Vol 11, No 2 (2017)

Original articles

Optimization of early rehabilitation of patients with ischemic stroke and sleep-disordered breathing

Lutokhin G.M., Geraskina L.A., Fonyakin A.V., Maksimova M.Y.


Introduction. Sleep-disordered breathing (SDB) is detected in 70% of stroke patients and impedes functional rehabilitation; it also increases the length of hospital stay and the risk of stroke recurrence and fatal outcome.

Objective: to study the dynamics of SDB in its correlation with neurological disorders in stroke patients and to develop the approaches to optimization of early rehabilitation.

Materials and methods. A total of 78 patients with acute ischemic stroke were examined. SDB was verified by cardiorespiratory monitoring; the neurological deficit was assessed using the NIHSS and mRS scales. Examination was carried out upon admission (days 2–5 post stroke) and again after 3 weeks. The effect of SDB correction on effectiveness of neurological recovery was studied using positional therapy (position elevated by 30о) in combination with oxygen therapy (insufflation of O2 with the saturation level maintained no less than 95% under control of a digital sensor).

Results. Upon admission, SDB was revealed in 88% of patients; moderate and severe disorders being predominant (the apnea/hypopnea index (AHI) ≥15 h-1), most frequently presenting as obstructive apnea. In patients with AHI < 15 h-1, the positive dynamics of neurological disorders (p<0.04) were observed along with stable SDB parameters. Neurological improvement (р<0.05) was observed in patients with AHI ≥ 15 h-1, which was associated with decreased severity of SDB. A direct correlation between the severity of neurological disorders and AHI after 3 weeks was revealed: RNIHSS/AHI = 0.45 (р=0.003), RmRS/AHI = 0.44 (р=0.004). Patients with AHI ≥ 15 h-1 were distributed into 2 groups: group A (without corrective interventions) and group B (the use of positional and oxygen therapy during the night sleep during 7 days). A positive effect of the course of corrective therapy on restoration of neurological functions, along with a decrease in AHI, was revealed.

Conclusions. SDB is a frequent and persistent disorder in patients with ischemic stroke. Early detection and correction of SDB should be regarded as an important component of post-stroke rehabilitation.

Annals of Clinical and Experimental Neurology. 2017;11(2):5-14
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The lack of H-reflex as an additional neurophysiological sign of development of acute inflammatory demyelinating polyneuropathy in children

Voitenkov V.B., Klimkin A.V., Skripchenko N.V., Grigor’ev S.V., Aksenova A.I.


Early diagnosis of acute inflammatory demyelinating polyneuropathy (AIDP) is of fundamental importance for the timely prescription of therapy. The conventionally used techniques of electrophysiological diagnosis are not sensitive enough at early stages of development of the condition.

The objective of this work was to assess the applicability of studying H-reflex as a tool for early diagnosis of AIDP in children.

Materials and Methods. A total of 57 children were examined: 20 healthy children (range: 7–14 years; mean age 12 years) and 37 patients diagnosed with AIDP (range: 8-13 years; mean age 11 years). Electroneuromyography (ENMG) was performed on day 3–7 after the first symptoms had emerged. The velocity of impulse conduction along motor fibers, the amplitude of M responses during stimulation of nn. tibialis, ulnaris and medianus, as well as latency and threshold of M response and H-reflex during stimulation of m. soleus, was evaluated.

Results. No significant intergroup differences in amplitudes of motor responses and the velocity of impulse conduction were recorded, while the residual latency of M-response was significantly higher in the AIDP group. In individuals in the control group, the H-reflex was recorded in 100% of cases, while being recorded only in 2 (5.4%) patients in the AIDP group. In both patients, examination was performed as early as possible (day 3) after the onset of the first symptoms among the entire group examined.

Conclusions. In pediatric patients with AIDP, which develops on day 3–7 after the onset of the first symptoms, no H-reflex was recorded in 94.6% of cases. Investigation of the H-reflex at the early stage of AIDP in children can be used as an additional criterion for diagnosing the disease. 

Annals of Clinical and Experimental Neurology. 2017;11(2):15-21
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The features of physiological mechanisms of goal-directed activity in epilepsy patients in association with clinical characteristics of the disease

Zorin R.A., Zhadnov V.A., Lapkin M.M., Kulikova N.A.


Introduction. Investigation of systemic organization of goal-directed behavior and analysis of the physiological mechanisms ensuring productive activity in epilepsy patients are the variants of the integrative approach to study the mechanisms of epilepsy.

Objective. To refine the mechanisms of simulated goal-directed activity among epilepsy patients in its relationship with clinical characteristics of the disease.

Materials and methods. A total of 72 virtually healthy persons and 163 epilepsy patients were examined. Seizure frequency, the levels of cognitive and emotional impairments, and the number of administered anticonvulsants were assessed. Electroencephalograms, parameters of visual and auditory evoked potentials, the cognitive evoked P300 potential, parameters of the motor systems, and autonomous maintenance of activity were recorded. Division into groups was performed by clustering analysis using the results of the Schulte–Gorbov test.

Results. The high- (99 patients) and low-effectiveness (64 patients) groups of epilepsy patients were revealed. The low-effectiveness group of patients was characterized by predominantly symptomatic forms of the diseases. High cross-correlation values, reduced frequencies of EEG alpha oscillations, reduction in the amplitude of the components of visual evoked potentials and the P300 potential, an increase in N2 and P3 peak latency in the low-effectiveness group of epilepsy patients were determined. Increased amplitude of the wave of conditionally negative deviation, slower latency of sensorimotor responses, reduced variability of heart rate, and increased respiratory rate group of patients were observed in this group of patients.

Conclusions. The inadequate performance in epilepsy patients is associated with the reduced activity of specific afferent associative subsystems and mechanisms of motor-based maintenance of performance, as well as with excessive activity of stress-inducing mechanisms, which increases the physiological costs and reduces the effectiveness of simulated activity.

Annals of Clinical and Experimental Neurology. 2017;11(2):22-28
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The use of mesenchymal stem cells in optic nerve atrophy in patients with multiple sclerosis: A pilot study

Bisaga G.N., Kovalenko A.V., Isaeva G.E., Kovalenko I.Y., Novitsky A.V., Litvinenko I.V.


Introduction. Cellular therapy of multiple sclerosis is currently considered to be one of the most promising treatment alternatives for this severe pathology of the nervous system.

Materials and Methods. Two patients with relapsing-remitting multiple sclerosis (RRMS) complicated by partial optic nerve atrophy (ONA) caused by bilateral retrobulbar optic neuritis received treatment using autologous multipotent mesenchymal stem cells (MSCs). MSCs were derived by bone marrow aspiration/biopsy followed by isolation, culturing, and cryostorage. MSCs were administered in compliance with the developed protocol by short-term intravenous infusion of resuspension solution of 5% glucose supplemented with 10% autoserum at a dose of 2.0×106/kg body weight in combination with local parabulbar administration of MSCs at a dose of 10×106 once per month during 4 months. The control group consisted of 2 patients of the same age with RRMS with partial ONA of the same severity who received background (metabolic and glucocorticoid) therapy.

Results. Neurological and neuro-ophthalmological examination was carried out before and 6 months after treatment. The pilot study performed demonstrated that the elaborated protocol for MSC therapy is safe and, according to the preliminary data, therapy was characterized by moderate clinical effectiveness in incurable patients with RRMS and ONA.

Conclusions. The findings make it possible to broaden the range of clinical studies focused on cellular therapy for multiple sclerosis.

Annals of Clinical and Experimental Neurology. 2017;11(2):29-35
pages 29-35 views

Assessment of the effects of cellular therapy on reproduction of the conditioned passive avoidance reflex in rats with quinoline-induced model of Huntington’s disease

Stavrovskaya A.V., Novosadova E.V., Yamshchikova N.G., Olshansky A.S., Gushchina A.S., Konovalova E.V., Grivennikov I.A., Illarioshkin S.N.


Introduction. The model involving injection of quinolinic acid (QA) into the rat striatum simulates many clinical and morphological characteristics of Huntington’s disease (HD). Searching for effective treatment methods is rather topical because of the fatality of HD. One of such methods is to create a neuroprotective environment to slow down the current degenerative process and/or replace dead neurons. In particular, this can be performed by transplantation of cells capable of undergoing neuronal differentiation and integration into the proper structural and functional brain networks.

Objective. To assess effectiveness and safety of transplantation of neural progenitors differentiated from induced pluripotent stem cells (iPSCs) harvested from a healthy donor into the striatum with QA-induced model of HD.

Materials and methods. The effects of neurotransplantation on reproduction of the conditioned passive avoidance reflex were studied in rats with the model of HD induced by injection of QA into the caudate nuclei of the striatum. In the study group (n=8), human neural progenitors (1×106 per 10 µl of normal saline unilaterally, on the injured side) derived from iPSCs harvested from a healthy donor were injected into the caudate nuclei as the transplanted material; normal saline was injected in the control group. The conditioned passive avoidance responses were tested using the ShutАvoid 1.8.03 software on a Harvard apparatus (Panlab, Spain).

Results. When testing the reproduction of the passive avoidance responses, we found that injection of QA into the caudate nuclei of the rat brain reliably reduced the conditioned responses. Neurotransplantation of neural progenitors derived from iPSCs had a clear therapeutic effect and reinforced the passive avoidance reflex. During the entire testing period (7 days after exposure to the pain stimulus), the experimental animals either did not visit the dark compartment at all or visited it with a long latency period.

Conclusions. Experimental neurotransplantation using iPSC derivatives allowance to improve storage of trace memory in rats with QA-induced model of HD, which contributes to correction of cognitive impairments caused by administration of the neurotoxin.

Annals of Clinical and Experimental Neurology. 2017;11(2):36-41
pages 36-41 views

Alterations in the somatodendritic structure of spiny neurons in human putamen during physiological aging

Ivanov M.V., Kutukova K.A., Berezhnaya L.A.


Introduction. The striatum is involved in regulation of cognitive functions and behavior, including planning motor behavior, decision making, motivation, and rewarding. The human striatum contains the putamen, in whose medium spiny neurons certain qualitative and quantitative alterations in somatodendritic structure occur with aging.

Materials and methods. The morphometric parameters of spiny neurons in the striatum of humans (females) during the second maturity period and senility were investigated. The Golgi silver impregnation method was used as the staining technique. The following parameters were assessed: the area of neuronal body, the number of dendrites, the number of free ends of all dendrites, the largest dendritic field radius, the total length of all dendrites, the dendritic field area, and the specific density of dendrites.

Results. It was demonstrated that in terms of soma size, the number of dendrites, the number of free ends of dendrites, and specific density of dendrites, there are negligible differences in spiny neurons in the putamen in humans of both ages in the samples under study. The parameters of the largest dendritic field radius, the total length of all dendrites and the dendritic field area for the senile individuals were significantly lower (p<0.05) than for the mature ones by 11, 13, and 15%, respectively. The total number of spines per 100 µm of dendrite in senile individuals was lower by 18% compared to that in women during the second period of maturity. The features of distribution of spines of different types over the putamen neurons in mature and senile individuals show the role played by mushroom-like spines in preservation and maintenance of synaptic connections required to ensure the elementary functions of putamen neurons.

Conclusions. Hence, we have demonstrated reduction in dendrite length and density of dendrite spines upon aging in women. The results broaden the views about the nature of plastic alterations that take place in cerebral neurons in humans upon aging.

Annals of Clinical and Experimental Neurology. 2017;11(2):42-47
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Structural and functional neuroimaging in amyotrophic lateral sclerosis

Bakulin I.S., Chervyakov A.V., Kremneva E.I., Konovalov R.N., Zakharova M.N.


Abstract. Amyotrophic lateral sclerosis (ALS) is a fatal progressive central nervous system disorder affecting the upper and lower motor neurons. It is important to study the features of the course and progression of neurodegeneration in ALS, since no effective methods for treating this disease have been developed yet. Despite the clear evidence that brain lesions in ALS are of multisystem nature, there are no objective biomarkers of lesions of the upper motor neuron and the extramotor areas of the brain. Structural and functional neuroimaging, such as MR brain morphometry, diffusion tensor imaging, MR spectroscopy, functional MRI, positron emission tomography (PET), etc., have recently been playing a significant role in studying ALS. The results of neuroimaging studies are analyzed in this review in the context of using them to diagnose, predict, and monitor the course of ALS. Diffusion tensor imaging, MR spectroscopy, PET, combination of several neuroimaging methods and their combination with transcranial magnetic stimulation are the most sensitive and specific techniques to be used to diagnose the disease. Diffusion tensor imaging and MR spectroscopy can be used to monitor and predict the disease course. The main limitations and shortcomings of the performed studies, as well as the possible outlook for using neuroimaging in ALS, are discussed.

Annals of Clinical and Experimental Neurology. 2017;11(2):76-87
pages 76-87 views

Monoclonal Antibodies: Present and Future in the Treatment of Multiple Sclerosis (Based on the Proceedings of the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis - ECTRIMS)

Votintseva M.V., Petrov A.M., Stolyarov I.D.


The development of new highly effective medications with acceptable safety profile targeted at the treatment of multiple sclerosis (MS) is one of the most important problems of modern neurology. In recent years, MS pathogenesis studies and clinical trials of new treatments enabled regulatory authorities of many countries to approve the use of monoclonal antibody pharmaceuticals. At the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), special consideration was given to natalizumab, alemtuzumab, daclizumab, ocrelizumab, rituximab, opicinumab, and ofatumumab. This publication provides an overview of the main results of the Congress. It was noted that decrease of disability rate in MS patients with a view to completely stopping disease progression is the most important objective of the use of the modern medications modifying MS course (MMMSC). Careful analysis is required to assess the long-term effects of the MMMSC and switching algorithms from the first line of MS therapy to the second one, as well as subsequent switching to the other regimens.

Annals of Clinical and Experimental Neurology. 2017;11(2):88-93
pages 88-93 views


The potential of resting-state functional magnetic resonance imaging for studying the pathophysiology of primary focal dystonia

Semenova O.V., Timerbaeva S.L., Konovalov R.N.


Resting-state functional magnetic resonance imaging (R-fMRI) assesses the state of low-frequency fluctuations of the BOLD-signal showing spontaneous neuronal activity in different areas of the brain. Hence, R-fMRI allows one to visualize the synchronicity of generation of certain neurophysiological phenomena in different regions of the central nervous system, including the ones being remote from one another, by linking them into a functional network and assessing brain connectivity in normal state and in pathology. This technique has proved itself in the study of neurodegenerative diseases. In this review, we present the results of using R-fMRI for the most common forms of primary focal dystonia (blepharospasm and cervical dystonia) compared to the data of task-based fMRI and some other neuroimaging technologies such as positron emission tomography and voxel-based morphometry. It has been demonstrated in many studies that R-fMRI allows to assess disturbances in cerebral architecture and complex rearrangements in the neural network in patients with focal dystonia, including those after administration of botulinum toxin. This makes it possible to study more thoroughly the pathophysiological foundations of focal dystonia and the variety of mechanisms of botulinum toxin therapy in patients with these pathologies, including the central (indirect) mechanisms of action of botulinum toxin.

Annals of Clinical and Experimental Neurology. 2017;11(2):48-54
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Electrophysiological methods for estimation of the number of motor units

Murtazina A.F., Belyakova-Bodina A.I., Brutyan A.G.


Various neurological diseases involving motor neurons or their axons lead to decrease in the number of functioning motor units (MU). Counting the number of intact MUs plays significant role in assessing the progression of the pathological process associated with motor neuron death. Quantitative estimation of MUs using routine electromyography methods is usually impossible. Therefore, electrophysiological methods for estimation of the number of MUs, currently known under the common name MUNE (motor unit number estimation), are being discovered over the past decades. The first publication on MUNE was issued in 1971. Since that time, promising, more accurate, and less time-consuming modifications have been developed, and new MU counting methods have been proposed. In recent years, we can see increasing interest in MUNE in connection with the search for new treatments for motor neuron disease, assessment of their effectiveness, and dynamic control of the disease. Today, MUNE is considered as a potential biomarker in clinical trials of new treatments for motor neuron disease. This review presents the available MUNE techniques, describes their comparative characteristics, advantages and disadvantages of each method, and discusses the experience and prospects of their application.

Annals of Clinical and Experimental Neurology. 2017;11(2):55-65
pages 55-65 views

Clinical analysis

Agenesis of the corpus callosum associated with hereditary syndromes

Milovanova O.A., Tarakanova T.Y., Pronicheva Y.B., Katasonova L.P., Biche-Ool S.K., Vorozhbieva T.E.


Abstract: Agenesis of the corpus callosum (ACC) is detected in patients with cerebral dysgenesis associated with various hereditary syndromes. It is conventionally subdivided into total (the absence of commissural fibers) and partial (agenesis of the rostral and caudal areas of the corpus callosum) ACC. The disorder can either be individual or associated with other developmental brain malformations. Isolated pathologies of the corpus callosum can be clinically occult, thus significantly impeding diagnosis of this pathology. AAC can be verified using various neuroimaging data, including fetal brain ultrasonography. In this study, we report two cases of patients with ACC associated with hereditary syndromes from our own clinical experience. In one case, the course of the disease was relatively favorable. The severe infantile form with fatal outcome is reported in the second case. The detailed autopsy data and results of morphological examination of the brain are presented. Special attention is paid to the issues associated with analysis of clinical phenotypes, as well as lifetime and postmortem diagnosis of the disease.

Annals of Clinical and Experimental Neurology. 2017;11(2):66-71
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Hepatolenticular degeneration with hidden pathology of liver: Case report

Vyalova N.V., Doloka D.S., Proskokova T.N., Khelimskiy A.M.


A case of hepatolenticular degeneration (HLD) in a 27-year-old patient is reported. The earliest signs of the disease were observed as isolated psychoneurological symptoms (mainly as polymorphic extrapyramidal and cerebellar disorders). Neither clinical, nor laboratory, nor sonographic signs of liver pathology were detected. Liver pathology was revealed only during special examination by elastography. The diagnosis was verified by molecular genetic testing (detecting mutations in the АТР7В gene). Challenges of timely recognizing HLD and the modern potential of diagnosing the disease using the laboratory and instrumental techniques are discussed.

Annals of Clinical and Experimental Neurology. 2017;11(2):72-75
pages 72-75 views

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