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Neurology, Neuropsychiatry, Psychosomatics

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Scientific and practical reviewed journal

Since 2009 the “Nevrologiya, Neiropsikhiatriya, Psikhosomatika" (Neurology, Neuropsychiatry, Psychosomatics) journal publishes timely articles, balancing both clinical and experimental research, case reports, reviews and lectures on pressing problems of neurology. The Journal is aimed to provide a forum to discuss etiology and pathogenesis, clinical features, modern diagnostic and treatment approaches to neurology, psychiatrics and its complications, as well as associated conditions.

The journal is intended for a wide range of neurologists, psychiatrists, neuropsychologists, and specialists of related occupations.

Articles from all specialized medical institutions of the Russian Federation and neighboring countries and materials prepared by Western partners are submitted to the journal.

Among editorial board members of the journal there are 24 Russian and foreign doctors of medical sciences and 3 candidates of medical sciences.

Federal Supervision Agency for Information Technologies and Communications registration ПИ № ФС77-35419 from 20.02.2009.

 

 

Current issue

Vol 12, No 1 (2020)
View or download the full issue PDF (Russian)

LECTURES

4-12 152
Abstract
A.R. Luria is one of the most prestigious scientists in neuroscience, neuropsychology in particular. His contribution to aphasiology and neurolinguistics is well known. However, today some researchers believe that A.R. Luria's main ideas have lost their relevance and have little influence on contemporary discussions. The paper presents the views of A.R. Luria on the brain organization of speech and aphasia. Although he developed his concept of the relationship between cognitive processes and brain work several decades ago, scientific and technological achievements in our days largely confirm many of his ideas and hypotheses. A.R. Luria's basic views of the brain and language are considered in this article in the light of modern neuroscience. Two main monographs and some works of A.R. Luria, which are dedicated to the brain organization of speech and to the classification of aphasia, are analyzed. In particular, comparisons are made between his initial assumptions about aphasia and their theoretical rationale in the  book «Traumatic Aphasia» (1947) and his more complex interpretation of the cerebral organization of speech, which is presented in his work «Basic Problems of Neurolinguistics» (1975). The paper discusses differences between these two books and also linguistic issues, which received much attention in his later publication. It considers the concepts of functional systems, systemic and dynamic organization of speech, proposed by A.R. Luria. It is shown that his interpretation of the cerebral organization of speech as a specific contribution of various brain regions to the speech system continues to be widely used, and his significant contribution to neurolinguistics is widely recognized.
Many ideas of A.R. Luria have been integrated into contemporary aphasiology, while some questions of his proposed classification of aphasia remain debatable.



ORIGINAL INVESTIGATIONS

13-21 150
Abstract
Patent foramen ovale (PFO) is an important cause of embolic cryptogenic stroke (ECS) in young patients. The main mechanism in this case is paradoxical embolism (PE), the basis for which is a right-to-left (R-L) shunt.
Objective: to comparatively characterize patients who have undergone ECS, with and without an R-L shunt, as evidenced by transcranial Doppler with the bubble test (TCD-BT).
Patients and methods. In 40 patients with acute ECS, an R-L shunt was sought using TCD-BT, followed by transesophageal echocardiography (TEE). The left atrial volume index (LAVI) was additionally calculated. Brain damage was analyzed by probabilistic mapping of foci according to magnetic resonance imaging.
Results and discussion. The mean age of the examined patients was 51.5 (39.5–60.0) years; of them there were 22 women and 18 men. An RL shunt was detected in 24 (60.0%) of patients with cryptogenic embolism that was mainly grades 2 and 3 (41.0 and 35.0%). TEE could visualize PFO (1.0 to 5.5 mm in size) in 16 (40%) patients and atrial septal aneurysm in 3 (7.5%). PFO was not found in 5 patients with positive results of TCD-BT, which may suggest that there is either a pulmonary shunt or a false-negative TEE. The patients with an R-L shunt versus those without an R-L-shunt showed lower LAVIs (23.9 and 26.5 mL/m2) (p=0.016). This fact may additionally confirm the causative role of PFO in the development of stroke, whereas higher LAVIs in the non R-L shunt subgroup should alert to the presence of atrial cardiopathy and initiate an appropriate diagnostic search for latent atrial fibrillation. According to the presence or absence of an R-L shunt, the groups did not significantly differ in gender, age, and clinical characteristics of the stroke. In patients with PFO, a lesion focus was most commonly localized in the middle cerebral artery bed (35.3%), cerebellum (23.5%), and posterior cerebral artery (17.6%). Five (29.0%) patients were ascertained to have several foci of acute stroke. There was a trend towards the larger size of cerebral infarction foci and their specific localization in the vertebrobasilar bed in PE, which determined the high (35.3%) incidence of ataxia with the onset of the disease.
Conclusion. PE causes ECS in 60.0% of cases. The distinctive feature of patients with an R-L shunt is lower LAVIs and a trend towards the larger size of cerebral infarction foci and their specific localization in the vertebrobasilar bed.
22-26 102
Abstract
The cytokine of the tumor necrosis factor (TNF) family B-cell activating factor (BAFF) (TNFSF13B) that regulates the proliferation, differentiation, and survival of B cells is assumed to be involved in the pathogenesis of multiple sclerosis (MS).
Objective: to analyze the association of BAFF gene polymorphisms (rs1224141, rs9514827) with the progression rate and frequency of MS exacerbations.
Patients and methods. A total of 100 Caucasian patients (24 males and 76 females) with relapsing-remitting MS, who were born and lived in the Altai Territory of the Russian Federation, were examined. Genotyping was performed by real-time polymerase chain reaction using competitive TaqMan probes. 
Results and discussion. The annual risk of a>0.75 point disability increase in the Expanded Disability Status Scale (EDSS) score was ascertained to be associated with the first remission duration of less than 2 years, with the G/G genotype of BAFF (rs1224141) in males and females, and with the C/C genotype of BAFF (rs9514827) in females. The likelihood of the first remission duration of less than 2 years was increased in female carriers of the G allele of BAFF (rs1224141). There was no association of BAFF gene polymorphisms (rs1224141, rs9514827) with the frequency of MS exacerbations.
It seems promising to further study the role of BAFF in the pathogenesis of MS and the effect of this cytokine on the specific features of the course of the disease. The investigation results will be able to predict the efficiency of MS therapy with anti-BAFF drugs and to identify criteria for their individualized use.
Conclusion. In patients with MS in the Altai Territory of the Russian Federation, the risk for a high MS progression rate is related to the carriage of BAFF genotypes with rare alleles in homozygous state: G/G polymorphism rs1224141, C/C polymorphism rs9514827 in combination with the female sex. The G allele of BAFF (rs1224141) in women is associated with the risk of the unfavorable prognostic duration of the first MS remission of less than 24 months.
27-32 68
Abstract
Early diagnosis of susceptibility to psychoactive substance (PAS) use and addiction is a pressing problem of addictology. The development of PAS dependence involves a reward system that also plays a key role in the modulation of nociception. The PRDM12 gene associated with congenital insensitivity to pain is involved in neurogenesis and affects the properties of nerve cells.
Objective: to comparatively assess pain sensitivity in mental and behavioral disorders caused by the use of PASs in healthy individuals and subjects with their occasional uses according to the genotype of rs10121864 in the PRDM12 gene.
Patients and methods. Examinations were made in 103 patients with addiction to PAS (F1x.2), in 114 apparently healthy individuals (a control group) and in 36 subjects who occasionally used PASs (a risk group). The pain sensitivity threshold and pain tolerance were determined by tensoalgometry; a subjective assessment of pain thresholds was made using a visual analogue scale. Genotyping was performed using the PRDM12 rs10121864 polymorphism.
Results and discussion. The distribution of the genotypes of PRDM12 rs101218 was statistically significantly different in the comparison groups. Odds ratio (OR) calculation showed that in the subjects who occasionally used PASs, the risk of their dependence was several times greater than that in carriers of the mutant A allele (OR, 2.52; 95% confidence interval (CI), 1.42–4.50) of rs10121864 and its homozygous genotype AA (OR, 6.66; 95% CI, 1.50–29.54) and in those of alternative genotypes. The PRDM12 was also found to be associated with the parameter of subjective assessment of pain sensitivity in PAS-dependent subjects. Thus, this parameter was significantly lower in the carriers of the mutant A allele than in those of the GG genotype.
Conclusion. The A allele and AA genotype of PRDM12 rs10121864 were established to be associated with the risk of PAS dependence and with the parameter of subjective perception of the upper pain threshold.

33-38 84
Abstract
The increase in the number of patients with mental disorders in general hospitals with the shorter patient length of stay there requires diagnostic and therapeutic measures as soon as possible. Group hypnotic suggestive psychotherapy (HSPT) is an effective psychotherapeutic technique that is capable of covering a large number of patients in a short time.
Objective: to evaluate the efficiency of short-term group HSPT in multidisciplinary hospital patients with borderline psychic disorders accompanying the underlying disease and to determine the impact of a single session of such therapy on the patients' condition.
Patients and methods. A study group consisted of 78 patients who received HSPT; a control group included 37 patients who did not have such therapy. Treatment-induced changes in their mental state were evaluated using the Symptom Checklist-90-Revised questionnaire; the patients' current state was rated with the Mood and Feelings (health, activity, and mood) questionnaire, and the situational anxiety subtest of the integrative anxiety test (IAT-st).
Results and discussion. The study group showed a more pronounced reduction in mental disorders, especially the symptoms of anxiety and depression, than that in the control group. A single HSPT session was shown to have a positive impact on the current state of patients, considerably improving their well-being and reducing the  manifestations of anxiety. Improving both the somatic and mental state of patients immediately before their discharge from a hospital seems to be an important therapeutic and social factor also for successful outpatient treatment.
Conclusion. It is necessary to conduct a follow-up study to clarify how long the impact of short-term intervention using HSPT can persist. The latter can be effective in multidisciplinary hospital patients.

39-44 87
Abstract
Objective: to evaluate the clinical efficacy and tolerability of the Russian drug tolperisone (calmyrex) versus tizanidine and baclofen in the therapy of acute nonspecific musculoskeletal pain (NSMSP) in the elderly.
Patients and methods. Examinations were made in 135 elderly (60–75-year-old) patients with acute NSMSP. To relieve pain syndrome, all the patients were prescribed nimesulide suspension 100 mg twice a day after meals. The patients were randomized using an envelope method to three groups, each of which took a muscle relaxant as tablets for 15 days: Group 1 received the Russian drug tolperisone (calmyrex) 150 mg thrice a day; Group 2 used tizanidine 2 mg thrice a day; Group 3 had baclofen 10 mg twice a day. Pain syndrome was rated on a visual analogue scale (VAS). To measure orthostatic blood pressure, to check the coordinator system, and to record adverse events (AEs) were mandatory.
Results and discussion. At 15 days, treatment substantially reversed pain syndrome according to VAS scores in all the groups: from 68 to 14 in Group 1, from 64 to 17 in Group 2, and from 62 to 18 in Group 3 (without significant differences between the groups). AEs were more common in Groups 2 and 3 patients who received tizanidine or baclofen. Orthostatic hypotension was reported in 3 patients taking baclofen. The high safety and good tolerability of a combination of a non-steroidal anti-inflammatory drug (NSAID) and a muscle relaxant were noted in the calmyrex group.
Although muscle relaxants ensure clinically significant short-term pain relief in acute nonspecific back pain, it is necessary to take into account that elderly patient can develop AEs when taking the drugs, which is associated with delayed metabolic reactions, reduced hepatic blood flow and glomerular filtration rate, and a larger number of diseases and used medications.
Conclusion. Therapy with NSAIDs and centrally acting muscle relaxants for acute NSMSP in elderly people calls for special precautions due to the fact that there may be AEs that are less likely to occur with calmyrex than with tizanidine and baclofen.
45-49 189
Abstract
Post-stroke depression significantly impairs functional recovery in patients and their quality of life.
Objective: to evaluate the efficacy of vortioxetine in correcting depressive symptoms in the early recovery period of ischemic stroke, as well as its effect on the cognitive functions of patients.
Patients and methods. The investigation enrolled 60 patients with ischemic stroke in the carotid bed with symptoms of mild and moderate depression according to the Montgomery-Asberg Depression Rating Scale (MADRS). Group 1 (a study group) included 30 patients who received vortioxetine 10 mg/day for 8 weeks; Group 2 (a comparison group) consisted of 30 patients who refused to take an antidepressant. The investigators evaluated the severity of focal neurological deficit using the US National Institutes of Health Stroke Scale (NIHSS), the degree of functional deficit with the modified Rankin Scale (mRS) and the Functional Independence Measure (FIM). The diagnosis of poststroke depression was established according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria; the authors analyzed the severity of depression using the Hospital Anxiety and Depression Scale (HADS) and MADRS and cognitive functions with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). For evaluation of higher mental dysfunctions, they used a set of neuropsychological techniques developed by A.R. Luria and his followers, by applying the classic stimulus materials.
Results and discussion. At 8-week follow-up, in Group 1 there were no patients with symptoms of moderate depression, only 14 (46.7%) patients had symptoms of mild depression, and the remaining 16 (53.3%) patients did not have emotional disturbances. At the same time, in Group 2, 14 (46.7%) patients were observed to have signs of moderate depressive disorder and 15 (50%) had symptoms of mild depression; 1 (0.3%) patient had symptoms of major depressive disorder. During treatment with vortioxetine, there was a considerable decrease in the severity of depressive symptoms according to the total MADRS score (U=87.0; p<0.0001) and a better functional recovery after a stroke, as shown by FIM (U=296.0, p= 0.023) and NIHSS scores (p<0.05). Analyzing the MoCA subtest scores revealed that Group 1 patients statistically significantly better coped with attention tasks (U=237.0; p<0.001).
Conclusion. Vortioxetine significantly reduces the severity of depressive symptoms, has an obvious positive effect on the cognitive status of patients, by improving neurodynamic functions and memory in patients in the early recovery period of ischemic stroke.
50-55 159
Abstract
Valproate is generally the drug of choice in genetic generalized epilepsy (GGE). But its therapy was changed after the appearance of the 2015 International League against Epilepsy (ILAE) recommendations to limit the dose of valproates in women.
Objective: to assess the spectrum of antiepileptic drugs (AEDs) and to evaluate the efficiency of therapy in adults with GGE, in terms of the gender characteristics of the latter and the ILAE recommendations.
Patients and methods. A retrospective open-label observational study was conducted. A cohort of patients was formed according to their visits to physicians in 2013 to 2017. Two patient groups were identified. Group 1 included 80 patients (35 males, 45 females); their mean age was 27.1±3.6 years; they were followed in 2013–2014. Group 2 consisted of 137 patients (53 males, 84 females); their mean age was 29.4±4.6 years; they visited their physicians in 2015–2017. The spectrum of AEDs that were used in monotherapy or polytherapy was assessed. The efficiency of therapy was determined by the onset of remission.
Results and discussion. The patients of the two groups were matched for the spectrum of GGE syndromes. Most patients received valproates; more than 35% took levetiracetam; lamotrigine was used slightly less often. In Group 2, females used polytherapy more frequently than males (p=0.03). The percentage of achievement of clinical and encephalographic remission (CER) was higher in Group 2 (p=0.05); there was no significant difference in this indicator between men and women in the two groups. In Group 2, among those achieving CER, the percentage of
patients receiving monotherapy decreased and that of those having polytherapy increased (p=0.02). The spectrum of AEDs used to achieve CEP
remained unchanged in both groups; however, there was a significant difference in the drug dosing regimens.
Conclusion. Current therapy for GGE is successful and leads to remission in most patients. After 2015, dual therapy for GGE is used significantly
more often in women than in men (p<0.05). The combination of valproate with levetiracetam or lamotrigine predominates.

56-60 86
Abstract
Objective: to investigate the efficacy and safety of Mexidol® FORTE 250 in patients with chronic cerebral ischemia (CCI) in the presence of hypertension and atherosclerosis.
Patients and methods. The investigation enrolled 20 patients aged 45 to 75 years with CCI in the presence of hypertension and atherosclerosis, who received intravenous Mexidol® administered dropwise at a dose of 500 mg once a day for 14 days, followed by oral Mexidol® FORTE 250 mg thrice a day for 60 days (a study group). A control group consisted of 14 patients with CCI in the presence of hypertension concurrent with atherosclerosis, who were prescribed combination therapy for CCI without using these drugs. The patients were examined before and at 14 and 60 days of treatment. The investigators studied subjective complaints, neurological symptoms, and the indicators of the Tinetti Performance-Oriented Mobility Assessment in Elderly Patients; the Montreal Cognitive Assessment (MoCA); the Hamilton Anxiety Rating Scale (HARS); asthenia rating scales (Multidimensional Fatigue Inventory, MFI-20); and the Clinical Global Impression (CGI) scale over time.
Results and discussion. Therapy with Mexidol® in patients with CCI in the presence of hypertension and atherosclerosis was found to be accompanied by positive changes in the asthenia rating scale MFI-20, cognitive functions assessed by MoCA, as well as Tinetti movement coordination. No significant differences in these indicators were noted in patients of the control group. Combination treatment for CCI with Mexidol®and Mexidol® FORTE 250 as a sequential therapy was twice more effective than that without using these drugs, as shown by the scales as a whole and it was up to 10 times greater for individual scale parameters. 
Conclusion. The study of Mexidol® FORTE 250 as part of the sequential therapy, which was used according to the above regimen, indicates its clinical efficacy and safety in patients with CCI.

EXPERIMENTAL STUDIES

61-67 59
Abstract
Objective: to elucidate whether cerebrolysin contains peptide fragments that promote geroprotection.
Material and methods. The peptide composition of cerebrolysin underwent a comprehensive mass spectrometric analysis, followed by a systemic biological assessment.
Results and discussion. Thirty-six peptides with geroprotective properties were isolated in the multipeptide composition of cerebrolysin. These peptides included those of mimetics of adrenomedullin and enkephalins; those of inhibitors of seven targeted human proteins (the protein kinases MAPK1, VPRBP, and PKC, the gamma-secretase PS1, the kinases CDK1, SGK1 and mTOR). The established cerebrolysin peptides were shown to be competitive inhibitors of the seven targeted proteins. In particular, inhibition of PKC and mTOR stimulated the increased autophagy (the utilization of waste and abnormal proteins), which contributes to an increase in the survival of cells and model organisms.
Conclusion. Cerebrolysin can have geroprotective effects, by inhibiting the seven targeted proteins, by activating endorphinergic neurotransmission, and can be indirectly involved in vascular tone normalization.

CLINICAL OBSERVATIONS

68-71 60
Abstract
The paper describes a clinical case in which an 84-year-old patient with non-valvular atrial fibrillation (AF) who took dabigatran 110 mg twice a day developed recurrent ischemic stroke (IS) that caused dysarthria, left-sided hemiparesis, pain sensitivity and movement coordination impairments. At 170 minutes after IS development, idarucizumab was prescribed and thrombolytic therapy (TLT) was performed to neutralize the anticoagulant effect of dabigatran. At 24 hours after TLT, the National Institutes of Health Stroke Scale (NIHSS) scores were observed to decrease from 11 to 8; and repeated brain computed tomography revealed an ischemic focus in the left cerebellar hemisphere with hemorrhagic transformation to hemorrhagic heart attack type I. On day 19 of IS following the reversal of hemorrhagic transformation, dabigatran was resumed at a dose 110 mg twice a day.
The described case, as well as other authors' data that reflect real clinical practice, confirms that the administration of idarucizumab is safe and allows TLT to be performed in patients with AF who develop IS while taking dabigatran.

72-75 60
Abstract
The paper describes a clinical case of cerebral venous infarction developed due to sinus thrombosis in a young woman during pregnancy. Timely examination at the Regional Vascular Center and combination therapy could significantly improve the patient's status.

REVIEWS

76-80 69
Abstract
The key characteristics of migraine are its considerable predominance in reproductive-aged women. Studying the role of gender characteristics in the pathogenesis and clinical manifestations of migraine, as well as the patterns of changes in the level of female sex hormones depending on the menstrual cycle allow menstrual-related migraine to be considered as an independent subtype of the disease with the presence of characteristic clinical symptoms. The role of comorbidity in the development of menstrual-related migraine remains one of the little studied aspects of this problem.
The review presents an update on the patterns of the course of migraine in repriductive-aged women, the effects of hormonal drugs on migraine, and gynecological comorbidity.

81-86 81
Abstract
Tardive dyskinesia (TD) is a type caused by the use of different medications. The pathogenesis of TD is associated with dopamine receptor blockade, gamma-aminobutyric acid depletion, cholinergic deficiency, oxidative stress, impaired synaptic plasticity, and neurotoxicity. TD most often occurs after taking metoclopramide, antipsychotics, antidepressants, calcium channel blockers, and other drugs.
The review considers an adequate assessment of the potential risk of TD when the patient uses prescribed drugs, as well as the monitoring and correction of risk factors for TD, discontinuation or replacement of drugs that potentially cause TD, as well as its treatment.

87-92 85
Abstract
Levodopa remains the gold standard of treating Parkinson's disease (PD). However, the inevitable complication of levodopa therapy is druginduced dyskinesias, which significantly limits the therapeutic capabilities of this group of drugs and requires treatment adjustment. At the same time, patients with PD show not only a wide interindividual variability in the response to levodopa treatment, but also differences in the frequency and time to onset of drug-induced dyskinesias. Therefore, genetic predisposition can play an important role in the development of complications of levodopa therapy.
The paper reviews modern literature on the impact of mutations in the genes, the products of which are involved in the exchange of levodopa and are capable of provoking or, conversely, levelling the development of drug-induced dyskinesias in order to determine the possibilities of expanding the personalized approach to treating patients with PD.

93-99 53
Abstract
The paper presents data on the impact of infertility on the mental state of a woman in terms of both a change in her psychological profile and psychosocial, familial adjustment disorders, and the occurrence of mental disorders. It analyzes predictors (personality traits, familial, and sociocultural factors) for pathopsychological and psychopathological abnormalities in infertile women. The specific features of the impact of diagnosing infertility and uncertain reproductive status on the mental state of women are shown. Psychologically induced hormonal changes during infertility are described and data on the occurrence of somatic comorbidity of infertility are given. Mental health disorders in women using assisted reproductive technologies are touched upon.

100-104 68
Abstract
Acute pain, especially musculoskeletal and postoperative pain, is widespread pathology associated with quality of life deterioration, temporary disability, a tendency to relapse, and, in some cases, chronicity, so the timely and adequate treatment of this condition is important, including from the point of view of the prevention of serious medical, social, and economic consequences.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as first choices in modern guidelines for the treatment of musculoskeletal pain. Centrally acting muscle relaxants and their combinations with NSAIDs are also the basic component of dorsalgia treatment. However, the evidence base is available only for individual muscle relaxants, for orphenadrine in particular. The incorporation of NSAIDs as part of multimodal postoperative analgesia considerably reduces the need for opioids, lowers the risk of developing adverse reactions of the latter, and enhances patient satisfaction with the quality of pain relief. Centrally acting muscle relaxants having analgesic properties, for example tizanidine and orphenadrine, would be appropriate for use as part of multimodal analgesia.
The paper discusses the pharmacological properties of a fixed combination of diclofenac and orphenadrine (Neodolpasse®), its advantages over monotherapy with individual ingredients, and the results of clinical trials of this combination in spinal pain syndromes and in the postoperative period.

105-111 56
Abstract
Treatment for pain syndromes is one of the most relevant areas of modern medicine, which is of high social, economic and, individual importance. One of the most difficult questions is therapy for chronic pain (CP). This therapy should be based on a thorough analysis of the causes of pain. It is necessary to use combinations of drugs that potentiate the analgesic effects of each other and have a low risk of complications. The concept of adjuvant analgesics as one of the promising areas of treatment for chronic kidney disease is discussed.

112-117 92
Abstract
Cervicogenic headache (CH) is a syndrome of referred pain that originates in the neck structure. Despite the apparent simplicity of its determination, there is still no consensus on diagnostic criteria for cervicogenic headache amongst physicians of various specialties. In what cases is headache concurrent with neck pain a consequence of the pathology of the neck region, and in what cases is neck pain a consequence of a migraine attack?
The review deals with the diagnosis, differential diagnosis, and therapy of CH.

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