Progressive supranuclear palsy (PNP) or Steel-Richardson-Olszewski disease is a neurological chronic disease of a neurodegenerative nature with brain damage. At the same time, its middle section, nuclear-cortical tracts and some subcortical formations are mainly affected. The disease is part of the Parkinsonism-plus group and is detected in 4-7% of cases of this syndrome.
From the history
Until the middle of the 20th century, PNP was considered a consequence of epidemic encephalitis. But in 1963-1964. Canadian neurologists Steele and Richardson, together with the pathomorphologist Olszewski, described a hitherto unknown neurodegenerative independent disease, which was not and was not associated with previous encephalitis.
Researchers presented 7 cases of pathology that combined the presence of an akinetic-rigid manifestation of parkinsonism, pseudobulbar disorders, supranuclear ophthalmoplegia and dementia.
In the USSR, PNP was described later, only in 1980, using the example of 2 patients treated in the clinic of nervous diseases of Moscow State Medical University named after THEM. Sechenov in Moscow. The frequency of the disease, according to various sources, ranges from 1 to 6 people per 100 thousand people.
After 80 years, the indicator reaches 14.7 per 100 thousand people. This suggests that with age, the risk of pathology increases. The manifest period is manifested in pathology at the age of 55 to 70 years, men are sick 2 times more often.
PNP refers to taupathy, which also includes Peak and Alzheimer's disease, multisystem atrophy, corticobasal degeneration. Therefore, these listed pathologies have some common symptoms. All of them are united by the formation of inclusions in the neurons of the pathological protein - the tau protein. This is revealed by molecular genetic studies.
In ICD-10, progressive supranuclear palsy is assigned to the extrapyramidal and other motor disorders section, to the subsection of other degenerative diseases of the basal ganglia, encoded as G23.1.
Causes
Etiofactors, i.e. the causes of supranuclear palsy, triggering these degenerative processes, are not known reliably. The disease is sporadic, i.e. unsystematic. Supranuclear palsy does not occur after infections, injuries, stresses and other adverse moments.
After 1995, cases of familial transmission of the disease on an autosomal dominant basis were identified. What does this inheritance mean? A person receives from parents one copy of the normal gene and one changed.
This altered gene begins to dominate with the suppression of the normal gene copy. As a result, a degenerative disease develops . This gave reason to assume the genetic and hereditary nature of the disease. A photo of supranuclear palsy is presented below.
Pathogenesis
With supranuclear palsy of the brain, a 17q21 gene defect occurs. 31, which encodes a tau protein. What happens to such a protein? His selective aggregation of certain groups of brain neurons appears. These cells become non-viable, the program of their degradation and apoptosis (programmed death) is launched. Cell degradation primarily affects the midbrain, dentate cerebellar nuclei, subcortical structures located between the cortex and the medulla oblongata. They participate in the formation of motor reactions. These basal nuclei include: black nucleus, pale ball, thalamus, RES, etc. The bark is less affected.
The pathomorphology of supranuclear palsy of the brain under a microscope shows that neurofibrillary glomeruli form in these neurons. Macroscopically, the midbrain decreases in size: first sagittal, and later others. This indicates his atrophy. Degeneration of the midbrain tire (its dorsal part) leads to the fact that the connections between the neurons of the center of the eye in the cortex and the stem part of the brain are destroyed. The very nuclei of FMN, responsible for the work of the oculomotor muscles, are not affected.
Thus, oculomotor disorders in the clinic are mandatory and appear among the first. In turn, atrophy of the midbrain also causes degeneration of the cortical-nuclear pathways - hence the appearance of pseudobulbar disorders (swallowing and articulation disorders). Studies show a reduced concentration of dopamine, which underlies parkinsonism.
The development of symptoms of progressive supranuclear paralysis is increasing because the degeneration of neurons in these parts of the central nervous system has an irreversible and progressive character. The neurofibrillary tangles mentioned above in the cytoplasm of neurons are formed by the t-protein (tau protein), which from its normal state passes into the pathological state of hyperphosphorylation.
What is this protein for? Its main functions include:
- Maintaining the skeleton of a nerve cell, the so-called cytoskeleton of a neuron.
- The formation and growth of axonal processes that serve to transmit impulses.
- Participation in the restoration of damaged neurons.
- The protein also regulates the transport of cytoplasmic vesicles with synthesized neuropeptides inside the cells.
When a tau protein is violated, the protein functions are violated, as a result, the affected neuron loses its biochemical connection with other neurons, and new connections and their retention are also impossible. The cytoskeleton is destabilized, its lifespan drops sharply. Over time, such neurodegradation begins to spread to other parts of the brain.
Symptoms of PUP
Supranuclear cerebral palsy makes its debut later than Parkinson's disease itself, at the age of the patient from 55 to 70 years. Progressive supranuclear paralysis of an early period manifests itself as fast unusual fatigue, decreased working capacity, cephalalgia, dizziness, narrowing of the circle of interests, which becomes too commonplace.
Sleep disturbances occur - insomnia at night and drowsiness during the day. Within a few years, specific symptoms become:
- in 60% of cases - postural instability with frequent falls;
- dysarthria (33%),
- bradykinesia (13%),
- ophthalmoparesis (13%).
Symptom Grouping
Thus, all manifestations of supranuclear palsy can be grouped:
- Oculomotor disorders - they appear in the form of paralysis of the gaze, accompanied by a rise in the upper eyelids (retraction) and the patient has a forever surprised look or even an amazed facial expression.
- The appearance of parkinsonism (akinetic-rigid form). Its manifestations in PNP have their own peculiarities: the stiff muscles of the neck and shoulder girdle prevail, which makes the posture more characteristic of pride. This does not pass without a trace - patients often complain of stiffness in the neck and back; oligobradikinesia appears (slow movement); from the very beginning, all violations are symmetrical.
- Postural instability appears early (balance becomes difficult to maintain in a certain position or when changing it). All these pathological symptoms do not respond at all to the use of anti-Parkinsonian drugs.
- Also, unlike the most tremulous paralysis, with PUP, tremor does not occur, there are no obvious autonomic and pelvic disorders.
- Disorders of walking according to the type of subcortical astasia (loss of ability to stand). Patients, therefore, already in the early stages of the disease suddenly lose their ability to hold steady when cornering, changing their speed of movement, aftershocks or walking downhill. The result is a fall back, and the patient cannot make attempts to maintain balance. This is characteristic in the first year of the disease. At the same time, the area of the support, the stride length, the friendliness of the movements of the arms and legs of the movements do not change immediately, they have been preserved for a long time.
- Cognitive impairment is characteristic, in which lesions of the fronto-subcortical zone lead to the rapid development of dementia. They are manifested in the impoverishment of speech, abstract and generalize to the patient becomes inaccessible. Apathy, isolation, speech activity become characteristic, echopraxia (involuntary repetition of the movements and postures of the people around him) appears, and field behavior. What it is? In field behavior, a person’s actions are not dictated by his needs and goals, but by random emotions and stimuli of the external environment. A man becomes a puppet for any external circumstances: he was called - he went, they showed him - he was carried away, he was hurt - he started up, etc.
- Pseudobulbar syndrome is also the result of damage to the cerebral cortex in the frontal region and its pathways. It is considered a fairly early manifestation of supranuclear palsy of the brain. There is a fuzzy pronunciation of words due to fuzzy sounds (dysarthria), swallowing (dysphagia) is impaired. But the pharyngeal reflex itself is fully preserved. But nonsense and hallucinations, illusions, affective disturbances and impaired consciousness are uncharacteristic.
- Parkinson's ataxia (partial or complete loss of coordination of voluntary muscle movements) is characteristic. It occurs due to impaired coordination of the position of the trunk and legs relative to the center of gravity. The patient cannot coordinate the movements of his body and legs with his center of gravity correctly, which leads to frequent falls back.
- A distinctive feature of progressive supranuclear palsy is ophthalmoplegia, which develops after the onset of pathology within 2-3 years. Eyeballs begin to move slowly, and gaze paralysis occurs in a vertical plane, as a result of which the patient cannot look down. Progressive supranuclear palsy of the gaze, i.e. Ophthalmoparesis is manifested not only by the fact that restrictions arise when looking down, but also later already up. Later, over time, oculomotor disorders develop in the horizontal plane. Blinking becomes rare, because of this, patients complain of a burning sensation and discomfort in the eyes. Often, all this is accompanied by blurry vision, blepharospasm and impaired convergence. The development of the phenomenon of puppet eyes is characteristic, when with any movements of the head the gaze is fixed only in the midline. It is preceded by a discontinuity and “lagging” of the gaze when tracking a moving object (during examination, a neurological hammer), which makes it possible for a neurologist to see jump-like “catching up” movements of eyeballs. The amplitude and speed of saccadic eye movements decreases.
When examined by a neurologist in a patient with movements of the malleus in the extreme lateral leads, each subsequent eye movement is difficult for the patient, eye mobility is limited (hypometry).
Cognitive function
They are violated in PNP in such a way that already 60% of patients develop dementia. In 30% of cases, such violations generally become the first sign of PUP. The severity of cognitive impairment may prevail over the severity of motor impairment. But in 20% of patients it is moderately impaired even when the patient is already bedridden. Fewer cognitive impairments affect memory. It usually breaks fast, i.e. short-term memory - for current events. Long-term remains quite intact.
Of the types of memory, visual disturbance is more impaired, auditory-speech suffers less. Along with impaired memory, attention, criticism and behavior are simultaneously violated.
Understanding of speech is not impaired. Depression is rare. The progression of the pathology occurs much faster, as a result of which the patient is already bedridden by 4-5 years of illness.
Complications
Since coordination of movements is broken and falls become frequent, bruises and fractures are possible with them. As the pathology progresses, the oligobradikinetic syndrome puts the patient bedridden after several years.
If there is no proper care, in such patients all the delights of bed rest develop - bedsores, joint contractures, congestive pneumonia. In such patients, night apnea often occurs, which can lead to death in a dream.
In connection with a decrease in immunity, it is not uncommon for intercurrent diseases and infections to join - pneumonia, cystitis, pyelonephritis, which becomes a serious complication for the patient. There is a high risk of sepsis in this regard.
With the progression of paralysis, choking appears and food aspiration is possible. As a result, the patient is depleted. Life expectancy usually does not exceed 10 years.
Diagnostics
The diagnosis of progressive supranuclear palsy (supranuclear) is made according to clinical data, even in the presence of many instrumental techniques. When diagnosing, a neurologist examination and a study of cognitive functions are mandatory. When consulting a neurologist, the following will be revealed: symmetric oligobradikinesia is the leading syndrome. Weakening of facial expressions is also noted, the installation of the neck becomes pathological - retrocollis - proud posture, vertical gaze paralysis, tendon reflexes are increased. Necessarily present postural instability.
Used informative additional techniques
MRI with progressive supranuclear palsy - allows you to confirm the presence of cerebral atrophy in the anterior sections of the cerebral hemispheres, midbrain and frontal region. Also, MRI will help differentiate a brain tumor, ALS, encephalitis, stroke, which can also be accompanied by parkinsonism and cognitive impairment.
EEG - with PNP, the rhythm of brain waves is slowed down with the dominance of D-waves in the frontal or frontotemporal region. Standard blood and urine tests are not carried out due to their lack of information.
The likely early criteria for progressive supranuclear palsy for doctors are:
- the disease begins after 40 years;
- pathology is progressive from the very beginning, later its irreversibility is also revealed;
- ophthalmoparesis;
- postural instability with falls.
For making a final diagnosis, histologically confirmed pathognomonic changes in the brain tissue with PNP can play a role.
Neuropsychological testing is also necessary. It is carried out by such narrow specialists as a psychiatrist, neuropsychologist who use special tests in their work (MMSE scales, clock drawing test). This study reveals a degree of cognitive impairment. Supranuclear paralysis is characterized by inhibition of thinking, increased exhaustion as in any organic. Intellectual disorders are moderate.
PUP treatment
Effective treatments that could reverse the process of degeneration have not been found to date. Only symptomatic treatment of supranuclear paralysis is carried out, mitigating the symptoms, which somewhat alleviates the patient's condition.
In the treatment of cognitive impairment, it is possible to use neurotropes - memantine, AChE inhibitors. To improve the state of the emotional sphere, activating antidepressants are used (Fluoxetine, Paroxetine).
In the treatment of progressive supranuclear palsy, amantadine preparations (up to 200 mg / day) are also used to improve cognitive function. They give a temporary partial effect in only 20% of patients.
Antidepressants such as SSRIs and SSRIs (reuptake of serotonin) - some neurologists believe that this group of drugs alleviates postural instability and some other symptoms. But it is impossible to use them for proper treatment, there is no effect with PUP.
Most neurologists consider the use of dopamine at the very beginning of treatment to be a necessary type of treatment for progressive supranuclear palsy - this refers to the appointment of levodopa.
In half of the patients in this case, indeed, the condition is relieved in a certain way. Levodopa drugs are prescribed in some cases at a dose of up to 2 grams per day. What is facilitated? Manifestations of parkinsonism, but there is no radical change in oligobradikinesia and gait disorders. Even the best effect lasts no more than 2 years.
Antiparkinsonian pharmaceuticals of other groups (MAO inhibitors, dopaminomimetics, COMT inhibitors) are not effective in the treatment of PNP.
Forecast
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Actual bed rest occurs within 5-7 years. A fatal outcome with progressive supranuclear paralysis occurs due to the addition of intercurrent diseases, which is quite explainable by a prolonged bed rest. It can be infections, aspiration pneumonia, kidney disease, etc.
The most disabling factor is postural disorders, and later, during bed rest, such consequences of inactivity as bedsores and dysphagia increase.
Prevention
As such, it does not exist - simply due to the lack of a revealed etiology and clear pathogenesis of the disease. Today, the disease and its treatment are under study.