I. V. Chernykh, A. Shchulkin, P. Mylnikov, E. E. Kirichenko, M. V. Gatsanoga, E. Yakusheva
Introduction. Increased functional activity of the P-glycoprotein transporter (ABCB1) in the blood-brain barrier (BBB) is a possible reason why neuroprotective pharmacotherapy is ineffective after ischaemic stroke. Study aim to develop a way to inhibit the functional activity of ABCB1 at the BBB. Materials and methods. The study was performed on 60 male Wistar rats weighing 200-280 g. The functional activity of ABCB1 at the BBB was assessed by measuring the plasma and cortical levels of the marker transporter substrate fexofenadine (intravenous administration of 10 mg/kg). Thirty minutes before the administration of fexofenadine, 1 ml/kg of intravenous saline (n = 30) or 17.6 mg/kg of omeprazole, the transporter's systemic inhibitor (n = 30), was administered to the rats. The total amount of fexofenadine in the systemic circulation and the cerebral cortex was assessed using high performance liquid chromatography, by calculating the area under the blood concentrationtime curve (AUC0-t(plasma)) or the cerebral cortex concentration (AUC0-t(brain)). BBB permeability was calculated using the ratio AUC0-t(brain)/AUC0-t(plasma). Results. The administration of omeprazole before fexofenadine did not affect the plasma level of the latter at any time point under analysis. Fexofenadines AUC0-t(plasma) also did not differ between the series. However, the administration of omeprazole increased the cortical level of fexofenadine by 2.96 times (p = 0.009), 5 minutes after administration of the latter, and increased the AUC0-t(brain) by 1.49 times (p = 0.012). AUC0-t(brain)/AUC0-t(plasma) increased by 1.71 times when omeprazole was used (p = 0.003). Therefore, omeprazole inhibits the functional activity of ABCB1 at the BBB. Conclusions. We developed and tested a method for inhibiting ABCB1 activity at the BBB.
{"title":"A method of inhibiting the ABCB1 protein in the blood-brain barrier in vivo","authors":"I. V. Chernykh, A. Shchulkin, P. Mylnikov, E. E. Kirichenko, M. V. Gatsanoga, E. Yakusheva","doi":"10.54101/acen.2022.3.6","DOIUrl":"https://doi.org/10.54101/acen.2022.3.6","url":null,"abstract":"Introduction. Increased functional activity of the P-glycoprotein transporter (ABCB1) in the blood-brain barrier (BBB) is a possible reason why neuroprotective pharmacotherapy is ineffective after ischaemic stroke. \u0000Study aim to develop a way to inhibit the functional activity of ABCB1 at the BBB. \u0000Materials and methods. The study was performed on 60 male Wistar rats weighing 200-280 g. The functional activity of ABCB1 at the BBB was assessed by measuring the plasma and cortical levels of the marker transporter substrate fexofenadine (intravenous administration of 10 mg/kg). Thirty minutes before the administration of fexofenadine, 1 ml/kg of intravenous saline (n = 30) or 17.6 mg/kg of omeprazole, the transporter's systemic inhibitor (n = 30), was administered to the rats. The total amount of fexofenadine in the systemic circulation and the cerebral cortex was assessed using high performance liquid chromatography, by calculating the area under the blood concentrationtime curve (AUC0-t(plasma)) or the cerebral cortex concentration (AUC0-t(brain)). BBB permeability was calculated using the ratio AUC0-t(brain)/AUC0-t(plasma). \u0000Results. The administration of omeprazole before fexofenadine did not affect the plasma level of the latter at any time point under analysis. Fexofenadines AUC0-t(plasma) also did not differ between the series. However, the administration of omeprazole increased the cortical level of fexofenadine by 2.96 times (p = 0.009), 5 minutes after administration of the latter, and increased the AUC0-t(brain) by 1.49 times (p = 0.012). AUC0-t(brain)/AUC0-t(plasma) increased by 1.71 times when omeprazole was used (p = 0.003). Therefore, omeprazole inhibits the functional activity of ABCB1 at the BBB. \u0000Conclusions. We developed and tested a method for inhibiting ABCB1 activity at the BBB.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84200649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Bakulin, A. Poydasheva, A. Zabirova, N. Suponeva, M. Piradov
Metaplasticity (plasticity of synaptic plasticity) is defined as a change in the direction or degree of synaptic plasticity in response to preceding neuronal activity. Recent advances in brain stimulation methods have enabled us to non-invasively examine cortical metaplasticity, including research in a clinical setting. According to current knowledge, non-invasive neuromodulation affects synaptic plasticity by inducing cortical processes that are similar to long-term potentiation and depression. Two stimulation blocks are usually used to assess metaplasticity priming and testing blocks. The technology of studying metaplasticity involves assessing the influence of priming on the testing protocol effect. Several dozen studies have examined the effects of different stimulation protocols in healthy persons. They found that priming can both enhance and weaken, or even change the direction of the testing protocol effect. The interaction between priming and testing stimulation depends on many factors: the direction of their effect, duration of the stimulation blocks, and the interval between them. Non-invasive brain stimulation can be used to assess aberrant metaplasticity in nervous system diseases, in order to develop new biomarkers. Metaplasticity disorders are found in focal hand dystonia, migraine with aura, multiple sclerosis, chronic disorders of consciousness, and age-related cognitive changes. The development of new, metaplasticity-based, optimized, combined stimulation protocols appears to be highly promising for use in therapeutic neuromodulation in clinical practice.
{"title":"Metaplasticity and non-invasive brain stimulation: the search for new biomarkers and directions for therapeutic neuromodulation","authors":"I. Bakulin, A. Poydasheva, A. Zabirova, N. Suponeva, M. Piradov","doi":"10.54101/acen.2022.3.9","DOIUrl":"https://doi.org/10.54101/acen.2022.3.9","url":null,"abstract":"Metaplasticity (plasticity of synaptic plasticity) is defined as a change in the direction or degree of synaptic plasticity in response to preceding neuronal activity. Recent advances in brain stimulation methods have enabled us to non-invasively examine cortical metaplasticity, including research in a clinical setting. According to current knowledge, non-invasive neuromodulation affects synaptic plasticity by inducing cortical processes that are similar to long-term potentiation and depression. Two stimulation blocks are usually used to assess metaplasticity priming and testing blocks. The technology of studying metaplasticity involves assessing the influence of priming on the testing protocol effect. \u0000Several dozen studies have examined the effects of different stimulation protocols in healthy persons. They found that priming can both enhance and weaken, or even change the direction of the testing protocol effect. The interaction between priming and testing stimulation depends on many factors: the direction of their effect, duration of the stimulation blocks, and the interval between them. \u0000Non-invasive brain stimulation can be used to assess aberrant metaplasticity in nervous system diseases, in order to develop new biomarkers. Metaplasticity disorders are found in focal hand dystonia, migraine with aura, multiple sclerosis, chronic disorders of consciousness, and age-related cognitive changes. \u0000The development of new, metaplasticity-based, optimized, combined stimulation protocols appears to be highly promising for use in therapeutic neuromodulation in clinical practice.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75625955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Annushkin, A. A. Nikonov, M. Maksimova, Оlga V. Lagoda, M. Tanashyan
The article describes two clinical cases of stroke in the artery of Percheron territory. The difficulty in recognizing the causes of ischaemic stroke in these patients was due to the polymorphism in the mental disorders and the rare "strategic infarct dementia", as well as impaired consciousness. We hereby present the clinical features of this condition, which can be used together with neuroimaging methods (including various MRI sequences) to ensure a timely and accurate diagnosis. The authors describe a clinical case to demonstrate their approach to the diagnosis and management of this patient group.
{"title":"Clinical features of stroke in the artery of Percheron territory (case series)","authors":"V. Annushkin, A. A. Nikonov, M. Maksimova, Оlga V. Lagoda, M. Tanashyan","doi":"10.54101/acen.2022.3.11","DOIUrl":"https://doi.org/10.54101/acen.2022.3.11","url":null,"abstract":"The article describes two clinical cases of stroke in the artery of Percheron territory. The difficulty in recognizing the causes of ischaemic stroke in these patients was due to the polymorphism in the mental disorders and the rare \"strategic infarct dementia\", as well as impaired consciousness. We hereby present the clinical features of this condition, which can be used together with neuroimaging methods (including various MRI sequences) to ensure a timely and accurate diagnosis. \u0000The authors describe a clinical case to demonstrate their approach to the diagnosis and management of this patient group.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75179922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ekaterina A. Ruina, Ekaterina A. Aleksandrova, Elena V. Parshina, Danil N. Rodygin, V. S. Yulin
A review of Russian and foreign medical literature, as well as the Web of Science, PubMed and Scopus databases, revealed 8 cases of multiple sclerosis and Parkinson's disease co-occurrence. Parkinson's disease is a chronic, progressive neurological disease caused by degeneration of dopaminergic neurons in the substantia nigra. Multiple sclerosis is a chronic demyelinating disease, in which a range of autoimmune-driven inflammatory and neurodegenerative processes lead to formation of numerous focal and diffuse lesions in the central nervous system, resulting in disability and a significant decrease in patient quality of life. The co-occurrence of these two neurodegenerative CNS disorders is rarely seen in clinical practice. The authors describe a clinical case to demonstrate their approach to the diagnosis and management of this patient group.
通过对俄罗斯和国外医学文献以及Web of Science、PubMed和Scopus数据库的回顾，发现8例多发性硬化症和帕金森病共存。帕金森病是一种由黑质多巴胺能神经元退化引起的慢性进行性神经系统疾病。多发性硬化症是一种慢性脱髓鞘疾病，在这种疾病中，一系列自身免疫驱动的炎症和神经退行性过程导致中枢神经系统形成许多局灶性和弥漫性病变，导致残疾和患者生活质量显著下降。这两种神经退行性中枢神经系统疾病同时发生在临床上是很少见的。作者描述了一个临床病例，以证明他们的方法来诊断和管理这个病人组。
{"title":"Rare co-occurrence of multiple sclerosis and Parkinson's disease: a case report","authors":"Ekaterina A. Ruina, Ekaterina A. Aleksandrova, Elena V. Parshina, Danil N. Rodygin, V. S. Yulin","doi":"10.54101/acen.2022.3.10","DOIUrl":"https://doi.org/10.54101/acen.2022.3.10","url":null,"abstract":"A review of Russian and foreign medical literature, as well as the Web of Science, PubMed and Scopus databases, revealed 8 cases of multiple sclerosis and Parkinson's disease co-occurrence. Parkinson's disease is a chronic, progressive neurological disease caused by degeneration of dopaminergic neurons in the substantia nigra. Multiple sclerosis is a chronic demyelinating disease, in which a range of autoimmune-driven inflammatory and neurodegenerative processes lead to formation of numerous focal and diffuse lesions in the central nervous system, resulting in disability and a significant decrease in patient quality of life. The co-occurrence of these two neurodegenerative CNS disorders is rarely seen in clinical practice. \u0000The authors describe a clinical case to demonstrate their approach to the diagnosis and management of this patient group.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86896638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction. As Parkinson's disease (PD) develops, a number of non-motor signs precede motor symptoms, including gastrointestinal tract dysfunction. Modelling early-stage PD to comprehensively assess the pattern of morphofunctional changes in the gastrointestinal tract is important in order to develop methods of early disease diagnosis and more effective treatment of autonomic disturbances that are typical in PD, and to increase the patients' quality of life. Study aim to offer a model of early-stage PD through long-term oral administration of small doses of the neurotoxin rotenone to rats, and to study the functional and immunohistochemical changes in the gastrointestinal tract of the experimental animals, as well as changes in the substantia nigra. Materials and methods. The experiment was conducted in male Wistar rats aged 3.03.5 months. The study group rats (n = 10) were given rotenone orally at a dose of 5 mg/kg, as a suspension in a 4% carboxymethyl cellulose solution, every second day for 7 months. The control group rats (n = 10) received only the 4% carboxymethyl cellulose solution. The animals' mobility was assessed at the start and end of the experiment using the open field and narrowing beam-walking test. Gastrointestinal motility was assessed by measuring the passage of dye from the pylorus in a caudal direction along the small intestine. The rats were decapitated and immunohistochemistry was used to assess the density of dopamine neurons in the substantia nigra, nerve fibres, and glia in the Auerbach's plexus of the small intestine, and the location of the total and phosphorylated alpha-synuclein in the enteric nervous system. Results. Rats in the study group had a statistically significant reduction in the number of dopamine neurons in the substantia nigra. Auerbach's plexus of the small intestine contained significantly less nerve fibres and glia, while fluorescence intensity for alpha-synuclein was increased. Phosphorylated alpha-synuclein was identified in the cholinergic and adrenergic fibres of Auerbach's plexus. Experimental animals had a statistically significant reduction in the gastric emptying rate and small intestine motility compared to the control group. Conclusion. The presented model of early-stage PD enables the physiological and immunohistochemical symptoms of gastrointestinal dysfunction, similar to that of patients with PD, to be replicated. They are based on intestinal denervation changes and accumulation of abnormal forms of alpha-synuclein in the enteric nervous system.
{"title":"Modelling motor and non-motor signs of early-stage Parkinson's disease","authors":"M. Ivanov, K. A. Kutukova","doi":"10.54101/acen.2022.2.6","DOIUrl":"https://doi.org/10.54101/acen.2022.2.6","url":null,"abstract":"Introduction. As Parkinson's disease (PD) develops, a number of non-motor signs precede motor symptoms, including gastrointestinal tract dysfunction. Modelling early-stage PD to comprehensively assess the pattern of morphofunctional changes in the gastrointestinal tract is important in order to develop methods of early disease diagnosis and more effective treatment of autonomic disturbances that are typical in PD, and to increase the patients' quality of life. \u0000Study aim to offer a model of early-stage PD through long-term oral administration of small doses of the neurotoxin rotenone to rats, and to study the functional and immunohistochemical changes in the gastrointestinal tract of the experimental animals, as well as changes in the substantia nigra. \u0000Materials and methods. The experiment was conducted in male Wistar rats aged 3.03.5 months. The study group rats (n = 10) were given rotenone orally at a dose of 5 mg/kg, as a suspension in a 4% carboxymethyl cellulose solution, every second day for 7 months. The control group rats (n = 10) received only the 4% carboxymethyl cellulose solution. \u0000The animals' mobility was assessed at the start and end of the experiment using the open field and narrowing beam-walking test. Gastrointestinal motility was assessed by measuring the passage of dye from the pylorus in a caudal direction along the small intestine. The rats were decapitated and immunohistochemistry was used to assess the density of dopamine neurons in the substantia nigra, nerve fibres, and glia in the Auerbach's plexus of the small intestine, and the location of the total and phosphorylated alpha-synuclein in the enteric nervous system. \u0000Results. Rats in the study group had a statistically significant reduction in the number of dopamine neurons in the substantia nigra. Auerbach's plexus of the small intestine contained significantly less nerve fibres and glia, while fluorescence intensity for alpha-synuclein was increased. Phosphorylated alpha-synuclein was identified in the cholinergic and adrenergic fibres of Auerbach's plexus. Experimental animals had a statistically significant reduction in the gastric emptying rate and small intestine motility compared to the control group. \u0000Conclusion. The presented model of early-stage PD enables the physiological and immunohistochemical symptoms of gastrointestinal dysfunction, similar to that of patients with PD, to be replicated. They are based on intestinal denervation changes and accumulation of abnormal forms of alpha-synuclein in the enteric nervous system.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73347307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. I. Solovyeva, M. Sinkin, A. E. Talypov, D. I. Abzalova, G. R. Ramazanov, Ester D. Mehia-Mehia, E. Y. Bakharev, K. A. Popugayev, A. Grin
Introduction. Clinical assessment of consciousness in patients coming out of a coma remains a topic of discussion. Monitoring these patients over time is challenging not only because of the slow fluctuations in their neurological status, but also because doctors are not fully aware of the classification of chronic disorders of consciousness (CDC), and how to use the Coma Recovery Scale-revised (CRS-R), which was specifically developed for this group of patients. In practice, most doctors use standard neurological examination to assess consciousness rather than the CRS-R. We have hypothesized that this approach leads to contradictory and poorly standardized results. Materials and methods. We investigated the level of inter-expert reliability in pairs of three medical specialists: neurologists, neurosurgeons and neurocritical care specialists (working in neurocritical care units) in the clinical assessment of consciousness. Their examination findings were compared to the CRS-R scores. Results. The inter-expert reliability was poor in all three specializations when using clinical examination to determine the degree of impaired consciousness in patients with CDC. An average level of IER (Cohen's kappa = 0.46) was found only in the neurosurgeonCRS-R pair. Conclusion. A scale with detailed criteria is different to a standard clinical examination and has a higher level of IER. Moving from subjective evaluation to a standardized CRS-R will enable medical specialists to determine a patients rehabilitation potential and predict disease progression more accurately. Educational programmes, including virtual platforms, should be developed to encompass most of the medical community.
{"title":"Clinical assessment of patients with chronic disorders of consciousness by different medical specialists","authors":"P. I. Solovyeva, M. Sinkin, A. E. Talypov, D. I. Abzalova, G. R. Ramazanov, Ester D. Mehia-Mehia, E. Y. Bakharev, K. A. Popugayev, A. Grin","doi":"10.54101/acen.2022.2.5","DOIUrl":"https://doi.org/10.54101/acen.2022.2.5","url":null,"abstract":"Introduction. Clinical assessment of consciousness in patients coming out of a coma remains a topic of discussion. Monitoring these patients over time is challenging not only because of the slow fluctuations in their neurological status, but also because doctors are not fully aware of the classification of chronic disorders of consciousness (CDC), and how to use the Coma Recovery Scale-revised (CRS-R), which was specifically developed for this group of patients. In practice, most doctors use standard neurological examination to assess consciousness rather than the CRS-R. We have hypothesized that this approach leads to contradictory and poorly standardized results. \u0000Materials and methods. We investigated the level of inter-expert reliability in pairs of three medical specialists: neurologists, neurosurgeons and neurocritical care specialists (working in neurocritical care units) in the clinical assessment of consciousness. Their examination findings were compared to the CRS-R scores. \u0000Results. The inter-expert reliability was poor in all three specializations when using clinical examination to determine the degree of impaired consciousness in patients with CDC. An average level of IER (Cohen's kappa = 0.46) was found only in the neurosurgeonCRS-R pair. \u0000Conclusion. A scale with detailed criteria is different to a standard clinical examination and has a higher level of IER. Moving from subjective evaluation to a standardized CRS-R will enable medical specialists to determine a patients rehabilitation potential and predict disease progression more accurately. Educational programmes, including virtual platforms, should be developed to encompass most of the medical community.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82937770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cerebellar degeneration remains a poorly studied topic. Excitotoxicity, i.e. neuronal damage and death due to excess activation of postsynaptic N-methyl-D-aspartate receptors (NMDAR) by glutamate, is considered to be a universal mechanism of most neurodegenerative conditions. The use of antagonists that predominantly block NMDAR in cases of excitotoxicity is a very promising treatment strategy for neurodegenerative disorders. This review presents the known structure and function of NMDAR. Information on studies investigating the use of NMDAR antagonists in the treatment of neurodegenerative diseases is provided. Creation of new therapies to correct excitotoxicity in various neurodegenerative disorders, for example, spinocerebellar ataxias, requires further study of the subunit composition and the role of NMDAR in the cerebellum. Treatment methods that combine the use of extrasynaptic NMDAR antagonists or synaptic NMDAR agonists with drugs that affect the total amount of glutamate in the synaptic cleft are promising.
小脑变性仍然是一个研究较少的话题。兴奋性毒性，即由于谷氨酸过度激活突触后n -甲基- d -天冬氨酸受体(NMDAR)而导致的神经元损伤和死亡，被认为是大多数神经退行性疾病的普遍机制。在兴奋性毒性的情况下，使用主要阻断NMDAR的拮抗剂是一种非常有前途的治疗神经退行性疾病的策略。本文综述了NMDAR的结构和功能。提供了研究NMDAR拮抗剂在神经退行性疾病治疗中的应用的信息。创造新的治疗方法来纠正各种神经退行性疾病(例如脊髓小脑共济失调)的兴奋性毒性，需要进一步研究NMDAR的亚基组成和在小脑中的作用。结合使用突触外NMDAR拮抗剂或突触性NMDAR激动剂与影响突触间隙中谷氨酸总量的药物的治疗方法是有希望的。
{"title":"NMDA receptor antagonists as potential therapy in cerebellar degenerative disorders","authors":"O. Belozor, A. Shuvaev, Y. Fritsler, A. Shuvaev","doi":"10.54101/acen.2022.2.7","DOIUrl":"https://doi.org/10.54101/acen.2022.2.7","url":null,"abstract":"Cerebellar degeneration remains a poorly studied topic. Excitotoxicity, i.e. neuronal damage and death due to excess activation of postsynaptic N-methyl-D-aspartate receptors (NMDAR) by glutamate, is considered to be a universal mechanism of most neurodegenerative conditions. The use of antagonists that predominantly block NMDAR in cases of excitotoxicity is a very promising treatment strategy for neurodegenerative disorders. \u0000This review presents the known structure and function of NMDAR. Information on studies investigating the use of NMDAR antagonists in the treatment of neurodegenerative diseases is provided. Creation of new therapies to correct excitotoxicity in various neurodegenerative disorders, for example, spinocerebellar ataxias, requires further study of the subunit composition and the role of NMDAR in the cerebellum. Treatment methods that combine the use of extrasynaptic NMDAR antagonists or synaptic NMDAR agonists with drugs that affect the total amount of glutamate in the synaptic cleft are promising.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89733856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Bril, E. Belova, A. S. Sedov, A. Gamaleya, A. Poddubskaya, N. Fedorova, Аleksey A. Tomskiy
Specific mechanisms underlying the therapeutic effects of neurostimulation in Parkinson's disease remain a topic of discussion and intense study. Understanding these mechanisms can serve as the foundation for developing and selecting more effective parameters to relieve the symptoms of Parkinson's disease, maximize the advantages, and reduce the adverse effects and need for surgical intervention. The article discusses existing models of motor control in the basal ganglia in healthy individuals and in PD from the point of view of neuromodulation (changes in the impulse flow model, oscillatory model), as well as the current understanding of the mechanisms of action of deep brain stimulation (DBS): the block depolarization hypothesis, neural interference hypothesis, synaptic depression hypothesis, synaptic modulation hypothesis, and the DBS astrocytes hypothesis. Factors such as DBS location and neurostimulation parameters, affecting the clinical outcome, are considered in detail. The neuroprotective effect of DBS is also touched on.
{"title":"Current understanding of neurostimulation for Parkinson's disease","authors":"E. Bril, E. Belova, A. S. Sedov, A. Gamaleya, A. Poddubskaya, N. Fedorova, Аleksey A. Tomskiy","doi":"10.54101/acen.2022.2.10","DOIUrl":"https://doi.org/10.54101/acen.2022.2.10","url":null,"abstract":"Specific mechanisms underlying the therapeutic effects of neurostimulation in Parkinson's disease remain a topic of discussion and intense study. Understanding these mechanisms can serve as the foundation for developing and selecting more effective parameters to relieve the symptoms of Parkinson's disease, maximize the advantages, and reduce the adverse effects and need for surgical intervention. The article discusses existing models of motor control in the basal ganglia in healthy individuals and in PD from the point of view of neuromodulation (changes in the impulse flow model, oscillatory model), as well as the current understanding of the mechanisms of action of deep brain stimulation (DBS): the block depolarization hypothesis, neural interference hypothesis, synaptic depression hypothesis, synaptic modulation hypothesis, and the DBS astrocytes hypothesis. Factors such as DBS location and neurostimulation parameters, affecting the clinical outcome, are considered in detail. The neuroprotective effect of DBS is also touched on.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80449933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Legostaeva, E. Kremneva, D. Sinitsyn, E. Iazeva, D. Sergeev, A. Poydasheva, I. Bakulin, D. Lagoda, A. Sergeeva, Sofya N. Morozova, Y. Ryabinkina, M. Krotenkova, N. Suponeva, M. Piradov
Introduction. Rapid advances in critical care medicine have led to an increased survival rate of patients with severe brain damage and, consequently, to an increased prevalence of chronic disorders of consciousness (CDC). The lack of or fluctuations in signs of consciousness, which accompany the restoration of alertness after recovery from coma, indicate whether the type of CDC is a vegetative state or minimally conscious state. Correct diagnosis determines not only the rehabilitation outcome but also the economic outlook for a particular patient. However, the subjective nature of signs of consciousness, which are identified during clinical examination using neurological scales, is a common cause of diagnostic errors. The study of spontaneous activity using resting-state functional magnetic resonance imaging (fMRI) has helped to identify resting state networks. The default mode network (DMN) is one of the most studied brain networks. Its signal can change or be absent in patients with various types of CDC. Purpose. To study the signal of residual spontaneous brain activity in patients with CDC at rest. Materials and methods. Twenty-two patients with permanent CDC underwent resting state fMRI as an additional tool in the differential diagnosis between vegetative state and minimally conscious state at the Research Centre of Neurology. Results. It was found that the nature of the signal coming from anatomical regions that are part of the DMN changes when signs of consciousness emerge. Conclusion. These changes confirm that resting state fMRI is an important additional tool for differential diagnosis of CDC types. Accumulating knowledge about the brain's functional state helps us to expand our overall understanding of the nature of consciousness.
{"title":"Features of residual brain activity in patients with chronic disorders of consciousness on resting-state functional MRI","authors":"L. Legostaeva, E. Kremneva, D. Sinitsyn, E. Iazeva, D. Sergeev, A. Poydasheva, I. Bakulin, D. Lagoda, A. Sergeeva, Sofya N. Morozova, Y. Ryabinkina, M. Krotenkova, N. Suponeva, M. Piradov","doi":"10.54101/acen.2022.2.2","DOIUrl":"https://doi.org/10.54101/acen.2022.2.2","url":null,"abstract":"Introduction. Rapid advances in critical care medicine have led to an increased survival rate of patients with severe brain damage and, consequently, to an increased prevalence of chronic disorders of consciousness (CDC). The lack of or fluctuations in signs of consciousness, which accompany the restoration of alertness after recovery from coma, indicate whether the type of CDC is a vegetative state or minimally conscious state. Correct diagnosis determines not only the rehabilitation outcome but also the economic outlook for a particular patient. However, the subjective nature of signs of consciousness, which are identified during clinical examination using neurological scales, is a common cause of diagnostic errors. The study of spontaneous activity using resting-state functional magnetic resonance imaging (fMRI) has helped to identify resting state networks. The default mode network (DMN) is one of the most studied brain networks. Its signal can change or be absent in patients with various types of CDC. \u0000Purpose. To study the signal of residual spontaneous brain activity in patients with CDC at rest. \u0000Materials and methods. Twenty-two patients with permanent CDC underwent resting state fMRI as an additional tool in the differential diagnosis between vegetative state and minimally conscious state at the Research Centre of Neurology. \u0000Results. It was found that the nature of the signal coming from anatomical regions that are part of the DMN changes when signs of consciousness emerge. \u0000Conclusion. These changes confirm that resting state fMRI is an important additional tool for differential diagnosis of CDC types. Accumulating knowledge about the brain's functional state helps us to expand our overall understanding of the nature of consciousness.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84405047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. M. Galimova, D. I. Nabiullina, S. Illarioshkin, S. Safin, Y. Sidorova, G. Akhmadeeva, N. R. Mukhamadeeva, N. Zagidullin, Olga V. Kachemaeva, D. Krekotin, I. Buzaev
Introduction. Treatment with MRI-guided focused ultrasound (MRgFUS) is a new, non-invasive surgical technique for treating extrapyramidal movement disorders. This article presents the first use of MRgFUS in Russia for treating patients with essential tremor (ET). Materials and methods. Patients (n = 26; 17 men and 9 women) aged 2182 years (median age 46.0 years) and with severe and refractory ET, underwent MRgFUS thalamotomy (ExAblate 4000, Insightec). One side was treated in 22 patients (left thalamus in 18 and right thalamus in 6), both sides were treated concurrently in two patients, and both sides were treated consecutively in two patients. Tremor was assessed using the Clinical Rating Scale for Tremor (CRST). Because international clinical specialists could not visit Russia due to the COVID-19 pandemic, MRgFUS was performed via telehealth on May 5, 2020, in a world first. Results. A satisfactory result was achieved in 25 (96%) out of 26 patients. CRST scores improved by 64.7% on the side of the operation, by 10.2% on the control side, and by 37.5% overall. Intraoperative side effects included headache during sonication (42.3%), vertigo (15.4%), nausea (11.5%), vomiting (7.7%), numbness (3.8%), ataxia (3.8%), and pathological response to cold exposure (3.8%). The symptoms resolved immediately after surgery. Unstable gait was noted in five patients, which completely resolved two weeks after surgery. Median postoperative follow-up duration was 109 days [53; 231], with a maximum of 625 days. No relapses (if the hyperkinesia had completely disappeared) or increased tremor (if reduced after surgery) were observed. Conclusion. The efficacy of MRgFUS for ET was 96%, with no long-term complications. Both bilateral concurrent and bilateral consecutive MRgFUS thalamotomy is possible, but its efficacy and safety should be assessed in a randomized study. In a world first, MRgFUS was successfully implemented using telehealth.
{"title":"First use of MRI-guided focused ultrasound to treat patients with essential tremor in Russia","authors":"R. M. Galimova, D. I. Nabiullina, S. Illarioshkin, S. Safin, Y. Sidorova, G. Akhmadeeva, N. R. Mukhamadeeva, N. Zagidullin, Olga V. Kachemaeva, D. Krekotin, I. Buzaev","doi":"10.54101/acen.2022.2.1","DOIUrl":"https://doi.org/10.54101/acen.2022.2.1","url":null,"abstract":"Introduction. Treatment with MRI-guided focused ultrasound (MRgFUS) is a new, non-invasive surgical technique for treating extrapyramidal movement disorders. This article presents the first use of MRgFUS in Russia for treating patients with essential tremor (ET). \u0000Materials and methods. Patients (n = 26; 17 men and 9 women) aged 2182 years (median age 46.0 years) and with severe and refractory ET, underwent MRgFUS thalamotomy (ExAblate 4000, Insightec). One side was treated in 22 patients (left thalamus in 18 and right thalamus in 6), both sides were treated concurrently in two patients, and both sides were treated consecutively in two patients. Tremor was assessed using the Clinical Rating Scale for Tremor (CRST). Because international clinical specialists could not visit Russia due to the COVID-19 pandemic, MRgFUS was performed via telehealth on May 5, 2020, in a world first. \u0000Results. A satisfactory result was achieved in 25 (96%) out of 26 patients. CRST scores improved by 64.7% on the side of the operation, by 10.2% on the control side, and by 37.5% overall. Intraoperative side effects included headache during sonication (42.3%), vertigo (15.4%), nausea (11.5%), vomiting (7.7%), numbness (3.8%), ataxia (3.8%), and pathological response to cold exposure (3.8%). The symptoms resolved immediately after surgery. Unstable gait was noted in five patients, which completely resolved two weeks after surgery. Median postoperative follow-up duration was 109 days [53; 231], with a maximum of 625 days. No relapses (if the hyperkinesia had completely disappeared) or increased tremor (if reduced after surgery) were observed. \u0000Conclusion. The efficacy of MRgFUS for ET was 96%, with no long-term complications. Both bilateral concurrent and bilateral consecutive MRgFUS thalamotomy is possible, but its efficacy and safety should be assessed in a randomized study. In a world first, MRgFUS was successfully implemented using telehealth.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83405976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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