Parkinson’s disease: symptoms, treatment,the reasons

Update: December 2018

Parkinson’s disease is a slowly progressive disease.
degenerative nature which is characterized by selective
lesion of brain neurons.

Clinically, it is manifested by movement disorders:
hypokinesia (lack of motor activity, restriction
movements), muscle rigidity and tremor appearing at rest.

In Parkinson’s disease, symptoms are also characterized.
increasing mental disorders – decrease
mental abilities and depressive state.

Symptoms of trembling paralysis were first described by James.
Parkinson in 1817, and in 1877 a clinical characteristic
The disease was supplemented by the French psychiatrist Charcot. Parkinson’s disease
is a common pathology. Among people over 65, she
meets with a frequency of 1: 100.

Causes of disease

Today medicine has a lot of knowledge in
the biochemical and molecular mechanisms of this disease, however
истинные the reasons болезни Паркинсона остаются не известными до сих
since then The main assumptions of the occurrence of the disease are as follows:

  • Hereditary predisposition
  • Age changes
  • External environment – unfavorable ecology, the impact of heavy
    metals, toxic substances, viruses, infectious
    diseases

Age is considered the only clear risk factor.
diseases, чем старше человек, тем выше вероятность, особенно в
combination with hereditary location. 5-10% of people with this
disease symptoms occur after 50 years – this
previously-original form of Parkinson’s disease, which may be associated
with gene mutations. In the presence of sick relatives of PD, the risk
развития diseases достигает 25% у населения старше 60 лет, при
the absence of a family history of BP – this figure is 1 –
five%.

  • Men suffer from Parkinson’s disease 1.5 times more often.
    women.
  • In developed countries (possibly due to environmental factors),
    higher incidence – toxins in the air due to development
    industry, a powerful electromagnetic field, radiation, etc.
    adverse factors affecting the health of residents
    megacities.
  • Scientists, conducting surveys of patients with parkinsonism, draw conclusions,
    that work associated with frequent or constant vibration reduces
    Parkinson’s disease risk is 33% higher than professional
    activities not related to it.
  • Scientists also suggest that a possible trigger
    diseases служат вирусные интоксикации, частые травмы головы и
    various chemical poisonings.

Researchers from Canada (University of British Columbia)
claim that complications from the flu increase 2 times
The likelihood of a person developing Parkinson’s disease to the elderly
age Also, scientists have found that people who have had measles,
наоборот, снижается риск diseases на 3five%.

The causes of the disease also depend on the type:

  • Первичный паркинсонизм –  в 80% случаев вызван
    genetic predisposition.
  • Secondary parkinsonism – occurs on the background of various pathologies
    and existing diseases.

The most frequent pathologies that are provoking factors
development of secondary parkinsonism following:

  • A brain tumor
  • Атеросклероз сосудов головного мозга, Parkinson's disease симптомы угрожаемый инсультом
    и дисциркуляторной энцефалопатией
  • Хронические наследственные diseases
  • Frequent traumatic brain injury
  • Poisoning with technical alcohol, manganese, cyanides, carbon monoxide
    gas
  • Acceptance of neuroleptics and some other drugs.
    drugs
  • Transferred encephalitis
  • Addiction

Parkinson’s disease происходит из-за разрушения клеток головного
brain function in the synthesis of neurotransmitter
dopamine, so the brain begins to lose its ability to transmit
impulses to the muscles of the body.

If you go into the deep processes of disorders in the brain, you can
констатировать следующее —  развитие diseases связано со
decreased activity of inhibitory dopaminergic neurons in the “black
substance “and” striatum “(non-striatum) – the basal
brain ganglia, which are responsible for controlling movements.

Normally, black matter neurons send their processes in
striatum. In their synapses, dopamine is released, which inhibits
neostriatum The processes of neurons going in the opposite direction
by GABA (gamma-aminobutyric acid) inhibit the activity
black matter. This complex system is a mutual
braking paths, “filtering” motor impulses.
Dopaminergic neurons of the substantia nigra in Parkinson’s disease
die, which leads to motor disturbances.

Symptoms of Parkinson’s Disease

In the early stages of development, Parkinson’s disease is diagnosed
difficult due to the slow development of clinical symptoms. She can
to manifest pain in the limbs that can be mistakenly associated
с diseasesми позвоночника. Can often occur
depressive states.

The main manifestation of parkinsonism is akinetiko-rigid
a syndrome that is characterized by the following symptoms:

  • Tremor

It is a fairly dynamic symptom. Him appearance may be
associated with both the emotional state of the patient and his
movements. For example, the tremor in the hand may decrease during
conscious movements, and intensify when walking or moving another
by hand. Sometimes it may not be. Oscillation frequency
small – 4-7 Hz. They can be observed in the arm, leg, individual
fingers In addition to the limbs, “shake” may occur at the bottom
jaws, lips and tongue. Characteristic parkinsonian tremor in
thumb and forefinger are reminiscent of “rolling pills” or
�”Coin counting”. In some patients it may occur not only in
rest, but also when moving, causing additional difficulties
eating or writing.

  • Bradykinesia (akinesia)

It is a significant slowdown and impoverishment.
motor activity and is the main symptom of the disease
Parkinson’s It manifests itself in all muscle groups, but most of all
visible on the face due to the weakening of mimic muscle activity
(hypomimia). Due to the rare blinking of the eyes, the look seems heavy,
shrill. With bradykinesia, speech becomes monotonous,
muffled. Due to impaired swallowing movements may appear
salivation. Fine motility of the fingers is also depleted:
patients can hardly make habitual movements, such as
buttoning. When writing is observed transient
micrographics: by the end of the line the letters become small,
illegible.

,jktpym gfhrbycjyf ,jktpym gfhrbycjyf 2
  • Rigidity

Movement disorders caused by akinesia, are aggravated by
account rigidity – increase muscle tone. During external examination
patient, it is manifested by increased resistance to passive
movements. Most often it is uneven, which causes
the emergence of the phenomenon of “gear” (there is a feeling that
the joint consists of gears). Normal muscle flexor tone
prevails over the extensor muscle tone, so the rigidity in them
more pronounced. As a result, characteristic changes are noted.
posture and gait: the torso and head of these patients are bent forward,
arms bent at the elbows and brought to the body, legs slightly bent
in the knees (“petitioner posture”).

  • Postural instability

It is a special violation of motor coordination during
walking due to the loss of postural reflexes involved in
maintaining balance. This symptom manifests itself at a late stage.
diseases. Such patients have some difficulties with
change of a pose, change of the direction of the movement and the beginning of walking. If a
a slight push to bring the patient out of balance, he is forced
will take a few quick short steps forward or backward
(propulsion or retropulsion) to “catch up” with the center of gravity of the body and
do not lose balance. The gait thus becomes mincing,
�”Shuffling.” The consequence of these changes are frequent falls.
Postural instability сложно поддается терапии, поэтому часто
is the reason why a patient with Parkinson’s disease
turns out to be bedridden. Movement Disorders
Parkinsonism is often combined with other disorders:

Vegetative disorders:

  • Disorders of the gastrointestinal tract associated with impaired intestinal motility –
    constipation associated with inertia, poor nutrition, restriction
    drinking. Также причиной запоров является прием drugs от
    parkinsonism.
  • Ортостатическая гипотензия —  снижение артериального
    pressure when changing body position (when a person rises abruptly), this
    leads to reduced blood supply to the brain, dizziness and sometimes
    faint
  • Increased urination or vice versa
    emptying the bladder.
  • Decrease in sweating and increase in greasiness of skin – skin on
    face becomes oily, especially in the nose, forehead, head
    (provokes the occurrence of dandruff). In some cases it may be
    on the contrary, the skin becomes too dry. Conventional dermatological
    treatment improves skin condition.

Mental disorders:

  • Emotional changes – depression, she is the very first
    symptom of Parkenson’s disease. Patients lose confidence in themselves
    they are afraid of new situations, they avoid communication even with friends;
    pessimism, irritability. There is increased sleepiness in
    daytime, disturbed sleep at night, nightmares,
    too emotional dreams. It is not allowed to use any
    drugs to improve sleep without a doctor’s recommendation.
  • Cognitive disorders (dementia) – memory is impaired,
    there is a slow look. With a severe course
    diseases возникают серьезные когнитивные проблемы — слабоумие,
    cognitive decline
    reason, express thoughts. Effective way to slow down
    there is no development of dementia, but clinical studies prove that
    the use of rivastigmine, donepezil somewhat reduces such
    symptoms.

Other characteristic symptoms:

  • Problems with speech – difficulty starting a conversation, monotony
    speeches, repeating words, too fast or slurred
    observed in 50% of patients.
  • Трудности с приемом пищи —  это связано с ограничением
    motor activity of the muscles responsible for chewing, swallowing,
    increased salivation occurs. Delay of saliva in the mouth
    may cause suffocation.
  • Sexual dysfunction – depression, antidepressants,
    deterioration of blood circulation lead to impaired erection, reduce
    sexual attraction.
  • Быстрая утомляемость, слабость —  повышенная усталость
    usually intensifies in the evening and is associated with problems of the beginning and
    ending movements, it can also be associated with depression,
    insomnia. Establishing a clear sleep pattern, rest, reduction
    physical activity helps reduce fatigue.
  • Muscle spasms – due to lack of movement in patients
    (muscle stiffness) muscle spasms occur, often in the lower
    limbs, to reduce the frequency of seizures helps massage,
    warming up, stretching.
  • Muscle aches – aching joints, muscles caused by impairment
    posture and muscle rigidity, the use of levodopa reduces such
    pain also helps some types of exercise.

The forms and stages of Parkinson’s disease

Существует 3 формы diseases: Ригидно-брадикинетическая.
It is characterized mainly by increased muscle tone (especially
flexors) by plastic type. Active movements are slowing.
up to immobility. This form is characterized by a classic
�”Hunched” pose.

Shivering-rigid. Manifested by distal tremor
limbs, which over time joins stiffness
movements.

Trembling. It manifests a constant tremor of the limbs,
lower jaw, tongue. The amplitude of oscillatory movements can be
great, but the rate of voluntary movements is always maintained. Tone
The muscles are usually elevated.

In Parkinson’s disease, symptoms and treatment depend on the degree
тяжести diseases:

zero stage – the absence of motor disorders stage 1 –
unilateral symptoms stage 2 – bilateral manifestations without
postural disorders stage 3 – minor postural
instability, the patient is still able to do without
relief stage 4 – a serious loss of motor activity, the patient
can still move himself and able to stand stage 5 – sick
bedridden, armchair, needs constant strangers
assistance, becomes disabled.

Parkinson’s disease treatment

This disease is incurable, all modern drugs
для терапии только облегчают симптомы болезни Parkinson’s
Symptomatic treatment aims to eliminate motor
violations. How to treat Parkinson’s disease? In the early stages
diseases показана посильная физическая нагрузка, лечебная
physical Culture. Treatment with drugs should begin as late as possible.
because with long-term long-term medication in a patient
addictiveness develops, forced dosage increase and how
consequence of increased side effects.

Symptomatic treatment:

  1. Hallucinations, psychosis – psychoanaleptics (Ekselon, Reminil),
    neuroleptics (Seroquel, Clozapine, Azaleptin, Leponex)
  2. Vegetative disorders – laxatives for constipation,
    GI motility stimulants (Motilium), antispasmodics (Detruzitol),
    antidepressants (Amitriptyline)
  3. Sleep disturbances, pain, depression, anxiety – antidepressants
    (tsipramil, iksel, amitriptyline, paksil) zolpidem, sedatives
    facilities
  4. Decreased concentration, impaired memory – Exelon,
    Memantine-akatinol, Reminyl

In order to avoid the development of addiction to strong drugs should
follow the basic principle of treatment of Parkinson’s disease:

  • Therapy should start with soft medicines.
    restraining the transition to high doses
  • Желательно использовать комбинацию drugs с различным
    mechanism of action
  • Add a new drug only when needed.
  • To prescribe levodopa preparations (the most effective) in the extreme
    the last case, especially for patients under 65
    years old.
  • Применение сильных drugs обосновано только при
    the occurrence of motor limitations, strongly interfering
    performance of domestic duties, professional
    activities.

In the treatment of Parkenson’s disease, drug therapy solves 2
objectives: reducing the rate of death of brain cells with dopamine and
reduction of symptoms of the disease. In the complex treatment of the disease
Parkinson should include antioxidants (for example, natural
витамин Е, а не синтетический), лечебная physical Culture. Insofar as
the disease is not fully understood, scientists are still arguing that
is it possible to slow down the inevitable progression of the disease when
started parkinsonism.

Drugs that increase inhibition of neostriatum neurons
dopamine

The precursors of dopamine (levodopa). This drug represents
is a spatial isomer of dioxyphenylalanine (DOPA). DOPA –
the precursor of dopamine, which, unlike dopamine itself,
penetrates well into the central nervous system. Under the action of the enzyme DOPA decarboxylase,
Levodopa is converted to dopamine, thereby increasing its level in
non-striatum. The symptoms of parkinsonism disappear within a short
time span. Levodopa is effective only in maintaining its
constant concentration in the body. With the progression
diseases, и уменьшением количества клеток нейронов black
substance, its effectiveness is sharply reduced. 97-99% levodopa
transformed into dopamine in peripheral tissues, causing
many side effects of the drug. In order to reduce them
amounts, levodopa is used in combination with inhibitors
DOPA decarboxylase (carbidopa, benserazide), not penetrating into the central nervous system.
With this combination, the metabolism of levodopa can only occur in
the brain. Levodopa combination products:

  • Levodopa + Carbidopa: Nakom (10: 1), Sinemet (10: 1 or 4: 1).
    When using combinations of levodopa and carbidopa increases
    the likelihood of side effects from the CNS, such as
    dyskinesia (up to 80% of cases), anxiety, depression, delirium,
    hallucinations.
  • Levodopa + Benserazid: “Madopar” (4: 1). Potent
    a drug. It is used for long-term treatment of the disease.
    Parkinson’s

MAO-B inhibitors (monoamine oxidase-B): Selegilin, Razagilin.
Selectively inhibit MAO-B, which metabolizes dopamine,
raising its level in the non-striatum. Применение этих drugs
together with levodopa reduces the dose of the latter.

COMT inhibitors (tolcapon, entacapone).
Catechol-O-methyltransferase (KOMT) is an enzyme responsible for
dopamine distribution in neurons. Application of combined
dopamine precursors leads to a compensatory activation of this
enzyme. The effectiveness of treatment is reduced. Tolcapone and
entacapone block the action of COMT, allowing you to reduce the dose
levodopa.

Drugs that increase the release and inhibit the reverse
dopamine uptake:

  • Amantadine. Противовирусный a drug. Parkinsonian
    эффект слабее, чем у levodopa. There is a decrease in rigidity and
    akinesia. Tremor не устраняет.
  • Gludantan. Compared to amantadine, it eliminates more
    tremor, but weaker effect on rigidity and akinesia. Applied to
    complex with levodopa and trihexyphenidyl.

Dopamine receptor stimulants:

  • Bromocryptyline. Dopamine receptor partial agonist
    (D2).
  • Lesurid. Derivative of ergot alkaloids.
  • Pergolid. Dopamine receptor agonist (D1 and D2).
Drugs that inhibit the excitation of neostriatum neurons
acetylcholine

Trihexyphenidyl (cyclodol). It is an antagonist.
muscarin Him действие при болезни Паркинсона слабее, чем у
levodopa. Well eliminates tremor and muscle stiffness, but does not affect
on bradykinesia. Applied to составе комплексной терапии.

Glutamate Receptor Blockers (NMDA)

Это сравнительно новая группа drugs. Glutamate is
excitotoxic transmitter for pathways. Him
action on NMDA receptors induces calcium ions,
which leads to a sharp increase in stimulation, and subsequent death
нейронов при болезни Parkinson’s Glutamate blockers
receptors:

  • Adamantine derivatives (midantan, simmetrel). Reduce
    toxic effect due to stimulation
    NMDA receptor.
  • Anticholinergic drugs (procyclidine, etopropazin).
    Weak glutamine receptor antagonists.

Surgical treatment of Parkinson’s disease

Previously, talamotomy was used to treat this pathology.
(destruction of the intermediate ventral nucleus of the thalamus). At present
time this intervention gave way to pallidotomy – partial
surgical destruction of the pale ball (part of the basal ganglia).
Surgical treatment is used only in cases where
patients do not respond to standard drug therapy.
Pallidotomy can reduce hypokinesia in 82%
cases.

From minimally invasive surgical procedures, everything is big
spread gets neurostimulation. This method is to
point electric shock on certain structures
the brain.

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