Progressive Supranuclear Palsy

What is Progressive Supranuclear Palsy?

Progressive supranuclear palsy (PSP) is a rare disorder that affects the brain and nerves, making it difficult for patients to move, walk, balance, speak, swallow, see properly, or control their mood, behavior, and thinking abilities. This disease was first identified in 1964 by doctors Steele, Richardson, and Olszewski. They described it as a unique case where patients had problems with moving their eyes, stiffness in their bodies, issues with speaking and swallowing, and mild memory and thinking problems. Today, we understand this ailment as a form of Parkinson’s disease, but a bit different and hence known as atypical parkinsonian syndrome or Parkinson-plus disorder.

In 1972, Steele hypothesized that there could be different types of this syndrome, based on which specific parts of the brain were affected at what times and to what extent. Since then, medical scientists have indeed discovered different types of PSP, which are linked to the severity of abnormal proteins called tau, found in various parts of the brain. While each type of PSP might show different symptoms and progress at different rates, they all share similar features when brain pathology is examined.

What Causes Progressive Supranuclear Palsy?

The exact reason for the occurrence of progressive supranuclear palsy, a kind of brain disorder, is currently not known. Some theories suggest that factors like older age and being exposed to harmful substances in the environment could cause it. The tau protein, which helps in the structure and function of nerve cells in the brain, tends to clump together abnormally in this condition.

These irregular tau protein clusters might occur because of an unusual infectious agent (a germ or virus), random changes in the genes, or exposure to a harmful chemical present in food, air, or water that slowly damages specific areas of the brain. It’s important to remember that these are possible theories and the actual cause is still unknown.

Risk Factors and Frequency for Progressive Supranuclear Palsy

Recent studies highlight that progressive supranuclear palsy affects between 5.8 and 6.5 out of 100,000 people. Although earlier investigations reported a yearly rate of 0.3 to 0.4 cases per 100,000 people, more recent research from 1999 found this number to be slightly higher at 1.1 per 100,000 people annually. This increase is probably due to better detection and understanding of the disorder.

The yearly rate of this condition rises with age, ranging from 1.7 cases per 100,000 people aged between 50 and 59, to 14.7 per 100,000 people aged between 80 and 89. The average age at which progressive supranuclear palsy starts is around 65, which is older than for Parkinson’s disease. It is quite rare for this condition to affect anyone below the age of 40.

Initially, it was believed that progressive supranuclear palsy was much more common in men, with a ratio of eight men for every woman affected. However, later investigations have found no significant gender difference.

Signs and Symptoms of Progressive Supranuclear Palsy

Progressive supranuclear palsy is a specific kind of parkinsonism, which refers to condition characterized by slowed, rigid movements much like Parkinson’s disease. This condition subtly and slowly creeps in and generally affects both sides of the body. In the beginning, motor difficulties are usually observed in the body’s center rather than the limbs. Common early signs include difficulty walking and falling. Others might initially feel dizzy, move slower, or experience changes in personality. Only on rare occasions would someone first experience a resting tremor with progressive supranuclear palsy.

As the disease gets worse, the person might find it hard to talk or swallow, find it hard to move certain eye muscles, and struggle with cognitive tasks. Though eye movement issues, specifically supranuclear ophthalmoplegia, are a definitive sign of progressive supranuclear palsy, not all patients show this in the initial stages. It’s often slower eye movements towards vertical objects that’s first noticed. As the disease progresses, the person might experience a lack of saccadic intrusions, blepharospasm, and eyelid apraxia, and at a later stage, their eyes could become virtually immobile.

Progressive supranuclear palsy is classified into several clinical subtypes: classic progressive supranuclear palsy-Richardson syndrome, progressive supranuclear palsy-parkinsonism, progressive supranuclear palsy-pure akinesia with gait freezing, progressive supranuclear palsy-corticobasal syndrome, progressive supranuclear palsy-behavioral variant of frontotemporal dementia, and progressive supranuclear palsy-progressive non-fluent aphasia.

Classic progressive supranuclear palsy-Richardson syndrome
Progressive supranuclear palsy-parkinsonism
Progressive supranuclear palsy-pure akinesia with gait freezing
Progressive supranuclear palsy-corticobasal syndrome
Progressive supranuclear palsy-behavioral variant of frontotemporal dementia
Progressive supranuclear palsy-progressive non-fluent aphasia

Motor issues like slowed movement and significant tremors are common in all forms of progressive supranuclear palsy. Rigidity, in particular, is often more apparent in the body’s center rather than the limbs, notably the neck and trunk. Cognitive and behavioral abnormalities like severe frontal cognitive deficits, depression, obsessive-compulsive symptoms, and impulsivity are also common in progressive supranuclear palsy patients. Some might behave inappropriately due to impulsive behavior and may also struggle to change mental tasks or repeat certain behaviors. Severe trouble speaking and swallowing are often noticeable by the mid to later stages of the disease.

Progressive supranuclear palsy can also lead to sleep disturbances like insomnia or trouble staying asleep due to rigidity. Rarely are all these symptoms present at onset. Most symptoms start appearing around 4 years after diagnosis and can evolve to other symptoms over time.

Depending on the subtype, progressive supranuclear palsy could have a different progression and lifespan post-diagnosis. The classic subtype typically begins in the 60s and progresses to death in around 7 years. Other subtypes, however, offer better outcomes with longer survival rates.

Testing for Progressive Supranuclear Palsy

In 2017, a group of specialists from The International Parkinson and Movement Disorder Society developed new criteria for diagnosing Progressive Supranuclear Palsy (PSP), a condition that affects movement and balance. Before this, doctors primarily used criteria from the National Institute of Neurological Disorders and Stroke and the Society for PSP. To diagnose PSP, doctors looked for specific eye movement issues and balance problems leading to falls within the first year of disease onset.

For a possible PSP diagnosis, either these specific eye movement issues had to be present or the person needed to show other symptoms including being more rigid or less mobile in their upper body than their lower body, neck posture problems, not responding well to levodopa (a common Parkinson’s disease medication), difficulty swallowing or slurred speech, and cognitive or behavioral issues.

Neuroimaging, like MRI scans, can also help doctors diagnose PSP. These scans often show changes in the brain such as atrophy (shrinking of brain tissue), increased signals in the midbrain and inferior olives, degeneration of the red nucleus, and size increase in the aqueduct and third ventricle. As the disease progresses, the frontal and temporal lobes of the brain may also start to atrophy.

One sign often seen in PSP patients’ MRI scans is the “hummingbird sign” – the rostral midbrain atrophy (shrinkage in the front part of the midbrain) looks like a hummingbird. Another technique, called the DaTscan, can be useful as it shows reduced tracer uptake in the striatum, a part of the brain responsible for various functions like reward, cognition, and movement. However, DaTscan can’t differentiate between PSP and Parkinson’s disease. That said, PET imaging with a tau ligand, a molecular compound used in brain imaging, is showing promise as a tool to help diagnose and track the progress of PSP.

Treatment Options for Progressive Supranuclear Palsy

Progressive supranuclear palsy is a condition that impacts your brain, which can cause problems with movement, balance, and mental abilities. Managing the symptoms can be tough, and so far, the available treatments are only symptomatic and supportive. Currently, there are ongoing trials to find treatments that may modify the disease itself, focusing mainly on the tau pathology, which involves irregularities in the brain cells.

For symptoms related to movement, a medication called levodopa combined with a dopa decarboxylase inhibitor (like carbidopa) is usually used. However, this usually has limited success. Nevertheless, levodopa is often tried due to the lack of other options. Sometimes, a medicine called amantadine may also be tested but there is only limited evidence to support its effectiveness. If you have focal dystonias, which are abnormal muscle contractions, botulinum toxin injections can be helpful.

Physical therapy seems to be a promising approach for these patients. Just like in Parkinson’s disease, physical therapy might provide benefits. Two studies have shown this potential; one study showed some improvement in the Progressive Supranuclear Palsy Rating Scale, and another proposed some benefit from the Lee Silverman Voice Treatment. In addition to physical therapy, occupational therapy can help minimize the chance of injury by teaching balance and safe ways to fall. Diet consultation for safe swallowing may be necessary as well. In later stages, a wheelchair may be required as patients might not be able to maintain balance using a walker.

There are reports suggesting potential benefits from deep brain stimulation, a procedure that involves placing electrodes in your brain. However, a recent clinical trial showed that this approach may not improve gait, posture, or balance. Thus, deep brain stimulation is not currently recommended outside research studies.

No accepted treatments are available for the cognitive, or thinking and memory, issues that can come with this condition. Small studies have suggested that certain medications might help mental function, but may worsen physical function. Depression is a common symptom that can be potentially treated. Although there are no specific recommendations, it’s crucial to manage depression.”

Up until now, many trials have tried to find medications that can modify the course of the disease, unfortunately with no success. It’s important to always consider palliative or end-of-life care as part of treating progressive supranuclear palsy, especially in the later stages.

Current research is focusing on therapies such as TPI-287, a microtubule stabilizer that could help to compensate for brain cell dysfunction; C2N-8E12/ABBV-8E12 and BMS-986168/BIIB092, both anti-tau monoclonal antibodies which could obstruct the spread of harmful tau; and salsalate, a tau acetylation inhibitor which could prevent soluble tau from becoming hyperphosphorylated. These research efforts are all aimed at slowing down or stopping the disease.

When attempting to diagnose progressive supranuclear palsy, there are several other conditions that might cause similar symptoms and need to be considered. These include:

Corticobasal ganglionic degeneration (CBGD)
Parkinson’s disease
Multiple system atrophy (MSA) of the parkinsonian type
Pick disease
Microvascular disease of the brain stem
Tumors in the midbrain area
Whipple disease
Mitochondrial myopathies
Wilson disease
Adult-onset Niemann-Pick disease
Myasthenia gravis
Amyotrophic lateral sclerosis

These conditions can mimic the symptoms of progressive supranuclear palsy, so it’s vital for physicians to carry out appropriate tests to ensure an accurate diagnosis.

What to expect with Progressive Supranuclear Palsy

In progressive supranuclear palsy, a type of brain disorder, the disease typically progresses quite fast, meaning symptoms get worse at a fast pace. As a result, most patients need assistance with their daily activities within 3 to 4 years of starting to show symptoms. People diagnosed with this condition often have their lifespan reduced and may only live for an average of 6 to 9 years after diagnosis. Moreover, their overall quality of life may significantly decline.

In a research review from 2017, certain factors were found to relate to a shorter lifespan. These included a certain type of the disease called progressive supranuclear palsy-Richardson (PSP-RS), experiencing falls earlier, and having cognitive symptoms (like memory loss and confusion) early on. These are more common with the PSP-RS type. Another factor was the early-onset of dysphagia (trouble swallowing), which occurs in both PSP-RS and another type called progressive supranuclear palsy-parkinsonism (PSP-P).

However, having a certain eye movement disorder called supranuclear gaze palsy didn’t consistently predict lifespan across all studies. Also, how well patients responded to a common Parkinson’s disease medication called Levodopa didn’t predict longer survival, even though it’s often used in the early stages of the PSP-P type.

Frequently asked questions

The prognosis for Progressive Supranuclear Palsy (PSP) is generally poor. Most patients require assistance with daily activities within 3 to 4 years of symptom onset, and the average lifespan after diagnosis is 6 to 9 years. Factors that may relate to a shorter lifespan include having the PSP-Richardson type, experiencing falls earlier, having cognitive symptoms early on, and early-onset dysphagia. However, the presence of supranuclear gaze palsy and response to Levodopa medication do not consistently predict survival.

The exact reason for the occurrence of progressive supranuclear palsy is currently not known. Some theories suggest that factors like older age and being exposed to harmful substances in the environment could cause it. The tau protein, which helps in the structure and function of nerve cells in the brain, tends to clump together abnormally in this condition. These irregular tau protein clusters might occur because of an unusual infectious agent (a germ or virus), random changes in the genes, or exposure to a harmful chemical present in food, air, or water that slowly damages specific areas of the brain. However, it's important to remember that these are possible theories and the actual cause is still unknown.

Signs and symptoms of Progressive Supranuclear Palsy include: - Slowed, rigid movements similar to Parkinson's disease - Motor difficulties, especially in the body's center rather than the limbs - Difficulty walking and falling - Dizziness and slower movement - Changes in personality - Lack of resting tremor (rarely present) - Difficulty talking and swallowing - Difficulty moving certain eye muscles - Cognitive difficulties - Supranuclear ophthalmoplegia (eye movement issues) - Slower eye movements towards vertical objects - Lack of saccadic intrusions - Blepharospasm (involuntary eyelid closure) - Eyelid apraxia (inability to open or close the eyelids) - Immobility of the eyes in later stages - Classified into several clinical subtypes, including classic progressive supranuclear palsy-Richardson syndrome, progressive supranuclear palsy-parkinsonism, progressive supranuclear palsy-pure akinesia with gait freezing, progressive supranuclear palsy-corticobasal syndrome, progressive supranuclear palsy-behavioral variant of frontotemporal dementia, and progressive supranuclear palsy-progressive non-fluent aphasia - Motor issues like slowed movement and significant tremors - Rigidity, particularly in the body's center (neck and trunk) - Cognitive and behavioral abnormalities, such as severe frontal cognitive deficits, depression, obsessive-compulsive symptoms, and impulsivity - Inappropriate behavior due to impulsive behavior - Difficulty changing mental tasks or repeating behaviors - Severe trouble speaking and swallowing - Sleep disturbances like insomnia or trouble staying asleep due to rigidity - Symptoms usually appear around 4 years after diagnosis and can evolve over time - Different subtypes have different progression and lifespan post-diagnosis, with the classic subtype typically progressing to death in around 7 years and other subtypes offering better outcomes with longer survival rates.

To properly diagnose Progressive Supranuclear Palsy (PSP), doctors may order the following tests: 1. Eye movement assessment: Doctors look for specific eye movement issues, such as vertical gaze palsy or slowed horizontal saccades. 2. Balance assessment: Patients with PSP often experience balance problems leading to falls within the first year of disease onset. 3. Neuroimaging: MRI scans can show changes in the brain, including atrophy, increased signals in the midbrain and inferior olives, degeneration of the red nucleus, and size increase in the aqueduct and third ventricle. PET imaging with a tau ligand is also showing promise as a tool to help diagnose and track the progress of PSP. 4. DaTscan: This technique shows reduced tracer uptake in the striatum, but it cannot differentiate between PSP and Parkinson's disease. 5. Cognitive and behavioral assessments: Doctors evaluate cognitive and behavioral issues that may be present in PSP patients. It's important to note that these tests are used in combination with clinical evaluation and medical history to make a proper diagnosis of PSP.

Corticobasal ganglionic degeneration (CBGD), Parkinson's disease, Multiple system atrophy (MSA) of the parkinsonian type, Pick disease, Microvascular disease of the brain stem, Tumors in the midbrain area, Whipple disease, Mitochondrial myopathies, Wilson disease, Adult-onset Niemann-Pick disease, Myasthenia gravis, Amyotrophic lateral sclerosis.

When treating Progressive Supranuclear Palsy, the available treatments may have side effects. Here are some potential side effects associated with the treatments: - Levodopa combined with a dopa decarboxylase inhibitor (like carbidopa): limited success in managing movement symptoms. - Amantadine: limited evidence to support its effectiveness. - Botulinum toxin injections: can be helpful for focal dystonias, but specific side effects are not mentioned. - Deep brain stimulation: a recent clinical trial showed no improvement in gait, posture, or balance. - Medications for cognitive issues: certain medications might help mental function but may worsen physical function. - No specific recommendations for managing depression, a common symptom. It's important to note that the text does not provide a comprehensive list of all possible side effects, and individual experiences may vary.

A neurologist.

Progressive Supranuclear Palsy affects between 5.8 and 6.5 out of 100,000 people.

Progressive Supranuclear Palsy is currently treated with symptomatic and supportive measures. Medications such as levodopa combined with a dopa decarboxylase inhibitor may be used to manage movement symptoms, although their success is limited. Botulinum toxin injections can be helpful for abnormal muscle contractions. Physical therapy and occupational therapy can provide benefits, and deep brain stimulation may be considered in research studies. There are no accepted treatments for cognitive issues, but certain medications may help mental function. Palliative or end-of-life care should also be considered, especially in later stages. Ongoing research is focused on finding treatments that can modify the disease itself.

Progressive Supranuclear Palsy (PSP) is a rare disorder that affects the brain and nerves, causing difficulties in movement, walking, balance, speech, swallowing, vision, and mood, behavior, and thinking abilities.