Progressive supranuclear palsy: symptoms, treatment, prognosis

What is progressive supranuclear palsy?

Progressive supranuclear palsy (Tnp or also called progressive supranuclear paresis of the gaze or Steele-Richardson-Olshevsky syndrome) Is an unusual degenerative neurological disease that causes progressive imbalance and imbalance in walking; violation of eye movement, especially in the downward direction; Abnormal muscle tone (muscle stiffness) speech problems (dysarthria); and problems with swallowing and eating (dysphagia).

Patients often experience personality changes and cognitive impairments. Symptoms usually appear after age 60, but may appear earlier. The exact cause of progressive supranuclear palsy is unknown. PUP is often mistaken for Parkinson's disease, Alzheimer's disease, corticobasal degeneration and other neurodegenerative disorders.

Dr. John C. Steele, J. TO. Richardson and J. Olszewski identified progressive supranuclear palsy as a distinct neurological disorder in 1963. Hence the second name, Steele-Richardson-Olshevsky syndrome.

Signs and symptoms

The signs and symptoms of progressive supranuclear palsy vary from person to person, but patients usually fall into one in four clinical syndromes (phenotypes): Richardson's syndrome, atypical parkinsonism, corticobasal syndrome and pure akinesia with freezing gait. Less commonly, patients have cognitive impairment and lack of motor signs.

The most common manifestation is Richardson syndromewhich includes impaired gait and balance, wide-eyed facial expressions, abnormal speech, memory impairment, and cognitive functions, as well as slowing down or loss of voluntary eye movement, especially in the downward direction (supranuclear ophthalmoplegia). Cognitive symptoms include forgetfulness and personality changes such as loss of interest in previously enjoyable activities, impaired attention and concentration, depression and increased irritability.

Less than half of all PSP patients are initially diagnosed correctly because many patients do not have classic Richardson's syndrome. Many of these patients are initially sluggish, have muscle rigidity, and sometimes tremorresembling Parkinson's diseaseand they may initially respond somewhat to the antiparkinsonian drug, levodopa. Other patients have unusual rigidity (stiffness and dystonia) and loss of voluntary function in one upper limb, as seen in corticobasal degeneration. Rarely, patients show primary akinesia syndrome with freezing gait. These patients show an uncertain gait start and a tendency to freeze or stop when cornering and crossing thresholds (doorways). Their eye movements and cognitive sensations are normal.

Small handwriting and low-volume, fast, mumbled speech (tachyphemia or incoherent speech) is typical and similar to that which occurs with Parkinson's disease, but unlike Parkinson's disease, there is no slowness (bradykinesia) or muscle stiffness (rigidity).

Finally, some patients with PNP have cognitive impairments that resemble Alzheimer's disease or frontotemporal dementia. Most patients with atypical manifestations eventually develop problems with eye movement, speech, swallowing, and gait (Richardson syndrome) after a few years. Thus, the diagnosis of PNP usually becomes more reliable as the disease progresses.

The impaired eye movement ultimately makes reading, driving, and interpersonal eye contact difficult or impossible. Improper eyelid control causes the eyes to involuntarily close (blepharospasm) for a few seconds or more, and some affected people may be unable to open their eyes (oculomotor apraxia) even when the spasm stops. Other patients have trouble closing their eyes or blink less than usual, resulting in dry, red eyes.

The muscles in the body can involuntarily contract, causing the affected body part (such as the upper or lower limbs) to assume strange postures. This is called dystonia. Blepharospasm is a form of dystonia that affects the muscles around the eyes.

Mild to moderate mental distress eventually occurs in most patients and can be misdiagnosed as Alzheimer's disease (AD), if it occurs at an early stage of the disease, before significant difficulties with speech, coordination and movement appear eye.

Some patients experience sleep disturbances such as frequent awakenings and changes in sleep patterns. Sleep disturbances can be a sign of depression or a side effect of medications. REM sleep behavior disorder (REM) is not a symptom of PSP, but is sign of dementia with Lewy bodies, Parkinson's disease and multiple systemic atrophy. In REM sleep behavior disorder, patients talk and move during sleep, and this movement can result in injury to the person or injury to the bed partner.

Causes and risk factors

The cause of progressive supranuclear palsy is unknown, but it is a form of taupathy (i.e., a neurodegenerative disease associated with abnormal adhesion of tau protein to called neurofibrillary tangles in brain tissue), in which abnormal phosphorylation of tau protein leads to the destruction of vital protein filaments in nerve cells, causing their death. Recent work suggests that the disease is at least partially genetic. Many researchers now believe that various genetic and environmental factors contribute to the development of this disorder.

In the medical literature, the word "taupathies" is used to refer to several neurodegenerative diseases, including ANP, in which tau is not properly processed. Other neurodegenerative disorders classified as taupathies include corticobasal degeneration and Pick's disease.

Patients with a family history of PNP are very rare, and the underlying genetic abnormality is generally unknown in these families. Some cases of PNP are associated with a mutation or genetic variation in a gene MAPT, which helps to produce (encodes) tau protein. This gene is located on chromosome 17 (17q21.1). Variants of at least three other genes (STX6, EIF2AK3 and MOBP) are associated with an increased risk of developing PNP. The study of genetic mechanisms should ultimately lead to effective medical treatments.

Affected populations

PNP is an underdiagnosed disease, so it is difficult to determine how many people have it. It is estimated that about 20,000 people are affected by the disorder in the United States alone. However, far fewer cases have been diagnosed. According to some reports, up to 5 people out of 100,000 suffer from PNP. The onset of this disorder is between 45 and 75 years of age, with an average age of onset about 63 years. Men get sick more often than women.

Symptomatic disorders

Symptoms of the following conditions may be similar to those of progressive supranuclear palsy (PNP). Comparisons can be useful for differential diagnosis.

• Corticobasal degeneration (CBD) is a rare progressive neurological disease characterized by the loss and shrinkage (atrophy) of cells in certain areas of the brain (cerebral cortex and basal ganglia). The symptoms and signs of this disease are reminiscent of some PNP patients, and some experts believe that CBD and PNP are variations of the same disease. Both are taupathies.
• Multiple systemic atrophy (MCA) is a rare progressive neurological disease characterized by a variable combination of parkinsonism and cerebellar ataxia (poorly coordinated limb movement, unsteady gait and dysarthria). Many patients with MSA also develop a dysfunction of the autonomic nervous system, which controls blood pressure, heart rate, sweating, bowel and urinary bubble. The exact cause of multiple systemic atrophy is unknown.
• Shy-Drager Syndrome - a subtype of multiple systemic atrophy with autonomic failure. Most experts no longer use this term.
• Parkinson's disease - a slowly progressive neurological condition characterized by involuntary tremors (resting tremor), muscle stiffness or stiffness, slow movement (bradykinesia), and difficulty performing voluntary movements (akinesia). Degenerative changes occur in areas deep within the brain (substantia nigra and other pigmented areas of the brain), causing a decrease in dopamine levels in the brain. Dopamine is a neurotransmitter, a chemical that sends a signal from one nerve cell to another in the brain. Parkinson's disease progresses much more slowly than PNP, and usually does not lead to disability for ten years or more.

Diagnostics

The diagnosis of progressive supranuclear palsy can be suspected on the basis of careful clinical evaluation, a detailed history of the patient, and identification of characteristic physical signs.

Standard treatments

Treatment of progressive supranuclear palsy is symptomatic and supportive. There is currently no cure. In some cases, drugs used to treat Parkinson's disease (antiparkinsonian drugs) such as levodopa may have some benefit in relieving congestion symptoms, but the effect is usually limited and temporary. In some cases, antidepressants may be helpful. The use of these drugs should be closely monitored by a neurologist experienced in their use.

Walking aids, such as forward weighted walkers and knurled shoes, can help prevent the victim from falling backwards. Bifocals or special glasses with prisms may be prescribed for some people with PNP to treat certain vision problems (for example, difficulty looking down). Botulinum toxin injections help with blepharospasm.

When the patient can no longer swallow, a surgical procedure known as percutaneous gastrostomy may be performed, depending on the patient's desires and quality of life. During the procedure, a tube is inserted through the skin of the abdomen into the stomach to provide nutrition.

Forecast

Patients with PNP tend to have progressive deterioration, with a median survival of 9.7 years from the onset of symptoms. Gait disorders occur early and patients need help for 3 years. Bed rest or a wheelchair is usually needed for 8 years.