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Progressive Supranuclear Palsy

Disease Details

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Description: Progressive supranuclear palsy is a rare brain disorder that causes problems with movement, balance, vision, speech, and swallowing due to the deterioration of specific brain cells.
Type: Progressive supranuclear palsy (PSP) is a neurodegenerative disease. It is generally not considered to have a specific type of genetic transmission and is typically seen as sporadic. However, some cases may have genetic associations or risk factors that are still being studied.
Signs And Symptoms: The initial symptoms in two-thirds of cases are loss of balance, lunging forward when mobilizing, fast walking, bumping into objects or people, and falls. Dementia symptoms are also initially seen in about one in five cases.Other common early symptoms are changes in personality, general slowing of movement, and visual symptoms. The most common behavioural symptoms in patients with PSP include apathy, a lack of inhibition, anxiety, and a profound state of unease or dissatisfaction.Later symptoms and signs can include, but do not necessarily include dementia (typically including loss of inhibition and ability to organize information), slurring of speech, difficulty swallowing, and difficulty moving the eyes, particularly in the vertical direction. The latter accounts for some of the falls experienced by these patients, as they find it difficult to look up or down.Some of the other signs are poor eyelid function, contracture of the facial muscles, a backward tilt of the head with stiffening of the neck muscles, sleep disruption, urinary incontinence, and constipation. Some patients retain full cognitive function up to the end.The visual symptoms are of particular importance in the diagnosis of this disorder. Patients typically complain of difficulty reading due to the inability to look downwards. The ophthalmoparesis experienced by these patients mainly concerns voluntary eye movement and the inability to make vertical saccades, which is often worse with downward saccades. Patients tend to have difficulty looking down (a downgaze palsy) followed by the addition of an upgaze palsy. This vertical gaze paresis will correct when the examiner passively rolls the patient's head up and down as part of a test for the oculocephalic reflex. Involuntary eye movement, as elicited by Bell's phenomenon, for instance, may be closer to normal.
On close inspection, eye movements called "square-wave jerks" may be visible when the patient fixes gaze at distance. These are fine movements, that can be mistaken for nystagmus, except that they are saccadic in nature, with no smooth phase. Although healthy individuals also make square-wave jerk movements, PSP patients make slower square-wave jerk movements, with smaller vertical components. Assessment of these square-wave jerks and diminished vertical saccades is especially useful for diagnosing progressive supranuclear palsy, because these movements set PSP patients apart from other parkinsonian patients. Difficulties with convergence (convergence insufficiency), where the eyes come closer together while focusing on something near, like the pages of a book, is typical. Because the eyes have trouble coming together to focus at short distances, the patient may complain of diplopia (double vision) when reading.A characteristic facial appearance known as procerus sign, with a wide-eye stare, furrowing of forehead with a frowning expression, and deepening of other facial creases, is also diagnostic of PSP.
Prognosis: No effective treatment or cure has been found for PSP, although some of the symptoms can respond to nonspecific measures. The poor prognosis is predominantly attributed to the serious impact this condition has on the quality of life. The average age at symptoms onset is 63 and survival from onset averages seven years with a wide variance. Pneumonia is a frequent cause of death, often caused by accidental aspiration of food particles.
Onset: Progressive supranuclear palsy (PSP) typically has an onset in late middle age, most commonly between the ages of 60 and 65.
Prevalence: Progressive supranuclear palsy (PSP) is a rare neurological disorder. Its prevalence is estimated to be approximately 5 to 7 cases per 100,000 people.
Epidemiology: Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder. The prevalence is estimated to be about 5-6 cases per 100,000 individuals. PSP typically affects people aged 60 and older, with the onset usually occurring in the early 60s. It is slightly more common in men than in women.
Intractability: Yes, progressive supranuclear palsy (PSP) is generally considered an intractable disease. It is a rare, progressive neurodegenerative disorder that currently has no cure, and treatment primarily focuses on managing symptoms and improving quality of life. The disease progressively impairs movement, balance, vision, speech, and cognitive function, and available therapies do not significantly alter the disease course.
Disease Severity: Progressive supranuclear palsy (PSP) is a severe neurodegenerative disorder characterized by a variety of symptoms including issues with balance, movement, vision, speech, and cognitive function. It is a progressive condition, meaning symptoms worsen over time.
Healthcare Professionals: Disease Ontology ID - DOID:678
Pathophysiology: The affected brain cells are both neurons and glial cells. The neurons display neurofibrillary tangles (NFTs), which are clumps of tau protein, a normal part of a brain cell's internal structural skeleton. These tangles are often different from those seen in Alzheimer's disease, but may be structurally similar when they occur in the cerebral cortex. Their chemical composition is usually different, however, and is similar to that of tangles seen in corticobasal degeneration. Tufts of tau protein in astrocytes, or tufted astrocytes, are also considered diagnostic. Unlike globose NFTs, they may be more widespread in the cortex. Lewy bodies are seen in some cases, but whether this is a variant or an independent co-existing process is not clear, and in some cases, PSP can coexist with corticobasal degeneration, Parkinson's, and/or Alzheimer's disease, particularly with older patients.The principal areas of the brain affected are the:
basal ganglia, particularly the subthalamic nucleus, substantia nigra, and globus pallidus
brainstem, particularly the tectum (the portion of the midbrain where "supranuclear" eye movement resides), as well as dopaminergic nuclei
cerebral cortex, particularly that of the frontal lobes and the limbic system (similarly to frontotemporal degeneration)
dentate nucleus of the cerebellum
spinal cord, particularly the area where some control of the bladder and bowel residesSome consider PSP, corticobasal degeneration, and frontotemporal dementia (especially FTDP-17) to be variations of the same disease. Others consider them separate diseases. PSP has been shown occasionally to co-exist with Pick's disease.
Carrier Status: Progressive supranuclear palsy (PSP) is not a genetic disorder with a carrier status. It is a rare, neurodegenerative disease characterized by symptoms such as balance problems, stiffness, and difficulty with eye movements. The exact cause is unknown, but it involves the accumulation of abnormal tau protein in the brain. While the carrier status concept does not apply to PSP as it might for genetic diseases like cystic fibrosis or sickle cell anemia, there may be genetic factors that contribute to an individual's risk of developing the disease. However, these factors are not well-defined and PSP is generally considered sporadic rather than inherited.
Mechanism: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by deterioration of specific regions of the brain.

**Mechanism:**
The disease primarily affects the brainstem, basal ganglia, and frontal lobes, leading to symptoms such as loss of balance, gait disturbances, stiffness, and difficulties with eye movement, particularly vertical gaze. PSP also impacts cognitive functions and can induce behavioral changes.

**Molecular Mechanisms:**
At the molecular level, PSP is associated with the accumulation of abnormal tau protein in the brain, particularly in the form of neurofibrillary tangles. These tangles disrupt normal cell function and contribute to cell death. The tau protein is normally involved in stabilizing microtubules in neurons, but in PSP, it becomes hyperphosphorylated and aggregates. Genetic factors, such as mutations in the MAPT gene, have been implicated in the pathogenesis of PSP. These molecular disturbances lead to the characteristic neurodegenerative changes observed in PSP.
Treatment: Management is only supportive as no cure for PSP is known. PSP cases are often split into two subgroups, PSP-Richardson (the classic type) and PSP-Parkinsonism, where a short-term response to levodopa can be obtained. Dyskinesia is an occasional but rare complication of treatment. Amantadine is also sometimes helpful. After a few years the Parkinsonian variant tends to take on Richardson features. Other variants have been described.Botox can be used to treat neck dystonia and blepharospasm, but this can aggravate dysphagia.Two studies have suggested that rivastigmine may help with cognitive aspects, but the authors of both studies have suggested that larger studies are needed. There is some evidence from small-scale studies that the hypnotic zolpidem may improve motor function and eye movements.
Compassionate Use Treatment: Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder with limited treatment options. Currently, there is no cure for PSP, and treatment primarily focuses on managing symptoms. Compassionate use treatments and off-label or experimental treatments may include:

1. **Levodopa**: Commonly used to treat Parkinson's disease, levodopa is sometimes tried in PSP, although its effectiveness is generally limited.

2. **Amantadine**: This antiviral with dopaminergic properties can be used off-label to help with gait and balance issues.

3. **Coenzyme Q10**: Though evidence is limited, this antioxidant might be explored for its neuroprotective effects.

4. **Riluzole**: Originally approved for ALS, its neuroprotective properties are being investigated for PSP.

5. **Davunetide**: An experimental neuroprotective drug that has shown promise in preliminary studies but requires further research.

6. **Stem Cell Therapy**: An experimental approach aiming to regenerate damaged neurons. This is still in the early stages of research.

7. **Tau-directed Therapies**: As PSP is a tauopathy, therapies targeting tau protein accumulation, such as monoclonal antibodies, are being explored in clinical trials.

Patients considering these options should consult with their healthcare provider to understand the potential benefits and risks.
Lifestyle Recommendations: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder with no cure. Lifestyle recommendations for managing PSP primarily focus on symptom relief and maintaining quality of life:

1. **Regular Exercise**: Engaging in physical therapy and regular low-impact exercises can help maintain mobility and strength.
2. **Healthy Diet**: A balanced diet rich in nutrients supports overall health. Speech therapy may help with swallowing difficulties.
3. **Safety Measures**: Implementing home modifications, such as removing tripping hazards and installing grab bars, can prevent falls.
4. **Supportive Equipment**: Using mobility aids like walkers or wheelchairs can provide stability and reduce the risk of injury.
5. **Speech Therapy**: This can assist in managing speech and swallowing difficulties.
6. **Occupational Therapy**: Helps in adapting daily activities to maintain independence.
7. **Mental Health Support**: Counseling or support groups can provide emotional support for patients and caregivers.
8. **Regular Medical Check-ups**: Continued monitoring and symptom management by healthcare professionals are crucial for adjusting treatment plans.

These recommendations aim to enhance daily functioning and quality of life for individuals with PSP.
Medication: Progressive supranuclear palsy (PSP) currently has no cure, but certain medications can help manage symptoms. These may include:

1. **Levodopa/Carbidopa**: Often used to treat Parkinson's disease-like symptoms, although its effectiveness in PSP is usually limited and temporary.
2. **Amantadine**: Can help with balance and control of movement.
3. **Antidepressants**: Such as fluoxetine or amitriptyline, to treat mood and behavioral changes.

Treatment is primarily focused on improving quality of life and managing symptoms through a combination of medication, physical therapy, and supportive care. Note that individual responses vary, so treatments are typically tailored to the patient's specific needs.
Repurposable Drugs: As of now, there are no specific FDA-approved drugs for progressive supranuclear palsy (PSP). However, some drugs approved for other conditions have been explored for potential benefits in PSP. These include:

1. **Levodopa**: Commonly used in Parkinson's disease, it may offer limited and temporary symptom relief for PSP patients.
2. **Antidepressants**: Such as fluoxetine or amitriptyline, for mood and emotional symptoms.
3. **Botulinum toxin**: For managing dystonia or abnormal muscle contractions.

Clinical trials and research are ongoing to identify effective treatments for PSP.
Metabolites: Progressive Supranuclear Palsy (PSP) does not have specific metabolites that serve as biomarkers for the disease. The diagnosis often relies on clinical evaluation and neuroimaging rather than metabolic profiling. Researchers continue to study metabolic changes in PSP, but as of now, no distinct metabolites have been identified for diagnostic purposes.
Nutraceuticals: Nutraceuticals refer to products derived from food sources that offer health benefits in addition to their basic nutritional value. There is currently limited evidence that nutraceuticals have significant effects on the progression or symptoms of Progressive Supranuclear Palsy (PSP). While some supplements, such as coenzyme Q10, omega-3 fatty acids, and antioxidants, are sometimes considered for general neuroprotective effects, robust clinical data supporting their efficacy in PSP is lacking. It's essential for patients to consult healthcare providers before starting any nutraceuticals to ensure they do not interfere with prescribed treatments.
Peptides: Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by the accumulation of abnormal tau proteins in the brain. Researchers are investigating various peptides and nanoparticles (nan) for potential therapeutic interventions. Peptides may be designed to inhibit tau aggregation or to target tau for degradation. Nanoparticles could be employed to deliver drugs or therapeutic molecules directly to affected brain regions, potentially improving treatment efficacy and reducing side effects. Currently, there is no cure, and treatments primarily focus on managing symptoms.