Vol 13, No 2 (2019)

Original articles

Sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO syndrome): characteristics of a series of clinical observations in Russia

Nuzhniy Y.P., Klyushnikov S.A., Seliverstov Y.A., Krylova T.D., Tsygankova P.G., Zakharova Y.Y., Kasatkin D.S., Spirin N.N., Abramycheva N.Y., Illarioshkin S.N.

Abstract

Introduction. Mitochondrial ataxias are an extremely heterogeneous group of diseases, which include the SANDO (an acronym stands for sensory ataxic neuropathy, dysarthria and ophthalmoparesis) syndrome. SANDO syndrome is one of the characteristic phenotypes associated with mutations in the POLG gene.

Study objective. To analyse the clinical picture and the results of clinical and laboratory tests in a Russian case series of genetically confirmed SANDO syndrome.

Materials and methods. Nine patients (4 men and 5 women aged 33.4±11.3 years) with SANDO syndrome and identified mutations in the POLG gene were examined. A clinical evaluation using the SARA and ICARS (for ataxia) and MoCA (cognitive function) scales, laboratory study of liver function, electrocardiography, stimulation electromyography and brain MRI were performed; 6 patients underwent electroencephalography. MLPA analysis and the original multigene NGS panel were used for genetic screening.

Results. The average age of disease onset was 27.7±8.2 years, with significant variability (from 14 to 49 years). The disease was characterized by a rather typical clinical picture, which included sensory ataxia, polyneuropathy, dysarthria and external ophthalmoparesis in all patients; the median score was 13.5/40 [11; 25] points on the SARA scale, 39.5/100 [33; 63] points on the ICARS scale, and 22 [20; 25] points on the MoCA scale. Two patients showed signs of frontal lobe dysfunction. In most patients, MRI revealed changes in the white matter of the cerebellar hemispheres, brainstem, thalamus and semioval centres, but no pathology was detected on MRI in 3 patients. The p.W748S mutation in the POLG gene made up 83% of the mutant alleles, while the p.L931R and p.L311P pathogenic mutations found in 2 patients are new variants and have not been described in international databases.

Conclusion. Our findings suggest that the true frequency of SANDO syndrome in the population may be higher than previously thought. Therefore, a suspicion of this disease should be maintained even in the absence of characteristic changes on neuroimaging. For the timely detection of SANDO syndrome, we propose an appropriate diagnostic algorithm, which should be followed when examining patients with ataxia.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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The effect of transcranial direct current stimulation on the short-term spatial memory in healthy volunteers

Kislitskiy V.M., Yatsenko E.A., Yatsenko A.A., Kushnarev V.A., Pomazkov M.S.

Abstract

Introduction. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation. The application of a weak, subthreshold direct current on the cerebral cortex leads to a change in cortical neuron activity, which continues for a certain amount of time after exposure. The main mechanism of this effect is subthreshold changes in the membrane potential, while the after-effect phenomenon is associated with the influence of tDCS on synaptic plasticity.

Study objective. To examine the effect of tDCS of the posterior parietal cortex on certain types of spatial memory with the electrodes positioned P3– P4+ and P3+ P4–.

Materials and methods. The study included 18 healthy volunteers (10 men and 8 women) aged 18–23 years. The experiment used stimulation points P3 and P4 according to the 10–20 international electrode positioning system. Stimulation was performed using a direct current of 0.7 mA for 20 min. The study participants underwent three stimulation sessions (P3– P4+, P3+ P4–, P30 P40) in a randomized order with an interval of 3 days between them. After each session, the state of their short-term spatial memory was assessed using the Spatial Memory (categorical spatial memory) and Spatial Span (coordinate spatial memory) tests by Cambridge Brain Sciences, as well as the subjective effect of tDCS.

Results. There were no statistically significant differences in the results of neuropsychological tests between ‘active’ stimulation (P3– P4+ and P3+ P4–) and sham stimulation. The lack of effect may be due to the use of insufficient current (0.7 mA) or other factors (duty cycle, electrode location, stimulation time, etc.). No adverse effects of stimulation were reported.

Conclusion. tDCS with 0.7 mA current does not affect spatial memory in healthy people when using P3– P4+ and P3+ P4– electrode mountings.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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The role of arterial and venous blood flow and cerebrospinal fluid flow disturbances in the development of cognitive impairments in cerebral microangiopathy

Dobrynina L.A., Akhmetzyanov B.M., Gadzhieva Z.S., Kremneva E.I., Kalashnikova L.A., Krotenkova M.V.

Abstract

Cerebral microangiopathy (CMA) is the main cause of vascular cognitive disorders, the leading cause of mixed dementia, and the main modifiable risk factor in Alzheimer’s disease.

Study objective. To investigate the role of arterial and venous blood flow and cerebrospinal fluid flow, as well as their interrelation in the development of cognitive disorders in patients with CMA.

Materials and methods. Ninety-six patients (32 men and 64 women, mean age 60.6±6.3 years) with cognitive complaints and CMA, diagnosed according to the STRIVE international MRI criteria, were examined. The severity of cognitive disturbance was assessed based on the overall cognitive level (MoCA scale and independence in daily life), the results of memory tests (10 words memory test) and executive brain function tests (TMT B-A). Phase contrast MRI was used to measure blood flow in the internal carotid and vertebral arteries (total arterial blood flow), the internal jugular veins and the straight and superior sagittal sinuses, as well as the aqueductal cerebrospinal fluid flow. Arterial pulsation and intracranial compliance indices were calculated.

Results. Dementia and severe memory impairment were statistically significantly associated with an increase in the arterial pulsation index, intracranial compliance index and the aqueductal CSF stroke volume. Significant disturbances in brain executive function were also associated with a decrease in the total arterial blood flow, as well as the venous blood flow in the straight and superior sagittal sinuses. The characteristics of blood flow and cerebrospinal fluid are closely related, and the arterial pulsation index affects all the studied parameters.

Conclusion. The severity of cognitive disturbance in CMA is determined by an increase in the arterial pulsation index, the intracranial compliance index and the aqueductal CSF stroke volume, while the severity of dysregulation disorders is determined by a concurrent decrease in the total arterial blood flow and venous blood flow in the straight and superior sagittal sinuses. The specific changes in blood flow and CSF flow and their interrelation in patients with cognitive impairment due to CMA suggest the pathogenetic importance of cerebral hydrodynamic disturbances in the aetiology of brain damage and the development of cognitive impairment in CMA.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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The migration of multipotent mesenchymal stromal cells after systemic and local administration in an experimental model of Parkinson’s disease

Zafranskaya M.M., Nizhegorodova D.B., Aleynikova N.E., Kuznetsova T.E., Vanslav M.I., Ignatovich T.V., Boiko A.V., Ponomarev V.V.

Abstract

Parkinson’s disease is an important medico-social problem worldwide, with a lot of attention paid to preclinical studies to assess the efficacy of new treatments, including cell therapy.

Study objective. To assess the migratory ability of multipotent mesenchymal stromal cells (MMSC) using different methods of administration in an experimental model of Parkinson’s disease in laboratory rats.

Materials and methods. MMSC, stained with the PKH26 fluorescent dye, were systemically (intravenously) or locally (intranasally and intrathecally) administered to experimental animals with rotenone-induced Parkinson’s disease. The migratory ability of MMSC was assessed on days 1 and 21 after administration, using immunofluorescence microscopy.

Results. The migratory ability of MMSC after both systemic and local administration was more pronounced in the animal group with the experimental model of Parkinson’s disease compared with the control group. It was characterized by maximum accumulation of cells in the brain on the first day after administration, with viability preserved in the area of neuronal inflammation throughout 21 days.

Conclusion. Local administration (intranasal and intrathecal) leads to faster accumulation of MMSC in the brain of both the animals with the experimental model of Parkinson’s disease and healthy rats. Intravenous administration of cell cultures also helps to reveal the migratory properties of MMSC and can form the basis for planning further studies of cell therapy in Parkinson’s disease.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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Interhemispheric asymmetry of the cerebral amino acid pool in rat with subtotal cerebral ischaemia

Razvodovsky Y.E., Smirnov V.Y., Troyan E.I., Maksimovich N.E.

Abstract

The pathogenetic mechanisms of ischaemic stroke are complex and have not been fully studied, including the role of interhemispheric asymmetry in the brain’s biochemical organization.

Study objective. To study the levels of free amino acids (AA) and their derivatives in the cerebral cortex of rats with subtotal cerebral ischaemia.

Materials and methods. Subtotal cerebral ischaemia was modelled in 6 rats in the experimental group by ligation of both carotid arteries for 2 hours. Six rats with sham surgeries served as the control. The levels of AA and their derivatives was analysed in perchlorate tissue extract using reversed-phase chromatography.

Results. Subtotal cerebral ischaemia was accompanied by changes in the AA pool, with differences found between the cortex of the left and right hemispheres. Glutamate, threonine, taurine, tyrosine, tryptophan and α-aminoadipic acid levels decreased in the left frontal lobe cortex, and ornithine levels increased. Asparagine, serine and phenylalanine levels decreased in the right frontal lobe cortex.

Conclusion. The nature of changes in the AA levels in the left and right halves of the cerebral cortex indicates interhemispheric asymmetry of amino acid imbalance, which develops in cerebral ischaemia.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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The haemorrhagic transformation of cerebral infarction: classification; pathogenesis; predictors and effect on the functional outcome

Khasanova D.R., Kalinin M.N., Ibatullin М.M., Rakhimov I.S.

Abstract

Using specific keywords; we searched for articles from the last 10 years on haemorrhagic transformation (HT) of cerebral infarction (CI); which were available on the PubMed database. This article provides an analysis and a summary of the information on the classification; pathogenesis and predictors (clinical; laboratory; neuroimaging; including the use of integrative assessment scales) of HT; as well as its impact on the functional outcome of the condition. It is emphasized that HT is a multifactorial pathological process in its phenomenology; including brain ischaemia; the development of coagulopathy; disturbances in the integrity of the blood–brain barrier and reperfusion injury. The emphasis is placed on careful monitoring of patients with acute ischaemic infarct after intravenous thrombolytic therapy and/or endovascular intervention; as well as those patients with a high predicted risk of HT. Timely and regular neuroimaging should be carried out to detect HT as soon as possible. Type 2 parenchymal haematomas; the most severe type of HT; are most often associated with high mortality and an unfavourable functional outcome.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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Sacroiliac joint syndrome: aetiology, clinical presentation, diagnosis and management

Yarikov A.V., Morev A.V., Shpagin М.V., Fryerman A.P.

Abstract

Sacroiliac joint (SIJ) syndrome is a relevant disorder to study because of the high prevalence of back pain conditions in people of working age. SIJ syndrome is a cause of pain in 15–30% of people with chronic pain in the lower lumbar spine. This review describes the anatomical structure of the SIJ and the aetiological factors that can lead to its dysfunction. Pathogenetic links in the development of this condition are identified separately. The issue of differential diagnosis with other vertebrogenic pain syndromes is considered in detail, and diagnostic tests are presented. The main current approaches to treating SIJ syndrome are described. Interventional methods for treating SIJ dysfunction are described in detail, including radiofrequency neuroablation as an alternative to conservative management.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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PET and SPECT in the assessment of monoaminergic brain systems in extrapyramidal disorders

Selikhova M.V., Katunina E.A., Whone A...

Abstract

In clinical neurology, biomarkers of central neurotransmitter imbalance have been of particular interest in the study of motor disorders and examination of patients with Parkinson’s disease (PD) and other extrapyramidal diseases, primarily to assess the exchange of dopamine and other monoamines in the brain. Radioisotope visualization methods, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) with the corresponding radiopharmaceuticals, are the most informative for these purposes. This article presents a comparative analysis of the wide range of existing ligands and molecular targets for functional neuroimaging using radioisotopes of the nigrostriatal system and the other monoaminergic systems of the brain, with emphasis on the study of the dopamine transporter, dopamine receptors and dopamine-metabolysing enzymes. The modern possibilities of PET and SPECT for the early diagnosis of PD, and the differential diagnosis of this disease with clinically similar syndromes (dystonia, atypical and drug-induced parkinsonism, essential tremor), as well as for monitoring the pathological process and assessing the results of various therapeutic interventions are evaluated. The role of functional neuroimaging in the objective assessment in vivo of the non-motor symptoms of PD, such as depression, impulse control disorders, pathological fatigue and orthostatic hypotension, is emphasized.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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Polymorphism of autoimmune encephalitis

Polonskii E.L., Skulyabin D.I., Lapin S.V., Krasakov I.V., Tikhomirova O.V., Nazarov V.D., Моshnikova A.N., Litvinenko I.V., Slashcheva I.M., Маматова Н.Т., Zakharova N.I., Sokolova N.A., Маzing A.V., Lyamina A.V., Belozerova Y.B.

Abstract

This review analyses the current understanding and diagnostic approaches to the management of patients with autoimmune encephalitis. Cellular and synaptic targets, involved in the pathological process in autoimmune encephalitis, are described. The presence of clinical and immunological differences in the pathology is emphasized: on the one hand, non-structural damage to the nervous system is combined with the subacute development of cognitive impairment, epileptic and psychopathological syndromes, which, on the other hand, are associated with polymorphic immunological heterogeneity. The algorithm for clinical and laboratory diagnosis is described, based on our own clinical observations of three patients. The first patient was diagnosed with a cross-autoimmune syndrome with a combination of Hodgkin’s lymphoma and anti-NMDA encephalitis, probably triggered by the reactivation of the Epstein–Barr virus with a fatal outcome. The second patient was diagnosed with autoimmune anti-LGI1 limbic encephalitis, and the third patient was seronegative to the available immunological antigens. The authors note the need to rethink the concept of ‘encephalitis of unknown aetiology’ and its transformation into ‘autoimmune encephalitis’ with the immunological diagnosis of three antigens (NMDA, LGI1, CASPR2). Considering the rarity of the disease, the high probability of initial admission to an infectious diseases or psychiatric hospital, it is worthwhile to explore this problem more widely at various research forums and to create a comprehensive, interdisciplinary approach to the diagnosis of this disease in the Russian Federation.

Annals of Clinical and Experimental Neurology. 2019;13(2):
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