Vol 14, No 4 (2020)

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Full Issue

Original articles

Sleep-disordered breathing and quality of life in patients with chronic cerebrovascular diseas

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


Introduction. Chronic cerebrovascular disease (CeVD) is usually accompanied by a decrease in the quality of life (QoL). A possible cause of decreased QoL is sleep-disordered breathing.

Aim: to assess the frequency of sleep-related breathing disorders and QoL in patients with chronic CeVD.

Materials and methods. The study included 100 patients (50 men and 50 women), with an average age of 65 (58; 74.5) years. Cognitive (MoCA-test) and affective disturbances (HADS), severity of daytime sleepiness and fatigue (the Berlin questionnaire to identify patients at risk for the sleep apnea syndrome) were assessed. QoL was evaluated using the SF-36 health survey. Sleep-disordered breathing (SDB) was verified using cardiorespiratory monitoring. The apnoea/hypopnoea index was also calculated.

Results. On average, the cognitive impairment score was 25 (23, 27) points; the anxiety level was 6 (4; 9), depression level was 6 (3.5; 8), daytime sleepiness and fatigue were 4 (1.5; 7). QoL was reduced in the majority of patients. SDB was registered in 82% of patients. Multiple comparisons found no differences in QoL scores depending on the presence and severity of sleep-related breathing disorders. Patients with a history of stroke had higher scores for general health (p = 0.06), mental health (p = 0.01), and overall psychological health (p = 0.04). The stroke patients were younger (p = 0.02) and experienced less daytime sleepiness and fatigue (p = 0.007). Women had lower QoL scores compared to men. At the same time, the women were older than the men (p = 0.006) and had higher levels of anxiety (p = 0.0008). Statistically significant correlations were found between the various QoL components and age, anxiety and depression levels, severity of daytime sleepiness and fatigue, and cognitive dysfunction, but not the apnoea/hypopnoea index.

Conclusion. Patients with chronic ischaemic CeVD and SDB had reduced QoL; however, the mental health component remained slightly higher than the physical component. The main factors associated with a decrease in QoL were age, female gender, anxiety and depression levels, and excessive daytime sleepiness/fatigueo.

Annals of Clinical and Experimental Neurology. 2020;14(4):5-14
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Glutamate biomarkers in comprehensive diagnostics of acute and chronic brain ischemia

Ponomarev G.V., Vozniuk I.A., Izumi M.A., Skoromets A.A.


The development and implementation of biomarkers of ischaemic brain damage at the pre-hospital and hospital stages, as well as during screening and regular medical examinations, are a priority in neurology. This review describes the role of NR2 peptide, a subunit of the NMDA ionotropic glutamate receptors, in the pathogenesis of cerebral ischemia. Experimental data are presented, showing that NR2 peptide expression increases in brain ischemia, its fragments passing through the blood-brain barrier and entering the bloodstream, thus stimulating the immune response and autoantibody production. Key studies are reviewed that have demonstrated the possibility of using glutamate receptors and their antibodies as potential biomarkers of acute and chronic cerebral ischemia. The sensitivity and specificity of NR2 peptide and NR2 antibodies in these studies averaged >90%. It has been shown that NR2A/B is the only marker with high negative and positive predictive value in people with suspected ischaemic stroke. Monitoring treatment effectiveness is another promising area of application for glutamate biomarkers.

Previous studies have shown that the NR2 peptide and its antibodies are potential biomarkers of cerebral infarction, transient ischaemic attack, and chronic cerebral ischemia and may become important components in a successful and comprehensive approach to treatment, screening, and monitoring of disease outcomes.

Annals of Clinical and Experimental Neurology. 2020;14(4):15-22
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The correlation between motor and cognitive dysfunction in multiple sclerosis

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


The correlation between motor and cognitive dysfunction in multiple sclerosis

Konstantin K. Mineev, Andrey M. Petrov, Marina V. Votintseva, Igor' D. Stolyarov

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences, St. Petersburg, Russia

Introduction. Impaired ambulation is one of the most common and disabling symptoms in multiple sclerosis (MS). Cognitive impairment occurs in the early stages of MS and worsens as the disease progresses.

The aim of the study was to investigate the correlation between walking speed and distance and the severity of neurological and cognitive impairment in MS.

Materials and methods. We examined 59 patients with relapsing-remitting MS in clinical remission. Motor function was evaluated using the timed 25-foot walk (mobility and leg function performance test based on a timed 25-walk), the nine-hole peg test was used to assess upper limb motor function, the Ashworth Scale was used to evaluate lower limb spasticity, the EDSS scale (pyramidal function) was used to evaluate gait spasticity, and tests for sustained attention, counting skills, short-term and delayed memory, mathematical logic, speech fluency, and sensorimotor reaction speed were used to assess cognitive function.

Results. In MS, an increased score on the disability scale was accompanied by increased motor disturbances, reduced distance covered when walking, decreased walking speed, and slower hand movements. Increased spasticity was accompanied by a deterioration in cognitive test performance. The study showed a high correlation between spasticity and reduced computational abilities, mathematical logic, and the ability to remember shapes. Walking distance correlated with attention span and short-term and delayed memory while walking speed characteristics correlated with the movement speed of the non-dominant hand. Slower hand activity correlated with the conducted cognitive tests, with the most significant differences recorded in the non-dominant hand.

Conclusion. The study results indicate significant and varied motor and cognitive dysfunction in MS patients, caused by damage to both the conduction pathways in the brain and spinal cord and the cortical grey matter. The obtained data on the close correlation between motor and cognitive impairments allow us to better understand the mechanisms of MS development and to apply this knowledge in clinical practice.

Annals of Clinical and Experimental Neurology. 2020;14(4):23-28
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Spastic paraplegias types 11 and 15

Rudenskaya G.E., Kadnikova V.A., Ryzhkova O.P., Anisimova I.V., Dadaly E.L., Dyomina N.A., Mishina I.A., Kanivets I.V., Antonetz A.V., Polyakov A.V.


Introduction. A heterogeneous group of hereditary spastic paraplegias (HSP) with known causative genes, alongside the predominant autosomal dominant ones, includes numerous and diagnostically more complex autosomal recessive (AR) forms with diverse phenotypes. Massive parallele sequencing (MPS) techniques are widely used in HSP diagnosis.

The aim of the study was to determine the clinical and molecular genetic characteristics of two AR-HSPs — SPG11 and SPG15 — in Russia based on the first study of HSP using MPS.

Materials and methods. We examined 8 unrelated Russian families: seven with SPG11 and one with SPG15. Clinical and molecular analysis and multiplex ligation-dependent probe amplification (MLPA) were used.

Results. SPG11, diagnosed in seven families, was the most common AR form, accounting for 5.1% of the total group of 120 families with verified HSP (4th common) and 30.5% of the AR-HSP subgroup. Three of the nine identified SPG11 mutations have not been previously described; 2 families had identical genotypes, with one of the allelic mutations consisting of a large duplication; one previously described mutation was detected three times. Two patients had an atypical late onset, six cases had complicating concomitant symptoms, such as ataxia and/or dysarthria, cognitive impairment, while 3 out of 6 patients showed thinning of the corpus callosum on MRI. SPG15 was diagnosed in one patient at 13 years; two new mutations were found in the ZFYVE26 gene with a reading frame shift in the compound heterozygous state. Clinical phenotype in this patient included progressive cognitive decline in addition to spastic paraparesis; there was no macular degeneration typical (but not mandatory) of SPG15 up to the age of 17 years (according to follow-up data).

Conclusion. In a large group of patients in Russia, AR-HSP was represented by 12 different forms, with SPG11 being the most frequent and SPG15 also being present. A total of 11 mutations were found in the genes of both forms, 5 of which had not been previously described. Two complicated forms of HSP had a similar clinical presentation and were difficult to diagnose. MPS methods are indispensable in diagnosing diseases with pronounced genetic heterogeneity, such as HSP. Cases with major gene rearrangements confirm the importance of combining MPS with MLPA.

Annals of Clinical and Experimental Neurology. 2020;14(4):29-38
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Resting-state neural networks in cognitive decline in patients with vascular encephalopathy

Fokin V.F., Ponomareva N.V., Konovalov R.N., Krotenkova M.V., Medvedev R.B., Lagoda O.V., Tanashyan M.M.


We evaluated the connectivity reorganization of resting-state neural networks in patients with cognitive decline secondary to vascular encephalopathy (VE). Quantitative cognitive functions were evaluated using the Montreal Cognitive Assessment (MoCA) scale and compared with the organization of resting-state neural networks recorded using functional magnetic resonance imaging (fMRI).

The aim of this work was to assess the relationship between various resting-state neural networks and cognitive function.

Materials and methods. The study involved 29 people with VE, divided into two groups: without cognitive decline (≥ 26 points on the MoCA) and with cognitive impairment (24–18 points on the MoCA). Connectivity between different brain regions was evaluated in all patients using resting-state fMRI, with SPM-12 and CONN18b software applications in Matlab.

Results and conclusion. Statistically significant differences in connectivity were found between groups in the dorsal attention network, visual network, and sensorimotor networks, as well as in the left parahippocampal cortex. New, negative connectivity was observed alongside cognitive decline, which, together with reduced connectivity in resting-state neural networks, can be considered an obligatory sign accompanying cognitive impairment in VE.

Annals of Clinical and Experimental Neurology. 2020;14(4):39-45
pages 39-45 views

Atypical (deafferentation) odontalgia

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


The difficulty of clinical interpretation of atypical (deafferentation) odontalgia with respect to its connection, on the one hand, with endodontic interventions in the dentoalveolar region, and on the other hand, with psychogenic and personality disorders, remains a subject of discussion. We examined 93 patients with deafferentation odontalgia to clarify the psychological factors and quality of life parameters that affect this chronic pain syndrome. Most patients were women (79.6%) of working age (40–50 years old). The visual analog scale and the McGill Pain Questionnaire were used to rate pain intensity, and the Pain Catastrophizing Scale was used to evaluate the negative psychoemotional response to pain. Depression was assessed using the Beck Depression Inventory and Hamilton Rating Scale, while the Spielberg Scale was used to evaluate the level of reactive and personal anxiety. Quality of life was assessed using the SF-36. It was shown that depression, anxiety, affective disorders, negative psychoemotional response to pain, and low quality of life were more often present in patients with chronic deafferentation odontalgia.

Annals of Clinical and Experimental Neurology. 2020;14(4):46-53
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Preconditioning with ouabain reduces the neurological deficit in rats caused by compression-induced cerebral ischemia

Stelmashook E.V., Genrikhs E.E., Isaev N.K., Novikova S.V., Khaspekov L.G.


Ischaemic brain damage is a major neurobiological and medical social problem, making experimental research of the pathogenesis of cerebral ischemia and the search for ways to minimize its consequences particularly relevant.

The aim of the study was to determine the possibility of reducing the neurological deficit and functional limb asymmetry in laboratory rats through ischaemic tolerance using ouabain, a Na+/K+- ATPase inhibitor.

Materials and methods. Cerebral ischemia was modeled using 20-minute focal compression of the left sensorimotor cortex in the rat brain. To induce tolerance, laboratory animals were given a single intravenous injection of 0.7 mg/kg of the Na+/K+-ATPase inhibitor ouabain 24 or 72 hours before the ischaemic event. Functional impairment was assessed with tests for neurological deficits in the limbs and a test for forelimb performance in laboratory animals.

Results. Preliminary ouabain administration prevented the development of functional impairment due to compression-induced ischemia of the sensorimotor cortex, with a decrease in limb asymmetry and the severity of motor dysfunction.

Conclusion. In animals, pharmacological preconditioning with ouabain increases the brain's resistance to subsequent compression-induced ischemia, preventing functional asymmetry and improving both right and left limb function. The obtained data expand the possibilities of using Na+/K+-ATPase inhibitors to treat cerebral ischemia.

Annals of Clinical and Experimental Neurology. 2020;14(4):54-60
pages 54-60 views

Effects of zolpidem and protons on GABA-induced current in the hippocampal pyramidal neurons in the presence of penicillin

Solntseva E.I., Bukanova J.V., Skrebitsky V.G.


Introduction. Type A receptors activated by gamma-aminobutyric acid (GABAAR) play an inhibitory role in the nervous system due to the generation of chlorine current (IGABA). Penicillin is a “sequential blocker” of the GABAAR open channel, which can inhibit dissociation of the GABA-receptor complex. This GABA site modulation suggests that the effects of competitive GABAAR modulators may change in the presence of penicillin.

The aim of the study was to evaluate the effect of zolpidem, the positive competitive GABAAR modulator, and hydrogen ions (protons), the negative competitive GABAAR modulator, on IGABA in the presence of penicillin.

Materials and methods. IGABA was measured on isolated pyramidal neurons of the rat hippocampus, using the patch clamp technique and fast application system. GABA, penicillin, and zolpidem were applied to the neuron for 600 msec via a lateral shift pipette. To study the effect of protons on IGABA, the GABA solution in the application pipette was acidified to pH 6.0–7.0.

Results. The application of 1 mmol of penicillin reduced the IGABA amplitude to 67 ± 4% of the control value. Zolpidem, with a concentration of 0.5 µmol, increased the IGABA amplitude to 167 ± 9% of the control value. When penicillin and zolpidem were co-applied, the stimulating effect of zolpidem was not observed, and the IGABA amplitude was 68 ± 4%. Reducing the pH of the GABA solution to 7.0 or 6.0 caused the IGABA amplitude to decrease to 80±4 and 35 ± 4%, respectively. The effect of protons on IGABA did not change in the presence of penicillin.

Conclusion. For the first time, it has been shown that the stimulating effect of zolpidem on IGABA is cancelled out by penicillin, while the inhibitory effect of protons on IGABA is preserved.

Annals of Clinical and Experimental Neurology. 2020;14(4):61-65
pages 61-65 views


Rehabilitation of elderly patients at risk of falling: the value of psychophysiological parameters and cognitive-motor training using virtual reality

Klochkov A.S., Khizhnikova A.E., Fuks A.A., Kotov-Smolenskiy A.M., Suponeva N.A., Piradov M.A.


Due to the slowing of the neurodynamic and cognitive processes, as well as changes in the musculoskeletal system that accompany aging, attention, reaction, and movement coordination are impaired in elderly patients. Decreased overall brain adaptability leads to an increased risk of falls and disability, thus reducing the age of active aging. According to the World Health Organization, 37.3 million falls occur annually that are not fatal but have serious consequences requiring medical attention. These falls are most common among people over the age of 65 years. An objective assessment of psychophysiological characteristics identified a correlation between the duration of simple and complex reactions and the risk of falls and served as a tool for evaluating the effectiveness of balance retraining. Studies have shown that cognitive-motor training improves postural stability and functional performance in daily life. This type of training is widely used to rehabilitate patients with balance disorders, and virtual reality systems are increasingly being used in its implementation. There is a theory that the virtual environment can improve responses to rapid environmental changes, as well as modulate various characteristics of attention, spatiotemporal memory, and planning, which favorably affects postural function. This review describes the changes in psychophysiological parameters in the elderly, as well as balance retraining techniques using cognitive-motor training, including the use of virtual reality technology.

Annals of Clinical and Experimental Neurology. 2020;14(4):66-74
pages 66-74 views

DNA methylation in Parkinson disease

Yakovenko E.V., Fedotova E.Y., Illarioshkin S.N.


Parkinson disease (PD) is one of the most widespread neurodegenerative diseases in the elderly. It causes motor impairment and the development of non-motor symptoms, which reduce the quality of life and gradually lead to patient disability. However, PD pathogenesis remains unclear. Both genetic and environmental factors play a role in PD development. Recently, researchers have focused more on epigenetic mechanisms and their significance in multifactorial diseases. Epigenetic modifications lead to changes in gene expression and function without changing the DNA sequence. The main epigenetic mechanisms include histone modifications, non-coding RNA activity, and DNA methylation, with most studies of PD focusing on the methylation of various genes. Differential DNA methylation occurs mainly in gene regions important for transcription, contributing to either activation of expression (at low methylation levels) or suppression of gene activity (at hypermethylation). This review analyses most of the recent studies on DNA methylation, with an emphasis on analyzing genes whose participation in PD development has been confirmed in numerous research papers, specifically, the alpha-synuclein gene (SNCA) and the Tau protein gene (MAPT). The possible use of this analysis of the methylation level of various genes as biomarkers of PD is discussed, as well as the potential for future therapeutic strategies based on epigenetic modifications.

Annals of Clinical and Experimental Neurology. 2020;14(4):75-81
pages 75-81 views


Ultrasound imaging of the brachial plexus in healthy adults and those with neurogenic thoracic outlet syndrome

Mukhambetalieva I.K., Druzhinina E.S., Druzhinin D.S.


Ultrasound of the brachial plexus (BP) is a readily available and informative imaging method. Good knowledge of normal BP anatomy and its variations, as well as the ultrasound technique for examining the BP, is the key to success. We present an ultrasound technique for BP assessment in healthy adults and patients with neurogenic thoracic outlet syndrome.

Annals of Clinical and Experimental Neurology. 2020;14(4):82-87
pages 82-87 views

Clinical analysis

A clinical case of fatal familial insomnia with a transient positive response to corticosteroids

Shpilyukova Y.A., Seliverstov Y.A., Nuzhny E.P.


Fatal familial insomnia (FFI) is a rare genetic human prion disease with an autosomal dominant pattern of inheritance caused by a D178N mutation in the PRNP gene. FFI is characterized by a variable clinical presentation and subacute manifestation. The latter prompts to consider autoimmune encephalitis as a differential diagnosis in the diagnostically challenging patients. Here, we present a clinical case of FFI that was initially misdiagnosed with autoimmune encephalitis. A 26-year-old woman presented with rapid development of diverse neurological features, autonomic and endocrine disturbances, which initially were considered as manifestations of an autoimmune disease due to the lack of clear indications of positive family history. She was started on corticosteroids with temporary stabilization and even with a mild improvement for several months. Progressive deterioration of her symptoms with development of the psychiatric and cognitive impairment, as well as subsequently received additional information regarding positive family history, prompted us to perform a PRNP gene test that revealed a D178N mutation and confirmed an FFI diagnosis.

Annals of Clinical and Experimental Neurology. 2020;14(4):88-95
pages 88-95 views

Surgical treatment of epilepsy secondary to a hypothalamic hamartoma: a case report

Areshkina I.G., Dmitrenko D.V., Dmitrenko A.I., Narodova E.A.


A hypothalamic hamartoma is a benign, congenital, heterotopic, neoplastic space-occupying mass located in the interpeduncular fossa, corresponding to a gangliocytoma according to the morphological classification. Patients with hypothalamic hamartoma often experience gelastic seizures and early puberty. Increasing evidence that hypothalamic hamartomas are the cause of gelastic seizures and secondary epileptogenesis has led to surgery being used more often as a permanent cure. Several minimally invasive procedures have been developed, including neuroendoscopic approaches and various stereotactic techniques in radiofrequency and laser ablation. Each method can lead to its own unique side effects. We conducted a review of the available Russian and international literature. This case report describes the surgical treatment of epilepsy secondary to a hypothalamic hamartoma.

Annals of Clinical and Experimental Neurology. 2020;14(4):96-102
pages 96-102 views

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