Progressive supranuclear palsy

Overview

Progressive supranuclear palsy (PSP) is a rare, degenerative brain disorder that affects movement, balance, vision, speech, and cognitive function. It is classified as a tauopathy, meaning it involves abnormal accumulation of tau protein in the brain, which leads to the destruction of brain cells, especially in areas that control movement and coordination. PSP is often misdiagnosed as Parkinson’s disease in its early stages due to overlapping motor symptoms. However, PSP progresses more rapidly and does not typically respond to Parkinson’s medications. The condition usually begins in late middle age and leads to significant disability over time.

Causes

The exact cause of progressive supranuclear palsy is not fully understood, but it is linked to abnormal accumulation of tau protein in the brain. Tau is normally involved in stabilizing microtubules in nerve cells, but in PSP, defective tau forms tangles that disrupt cell function and lead to cell death. Key contributing factors include:

• Genetic predisposition: Although most PSP cases are sporadic, some rare familial cases have been linked to mutations in the MAPT gene, which encodes the tau protein.

• Environmental influences: No specific environmental cause has been identified, but ongoing research suggests possible links to toxins or oxidative stress.

PSP is not considered a hereditary disease in the majority of cases, and no clear risk factors have been established for most individuals diagnosed with the condition.

Symptoms

Symptoms of PSP typically appear gradually and worsen over time. The most distinguishing clinical feature is vertical gaze palsy—difficulty moving the eyes, particularly in the up-and-down direction. Other hallmark symptoms include:

Motor Symptoms

• Frequent falls, particularly backward (early and unexplained)

• Stiffness and rigidity, often more pronounced in the neck and trunk

• Bradykinesia (slowness of movement)

• Impaired balance and postural instability

• Dysphagia (difficulty swallowing)

• Dysarthria (slurred or slowed speech)

Eye and Vision Abnormalities

• Supranuclear gaze palsy (especially vertical eye movements)

• Blurred vision and difficulty focusing

• Difficulty maintaining eye contact

Cognitive and Behavioral Changes

• Slowed thinking and cognitive decline

• Apathy or lack of motivation

• Depression and emotional lability

• Problems with executive function and planning

As the disease progresses, patients may become dependent on others for basic activities of daily living, including eating, dressing, and walking.

Diagnosis

There is no single test that definitively diagnoses PSP. Diagnosis is made based on clinical evaluation, medical history, symptom progression, and the exclusion of other conditions. Diagnostic steps include:

• Neurological examination: Evaluates eye movements, reflexes, muscle tone, and balance

• Brain imaging (MRI): May show atrophy in midbrain structures such as the “hummingbird sign,” suggestive of PSP

• DaTscan: Can help distinguish PSP from Parkinson’s disease by visualizing dopamine transport in the brain

• Neuropsychological testing: Assesses cognitive function and helps differentiate PSP from other dementias

• Exclusion of other disorders: Such as Parkinson’s disease, multiple system atrophy, or corticobasal degeneration

Definitive diagnosis can only be made through postmortem brain examination, revealing tau protein aggregates in affected regions.

Treatment

There is currently no cure for progressive supranuclear palsy, and treatment is focused on alleviating symptoms and improving quality of life. A multidisciplinary approach is essential for effective care.

Medications

• Levodopa: May provide mild and temporary benefit, but most PSP patients are unresponsive

• Antidepressants: Such as SSRIs may help with mood and behavioral symptoms

• Botulinum toxin injections: Can be used for dystonia or eyelid spasms (blepharospasm)

Supportive Therapies

• Physical therapy: Aims to maintain mobility, improve balance, and prevent falls

• Occupational therapy: Assists with adaptations for daily activities and home safety

• Speech and swallowing therapy: Addresses dysarthria and dysphagia to prevent aspiration and communication difficulties

• Nutritional support: Including modified diets or feeding tubes in advanced cases

Assistive Devices

• Walking aids with stability features to reduce fall risk

• Communication tools for speech difficulties

Prognosis

Progressive supranuclear palsy is a relentlessly progressive disorder with no curative treatment. The average life expectancy following diagnosis is approximately 6 to 10 years. The most common causes of death are complications related to immobility, including aspiration pneumonia, infections, and falls. While early intervention and supportive care can enhance quality of life and slow functional decline, most patients eventually require full-time assistance.

Ongoing research into tau-targeting therapies and neuroprotective agents offers hope for more effective treatments in the future. Participation in clinical trials may be an option for some patients seeking advanced care and contributing to scientific progress.