One of the most common neurodegenerative diseases in society is Parkinson's disease, which affects most people over the age of 50. It is estimated that this condition affects 0.15% of the population, and as much as 1.5-2% among the age group over 70 years of age. Studies have shown that Parkinson's affects men more than women.
The disease was first diagnosed and described by the British physician James Parkinson in 1817. However, the original name of the disease was paramedic tremor, and it described the characteristic symptoms associated with motor skills problems. Information describing the condition was first included in Parkinson's work, An Essay on the Shaking Palsy. The term "Parkinson's disease" was introduced into use only by the French neurologist Jean-Martin Charcot. Konstantin Tretiakoffow in his 1917 doctorate described for the first time the influence of changes in the substantia nigra on the course of the disease development. On the other hand, a breakthrough discovery about the biochemical changes responsible for the development of the disease was made by the Swedish biochemist, Arvid Carlsson. In 2000, the scientist was awarded the Nobel Prize for this discovery important for medicine. In the works published in 1960 by Ehringer and Hornykiewicz, the particularly important role of dopamine (a neurotransmitter) in the pathogenesis of the disease was presented.
Parkinson's arises as a result of the neurodegeneration of the structure of the midbrain or the central nervous system. The aging of the substantia nigra and the gradual loss of cells in the substantia nigra occurs too quickly, as a result of which the level of dopamine in the brain decreases. However, the process of developing Parkinson's disease is much more complex in reality and is influenced by many environmental and genetic factors, including oxidative stress and free radicals.
During the development of Parkinson's disease, the structure of the brain is disrupted by the accumulation of deformed α-synuclein protein in the form of inclusions (called Lewy bodies) in nerve cells, which leads to cell death by apoptosis (programmed cell death). This is most often due to the genetic makeup of Parkinson's disease. Most neurodegenerative diseases support the malformed protein theory, as is also the case with most prion diseases. Protein misconformation follows a cascade of adjacent protein molecules. Tests carried out on an animal model have shown that the abnormal synuclein molecule, as a result of the transformation of the α conformation, changes into the β-sheet arrangement, which leads to the defect being transferred to the remaining synuclein molecules. As a result, the protein transformed into the β form accumulates in the form of β-amyloid and accelerates the process of cell death. Cell death in the black matter causes a high drop in dopamine in the striatum (part of the forebrain). The normal level of this neurotransmitter decreases in each decade of a healthy person's life by an average of 6-8%, amounting to 40-60% in the 60th year of life. However, in the case of disturbances in the structure of proteins caused by Parkinson's disease, this threshold is much lower, because, based on pathomorphological and biochemical studies, it appears that the first clinical symptoms of the disease develop at the dopamine level of about 20%.
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Parkinson's symptoms
One of the most basic symptoms of Parkinson's disease is slowness of movement (or bradykinesia), postural disturbances, increased plastic-type muscle tone, and resting tremor. It also contributes to the frequent occurrence of micrographs or, more simply put, changes in handwriting due to greater muscle stiffness. Vegetative ailments such as seborrhea, constipation and drooling are also very characteristic of Parkinson's. At the same time, the aforementioned autonomic symptoms, which are preclinical, may precede the most characteristic features of the disease (movement problems) by up to a decade. This is evidenced by the pathomorphological picture of the brain obtained in the course of Braak's research, in which individual stages of neurodegeneration in Parkinson's disease were distinguished and the initial place of this degeneration in the olfactory bulb and dorsal nucleus of the vagus nerve was determined. The problems with the sense of smell often belong to the group of preclinical symptoms, occurring long before the actual symptoms.
Methods and difficulties in diagnosing Parkinson's
Contrary to appearances, the diagnosis of Parkinson's disease is a complex process and is based primarily on clinical criteria. Symptoms typical of the disease may also be present in other conditions temporarily. The first priority is therefore to rule out the possibility of symptoms arising from the use of antipsychotics (neuroleptics) or from carbon dioxide poisoning. Parkinson's has a high level of recognition, ranging between 75-85%. The basic diagnostic method is a multicentre examination with the use of neuroimaging tests, on the basis of which it is estimated that the phenomenon may affect up to 47% of patients. However, a high percentage of the diagnosis may differ from the actual state due to the lack of additional clinical tests that could confirm the diagnosis.
Unfortunately, many diseases presently exhibit parkinsonism-like symptoms that lead to neuroimaging studies due to suspicion of Parkinson's disease. First, a distinction needs to be made between Parkinson's and ailment-like illnesses. The main conditions impersonating Parkinson's syndrome are a tumor in the frontal lobe (similar to Parkinson's with slowness of movement), depression or essential tremor symmetrically present in specific positions (such tremors are reduced under the influence of alcohol and increased under stress, while parkinsonian tremor occurs in a state of muscle relaxation). A completely separate category is atypical parkinsonism, because apart from parkinsonian syndrome, there are also a number of additional ailments, including primarily disorders of the autonomic system (orthostatic hypotension or multiple system atrophy), memory disorders, the symptom of "foreign hand" (the patient's hand is not only trembling, but also independently performs uncontrolled movements), dementia, corticobasal degeneration, oculomotor degeneration or supranuclear palsy. In order to exclude other conditions that coincide with Parkinson's symptoms, neuroimaging tests are used, mainly brain magnetic resonance and computed tomography.
In the diagnosis of Parkinson's disease, isotope markers are used, which enable the neuroimaging method of SPECT / CT scintigraphy (Single Photon Emission Computed Tomography) and the assessment of the extrapyramidal system in Parkinson. The study uses ioflupane labeled with I-123 iodine, thanks to which it is possible to confirm parkinsonism at the confidence level of 97%. SPECT / CT images are acquired 3-6 hours after administration of the radiopharmaceutical and last from 30 to 45 minutes. Since 2019, this method is also available in Poland (a radiopharmaceutical with its own name DaTSCAN®), but due to the high costs, the test is performed in a limited number of centers.
Parkinson's treatment
Due to the imbalance in the body between the cholinergic and dopaminergic systems, the basis of Parkinson's treatment is the stimulation of the latter system in order to increase the level of endogenous dopamine or block its metabolism, thanks to the appropriate blockade of the enzymes that break down dopamine monoamine oxidase and COMT (catechol - O-methyltransferase). ). Levodopa, which can be considered a dopamine protoplast, travels through the bloodstream to the brain, converting into dopamine to make up for the neurotransmitter deficiencies. Levodopa was first used in such a process more than 40 years ago, which has proved to be a breakthrough in today's Parkinson's treatments. In the treatment with levodopa, it is important to gradually increase the dose. Thanks to this, side effects of the therapy in the form of pressure surges and nausea should not appear. Unfortunately, levodopa is short-acting and is rapidly broken down in the body, so it must be given several times a day to maintain a stable effect. It is very important in the case of the advanced form of the disease, because the physical condition of the sick person depends mainly on taking the drug due to the large deficiencies of dopamine. Currently, it is not recommended to support therapy with anticholinergic drugs, as they are believed to have a negative effect on the memory of patients.
The drug used in the treatment of Parkinson's is also ropinirole, which has a prolonged stimulating effect on the dopaminergic system. The drug is released gradually and longer than levodopa, and in addition, it does not have to be administered several times a day, and the patient is not forced to maintain a schedule taking into account the time of meals. Ropinirole is used frequently in people with advanced Parkinson's disease, a so-called dopaminergic receptor agonist, who are experiencing side effects. The most common are limb edema and drops in blood pressure. Unfortunately, ropinirole, unlike levodopa, is more likely to contribute to the appearance of psychotic symptoms. It is not recommended for patients with dementia syndrome as it may aggravate their condition.
The main aim of Parkinson's treatment is to restore continuous dopaminergic stimulation in the brain, most often using one of the two basic methods - stimulation by administering primary dopamine or by blocking dopamine metabolism in the body. In the case of attempts to stop the metabolism, the COMT inhibitor or selegiline and rasagiline (monoamine oxidase B inhibitors) are most often used - they slow down the progression of the disease.
Source:
- Astrid van der Made. α-Synuclein aggregation in Parkinson’s disease, Utrecht: Utrecht University, 2011.
- Gaweł M., Potulska-Chromik A., Choroby neurodegeneracyjne: choroba Alzheimera i Parkinsona, „Postępy Nauk Medycznych”, t. XXVIII, nr 7, 2015, s. 468-476.
- Hornykiewicz O., The discovery of dopamine deficiency in the parkinsonian brain, „J Neural Transm” 70, s. 9–15.
- Hye GyeongSon, Eun Ok Cho, The Effects of Mindfulness Meditation-based Complex Exercise Program on Motor and Non-Motor Symptoms, and Quality of Life in Patients with Parkinson’s Disease, „Asian Nursing Research”, 2018.
