Молодежный инновационный вестникМолодежный инновационный вестник2415-7805Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации6718NEURONAL SUBSTRATES OF FORMATION AND POTENTIAL TREATMENTS FOR LEVODOPA-INDUCED DYSKINESIA IN PARKINSON'S DISEASEKutashovVyacheslav A.<pre id="tw-target-text" class="tw-data-text tw-text-large XcVN5d tw-ta" dir="ltr" data-placeholder="Перевод"><span lang="en">Doctor of Medical Sciences, Professor, Head of the Department of Neurology</span></pre>
<p> </p>kutash@mail.ruhttps://orcid.org/0000-0001-7535-8718VostrikovaKarina V.prudnikova.2012@inbox.ruhttps://orcid.org/0000-0003-2103-5328VGMU N.N.BurdenkoVGMU N.N. Burdenko1405202110S12682692703202112042021Copyright © 2021, Молодежный инновационный вестник2021<p>Relevance: Today, one of the main drugs for the treatment of Parkinson's disease is levodopa. Prolonged treatment leads to so-called dyskinesia.In this regard, at the moment, this problem continues to be relevant.</p>
<p>Objective: To evaluate possible clinical features, neuronal substrates of formation, as well as psychopharmacological and surgical methods of treatment of DVL.</p>
<p>Materials and methods: The studies for this review were selected from the PubMed and PsychINFO databases using the keywords "deep brain stimulation", "dopamine"," levodopa-induced dyskinesia", "Parkinson's disease".</p>
<p>Results: The most common symptoms of DVL were chorea and dystonia. It was found that the use of continuous infusion of levodopa was successful in the treatment of patients with severe PD and there was no risk of an increase in the formation of dyskinesia compared to oral therapy with levodopa.</p>
<p>Conclusion: DVL is a common side effect of PD treatment with dopamine. With parenteral administration of levodopa (including subcutaneous, intramuscular, and intravenous administration), there is a lower probability of DVL.</p>Parkinson's diseasedopaminelevodopa-induced dyskinesiadeep brain stimulation.Болезнь Паркинсонадофаминдискинезия, вызванная леводопойглубокая стимуляция мозга.<p><strong>RELEVANCE</strong></p>
<p>Today, one of the main drugs for the treatment of Parkinson's disease is levodopa. Prolonged treatment leads to the so-called dyskinesia. In this regard, at the moment, this problem continues to be relevant.</p>
<p><strong>PURPOSE</strong></p>
<p>To evaluate possible clinical features, neuronal substrates of formation, as well as psychopharmacological and surgical methods of treatment of DVL.</p>
<p><strong>MATERIALS AND METHODS</strong></p>
<p>The studies for this review were selected from PubMed and PsychINFO databases using the keywords "deep brain stimulation", "dopamine"," levodopa-induced dyskinesia","Parkinson's disease". Exclusion criteria: studies that included patients with neurological disorders other than Parkinson's disease; no control group; and non-English-language research publications. In addition, studies with neuroimaging, neurophysiological and pharmacological data on the topic under study were taken into account.</p>
<p><strong>RESULTS</strong></p>
<p>The most common symptoms of DVL were chorea and dystonia. In the course of the research, it was found that it is a single-nucleotide polymorphism in the DA transporter gene that is associated with the risk of DVL. fMRI studies at rest showed a positive relationship between the right inferior frontal gyrus cortex and the right shell and a negative relationship with the left motor cortex in the DVL group, but continuous repetitive transcranial magnetic stimulation of the lower frontal cortex reduced DVL [2]. It was found that the use of continuous infusion of levodopa was successful in the treatment of patients with severe PD and there was no risk of an increase in the formation of dyskinesia compared to oral therapy with levodopa. To assess the level of the PDE10A enzyme in the basal ganglia of 24 patients with PD treated with levodopa, compared with 12 healthy people, PET was used. Patients with PD without DVL showed reduced levels of PDE10A, patients with PD and DVL had even lower concentrations of PDE10A in the caudate nucleus and black matter.</p>
<p><strong>DISCUSSION</strong></p>
<p>It was found that the use of 5 HT agonists, PDE10A antagonists and DHA preparations was stopped by DAL. If drug therapy is ineffective, surgical interventions can be used: pallidotomy, subthalamotomy, or deep brain stimulation (DSM).</p>
<p><strong><span lang="EN-US">CONCLUSION</span></strong></p>
<p>DVL is a common side effect of PD treatment with dopamine. With parenteral administration of levodopa (including subcutaneous, intramuscular and intravenous administration), there is a lower probability of DVL. It has also been shown that DVL symptoms can be reduced by supplementing treatment with drugs that target other neural transmitters, such as 5HT agonists, PDE10A antagonists, and DHA drugs. These treatments reduce the symptoms of DVL by increasing the effectiveness of levodopa, which makes it possible to take it in a lower dosage.</p>[1. The motor inhibition system in Parkinson’s disease with levodopa-induced dyskinesias / Cerasa A., Donzuso G., Morelli et al. //Mov. Disord. 2015. N30. P. 1912–1920.][2. A network centered on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias /Cerasa A., Koch G., Donzuso G., et al.//Brain. 2015. N138. P. 414–427.][3. Chiken S. Mechanism of deep brain stimulation / Chiken S., Nambu A. // Neuroscientist. 2015. N22. P. 313–322.][4. Levodopa-induced dyskinesias / Fabbrini G., Brotchie J.M., Grandas F., et al.// Mov. Disord. 2007. N22. P. 1379–1389.][5. Fahn S. The spectrum of levodopa-induced dyskinesias / Fahn S., Neurol Ann.// 2000. Vol. 4, N47. P. 2–9.]