In 1887, S.A. Belyakov, a physician of the Imperial Medical and Surgical Academy, first described amyloid deposits in the brain of patients with dementia. Later, in 1906, A. Alzheimer revealed amyloid plaques and tau tangles in a patient with clinical signs of dementia. Over the following 100 years, the development of the concept of the amyloid origin of Alzheimer's disease (AD) confirmed numerous relationships between the brain accumulation of APs and cognitive decline. And if at the beginning of the amyloid era many researchers considered that the disease was caused by amyloid beta (Aβ) protein overproduction, in recent years they have increasingly pointed to a defect in the mechanisms of Aβ clearance, especially after the discovery of the lymphatic system of the brain. The role of disturbed homeostasis of redox-active metals, primarily iron and copper, in the development of the disease is also considered.

The amyloid hypothesis of AD has served as the basis for several areas in the design of drugs, such as secretase inhibitors, immunomodulatory drugs for active and passive immunization. However, only one drug (Akatinol memantine, an inhibitor of NMDA receptors and glutamatergic excitotoxicity) for the treatment of AD has been introduced into clinical practice over the past 20 years. Of interest are the data obtained in new studies of Akatinol memantine, which suggest that the latter is able to some extent affect the main pathophysiological processes underlying the development of cognitive impairment in Alzheimer-type pathology. 

The paper is devoted to the safe use of hormonal contraception in women with migraine, an urgent interdisciplinary problem daily faced by gynecologists, neurologists, and specialists in headache diagnosis and treatment. It gives information on the prevalence of migraine, the risk of ischemic stroke and other cardiovascular disorders in women with different types of migraine, including those receiving contraception and hormone replacement therapy. The paper presents the main provisions of the new interdisciplinary consensus «Hormonal contraceptives and the risk of ischemic stroke in women who have migraine», which are recommended to be taken into account by specialists of any profile when prescribing hormonal therapy to women with migraine in order to avoid cardiovascular events.

The paper presents a detailed algorithm for the treatment and follow-up of patients with recurrent multiple sclerosis and primary progressive multiple sclerosis in the use of ocrelizumab.

Fractional anisotropy (FA) estimated using diffusion tensor magnetic resonance imaging (dMRI) is considered as a promising biomarker in ischemic stroke (IS). The basis of this study is the assumption that the assessment of FA indices for different white matter tracts will be able to predict the main aspects of the rehabilitation potential even without determining the structural and functional bases of these influences.

Objective: to study the diagnostic significance of changes in FA indices to assess various aspects of the rehabilitation potential in acute IS.

Patients and methods. Examinations were made in 100 patients with IS and in 10 individuals without stroke and cognitive impairment. All the patients underwent dMRI and assessments of rehabilitation potential indicators on days 3 and 10 of the disease and at discharge.

Results and discussion. The indices of FA of the ipsilateral upper longitudinal and cingulum bundles, FA and the size of an infarct focus, asymmetry of FA of the cingulum bundle (rFA), corticospinal tract (at the level of the knee of the internal capsule and bridge) and the anterior limb of the internal capsule, as well as the FA of the splenium and knee of the internal capsule of the intact hemisphere are of the most value for the functional outcome of acute IS. The microstructure of these zones determines the state of most rehabilitation domains. With respect to global outcome, the integrity of the associative tracts of the affected hemisphere is more valuable than the microstructure of the intact hemisphere and rFA. The tracts of the intact hemisphere are of particular importance for the restoration of complex rehabilitation spheres, such as cognitive status and daily living and social skills, which is necessary to ensure patient independence.

Conclusion. The FA indices of the tracts under study seem to be a clinically acceptable biomarker of various aspects of the rehabilitation potential in acute IS. 

Posthypoxic encephalopathy is a frequent complication after coronary artery bypass surgery (CABG), which includes stroke, early postoperative delirium, and postoperative cognitive dysfunction (PCD). The more pronounced prevalence and severity of the latter during surgery using extracorporeal circulation are currently being discussed.

Objective: to analyze various types of cerebral dysfunction in patients undergoing CABG and to determine the role of perioperative factors in its development.

Patients and methods. The investigation enrolled 53 patients who had undergone elective CABG for coronary heart disease. Group 1 included 20 patients who had undergone beating-heart surgery; Group 2 comprised 33 patients, in whom CABG had been performed using extracorporeal circulation (ECC). Neuropsychological testing and brain magnetic resonance imaging (MRI) (structural and functional techniques) were carried out.

Results and discussion. Posthypoxic encephalopathy was diagnosed in 10 and 67% of patients in Group 1 and 2, respectively (p=0.05); these were precisely all the three types of brain dysfunction which were observed in Group 2 patients. Factors, such as over 70 years of age; median level of education; smoking; body mass index >30 kg/m2 ; ejection fraction <50%; class III effort angina; >210-min surgery duration; >55-min aortic ligation; and >115-min ECC, showed a statistically significant association with the onset of PCD (p<0.05). In Group 2, MRI revealed a weaker positive functional relationship of the medial prefrontal cortex with the posterior cingulate gyrus (<0.005); 18% of patients were found to have acute ischemic zones.

Conclusion. Surgical myocardial revascularization using ECC is associated with a greater likelihood of PCD than beating-heart CABG. The factors that favored the development of PCD, such as increased age, low preoperative cognitive status, smoking, and long-term use of ECC, were identified when applying ECC. 

Mitochondrial DNA (mtDNA) polymorphism makes a certain contribution to the formation of a genetic risk of multiple sclerosis (MS).

Objective: to analyze the frequency of mtDNA variants in patients with MS and control individuals in the Russian population. A similar study was conducted for the first time.

Patients and methods. The polymorphism of mtDNA was studied in the Russian population: in 283 unrelated patients with relapsing-remitting MS and in 290 unrelated healthy controls matched for gender and age.

Results and discussion. The frequency of haplogroup J in the patients with MS was twice higher than that in the control group (p=0.0055) (odds ratio (OR) 2.00; 95% confidence interval (CI). 1.21–3.41). This association was mostly observed in women (p=0.0083) (OR 2.20; 95% CI, 1.19–4.03). There was also a significant association of the A allele of MT-ND5 (m. 13708G>A) with MS (p=0.03) (OR 1.89; 95% CI 1.11–3.32). Sex stratification showed that the association with MS was significant only in women (p=0.009; OR, 2.52; 95% CI, 1.29–5.14). Further investigations will aim to analyze mtDNA variability (at the level of individual polymorphisms, haplogroups, and whole genome) in patients with relapsing-remitting MS and in those with primary progressive MS versus healthy individuals and patients with relapsing-remitting MS according to disease severity.

Conclusion. The data obtained in the Russian population suggest that mtDNA variations are involved in MS risk, to a greater extent in women. 

Owing to the advent of current methods for the prevention of exacerbations of multiple sclerosis (MS), it has become possible to increase the period to the development of obvious persistent cerebellar and motor disorders that mainly lead to disability. This makes it possible to focus on less evident and latent symptoms, in particular on cognitive impairment (CI) that are recorded since the diagnosis of MS and slowly progress over time.

Objective: to assess the prognostic capabilities of the Paced Auditory Serial Addition Test (PASAT) to identify a group of patients with early disability (10-year risk of reaching 6.5 Expanded Disability Status Scale (EDSS) scores.

Patients and methods. The paper presents the data of a 12-year (2005–2018) follow-up of 36 patients having MS with and without mild CI. The patients' mean age at the time of study inclusion was 31.7 years (confidence interval (CI) 29.2–34.1; α<0.05); the disease duration was 4.69 months (CI 3.31–6.08; α<0.05); the EDSS scores averaged 2.51 (CI 2.23–2.82; α<0.05). Severe disability (6.5 EDSS scores) was observed in 75% of cases in the presence of mild CI and in 25% of cases in the absence of mild CI; it occurred an average of 118.3 (CI 93.1–143.4; α<0.05) and 141.2 (CI 126.0–156.5; α<0.05) months later, respectively.

Results and discussion. The findings suggest that the patients with MS in the presence of impaired information processing speed and decreased attentional function (failure to complete more than 25% of the PASAT tasks) had a significantly greater risk for persistent disability than the patients without CI or with its minimal manifestations. Limitation in walking function (4.5 EDSS scores) occurred an average of 3.5 years earlier, and its significant limitation (6.5 EDSS scores) did 2 years earlier in the severe CI group, which may be important in planning therapy.

Conclusion. The presence of CI in early MS is likely to have a prognostic value in relation to the course of the disease. 

Objective: to investigate the features of clinical manifestations and course of secondary hypokalemic myoplegia (SHM) of various etiologies.

Patients and methods. The investigation enrolled 10 patients with SHM. The patients' mean age was 39.5±16.2 years. The cause of SHM was hyperaldosteronism in 3 cases, thyrotoxicosis in 1, nontraumatic rhabdomyolysis in 2, and severe toxicosis and massive obstetric hemorrhage in 4.

Results and discussion. The blood potassium level difference between days 7 and 1 of hospitalization in patients with hyperaldosteronism and thyrotoxicosis was 2.2±0.4 mmol/l; this indicator in the other patients was less (1.6±0.8 mmol/l). The dynamics of an increase in the blood potassium concentrations during the 7 days differed significantly in 4 pregnant women who had undergone a cesarean section for placental abruption, antenatal fetal death, or their severe toxicosis with suddenly developed neuromuscular disorders (2.1±0.8 mmol/l), and in other patients with SHM (1.4±0.2 mmol/l). SHM in Conn's syndrome and thyrotoxicosis was characterized by long-term (11.8±3.6-day) neuromuscular disorders, while in SHM of another etiology, there were shorter (5.8±4-day) muscle weakness episodes (p<0.05). The SHM duration was recorded to be shorter in 4 pregnant women (4.3±4 days) than that in the other patients (10.3±2.9 days) (p<0.05). In nontraumatic rhabdomyolysis, the duration of hypokalemic paralysis (HP) was significantly longer (9±1.4 days) than in pregnancy (4.3±3.9 days). The episodes of HP in thyrotoxicosis and aldosteroma turned out to be longer (495.8±331.5 days) (p<0.05) than those in the presence of electrolyte changes in pregnant women and in rhabdomyolysis (14±5.7 days). In patients without adrenal tumors, thyrotoxicosis, the SHM periods requiring urgent hospitalization were more prolonged in nontraumatic rhabdomyolysis (30±8.5 days) (p<0.05) than those in the presence with electrolyte disorders in pregnant women (11.2±3.7 days).

Conclusion. The differential diagnostic algorithm for examining patients with acute flaccid paralysis of various etiologies due to hypokalemia has not been well elaborated, especially in endocrine disease and rhabdomyolysis. The differences in the rate of hypokalemia reversal in hyperaldosteronism, thyrotoxicosis, and rhabdomyolysis are likely to be associated with the multifactorial etiology of SHM. An incorrect assessment of the etiology of SHM is a common reason for its late diagnosis and inadequate treatment.

No effect of outpatient treatment is observed in some patients with acute nonspecific lumbodynia and lumbar ischialgia; therefore they are referred to pain management departments or centers for specialized examination and treatment.

Objective: to study of the anatomical causes of pain and the efficiency of celecoxib (Dilaxa) treatment in patients with acute and subacute lumbodynia and lumbar ischialgia in the inpatient setting.

Patients and methods. Eighty patients (47 women and 33 men; mean age, 51.0±15.3 years) with acute and subacute lumbodynia (n=11) or lumbar ischialgia (n=69) were followed up. Pain intensity was assessed using a visual analogue scale (VAS); functional limitation was rated according to the Roland–Morris scale (RMS). To reduce the intensity of pain syndrome, patients took oral celecoxib (Dilaxa) 200 mg twice daily. Therapeutic blockades with anesthetics and glucocorticoids were used in some cases of damage to the sacroiliac joint (SIJ) or facet joints (FJ). Patients were informed of the benign nature of the disease; they did therapeutic exercises.

Results and discussion. The causes of pain were ascertained to be injuries of SIJ (48,8%), FJ and SIJ (18,8%), FJ (17,5%), herniated disc (10%), piriformis syndrome (2.5%), and piriformis syndrome and SIJ injury (2.5%). The duration of treatment averaged 11.0±2.4 days. By the end of the study, there was a clinically significant reduction in pain in 86% of patients. The treatment resulted in a 2.4-fold average reduction in pain intensity (from 7.0 to 2.9 VAS scores): a 4-fold reduction in patients with lumbodynia (from 6.4 to 1.6 scores) and a 2.3-fold one in those with lumbar ischialgia (from 7.1 to 3.1. scores); the degree of disability reduced by an average of 1.9 times (from 8.1 to 4.3 RMS scores): by 3.6 times (from 6.8 to 1.9 scores) and 1.9 (from 8,3 to 4,7 scores) times in patients with lumbodynia and in those with lumbar ischialgia, respectively. No adverse events were observed during the treatment period.

Conclusion. There were high SIJ and FJ injury rates in subacute lumbar ischialgia. Celecoxib was noted to be highly effective and safe in treating acute and subacute lumbar ischialgia and lumbodynia.

The aging process is accompanied by a structural change and a decrease in the functional activity of organs and tissues, including the bone, with the development of osteoporosis (OP).

Objective: to assess the characteristics of pain syndrome in OP patients with nonspecific chronic vertebrogenic lumbar ischialgia (CLI).

Patients and methods. Sixty elderly patients with CLI in the presence and absence of OP were examined. All the patients underwent dual-energy X-ray absorptiometry and ultrasound to diagnose the degree of OP and spinal deformity; a flexible rod was used according to the method described by M.A. Kathleen to estimate the angle of kyphosis, lordosis, and scoliosis. The investigators determined pain intensity by a numerical rating scale, the presence of a neuropathic pain component by the DN4 pain scale, the level of anxiety and depression by the Hospital Anxiety and Depression Scale, cognitive status by the Montreal Cognitive Function Rating Scale, the degree of disability by the Oswestry questionnaire, and quality of life by the SF-12 Health Survey.

Results and discussion. Our study showed that OP alone is not a cause of CLI in elderly patients. There were no statistically significant differences in the sources and intensity of pain, the degree of anxiety and depressive disorders, impaired quality of life, cognitive status, and degree of disability in patients with chronic lumbar pain syndrome in the presence and absence of OP. Vertebral deformity resulting from OP leads mainly to an obvious poor posture with an increase in thoracic kyphosis, straightening of lumbar lordosis, and S-curve lumbar and thoracic scoliosis, which can also cause secondary muscle spasm.

Patients with back pain in the presence of OP are treated in accordance with the general principles of management of patients with non-specific back pain, but taking into account the underlying disease. The paper presents current recommendations for the treatment of nonspecific back pain, for the management of patients with OP, as well as the updated clinical recommendations for the prevention of fractures in OP and osteopenia.

Conclusion. Patients with OP are noted to have predominantly chronic musculoskeletal pain in the presence of severe spinal deformity, but the level of this evidence is very low. The features of pain syndrome in patients with nonspecific vertebrogenic chronic lumbar ischialgia in the presence of OP call for further investigations. 

Objective: to identify psychosomatic and somatopsychic ratios in the clinical picture of disorders detected by internists as functional disorders (FD) of unexplainable or insufficiently explainable origin.

Patients and methods. In 2000 to 2017, an internist and a psychiatrist in the Internal Medicine Clinic made a joint examination of 640 patients (175 men and 465 women; the mean age of those in cardiology practice was 27.52±9.03 years; that of those in gastroenterology practice was 42.44±17.2 years, and that of those in pulmonology practice was 40.20±11.4 years) with various risk factors (RFs), who had for many years exhausted the clinical picture of diseases: neurocirculatory dystonia (NCD), irritable bowel syndrome (IBS), functional dyspepsia (FD), hyperventilation syndrome (HVS), and thermoneurosis (TN) (a study group). A comparison group included 245 patients (81 men and 164 women; their mean age was 38.78±8.07 and 48.12±10.92 years, respectively) with verified somatic diseases: hypertension, duodenal ulcer, asthma, and inflammatory bowel diseases. The patients were examined using both clinical and paraclinical studies in accordance with the standards for the above diseases and applying psychopathological and psychometric tests.

Results and discussion. A comparative interdisciplinary study established that the general medical practice patients with NCD, IBS, FD, HVS, and TN had two etiopathogenetically different clinical RFs: a) RF as the clinical essence of the current somatic disease and b) RF comorbid in certain psychopathological disorders: affective (F30–F39) (57.9%), neurotic (F40–F48) (27.1%), and schizotypic (F21) (15.0%). In the structure of complex psychosomatic syndromes that are often encountered in therapeutic practice, they represent the pivotal manifestations of disease, the adequate diagnosis of which is supposed to require cooperative interdisciplinary work.

Conclusion. Thus, our long-term study that is based on a single interdisciplinary approach has allowed us to formulate a modern concept of unity of the clinical stereotype of development of psychosomatic syndromes.

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a slowly progressive ataxic disorder characterized by the triad of cerebellar impairment, bilateral vestibular hypofunction, and sensory polyneuropathy. The paper describes a clinical case of this syndrome in a 40-year-old patient who has been followed up by hematologists for polycythemia vera for 10 years.

The prevalence of depression in Parkinson's disease (PD) amounts to as much as 90%. The paper describes patients at different ages and with different durations of PD in its early and advanced stages and with various types of depressive disorder.

The described clinical cases show that depression substantially worsens quality of life in a patient with PD and makes it difficult to choose antiparkinsonian therapy. Depression remains unrecognized on average in half of patients, while only a quarter of patients with identified depression receive timely treatment with antidepressants. PD complicated by depression is characterized by a faster progression and more significantly impaired quality of life and cognitive status than PD without affective disorders. Patients with PD and depressive disorder are characterized by an insufficient response to standard doses of antiparkinsonian drugs, which often leads to an irrational increase in the dose of dopaminergic drugs and to the development of complications.

Difficulties in choosing an antidepressant for PD are associated with the development of a complex multicomponent neurotransmitter imbalance in this disease. The prescription of multimodal antidepressants can solve this problem.

It is necessary to timely detect and correct depression in patients with PD using the currently available drugs and nonpharmacological methods (psychotherapy and physical rehabilitation). 

Nonsuicidal self-injuries (autotomy, self-inflicted destruction, self-mutilation) is a variant of autoaggression in a patient without the intent to take his/her own life. Patients with the consequences of self-injuries receive help from physicians of various specialties, who often cannot determine their motivation for autoaggressive actions, since it is associated with mental disorders.
The paper presents data on phenomenology, some classifications and motivation of nonsuicidal self-injuries. Various mental disorders are noted to be the most common cause of autoaggressive behavior. The paper describes a clinical case of a female patient who has mutilated her face for a long time, hiding the cause of her autoaggressive action. A detailed clinical and psychopathological analysis of her medical history and mental status allowed for classifying hypochondriacal delirium within schizophrenia as a cause of self-mutilating actions. The motivation for this behavior was to fight against a pseudotumor, for which the patient suffered pain and prolonged suppurative processes on the skin of the face, without visiting physicians.

The paper discusses the specific features of clinical presentations in patients with muscle dystonia, the presence of cognitive and mental disorders in dystonia. It presents a clinical case of severe segmental dystonia in a 72-year-old patient with cognitive and mental disorders. The manifestations of dystonia regressed during treatment with botulinum toxin; however, the patient did not report any improvement. An improvement could not be achieved after a psychiatrist's consultation and treatment for mental disorders.

In the past decades, there has been evidence on the relationship between Parkinson's disease (PD) and essential tremor (ET). In addition, PD frequently develops in already existing ET. The occurrence of PD in ET seems to be a problem of relevance, since the risk of PD is higher in patients with ET than that in the population. However, due to the lack of awareness about this nosological phenomenon among physicians, it can be difficult to formulate a diagnosis of PD that has developed in ET.

This paper gives an update on the clinical, epidemiological, pathogenetic, and neuroimaging characteristics of ET concurrent with PD. 

The review highlights the fundamental principles of early rehabilitation in ischemic stroke, the benefits and risks of early and very early patient mobilization. It presents data on the efficiency of CIMT-kinesiotherapy and mirror therapy in restoring upper extremity function, as well as procedures for nonpharmacological correction of spatial neglect syndrome. The effect on the rehabilitation of concomitant Alzheimer's disease is analyzed. The areas of pharmacological potentiation of poststroke rehabilitation, the efficiency of cerebrolysin in particular, are considered.

The review gives data on the etiology, pathogenesis, and clinical manifestations of sarcoidosis, which are associated particularly with damage to the central and peripheral nervous system. Sarcoidosis is currently regarded as a genetically determined, polyetiologic, and multisystem, disease of mainly autoimmune origin, which is accompanied by a productive inflammatory response with the formation of space-occupying noncaseous granulomas. The detection rates for the classical forms of sarcoidosis of the lungs, lymph nodes, and eyes are increasing, while the intravital diagnosis of neurosarcoidosis is still difficult. The latter mimics many other neurological diseases, frequently in persistent disabling disorders and death. Studies focus on searching for imaging, biological and/or immune markers that can reliably diagnose this disease. The problem of small fiber neuropathy that is considered to be the most common and early manifestation of neurosarcoidosis is being actively studied. In 2018, Neurosarcoidosis Consortium Consensus Group (NCCG), USA, proposed the diagnostic criteria for neurosarcoidosis, which are presented in this article.

Cognitive impairment (CI) associated with brain aging is a consequence of disorders varying in etiology and pathogenesis, which often coexist in elderly patients and can have a mutual impact on the clinical manifestation, severity, and rate of progression of CI. Alzheimer's disease (AD) and vascular CI are the most common forms of dementia in the elderly. In recent decades, there has been increasing evidence that there is a close relationship between these forms due to a substantial overlap of their risk factors, clinical manifestations, neuromorphological changes, as well as genetic and neuroimaging biomarkers. The complex multicomponent relationship of these disorders also makes it difficult to elaborate effective preventive and therapeutic approaches in these patients.

Mild to moderate cognitive impairment (CI) in elderly and senile age may be caused by various neuropsychiatric diseases, including Alzheimer's disease (AD) and depression. The literature review presents the mechanisms of CI development in AD and depressive disorders, as well as their course, prognosis, and differential diagnosis. Mild and moderate depressions in AD, their clinical variants, course and treatment approaches are described. Treatment for CI is shown to focus on therapy of the underlying disease, in which the former occurs. Antidepressants are used to treat depression and depressive disorders in AD, by taking into account the efficacy and tolerability of the drugs at old age.

The problem of alcohol abuse and its social and medical consequences has remained relevant for many years. Damage to the nervous system is one of the most common manifestations of alcoholic disease. The effect of ethanol and its metabolites results in damage to all parts of the nervous system and skeletal muscles. The paper provides a brief overview of Russian and foreign literature on the neurological manifestations of chronic alcohol intoxication. It considers modern ideas about the pathogenesis of alcoholic neuropathy (APN). It also discusses differences in the clinical presentation, course, and developmental mechanisms of the main (chronic toxic and acute/subacute) forms of APN associated with thiamine deficiency. The paper notes difficulties in diagnosing peripheral nerve damage, especially in the early stages of the disease and describes modern methods for objectifying damage to thin nerve fibers in chronic APN. It presents approaches to treating alcohol-induced damage to the peripheral nervous system, by taking into account the leading mechanisms of pathogenesis. Special attention is paid to B-complex vitamins and alpha-lipoic acid preparations frequently used in this disease, to the mechanisms of their therapeutic action, and to the evaluation of their efficacy in APN.

Actovegin is a calf blood extract that contains more than 200 biologically active compounds. Experiments have shown that Actovegin reduces the neurotoxic effect of amyloid, neutralizes reactive oxygen species, and normalizes the endothelial function of small vessels. The drug has not been shown to stimulate tumor growth in the neuroblastoma model. Clinical experience with Actovegin suggests that the drug has an undoubted efficacy in treating moderate vascular cognitive impairment and chronic distal symmetric diabetic polyneuropathy and that it is used as additional therapy for primary degenerative and vascular dementia. The clinical efficacy of Actovegin in chronic obliterating diseases of the lowerlimb arteries is being actively studied now.

Chondroitin sulfate (CS) and glucosamine sulfate (GS) are widely used as chondroprotectors. Data mining of 42,051 publications on the effects of CS/GS showed that impairments in the their metabolism were characteristic of ischemic, neurodegenerative diseases, convulsive disorders or conditions, and neuropsychological diseases (schizophrenia, affective disorders). The results of experimental studies indicate that it is expedient to use CS and GS in the therapy of ischemic and neurodegenerative diseases.