Parkisson's disease: clinical and epidemiological features, modern methods of diagnosis and therapy (literature review)



Parkinson's disease is a common neurodegenerative disease, the diagnosis and treatment of which is challenging. The diagnosis is clinical and sometimes difficult, given the large number of motor and non-motor symptoms in patients with PD. Medical treatment of patients with PD is difficult because the choice of drugs is limited and the main treatment is levodopa. The article presents a review of literature data for 5 years reflecting current data on the etiopathogenesis, clinical picture, diagnosis and treatment of Parkonson's disease.

Keywords : Parkinson's disease, black substance, tremor, rigidity, bradykinesia.

Parkinson's disease is a prevalent neurodegenerative disorder characterized by the degeneration of dopamine-producing neurons in a specific region of the brain called the substantia nigra. This disease is primarily associated with the accumulation of a protein called alpha-synuclein and the formation of intracellular inclusions known as Levy's corpuscles. Parkinson's disease is the leading cause of Parkinson's syndrome, accounting for approximately 80 % of all cases [1]. Parkinson's disease primarily affects people aged 50 years and older, and the prevalence and risk of developing sporadic Parkinson's disease increases substantially with age, with an incidence rate of 18 per 100,000 per year [3]. No definitive diagnostic tests, such as magnetic resonance imaging, computed tomography, or genetic tests, can confirm PD. Its diagnosis is usually based on the presence of a combination of key motor signs as well as response to levodopa. As the disease progresses, patients with Parkinson's disease experience significant motor disability, even when treated with symptomatic medications [8].

Objective . To review the literature sources of English-speaking authors, to study the clinical and epidemiological features of Parkinson's disease, modern methods of diagnosis and treatment.

Materials and methods . It is based on the results of the analysis of literary sources in English for the period 2018–2023 based on the Pubmed database.

Results and discussion .

Epidemiology. The prevalence of Parkinson's disease is estimated to be around 140 cases per 100,000 individuals, with some variation across different populations. While the disease typically manifests after the age of 50, it can also occur at earlier ages, with onset possible from the age of 16. Men are slightly more affected by Parkinson's disease than women. Epidemiological studies have found an increased risk of Parkinson’s disease with environmental factors such as exposure to substances derived from industrial processes, use of agrochemicals, or living in a rural environment. The hypothesis that certain environmental toxins could be the source of the PD is supported by the discovery that chemicals such as herbicides, diquat, and the fungicide maneb are selectively toxic in nigrostriatal dopaminergic neurons [1,2].

Etiology and pathogenesis. The exact cause of Parkinson's disease remains largely unknown, although it is believed to be influenced by a combination of genetic factors, environmental exposures to toxins, and the natural aging process. Genetic factors play a significant role, particularly in the early development of the disease. However, the interplay between genetic and environmental factors is complex and requires further investigation. Recent studies have established that systemic inflammation and neuroinflammation are both present in the prodromal phase and sustained during the progression of the disease. Evidence suggests that the activation of the peripheral immune system exacerbates the brain inflammatory response, which may initiate or enhance neurodegenerative processes. Understanding the impact of modern methods of diagnosis, inflammation in the neuroinflammation and the progression of the disease will provide a broader view of the etiology and pathology of Parkinson Disease [11,17,30].

Clinical picture. Parkinson's disease is characterized by a range of motor symptoms, including tremors, rigidity, bradykinesia (slowness of movement), and postural instability. Non-motor symptoms such as cognitive impairment, mood disorders, and autonomic dysfunction may also occur. The diagnosis of Parkinson's disease is primarily based on clinical evaluation, as there are no specific biomarkers or definitive tests available [2,5,11].

Based on a series of pathomorphological studies, it has been shown that already at an early stage of the disease, Lewy bodies are found in the olfactory bulbs and lower parts of the brain stem. Clinically, this is manifested by dysfunction of the sense of smell and disruption of the gastrointestinal tract. The process then spreads to the overlying structures of the brainstem, involving serotonergic, noradrenergic and cholinergic neurons, which leads to behavioral disturbances in the sleep phase with rapid eye movements, anxiety and depressive disorders, and cognitive dysfunction. It is only at the 3rd stage that the neurodegenerative process moves to the substantia nigra, resulting in the development of motor symptoms [14,19,29].

In recent years, the hypothesis about the presence of two subtypes of the onset of the pathological process in PD has been actively discussed: body-first or brain-first. In the first subtype, the peripheral nervous system is initially involved, in the second — brain structures. The body-first variant is characterized by the early appearance of symptoms of autonomic failure in the form of intestinal dysfunction, most often constipation, 10–20 years before the development of typical motor signs of the disease. On the contrary, the brain-first variant of the development of the disease leads to asymmetric ipsilateral degeneration of neurons in the substantia nigra and significantly greater motor asymmetry during the development of symptoms [4].

Another common symptom of Parkinson's disease is postural instability. It appears already in the early stages of the disease and only increases as the disease progresses. Since the vestibular system plays an important role in the sensation of dizziness, as well as in providing postural stability, it is assumed that damage to it may be partly responsible for these symptoms of Parkinson's disease. It is known that the vestibular system, together with the visual and proprioceptive systems, provides afferent information about the movement and location of the body in space, which is necessary for maintaining balance and postural control. Moreover, there is evidence of a close connection between the vestibular system and the basal ganglia: vestibular signals enter, in particular, the striatum, which is one of the first to suffer in Parkinson’s disease. Indirect confirmation of the participation of the vestibular system in the development of Parkinson's disease can be provided by data on a temporary decrease in symptoms of the disease under the influence of caloric and galvanic vestibular stimulation [22].

Cognitive impairment is one of the common non-motor complications in Parkinson’s disease. The underlying mechanism remains elusive due to multiple reasons. As a result, treatment options for cognitive decline in Parkinson’s disease are limited and not as effective as those for motor symptoms. Recent advances in neuroscience have developed new models for the pathophysiology of Parkinson’s disease dementia, based on which clinical research have showed promising results. The role of multiple neurotransmitter systems in cognitive impairment have been emphasized. Several preliminary studies on deep brain stimulation have demonstrated positive results. The nucleus basalis of Meynert, a hub in the cognitive network, is chosen by most studies as the stimulation target. Deep brain stimulation for motor symptoms, on the other hand, may also cause or aggravate patients’ cognitive dysfunction [7,10,17,22].

Diagnostic methods. The diagnosis of PD today can be established on the basis of the characteristic motor manifestations of the disease: a combination of bradykinesia with resting tremor and muscle rigidity, corresponding to parkinsonism syndrome. The most significant supporting criteria are: the presence of a pronounced response to levodopa drugs, identification during examination of a characteristic resting tremor with a rotatory component and loss of smell. Among additional research methods, the most highly specific are functional neuroimaging methods — positron emission tomography with fluorodopa and single-photon emission computed tomography, scanning with a dopamine transporter. These methods are highly expensive and are not routine or mandatory in the diagnosis of PD in any country in the world. Ultrasound examination of the substantia nigra (transcranial sonography) and high-field magnetic resonance imaging (MRI) of the brain in SWI (Susceptibility Weighted Imaging) mode are also used as additional techniques. There are currently no specific laboratory methods for diagnosing PD. Young patients (up to 40 years old) with symptoms of parkinsonism must exclude hepatolenticular degeneration based on blood tests (for the content of ceruloplasmin, total and free copper), urine (daily excretion of copper in urine), and the presence of a Kayser-Fleischer ring along the periphery of the cornea. It is also recommended to conduct DNA diagnostics for patients with familial cases (if two or more relatives have the disease) to determine their risk of developing PD [16,23,29].

Treatment. Medical treatment consists of levodopa; dopamine agonists like bromocriptine, anticholinergic drugs like pacitane etc. Among this levodopa is the main drug, which directly introduces dopamine in the brain, the deficiency of which causes the disease. The dose is decided on the basis of the severity of the symptoms. This medicine can be given to the patient in different proportions and forms like tablets, liquids and pumps [10,14].

In addition to drug treatment, there are non-drug treatments for Parkinson's disease. These approaches aim to improve symptoms, improve quality of life, and improve overall well-being. Physical therapy focuses on improving mobility, balance and coordination through exercises and techniques tailored to the individual's needs. Physical therapy can help reduce muscle stiffness, improve gait, and improve overall physical function. Occupational therapy aims to improve the ability to perform daily activities and maintain independence. Emphasis is placed on coping strategies for fine motor difficulties, self-care tasks, and environmental adaptations to improve safety and functionality. Speech and language therapy can help people with Parkinson's disease overcome difficulties with speaking and swallowing. Techniques such as voice exercises, breathing exercises, and strategies to improve articulation and swallowing can be used [29].

Deep brain stimulation (DBS) is a surgical procedure that involves implanting electrodes in specific areas of the brain that transmit electrical impulses that help regulate abnormal brain activity and relieve motor symptoms. DBS is usually recommended for people with advanced Parkinson's disease who do not respond well to medication alone [12].

Conclusion: Parkinson's disease is a common neurodegenerative disorder characterized by the degeneration of dopamine-producing neurons in the substantia nigra. Its exact cause remains elusive, but genetic factors, environmental exposures, and aging are believed to contribute. Early diagnosis and appropriate management are crucial for improving the quality of life for individuals living with Parkinson's disease. Continued research is essential to unravel the complexities of this condition and develop more effective treatments

References:

1. Alberts JL, Rosenfeldt AB. The Universal Prescription for Parkinson's Disease: Exercise. J Parkinsons Dis. 2020;10(s1):S21-S27. doi: 10.3233/JPD-202100
2. Ben-Joseph A, Marshall CR, Lees AJ, Noyce AJ. Ethnic Variation in the Manifestation of Parkinson's Disease: A Narrative Review. J Parkinsons Dis. 2020;10(1):31–45. doi: 10.3233/JPD-191763.
3. Bidesi NSR, Vang Andersen I, Windhorst AD, Shalgunov V, Herth MM. The role of neuroimaging in Parkinson's disease. J Neurochem. 2021;159(4):660–689. doi: 10.1111/jnc.15516
4. Borghammer P, Van Den Berge N. Brain-First versus Gut-First Parkinson's Disease: A Hypothesis. J Parkinsons Dis. 2019;9(s2):S281-S295. doi: 10.3233/JPD-191721
5. Cabreira V, Massano J. Doença de Parkinson: Revisão Clínica e Atualização [Parkinson's Disease: Clinical Review and Update]. Acta Med Port. 2019;32(10):661–670. Portuguese. doi: 10.20344/amp.11978
6. Cartella SM, Terranova C, Rizzo V, Quartarone A, Girlanda P. Covid-19 and Parkinson's disease: an overview. J Neurol. 2021;268(12):4415–4421. doi: 10.1007/s00415–021–10721–4
7. Cattaneo C, Jost WH. Pain in Parkinson's Disease: Pathophysiology, Classification and Treatment. J Integr Neurosci. 2023;22(5):132. doi: 10.31083/j.jin2205132
8. Cerri S, Mus L, Blandini F. Parkinson's Disease in Women and Men: What's the Difference? J Parkinsons Dis. 2019;9(3):501–515. doi: 10.3233/JPD-191683
9. Chia SJ, Tan EK, Chao YX. Historical Perspective: Models of Parkinson's Disease. Int J Mol Sci. 2020;21(7):2464. doi: 10.3390/ijms21072464
10. Chen Z, Li G, Liu J. Autonomic dysfunction in Parkinson's disease: Implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis. 2020;134:104700. doi: 10.1016/j.nbd.2019.104700
11. Day JO, Mullin S. The Genetics of Parkinson's Disease and Implications for Clinical Practice. Genes (Basel). 2021;12(7):1006. doi: 10.3390/genes12071006
12. De Miranda BR, Goldman SM, Miller GW, Greenamyre JT, Dorsey ER. Preventing Parkinson's Disease: An Environmental Agenda. J Parkinsons Dis. 2022;12(1):45–68. doi: 10.3233/JPD-212922
13. Di Paolo M, Papi L, Gori F, Turillazzi E. Natural Products in Neurodegenerative Diseases: A Great Promise but an Ethical Challenge. Int J Mol Sci. 2019;20(20):5170. doi: 10.3390/ijms20205170
14. Durães F, Pinto M, Sousa E. Old Drugs as New Treatments for Neurodegenerative Diseases. Pharmaceuticals (Basel). 2018;11(2):44. doi: 10.3390/ph11020044
15. Elsworth JD. Parkinson's disease treatment: past, present, and future. J Neural Transm (Vienna). 2020;127(5):785–791. doi: 10.1007/s00702–020–02167–1
16. Fan B, Jabeen R, Bo B, Guo C, Han M, Zhang H, Cen J, Ji X, Wei J. What and How Can Physical Activity Prevention Function on Parkinson's Disease? Oxid Med Cell Longev. 2020;2020:4293071. doi: 10.1155/2020/4293071
17. Gao C, Liu J, Tan Y, Chen S. Freezing of gait in Parkinson's disease: pathophysiology, risk factors and treatments. Transl Neurodegener. 2020;9:12. doi: 10.1186/s40035–020–00191–5
18. Gazerani P. Probiotics for Parkinson's Disease. Int J Mol Sci. 2019;20(17):4121. doi: 10.3390/ijms20174121
19. Hanif S, Muhammad P, Chesworth R, Rehman FU, Qian RJ, Zheng M, Shi BY. Nanomedicine-based immunotherapy for central nervous system disorders. Acta Pharmacol Sin. 2020;41(7):936–953. doi: 10.1038/s41401–020–0429-z
20. Jagaran K, Singh M. Nanomedicine for Neurodegenerative Disorders: Focus on Alzheimer's and Parkinson's Diseases. Int J Mol Sci. 2021;22(16):9082. doi: 10.3390/ijms22169082
21. Murata H, Barnhill LM, Bronstein JM. Air Pollution and the Risk of Parkinson's Disease: A Review. Mov Disord. 2022;37(5):894–904. doi: 10.1002/mds.28922
22. Nielsen NS, Skovbølling SL. [Non-motor symptoms in Parkinson's disease]. Ugeskr Laeger. 2021;183(27):V01210089
23. Nwabufo CK, Aigbogun OP. Diagnostic and therapeutic agents that target alpha-synuclein in Parkinson's disease. J Neurol. 2022;269(11):5762–5786. doi: 10.1007/s00415–022–11267–9
24. Pauwels EKJ, Boer GJ. Parkinson's Disease: A Tale of Many Players. Med Princ Pract. 2023;32(3):155–165. doi: 10.1159/000531422
25. Post B, van den Heuvel L, van Prooije T, van Ruissen X, van de Warrenburg B, Nonnekes J. Young Onset Parkinson's Disease: A Modern and Tailored Approach. J Parkinsons Dis. 2020;10(s1):S29-S36. doi: 10.3233/JPD-202135
26. Rocca WA. The burden of Parkinson's disease: a worldwide perspective. Lancet Neurol. 2018;17(11):928–929. doi: 10.1016/S1474–4422(18)30355–7
27. Simon DK, Tanner CM, Brundin P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin Geriatr Med. 2020;36(1):1–12. doi: 10.1016/j.cger.2019.08.002
28. Salamon A, Zádori D, Szpisjak L, Klivényi P, Vécsei L. Neuroprotection in Parkinson's disease: facts and hopes. J Neural Transm (Vienna). 2020;127(5):821–829. doi: 10.1007/s00702–019–02115–8
29. Taximaimaiti R, Luo X, Wang XP. Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson's Disease. Curr Neuropharmacol. 2021;19(12):2233–2249. doi: 10.2174/1570159X19666210517115706
30. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021;20(5):385–397. doi: 10.1016/S1474–4422(21)00030–2
31. Tremblay C, Frasnelli J. Olfactory-Trigeminal Interactions in Patients with Parkinson's Disease. Chem Senses. 2021;46:bjab018. doi: 10.1093/chemse/bjab018
32. Varesi A, Campagnoli LIM, Fahmideh F, Pierella E, Romeo M, Ricevuti G, Nicoletta M, Chirumbolo S, Pascale A. The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment. Int J Mol Sci. 2022;23(20):12289. doi: 10.3390/ijms232012289
33. Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AF, Rodriguez-Violante M, Schrag A. The neuropsychiatry of Parkinson's disease: advances and challenges. Lancet Neurol. 2022;21(1):89–102. doi: 10.1016/S1474–4422(21)00330–6