Vol 14, No 3 (2020)

Original articles

The World Stroke Organization’s Declaration for worldwide primary stroke and dementia prevention

Brainin M., Feigin V.l., Norrving B., Martins S.C., Hankey G.J., Hachinski V.


Сurrent strategies of primary stroke and cardiovascular disease prevention are aimed at addressing the main risk factors primarily in patients with higher cardiovascular disease risk. Since the number of people with incident stroke and ischaemic heart disease cases is rapidly growing across all countries of the world, this preventive strategy appears to be not sufficiently effective. World Stroke Organization recently (2020) endorsed a different concept of stroke and dementia prevention based on a population-wide approach to dealing with risk factors, which involves all individuals regardless of their cardiovascular disease risk level. This article describes four main primary prevention strategies suggested by the World Stroke Organization to effectively reduce stroke and dementia incidence by 50% and 30% respectively. These strategies include (1) population-wide prevention; (2) polypill therapy; (3) free e-Health application “Stroke Riskometer”; and active engagement of community health workers.

Annals of Clinical and Experimental Neurology. 2020;14(3):5-10
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Epilepsy as part of paroxysmal disorders after ischaemic stroke

Maksimova M.Y., Brutian A.G., Shalimanova E.V.


Introduction. Epilepsy is a common cause of paroxysmal disorders appearing after ischaemic stroke.

The aim of the study was to clarify the clinical, neuroimaging, and neurophysiological features of post-stroke epilepsy (PSE).

Materials and methods. We examined 17 (81%) men and 4 (19%) women aged 25–89 years with paroxysmal disorders after ischaemic stroke. Fourteen (66.7%) patients were diagnosed with PSE, while 7 (33.3%) had non-epileptic paroxysmal disorders (NEPD). We conducted a comparative assessment of the groups, considering the clinical, neuroimaging, and 10-hour night-time video-EEG monitoring data.

Results. In patients with PSE, 64.8% of cases had total damage of the insular lobe, and infarcts more often included the cerebral cortex (100%) and white matter, as well as the basal nuclei and other deep brain structures. The EEG recorded epileptiform activity and/or hemispheric slowing on the side of the infarction (64.3%). In patients with NEPD, the infarct was more often located in the vertebrobasilar artery territory, and the paroxysmal disorders were recurrent.

Conclusion. Differential diagnosis of post-stroke paroxysmal disorders is based on the analysis of their clinical signs and medical history. In some cases, data from long-term video EEG monitoring are crucial for the diagnosis of PSE.

Annals of Clinical and Experimental Neurology. 2020;14(3):11-20
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The significance of thalamic nuclei degeneration in relapsing-remitting and secondary progressive multiple sclerosis: results of neuropsychological and morphometry studies

Trufanov A.G., Bisaga G.N., Skulyabin D.I., Tyomniy A.V., Yurin A.A., Poplyak M.O., Poltavskiy I.D., Litvinenko I.V., Odinak M.M., Tarumov D.A.


Introduction. The thalamus is a 'transmitting organ' that is involved in a wide range of neurological functions. Its functional uniqueness and high sensitivity to damage during the earliest stages of multiple sclerosis (MS) make the thalamus a kind of barometer of diffuse brain damage in MS.

The aim of the study was to examine the structural and functional changes in the thalamus and its subregions using magnetic resonance morphometry and to determine their clinical significance in different types of MS.

Materials and methods. We examined 68 patients with relapsing-remitting (n = 40) and secondary progressive (n = 28) MS. The control group consisted of 10 healthy people matched for age and gender. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) were used to assess the patients' neurological status. The cognitive and mental domains were tested using the MMSE, FAB, MoCA, SDMT, Beck's test, and HADS. All patients underwent a brain MRI and morphometric evaluation of the obtained data using the FreeSurfer 6.0 software.

Results. The size of the thalamic pulvinar in relapsing-remitting MS was reduced on the left (M (anterior : posterior) = 186.6 : 149.4 mm3) compared with the controls (229.5 : 187.5 mm3) and on the right (219.5 : 187.1 mm3) compared with the controls (261.6 : 240.5 mm3; p < 0.05). The size of the left thalamic nuclei was significantly reduced in secondary progressive MS when compared with relapsing-remitting MS and the controls. EDSS was correlated with a decrease in the dimensions of the geniculate nucleus on the left (r = –0.48) and the pulvinar nuclei on the left (r = 0.46–0.54). Standard neuropsychological scales correlated with the size of the medial dorsal nucleus (r (MMSE:FAB:MoCA) = 0.51; 0.45; 0.59). The greatest correlation was between the SDMT test (written section) and the left ventral anterior nucleus (r = 0.71).

Conclusion. The obtained data indicate that thalamic nuclei atrophy plays a significant role in the progression of disability and cognitive disorders in MS. Mag- netic resonance morphometry of the thalamic nuclei can be considered an important marker and predictor of MS progression.

Annals of Clinical and Experimental Neurology. 2020;14(3):21-30
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Magnetic resonance imaging in patients with migraine: the results of unsubstantiated referral

Pozhidaev K.A., Parfenov V.A.


Introduction. Magnetic resonance imaging (MRI) in patients with migraines often reveals structural brain changes of an unclear aetiology. The effect of these changes on the patients’ management plan requires further investigation.

The aim of the study was to analyse the management of patients with migraine, in whom structural brain changes were detected on MRI and the validity of MRI referral for migraine.

Materials and methodsWe examined 50 patients (8 men and 42 women, average age 41.9 ± 11.9 years) with migraine (mainly chronic) and changes on brain MRI. We compared clinical and MRI data, analysed typical medical practice, and conducted a prospective follow-up of the patients for 6 months, during which preventive therapy was administered.

Results. Most patients (78%) had predominantly white matter damage of the cerebral hypoperfusion type. None of the patients had indications for MRI. Misinterpretation of the changes on MRI led to most patients (86%) being mistakenly diagnosed with another disease (mainly chronic brain ischaemia) and prescribed inappropriate treatment. Six months of patient follow-up showed the effectiveness of preventive migraine therapy, with a reduction in headache frequency from 19.4 ± 2.9 to 12.6 ± 4.4 days per month (p < 0.05).

Conclusion. We found unreasonable referrals for brain MRI because of migraine, widespread misinterpretation of MRI changes, and an erroneous diagnosis of cerebrovascular changes as the cause of the migraines.

Annals of Clinical and Experimental Neurology. 2020;14(3):31-35
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Progressive ischaemic stroke: the difficulty in choosing antithrombotic therapy

Shirokov E.A., Lomakin N.V., Buryachkovskaya L.I.


Progressive ischaemic stroke is a clinical form of unfavourable progression of an acute cerebrovascular accident, found in around 20% of cases during the acute period. The strategy and approach to managing patients with an apparent deterioration during the acute period of stroke have not been fully established. Various types of antithrombotic therapy are discussed in the literature, with the use of antiplatelet drugs considered the most promising.

The authors analyse all types of antithrombotic therapy for progressive ischaemic stroke and examine in detail the only known case of late thrombolysis, which was performed in 1968.

Annals of Clinical and Experimental Neurology. 2020;14(3):36-42
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LYVE-1 expression in the endothelium of newly formed vessels of carotid atherosclerotic plaque

Evdokimenko A.N., Kulichenkova K.N., Gulevskaya T.S.


Introduction. The discovery of specific markers of lymphatic endothelium, including LYVE-1, has led to a much better understanding of the structure and function of the lymphatic system. It has been shown that lymphatic system regulates immune responses, reverse cholesterol transport, and inflammation in atherosclerosis. LYVE-1 plays an important role in activating the function of the lymphatic system and is also one of the first markers of lymphangiogenesis. There are few morphological studies of lymphatic vessels in atherosclerotic plaques, and the obtained data are contradictory.

The aim of the study was to characterize the LYVE-1 receptor expression in the endothelium of newly formed vessels in carotid atherosclerotic plaques and to evaluate its relationship with the plaque structure.

Materials and methods. 34 carotid atherosclerotic plaques obtained during carotid endarterectomies were investigated using histological and immunohistochemical techniques. The density of LYVE-1+ vessels per 1 cm2 of plaque, combined expression of LYVE-1 and CD34, proportion of atheromatosis and calcifications, as well as severity of dust-like calcification, haemorrhage, overall macrophage response (CD68+), and plaque infiltration by M2 macrophage (CD206+) were evaluated.

Results. LYVE-1+ vessels were detected in 32 carotid atherosclerotic plaques, with a range of 5.7–1698 per 1 cm2 of the plaque (37.4 [15.3; 76]). Marker expression was heterogeneous: it was observed in all or only some endothelial cells of the newly formed vessel, and the expression intensity varied from weak to strong. Both CD34+LYVE-1+ and CD34+LYVE-1– vessel phenotypes were identified. A relationship between endothelial LYVE-1 expression and the structure or type of plaque was not established, except for the macrophage response. The density of LYVE-1+ vessels in atherosclerotic plaques correlated weakly with the overall macrophage response (r = 0.37; p = 0.03), more significantly with the number of anti-inflammatory M2 macrophages (r = 0.47; p = 0.005), especially for vessels with moderate and strong marker expression (r = 0.56; p = 0.0006).

Conclusion. The combined expression of LYVE-1 and CD34 in the endothelium of plaque neovessels was demonstrated for the first time, and a possible association between endothelial LYVE-1 expression in newly formed vessels and the reparative processes in atherosclerotic plaques was shown.

Annals of Clinical and Experimental Neurology. 2020;14(3):43-52
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Expanding the horizons of antiplatelet therapy. A pilot study of the antiplatelet properties of a new tropane alkaloid

Mirzoian R.S., Shabalina A.A., Gan’shina T.S., Kurdyumov I.N., Turilova A.I., Kostochka L.M., Kozlov A.V., Annushkin V.A., Kornilova A.A., Tanashyan M.M.


Introduction. The article discusses the search for new and highly effective drugs for the prevention and treatment of cerebrovascular disease. The aim was to examine the effect of the acyl hydrazone tropane derivative on individual platelet aggregation (PA) sensitivity in in vitro studies.

Results. We present the results of a pilot study on the effect of a new acyl hydrazone tropane derivative — acyl hydrazone (2,3,4-trimethoxy-N'-(8-methyl-8-azabicyclo [3.2.1.] octane-3-ylidene) benzohydrazide hydrochloride on PA properties in vitro in healthy volunteers and in patients with chronic cerebrovascular disease.

Conclusion. The studied compound has a pronounced ability to suppress PA when administered intravenously in vivo in two concentrations, equivalent to doses of 10 and 100 mg/kg, and its effect is superior to the comparator acetylsalicylic acid, which is used in clinical practice as an antiplatelet drug.

Annals of Clinical and Experimental Neurology. 2020;14(3):53-59
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Non-pharmacological prevention and correction of cognitive disorders

Raskurazhev A.A., Kuznetsova P.I., Tanashyan M.M.


This review deals with research on the effect of board games on the prevention of cognitive disorders in the older population. It is known that activities using board games significantly enhance educational and intellectual abilities in children. However, data on the effect of such interventions in older patients (including those at risk for developing dementia) are few and equivocal. In the Bronx Aging Study, reading, board games, playing musical instruments, and dancing were associated with a reduced risk of cognitive disorders. The MoVIES study assessed the cognitive status of 942 participants aged 65 years and older, and a lower risk of dementia was found in those who devoted more than 1 hour per day to 'recreational activities'. The French study of the PAQUID cohort showed that those who regularly played board games had a 15% lower risk of developing dementia than those who did not.

This review attempts to systematize the known data (including functional MRI data) on how playing board games influences changes in cognitive function. The article covers memory mechanisms that are necessary components of cognitive health. Structures that are directly involved in long-term memory formation, especially explicit memory, including the hippocampus, parahippocampal gyrus, and entorhinal cortex, are described.

The article includes studies covering not only geographical, economic and social status, age, gender, and level of cognitive load, but also the different assessments measuring the effect board games have on the brain. Different assessment methods and functional MRI data have demonstrated the potential effectiveness of using board games in the prevention of both age-related and pathological intellectual ageing.

Annals of Clinical and Experimental Neurology. 2020;14(3):60-65
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Electrocorticography in patients with severe traumatic brain injury

Sinkin M.V., Talypov A.E., Kordonskaya O.O., Komoltsev I.G., Solodov A.A., Grin A.A., Krylov V.V.


Introduction. The frequency of adverse outcomes in patients with severe traumatic brain injury (TBI) exceeds 25%. Epileptic seizures and vasospasm, in the absence of pathogenetic treatment, cause irreversible brain damage and thus complicate the course of severe TBI. Bedside electroencephalography (EEG) is traditionally used to diagnose these conditions. However, its low spatial resolution when recording from the scalp and a large number of artefacts that make it challenging to analyse the data.

Materials and methods. Electrocorticography (ECoG) monitoring was performed using subdural electrodes implanted in the traumatic brain lesion during TBI surgery in 11 patients during the acute period of severe TBI. All patients were concurrently monitored using scalp EEG with subdermal needle electrodes.

Results. Analysis of scalp recordings showed frequency disturbances and oscillation asymmetry in all patients, while sporadic epileptiform activity and rhythmic and periodic patterns were detected in 18% and 64% of subjects, respectively. Analysis of invasive EEG showed sporadic epileptiform activity in 27% of patients, while rhythmic and periodic patterns were present in 91%. Moreover, epileptiform activity was registered only by the subdural leads in 3 patients. The total percentage of subjects in whom we registered clinical and electrographic signs of convulsive and non-convulsive status epilepticus using EEG and ECoG was 55%. We found indirect EEG signs of slow-spreading cortical depolarization in one patient whose level of consciousness was coma, followed by an electrographic pattern of status epilepticus on ECoG.

Conclusion. ECoG recording, while patients with severe TBI are in the intensive care unit, increases the diagnostic capabilities of this method, allowing electrographic seizures to be recorded more often and more accurately, but also to detect indirect signs of slow-spreading cortical depolarization using standard EEG amplifiers. Electrode implantation during TBI surgery is safe and does not significantly change the surgical approach.

Annals of Clinical and Experimental Neurology. 2020;14(3):66-76
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Somatosensory evoked potentials in the evaluation of motor rehabilitation efficacy in patients with ischaemic stroke

Alifirova V.M., Tolmachev I.V., Koroleva E.S., Kucherova K.S.


Introduction. The quality of rehabilitation measures used during early functional recovery can be assessed by registering somatosensory evoked potentials (SSEP). In many patients, SSEP are either not recorded, or the results are poorly reproducible. To overcome these difficulties, we proposed to modify the method of recording SSEP in patients post ischaemic stroke.

The aim of the study was to evaluate changes in SSEP after patients with ischaemic stroke underwent motor rehabilitation in the early recovery period. 

Materials and methods. We examined 36 patients with acute ischaemic stroke in the middle cerebral artery territory. The severity of neurological deficits and the functional state of the nervous system were assessed using international clinical scales, based on electrophysiological and neuroimaging studies. The motor rehabilitation consisted of 10 sessions. SSEP were measured before and after the full motor rehabilitation course. We calculated the standard values for SSEP. 

Results. Before rehabilitation, SSEP were not detected in the ipsilateral hemisphere in 40% of patients. After a course of rehabilitation, SSEP were detected in the majority (83%) of patients, but the values showed significant inter-individual variation, and in such patients, SSEP cannot be used as an indicator of rehabilitation effectiveness. In the group of patients whose SSEP could be reliably recorded and the main components P and N were measurable, we found that the average component latency in the ipsilateral hemisphere was N = 48 ± 15 msec and P = 55 ± 16 msec. These values are significantly higher than in the healthy population. The amplitude parameters corresponded to the published normal values. No statistically significant changes in the latency of components N and P were observed after the course of rehabilitation.

ConclusionUsing a method for measuring SSEP with spatiotemporal separation will significantly expand the range of patients whose condition, as well as the effectiveness of the rehabilitation procedures aimed at restoring lost motor function caused by ischaemic brain damage, can be monitored over time.

Annals of Clinical and Experimental Neurology. 2020;14(3):77-80
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Clinical analysis

Bilateral hypertrophic olivary degeneration in genetic neurological disorders

Suslin A.S., Seliverstov Y.A., Kremneva E.I., Krotenkova M.V.


Hypertrophic olivary degeneration (HOD) is a rare variant of transsynaptic degeneration in the inferior olivary nuclei due to a lesion within the dentato-rubro- olivary pathway, also known as the Guillain–Mollaret triangle. Bilateral HOD can be identified on MRI in patients with not only acquired but also genetic neurological disorders. The article describes patients with both common and rare genetic causes of the bilateral HOD. The pathophysiology of HOD is also briefly reviewed.

Annals of Clinical and Experimental Neurology. 2020;14(3):81-87
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