Treatment of hand tremors in Parkinson's. Tremor. Typical parkinsonian tremor. The main enemy of Parkinson's disease

Introduction

Every person has heard about such a disease as Parkinson's disease. Many people think that you can only get it in old age. In this article we will consider this issue in more detail, as well as the symptoms of the disease, treatment methods and the first signs.

Parkinson's disease, what is it?

Parkinson's disease is a degenerative change that occurs in the nervous system. Gradually, at a slow speed, they progress, and the symptoms appear more clearly. There is a destruction of neurons that are responsible for the production of the neurotransmitter - dopamine. This leads to muscle rigidity, tremors of the limbs, and impaired coordination of movements. This disease is also called “shaking paralysis.” Statistics show that every hundred elderly people suffer from parkinsonism. It is more often registered in men than in women. The reasons for its appearance are not fully known.

How does Parkinson's syndrome manifest?

The first manifestations are not associated with a disorder of motor coordination and may appear several years before the onset of the disease itself. These include:

  • Hyposmia.
    • This is a disturbance in the sense of smell, a very common symptom in Parkinson's patients.
  • Depression.
    • May be accompanied by anxiety and apathy.
  • Constipation.
  • Various sleep disorders.
    • A person behaves restlessly in his sleep, screams, and involuntarily jerks his limbs.
  • Urinary disorders.
  • Fast fatiguability.
  • Changing handwriting.
  • Facial muscle stiffness
    • The patient blinks slowly, speech becomes unintelligible and the face looks like a mask.

The first signs of the disorder appear in various areas of brain activity. This can be explained by the fact that while the pathological process “gets” to the substantia nigra, it destroys other structures on its way.

For a long time, a person may not pay attention to the first manifestations and attribute them to natural processes. A long period of time must pass before symptoms become apparent. These include:

  • Tremor of the limbs.
    • It appears even when a person is at rest. There may be postural or intention tremor.
  • Trembling of the eyelids and jaw.
  • Muscle stiffness.
    • The muscles are in a state of tension. The back is stooped, the limbs are bent at the joints. The patient experiences muscle pain syndrome.
  • Hypokinesia.
    • Characteristic of any form of the disease. Movements are slow and their number is minimal. The speed of action decreases.
  • Postural disorders.
    • A person often stumbles and falls, and their gait is disturbed. It's hard to maintain your center of gravity.
  • Salivation.
    • The volume of secretions from the salivary glands increases, this makes speech difficult and becomes unintelligible. There are problems with swallowing.
  • Dementia.
    • Intellectual abilities and memory decrease, attention is scattered. A person has difficulty learning new things. Personality changes may occur.
  • Impotence.

Manifestation of the disease at a young age

The idea that Parkinson's syndrome is characteristic only of older people is erroneous. There are cases when the disease occurs in young people aged 20-45 years, and is called early parkinsonism. Of the total number of registered cases, early parkinsonism accounts for 10%. Symptoms are unusual, which makes diagnosing the disease difficult.

Genetic factors coupled with external ones have a great influence on the possibility of manifestation. Not only the neurons responsible for movement are affected, but also other parts of the brain, so at a young age the disease manifests itself not only as motor disorders.

In young people, the disease has a sluggish, mild development. In old age, the disease develops more rapidly. The presence of chronic diseases and general health also affects the course of the process.

Atypical symptoms include:

  • Dystonia is painful contractions of the muscles of the limbs. A doctor may confuse such manifestations with arthritis of the joints, which makes diagnosis much more difficult.
  • Dyskinesia - involuntary twitching and movements of the limbs, can occur due to taking dopamine-containing medications.

The most common classification of disease stages is that proposed by Hoehn and Yahr in 1967. There are five stages in total. Each of them describes the severity of the disease. Take a closer look.

Zero stage

The disease has already begun to develop, but has not yet revealed itself, but is already destroying certain areas of the brain. This may manifest itself in minor forgetfulness or absent-mindedness. The perception of smells changes slightly.

First stage

Signs appear on one side of the body. Extremities on the left or right are affected. The arms and legs tremble barely noticeably, the tremor increases with stress and nervous tension. You can notice some changes in a person’s gestures, speech, and posture.

Second stage

Other parts of the body are also affected, and postural instability appears slightly. Symptoms such as impaired coordination of movements, impaired balance develop, and it is difficult for the patient to withstand physical activity.

Third stage

It is characterized by moderate postural instability, but the person is still able to cope without outside help.

Fourth stage

The patient is no longer able to cope with his needs on his own. Special medical care or help from relatives is required. Motor activity is lost, the person cannot walk or stand without support.

Fifth stage

The patient is bedridden.

How quickly does Parkinson's disease progress?

The rate of development of the disease depends on the age at which it appeared, the environment, and the level of medical care. On average, in people who become ill at a young age, the disease develops within 30-40 years. In patients of forty years of age - 20 years, and in older people - 5-7 years. In a quarter of cases, during the first five years of development of the disease, disability may occur, and then death. Almost 100% of people suffering from the disease for 15 years or more experience severe disability and inevitable death.

Is Parkinson's disease curable?

No, it is not yet possible to completely cure the disease. However, there are a large number of medications aimed at slowing down development processes and improving motor functions. People can be capable for a long time and not be bedridden.

How to reduce tremors in Parkinson's disease?

It is impossible to completely cure tremor, but there are options to reduce its symptoms and restore the patient's daily activities. The following drugs are used:

Adrenoreceptor antagonists

They are very often used and have a strong effect due to their effect on P2 receptors of peripheral muscle spindles. Not recommended for patients with heart failure and diabetes. Do not cause side effects from the central nervous system.

Primidon

Special anticonvulsant. Side effects include drowsiness. Prescribed in small doses of 25 mg and gradually increased to 50 mg. Should be taken at night.

Carbonic anhydrase inhibitors

They are successfully used to correct tremor, sometimes causing side effects such as paresthesia and changes in taste.

Benzodiazepines

They are used when other medications do not give the desired results. They bring slight relief, but do not eliminate the tremor completely. The most famous of them are Clonazepam (long-acting) and Xanax (short-acting).

Surgery

An extreme measure when tremor cannot be treated with conservative methods and greatly interferes with the patient’s existence. An effective method is stereotactic thalamotomy. It is performed unilaterally and significantly reduces symptoms in the contralateral limbs.

Postural disorders in Parkinson's disease

The ability to maintain body balance in various poses is one of the most important features of the locomotor system. Maintaining a person’s vertical state is a very complex process that involves not only the musculoskeletal system, but also the central nervous system, vestibular, and visual. In PD, dopaminergic neurons are destroyed, which leads to coordination problems, loss of balance, and other postural disturbances. Changes in postural functions have not been fully studied, but they are currently considered one of the main symptoms of PD, along with tremor, rigidity and hypokinesia.

Postural disturbances appear in the last stages of the disease. Reflexes are impaired, weakened or completely absent. The degree of severity can be assessed by the number of falls per day, freezing syndrome and its frequency, the presence of propulsions, imbalance and stability, and the ability to overcome retropulsion. Correcting the posture does not produce significant results.

Gait changes

One of the most striking symptoms of PD is gait disturbance. As it changes, the severity of the patient's condition can be determined. Degradation of motor functions is an independent manifestation of the disease. Initially, walking speed decreases and step size decreases. The gait takes on a shuffling character. The man almost never lifts his feet off the floor. The step is mincing. If the patient is in a hurry, he increases his walking speed, but cannot increase his step length. The cervical spine suffers, this forms a hunched posture and subsequently kyphosis. When moving, the body leans forward. It is difficult for a person to maintain his center of gravity; he may suddenly freeze while walking. Hardening can be lengthy. Propulsion, leteropulsion and retropulsion are observed. In later stages, the patient is unable to balance, which leads to frequent falls.

How to improve the patient's condition?

If Parkinson's disease has been diagnosed, this means that the doctor will immediately prescribe medications. The rate of development of the disease, its duration, severity, stage, and chronic diseases in the patient’s history are established. Not the most powerful drugs are prescribed - Selegiline and Pramipexole. For the initial stage they will be quite sufficient. In addition, physiotherapy, a special diet and physical therapy are recommended.

In recent years, the high effectiveness of the drug Levodopa has been noted. Its active substances are converted into dopamine in the brain. This allows you to reduce tremors, relax muscles, and improve motor activity. With timely administration of the drug, even partially immobilized patients gain the ability to move normally. Unfortunately, after 5 years of constant use of this drug, it becomes ineffective. The patient may lose control of movements. Dosing does not restore previous activity.

Surgery is performed very rarely, in cases where the patient does not respond to drug therapy.

Even with the highest quality treatment, the disease will progress inexorably. Therefore, relatives and friends should inquire in advance where they can obtain specialized skills for caring for the patient.

Parkinson's disease leads to serious consequences, for example:

  • Akinesia.
    • Immobility occurs in the later stages.
  • Frequent constipation.
    • It is associated with the impossibility of normal consumption of food and water, which leads to malfunctions of the gastrointestinal tract. There are cases where constipation led to death.
  • Inflammation of the eyes.
    • Due to Parkinson's disease, the number of blinking movements is reduced, which leads to conjunctivitis and inflammation.
  • Seborrhea.
    • Increased sebum production, resulting in various inflammations.
  • Dementia.
    • Disorders of memory, intellectual abilities, personality changes. The patient is prone to depression and apathy.

Swallowing disorders

One of the unpleasant symptoms of parkinsonism is dysfunction of the pharyngeal muscles. Food falls out of a person's mouth, or vice versa falls into the esophagus. The patient does not control the swallowing process and drool remains in the mouth.

The main inconveniences include:

  • eating slowly;
  • food gets stuck in the throat;
  • food accumulates in the mouth;
  • cough while eating;
  • difficult to swallow tablets;
  • dry mouth.

These symptoms can be alleviated by:

  • sit up straight while eating;
  • eat in small portions;
  • repeat swallowing movements until all food is swallowed;
  • do not rush;
  • after eating, you need to sit upright for half an hour;
  • keep your lips closed.

Treatment of Parkinson's syndrome with high doses of vitamin D

Everyone knows, and we have already discussed above, that Parkinson’s disease cannot be completely cured. But it can and should be treated, i.e. maintain the patient’s normal condition throughout his life. Such a method exists. And no matter how simple it may sound, the treatment consists of taking vitamin D. Yes, yes, that’s right, just vitamin D. But in fact, not only vitamin D.

There is such a wonderful doctor in Brazil - Cicero Galli Coimbra. This is a scientist, neurologist, professor. It was he who, many years ago, developed a method for treating autoimmune diseases with high doses of vitamin D, which is called the “Coimbra Protocol”. Parkinson's disease is an autoimmune disease that is also treatable. The essence of the protocol is taking high doses of vitamin D (from 30,000 IU) per day. In addition to vitamin D, the doctor prescribes a number of supplements after examining the test results. The patient must follow a diet (no dairy products), as well as plenty of hydration (at least 2.5 liters of fluid per day).

Attention!!! Self-medication is not allowed!!! All treatment should ONLY be carried out under the guidance of a doctor who has been officially trained by a professor in Brazil and has received a certificate.

Conclusion

In conclusion, we can say that PD is not only a disease of old age, but also manifests itself at an early age. There are not many such cases, but they do exist. The main symptoms include tremors, changes in gait and muscle rigidity. It cannot be completely cured and over time the patient ceases to be capable. There are medications and surgical operations that will help slow down the destructive processes and ensure a comfortable existence for as long as possible.

RELEVANCE OF THE PROBLEM

According to epidemiological studies:
in 10-20% Parkinson's disease remains unrecognized
in 25% of cases the opposite trend occurs - a false positive diagnosis of Parkinson's disease

The situation is getting more complicated because there are rare cases where two diseases (Parkinson's disease and essential tremor) develop sequentially in the same patient. In most of these observations, diagnosis does not present any particular difficulties, although exceptions are possible here, which are extremely difficult to interpret.

These errors are in the form hypo- And overdiagnosis Parkinson's disease is largely (but not exclusively) associated with difficulties in diagnosing the shaking form of the disease.

As a rule, errors in diagnosing Parkinson's disease arise from stage of syndromic diagnosis parkinsonism. Although diagnostic criteria have now been developed not only for Parkinson's disease, but also for parkinsonism syndrome in general, the latter, unlike the former, for objective reasons are not as effective and do not guarantee adequate recognition of parkinsonism.

!!! A syndromic diagnosis, if incorrect, cancels out all subsequent diagnostic efforts and therefore predetermines erroneous diagnosis, that is, unrecognized Parkinson's disease or, conversely, its overdiagnosis.

Parkinsonism, including notebook known symptoms (hypokinesia, tremors, rigidity and postural disturbances), is easily recognized when all four of its constituent clinical manifestations are present, which is typical for the advanced stage of Parkinson's disease.

!!! At the early stage of this disease, all four parkinsonian symptoms may not be present, and then the likelihood of recognizing parkinsonism is significantly reduced.

It is believed that at least two symptoms are sufficient to correctly make a syndromic diagnosis:
according to accepted criteria, the only mandatory symptom should be hypokinesia, without which parkinsonism does not exist
in addition to hypokinesia, for diagnosing parkinsonism syndrome the presence in the clinical picture of at least one more parkinsonian symptom, any of the other three, is sufficient: muscle rigidity, resting tremors or postural disturbances

However, these three characteristic components of parkinsonian syndrome have different diagnostic value:
muscle rigidity usually accompanied by hypokinesia (akinetic-rigid syndrome)
tremor is common in Parkinson's disease, however it may be absent in approximately 20% of cases of this disease
postural disturbances least specific for Parkinson's disease and found in many other diseases

In the trembling form of Parkinson's disease, tremor is the first symptom noticed by the patient and doctor, A hypokinesia can be expressed so slightly that it remains “invisible” not only for the patient, but also for the doctor aimed at identifying it. In such cases, a clinical diagnosis of parkinsonism syndrome formally becomes impossible, but suspicion of parkinsonism should always be present, especially when the trembling has the characteristic features that will be listed below. Analysis of these features or characteristics of tremor becomes of fundamental importance for adequate diagnosis of the etiology of tremor.

Considering the above, consider the following questions:
(1)Principles of clinical assessment of tremor
(2)differential diagnosis of Parkinson's disease and essential tremor
(3) the possibilities of drug correction of tremor in the context of complex therapy of these diseases

PRINCIPLES OF CLINICAL EVALUATION OF TREMOR (1)

Clinical assessment of the characteristics of trembling begins with determining its type, which can be presented in the form of one of three known options:
rest tremor
postural remora
intention tremor

!!! The first type of tremor is typical for Parkinson's disease - resting tremor.

It is no coincidence that resting tremor, in contrast to other types of tremor, is called parkinsonian. But in clinical practice, sometimes there are cases of the trembling form of Parkinson’s disease, in which the trembling does not show typical Parkinsonian features, which does not make it easy to recognize its Parkinsonian nature.

Such cases include:
the earliest stages of Parkinson's disease, when the tremor is episodic and there may be no tremor during the patient's visit to the doctor (the so-called prodromal tremor)
a sometimes occurring tremor form of parkinsonism, in which the tremor is represented by an isolated postural tremor
tremor in the form of equally pronounced postural tremors and resting tremor without a noticeable predominance of one or another component
monosymptomatic resting tremor, when there are no other manifestations of parkinsonism
hypokinesia, rigidity and postural disturbances

Diagnostic difficulties increase if these features of tremor are detected in old age.

DIFFERENTIAL DIAGNOSIS OF PARKINSON'S DISEASE AND ESSENTIAL TREMOR (2)

The most common conditions known to cause tremors are Parkinson's disease and essential tremor. Their differential diagnosis can be difficult and fraught with diagnostic errors.

Methods for differential diagnosis of essential tremor and the shaking form of Parkinson's disease include:
in-depth clinical assessment
sometimes pharmacological tests
electromyographic study
accelerometry
neuroimaging, in particular the DaTSCAN method

To identify clinical differences between tremor in Parkinson's disease and essential tremor, it is advisable to take into account:
type of tremor
correlation of different types of tremor
pay attention to some important features of postural and kinetic tremor
assess syndromic environment
opening features
course of the disease
possible effect of alcohol

"Diagnostic antinomies":
For Parkinson's disease resting tremor is typical essential tremor– postural or postural-kinetic tremors.
At Parkinson's disease As the disease progresses, there is a tendency towards generalization of tremor with an asymmetrical “hemitype” distribution, with essential tremor The spatial coordinates of bilateral tremor in typical cases look different: the tremor is distributed predominantly in the upper part of the body (arms-head or head-arms).
At Parkinson's disease, if all types of tremor are detected simultaneously, the following ratio is typical: resting tremor then postural tremors then intention tremor. With typical essential tremor other relationships: postural tremor then intentional tremors then rest tremor.
Postural trembling when essential tremor manifests itself immediately from the moment the postural load begins, with Parkinson's disease it may appear after an initial delay (so-called re-emergent tremor).
Kinetic tremor at Parkinson's disease during the finger-nose test, the amplitude decreases significantly compared to the initial position (arms extended forward), whereas during essential tremor trembling increases significantly during movement and decreases in the starting position.

The main diagnostic difficulties arise in older patients with pronounced postural tremor and resting tremor of smaller amplitude, which occurs both in essential tremor and in Parkinson's disease.

The index of the ratio of the amplitude of postural tremor to the amplitude of kinetic tremor acquires a certain diagnostic significance here: it differs significantly in these groups:
0.1 for essential tremor
1.5 for Parkinson's disease

Syndromic environment
when essential tremor usually quite scanty, sometimes it manifests itself as a uniform decrease in muscle tone - writer's cramp syndrome
at Parkinson's disease the syndromic environment is manifested by constipation, a tendency to increase muscle tone - primarily in the neck muscles, impaired sense of smell, nocturnal or selective hypokinesia
Essential tremor usually develops at a younger age, progresses much more slowly and is characterized by more intact adaptation in daily activities and household self-care compared to Parkinson's disease.
Alcohol has a more pronounced anti-tremor effect when essential tremor than with Parkinson's disease.

Pharmacological loads
Pharmacological loads have limited diagnostic value(levodopa, dopamine agonists pronoran, pramipexole and rasagiline). Effect of levodopa becomes clinically noticeable in the case of parkinsonian tremor and is absent if the tremor is of an essential nature - then this pharmacological load acquires a certain diagnostic weight.
b-Adrenergic blockers They show a therapeutic effect in the case of kinetic and postural tremor in both diseases and are less effective in resting tremor, so they are not used for differential diagnosis.
Generally b-blockers more effective in patients with essential tremor than in patients with Parkinson's disease.

Surface electromyography
Surface EMG sometimes helps to objectify the parkinsonian nature of tremor, revealing the characteristic low frequency of this type of tremor.

Accelerometry
This method has great diagnostic value.
Evaluate the waveform:
with essential tremor it looks like correct sinusoid
in Parkinson's disease it less correct
The number of peaks in the frequency spectrum is estimated:
with essential tremor there are 1-2 of them
in Parkinson's disease there are 3-4 of them
The amplitude ratio index A1/A2 is assessed:
with essential tremor it is 0.1
in Parkinson's disease it is 0.7

Neuroimaging
Has the most reliable differential diagnostic capabilities DaTSCAN- a type of computed tomographic radioisotope study.
This is the (only) method that allows you to:
assess dopaminergic activity in the human striatum in vivo
allows for dynamic monitoring as the disease progresses

When Parkinson's disease dopaminergic activity is reduced and tends to decrease even more over time, with essential tremor it remains normal at all stages of the disease.

POSSIBILITIES OF DRUG CORRECTION OF TREMOR (3)

According to the latest Cochrane meta-review(2008), tremor in Parkinson's disease can decrease both with the prescription of antiparkinsonian drugs and with the use of beta-blockers.

It is important to find out which type of tremor predominates in a given patient with Parkinson's disease:
resting tremor responds better to antiparkinsonian drugs - levodopa, some dopamine receptor agonists, amantadines
tremor action (postural and kinetic tremor) responds better to beta-blockers and is more effective than antiparkinsonian drugs

More often a combination of both classes of drugs is justified, which is determined by the ratio of different types of tremors in each individual patient.

Other drugs that have anti-tremor activity are also used - the following have this effect:
obzidan (propranolol)
hexamidine (primidone)
atenolol, alprazolam, anticonvulsants gabapentin and topiramate are considered effective
some authors indicate the effect of clonazepam, clozapine, nimodipine, flunarizine, botulinum toxin

Various combinations of the mentioned remedies, as a rule, can reduce tremor in most cases.

Currently rarely used anticholinergics, isoniazid and verapamil.

Increasingly used neurosurgical treatment of tremor . It is considered an effective treatment for both essential tremor and parkinsonian tremor. stereotactic intervention, especially deep electrical brain stimulation.

Parkinson's disease is a disease of the central nervous system that causes a gradual loss of muscle control. Symptoms are mild at first and often go unnoticed. The main signs of the disease are tremors, rigidity, slow body movements and a poor sense of balance. Parkinson's disease was first called "shaking palsy", but not all patients with this disease have tremors.

Development of the disease

Although this diagnosis can be frightening, the life expectancy of those affected is approximately the same as that of people without the disease. For some people, symptoms develop slowly over 20 years. Early treatment can give you years of symptom-free life. Between 5 and 10 percent of cases occur in people under age 50. Two famous people and supporters of the disease's research developed Parkinson's disease early, boxer Muhammad Ali at the age of 42 and actor Michael J. Fox at the age of 30.

Early symptoms

Early signs may be subtle and easily confused with other diseases. These include the following symptoms:

  • Slight trembling of fingers, arms, legs and lips
  • Stiffness when walking
  • Heaviness when rising from a sitting position
  • Small, dense handwriting
  • Slouched posture
  • A face with a “mask” frozen in a serious expression.

Let's tell you more about the symptoms

Tremor is an early symptom for about 70% of people with Parkinson's disease. It usually occurs in the fingers or palms when the hands are at rest. But when his hands are busy with something, he is absent. In this case, the shaking occurs rhythmically, usually from four to six beats per second, or like a “ball rolling”, as if the patient were rolling a ball between the thumb and forefinger. However, tremor can be a symptom of other diseases; in itself, it does not indicate any diagnosis.

Naturally, as people get older, their movements slow down. But when bradykinesia occurs, such slow movement can affect daily life. When a person wants to start moving, his body may not respond immediately, suddenly stop or “freeze”. The shuffling gait and masked face sometimes seen in Parkinson's patients may also be caused by bradykinesia.

Balance imbalance

People with Parkinson's disease tend to slouch, their shoulders droop, and their head moves forward. In addition to other movement problems, these patients may have problems maintaining balance and an increased risk of falling.

With rigidity, the muscles remain tense and do not relax. For example, when walking, your arms may not move. Muscle cramps or pain may occur. Most patients experience some degree of rigidity.

Other symptoms

Other symptoms are common (although not all patients experience them). This:

  • Restless sleep or daytime fatigue
  • Slurred speech, loss of intonation
  • Difficulty swallowing
  • Memory problems, confusion, or dementia
  • Oily skin and dandruff
  • Constipation

Brain scans are not usually used to diagnose Parkinson's disease, although they can be used to rule out other possible conditions. As part of the diagnosis, doctors usually ask:

  • Squeeze your thumb and index finger together or touch your foot to check your speed.
  • Relax your hand to observe the tremor
  • Move your neck, arms and legs in a relaxed manner to check for stiffness.
  • Stand while rocking slightly to check your overall balance.

Parkinson's disease or idiopathic tremors?

If tremors are present and there are no other symptoms such as muscle stiffness or slowness of movement, idiopathic tremor may be diagnosed. This type of tremor is hereditary and is more common than Parkinson's disease; it affects both hands to the same extent. Unlike Parkinson's disease, this tremor is worse when the arm is in motion. Idiopathic tremors do not respond to the drug levodopa, but can be treated with other medications.

Who is at risk?

The average age of onset of the disease is 55 years; over the age of 60 years, the probability of developing the disease ranges from 2% to 4%. If a family member has been diagnosed with Parkinson's, the risk of the disease increases slightly. Men are susceptible to the disease 1.5 times more often than women.

What causes Parkinson's disease?

Movement is controlled by a small area in the brain stem called the substantia nigra. In the case of this disease, cells in the substantia nigra stop producing dopamine (dopamine), a chemical that promotes the interaction of nerve cells. Because in this case these cells die, the brain does not receive the necessary information about how and when to move.

Parkinson's disease progresses over time. At the same time, certain changes occur inside the brain. Doctors determine the stages of the disease by carefully assessing symptoms. The Hoehn and Yahr Rating Scale is one of the most common tools used to assess the severity of symptoms. A unified rating scale is also used to determine mental clarity, general mood, activity in everyday behavior and the efficiency of motor functions. Accurately determining the stage of the disease helps determine the best treatment.

Levadopa treatment

Levadopa (L-dopa) is an amino acid that the brain converts into dopamine. This medicine has been used since 1970 and is still one of the most effective in treatment. The drug reduces bradykinesia and rigidity, improving motor skills. Over time, the effectiveness of levadopa decreases. The medicine should not be used on a diet high in protein foods. Its common side effects are nausea, vomiting and drowsiness. Long-term use of the medicine may cause hallucinations, paranoia and involuntary movements (dyskinesia).

Treatment with dopamine agonists

To treat motor dysfunction, medications that mimic dopamine, called dopamine agonists, may be prescribed. These are drugs such as Apokine, Mirapex, Parlodel and Requip. Apokine in the form of injections can be used if the effectiveness of levadopa decreases. Side effects of this drug may include nausea, vomiting, drowsiness, fluid retention, and psychosis.

Treatment with other drugs

The drugs Comtan and Tasmar can increase the effectiveness of levadopa, but a possible side effect is diarrhea. Patients taking Tasmar require regular monitoring of liver function. The drug Stalevo is a combination of levadopa, carbidopa, entacapone (Comtane).

The drugs Azilect, Eldepril and Zelapar, which slow down the breakdown of dopamine, can be prescribed either in the early stages of the disease or together with levadopa. These drugs cannot be used with some antidepressants.

Surgery. Deep brain stimulation

Electrodes can be implanted in one of three areas of the brain - the globus pallidus, the thalamus, and the subthalamic nucleus (on one or both sides). In this case, the pulse generator is located in the chest, near the collarbone. The electrical impulses it produces stimulate the brain, helping to reduce the patient's rigidity, tremor and bradykinesia. However, surgery does not affect other symptoms or the progression of this disease. In general, this treatment method may not be suitable for every patient.

Surgery. Pallidotomy (destruction of the globus pallidus of the brain) and thalamotomy (destruction of certain nuclei of the thalamus)

These surgeries use radiofrequency energy to destroy the lenticular nucleus of the globus pallidus, or thalamus. These areas are associated with tremor, rigidity, and bradykinesia, so overall motor function improves and the need for levadopa decreases after surgery. Because these surgeries are irreversible, they are less common than deep brain stimulation.

Diet for Parkinson's disease

To maintain bone strength, it is important to eat a well-balanced diet high in calcium and vitamin D. Although protein in general may reduce the effectiveness of levadopa, this can be avoided by taking the drug about half an hour before meals. For nausea, the medicine can be taken with crackers or ginger ale. Constipation can be prevented by a diet rich in fluids and fiber.

Can symptoms be prevented?

Researchers are currently studying various dietary supplements and other substances that may be able to prevent neuronal damage, but it is too early to say whether they will be effective. Coffee drinkers and smokers may have a lower risk of developing this disease, although it is clear that smoking has other serious health consequences.

Impact of environmental toxins

New research shows that exposure to pesticides and herbicides may increase the risk of developing this disease. Some people may be more susceptible to environmental influences genetically. In general, research in this important area is still ongoing.

Parkinson's disease and exercise

Exercise can actually have a positive effect and allows the brain to use dopamine more efficiently. It also helps improve coordination, balance, and reduce tremors. To obtain maximum results, exercises should be performed regularly and as intensely as possible, preferably three to four times a week for an hour. Walking on a treadmill or cycling has a positive effect. Tai Chi and yoga can help improve balance and flexibility.

Living with Parkinson's disease

This disease affects many aspects of daily life, but with the help of medications and accessories, a person can remain active. Medications help manage mood disorders such as depression and anxiety. An occupational therapist can assess the livability of the home for such a patient. It will be necessary to remove all possible hazards from the house, such as rugs and lying wires, and install special grab bars in the bathroom. Speech therapists for Parkinson's disease provide special consultations on swallowing and speech.

Help from loved ones

Caring for such a person can be a difficult task. As motor skills deteriorate, simple tasks may become difficult, but patients with this diagnosis may struggle to maintain independence. Both medications and the illness itself can lead to mood changes. People with Parkinson's disease can benefit from various self-help groups and online forums.

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Video lecture

Parkinsonism is a group of symptoms that can be caused by various diseases, the most important of which are primary Parkinson's disease and postencephalic parkinsonism. Shaking palsy, or Parkinson's disease, usually occurs around age 50, but can affect both young and old. This is a multisystem disease characterized by histological changes in the substantia nigra. The disease is observed mainly in men and in most cases begins on one side, but soon becomes bilateral and progresses very slowly. The most important symptom of the disease is tremor, which, however, is absent in 20% of patients (shaking paralysis without trembling).

Features of the disease

Parkinsonism is accompanied by rhythmic, rough, involuntary movements with large amplitude, which occur when the globus pallidus and substantia nigra of the brain are affected. These movements are reminiscent of those when counting money. In this case, the fingers of the hand, which are in a flexion position, oppose the thumb: the forearm, bent at the elbow joint, is capable of performing outward and inward rotational movements, and the wrist - flexion and extension.

The lower limbs move in a similar manner; if they are not fixed, tremors of the head and lips may be seen in the late stage of the disease. The head performs nodding movements and swaying movements. Involuntary movements of the supporting limb stop if the patient reaches for or takes something. Along with tremor, there are many symptoms that make it easy to recognize the disease. The rigidity of the patient's muscles is striking.

Reflexes are strengthened in most cases. With this disease, there is a predominant contraction of the flexors and their rigidity, therefore, when standing and walking, the torso leans forward, the limbs, especially the upper ones, are bent at all joints. Characteristically tense, expressionless, mask-like face with no facial expressions. The gaze wanders, normal blinking of the eyes is absent.

Facial stiffness, usually accompanied by a forced smile, can be the result of bilateral facial palsy, but in this case there are no symptoms of Parkinson's disease and facial palsy can be easily recognized.

The gait in Parkinsonism is shuffling, the body is tilted forward, and there is no normal arm movement observed when walking. If the patient is slightly pushed, he takes several quick steps forward, otherwise he would fall forward (propulsion). The same thing happens if the patient is pushed back: he takes several steps back so as not to fall on his back (retropulsion).

Movements in such patients are usually slow and difficult (bradykinesia). If you try to bend or straighten the patient’s arm or leg, muscle resistance will arise, which is overcome step by step, in parts (“gear wheel symptom”). Stiff muscles are painful in most cases. It is characterized by angular handwriting with gradually decreasing letters (micrography).

Tremor and other symptoms

Not only movements, but also the patient’s speech may be difficult. , which often prevents the patient from performing the most basic actions, and speech impairment are the reasons why the patient gradually stops contacting the outside world and becomes depressed. However, mental abilities do not decrease with parkinsonism, even in severe conditions, if it is not accompanied by atherosclerosis or another disease, patients are capable of significant mental activity. In most cases, the disease is accompanied by vegetative symptoms (increased salivation and sweating, heat flushes).

Hypokinesis

In young people, in most cases, postencephalitic parkinsonism of inflammatory origin is observed. The clinical picture of this disease may not differ from that of shaking paralysis, but instead of tremor, hypokinesis and increased muscle tone come first, in addition, there are more vegetative symptoms; especially characterized by increased secretion of saliva and sweat. This disease progresses faster than shaking paralysis, with it there is a more pronounced change in the patient’s personality, more complete amymia, changes in the pupils, double vision, and symptoms of damage to the pyramidal system are observed. All these symptoms make it possible to recognize the disease. However, the following data from the anamnesis are decisive in making a diagnosis:

  • heat;
  • paralysis of the eye muscles;
  • drowsiness.

The rapid development of clinical symptoms is also observed in atherosclerotic parkinsonism. The most important symptom is increased muscle tone. Symptoms are often unilateral and asymmetrical. Pyramid signs, phenomena, focal symptoms that develop as a result of blockage of blood vessels or softening of the brain accompany manifestations of parkinsonism. In senile parkinsonism, head tremors are observed, as well as other age-related symptoms.

Parkinson's disease and poisoning

Parkinsonism can be associated with various poisonings, for example, carbon monoxide, manganese, and chronic poisoning. In these cases, the disease is fleeting. A diagnosis of poisoning is made only when a toxic substance is identified. Among medications, transient symptoms of parkinsonism can be caused by chlorpromazine derivatives and rauwolfia alkaloids. Sometimes parkinsonism is observed with brain tumors. In this condition, unilateral parkinsonian symptoms develop rapidly and tumor-like symptoms and focal lesions appear. When rapidly developing, mostly unilateral, symptoms of parkinsonism suggest the possibility of a brain tumor.

TREMOR IN PARKINSON'S DISEASE: FEATURES OF PHENOMENOLOGY AND TREATMENT

O.S. Levin, V.K. Datieva Department of Neurology RMAPO

The nature and specificity of tremor in general and in Parkinson's disease (PD) in particular are considered. The possibilities of pharmacotherapy for tremor and the rationale for choosing a drug for PD are considered. The results of an open-label 6-month study assessing the effect of pramipexole on various types of tremor, conducted in Parkinsonology offices of district neurological departments of Moscow, are presented.

Key words: tremor, Parkinson's disease, dementia, levodopa, pramipexole.

Tremor is one of the most mysterious manifestations of Parkinson's disease (PD). Well known to all doctors since their student days, rest tremor of the “counting coins” or “rolling pills” type is the most important symptom of the disease, often the key to its diagnosis. But on the other hand, in a significant proportion of PD cases there is no resting tremor, which usually predetermines a more severe course of the disease, at least in the early stages of the disease, with faster progression and earlier cognitive decline. As the disease progresses, tremor may decrease, and with the start of dopaminergic therapy, it may increase, while the other two cardinal signs of PD (hypokinesia and rigidity) decrease under the influence of treatment. Moreover, no other symptom leads to such frequent overdiagnosis of PD as tremor.

“WORLD OF TREMORS” IN PD

PD is traditionally associated with rest tremor, but in PD any type of action tremor (action tremor) is possible, with the exception of intention tremor. Rest tremor manifests itself in a resting limb (most often in the distal arm or leg), decreases with its movement, but increases with active movements of other limbs. Pronounced rest tremor in the hand has a rotatory component and resembles “rolling pills” or “counting coins.” It can be observed in the hands while walking or

in a sitting position. The frequency of tremor is 4-7 Hz, tremor with a frequency of 6 Hz is especially characteristic of the early stages of PD. Rest tremor is the initial symptom in approximately half of patients, and during the course of the disease it develops in 85% of patients with PD.

Some patients with PD, both with and without resting tremor, also exhibit postural tremor that occurs when holding a posture (for example, when holding arms outstretched), or kinetic tremor that occurs when moving (for example, tremor in the hand when performing finger-nose test). Intention tremor, which occurs when approaching a target and is characterized by oscillations in the horizontal plane, excludes PD, however, in some patients with PD, a terminal increase in postural tremor is possible (immediately at the moment of hitting the target), which, in contrast to true intention tremor (with lesions of the cerebellum ), occurs in the vertical rather than horizontal plane. In some patients with PD, tremor may be briefly aggravated by yawning and straining. In general, there are 4 main types of tremor in Parkinsonism:

1) resting tremor 3-6 Hz in combination with postural/kinetic tremor of the same frequency (type I);

2) rest tremor combined with postural/kinetic tremor of a higher frequency up to 9 Hz (type II);

3) isolated postural/kinetic tremor with a frequency of 4-9 Hz (type III);

4) monosymptomatic (isolated) rest tremor (type IV).

It should be emphasized that in the absence of signs of hypokinesia, rest tremor does not allow diagnosing either parkinsonism or PD. Pronounced rest tremor in PD can persist even when holding a pose; in this case, the phenomenon of “re-emergent” tremor is often observed, which is observed at rest, disappears when moving, and when stretching the arms does not appear immediately, but after a certain latent interval , usually a few seconds. The pathophysiological mechanism of this type of tremor is presumably identical to resting tremor. Unilateral tremors in the arm and/or leg are often present. These types of tremor

can be considered as typical variants of type I tremor. Postural tremor can be not only a “continuation” of resting tremor, but also hyperkinesis independent of it. In the latter case it has a higher frequency (usually more than 1.5 Hz). Sometimes a resting tremor appears initially, and then a postural tremor, but more often a postural tremor appears first, and then a resting tremor is “layered” on it. Postural-kinetic tremor is detected in at least half of patients with PD, and although it is not specific to this disease, it is associated with more significant functional limitations than resting tremor.

“FREE AMONGST FOODS”: HOW TREMOR LEAD TO HYPERDIAGNOSIS OF PD

Unfortunately, many doctors, seeing a tremor of any nature, frequency and localization in their patient, immediately diagnose him with PD. Meanwhile, a much more common cause of trembling hyperkinesis is essential tremor (ET), which is the most common extrapyramidal disease.

The classic forms of PD and ET are easy to distinguish, but the differential diagnosis of the tremulous form of PD with minimal bradykinesia and rigidity and ET with resting tremor (which in this case is a “continuation” of postural tremor) and unsteadiness when walking can be difficult. In both cases, examination reveals a “gear wheel” symptom. “Gear wheel” is the result of a superimposition of tremor on normal or increased tone, a kind of “palpable tremor”. In PD, muscle tone increases due to rigidity; in ET, it is possible with normal muscle tone.

ET almost always affects the arms (95-100%), less often the head (34%), face (5%), voice (12%), torso (5%), lower extremities (10%). For most, tremor is detected only in the upper extremities. PD extremely rarely causes tremors of the head and vocal cords. Rest tremor can occur with ET, but usually due to incomplete relaxation of the arms, much less often with concomitant PD. ET does not cause pill rolling tremors or resting tremors in the lower extremities.

PD and ET can be combined in one patient. ET affects people of all ages, but its prevalence increases with age, affecting more than 5% of people aged 65 years and older. Therefore, it should be present in the same percentage of patients with PD of this age. Conversely, approximately 2% of patients with ET over 65 years of age also have PD.

“A STRANGER AMONG MY OWN”: FEATURES OF THE PATHOGENESIS OF TREMOR IN PD

Parkinsonian tremor is based on oscillations in the network - “motor cortex, ventrolateral thalamus, BSV, subthalamic nucleus”, and damage or dysfunction of any link in this chain suppresses tremor, but where the main source (pacemaker) of oscillations remains unknown. The cerebellum is also activated, with action tremor - to a greater extent than with resting tremor. On the other hand, according to Heltyu R. et al. , the single final link for the generation of any tremor is the cerebello-thalamic pathway. In this case, rest tremor occurs due to the modifying action of the pallidum. Some researchers have suggested that tremor may be the result of compensation for the underlying pathological process in PD. But it is more likely that the presence or absence of tremor in PD depends on the location of the lesion.

One of the mysteries of PD is the fact that classic type I tremor is a highly specific symptom of PD, but the correlation between the severity of tremor and disease progression and the severity of dopaminergic degeneration assessed using positron emission tomography (PET) or single photon emission computed tomography (SPECT) ) with radioligands tropic to nigrostriatal endings, no.

Moreover, pathomorphological examination in PD patients with tremor reveals classic pathomorphological changes, while in most patients with the akinetic-rigid form, more widespread brain lesions are revealed - with the presence of additional pathology. The latter assumption is supported by a decrease in tremor as the disease progresses, as the extent of the lesion increases.

Decreased serotonin (5-HT1A) binding at the midbrain raphe correlates with tremor severity but not with rigidity or bradykinesia. Thus, degeneration of neurotransmitter systems other than dopaminergic may be the cause of the “atypical behavior” of tremor as a symptom of PD. However, levodopa and dopamine receptor agonists (DRAs) remain effective treatments for tremor in PD.

SELECTION OF A DRUG FOR THE TREATMENT OF TREMOR IN PD

Levodopa is the most effective treatment for most symptoms in PD, but tremor is less responsive to

dopaminomimetics than hypokinesia or rigidity. Among all tremors, resting tremor has the best response to medications, but other types of tremor also respond to therapy to some extent. In general, the effect of dopaminergic drugs on tremor is variable and less predictable than the response of hypokinesia and rigidity. The tremor may even worsen, this is most typical for higher frequency action tremor. All dopaminergic drugs reduce resting tremor, while the effect of levodopa is approximately comparable to the effect of ADR: both groups of drugs at an average therapeutic dose reduce tremor by 30-50%. ADRs are especially useful in patients with tremors and normal neuropsychological status. They allow you to avoid premature escalation of the dose of levodopa and thereby delay the development of fluctuations and dyskinesias.

The addition of ADR at an average therapeutic dose to levodopa causes a reduction in rest tremor by 32-60%, however, the effect of ADR on action tremor remains an unresolved issue. Pramipexole appears to be one of the most effective drugs in the treatment of tremors. In cases of tremors, the administration of pramipexole reduced tremor by 61%.

Propranolol at a dose of 60-160 mg/day reduces rest tremor by 70%, and postural tremor by 50%; primidone and clonaze-pam are less effective. Amantadine is less effective than levodopa and anticholinergics, but this drug is switched on when fluctuations and dyskinesias appear. As a glutamatergic antagonist, it influences the pathway from the subthalamic nucleus to the SB and from the cortex to striatal cholinergic neurons. The antiparkinsonian effect of selegiline and rasagiline is usually minimal, but in some patients with relatively early-stage disease, MAO-B inhibitors provide beneficial effects, including on tremor.

The widespread belief about the relatively high effectiveness of anticholinergics in relation to resting tremor is not well substantiated, however, in a relatively small dose they can be added to ADR, levodopa, amantadine, if they do not provide sufficient control of resting tremor or dystonic tremor. Possible side effects include dry mouth, visual hallucinations, constipation, glaucoma, urinary problems, and memory problems. Stopping medications can provoke the development of severe withdrawal syndrome. Due to the adverse effects of anticholinergics on cognitive function, administration of ADRs and, if possible, dosing to the upper end of the therapeutic range should always precede the administration of anticholinergics.

Clozapine (average dose - about 40 mg/day) may be effective in resistant cases. Several controlled studies have confirmed the effectiveness of clozapine on resting tremor, even in cases where other drugs have failed. Drug resistance did not develop to the drug within 6 months of its use. Some patients experience dramatic effects when taking 1/4 to 1/2 tablet of clozapine at night. The possibility of leukopenia and agranulocytosis, which are serious, potentially fatal complications, limits its use and requires weekly white blood cell count determination.

PD patients with dementia are predisposed to hallucinations. They are prescribed only moderate doses of levodopa. High doses of levodopa are needed to treat tremor, but the risk of side effects makes it necessary to limit the dose of the drug. The use of cholinesterase inhibitors in patients with dementia may increase tremor, but the degree of increase in tremor rarely requires a change in treatment regimen in this case. However, the administration of memantine, which has a weak antitremor effect, or low doses of clozapine may be rational.

Jaw tremors in PD often do not respond to medications. Injections of botulinum toxin into the masticatory muscles have been found to reduce the severity of such tremors without significant side effects.

For disabling tremor that is refractory to pharmacotherapy, surgery should be considered, but all available medications should be tried first. Currently, stimulation of the Vim nucleus of the thalamus or subthalamic nucleus is most effective. Stimulation of the subthalamic nucleus (STN) has a therapeutic effect on tremor, as well as akinesia and rigidity. Recently, this type of intervention has been preferred. It is advisable to consider the possibility of deep Vim stimulation as a possible intervention in elderly patients whose clinical picture is dominated by tremor, with a slowly progressive course of the disease, in whom tremor is the main disabling factor. Stimulation of the Vim nucleus is a shorter neurosurgical intervention; it is characterized by a faster postoperative period for selecting medications; such manipulation can be performed unilaterally. Sometimes the use of higher doses of levodopa drugs is required to suppress tremor, with the risk of developing psychosis. One of the therapeutic options in such a situation is stimulation of the subthalamic

sky nucleus, since such an intervention can reduce the dose of levodopa by an average of 50%.

WHAT DID THE MIRAGE STUDY SHOW?

Despite the frequent mention in the literature of the ability of ADR, and in particular prami-pexole, to attenuate tremor, this effect remains poorly studied. The purpose of an open-label 6-month study conducted in Parkinson's departments of district neurological departments of Moscow was to assess the effect of pramipexole on various types of tremor (rest tremor, postural, kinetic tremor), as well as the state of affective and cognitive functions and health-related quality of life in patients with PD. The name “MIRAGE” was an abbreviation for the formal designation (Effect of MIrapex on tRemor, Affective Disturbances and Quality of Life in Patients with PD). The study included 98 patients (52 men and 46 women) with PD who had not previously taken levodopa and dopamine receptor agonists or had taken them but needed increased antiparkinsonian therapy. The age of the patients ranged from 42 to 75 years (average 63.2 ± 10.2 years), with 20% of the study population being patients over 70 years of age. The score on the Hoehn and Yahr scale ranged from 1 to 4 and averaged 2.5 ± 0.8. A prerequisite for including patients in the study was the presence of resting tremor, accompanied or not accompanied by postural tremor.

70% of patients took levodopa drugs (average dose 351.2 ± 279.4 mg). 62% of patients had motor fluctuations and 43% of patients had dyskinesia. In 23% of patients, pramipexole was prescribed instead of previously used piribedil. 30% of patients also took amantadine at a dose of 100 to 400 mg/day. Pramipexole was prescribed in increasing doses as monotherapy and in combination with other antiparkinsonian drugs. The dose titration period varied from 3 to 5 weeks. The period of taking the selected maintenance dose (0.5 or 1 mg 3 times a day) was 20 weeks.

The severity of various variants of trembling hyperkinesis was assessed using the corresponding items of Part III of the Unified Parkinson's Disease Rating Scale (UPDRS). The severity of resting tremor was assessed using item 20 of Part III of the UPDRS, and the severity of postural tremor was assessed using item 21.

To assess kinetic tremor, the spiralography method was used: patients were asked to draw an Archimedean spiral with each hand separately, “embedding” it into the drawn

a circle with a diameter of 10 cm with a center starting from the center indicated by a dot. The assessment was carried out according to the visual rating principle. The spiral drawn by each hand was scored separately, but then the score was averaged. The assessment was carried out at inclusion in the study (before starting the drug), after completion of dose titration, and after 1, 2 and 6 months.

In 4% of patients included in the study, rest tremor was initially mild, in 40% of patients it was moderate, in 32% it was severe, and in 24% of patients it was severe. Postural tremor was slight or absent in 29% of patients, moderate in 44%, and severe in 27% of patients. By the end of the study, the severity of resting tremor decreased by an average of 53%, the severity of postural tremor - by 37% (p< 0,05). Степень уменьшения кинетического тремора, оцениваемого с помощью спиралографии, снизилась на 38 % (р < 0,05).

The improvement achieved in the first 3 months of the study was persistently maintained by the end of the 6th month. By the end of the study, the severity of rest tremor decreased compared to the initial level by an average of 54%, the severity of postural tremor - by 50% (p< 0,01). Степень уменьшения кинетического тремора, оцениваемого с помощью спиралографии, к концу исследования несколько снизилась (до 15 %), но тем не менее различие с исходным уровнем осталось статистически достоверным (р < 0,01). Динамика выраженности тремора не зависела от изменений дозы леводопы в течение всего исследования.

At the same time, the severity of fluctuations and dyskinesias significantly decreased. No correlations were found between changes in the severity of tremor, fluctuations and dyskinesias. Reductions in depressive symptoms did not correlate with changes in levodopa dose or reduction in tremor, motor fluctuations, or dyskinesias.

According to the Clinical Global Impression scale, significant improvement was recorded in 30 (33%) patients, moderate improvement in 48 (53%) patients, slight improvement or no improvement in 13 (14%) patients. Positive dynamics on the global clinical impression scale correlated with improved quality of life (r = 0.46, p< 0,05), уменьшением кинетического тремора (г = -0,42, р < 0,05), симптомов депрессии по шкале Монтгомери-Асберга (г = -0,41, 0,38, р < 0,05), моторных флуктуаций (г = -0,37, р < 0,05).

The predictor of the effectiveness of pramipexole was the initial severity of rest tremor (r = 0.32, p< 0,01) и кинетического тремора (г=0,33, р < 0,01). Не влияли на эффективность прамипексола: возраст, длительность заболевания, тяжесть двигательного дефекта, выраженность аффективных и когнитивных нарушений, доза

levodopa, previous use of piribedil, concomitant use of amantadine. It should be specifically noted that in persons aged 70 years and older, the effectiveness of pramipex-sol did not differ from those in younger patients.

The main result of the study is to establish the positive effect of the drug on trembling hyperkinesis and affective disorders in patients with PD.

Previously, in a placebo-controlled study, RodageI O. et al. showed that the addition of pramipexole to levodopa (at an average dose of about 4 mg/day) leads to a decrease in the severity of parkinsonian tremor by an average of one third.

However, it remained unclear which types of tremor were affected by pramipexole.

Our study showed that pramipexole acts not only on resting tremor, but also on postural and kinetic types of tremor, which are considered resistant to levodopa drugs. This is indirectly evidenced by the data obtained in the study.

about a positive correlation between the severity of tremor and the dose of levodopa, which, apparently, reflects the unsuccessful attempts of doctors to reduce tremor by increasing the dose of levodopa. Thus, the use of pramipexole in patients with severe tremors helps not only to reduce hyperkinesis, but also to avoid unnecessary escalation of the levodopa dose. Moreover, we showed that the severity of tremor can be a predictor of the effectiveness of pramipexole, which allows us to recommend wider use of the drug in PD patients with tremulous hyperkinesis.

POSSIBILITIES OF USING THE EXTRA-LONG-RELEASE FORM OF PRAMIPEXOLE (MIRAPEX PD)

A new dosage form of pramipexole has been used in European countries and the USA since 2009. It is a matrix tablet in which the active substance is evenly distributed in a polymer matrix. In the gastrointestinal tract, the matrix absorbs liquid and turns into a gel, which releases pramipexole evenly over 24 hours. Since pramipexole is highly soluble in a liquid medium, regardless of its pH, the active substance is released from the matrix and absorbed throughout the intestine.

When developing a new dosage form, the possibility of a simple, immediate transition from the traditional form of the drug to the new one was taken into account. The condition for this is that equal daily doses of the immediate-release drug (taken 3 times a day)

and sustained release (taken

1 time per day) have the same anti-Parkinsonian effect.

The difference between the new and traditional dosage forms of pramipexole lies only in the rate of release of the active substance. Since the active substance is the same and has the same receptor action profile, significant differences in effectiveness between the two dosage forms can hardly be expected. The half-life of pramipexole itself is the same when using both forms, but controlled release ensures a longer maintenance of therapeutic concentrations of the drug in the blood.

The equivalence of equal daily doses of immediate- and extended-release pramipexole has been demonstrated in a number of clinical trials. Moreover, when switching to a sustained-release formulation, there was a trend toward lower UPDRS scores, higher global impression scores, and increased responders, although these differences did not reach the level of statistical significance. There were no significant differences in the frequency of side effects. At the same time, in 13.8% of patients, when switching to a drug with extended release, a dose increase was required, and in 3.8%, a dose reduction was required.

A similar result was obtained by M12 and Wu et al. in Japan, who successfully switched 83% of patients to the extended-release drug prami-pexole. Moreover, there was also a tendency towards a higher effect while maintaining the same daily dose.

The effectiveness of extended-release pramipexole in patients with early and advanced stages of PD has been confirmed in several placebo-controlled studies. It was shown that both dosage forms equally reduced the severity of parkinsonian symptoms, assessed by the total score of UPDRS parts II and III, as well as the global impression scale. There were no significant differences in the frequency of side effects.

It was shown that although clinician ratings (using the UPDRS or the Clinical Global Impression Scale) were similar with both formulations of pramipexole, patient global impression scores were higher with the extended-release formulation. This may reflect a more favorable effect of this dosage form on non-motor symptoms.

In a placebo-controlled study of an immediate- and extended-release formulation in 259 patients with long-standing PD

disease for about a year, the equivalence of the effect of equal daily doses of both dosage forms was also shown (scores for parts II and III of the UPDRS decreased by 7.5 and 7.4 points, respectively), while the profile and frequency of side effects were comparable.

It is worth emphasizing the particular convenience of the new dosage form of pramipexole, which is sufficient to take once a day, especially for patients with early stage PD who continue to work.

At the moment, it remains unclear whether an extended-release drug, when used early, can further reduce the risk of fluctuations and dyskinesias that occur while taking levodopa.

Experimental and clinical studies show that maintaining a relatively stable concentration of the drug in the blood, providing more constant dopaminergic stimulation, helps reduce the risk of dyskinesias and weaken them if they have developed. In addition, greater adherence to treatment, achieved by reducing the frequency of dosing, may allow for better control of disease symptoms. Empirical data show that early use of Mirapex PD can prevent the formation of persistent tremulous hyperkinesis.

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Tremor in parkinson's disease: features of the phenomenology and treatment

O.S. Levin, V.K. Darieva Department of neurology, RMAPO

Considered the nature and specificity of tremor in General and in Parkinson's disease in particular. Possibilities pharmacotherapy of tremor and justification of the choice of the drug in Parkinson's disease. Given the results of the open 6-month study assessing the impact of pramipexole on the different types of tremor, held in Parkinson's disease offices of district neurological Department, Moscow.

Key words: tremor, Parkinson's disease, dementia, levodopa, pramipexol.

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