Progressive supranuclear palsy

Person with progressive dementia, ataxia, and incontinence. A clinical diagnosis of normal-pressure hydrocephalus was entertained. Imaging did not support this, however, and on formal testing, abnormal nystagmus and eye movements were detected. A sagittal view of the CT/MRI scan shows atrophy of the midbrain, with preservation of the volume of the pons. This appearance has been called the "hummingbird sign" or "penguin sign". Also, atrophy of the tectum is seen, particularly the superior colliculi. These findings suggest the diagnosis of progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and dementia. PSP may be mistaken for other neurodegenerative diseases such as Parkinson's and Alzheimer's. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.

PSP affects about six people per 100,000. The first symptoms typically occur in persons aged 60–70 years. Males are slightly more likely to be affected than females. No association has been found between PSP and any particular race, location, or occupation.

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, disinhibition, anxiety, dysphoria.

Later symptoms and signs are 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 are unable 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.

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 down well. Notably, 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 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 diagnostic of PSP.

Cardinal manifestations:

• Supranuclear ophthalmoplegia
• Neck dystonia
• Parkinsonism
• Pseudobulbar palsy
• Behavioral and cognitive impairment
• Imbalance and walking difficulty
• Frequent falls

Cause

The cause of PSP is unknown. Fewer than 1% of those with PSP have a family member with the same disorder. A variant in the gene for tau protein called the H1 haplotype, located on chromosome 17, has been linked to PSP. Nearly all people with PSP received a copy of that variant from each parent, but this is true of about two-thirds of the general population. Therefore, the H1 haplotype appears to be necessary but not sufficient to cause PSP. Other genes, as well as environmental toxins, are being investigated as other possible contributors to the cause of PSP.

Besides tauopathy, mitochondrial dysfunction seems to be a factor involved in PSP. Especially, mitochondrial complex I inhibitors (such as acetogenins and quinolines contained in Annonaceae, as well as rotenoids) are implicated in PSP-like brain injuries.

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 portion of the midbrain where "supranuclear" eye movement resides
• cerebral cortex, particularly that of the frontal lobes
• dentate nucleus of the cerebellum
• spinal cord, particularly the area where some control of the bladder and bowel resides

Some consider PSP, corticobasal degeneration, and frontotemporal dementia to be variations of the same disease. Others consider them separate diseases. PSP has been shown occasionally to co-exist with Pick's disease.

Diagnosis

Diagnosing PSP can be challenging, as its symptoms often overlap with those of other neurodegenerative diseases such as Parkinson's and Alzheimer's. A thorough clinical examination, including a detailed medical history and assessment of symptoms, is essential for accurate diagnosis. Imaging studies, such as magnetic resonance imaging (MRI), may also be used to identify changes in the brain that are consistent with PSP.

Treatment

There is no cure for PSP, and treatment primarily focuses on managing symptoms and improving the quality of life for patients. Medications such as levodopa and amantadine may provide some relief for certain symptoms, though their effectiveness varies from patient to patient. Other medications may be prescribed to address specific symptoms, such as antidepressants for mood disturbances or anticholinergics for muscle stiffness.

Physical, occupational, and speech therapies can be beneficial in managing various aspects of the disease, including mobility, communication, and swallowing difficulties. Adaptive equipment, such as walking aids and communication devices, may also be helpful for patients with PSP.

Prognosis

The progression of PSP varies among individuals, with some experiencing a more rapid decline in function than others. In general, the disease tends to progress over a period of several years, with increasing disability and dependence on caregivers. Life expectancy for individuals with PSP is typically shortened, with most patients living an average of 7-10 years after the onset of symptoms. The most common causes of death are complications related to immobility, such as pneumonia and other infections.

History

Progressive supranuclear palsy was first described in 1964 by British neurologists John Steele, John Richardson, and Jerzy Olszewski. Their initial description of the disease emphasized the characteristic eye movement abnormalities and the presence of neurofibrillary tangles in affected brain regions. Since then, researchers have continued to study the disease, seeking to better understand its underlying causes and develop more effective treatments.

Societies

There are several organizations dedicated to supporting individuals with PSP and their families, as well as promoting research into the disease. These organizations often provide resources, educational materials, and support groups for those affected by PSP, and may also advocate for increased awareness and funding for research into the disease.

See also

• Parkinson's disease
• Alzheimer's disease
• Corticobasal degeneration
• Frontotemporal dementia

External links

CurePSP PSP Association

See also

• Lytico-bodig disease (Parkinsonism-Dementia Complex of Guam)
• Annonacin

Progressive supranuclear palsy Resources
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Classification	ICD-10: G23.1 ICD-9-CM: 333.0 OMIM: 601104 MeSH: D013494 DiseasesDB: 10723
External resources	MedlinePlus: 000767 eMedicine: neuro/328 Orphanet: 683