Vol 15, No 1 (2021)

Original articles

Internal carotid and vertebral artery dissection: an approach to patient management

Kalashnikova L.A., Dobrynina L.A., Maksimova M.Y., Tanashyan M.M., Danilova M.S., Dreval M.V.

Abstract

We aimed to evaluate the treatment results in patients with internal carotid artery (ICA) and vertebral artery (VA) dissection.

Materials and methods. We examined 285 patients (122 men and 163 women, mean age 37.7 ± 8.1 years) with ICA dissection (n = 147), VA dissection (n = 122), or a combination of both (n = 16). The dissection presented as ischemic stroke in 175 patients and with local symptoms in the others. Out of 173 patients, 156 were managed conservatively. Efficacy of the conservative treatment in first 3 months was assessed in 143 patients who received anticoagulants (AC; n = 38), antiplatelets (AP; n = 42), both (n = 45) or no antithrombotic therapy (n = 18).

Results. Good functional recovery (0–2 points on the modified Rankin Scale) after 3 months was noted in 70% of patients, with no statistically significant differences between the different treatment types. There were 3 (2%) deaths in patients with severe stroke receiving AC. Recurrent ischemic stroke occurred in 10% of patients most often (86%) occurring in the first 3 weeks and triggered by head movement, straining, or fluctuating blood pressure. No statistically significant differences were found between different conservative treatments. However, there was a tendency towards increased frequency of recurrent stroke in patients without antithrombotic therapy (22%), as compared with patients receiving AC (4%) or AP (12%). There were no strokes in 110 patients with local symptoms due to ICA/VA dissection during the observation period.

Conclusion. There were no statistically significant differences in AC and AP efficacy in patients with ICA or VA dissection. A neck brace to prevent head movement and control of blood pressure are advisable alongside pharmacological therapy.

For citation: Kalashnikova L.A., Dobrynina L.A., Maksimova M.Yu., Tanashyan M.M., Danilova M.S., Dreval M.V. [Internal carotid and vertebral artery dissection: an approach to patient management]. Annals of clinical and experimental neurology. 2021; 15(1): 5–12. (In Russ.). https://doi.org/10.25692/ACEN.2021.1.1

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Changes in the in-hospital mortality due to stroke and factors affecting its reduction in the European Union, Middle East, USA, Canada, Ethiopia and China

Vozniuk I.A., Morozova E.M., Prokhorova M.V.

Abstract

Introduction. While a specialized healthcare system is being developed for patients with stroke, early in-hospital mortality has been rightly chosen as a target indicator. It integrally reflects the correctness of organizational decisions, the completeness and quality of the diagnostic process, the availability of help, and factors relating to patient comorbidities.

Aim. To gather information reflecting the level of the in-hospital mortality due to stroke and factors leading to its reduction.

Materials and methods. PubMed was used to search the Medline database with the keywords ‘mortality rate’, ‘in-hospital mortality’, ‘stroke’, and ‘prediction’. The review included sources in any language from the year 2000 to the present if the full text was available online. Most of the statistical data were obtained from national stroke registries. 

Results. Direct indicators of the percentage of in-hospital mortality varied significantly between different countries, precluding direct comparison. In-hospital mortality varied significantly and depended on clinical features and healthcare administration, including hospitals’ size and their level. A change in the in-hospital mortality was reported in 9 out of 22 reports and enabled us to track the degree of its reduction. The mean rate of reduction was 0.36% per year. Faster changes in this parameter were typical for ischaemic stroke and accompanied the implementation and expansion of cerebrovascular surgery centers with dedicated stroke units. We identified ‘modifiable’ and ‘non-modifiable’ factors that influence in-hospital mortality in stroke patients.

Conclusion. To more accurately evaluate the role of factors affecting in-hospital mortality in different countries, a meta-analysis is required, which would consider the regional organizational features, the availability of trained specialists at cerebrovascular surgery centers, and the degree of population awareness. The most consistent predictors of the in-hospital mortality were age, stroke type, stroke location, level of consciousness according to the Glasgow Coma Scale, stroke severity as measured by the NIHSS, and comorbidities. Factors that can reduce in-hospital mortality rates include population awareness, increased availability of ICU beds for stroke patients, telehealth, monitoring for late complications, and primary prevention.

For citation: Vozniuk I.A., Morozova E.M., Prokhorova M.V. [Changes in the in-hospital mortality due to stroke and factors affecting its reduction in the European Union, Middle East, USA, Canada, Ethiopia, and China]. Annals of clinical and experimental neurology. 2021; 15(1): 13–20. (In Russ.). https://doi.org/10.25692/ACEN.2021.1.2

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The effect of modifiable stroke risk factors on systemic thrombolytic therapy in patients with acute stroke

Kotov S.V., Isakova E.V., Kolchu I.G., Belkina S.N.

Abstract

Introduction. Systemic thrombolytic therapy (STT) is an effective and accessible method of reperfusion treatment for ischaemic stroke. However, it is not yet evident how the risk factors preceding ischaemic stroke affect disease progression and outcome, as well as the efficacy of STT.

The study aimed to examine the results of STT in stroke patients, depending on their risk factors, severity of those risk factors, and the success in managing them at the prehospital stage.

Materials and methods. We examined 229 patients who underwent SST, of whom 201 survived and 28 died. The presence of hypertension, type 2 diabetes mellitus, atrial fibrillation, or metabolic syndrome, as well as blood sugar level, lipid panel results, and body mass index were assessed.

Results. Ischaemic stroke subtype, the length of time from symptom onset to start of STT, or the presence of hypertension did not have a statistically significant effect on 28-day mortality. Patient age, NIHSS score, presence/absence of type 2 diabetes mellitus and atrial fibrillation, modified Rankin Scale score, blood sugar level, body mass index, and the presence of metabolic syndrome had a statistically significant influence on 28-day mortality. Data from the survived 201 patients were used to analyze the correlation between risk factors and functional recovery after ischaemic stroke. For patients with moderate and mild ischaemic stroke, statistically significant inverse correlations were found for age, blood sugar level, and body mass index.

Conclusion. An inverse correlation was found between 28-day mortality and age, severity of neurological impairment, blood sugar level at onset, body mass index, and the presence of the metabolic syndrome. The ‘obesity paradox’ was not identified in regard to survival, but patients with hypercholesterolemia had more significant regression of neurological symptoms and better functional recovery. Receiving statins and having a target cholesterol level were not found to have a positive effect on patient recovery in the first 28 days after disease onset, likely because of greater severity of the overall vascular disease.

For citation: Kotov S.V., Isakova E.V., Kolchu I.G., Belkina S.N. [The effect of modifiable stroke risk factors on systemic thrombolytic therapy in patients with acute stroke]. Annals of clinical and experimental neurology. 2021; 15(1): 21–31. (In Russ.). https://doi.org/10.25692/ACEN.2021.1.3

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Does gender influence the clinical characteristics of ischaemic stroke in patients aged 45–74 years?

Maksimova M.Y., Airapetova A.S.

Abstract

Introduction. Modern studies seek to determine how age and gender affect morbidity and mortality, risk factors, causes, disease severity, and functional brain recovery after ischaemic stroke.

The study aimed to investigate the effect of gender on the main clinical characteristics of carotid territory infarction in patients aged 45–74 years who did not undergo thrombolysis or mechanical thrombectomy.

Materials and methods. We examined 124 patients: 77 (62.1%) men and 47 (37.9%) women of middle age and older, with carotid territory infarction, who were admitted to the Research Center of Neurology in the first 48 hours after neurological symptom onset. The ischaemic stroke subtype, stroke severity, level of functional dependence, and level of daily and motor activity in patients were established.

Results. In our group, women were older than men by 4 years on average (p = 0.018). The mean female age was 67 years (58–71 years), while the mean male age was 63 years (58–66 years). Women were more often diagnosed with cardioembolic stroke, while men were more often diagnosed with an atherothrombotic stroke. Ipsilateral internal carotid artery stenosis >50% and left ventricular hypertrophy were more common in men than women, while left atrial dilation was more common in women. No significant differences were found between the two genders in the clinical presentation, acute stroke severity, and functional brain recovery.

Conclusion. In middle and older age patients, gender does not affect ischaemic stroke morbidity and rate of functional brain recovery by the end of the acute stroke period.

For citation: Maksimova M.Yu., Airapetova A.S. [Does gender influence the clinical characteristics of ischaemic stroke in patients aged 45–74 years?]. Annals of clinical and experimental neurology. 2021. 15(1): 21–42. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.4

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The diagnostic significance of neurofilament heavy chains in cerebrospinal fluid in amyotrophic lateral sclerosis

Vladykina A.V., Nazarov V.D., Krasnov V.S., Koroleva E.I., Fedorova P.A., Moshnikova A.N., Mazing A.V., Lapin S.V., Emanuel V.L., Rudenko D.I., Stuchevskaya F.R., Zatakovenko S.M., Pavlova T.A., Alekseeva T.M., Goldobin V.V.

Abstract

Introduction. Early diagnosis of amyotrophic lateral sclerosis (ALS) is difficult because of the low sensitivity of clinical criteria at the early stages of the disease and the lack of reliable laboratory biomarkers. Neuron destruction leads to the release of excessively accumulated phosphorylated neurofilament heavy chains (pNFH) in the cerebrospinal fluid (CSF) and may potentially be used for early diagnosis of ALS. In addition, pNFH may have predictive significance.

Aim. To investigate the clinical significance of elevated neurofilament heavy chain levels in the CSF in ALS.

Materials and methods. The study included 33 patients with ALS diagnosed using the El Escorial criteria, 30 patients in the control group (post phlebectomy), as well as 28 patients in the comparison group: 16 patients with multiple sclerosis, 5 with autoimmune encephalitis, 1 with tick-borne encephalitis, 2 with primary lateral sclerosis, 1 with progressive muscle atrophy and 3 with other conditions (restless leg syndrome, compressive myelopathy and paraneoplastic cerebellar degeneration). All patients underwent a lumbar puncture, with pNFH levels measured using ELISA.

Results. A statistically significant difference in pNFH concentration was found between ALS patients and patients in the comparison group (p < 0.0001). At a threshold pNFH level, which was taken to be 0.785 ng/ml, the test sensitivity and specificity were 94% and 86%, respectively. Elevated pNFH levels in the CSF of patients with confirmed ALS were found in 94% of cases, compared with only 14% of patients in the comparison group. A statistically significant difference in pNFH concentration was found between the group with ALS and the control group (p < 0.0001). A negative correlation was found between pNFH level in the CSF and disease duration (r = –0.5172; p = 0.0029). A positive correlation was also found between the speed of disease progression and pNFH concentration (r = 0.5480; p = 0.001).

Conclusion. The results of this study demonstrate the high clinical significance of pNFH in the CSF in ALS.

For citation: Vladykina A.V., Nazarov V.D., Krasnov V.S., Koroleva E.I., Fedorova P.A., Moshnikova A.N., Mazing A.V., Lapin S.V., Emanuel V.L., Rudenko D.I., Stuchevskaya F.R., Zatakovenko S.M., Pavlova T.A., Alekseeva T.M., Goldobin V.V. [The diagnostic significance of neurofilament heavy chains in cerebrospinal fluid in amyotrophic lateral sclerosis]. Annals of clinical and experimental neurology. 2021; 15(1): 43–50. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.5

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The effect of reactive Bergmann glia on short-term synaptic plasticity in cerebellar neurodegenerative models, caused by chronic activation of ChR2 and expression of the mutant ataxin-1

Shuvaev А.N., Belozor О.S., Mozjei O.I., Yakovleva D.A., Shuvaev А.N., Smolnikova M.V., Pozhilenkova Е.A., Каsparov S..., Salmin V.V., Salmina А.B.

Abstract

Introduction. Synaptic plasticity is impaired in the early stages of a neurodegenerative process but is potentially reversible. The study of mechanisms associated with synaptic plasticity in neurodegenerative cerebellar conditions has enabled the search for potential therapeutic agents.

This study aimed to investigate the effect of the astrocytic link on paired-pulse facilitation (PPF) in cerebellar cortical synapses of mice, using a set of immunohistochemical, optogenetic, and electrophysiological analysis methods.

Materials and methods. Experiments were conducted on 12-week-old CD-1 mice. The model of murine cerebellar astrogliosis was created using chronic activation of light-sensitive ChR2 channels in Bergmann glia and after they expressed the mutant ataxin-1. To model astrocyte-mediated neurodegeneration, these mice were intracortically administered AVV GFAP-ChR2-mKate vector constructions with subsequent chronic 4-day light stimulation in vivo and LVV GFAP-ATXN1[Q85]-Flag without light stimulation. Mice in the control group were administered normal saline or LVV GFAP-ATXN1[Q2]-Flag. Changes in the PFF-excitatory postsynaptic currents in Purkinje cells were registered using the patch-clamp technique. Immunohistochemistry was used to examine anti-GFAP, mKate, and anti-ataxin-1 expression in the cerebellar cortex.

Results. For the reactive glia in the cerebellar cortex after chronic photostimulation, increased anti-GFAP immune reactivity and morphology changes in the form of process tortuosity were common. In Purkinje cell synapses with parallel fibers in these animals, the PPF coefficient was significantly increased because of impaired glutamate reuptake and presynaptic overexcitation with this neuromediator. However, photoactivation of reactive Bergmann glia led to a sharp slowing down of the glutamate-glutamine cycle and glutamate pool depletion in the presynapse, with a subsequent gradual reduction in the PPF coefficient. Such pathological mechanisms were found in the neurodegenerative model with selective damage to Bergmann glia by the mutant ataxin-1.

Conclusion. Astrocytes affect short-term synaptic plasticity such as PPF. In cerebellar astrogliosis, the PPF disturbance is multilevel: the high baseline level of PPF is significantly reduced after Bergmann glial activation, which is related to impaired glutamate reuptake by reactive glial cells.

For citation: Shuvaev А.N., Belozor О.S., Mozjei O.I., Yakovleva D.A., Shuvaev А.N., Smolnikova М.V., Pozhilenkova Е.A., Каsparov S., Salmin V.V., Salmina А.B. [The effect of reactive Bergmann glia on short-term synaptic plasticity in cerebellar neurodegenerative models, caused by chronic activation of ChR2 and expression of the mutant ataxin-1]. Annals of clinical and experimental neurology. 2021; 15(1): 51–58. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.6

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Giftedness and cytoarchitecture of the prefrontal cortex of the outstanding scientist and physiologist I.P. Pavlov

Piradov M.A., Illarioshkin S.N., Bogolepova I.N., Malofeeva L.I., Agapov P.A., Malofeeva I.G.

Abstract

The aim of this study was to examine the cytoarchitecture of area 10 in the frontal lobe of I.P. Pavlov, an outstanding scientist, physiologist, and Nobel Prize winner.

Materials and methods. We studied the cortical cytoarchitecture of area 10 in the brain's frontal region belonging to the scientist and physiologist I. P. Pavlov (aged 86 years), compared with similar brain cortices of 4 elderly males (75–90 years). Modern morphometric methods were used, on the basal surface of each cerebral hemisphere, to study the cortical thickness of area 10, thickness of the associated layer III, area of the specialized neural field in this layer, the number density of contained neurons, total glial cells, satellite glial cells, and the neurons surrounded by them.

Results. It was found that area 10 of the cerebral cortex of I.P. Pavlov is characterized by good preservation, pronounced radial striation, and significant asymmetry of the macroscopic and cytoarchitectural structure. Compared with ordinary men, area 10 of I.P. Pavlov’s brain has a significantly thicker cortex and associative layer III, as well as a higher proportion of large neurons, number density of neurons, total glial cells, satellite glial cells, and neurons surrounded by them.

For citation: Piradov M.A., Illarioshkin S.N., Bogolepova I.N., Malofeeva L.I., Agapov P.A., Malofeeva I.G. [Giftedness and cytoarchitecture of the prefrontal cortex of the outstanding scientist and physiologist I.P. Pavlov]. Annals of clinical and experimental neurology. 2021; 15(1): 59–64. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.7

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Inhibition of ABCB1 activity in cerebrovascular disease may increase pharmacotherapy effectiveness

Chernykh I.V., Shchulkin A.V., Pravkin S.K., Gatsanoga M.V., Yakusheva E.N.

Abstract

Introduction. Despite the development of numerous drugs with neuroprotective activity, their efficacy in cerebrovascular disease remains low, which may partly be due to the efflux function of protein ABCB1 and insufficient penetration of the blood-brain barrier by these drugs.

Aim — to evaluate the potential to inhibit ABCB1 functional activity in the blood-brain barrier to improve the efficacy of neuroprotective therapy against brain ischemia.

Materials and methods. An experimental study was performed on 60 adult male Wistar rats split up into 5 groups: group 1 with falsely operated animals; group 2 with rats with modeled cerebral ischemia using bilateral ligation of the common carotid arteries and preliminary intravenous injection of saline (control ischemia); group 3 with animals that were intravenously administered a neuroprotective agent, an АВСВ1 substrate (nimodipine), 30 min before arterial ligation; group 4 with rats that were intravenously administered an АВСВ1 inhibitor (omeprazole) 30 minutes before disease modeling; and group 5 with animals with ischemia that were intravenously administered nimodipine together with omeprazole before the operation. The efficacy of the tested substances was based on a reduction in animal deaths and the severity of neurological deficits 4, 12, 24, 48, and 72 hours after pathology modeling.

Results. The combination of nimodipine and omeprazole increased rat survival after ischemia modeling and decreased neurological deficits compared with the control rats with cerebral ischemia and the rats administered a neuroprotective agent.

Conclusion. The combination of a neuroprotective agent (ABCB1 substrate) and a transporter inhibitor provides an effective approach to improve the efficacy of neuroprotective pharmacotherapy in cerebral ischemia.

For citation: Chernykh I.V., Shchulkin A.V., Pravkin S.K., Gatsanoga M.V., Yakusheva E.N. [Inhibition of ABCB1 activity in cerebrovascular disease may increase pharmacotherapy effectiveness]. Annals of clinical and experimental neurology. 2021; 15(1): 65–70. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.8

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Reviews

Comparing the results of surgical and conservative treatment of patients with supratentorial hypertensive intracerebral hemorrhage. A new look at previously known randomized studies

Godkov I.M., Dashyan V.G.

Abstract

Hemorrhagic stroke is a medical and social problem, with an incidence of 15–35 per 100 000 people per year. It is characterized by high patient mortality (up to 53% in the first year) and disability, with most of the surviving patients having persistent neurological deficits and about 20% of them requiring continuous assistance.

The advantages of surgical or conservative treatment of patients with supratentorial hypertensive intracerebral hemorrhage (ICH) are still under discussion. This literature review is based on 12 open-source articles on prospective randomized trials comparing conservative and surgical treatment results in patients with supratentorial ICH, which demonstrate contradictory results.

Based on an analysis of all the works, we can conclude that surgical treatment has an advantage when performed early (within 12–72 hours) in patients whose level of consciousness is 9–12 points on the Glasgow Coma Scale. Needle aspiration and local fibrinolysis are effective for basal ganglia ICH, while open surgery and endoscopic aspiration are effective in subcortical ICH. For subcortical ICHs that are 20–80 cm3 in size, surgical treatment improved functional outcomes, while in ICHs larger than 50 cm3, it helped to reduce mortality.

For citation: Godkov I.M., Dashyan V.G. [Comparing the results of surgical and conservative treatment of patients with supratentorial hypertensive intracerebral hemorrhage. A new look at previously known randomized studies]. Annals of clinical and experimental neurology. 2021; 15(1): 71–79. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.9

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Clinical analysis

Results of percutaneous rhizotomy for trigeminal neuralgia in patients with multiple sclerosis

Tyurnikov V.M., Askarova L.S., Trifonova O.V., Zakharova M.N., Gushcha A.O.

Abstract

Introduction. Neuropathic pain in trigeminal neuralgia (TN) is one of the most common and debilitating symptoms in patients with multiple sclerosis (MS). This condition in MS is due to the demyelination of pontine afferent fibers in the sensory root of the trigeminal nerve. The area of demyelination is usually located in the ventrolateral pons between the exit of the trigeminal nerve root and the trigeminal nucleus, which is confirmed on MRI. In some cases, neurovascular compression also plays a role in afferent fiber injury, leading to the so-called double crush effect. Conservative therapy for TN in patients with MS is often insufficiently effective, thus increasing the pertinence of surgical treatment.

Materials and methods. The article reviews current pharmacological and surgical approaches to treating TN, findings from the literature, and our data on the safety and efficacy of percutaneous radiofrequency rhizotomy (PRR) for TN, based on the surgical treatment of 52 patients with MS at the Research Center of Neurology.

Results. PRR works by interrupting the connection between peripheral receptor zones and the hyperactive trigeminal structures in the brainstem. All patients were discharged from the hospital on day 2–3 after surgery, with complete pain resolution. There were early and late relapses in some instances, which required a repeated PRR.

Conclusion. PRR is a symptomatic surgical method that is safe, repeatable, and effective for treating TN in patients with MS, in whom pharmacological therapy has been ineffective or who could not tolerate it.

For citation: Tyurnikov V.M., Askarova L.Sh., Trifonova O.V., Zakharova M.N., Gushcha A.O. [Results of percutaneous rhizotomy for trigeminal neuralgia in patients with multiple sclerosis]. Annals of clinical and experimental neurology. 2021; 15(1): 89–94. (In Russ.). https://doi.org/10.25692/ACEN.2021.1.11

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Technologies

The first clinical use of a Russian stent retriever during thrombectomy in patients with ischaemic stroke

Grachev N.I., Malaev D.U., Andreev M.N., Trebushat D.V., Syrovnev G.I., Loskutnikov M.A., Vakin T.M., Konstantinov V.I., Domashenko M.A.

Abstract

Introduction. Endovascular thrombectomy with stent retrievers (SR) is effectively used to treat patients with ischaemic stroke due to thrombotic occlusion of large intracerebral arteries.

The aim of the study was to evaluate the ability of popular SR made overseas to grab the blood clot in vitro compared with the first Russian SR (Grasper, Angioline), as well as to analyze the first use of this SR in clinical practice.

Materials and methods. A comparative assessment of different SR: Trevo ProVue (Stryker), Penumbra (Penumbra Inc.), Solitaire (Medtronic), and Grasper (Angioline) and their ability to capture a blood clot in vitro was performed. A clinical evaluation of the safety and efficacy of the Grasper SR in patients with ischaemic stroke was conducted.

Results. No difference was found in the ability of the test devices to pass through torturous areas, and all devices successfully reached the target implantation zone without difficulty. The clot could be removed entirely in all cases, with no evidence of fragmentation during removal. Clinical testing of the Grasper SR demonstrated that its performance was comparable to the Solitaire SR in restoring intracerebral blood flow.

Conclusion. The obtained results from the in vitro study demonstrate comparable effectiveness of the Russian SR to its counterparts. The clinical study results show that the Grasper SR can effectively and safely remove blood clots in clinical settings but requires further study on a larger number of subjects.

For citation: Grachev N.I., Malaev D.U., Andreev M.N., Trebushat D.V., Syrovnev G.I., Loskutnikov M.A., Vakin T.M., Konstantinov V.I., Domashenko M.A. [The first clinical use of a Russian stent retriever during thrombectomy in patients with ischaemic stroke]. Annals of clinical and experimental neurology. 2021; 15(1): 80–88. (In Russ.). https://doi.org/10.25692/ACEN.2021.1.10

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