Vol 10, No 4 (2016)

Original articles

Pathogenetic stroke subtypes and their diagnostic criteria in patients with ischemic heart disease and intracranial atherosclerosis: a clinical-morphological study

Ablyakimov R.E., Anufriev P.L., Tanashyan M.M.

Abstract

Introduction. An important objective of vascular neurology is to improve understanding of the pathogenetic subtypes of ischemic stroke and their diagnostic criteria, making it possible to perform targeted treatment and adequate prevention of cerebral circulation disorders.
Objective. To identify the pathogenetic stroke subtypes and to specify whether their differential diagnosis is possible in patients with ischemic heart disease (IHD) combined with intracranial atherosclerosis.
Materials and methods. The results of the morphological study and the findings of intravital examination of patients in 40 postmortem cases are compared.
Results. It is shown that the same forms of IHD (atrial fibrillation, myocardial infarction, or postinfarction cardiosclerosis) combined with intracranial atherosclerosis may result in stroke classified as belonging to different pathogenetic subtypes: cardiogenic embolic or hemodynamic stroke, with an almost identical incidence rate (51 and 49%, respectively). In at least 90% of cases, diagnosis of cardiogenic embolic strokes can be based on revealing the infarction outside the regions of the adjacent blood supply of cerebral arteries if a patient had the embolic form of IHD and did not have pronounced stenosis and embologenic atherosclerotic plaques on the ipsilateral side to the infarction. In at least 72% of cases, hemodynamic strokes were determined by the IHD-related hemodynamic factor that was responsible for the development of infarction in the zones of adjacent blood supply or lacunar stroke if there was pronounced ipsilateral stenosis. The hemorrhagic component in brain infarctions (38%) and asymptomatic embolism of the internal organs (46%) were found to be associated with cardiogenic and embolic strokes, as well as hemodynamic strokes with atypical localization and extent of infarction related to intracranial tandem stenosis.
Conclusion. The early risks of developing both cardiogenic embolic stroke and hemodynamic stroke were shown to be equal in patients with IHD and intracranial atherosclerosis. It has been proved that these stroke subtypes have distinctive features that enable differential diagnosis of these two diseases.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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Prevalence of the risk factors of cerebrovascular disorders in the capital city residents aged 40–59: a clinical and epidemiological study

Gnedovskaya E.V., Kravchenko M.A., Prokopovich M.E., Andreeva O.S., Sergeev D.V., Oshchepkova E.V., Varakin Y.Y., Piradov M.A.

Abstract

Introduction. Circulatory system diseases and cerebrovascular disorders are among the principal causes of morbidity and mortality in the Russian Federation. Updated information on prevalence and structure of the risk factors is needed to elaborate populationwide prevention measures.
The aim is to assess the prevalence of the risk factors for cerebrovascular disorders in the working-age population of capital city residents and stratification of subjects into the risk groups using clinical scales for comprehensive evaluation.
Materials and methods. Thorough screening of the open population aged 40–59 was carried out at one outpatient medical service facility in Moscow in 2011–2012: 376 subjects (156 men, 220 women). The analysis took into account gender and agerelated differences (in the age groups of 49–49 and 50–59-yearold adults).
Results. We obtained the data on prevalence of the major risk factors of cerebrovascular disorders, men/women (%): family history – 38.5/55.9, smoking 40.4/25.9, low physical activity – 48.4/49.5, class 1 obesity – 21.8/21.4, class 2 and 3 obesity – 6.4/12.7, elevated serum cholesterol levels – 32.7/43.2, elevated serum triglyceride levels – 23.1/15.0, hypertension – 48.1/45.0, type 2 diabetes – 3.8/2.7, increased intima-media thickness in the carotid and femoral arteries – 44.9/65.9, atherosclerotic plaques of any localization (carotid and/or femoral arteries) 62.8/40.5, and >30% atherosclerotic stenosis of any localization – 12.2/7.7. Prevalence of the risk factors in the population and, in some cases, their severity increased with age (before and after age 50) up to 1.5–2 fold. When using SCORE and Stroke Riskometer ™ tools for stratification, 8.6% and 39.3% subjects fell into the high-risk groups, respectively.
Conclusion. Working-age capital city residents in the 40–59 years cohort show high prevalence of risk factors for cardiovascular and cerebrovascular disorders with the first significant rise of prevalence after reaching a 50-year age border; hypertension, low physical activity and increased intima-media thickness hold leading positions. The newest Stroke Riskometer™ appears to be the most relevant tool for the risk assessing as it has a variety of undoubted advantages compared to other clinical instruments.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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The features of sensorimotor integration in patients with levodopa-induced dyskinesia in Parkinson’s disease

Alenikova O.A., Likhachev S.A., Svinkovskaya T.V.

Abstract

Introduction. Parkinson’s disease (PD) is characterized not only by motor but also by a number of nonmotor symptoms, such as sensory, vegetative, and psycho-emotional disorders.
Objective. To study the states of the somatosensory system and the sensorimotor integration in patients with levodopa-induced dyskinesia (LID).
Materials and methods. Fifty-two patients with LID associated with PD (Hoehn and Yahr stage III–IV) and 29 patients free of dyskinesia were examined. The somatosensory evoked potentials (SSEPs) and blink reflex (BR) were studied.
Results. LID in PD were observed significantly more often among females than among males. No differences in disease duration and duration of levodopa administration were observed among patients free of dyskinesia and patients with LID. In the group of patients with LID, MRI examination showed increased brainstem reflex excitability. The acceleration of signal passing from the medulla oblongata to the cortex revealed according to the SSEP data in this group of patients is indicative of the increased reflex excitability at the spinal cord and brainstem, thalamic, and cortical levels. Significant differences in passage of sensory information were found between the two patient groups. Hence, in patients with LID, the latency N20 was 20 (19.6; 21.3) ms; P18, 16.0 (15.1; 16.6) ms; and N13, 13.7 (13.1; 14.8) and was reliably shorter than in the group of patients free of LID, where the latency N20 was 20.9 (20; 21.4) ms; Р18, 16.9 (16.2; 17.6); and N13, 14.2 (13.5; 15.2) ms.
Conclusions. The revealed alterations in parameters of blink reflex and SSEPs are hypothetically genetically determined in patients with LID. Objectification of these disorders at the earliest stages of the disease can help in assessing their role as predictor factors for development of LID. Allowance for these factors will make it possible to choose an appropriate treatment strategy and reduce the risk of complications associated with drug therapy.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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Activation of autophagy in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

Kochergin I.A., Tukhvatulin A.I., Logunov D.Y., Zakharova M.N.

Abstract

Introduction. Accumulation of intracellular protein aggregates is one of the key processes in pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is a complex process during which cell components and organelles are transferred inside lysosomes and are degraded. Autophagy disturbance was found to take place in various neurodegenerative diseases. Autophagy alteration can be observed not only in the central nervous system but also in peripheral blood mononuclear cells (PBMCs). Protein LC3 is the key marker of autophagy.
Objective. To determine protein LC3 concentration in PBMCs of ALS patients and to analyze the relationship between this parameter and clinical characteristics of the disease.
Materials and methods. The study involved 66 patients with definite ALS and 15 healthy volunteers. Past medical history was elicited in all patients; neurological examination and the pulmonary function test were performed. PBMCs were isolated from blood of patients and healthy volunteers. The cells were lysed and subjected to Western blot analysis using anti-LC3 antibodies.
Results. The LC3-I level in PBMCs of ALS patients was increased compared to that in the control group (p<0.001). The LC3-I/LC3-II level was elevated in patients with the lumbosacral form of ALS (stage II ALS and the slow rate of disease progression). The tendency towards increased LC3-II level was observed for the bulbar form and stage III ALS.
Conclusions. The results demonstrated for the first time that PBMCs of ALS patients tend to exhibit a higher level of autophagy activity compared to healthy volunteers.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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Immunohistochemical and ultrasonic signs of the disturbance of anti-thrombogenic properties of endothelium in atherosclerosis of the carotid sinus

Evdokimenko A.N., Gulevskaya T.S., Tanashyan M.M.

Abstract

Introduction. Endothelial dysfunction is currently believed to play a crucial role in pathogenesis of atherosclerosis. Nevertheless, there are only few studies that demonstrate the relationship between changes in parameters of the atherosclerotic process and the main functional properties of endothelium. In addition, the findings are often controversial, which served as an incentive for this study.
Materials and methods. Thirteen atherosclerotic plaques resected during carotid endarterectomy were subjected to immunochemical and electron microscopy examination. The intensity of expression of the von Willebrand factor, thrombomodulin, and endothelial nitric acid synthase was assessed semi-quantitatively and compared to the main parameters of activity and the course of atherosclerosis in a plaque (volume of atheromatosis, lipophage aggregation, infiltration of the fibrous cap by monocytes and macrophages). Complicated and uncomplicated plaques were also compared.
Results. The level of von Willebrand factor in the carotid sinus endothelium increased as lipids were accumulated in it and as the fibrous cap was infiltrated by monocytes and macrophages (р<0.017), as opposed to the levels of thrombomodulin and endothelial nitric oxide synthase whose expression did not show the activity of the atherosclerotic process and did not correlate with the level of von Willebrand factor. Meanwhile, the expression of thrombomodulin and endothelial nitric oxide synthase correlated with each other (р=0.004). No difference in staining intensity for all three markers was detected between the complicated and uncomplicated plaques. Ultrasonic analysis of endothelium demonstrated the strongly pronounced disturbance of anti-thrombogenicity of the vascular wall as a result of numerous defects of the endothelial stratum, adhesion of blood cells to the arterial surface causing microthrombi formation and activation of endotheliocytes along with dystrophic changes in them, necrosis, and exfoliation into the vascular lumen.
Conclusions. The von Willebrand factor is found to have high diagnostic significance in the assessment of activity of the atherosclerotic process in the carotid sinus and the risk of developing complications. Thrombomodulin and endothelial nitric acid synthase are not recommended to be used as biomarkers of progression of atherosclerosis of this localization, since they are not indicative of the intensity of inflammatory response and destructive processes in a plaque.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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Transplantation of neuronal precursors derived from induced pluripotent stem cells into the striatum of rats with the toxin-induced model of Huntington’s disease

Stavrovskaya A.V., Yamshchikova N.G., Ol’shanskiy A.S., Konovalova E.V., Illarioshkin S.N.

Abstract

Introduction. Huntington’s disease (HD) is a severe neurodegenerative disorder characterized by choreic hyperkinesis, cognitive decline, behavioral disorders, and progressive neuronal death, mostly in the striatum. Since HD is a fatal disorder, searching for efficient treatment methods, including those based on cell replacement therapy, is quite relevant. The experimental models of HD are used increasingly often.
The objective of the study was to assess effectiveness and safety of transplantation of neuronal precursors differentiated from induced pluripotent stem cells (iPSCs) from a healthy donor into the striatum of rats with 3-NPA-induced HD model.
Materials and methods. We studied the influence of neurotransplantation on the behavioral effects in rats with HD model induced by intrastriatal injection of 3-nitropropiotic acid (3-NPA). In the study group of animals (n=11), human neuronal precursors derived from iPSCs of a healthy volunteer were transplanted into the caudate nuclei (5×105 per 5 μl of normal saline solution bilaterally); the control group of animals (n=10) received normal saline solution. The animals were tested using the Any-maze video tracking system; the parameters of the open-field test and the conditioned avoidance response test were evaluated.
Results. An analysis of behavioral effects after transplantation demonstrated that introduction of neuronal iPSC derivatives into the caudate nuclei of rats with induced HD model was accompanied by recovery of motor activity of the animals (horizontal and vertical), as opposed to the control group. It was found during testing the reproducibility of the conditioned avoidance responses that the conditioned avoidance responses in control animals were weakened, whereas intrastriatal transplantation of neurons abruptly increased the latency of moving into the dark compartment of the chamber in the conditioned avoidance response test.
Conclusions. The pilot experiment using the HD model showed that neurotransplantation using iPSC derivatives recovers the reduced motor activity in rats and improves memory trace keeping, which contributes to correction of motor and cognitive disorders induced by 3-NPA neurotoxin.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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The vascular type of Ehlers–Danlos syndrome

Gubanova M.V., Dobrynina L.A., Kalashnikova L.A.

Abstract

Ehlers–Danlos syndrome (EDS) type IV (vascular type of EDS) is a rare inherited autosomal dominant connective-tissue disorder caused by a mutation in the procollagen III gene (the COL3A1 gene). Patients with this syndrome are prone to rupture of arteries and hollow body organs. Among all types of EDS, type IV involves ~5–10% of cases. Vascular complications may develop in any anatomical region; large and medium-sized arteries are affected most frequently. Typical complications include dissection of the vertebral and carotid arteries at the extra- and intracranial levels, carotid-cavernous fistulas, and aneurysms. The diagnosis is based on major and minor clinical criteria and can be confirmed by laboratory tests: by detecting a quantitative and qualitative disruption of type III collagen synthesis by fibroblast culture or identifying the mutation in the COL3A1 gene. Invasive diagnostic techniques and surgical intervention should be used in case of life-threatening complications. Today, there is no specific technique for treating EDS. Our findings demonstrate that vascular complications in patients with EDS type IV were reduced by using β-blocker celiprolol. Inhibitors of the renin–angiotensin system and the agents lowering the concentration of transforming growth factor-beta open up new prospects for conservative treatment of this pathology and improve the future outlook.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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High-intensity focused ultrasound in functional neurosurgery

Tyurnikov V.M., Gushcha A.O.

Abstract

Stereotactic functional neurosurgical interventions for basal ganglia are an important method for treating movement, pain, obsessive compulsive and depressive disorders. These interventions include destructive surgeries and deep brain stimulation through implanted electrodes. Destructive surgeries have a number of serious limitations, since they are associated with a higher risk of complications, especially in case of bilateral interventions.
High-intensity focused ultrasound (HIFU) is a novel noninvasive approach proposed for destruction of a certain target point in the brain. We discuss the technical foundations of HIFU, thoroughly analyze the advantages and drawbacks of the method compared to other methods of modern functional neurosurgery, and summarize the first results of using HIFU in the world’s leading clinics. Further accumulation of experience is needed to perform a weighted analysis of the potential of HIFU and to assess the long-term effects of the interventions performed and the role of this procedure in the algorithms for treating various nervous system diseases.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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Challenges with the differential diagnosis of progressive supranuclear palsy and Parkinson’s disease

Magzhanov R.V., Davletova A.I., Ibatullin R.А., Tunik V.F., Idrisova R.F., Bakhtiyarova K.Z.

Abstract

Progressive supranuclear palsy (PSP) is a severe old-age neurodegenerative disease that is characterized by pronounced clinical polymorphism and has different phenotypes. Practical differential diagnosis of PSP and Parkinson’s disease (PD) presents significant challenge, especially in onset of the disease. We report an atypical case of PSP characterized by symmetric levodopa-resistant parkinsonian syndrome, early postural instability, supranuclear oculomotor disorders (vertical gaze palsy), MR signs of midbrain atrophy, and a number of overlapping clinical symptoms similar with the manifestations of PD. A detailed algorithm of differential diagnosis of PSP and PD as well as a more adequate diagnostic formulation are proposed for this and similar cases of neurodegenerative pathology.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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Psychogenic dystonia

Shavlovskaya O.A., Baidauletova A.I.

Abstract

Psychogenic movement disorders pose a complex problem in modern neurology that requires using the interdisciplinary approach to solve a number of questions related to classification, diagnosis, treatment, and rehabilitation. The most frequent forms of psychogenic movement disorders include tremor, dystonia, myoclonus, and gait abnormality. A clinical case of a 46-yearold male patient with psychogenic movement disorder presenting as fixed hand dystonia not accompanied by pain is reported. The terminology issues related to the most accurate determination of this type of hyperkinesis, as well as clinical tests (standard motor-skill tasks, ballpoint pen writing) that allow one to identify the psychogenic nature of hyperkinesis, are discussed using the example provided. The clinical phenomenology of psychogenic dystonia is thoroughly analyzed and the differential diagnostic criteria of psychogenic and primary (idiopathic) dystonia are presented.
Annals of Clinical and Experimental Neurology. 2016;10(4):
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