Overview

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder. PSP is developed mainly due to the progressive loss of neuronal connections in certain brain regions, which results in non-cognitive impairments. One of the characteristics that distinguishes PSP from other similar disorders is symptoms affecting eye movements and vision.¹

Understanding progressive supranuclear palsy

Progressive supranuclear palsy (also known as Steele-Richardson-Olszewski syndrome) is a rare neurodegenerative disorder caused by damage to cells in certain areas of the brain resulting in impaired ability to walk, keep balance, and control eye movements. It often also causes problems with vision, speech, and swallowing.

To better understand what progressive supranuclear palsy means, let’s break it down:

• Progressive - means that the condition worsens over time resulting in more brain cells being damaged which leads to exacerbation of the symptoms of the disease.
• Supranuclear - refers to the area of the brain affected by the disorder. It is the section located above nerve nuclei in the brainstem.
• Palsy - a condition characterized by paralysis or significant loss of muscle function²

Brain atrophy as the main cause of progressive supranuclear palsy

The term ‘brain atrophy’ refers to the process of losing brain cells (neurons) and in consequence the connections between them, resulting in a reduction of brain volume. This in turn, often leads to impaired thinking process, memory loss, and other cognitive and non-cognitive symptoms.³

Brain atrophy is the main cause of progressive supranuclear palsy. The symptoms of the disorder are a result of neuronal connection loss and reduced brain volume. In the case of PSP, the damage to neurons is a result of abnormal accumulation of tau protein in the brain. Tau protein occurs naturally in the brain and helps to preserve the structure of neurons and therefore their functions. In the brain of PSP patients tau protein aggregates create clumps that damage neurons and lead to loss of connections between them.

Depending on the location of those aggregates different symptoms are developed. Additionally, the exact factor that triggers the accumulation of tau protein is unknown.²

Affected populations

PSP is difficult to identify and diagnose; however, it is estimated that there are approximately 4,000 people in the UK suffering from PSP.⁴ The onset of progressive supranuclear palsy occurs usually between 45 and 75 years of age. There is no evidence that the disease affects one sex more often than the other.⁵

Symptoms and signs of progressive supranuclear palsy

Initially, the onset of the disorder is subtle and may go unnoticed. Over time, however, the symptoms gradually worsen, becoming more pronounced and significantly impacting daily activities and overall quality of life. Most people with PSP develop severe disability within three to five years after the onset.

Often the first signs of PSP are difficulties with balance and coordination which gradually start affecting the ability to walk. People with progressive supranuclear palsy may fall easily or feel rigid and uncomfortable while walking. Other symptoms include difficulties swallowing and speaking. As the disease progresses problems with eye movements become more severe. The symptoms affecting eyes and vision may include:

• A tendency to move the head rather than just eyes to look in a different direction
• Difficulties controlling eyelid movements, which include decreased frequency blinking, involuntary closing of the eyes, and difficulties opening them
• Slow eye movements

People suffering from PSP might also develop behavioural and mood changes. These symptoms include depression, mood swings, lack of motivation, and irritability. Additionally, they may experience increased apathy and difficulty in controlling their emotions.

Many symptoms characteristic of progressive supranuclear palsy are also frequently observed in people suffering from Parkinson’s disease. It often leads to a misdiagnosis. However, there are several key factors that help distinguish between these two types of disorders.¹

How to differentiate between progressive supranuclear palsy and Parkinson’s disease

Early symptoms of PSP and Parkinson’s disease (PD) are similar. However, PSP usually develops later and progresses much more quickly than PD.

Several other differences between the two disorders include:

• Patients with PSP usually have the tendency to lean backward rather than forward, which is common for PD patients. Thus, people suffering from PSP fall backward and those with PD fall forward
• Difficulties with swallowing and speaking are much more frequent for patients with PSP than PD. They are also noticeable earlier in the disease
• PSP patients often develop unique symptoms regarding eye movements and control, which are not so common for PD patients
• Tremors are rare in PSP and very often noticed in PD patients
• PD patients respond to levodopa therapy (medicine that replenishes the brain's supply of dopamine, a neurotransmitter that is deficient in people with Parkinson's disease), while PSP patients show no or minimal improvement¹

Diagnosis of progressive supranuclear palsy

The early diagnosis of progressive supranuclear palsy is challenging. Due to the similarity of the PSP symptoms to this characteristic of Parkinson’s disease, PSP is often misdiagnosed as PD, especially in the early stages.

There is no specific test that could be used for PSP diagnosis. Healthcare providers usually rely on the following:

• Symptoms analysis and comparison to the symptoms characteristic of other similar disorders
• MRI - magnetic resonance imaging, which can help exclude other possible causes of the symptoms such as stroke. MRI might also point out the shrinking of certain brain regions that are associated with PSP development
• PET - positron emission tomography might serve as an additional source of information about the condition of a patient’s brain. It might show changes that do not appear on MRI

Furthermore, neurologists, as experts in nervous system disorders, can play a crucial role in the accurate diagnosis and management of PSP. Their specialized training allows them to discern the subtle differences between PSP and other similar conditions such as Parkinson’s disease. Consulting a neurologist ensures a comprehensive evaluation, including detailed clinical examinations and the interpretation of complex imaging results.²

Treatment methods

Currently, there is no cure for progressive supranuclear palsy; however, early diagnosis and an individualized treatment plan including a targeted therapeutic approach can help manage symptoms more effectively and improve the quality of patients’ lives.

The most often applied treatment methods include:

• Oral medications - in PSP cases most often applied pharmaceuticals are those used for the treatment of Parkinson’s disease. They are not as efficient as in PD patients but might help with balance, stiffness, and slowness of movements. Additionally, alongside psychotherapy, antidepressants might be prescribed in order to relieve the symptoms that affect the psychological condition of the patient
• Movement therapies - including physiotherapy (helps with muscle stiffness, movement, and balance difficulties), speech therapy (aims at improvement of speech and fighting swallowing issues), and occupational therapy (helps to improve the ability to perform daily tasks)
• Eye treatments - since the symptoms that affect eyes and vision in the case of progressive supranuclear palsy might become severe a number of treatments aim at their improvement. They include botulinum toxin injections in the area around the eyes, which might help in the case of difficulties controlling eyelid movements. Additionally, eye drops and artificial tears lubricate the eyes, reduce irritation, and reduce blinking
• Percutaneous endoscopic gastrostomy - a medical procedure performed in critical cases when the patient completely loses the ability to swallow. It involves surgically inserting a tube through the abdomen into the patient's stomach, allowing direct administration of medications, food, and liquids
• Palliative care - aims mainly at symptom relief but also provides comfort and support to patients suffering from chronic diseases such as progressive supranuclear palsy. Moreover, it helps the family and friends of the patients by providing support and guidance

There might also exist a possibility to participate in clinical trials for new PSP treatments. The patients might contact their healthcare providers to get information about ongoing clinical studies.^1,2

Summary

Progressive supranuclear palsy is a rare chronic progressive neurodegenerative disorder, which impairs mainly non-cognitive functions of the patient’s body by damaging neuronal connections in the brain (brain atrophy). The most common symptoms include difficulties walking and keeping balance; however, the most characteristic signs of progressive supranuclear palsy are issues with eye movements. The diagnosis of PSP is mostly based on the characteristic symptoms and brain imaging (MRI, PET). Unfortunately, no cure for PSP exists and the available treatment methods aim at managing the symptoms and improving the quality of patients’ lives.