Progressive supranuclear palsy: symptoms, treatment

Progressing supranuclear (supranuclear) paralysis is a relatively rare neurodegenerative disease of the taupathies group, also called Steele-Richardson-Olszewski's disease. Its symptoms are a consequence of accumulation in the neurons of the brain of a pathological protein. The process is irreversible and progressive, and at a significant stage a rather characteristic clinical picture is formed.

Study history

Until the middle of the XX century, this disease was not considered as an independent nosology, it was mistakenly interpreted as the consequences of the then widespread epidemic encephalitis. The fact is that a large number of cases of polymorphic postencephalitic parkinsonism masked more rare pathologies that were considered atypical forms. And in the absence of any history of any data for the neuroinfection, it was assumed that patients transferred encephalitis in an erased (subclinical) and not diagnosed form.

Progressive supranuclear palsy as an independent neuropathology was isolated in 1963-1964. a group of Canadian doctors: neurologists J. Steel and J. Richardson and pathologist J. Olszewski. They described and analyzed 7 cases of neurodegeneration with a characteristic clinical picture. In the USSR, progressive supranuclear palsy was first mentioned in 1980 by physicians of the clinic of nervous diseases of the Moscow Medical Academy named after A.Ya. THEM. Sechenov, who observed two patients.

Later the disease continued to be studied, it was identified in the domestic and world classifications as a separate nosological unit. In ICD-10, progressive supranuclear palsy refers to diseases of the nervous system (section of extrapyramidal and other impellent disorders, a subsection of other degenerative diseases of the basal ganglia), is encoded by G23.1.

Prevalence

At the heart of the disease is the progressive degeneration of neurons that arises from the accumulation of a pathological protein in them.

According to modern medical statistics, progressive supranuclear palsy causes 4-7% of cases of diagnosed parkinsonism. But even now, some patients with this disease have mistaken diagnoses, especially in the early stages. The general prevalence of progressive supranuclear palsy in the population is on the average 5 cases per 100 thousand. of the population, from 1.4 to 6.4 cases in different countries.

The disease is detected mainly in people of the older age group, even hereditarily conditioned forms usually appear at the age of 50 years.

Etiology: why this disease develops

The reasons for the development of progressive supranuclear palsy are not known reliably. This disease is not associated with any infections, traumatized or exposed to external adverse factors.

Progressing supranuclear palsy is considered a sporadic pathology (manifested in the population haphazardly). At the same time, since 1995, information on the presence of rare family cases of the disease with autosomal dominant type of inheritance has been published. This variant of the disease is associated with a heterozygous mutation of the gene encoding tau protein and located on 17q21.31.

Pathogenesis: what happens in the brain?

The development of symptoms of progressive supranuclear palsy is associated with the irreversible and steadily increasing degeneration of neurons in certain areas of the brain. This destructive process is based on the excessive intracellular accumulation of neurofibrillary glomeruli and the neuropilic threads that have lost the structure. They disrupt the functioning of neurons, promote their premature apoptosis (programmed self-destruction).

Neurofibrillary tangles in the cytoplasm of neurons of the brain are formed by a special τ-protein (tau-protein), which is in the pathological hyperphosphorylated state. Normally, it is attached to microtubules of tubulin, responsible for their polymerization and stabilization of microtubules and fixation of some intracellular enzymes.

The main functions of normal tau protein are:

1. participation in the processes of maintaining the neuronal cytoskeleton (the framework of the nerve cell);
2. formation and lengthening of axonal processes;
3. restoration of neurons after damage;
4. regulation of intracellular transport of vesicles (cytoplasmic vesicles) with synthesized neuropeptides.

Hyperphosphorylated tau protein is no longer able to retain the microtubule structure. They disintegrate, and the abnormal protein forms irregularly shaped filaments (tubules) that collect in the cytoplasm into the neurofibrillary tangles. The affected cell is disrupted biochemical contact with other neurons, the ability to form and retention of axonal connections, the cytoskeleton becomes unstable, the life span is significantly shortened. Such neurodegeneration is irreversible and progressive, gradually spreading from the characteristic primary zones to the entire brain.

Neurofibrillary tangles in neurons are formed not only with progressive supranuclear palsy. Similar degenerative changes in the brain are also found in Alzheimer's, corticobasal degeneration, frontotemporal dementia and in some other, more rare diseases. They have a number of common symptoms and are combined into a group of taupaties with parkinsonism. They are also called "parkinsonism plus" diseases, implying the mandatory presence of extrapyramidal disorders in the clinic in combination with other symptoms.

The study of various taupatii, the development of questions of their differential diagnosis and the specification of nosological criteria is a specially created Reisensburg Working Group (Reisensburg Working Group for Tauopathies With Parkinsonism).

What affects the progressing supranuclear palsy

With progressing supranuclear palsy, neurodegeneration in most cases begins in the subcortical and stem formations. The cortex of the cerebral hemispheres is initially captured to a lesser extent, but as the disease progresses, the process unfailingly spreads to it. The front sections of the cerebral hemispheres are mainly affected.

Localization of the main changes:

• black substance;
• subthalamic and peduncular nuclei;
• pale balloon;
• thalamus;
• middle brain;
• stem part of the reticular formation;
• temporal and prefrontal zones of the cortex of the cerebral hemispheres.

The primary lesion of these areas explains the characteristic sequence of the onset of symptoms and the typical parkinson-like debut of the disease. A mandatory presence of oculomotor disorders is associated with degeneration of the dorsal part of the midbrain, which leads to a separation of the centers between the gaze centers in the cortex and the brainstem. The nuclei of the cranial nerves responsible for the muscles of the eyeballs remain intact. Therefore, paralysis is called supranuclear.

Clinical picture

The tremor of rest for progressing supranuclear palsy is not typical.

All symptoms of progressive supranuclear palsy are grouped into several groups:

• Oculomotor disorders in the form of paralysis of the eye and a number of other symptoms, accompanied by retraction (lifting) of the upper eyelids with the formation of a characteristic "surprised" facial expression.
• Parkinsonism (akinetic-rigid form). Moreover, extrapyramidal disorders in the classical course of progressive supranuclear paralysis have a number of features that allow for correct differential diagnosis. Characteristic is the predominance of rigidity of the muscles of the neck and shoulder girdle with the formation of a characteristic "proud" posture, bradykinesia (slowness of movements), symmetry of disturbances even at the initial stages, early appearance of postural instability. This extrapyramidal symptomatology is not corrected by anti-Paskinsonian drugs. The tremor of rest, falls, obvious vegetative and pelvic disorders are not characteristic.
• Disorders of walking, usually by the type of subcortical astasia with pronounced influence of postural instability. At the same time, the length of the step, the area of ​​support and the initiation of movements do not initially change, friendly movements of the hands and feet are preserved. People with progressive supranuclear palsy already easily lose stability during the early stages of the disease during bends, changes in speed, jerks, walking on an inclined surface. During the first year of the disease there are falling back, and without trying to keep the balance.
• Cognitive impairment, with a fairly rapid development of dementia of the frontal-subcortical type. Speech dies, ability to abstract and generalization is lost, apathy, field behavior, low speech activity, echopraxia are characteristic.
• Pseudobulbar syndrome caused by damage to the frontal cortex and the regulatory pathways coming from it. Early development of dysarthria (fuzzy sound), dysphagia (swallowing disorders, and with a safe and even an increased pharyngeal reflex), symptoms of oral automatism, violent laughter and crying.

For progressive supranuclear palsy, illusions, hallucinatory-delusional syndrome, qualitative and quantitative disorders of consciousness, bright affective disorders are not characteristic.

There are also atypical clinical forms of progressive supranuclear palsy: with the predominance of Parkinsonism and the appearance of an asymmetric dystonia of the extremities, with a debut in the form of rapidly increasing cognitive impairment, with a predominance of primary progressive aphasia.

Oculomotor disorders with progressive supranuclear palsy

They are a mandatory manifestation of the disease and are characterized by a characteristic combination of symptoms:

• Loss of ability to arbitrarily move the eyeballs: usually initially in the horizontal and then in the vertical plane. The outcome is a complete out-palmoplergy with the inability to purposefully translate the view.
• Decrease in convergence, which already at the early stages of the disease is accompanied by complaints of blurred vision and double vision in the eyes when translating the look at disjointed objects.
• Preservation of reflex friendly movements of eyeballs.
• The appearance of the phenomenon of puppet eyes, when the eyeballs continue to involuntarily fix the object while moving the head. This is due to the lack of suppression of vestibulo-ocular syndrome. At earlier stages, the discontinuity and "lagging" of tracking by the gaze of a moving object is noted (when viewed - neurological malleus), which leads to the appearance of abrupt "catching up" movements of eyeballs.
• Gradual extinction of the amplitude and speed of arbitrary saccadic movements of eyeballs. During a neurological examination, this is revealed when checking follow-up movements, each repeated look in the extreme-lateral leads is accompanied by an increasing limitation of the mobility of the eyes (hypometry).
• Absence of spontaneous nystagmus.

A method of provoking an optokinetic nystagmus can be used, with the rotation of the striped drum in front of the patient's face. With progressive supranuclear palsy, the rapid phase of the nystagmus is initially slowed down in the vertical plane, and at later stages of the disease it is not caused at all.

The first signs of ophthalmopathy appear usually already in the early stages of the disease. Moreover, a decrease in convergence, changes in the optokinetic nystagmus, and a reduction in arbitrary vertical saccades are often detected in the absence of complaints of visual impairment in the patient. To make a presumptive diagnosis, it is necessary to have at least a limitation of the gaze downward, in combination with other signs of the neurodegenerative process.

Diagnostics

In the diagnosis of progressive supranuclear palsy, a neurological examination and a check of cognitive functions are used. Despite the presence of a large number of instrumental techniques, clinical analysis of symptoms remains the main way of diagnosing progressing supranuclear palsy.

Additional methods:

• MRI - allows to confirm the presence of cerebral atrophy in the anterior parts of the cerebral hemispheres, the cover of the midbrain. Used mainly for differential diagnosis, to exclude a number of other diseases that occur with Parkinsonism and cognitive impairment.
• EEG. It serves as an auxiliary diagnostic technique, although it is able to detect rather characteristic changes in the form of a general slowing of the rhythm with domination of D waves in the frontal or frontotemporal region.
• EMG and ENMG - with progressive supranuclear paralysis are not informative, do not reveal any specific changes, show the safety of neuromuscular transmission.
• General clinical laboratory tests of blood and urine are not informative.

Progressing supranuclear palsy must be differentiated with other diseases from the tau-patium group (corticobasal degeneration, Alzheimer's disease, frontal-temporal dementia), Parkinson's disease, multiple systemic atrophy, post-encephalitic and toxic Parkinsonism, Whipple's disease, etc.

Treatment

Treatment is exclusively symptomatic and is prescribed to the patient, taking into account the individual characteristics of the course of his illness.

Unfortunately, at the moment there are no really effective methods of cure, containment of the development of the disease or even a tangible relief of the condition. Progressing supranuclear palsy refers to chronic, steadily progressing and incurable cerebral pathologies. And the prescribed therapy is aimed at some mitigation of the symptoms.

The following are used in the treatment:

• Preparations of levodopa, in some cases up to 1500-2000 mg / day. Approximately in 50% of patients this therapy for a time somewhat facilitates the manifestation of Parkinsonism, although it is not capable of radically affecting oligoboradikinesia and gait disturbances.
• Preparations of amantadine (up to 200 mg / day). They give a temporary partial effect in about 20% of cases.
• SSRIs and SSRIs. They are prescribed by some specialists to alleviate postural instability and some other symptoms. Sometimes, antidepressants with a non-selective mechanism of action are also used.
• Medications for memantine to affect cognitive deficits.

In general, none of the drugs used and their combinations are sufficiently effective in progressing supranuclear palsy.

Forecast

Progressing supranuclear palsy is characterized by a steady progression of the neurodegenerative process and an increase in symptoms. The most disabling factor is initially postural disorders, and in more severe stages, the consequences of inactivity and swallowing disorders are becoming increasingly important. The total life expectancy after the appearance of obvious symptoms of the disease does not exceed 10-15 years, and a number of patients already in 5-7 years after the debut are actually semi-fast.

The cause of death in progressing supranuclear palsy is usually intercurrent infections, aspiration pneumonia, sleep apnea.