Parkinson’s disease is a slowly progressive degenerative disease of the central nervous system, the main manifestations of which are such motor disorders as hypokinesia, muscle rigidity, rest tremor, postural disorders. In addition, vegetative, affective and other disorders develop in Parkinson’s disease. There are true Parkinsonism (Parkinson’s disease) and Parkinsonism syndrome, which can accompany many neurological diseases (TBI, brain tumors, strokes, encephalitis, etc.). If Parkinson’s disease is suspected, the patient must undergo electroencephalography, rheoencephalography, and MRI of the brain.
G20 Parkinson’s Disease
Parkinson’s disease is a slowly progressive degenerative disease of the central nervous system, the main manifestations of which are such motor disorders as hypokinesia, muscle rigidity, rest tremor, postural disorders. In addition, vegetative, affective and other disorders develop in Parkinson’s disease.
Classification of Parkinson’s disease is based on the age of onset of the disease:
- juvenile (juvenile Parkinsonism)
- with early onset
- with late onset
Various classifications of Parkinsonism syndrome are also known:
However, these classifications of Parkinson’s disease and Parkinsonism syndrome are not considered flawless. Therefore, today there is no generally accepted approach to this issue.
Etiology and pathogenesis
Modern medicine has made some progress in understanding the molecular and biochemical mechanisms of Parkinson’s disease. Despite this, the true etiology of sporadic forms of this disease remains unknown. Genetic predisposition and environmental factors are of great importance. The combination and interaction of these two factors initiates the process of degeneration in pigment-containing, and subsequently other neurons of the brain stem. Such a process, once it has arisen, becomes irreversible and begins an expansive spread throughout the brain. More than other protein substances of the nervous system, alpha-synuclein undergoes the greatest destruction. At the cellular level, the mechanism of this process looks like a lack of respiratory functions of mitochondria, as well as oxidative stress — the main cause of apoptosis of neurons. However, other factors are involved in the pathogenesis of Parkinson’s disease, the functions of which remain undisclosed until now.
Parkinson’s disease symptoms
There is a tetrad of motor symptoms of Parkinson’s disease: tremor, rigidity, hypokinesia, postural regulation disorders. Tremor is the most obvious and easily manifested symptom. Rest tremor is most typical for Parkinsonism, but other types of tremor are also possible, for example: postural tremor or intentional tremor. Muscle rigidity may be hardly noticeable in the initial stages, more often with the tremulous form of Parkinson’s disease, but obvious with severe Parkinsonism syndrome. Early detection of minimal asymmetry of tone in the extremities is of great importance, since the asymmetry of symptoms is a characteristic feature of all stages of Parkinson’s disease.
Hypokinesia is an obligate symptom of parkinsonism of any etiology. In the initial stages of Parkinson’s disease, the detection of hypokinesia can be difficult, so they resort to demonstrative techniques (for example, quickly clench and unclench their fist). Early manifestations of hypokinesia can be observed in elementary actions aimed at self—care (shaving, brushing teeth, buttoning small buttons, etc.). Hypokinesia is bradykinesia (slowness of movements), oligokinesia (reduction in the number of movements), as well as a decrease in the amplitude of movements and a decrease in their speed. Due to hypokinesia in Parkinson’s disease, individual “body language” is disrupted, including gestures, facial expressions, speech and motor plasticity.
Postural disorders in Parkinson’s disease manifest themselves quite early (for example, asymmetry of outstretched arms). However, most often they attract the attention of doctors already in the maladaptation stage (stage III). The explanation for this is the fact that postural disorders are less specific for Parkinson’s disease in comparison with other symptoms.
In addition to the above-mentioned main manifestations of Parkinsonism, Parkinson’s disease is accompanied by other symptoms, which in some cases may come to the fore of the clinical picture. Moreover, the degree of maladaptation of the patient in such cases is no less. Let’s list just a few of them: salivation, dysarthria and/or dysphagia, constipation, dementia, depression, sleep disorders, dysuric disorders, restless legs syndrome and others.
There are five stages of Parkinson’s disease, each of which reflects the severity of the disease. The most widespread classification was proposed in 1967 by Hyun and Yar:
- Stage 0 — there are no motor manifestations
- Stage I — unilateral manifestations of the disease
- Stage II — bilateral symptoms without postural disorders
- Stage III — moderate postural instability, but the patient does not need outside help
- Stage IV — significant loss of motor activity, but the patient is able to stand and move without support
- Stage V — in the absence of outside help, the patient is confined to a chair or bed
Clinical diagnosis of Parkinson’s disease takes place in three stages.
Recognition of Parkinsonism syndrome and its syndromic differentiation from its neurological and psychopathological syndromes, one way or another similar to true Parkinsonism. True parkinsonism is hypokinesia in combination with one of the following symptoms: resting tremor (4-6 Hz), muscle rigidity, postural instability, unrelated to primary vestibular, visual and cerebellar disorders.
Exclusion of other diseases that may manifest as Parkinsonism syndrome. There are several criteria for excluding Parkinson’s disease:
- oculogyric crises
- therapy with neuroleptics before the onset of the disease
- the presence in the anamnesis of repeated strokes with a step-like progression of parkinsonism symptoms, reliable encephalitis or repeated TBI
- prolonged remission
- exclusively unilateral manifestations for more than 3 years
- cerebellar symptoms
- supranuclear paralysis of the eye
- previously a vivid manifestation of dementia
- previously a vivid manifestation of vegetative insufficiency
- Babinsky’s symptom
- is a brain tumor or open hydrocephalus
- inefficiency of high doses of levodopa
- intoxication of MFTP
Identification of symptoms confirming Parkinson’s disease. To do this, you must have at least three of the following criteria:
- unilateral manifestations in the onset of the disease
- the presence of a resting tremor
- asymmetry of symptoms (with a greater degree of severity on the side of the body from which the disease began)
- 70-100%-reaction to levodopa therapy
- progressive course of the disease
- effectiveness of levodopa for 5 years or more
- the duration of the disease is 10 years or more
To examine patients with suspected Parkinson’s disease, rheoencephalography, EEG, neuroimaging methods are used: CT brain and MRI.
Parkinson’s disease must be differentiated from all diseases that are accompanied by Parkinsonism syndrome: secondary Parkinsonism, pseudoparkinsonism, “Parkinsonism plus”. About 80% of cases of Parkinsonism syndrome are due to Parkinson’s disease.
It should be remembered about certain clinical features of Parkinsonism that should raise doubts about the diagnosis of Parkinson’s disease, for example: inefficiency of levodopa, absence of tremor, symmetry of motor disorders, early manifestations of signs of peripheral autonomic insufficiency.
Parkinson’s disease treatment
The ways of treating Parkinson’s disease differ significantly in the early and late stages of the disease, so they should be considered separately.
In the early stages
Earlier diagnosis of Parkinson’s disease does not always mean the immediate start of any drug therapy. To determine the timing of the start of drug treatment, it is necessary to take into account the severity of the disease, the duration of the disease, the rate of its progression, any concomitant diseases, as well as “personal factors” (professional, social and marital status of the patient, mental state, personality characteristics, etc.). The purpose of such therapy is to restore (sufficient regression) impaired functions by minimally possible doses.
Drug therapy at an early stage of Parkinson’s disease involves the use of drugs that increase the synthesis of dopamine in the brain, stimulate its release and block its reverse absorption, inhibit the breakdown of dopamine, stimulate dopamine receptors and prevent the death of neurons. Such drugs include amantadine, selective MAO-B inhibitors (selegiline, etc.), dopamine receptor agonists (piribedil, pramipexol, etc.). The use of the above drugs is allowed both in the form of monotherapy (more often) and in various combinations.
The above drugs are significantly inferior in effectiveness to levodopa drugs, but they are quite suitable for the treatment of Parkinson’s disease in the early stages. Theoretically, in the early stages of Parkinson’s disease, dopamine receptor agonists are able to delay the appointment of levodopa, and in the later stages — to reduce its dose. However, a large number of side effects (gastric ulcer, orthostatic hypotension, mental disorders, erythromelalgia, retroperitoneal fibrosis, etc.) and the ability to reduce the sensitivity of postsynaptic dopamine receptors do not speak in their favor.
There are no clear criteria determining the optimal time to start treatment with levodopa drugs. Nevertheless, it is necessary to take into account the age of the patient (if possible after 60-70 years), avoid early administration of levodopa, when selecting a dose, focus on the “responsiveness” of the patient to the drug, improvements in his professional and social activities.
In the later stages
Regardless of the nature of the course of Parkinson’s disease, there is necessarily a gradual transformation of the clinical picture of the disease. Over time, the already present disorders progress and new ones appear, most of which are difficult to treat, thereby exerting a strong stressful effect on the patient. In addition, the usual effect of levodopa changes — the effectiveness of the drug decreases, drug dyskinesia increases (as a result of hypersensitivity of dopamine receptors).
The decrease in the effectiveness of therapy is manifested by a decrease in the duration of the therapeutic effect of each levodopa vine. The phenomenon of “on-off” is being formed, the only way to deal with which is a gradual increase in the dose of levodopa, and this in turn triggers a vicious circle that generates new problems, which are becoming harder to deal with. Real help in this case can be provided in two ways: by prescribing an additional dose of levodopa in order to reduce the intervals between doses; by adding a COMT inhibitor to the treatment regimen and transferring the patient to therapy with a combined levodopa and entacapone.
Side effects of levodopa therapy. One of the manifestations of a decrease in the threshold of sensitivity to certain side effects is a tendency to the appearance of oral (or other) hyperkinesis against the background of hyperkinesia symptoms. Thus, the clinical picture of Parkinson’s disease paradoxically combines the symptoms of an excess of dopamine (oral hyperkinesis) and its deficiency (hypokinesia). Reducing the dose of levodopa in such a situation gives only a temporary elimination of hyperkinesis, after a while it reappears. Orthostatic arterial hypotension in Parkinson’s disease is usually manifested by a relatively sharp decrease in blood pressure shortly after taking levodopa. Both levodopa and dopamine receptor agonists have such a side effect, therefore, after determining the cause of the side effect, it is necessary to reduce the dose of the corresponding drug.
Mental disorders in Parkinson’s disease can manifest themselves in the form of depression, anxiety, apathy, visual hallucinations, agitation. In addition, the appearance of memorable, vivid dreams is typical. Over time, all of the above violations progress and sooner or later manifest themselves in the waking state. Therapy of such mental disorders should be carried out jointly with a psychiatrist. Sometimes it is enough to relieve the patient of anxiety and fear, since they provoke more severe mental disorders. Most drug dyskinesia manifests itself at the peak of the drug’s action. The most reliable way to eliminate them is to reduce the single dose of levodopa while maintaining the daily dose of the drug. Therefore, fractional intake of small doses of levodopa is the best way to prevent dyskinesia of this type.
In the terminal stage of Parkinson’s disease, the main difficulties are associated with cachexia, loss of the ability to stand, walk and self-care. At this time, it is necessary to carry out a whole complex of rehabilitation measures aimed at ensuring optimal conditions for the patient’s daily household activities. It should be remembered that in the late stages of Parkinson’s disease becomes a heavy burden not only for the patient himself, but also for his family, whose members may need not only therapeutic, but sometimes specialized care.
Surgical treatment of Parkinson’s disease consists in stereotactic destruction of the ventrolateral nucleus of the thalamus and the subthalamic nucleus, as well as deep brain stimulation. In the case of severe akinetic-rigid syndrome, pallidotomy is recommended, as well as deep electrical stimulation of the pale globe and the subthalamic nucleus.
Parkinson’s disease is characterized by a steady increase in pronounced symptoms. In 25% of cases, disability or death occurs during the first five years of the disease. 89% of patients who have survived 15 years of Parkinson’s disease inevitably experience severe disability or death. There was a decrease in the mortality rate of patients with Parkinson’s disease due to the start of levodopa use, as well as an increase in life expectancy.