16.1. Parkinson’s disease and parkinsonism
Parkinsonism syndrome is characterized by slowness of movement (bradykinesia), muscle rigidity, rest tremor and postural instability.
The following types of parkinsonism are distinguished:
- idiopathic parkinsonism (Parkinson’s disease);
- secondary parkinsonism (drug-induced, vascular, post-traumatic, posthypoxic, postencephalitic, etc.);
- atypical parkinsonism accompanied by other neurological syndromes within the framework of multiple system degenerations (multiple system atrophy, progressive supranuclear paralysis, dementia with Lewy bodies, etc.).
Parkinson’s disease is thought to be the most common form of parkinsonism, accounting 50 to 80% of cases. The prevalence of this disease is 120–180 per 100,000; its frequency increases dramatically with age. According to statistics, parkinsonism is diagnosed in 1% of the population under 60 years of age and in 5% of older people. Men are a little more susceptible than women.
Etiology and pathogenesis
The disease is based on a neurodegenerative process that leads to a decrease in the number of neurons of the substantia nigra with the formation of inclusions called Lewy bodies. The risk of Parkinson’s disease increases with hereditary predisposition, in elderly and senile age, under the effect of exogenous factors. In addition, the etiology of the Parkinson’s disease may depend on a hereditary impairment of the metabolism of catecholamines in the brain or the defects of the enzyme systems that control this metabolism. A family history is detected in no more than 5–15% of all patients. To date, more than 20 genetic loci have been identified associated with both autosomal dominant and autosomal recessive types of inheritance. Hereditary predisposition is most important at the early onset of the disease (under 40 years) and juvenile forms with an onset under 20 years.
An increased risk of neurodegenerative process is associated with the exposure to pesticides and herbicides, prolonged contact with heavy (manganese) and transition (iron, copper) metals, organic solvents. Exposure to various exogenous factors can induce the appearance of gene mutations, synuclein aggregation, the development of mitochondrial dysfunction, and oxidative stress.
Secondary parkinsonism occurs as a result of acute and chronic infections of the nervous system (tick-borne and other types of encephalitis). The causes of the disease can be acute and chronic disorders of the cerebral circulation, injuries and tumors of the nervous system. Parkinsonism can develop due to drug intoxication with the prolonged use of phenothiazine drugs, i.e., chlorpromazine (Aminazine♠), trifluoperazine (Triftazine♠), methyldopa, some narcotic drugs. Parkinsonism syndrome can be one of the manifestations of CNS damage in other neurodegenerative diseases (progressive supranuclear paralysis, corticobasal degeneration, multiple system atrophy, Wilson’s disease, etc.).
The leading pathogenetic factor of both Parkinson’s disease and parkinsonism syndrome is impaired dopamine metabolism in the extrapyramidal system. Dopamine play a role of a mediator in the implementation of motor acts, mainly synthesized in the substantia nigra. The axons of dopaminergic neurons located in the substantia nigra (nigrostriatal neurons) travel to the striatum. Acting through dopaminergic receptors of various types, they reduce the degree of the inhibitory effect of the basal ganglia, facilitate thalamocortical transmission, thereby leading to disinhibition of the motor cortex. Normally, the effective functioning of the extrapyramidal system occurs due to the balance between the dopaminergic and cholinergic systems of the substantia nigra and the caudate nucleus, as well as the dopaminergic and GABAergic systems of the substantia nigra and the striatum, functioning according to the feedback principle. When the function of the substantia nigra is impaired, impulses coming from the extrapyramidal zones of the cerebral cortex and the striatum to the anterior horns of the spinal cord are blocked. At the same time, the cells of the anterior horns receive inhibitory impulses from the pallidum and substantia nigra. As a result, the circulation of impulses in the system of α- and γ-motor neurons of the spinal cord increases with a predominance of α-activity, which leads to extrapyramidal rigidity. In the pathogenesis, a violation of the activity of brain structures that use norepinephrine, substance P, and glutamate as neurotransmitters is also important.
Pathomorphology
The main pathoanatomic changes in parkinsonism are observed in the substantia nigra and pallidum in the form of degenerative changes and death of nerve cells. In place of the dead cells, foci of proliferation of glial elements appear. In the later stages, atrophy of the cerebral cortex occurs. In addition, in dopaminergic and noradrenergic neurons, as well as in the cells of the cerebral cortex, Lewy bodies containing α-synuclein form are detected.
Clinical presentation
The basis of clinical manifestations are akinetic-rigid or hypertensive-hypokinetic syndrome, which includes a triad:
- oligobradykinesia;
- muscle rigidity;
- tremor.
There is a specific flexion posture: the head and trunk are tilted forward, the arms are half-bent in the elbows, wrist and phalangeal joints, often tightly adducted to the lateral surfaces of the chest, the legs are half-bent in the knee joints. The range of motor synkinesias is sharply depleted. Facial expressions are also poor (hypomimia or amimia). The speech is quiet, monotonous, without modulations, with a tendency to fade at the end of the phrase. The rate of voluntary movements with the development of the disease is gradually slowed down, up to complete immobility. The patient walks with small shuffling steps, with no normal arm swing (acheirokinesis) when walking. At the moment of the beginning of walking, the phenomenon of trampling may occur.