Vol 15, No 3 (2021)

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Full Issue

Original articles

Resolved and unresolved issues of cerebrovascular disease in diabetes mellitus

Tanashyan М.М., Antonova K.V., Lagoda О.V., Shabalina А.А.


Significant contribution of type 2 diabetes mellitus (T2DM) to the development and progression of cerebrovascular disease (CVD) has been confirmed over the past few decades. The aim of this article is to present the results of many years of research, summarizing generally resolved problems in CVD and T2DM comorbidity, as well as raising several issues that still need to be clarified.

Materials and methods. The assessment results of 824 patients with CVD were selected from a large body of data for inclusion in the analysis. Ischaemic stroke was analysed in 250 patients: 128 patients with T2DM (aged 63 [54; 74] years) and 122 patients without T2DM (62 [52; 71] years). The group with chronic CVD consisted of 574 people: 300 patients with T2DM (62 [56; 69] years) and 274 patients without T2DM (63 [57; 68] years). The results of surgery for carotid artery stenosis were evaluated in 170 patients, including 72 patients with T2DM. The control group consisted of 86 persons without CVD (60 [54; 63] years). A wide range of clinical, laboratory and imaging assessments included physical and neurological examinations, neuropsychological tests, blood chemistry, haemorheological and haemostasis tests, as well as neuroimaging studies.

Results. T2DM has a significant effect on neurological, neuropsychological, cognitive and functional impairments, as well as on the outcome of acute and chronic CVD, progression of intracranial atherosclerotic lesions, and changes in cerebral and vascular tissue. The impact of the quality of glycaemic control and duration of chronic hyperglycaemia on neurocognitive and structural brain changes has not been completely determined yet. The role of non-glycaemic changes, including influence of several mediators on the vascular and neurodegenerative mechanisms of cerebral tissue damage, warrants further study.

Conclusion. The obtained results identify a wide range of unanswered questions and emphasize the need for both possible changes to several clinical algorithms and for ongoing in-depth studies of CVD associated with T2DM.

Annals of Clinical and Experimental Neurology. 2021;15(3):5-14
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Carotid sinus syndrome in carotid angioplasty with stenting

Polishchuk R.V., Piradov М.A., Ryabinkina Y.V., Shchipakin V.L., Koshcheev A.Y., Prokazova P.R.


Introduction. Significant progress has been made in primary stroke prevention, including through the widespread use of carotid angioplasty with stenting (CAS). At the same time, there is a growing number of publications reporting the development of carotid sinus syndrome (CSS) (haemodynamic instability) in the periope- rative period, as well as cerebral and cardiac complications and death, which requires in-depth study to improve the quality of medical care for patients with carotid artery stenosis.

The aim of the study was to determine the frequency, risk factors, clinical features and outcomes of CSS in patients with carotid artery stenosis undergoing CAS.

Materials and methods. The study included 120 patients with carotid artery disease, who underwent an elective surgical intervention consisting of transluminal balloon angioplasty. All patients underwent comprehensive clinical and laboratory tests and imaging studies.

Results. CSS developed in 70% of cases (n = 84) of carotid artery stenosis, and was significantly more common in men than women (71.4% vs. 28.6%, respectively) (p < 0.05). The median age of all patients with CSS was 68 (44–91) years. Mixed form of CSS was significantly more common than the cardioinhibitory or vasodepressor forms (p < 0.05). In more than half of all cases, symptoms developed during balloon dilatation or within an hour afterwards. The duration of CSS was 30–40 hours. Contralateral carotid occlusion was detected in 12 (10%) patients, significantly (p < 0.05) more often in patients with CSS (13%) compared to patients without CSS (2.8%).

Conclusion. Regardless of stenosis severity or symptoms, CAS is accompanied by CSS in 2/3 of cases. The CSS is predominantly a mixed type and can be accompanied by loss of consciousness in rare cases. CSS appears both intraoperatively and in the early postoperative period, and its average duration is 1.5 days. A factor that may be associated with CSS development is contralateral carotid artery occlusion (p > 0.05).

Annals of Clinical and Experimental Neurology. 2021;15(3):15-25
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Ischaemic stroke and oral inflammatory diseases

Maksimova M.Y., Ryazantsev N.A., Anisimova E.N., Anisimova N.Y., Piradov М.A.


The aim of this study was to establish clinical significance of oral inflammatory diseases in ischaemic stroke (IS), how aware doctors and nurses are of this problem, and the safety and possibility of performing dental hygiene in patients with acute IS.

Materials and methods. We examined 100 patients who had suffered an ischaemic stroke in the internal carotid artery territory within 6 to 48 hours. The efficacy of dental hygiene and the risk of developing chronic oral sepsis were evaluated using the Patient Hygiene Performance Index (PHP) and Chronic Oral Sepsis Risk index (COSR). Quality of life was assessed using the short version of the Oral Health Impact Profile (OHIP-14). The sociological study included 100 patients with ischaemic stroke, 38 nurses, and 18 neurologists.

Results. The severity of IS at study inclusion was 8 (3; 15) points on the NIHSS, while the Barthel Index score was 70 (45; 90) points. The modified Rankin Scale score was 1–3 points. The PHP index was 2.28 ± 0.05 and the COSR index was 20.13 ± 0.50. The OHIP-14 results (a total score of 28.1 ± 6.8 points) also indicated unsatisfactory quality of dental health. The results of sociological studies revealed low level of awareness regarding dental care during acute IS among doctors. After professional oral care, treatment of oral inflammatory diseases, and removal of significantly damaged teeth, patients with IS had a decrease in the PHP index to 1.17 ± 0.05 and the COSR index to 7.36 ± 0.50, which corresponds to a satisfactory level of dental hygiene by the end of the acute stroke period. The impact of dental health on quality of life parameters as measured by the OHIP-14 scale (22.4 ± 7.2 points) was satisfactory.

Conclusion. The most important aspect of early dental care in patients with IS is increasing the quality of oral health.

Annals of Clinical and Experimental Neurology. 2021;15(3):26-34
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Effectiveness of kinesiotherapy in chronic non-specific low back pain

Parfenov V.A., Lamkova I.A.


The aim of this study was to evaluate the effectiveness of physical therapy (kinesiotherapy or KT) for chronic non-specific low back pain (CNSLBP) in managing pain, improving functional and emotional state, and overall physical activity.

Materials and methods. The study included 71 patients (17 men and 54 women) aged 18–75 years (mean age 55.09 ± 13.0 years) with CNSLBP, of whom 34 patients received standard KT and 37 patients received enhanced KT. Patients were asked to complete the Numeric Pain Rating Scale (NPRS), the Oswestry Low Back Pain Disability Questionnaire, the Hospital Anxiety and Depression Scale (HADS), and the International Physical Activity Questionnaire (IPAQ-SF) at baseline, after 7 days and 90 days.

Results. In patients who received treatment, we observed a reduction in pain intensity as measured by the NPRS, from a score of 8 at baseline (6–8) to 3 (2–4) points after 7 days and down to 2 (0–4) after 3 months (p < 0.0001). Depression severity decreased from 7 (5–9) points to 5 (3–7) after 7 days (p = 0.002) and 4 (3–6) points after 90 days (p = 0.002). Anxiety decreased from 7 (5–10) to 6 (4–8) after 7 days (p = 0.0003) and 5 (3–7) points after 90 days (p = 0.0003). The Oswestry Low Back Pain Disability Questionnaire score decreased from 46% (34–57.77) to 28% (12–35.55) after 7 days (p < 0.0001), and then to 11.11% (4.44–26) after 90 days (p < 0.0001). Physical activity as measured by the IPAQ-SF increased from 11 (7–16) to 16 (13–19) points after 7 days (p = 0.001) and to 23 (15–26) points after 90 days (p = 0.0002).

The patient group receiving enhanced KT had a more significant reduction in pain as measured by the NPRS after 7 days and 3 months (p = 0.02 and p = 0.055, respectively), depression as measured by the HADS (p < 0.05), and disability as measured by the Oswestry Questionnaire (p = 0.015), accompanied by an increase in physical activity as measured by the IPAQ-SF after 90 days (p = 0.0002), as compared to the patient group receiving standard KT.

Conclusion. KT not only reduces pain but also improves the functional and emotional state, and increases physical activity in patients with CNSLBP. Enhancing KT by using a personalized approach and educational programmes improves long-term treatment outcomes.

Annals of Clinical and Experimental Neurology. 2021;15(3):35-42
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Analysing the reasons for rejection of neurosurgery intervention in patients with Parkinson’s disease referred to an extrapyramidal movement disorders clinic

Bril’ E.V., Tomskiy А.A., Poddubskaya A.A., Gamaleya A.A., Fedorova N.V.


We present findings of a 10-year retrospective study, analysing the reasons for rejection of neurosurgical intervention (deep brain stimulation or DBS) in patients with Parkinson’s disease, who were referred to an extrapyramidal movement disorders clinic and then to a neurosurgery centre. It was found that after screening, 78.6% of patients referred as candidates for neurosurgical treatment to an extrapyramidal movement disorders clinic were rejected, while 21.4% of patients were referred to a neurosurgery centre, where 12% underwent surgery. The main reasons for rejecting potential DBS candidates were: “early referral”, “inadequate pharmacotherapy”, “levodopa-resistant symptoms”, “atypical/secondary Parkinsonism”, “cognitive reasons”, “psychological reasons”, “comorbidity”, “abnormal MRI”, “poor response to levodopa medication” and “declined surgery”. Furthermore, the number of self-referrals decreased, the number of patients referred by neurologists increased, the number of rejections of ‘unsuitable’ DBS candidates decreased, and the number of ‘suitable’ candidates referred to the extrapyramidal centre increased during the time period of 10 years. In addition, the number of patients who were referred to the neurosurgery centre and underwent surgery there increased, which suggests greater awareness of the selection criteria among doctors, as well increased knowledge and experience among neurologists in both primary healthcare and specialized centres.

Annals of Clinical and Experimental Neurology. 2021;15(3):43-53
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Cognitive motor dissociation in patients with chronic disorders of consciousness: a literature review

Belkin V.A., Ilina K.A., Ryabinkina Y.V.


Chronic disorders of consciousness include several conditions that differ significantly in both clinical and neurophysiological features. As medical technology continues to develop, the differential diagnosis of disorders of consciousness extends beyond purely clinical work. Nevertheless, all types of consciousness disorders are united by varying degrees of dissociation between wakefulness, cognitive and motor activity. The external similarity and minimal differences in clinical symptoms in unresponsive patients may hide different morphofunctional variants of this condition. In particular, use of electroencephalography and functional magnetic re- sonance imaging techniques allows us to detect covert consciousness in some clinically unresponsive patients. Based on various estimates, this phenomenon occurs in 5–15% of all cases. A special instance of covert consciousness is cognitive motor dissociation (CMD), defined as activation of cortical motor centers, recorded using neurophysiological techniques, in response to a corresponding instruction to perform a movement without its visible performance. Some researchers believe that detection of CMD indicates a more favourable prognosis for the subsequent restoration of consciousness, rather than its absence. The aim of this review is to examine CMD and its potential significance for outcomes in patients with chronic disorders of consciousness.

Annals of Clinical and Experimental Neurology. 2021;15(3):54-61
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Mechanisms of neurogenesis and angiogenesis in ischaemic stroke: literature review

Koroleva E.S., Alifirova V.M.


Scientific achievements of recent decades indicate that neurogenesis and angiogenesis are interrelated processes in the struggle for functional recovery after ischaemic stroke. This literature review presents current data on the neurovascular interactions in ischaemic stroke, and describes the role of signalling molecules and growth factors in the regulation of neurogenesis and angiogenesis, which are crucial for neuronal survival and neuroplasticity. The authors conducted a literature search for abnormal neuroblast migration into the ischaemic penumbra and the role of signalling molecules, molecular targets of angiogenesis, and role of endogenous growth factors and neurochemical markers in post-stroke vascular regulation in acute cerebral ischaemia. Relevant keywords were entered into the PubMed and Google Scholar search engines, as well as Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, eLibrary, and other databases.

Despite promising results obtained in animal models, and the data from clinical studies, deeper interrelationships between molecular and cellular interactions of neurogenesis and angiogenesis are still not entirely clear. Further study and understanding of complex interactions between neurogenesis and angiogenesis is needed to find targets for exogenous growth factor administration and changes in endogenous molecule expression for treatment of ischaemic brain injury.

Annals of Clinical and Experimental Neurology. 2021;15(3):62-71
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Features of sodium magnetic resonance spectroscopy and its application in neurology

Sinkova V.V., Krotenkova I.A., Lyaskovik A.A., Konovalov R.N., Krotenkova M.V.


Magnetic resonance spectroscopy is an important non-invasive method that measures concentration and spatial distribution of certain biochemically significant tissue metabolites. This relatively new method has now evolved from a research tool to an independent diagnostic neuroimaging method, which provides answers to a number of important clinical and diagnostic questions at the early stages of the disease, and allows evaluation of treatment efficacy and determination of clinical outcome.

The article provides a review of data on sodium magnetic resonance spectroscopy, which is a very sensitive method for assessing cell viability and ion homeostasis. It can be used to measure early biochemical disturbances in the tissues in various degenerative diseases. We describe pathophysiology and technology underlying sodium magnetic resonance spectroscopy, as well as the most promising points of application of this method in central nervous system disorders seen by radiologists and neurologists in their clinical practice.

Annals of Clinical and Experimental Neurology. 2021;15(3):72-79
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Clinical analysis

Epilepsy in patients with MOG antibody disease

Avdeeva V.E., Kotov A.S.


Introduction. MOG (anti-myelin oligodendrocyte glycoprotein) antibody disease is a group of demyelinating disorders of the central nervous system, in which antibodies attack the glycoproteins on the oligodendrocyte myelin membrane. The aim of the study was to evaluate the course of the disease in patients with MOG antibody disease with epilepsy.

Materials and methods. We examined 11 patients (5 men and 6 women) with MOG antibody disease aged from 2 months to 46 years. Three case studies were described when patients with MOG antibody disease had epileptic seizures.

Results and discussion. Epileptic seizures preceded the diagnosis of MOG antibody disease in the first patient. The disease presented as right-sided optic neuritis in the second patient. Seven years later, an epileptic seizure occurred after childbirth, when the BBB could have become permeable to circulating MOG antibodies. The disease presented with headache in the third patient. Right-sided optic neuritis and ataxia developed after an acute viral respiratory infection. Myelitis was diagnosed, and an epileptic seizure occurred one year later. The patient had a combination of CADASIL syndrome with MOG antibody disease.

Conclusion. Epileptic seizures are common in patients with MOG antibody disease. In addition to antiepileptic therapy, treatment of MOG antibody disease is crucial. This leads to good seizure control and a favourable prognosis.

Annals of Clinical and Experimental Neurology. 2021;15(3):80-84
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A case of pseudodominant inheritance of limb-girdle muscular dystrophy caused by mutations in the CAPN3 gene

Sharkova I.V., Bulakh M.V., Bessonova L.А., Shchagina O.A., Dadaly E.L.


Introduction. Limb-girdle muscular dystrophy (LGMD) includes more than 30 forms caused by mutations in genes located on autosomes. The most common form is calpain-3-related LGMD, with autosomal recessive inheritance pattern (OMIM 253600). An autosomal dominant form of LGMD (OMIM 618129) caused by c.643_663del heterozygous mutation in the CAPN3 gene is also supposed to exist.

This article describes a family case of LGMD caused by mutations in the CAPN3 gene with pseudodominant inheritance.

Materials and methods. Two patients with LGMD were studied: a 59-year-old woman and her 38-year-old daughter. Clinical, genealogical and molecular genetics methods were used: limb girdle muscular dystrophy MPS panel, Sanger sequencing of DNA of the proband, her affected daughter, and six first- and second-degree relatives across four generations.

Results. It was found that identical variants of the nucleotide sequence, c.598_612del and c.1746-20C>G, identified in the CAPN3 gene of the proband and her daughter, are in the trans position (compound heterozygous state), causing autosomal recessive calpain-3-related LGMD. This is an example of an incredibly rare pseudodominant inheritance of an autosomal recessive disease, established through indirect evidence that the proband’s husband is a heterozygous carrier of a nucleotide substitution in the CAPN3 gene.

Conclusion. It is crucial to examine the marriage partner for heterozygous carrier status of a gene mutation responsible for the disease in family planning and when clarifying the child’s prognosis for a patient with an autosomal recessive disease. Considering the existence of a late-onset (after 30 years) LGMD phenotype associated with the CAPN3 gene, differential diagnosis should begin with testing this gene in families with late disease onset.

Annals of Clinical and Experimental Neurology. 2021;15(3):85-91
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