What is Progressive Supranuclear Palsy?

Jul 29

Progressive supranuclear palsy (PSP) is a rare brain disorder that creates difficulty with movement, balance, and eye movements. It is the consequence of degeneration in neurons in parts of the brain and brainstem that control movement and cognition. It shares many similar features with Parkinson’s disease, and is considered an atypical Parkinsonian variant. It is a progressive neurodegenerative disorder, with an incompletely understood cause. There is no known cure for PSP. Currently there is no effective medical treatment for PSP, with interventions focused on controlling symptoms.

People struggling with PSP tend to show stiffness and slow movements. They frequently have gait disturbances, and are prone to injuries in falls. As the disease progresses, they can develop difficulty with cognition and memory, and become emotionally unstable. They also have problems generating downward eye movements, leading to double vision and associated balance difficulties. Non motor symptoms are often observed in patients with PSP, with sleep, mood and sexual function commonly affected (1).

How Common is Progressive Supranuclear Palsy?

PSP is relatively rare, with a prevalence of 5 to 10 per 100 000 persons. The average age of onset is 65, affecting males and females equally (6).

What Causes Progressive Supranuclear Palsy?

The exact cause of PSP is yet to be determined. Most research suggests that it involves degeneration in cells in primarily the brainstem, however as it advances other systems become damaged as well. A brainstem region called substantia nigra seems to be involved. This produces dopamine, which is critical for regulating body movement. Failure of this system creates many of the motor symptoms that are seen in both Parkinson’s disease and PSP.

PSP belongs to a class of disorders called tauopathies. Tau is a structural protein in neurons that is constantly being broken down and remodeled. In tauopathies, this breakdown process fails, leading to abnormal buildup of tau within neurons. Ultimately the aggregation of tau impairs other cellular functions, which fail and the neuron dies. As more neurons die off, communication between pathways fail, and symptoms begin to present (3).

PSP is rare, and generally presents without a well-established cause. There appear to be some cases that are based on genetic variations (34). Others may be the result of infections, chemical exposures, or metabolic problems creating oxidative stress and cellular damage (35).

Despite growth in our understanding of tauopathies like PSP, early and accurate clinical prediction of PSP neuropathology remains challenging (2).

What are the Symptoms of Progressive Supranuclear Palsy?

PSP affects gross and fine motor control, regulation of gait and balance, production of speech, swallowing, eye movements and vision, cognition, behavior, and mood. Symptom presentation varies between individuals however the most common initial symptom is a loss of balance while walking. Often the first sign of PSP is an unexpected fall.

As the disease progresses, most people will begin to develop visual disturbances. These can include difficulty opening and closing the eyes, changes in blink frequency, eyes closing spontaneously, slow eye movements, and difficulty looking down. They may find themselves needing to move their head to look in different directions.

PSP usually involves changes in emotional regulation and behavior. They commonly show depression, apathy, cognitive challenges, difficulty with word finding, memory problems, and changes in personality. They may appear emotionally unstable, or have emotional responses that do not fit the situation. They also tend to develop changes in speech, difficulty swallowing, and loss of facial expression (36).

How is Progressive Supranuclear Palsy Different from Parkinson’s Disease?

PSP is often misdiagnosed as Parkinson’s disease, as they present at roughly the same stage of life, and many of the motor symptoms are shared between diseases. PSP can be differentiated from Parkinson’s disease by posture. Parkinson’s patients tend to be stooped forward, whereas PSP patients stand with very straight spines, at times with their necks extended. PSP progresses faster than Parkinson’s disease, and problems with speech and swallowing tend to show up earlier in the process. Tremors are common in Parkinson’s but are rarely seen in PSP. Parkinson’s patients respond well to levodopa medications, whereas PSP patients respond poorly if at all (8).

How is Progressive Supranuclear Palsy Diagnosed?

There are currently no clinical or imaging tests that can definitively diagnose PSP. At present, PSP can only be conclusively diagnosed based on neuropathological examination of the brain at autopsy (8).

PSP is largely a clinical diagnosis, made based on clusters of findings including:

Ocular motor dysfunction: vertical gaze palsy, slow velocity of vertical eye movements, frequent jerks while trying to stabilize gaze, or difficulty with eyelid opening
Postural instability: repeated unprovoked falls; tendency to fall on the clinical pull-test, or more than 2 steps backward on the pull-test.
Akinesia: progressive gait freezing, spinal stiffness and rigidity, and being unresponsive to levodopa
Cognitive dysfunction: speech and language disorder, progressive apraxia of speech, and frontal cognitive/behavioral difficulties (9).

How Does Progressive Supranuclear Palsy Affect the Brain?

PSP is a protein aggregation disorder, similar to Parkinson’s and Alzheimer’s diseases, although the proteins involved in these are different (alpha synuclein and amyloid beta). Compelling evidence suggests that misfolded proteins these disorders can lead to synaptic dysfunction, neuronal death and brain damage (11).

Microscopically, the hallmark of PSP includes buildup of tau with in neurons and supporting cells. Tau pathology affects multiple regions of the brain, including the neostriatum, globus pallidus, substantia nigra, subthalamic nucleus, brainstem nuclei, as well as the motor cortex (8).

Over time, the tauopathy leads to degeneration of systems at a level that becomes visible on imaging studies. MRI studies can show atrophy of the subthalamic nucleus, midbrain and superior cerebellar peduncle with depigmentation of substantia nigra as well as atrophy and discoloration of the cerebellar dentate nucleus (10).

How is Progressive Supranuclear Palsy Usually Treated?

There is currently no cure for those living with PSP (13). However, there are therapies for managing symptoms which include speech therapy, occupational therapy, and physical therapy. There are also options with medication management and Botox injections (14).

How is the NeuroRescue Program Different?

While we cannot cure PSP, we employ a host of advanced therapies and technologies that can help improve the function of your remaining systems. By doing so, we can often help restore some of your mobility, improve your balance and gait, improve your cognition and emotional regulation, and enhance your quality of life.

The best way to conceive of a protein aggregation disorder is to think of a garbage strike. Over time, garbage builds up on your front porch, to the point where cells may still be capable of working, but they can’t get past the huge pile of garbage at the front door. Many neurodegenerative disorders respond well to intermittent fasting. People are confined to an 8-hour feeding window, with no caloric intake for the remaining 16 hours. After several hours without eating, cells run out of energy from blood sugar regulation. Energy can still be made from proteins, so cells start to digest the garbage pile. Eventually, the pile is small enough that the door can open and the cell can go to work. Intermittent fasting has been shown to be helpful in reducing protein aggregation in neurodegenerative disorders (15), and specifically in Parkinsonian conditions (16).

Electrical therapies have been shown to improve brainstem motor function in a number of neurological conditions (12). Transcranial direct current stimulation has been shown to help with cognitive dysfunction (17), as well as to promote language improvement (18) in PSP.

Transcranial magnetic stimulation has been shown to promote improved motor control, as well as enhanced postural control and more fluent speech (19).

Hyperbaric therapy has been shown to reduce destruction of dopamine producing cells in the substantia nigra in Parkinsonian variants (20), as well as help with emotional dysregulation in similar cases (21).

Much of what happens in PSP is related to the inability to properly localize yourself in the environment. Your brain makes sense of where you are in the world through inputs from your muscles and joints, inputs from your inner ear, and inputs from your eyes. The eyes are constantly scanning the world to provide the brain with a visual map of the surrounding space. It does this with saccades, which are fast eye movements from target to target.

In order for you to move through and interact with the world, you first need to know where the world is. This requires that saccades are fast, accurate, stable, and have very quick reaction times. As the basal ganglia are involved in saccades, all of these functions break down with Parkinsonian variants. Saccades become slow, lose accuracy, and are easy to fatigue. Research shows that the breakdown in saccades seen in these disorders leads to postural instability (22), impairs the ability to turn (23), and leads to freezing of gait (24). We find that by rehabilitating saccades in a very precise manner, we can often improve balance, gait, and postural stability.

Another more complicated eye movement is called an anti-saccade, where a target is presented, and a person needs to inhibit the reflex to look at the target and instead consciously choose to look in the other direction. Anti-saccades are involved in a number of executive functions, and these give rise to foundational cognitive processes. Research shows that anti-saccades break down in Parkinsonian variants, leading to problems with planning, reasoning, and emotional regulation (25). We find that by rehabilitating these eye movements we can often restore some of the cognitive flexibility and emotional regulation lost to this disease.

There are a host of other therapies that we engage in with our Parkinsonian variant patients. All of these have different functions and allow us to rehabilitate specific capacities. These range from vestibular rehabilitation to improve balance, gait, and cognition (26), to visual optokinetic stimulation to improve motor control and postural stability (27,28). They include a number of different types of electrical stimulation to improve cognition, eye movements, balance, gait, tremor, cognition, blood pressure regulation, and even swallowing (29,30,31). They include therapies such as transcranial magnetic stimulation to improve motor function, emotional regulation and balance (32), and even virtual reality exercises to improve the ability to function in the world and decrease fall risk (33).

No two progressive supranuclear palsy presentations are alike, and the same holds true for the NeuroRescue program. A cookie-cutter approach will be doomed to fail in a condition as complicated as PSP. All of our therapy protocols are tailored to the unique needs of the individual.

How Does the NeuroRescue Program Work?

We design your unique NeuroRescue Program to be among the most comprehensive diagnostic and therapeutic protocols available today. We create individual NeuroRescue Programs based on a comprehensive analysis of every relevant neurological system and pathway, using gold-standard, cutting edge neurodiagnostic technologies and examination procedures and state-of-the-art therapies.

We begin with your Discovery Day, wherein we perform a comprehensive history of not only your condition, but your life on a timeline. This allows us to dive deeply into your case and see all of the factors that led to where you are now. It helps us uncover hidden problems and associated conditions that may be making it difficult for you to move your recovery forward.

In the case of PSP, this requires a deep dive into the gut microbiome, intestinal wall permeability, mechanisms of oxidative stress and mitochondrial failure, and many other factors that can be provoking your issues.

Our examination allows us to identify the areas and pathways of your brain that have been impacted by your PSP. We begin by precisely quantifying the function of your visual, vestibular, and proprioceptive systems through computerized analysis of your eye movements, your inner ear reflexes, and your balance in a host of different sensory conditions.

We employ technologies including Videooculography and Saccadometry to measure several classes of eye movements. We use Video Head Impulse Testing to measure the function of your inner ear, and Computerized Dynamic Posturography to assess your balance in different sensory conditions.

We use NeuroSensoryMotor Integration testing to evaluate hand-eye coordination and cognition, and Virtualis testing to assess dynamic eye tracking and perception of vertical in a virtual reality environment.

We combine all of this with a comprehensive physical and neurological examination of your sensory, motor, autonomic, and cognitive systems. We review any relevant laboratory testing, radiological imaging, and prior neurodiagnostic testing, and integrate that information with our findings.

We use this information to identify which parts of your brain are working properly, which systems are struggling, and the precise point at which your systems fatigue.

We can then design a NeuroRescue Program that is unique and specific to your brain, and yours alone. Your NeuroRescue Program works to rejuvenate and reintegrate the damaged neurons and pathways in your brain. It works to improve energy, endurance, and functional capacity within your fragile systems.

We use our technologies and procedures to not only see what we need to address, but also when it is time to stop and let you rest. We address your impaired neurological function from multiple angles of therapy, and provide metabolic support to improve neurological recovery.

While we cannot bring back neurons that have been lost to Parkinson’s disease, your NeuroRescue Program allows us to take the pathways that remain and maximize their efficiency and endurance. And by focusing on the integration of systems, we can do more than just get pathways working better, we can get them working together again. This gives us our best opportunity to help you live a healthy, vibrant, and fulfilling life.

Your Next Best Step:

Living with Progressive Supranuclear Palsy is challenging. While we cannot offer a cure for the condition, many of the symptoms can be manageable, function can be enhanced, and quality can often be significantly improved.

To see if the NeuroRescue Program is right for you, contact one of our patient care coordinators to schedule your Discovery Day.

And remember, it’s never too late to start getting better.