:

Atrophy - decrease in size of a normally developed organ or tissue

Gliosis - reactive change of the glial cells in response to damage to the central nervous system

Dysphagia - difficulty swallowing; results from impaired movement of the muscles used for swallowing

Dysarthia - motor speech disorder; results from impaired movement of the muscles used for speech production

Axial rigidity - inflexibility of neck and trunk


Quiz:


1. T/F: Tau maintenance is not an underlying cause for PSP.
2. T/F: PSP does not share similarities with Parkinson's disease.
3. T/F: There is currently no cure for PSP.
4. T/F: PSP causes neuronal loss in the basal ganglia.
5. T/F: The brainstem suffers damage in those with PSP.
6. What is tau and how does it affect the onset of PSP?
7. What sort of atrophy arises in the brain?
8. What are some of the symptoms of PSP?
9. What neuronal pathways are affected and what are the implications of such pathways being damaged?

Further Reading:



Tangled Up In Tau: http://protomag.com/articles/tangled-up-in-tau
Trouble with the protein may underlie most kinds of dementia, potentially including Alzheimer's. New drugs could help.

Progressive Supranuclear Palsy: http://www.mayoclinic.org/diseases-conditions/progressive-supranuclear-palsy/basics/definition/con-20029502
This website details the various symptoms, treatments, prognoses, etc. of PSP

CurePSP: http://www.psp.org/
This is the national website for Progressive Supranuclear Palsy


References:



Eggenberger, E. R. (2015, November 19). Progressive Supranuclear Palsy: Practice Essentials, Background, Pathophysiology. Retrieved from http://emedicine.medscape.com/article/1151430-overview

Hain, T. C. (2015, August 30). Progressive Supranuclear Palsy (PSP). Retrieved from http://www.dizziness-and-balance.com/disorders/central/movement/psp.htm

Poh, T. (2013, January 2). Hummingbird sign and Mickey Mouse sign. Retrieved from http://teddybrain.wordpress.com/2013/01/02/hummingbird-sign-and-mickey-mouse-sign/

Progressive Supranuclear Palsy | Association for Frontotemporal Degeneration. (n.d.). Retrieved from http://www.theaftd.org/understandingftd/disorders/psp

Whitwell JL, Master AV, Avula R, et al. Clinical Correlates of White Matter Tract Degeneration in Progressive Supranuclear Palsy. Arch Neurol.2011;68(6):753-760. doi:10.1001/archneurol.2011.107.

Whitwell, J. L., Avula, R., Master, A., Vemuri, P., Senjem, M. L., Jones, D. T., ... Josephs, K. A. (2011). Disrupted thalamocortical connectivity in PSP: A resting-state fMRI, DTI, and VBM study. Parkinsonism and Related Disorders,17(8), 599-605. 10.1016/j.parkreldis.2011.05.013

Wolf, U., Rapoport, M. J., & Schweizer, T. A. (2009). Evaluating the Affective Component of the Cerebellar Cognitive Affective Syndrome. The Journal of Neuropsychiatry & Clinical Neursciences, 21(3), 245-253. Retrieved from http://neuro.psychiatryonline.org/doi/abs/10.1176/jnp.2009.21.3.245