Vol 11, No 1 (2017)

Original articles

Personification of the approaches to reperfusion therapy of ischemic stroke

Domashenko M.A., Maksimova M.Y., Gafarova M.E., Tanashyan M.M., Antonova K.V., Piradov M.A.

Abstract

Introduction. Systemic thrombolytic therapy using recombinant tissue plasminogen activator (rtPA) is the “gold standard” of reperfusion therapy in certainpatients with ischemic stroke during the first 4.5 h after stroke onset.

Objective. To assess the clinical (severity of neurological symptoms) and laboratory (complete blood cell count test) factors that affect the disease prognosis aftersystemic thrombolytic therapy.

Materials and methods. Seventy patients (48 males and 22 females) aged 61 [54; 69] years with ischemic stroke who received systemic thrombolytic therapy withrtPA at a dose of 0.9 mg/kg were prospectively studied. Blood for the complete blood count test including neutrophil and lymphocyte counts was sampled before thethrombolytic therapy. The severity of neurological impairment was assessed using the NIH Stroke Scale. The functional prognosis was assessed 3 months afterstroke using the modified Rankin scale (mRS). Markers for the unfavorable prognosis of the acute phase of ischemic stroke (mRS score ≥3) were revealed by ROCanalysis involving sensitivity and specificity determination.

Results. Severity of neurological symptoms assessed using the NIH scale at admission was 15 [11; 17] points. Time between the manifestation of neurologicalsymptoms and admission to the hospital was 138 [117; 170] min; between admission and initiation of systemic thrombolytic therapy (the door-to-needle time),40 [30; 55] min. An unfavourable functional outcome of systemic thrombolytic therapy can be predicted according to the results of ROC analysis: the NIH score upon admissionbeing 12 or higher (sensitivity, 94%; specificity, 57%); neutrophil count, > 7.8•109/L (sensitivity, 45.5%; specificity, 90.6%); lymphocyte count, < 1.8•109/L(sensitivity, 81.8%; specificity, 59.4%).

Conclusions. The customized approach to systemic thrombolytic therapy can help predict its effectiveness and contribute to elaboration of adequate approachesto patient management. Patients with a potentially unfavourable prognosis for systemic thrombolysis can be the target group for using mechanical reperfusiontechniques such as thrombus extraction.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Behavioral disturbances in Parkinson's disease patients receiving dopaminergic therapy

Nikitina A.V., Fedorova N.V.

Abstract

Introduction. Parkinson’s disease (PD) is a progressive neurological disorder caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta. The most effective therapy for this disease includes dopaminergic drugs that may lead to the development of behavioral disturbances or impulse control disorders. The latter include compulsive buying, gambling addiction, hypersexuality, compulsive overeating, punding (nongoal oriented repetitive activity), and the dopamine dysregulation syndrome.

Objective. To reveal frequency of behavioral disturbances in patients with PD and assess their effect on quality-of-life parameters and activities of daily living in patients and their relatives.

Materials and methods. In order to determine the prevalence of impulse control disorders (ICD), 340 patients with PD were surveyed by completing the QUIPShort questionnaire to detect ICD. Sixty patients with PD with verified ICD (17% of the total number of patients examined) and 20 patients with PD without behavioral disturbances were included in further analysis; a number of specialized tests were used to assess ICD, impulsivity, activities of daily living, quality of life, anxiety, depression, and cognitive impairment.

Results. Dopamine dysregulation syndrome (DDS) was found in 8% of patients with PD; punding, in 10%; compulsive overeating, in 6%; hypersexuality, in 5%; compulsive buying, in 4%; and gambling addiction, in 1% of patients. The average parameter of activities of daily living for PD patients with ICD was 60.05 ± 9.76%; quality of life, 67.21 ± 18.54%. These values were significantly lower than those in patients without behavioral disturbances.

Conclusions. ICD is detected in every fifth patient with PD receiving dopaminergic therapy. DDS and punding are diagnosed most frequently. Development of ICD has a significant effect on patients’ activities of daily living and reduces quality of life both of the patients and their relatives.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Prediction of the outcome of the acute phase of ischemic stroke: the role of apoptotic markers

Sergeeva C.P., Savin A.A., Arkhipov V.V., Gul’tyaev M.M., Breslavich I.D., Litvitskii P.F.

Abstract

Introduction. Neuronal cell death (apoptosis) is not only a direct consequence of cerebral infarction, but also a crucial pathogenetic link of ischemic injury. Nevertheless, the role of apoptotic markers in prediction of the functional outcome of the acute phase of ischemic stroke (IS) has not been established.

Objective. To determine the possibility of predicting the outcome of the acute phase of ischemic stroke in the earliest period after its development by measuring thes FasL and sFas concentrations in peripheral blood.

Materials and methods. One hundred fifty-five individuals underwent in-hospital examination. They were subdivided into 3 groups: the control group included healthy volunteers (n=28) and two groups of patients depending on the outcome of the acute phase of IS: either with favourable (National Institutes of Health Stroke Scale score on day 21 ≤ 5) or unfavourable (the NIHSS score on day 21 > 5) outcomes. Concentrations of sFas and sFasL were measured on day 1, 7, and 21 after ischemic stroke by ELISA; the sFasL/sFas ratio was also determined.

Results. The outcome is favourable (NIHSS score on day 21 ≤ 5) if the sFasL/sFas ratio is ≤ 2.11 ± 0.58; otherwise, the outcome is unfavourable (NIHSS scoreon day 21 > 5).Conclusions. The proposed method is characterized by prognostic significance and high accuracy and can be used in clinical practice to determine the strategy for managing patients with IS.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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In-hospital stroke in patients after cardiovascular surgery

Filimonova P.A., Volkova L.I., Alasheev A.M., Grichuk E.A.

Abstract

Introduction. Strokes in patients managed at the department of cardiovascular surgery hold a leading position among all in-hospital strokes in multispeciality hospitals. According to the literature, the prevalence of stroke ranges from 0.2–0.4% for percutaneous cardiac interventions to 16% after heart valve surgeries.

Objective. To reveal the stroke risk factors in patients managed at the department of cardiovascular surgery, including depending on the type of surgical intervention.

Materials and methods. The study group included 58 cases of acute cerebrovascular accidents (ACVA) in patients at the department of cardiovascular surgery, amounting to 30.5% of the total amount of in-hospital strokes recorded over 5 years (2011–2016).

Results. Ischemic stroke was prevalent in the study group (54 patients; 93.1%, р<0.001); four (6.9%) patients had transient ischemic attacks. The largest number of strokes occurred in patients who had undergone heart bypass (23 patients, 41.1%) and heart valve replacement surgeries (25 patients, 44.6%); in 12 (21.4%) patients, ACVA occurred after mitral valve replacement combined with tricuspid annuloplasty. In most cases, stroke developed within the first three days after surgical intervention (36 patients, 64.3%, р<0.05).

Conclusions. Patients who had undergone cardiovascular interventions, especially after heart bypass and heart valve replacement surgeries, require hemodynamic monitoring and thromboelastography during the first 3 days to prevent a stroke. Despite the early detection of in-hospital strokes, systemic thrombolytic therapy was contraindicated for all patients. Mechanical thrombus extraction should be treatment of choice for this category of patients.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Activation of GPR81 lactate receptors stimulates mitochondrial biogenesis in cerebral microvessel endothelial cells

Khilazheva E.D., Pisareva N.V., Morgun A.V., Boitsova E.B., Taranushenko T.E., Frolova O.V., Salmina A.B.

Abstract

Introduction. Cerebral endothelial cells express monocarboxylate transporters MCT1 for blood–brain barrier (BBB) transfer of lactate, which are regulated by CD147 activity, as well as lactate receptors GPR81 (HCAR1). Metabolism and intercellular transport of lactate is the crucial mechanism for regulating the function of BBB cells.

Objective. To study the effect of activity of GPR81 receptors in cerebral endothelial cells on expression of MCT1, CD147 and the mitochondrial dynamics, which will make it possible to explain the effect of local production of lactate by perivascular astrocytes on angiogenesis in the cerebral tissue.

Materials and methods. The culture of cerebral endothelial cells isolated from the brain of 15–17-day-old Wistar rat embryos was used in this study. Mitochondrial biogenesis of cerebral endothelial cells was studied using the standard MitoBiogenesis In-Cell ELISA Kit protocol (Abcam). Chemical hypoxia was induced by incubation in the presence of 50 μM iodoacetate for 30 min. 3Cl-5OH-BA (Calbiochem) at concentrations of 5, 50, and 500 μM was used as an agonist of GPR81 lactate receptors during 24 h. The number of cells expressing GPR81, CD147, and MCT1 molecules was evaluated using indirect double-antibody ELISA.

Results. It was found for the first time that prolonged dose-dependent stimulation of GPR81 receptors with 3Cl-5OH-BA intensifies mitochondrial biogenesis (up to 1.5-fold, р<0.05). Meanwhile, a statistically significant (p<0.05) inhibition of expression of monocarboxylate transporters MCT1 (from 81±1.6% to 40.7±4.4%) and the conjugated CD147 protein (from 57.4±3.3% to 48.3±2.9%) in cerebral endothelial cells in the study group compared to the control group.

Conclusions. The findings broaden the range of potential applications of GPR81 agonists for modulating intercellular interactions in a neurovascular unit and controlling the functional activity of cerebral microvessel endothelial cells.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Immunocytochemical and morphometric changes in astroglial cells in the perifocal zone of the cerebral infarction model

Voronkov D.N., Sal’nikova O.V., Khudoerkov R.M.

Abstract

Introduction. The perifocal zone of cerebral infarction contains dying and reactively altered neurons whose fate depends on the type of intracellular interactions and, in particular, on the response of astrocytes partaking both in neuronal damage and neuroprotection. The features of the response of astrocytes to ischemic injury and the role of their activation in gliosis have been studied insufficiently.

Objective. To evaluate the changes in astroglia in the perifocal zone of cerebral infarction depending on its reproduction time by immunomorphology and computerassisted morphometry.

Materials and methods. Infarction was induced in the left hemisphere of rat brain cortex (n=10) by middle cerebral artery occlusion. Astrocyte distribution and shape were assessed on day 3 and 21 after surgery; localization of gliofibrillar acidic protein (GFAP), aquaporin 4 (AQP4), and glutamine synthetase (GlnS) in the perifocal zone was measured.

Results. Astrocyte shape and distribution, as well as GFAP expression, significantly altered depending on time that has passed since the infarction and distance to the injury focus. On day 3, the area occupied by astrocyte processes decreased by 15% of the control value, while increasing by 35% on day 21. Expression of GlnS and AQP4 near the infarction focus decreased on day 3, while opposite changes were observed on day 21. Redistribution of the studied proteins in processes of reactive astrocytes was also detected. Two morphological types of astrocytes were differentiated: the scarring polarized astrocytes, which were characterized by redistribution of marker proteins in processes, and the moderately altered transiently activated ones.

Conclusions. Astrocytes were found to be heterogeneous in the perifocal zone of cerebral infarction; a dependence between changes in their structure and function and the distance to the injury focus and time that passed after the infarction was revealed. The scarring and transiently activated astrocytes, which play different roles in remodeling and repair of ischemic neural tissue in the perifocal zone of cerebral infarction, were characterized by immunohistochemical and morphometric analysis.
Annals of Clinical and Experimental Neurology. 2017;11(1):
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Novel approaches to assessing the signs of atherosclerotic plaque instability in the carotid arteries

Chechetkin A.O., Druina L.D., Evdokimenko A.N., Gulevskaya T.S., Skrylev S.I., Tanashyan M.M.

Abstract

Introduction. Application of contrast agents in vascular untrasonography has become a new direction in noninvasive assessment of signs of atherosclerotic plaque (ASP) instability; the type of plaque neovascularization being the major sign. However, questions regarding the accuracy of the methods for quantitative evaluation of plaque neovascularization are still to be answered.

Objective. To evaluate signs of ASP instability in the carotid arteries according to the contrast-enhanced duplex scanning data and to elaborate our own approach to quantitative evaluation of neovascularization.

Materials and methods. Twenty-six patients with carotid atherosclerosis who had been subjected to carotid endarterectomy (n=27) followed by morphological plaque verification were enrolled in this study. All patients underwent standard duplex scanning and scanning using contrast agent SonoVue.

Results. Neovascularization was revealed in all 27 patients with ASP according to the pathomorphological and contrast-enhanced ultrasonography data. The total number of vessels per cm2 of plaque was 6–51 [21±14/cm2] according to the ultrasonography data and 19–1224 [236±249/cm2] according to the pathomorphological examination. According to the ultrasonography data, the absolute values were close to the density of plaque vessels ≥ 30 μm in diameter determined during pathomorphological examination and did not differ significantly from this value (p = 0.67). The morphology data show that vessels <20 μm in diameter, which constituted up to 96% of all microvessels in ASP, cannot be detected by ultrasonography. In one case, ulceration of the ASP surface was detected only by contrast medium injection. Calcified plaques with different degrees of calcination imposed the greatest difficulties when performing ultrasonic assessment of neovascularization.

Conclusions. Contrast-enhanced untrasonography can be used as an informative method to noninvasively detect signs of ASP instability enabling rather accurate assessment of neovascularization at microvessel diameter ≥30 μm. Calcification of ASPs may significantly affect the study results.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Quantitative sonographic parameters of the peripheral nerves in healthy individuals

Naumova E.S., Nikitin S.S., Druzhinin D.S.

Abstract

Introduction. Ultrasonography allows non-invasive scanning of the peripheral nerves to record quantitative and qualitative parameters.

Objective. To determine the normal cross-sectional area (CSA) of the nerves in arms and legs, as well as spinal nerves in healthy volunteers.

Materials and methods. Bilateral ultrasonography of the peripheral nerves in arms and legs, as well as the spinal nerves in the brachial plexus was carried out in healthy volunteers: 40 males and 40 females with the mean age of 40.3±15.1 (range, 18–70 years). A Sonoscape S20 ultrasound scanner (China) with an 8–15 MHz linear sensor. The cross-sectional area of the peripheral nerves was assessed. Height, weight, the body mass index (BMI), age, and gender were included in analysis.

Results. The reference CSA values for the major nerves of arms, legs, and spinal nerves of the brachial plexus were obtained. No reliable correlation of the main anthropometric parameters (height, weight, and BMI) as well as age and gender with the CSA of the peripheral nerves and the brachial plexus was found.

Conclusions. The findings are in accordance with the measured parameters reported by other authors, indicating that our methodological approach to nerve ultrasonography is similar to those used in other laboratories.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Trigeminal neuralgia associated with herpes zoster

Piradov M.A., Maksimova M.Y., Sineva N.A.

Abstract

Neuropathy of the ophthalmic nerve (the first branch of the trigeminal nerve, CN V: V1) is the most common manifestation of herpes zoster. Neuropathy of the ophthalmic nerve occurs in 20% of cases of herpes zoster. Three types of pain are differentiated in trigeminal neuralgia: chronic burning pain, paroxysmal pain, and pain resulting from nonpain stimulation. Cutaneous hypoesthesia, anesthesia, and dysesthesia develop. Postherpetic neuralgia is characterized by pain persisting 3 months and longer after herpetic eruption. Combination therapy including early administration of antiviral drugs and tricyclic antidepressants has been proved to be most effective.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Atypical clinical cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Moroz A.A., Abramycheva N.A., Ivanova E.O., Konovalov R.N., Timerbaeva S.L., Illarioshkin S.N.

Abstract

C

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary CNS disease with autosomal dominant inheritance caused by NOTCH3 gene mutations. In classic cases, CADASIL manifests with headaches, repeated cerebrovascular disorders, and progressive cognitive decline. Cerebral magnetic resonance imaging plays an important diagnostic role as it reveals multiple lacunar infarcts in the basal ganglia, brainstem, and cerebellum, as well as focal white matter lesions and diffuse leukoaraiosis changes. CADASIL can sometimes have other symptoms and be disguised as phenotypes atypical of this disease. We report two genetically confirmed cases of CADASIL with atypical clinical presentation that manifested with predominantly cerebellar or essential tremor combined with cognitive and affective disorders. The main principles of diagnosis of this disease characterized by clinical polymorphism are discussed.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Small fiber neuropathy

Suponeva N.A., Belova N.V., Zaitseva N.I., Yusupova D.G., Lagoda D.Y., Korepina O.S., Piradov M.A.

Abstract

Despite the fact that small fiber neuropathy (SFN) has already been studied for 30 years, it remains one of the most mysterious diseases that are extremely difficult to diagnose and cure. The prevalence of SFN is 52.95 per 100,000 population; diabetes mellitus is considered to be the most frequent cause of this disease. Chronic neuropathic pain syndrome, temperature sensation abnormalities, and vegetative disorders develop as a result of damage to fine myelinated Аδ- and unmyelinated C fibers. The disease mainly spreads in the upward direction: from feet to the proximal body parts and arms; primary axonal damage takes place. Although SFN is believed to be one of the most “benign” neuropathy types as it does not affect the large sensory and motor fibers, it significantly decreases patients’ quality of life.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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Prognostic factors for recovery of motor dysfunction following ischemic stroke

Barkhatov D.Y., Kadykov A.S.

Abstract

The problem of searching for the prognostic factors for recovery of motor dysfunction following stroke is very relevant because of the high prevalence of acute cerebrovascular events. The severe disabling sequelae of stroke are associated with the enormous economic burden all over the world, which is aggravated by the lack of customized approaches to rehabilitation with allowance for the clinical data and neuroplastic features of the brain of each individual patient. Although modern diagnostic tools, including neuroimaging, have been introduced, many potential predictors of recovery of functions lost following a cerebrovascular accident still remain to be elucidated or refined. The best-studied prognostic factors for recovery of the functions lost following ischemic stroke are reviewed in this article.

Annals of Clinical and Experimental Neurology. 2017;11(1):
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