The Russian experts’ guidelines on evaluation and treatment of medication-overuse headache are based on evidence-based medicine, the latest revision of the International Classification of Headache Disorders. Basic information about epidemiology, risk factors, pathophysiological mechanisms, evaluation, and the most effective pharmacological drug and non-pharmacological approaches to managing patients with medication-overuse headache are presented. 

Among drug-induced liver injuries (DILI), the cholestatic type is second in frequency (from 20 to 40%), the most common is the hepatocellular variant (up to 78%). For this reason, practitioners of various specialties, including neurologists and psychiatrists, do not monitor cholestasis parameters, and drug-induced liver injury with cholestasis (DILIС) remains unrecognized. The urgency of this problem is great, because the frequency of deaths in DILIС is only slightly lower than t in the hepatocellular type; in addition, it DILIС is much more likely to become persistent increasing the risk of chronic liver injury.

Among the drugs used in neurology and psychiatry, the “leaders” in terms of the number of DILIС are antidepressants, both tricyclic (amitriptyline, imipramine) and selective serotonin reuptake inhibitors (SSRIs: paroxetine, sertraline, fluoxetine, citalopram, escitalopram), antidepressants), antipsychotics (chlorpromazine, fluphenazine), anticonvulsants (mainly carbamazepine).

If the patient has a history of DILI caused by any of the forementioned medications, the agent should be switched to another drug from the same group with a minimal risk of DILI. If there is a history of DILI associated with antidepressants, it is recommended to choose SSRIs. It is necessary to monitor not only the activity of transaminases and bilirubin, but also the cholestasis parameters (alkaline phosphatase, γ-glutamyl transpeptidase) during treatment. 

Objective: to evaluate the efficacy and safety of cladribine tablets as a treatment for immune reconstitution of highly active multiple sclerosis (HAMS) in general clinical practice.

Patients and methods. 34 patients with HAMS who were followed up at the Moscow Multiple Sclerosis Center in 2018–2021 received two full treatment courses. HAMS diagnosis was established in the presence of two or more exacerbations per year without treatment or one exacerbation in patients receiving pathogenetic treatment in the presence of concomitant manifestations of the activity of the pathological process on MRI. Before initiation of cladribine therapy, the median exacerbation rate was 2.3 per year, i.e., 34 patients per year had a total of 78 exacerbations.

Results and discussion. Only two clinical exacerbations were registered (one each in the first and second year) during two years of treatment among all 34 patients, the average frequency of exacerbations was 0.05 per year; in three cases, a subclinical exacerbation was noted - new Gd+ lesions on T2-weighted images on MRI, the total number of events was 0.15 per year. No significant adverse events were reported.

Conclusion. Cladribine tablets are a highly effective and safe treatment option for HAMS. 

Up to 16–20% of patients with a history of traumatic brain injury (TBI), regardless of its severity, suffer from pronounced spasticity, cognitive, vestibular and motor disorders. At the same time, data on the effectiveness of botulinum neurotoxin (BoNT) in the treatment of post-traumatic spasticity is lacking.

Objective: to assess the effectiveness of peripheral myorelaxants (botulinum neurotoxin type A) in the treatment of past-traumatic spasticity.

Patients and methods. 21 male patients aged 25 to 48 years with post-traumatic spastic hemiparesis (at least 6 months after the injury) were examined. 450 to 850 U (mean – 650 U) of BoNT (incobotulinumtoxin) was injected into the spastic muscles of the upper and lower extremities. The follow-up assessment of spasticity and paresis was performed 24±3 days after BoNT injection. Patterns of spasticity were studied: shoulder adduction, elbow joint flexion, forearm pronation, hand and finger flexion, hip adduction, shin flexion, foot flexion, toe flexion. The following methods were used: original methods of manual testing (MMT) of spasticity, Tardieu scale (TS), modified Ashworth scale (MAS), Medical Research Council Scale (MRCS) to assess paresis.

Results and discussion. 24±3 days after incobotulotoxin administration, we observed a significant 1.5–2-fold decrease in spasticity angle (xS) and a reduction in the angle of neuromuscular reactivity (xV3) by 15–30° in all the studied patterns. Changes of xV1 (muscle extensibility) and xA (muscle strength) were not significant. No adverse reactions were observed. The use of MMT and TS has shown its effectiveness and specificity in the evaluation of spasticity and effectiveness of BoNT, and in the dynamics of muscle condition.

Conclusion. The study showed the feasibility of using MMT and TS in the evaluation and assessment of spasticity, as well as the effectiveness and safety of incobotulinumtoxin (Xeomin) in dosages from 450 to 850 U in the treatment of spasticity of the upper and lower extremities in patients with the consequences of TBI. 

Epidemiological studies demonstrate a strong relationship between depression and cerebral microangiopathy (CM) associated with arterial hypertension (AH) and cerebral atherosclerosis, but the pathogenetic mechanisms underlying this relationship are not fully understood.

Objective: to evaluate the relationship between the level of peripheral markers of endothelial inflammation and depression severity in patients with CM.

Patients and methods. The level of peripheral markers of endothelial inflammation was assessed by enzyme immunoassay, and the severity of depression was assessed using the HADS scale in 262 patients with CM. All patients had correction of hypotensive, antiplatelet, anticoagulant, lipid-lowering, hypoglycemic therapy. Observation of the patients lasted 3 months with an assessment of the follow-up clinical and laboratory parameters. Results and discussion. Comparative analysis shown that in the group of patients with clinically significant depression (n=146) C-reactive protein (CRP) level was составил 6.11 mg/l, monocytic chemoatactic factor-1 (МСР-1) – 2.02 ng/ml, which differed significantly from the group f patients with subclinical depression (n=116): CRP – 2.03 mg/l, МСР-1 – 0.66 ng/ml (р<0.05). Correlation analysis showed a direct strong significant linear relationship between the depression severity and the level of CRP (correlation coefficient r=0.85, p><0.05). A similar significant correlation was found between the depression severity and the MCP-1 level – a direct strong linear relationship (r=0.8, p><0.05). The odds ratio assessment revealed that increased peripheral markers of endothelial inflammation are associated with clinically significant depression. The use of drugs aimed at correcting the main cardiovascular risk factors contributed to a significant normalization of the levels of peripheral markers of inflammation (p><0.05), accompanied by a reduction in depressive symptoms in patients with CM without the use of specific antidepressant therapy. Conclusion. The study revealed a relationship between altered levels of peripheral markers of inflammation and the severity of depression in patients with CM associated with hypertension and cerebral atherosclerosis. The normalization of the peripheral markers of endothelial inflammation contributed to the restoration of the emotional background. Keywords: endothelial inflammation; inflammatory markers; depression; cerebral microangiopathy>˂0.05). Correlation analysis showed a direct strong significant linear relationship between the depression severity and the level of CRP (correlation coefficient r=0.85, p˂0.05). A similar significant correlation was found between the depression severity and the MCP-1 level – a direct strong linear relationship (r=0.8, p˂0.05). The odds ratio assessment revealed that increased peripheral markers of endothelial inflammation are associated with clinically significant depression. The use of drugs aimed at correcting the main cardiovascular risk factors contributed to a significant normalization of the levels of peripheral markers of inflammation (p˂0.05), accompanied by a reduction in depressive symptoms in patients with CM without the use of specific antidepressant therapy.

Conclusion. The study revealed a relationship between altered levels of peripheral markers of inflammation and the severity of depression in patients with CM associated with hypertension and cerebral atherosclerosis. The normalization of the peripheral markers of endothelial inflammation contributed to the restoration of the emotional background. 

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease. Consequently, there has been growing interest in identifying early preclinical disease symptoms and searching for their laboratory markers in recent decades.

Objective: to studythe relationship between vitamin D levels, phosphorus-calcium metabolism and clinical manifestations of PD.

Patients and methods. Serum levels of total vitamin D (VD), as well as total calcium, ionized calcium, alkaline phosphatase (AP), inorganic phosphorus, and parathyroid hormone (PTH) were assessed in 138 patients with PD. The severity of the disease was verified according to the Hoehn-Yar criteria, the clinical symptoms of the disease were verified using the Unified PD Rating Scale (UPDRS), the evaluation also included the quality of life (QoL) scales for patients with PD (PDQ-39), anxiety and depression (HADS), and Beck depression inventory, assessment of cognitive functions (CF) according to MoCA. Then, we analyzed the effect of vitamin D levels and other indicators of phosphorus-calcium metabolism on the severity of PD clinical symptoms.

Results and discussion. Patients with PD had a significant impact of phosphorus-calcium metabolism on CF, assessed by MoCA scale and the PDQ-39 subscale “Cognitive functions”. A joint direct impact of vitamin D levels (β=0.111; p=0.002), PTH (β=0.02; p=0.037) and the indirect effect of AP (β=-0.028; p=0.027) on CF was revealed. A direct effect of the level of inorganic phosphorus (β=5.932; p=0.001) and AP (β=0.055; p=0.025) on the QoL of patients with PD was observed.

Conclusion. Cognitive decline in PD patients is directly related to vitamin D and PTH levels. At the same time, the lower the QoL of patients with PD, the lower the serum vitamin D level was, serving as an early predictor of cognitive decline in patients with PD. 

Over the past two years, healthcare workers have been daily saving patients diagnosed with COVID-19 in life-threatening conditions. These circumstances contribute to an increase in the psychopathological disorders in this social group. However, today there is no validated questionnaire that allows to quickly and effectively identify the group of healthcare workers with high levels of stress and anxiety during the pandemic in Russia.

Objective: to validate the Russian version of Stress and Anxiety to Viral Epidemic scale (SAVE-9).

Patients and methods. The study was a cross-sectional online survey of 1090 frontline healthcare workers. Stress and anxiety symptoms were assessed using SAVE-9 and General Anxiety Disorder-7 (GAD-7) scales, respectively. Factor analysis with varimax rotation was performed to determine the internal structure of SAVE-9 scale. ROC-analysis was used to identify the validity of the SAVE-9 compared with GAD-7 and its cut-off score.

Results and discussion. The principal component analysis showed a two-factor structure of SAVE-9. Factor 1 was associated with anxiety and somatic symptoms, factor 2 – with social stress. Cronbach's alpha=0,787. The total score of SAVE-9 with a high degree of confidence predicted the GAD-7 value in ROC-analysis. The area under the curve (AUC) was 0.808; 95% confidence interval 0.768–0.847 (p=0.0001), which corresponded to the model's good quality. The appropriate cut-off score was determined as 18.

Conclusion. We demonstrated the validity of the new SAVE-9 scale, which can be used as a specific screening method to detect high levels of anxiety and stress in healthcare workers during a viral outbreak. 

Objective: to evaluate the treatment effectiveness for atypical depression (AtD) depending on its nosology: in bipolar affective disorder (BAD), recurrent depressive disorder (RDD) and psychogenic depression (PD).

Patients and methods. A total of 250 patients with depression were screened, of which 77 patients with symptoms of AtD were enrolled in the study, 35 of them with BAD, 18 with RDD, and 24 with PD. Patients in all three groups received an antidepressant (AD) or a mood stabilizer (MS) monotherapy, or a combination of AD and antipsychotic (A), AD and A, MS and A, as well as a combination of AD, A and MS. The patients' condition was assessed clinically using a specially designed questionnaire and MADRS and CGI scales at the baseline and the 2nd, 3rd, 4th, 6th, 12th weeks of treatment. Quality of life satisfaction was assessed with the Q-LES-Q-SF (Scoring the Quality-of-Life Enjoyment and Satisfaction Questionnaire) scale at the treatment onset and after the 12th week of treatment.

Results and discussion. Treatment regimens that included AD were the most eff in all groups of patients with AtD. The proportion of responders among those who received AD for bipolar disorder (75% or more) was significantly higher than among those who did not receive it (˂50%). In the RDD and PD groups, patients responded significantly better to AD monotherapy (RDD – 93.2%; PD – 91.5%) compared to other regimens. Agomelatine was the most frequently used (31.8%) and effective AD in all groups. Also, escitalopram, vortioxetine, and venlafaxine (p˂0.05) showed high efficacy, good tolerance, and absence of side effects that aggravate the main symptoms that characterize AtD. Among the antipsychotics in combination with AD, sulpiride was significantly more effective in patients with PD (p˂0.05). The highest rates of quality of life satisfaction were achieved in the BAD group, the lowest – in patients with PD (p˂0.05), which indirectly indicates the quality of remission, which is determined not only by the degree of reduction of depressive symptoms but also by the patients' subjective perception of their mental state.

Conclusion. The inclusion of AD in the AtD treatment regimen significantly increases its effectiveness in patients of all groups, including BAD. AtD treatment should be administered not only taking into account its clinical signs and severity, but also depending on the nosology of the disease, the characteristics of its course. During drug administration, it is necessary to consider the spectrum of side effects, especially those that increase the symptoms of AtD itself. 

Idiopathic facial nerve neuropathy (FNN), or Bell's palsy, is characterized by a manifest neurological defect and a pronounced decrease in the quality of life of patients.

Objective: to evaluate the efficacy and safety of ipidacrine in patients with FNN in an open-label observational study.

Patients and methods. The study included 35 patients with FNN, who were divided into two groups. Treatment in the main group (n=20) included the basic regimen (glucocorticoids, B vitamins, pentoxifylline, glycine, a complex of non-pharmacological therapies), as well as the anticholinesterase drug ipidacrine (Ipigrix). Treatment of patients in the control group (n=15) was limited to the basic regimen. The followup was six months. The treatment effectiveness was assessed with the House-Brackmann scale, FaCE (Facial Clinimetric Evaluation), SAQ (The Synkinesis Assessment Questionnaire), electroneuromyography (ENMG), and determining the number of patients with indications for botulinum therapy.

Results and discussion. After six months of treatment, more significant restoration of facial nerve function was observed in the main group, according to the House-Brackmann scale (1.4±0.5), FaCE (90±9.8), and ENMG results, compared to the control group (HouseBrackmann – 1.9±0.7 points, FaCE – 78±11.8 points; p<0.05). There were no intergroup differences in the SAQ scores (main group – 42.1±16.1 points, control group – 48.6±12.9 points; p=0.203) and the number of patients with indications for botulinum therapy. Predictors of the synkinesis were pronounced damage to the branches of n. facialis at the disease onset according to the clinical examination (4 and 5 points on the House-Brackmann scale), I degree of severity according to ENMG, pain >75 mm on the visual analog scale, poor recovery of facial nerve function in the first month of treatment (3 and 4 points on the House–Brackmann scale).

Conclusion. The use of ipidacrine in the complex treatment of patients with FNN improves the efficiency of restoration of the function of the facial nerve after 6 months without increasing the risk of pathological synkinesis. 

About 60% of women report menstrual-associated migraine attacks, characterized by a higher intensity and duration and more pronounced treatment resistance. Often, preventive treatment with drugs aimed to relieve menstrual attacks – non-steroidal anti-inflammatory drugs and triptans – is difficult in these patients due to a high risk of medication-overuse headache. In addition, due to a hormonal trigger – a perimenstrual decrease in estrogen – the effect of hormonal contraceptives on migraine attacks has been studied for a long time. This article discusses the results of studies indicating the successful administration of specific hormone therapy regimens, especially in patients with concomitant gynecological pathology or in patients using these drugs for contraception. 

This scientific review highlights the results of domestic and foreign studies aimed at researching the biological aspects of failure to control aggressive impulses. We analyze the role of serotonergic, dopaminergic, noradrenergic, glutamatergic systems, and neuroendocrine mechanisms in aggression manifestation. We discuss the inconsistency of modern concepts about the neurochemical nature of aggressive behavior. The relevance of evaluating the biomarkers of public danger is substantiated. Finally, questions of psychopharmacotherapy of aggressive behavior are reviewed. 

Sleep disturbances are common in patients with mental disorders. Sleep disturbances, in particular insomnia, are widespread in depression. Depressed patients have a lot of sleep complaints that are often confirmed by polysomnography. Most antidepressants impair sleep, so drugs that help to restore sleep are of particular value in clinical practice. Agomelatine (valdoxan) rapidly improves sleep in depressed patients by making it easier to fall asleep, increasing total sleep time, duration of rapid eye movement (REM), and slow-wave sleep (SWS), and improving functioning during the day. 

A combined approach is recommended to treat chronic non-specific low back pain (lumbago), including pharmacological and non-pharmacological methods. Kinesiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs) have a high level of evidence in chronic lumbago. Kinesiotherapy includes posture and daily motor activity regimen training, a complex of therapeutic and breathing exercises, post-isometric relaxation, and other physical exercises. NSAIDs reduce pain, improve functional status, and increase patients' adherence to kinesiotherapy, relieving pain in the first days of treatment. A specific NSAID administration is usually individualized, considering the comorbidities and the risk of possible side effects. The use of meloxicam (Movalis) for back pain is discussed. 

Guillain-Barre’ syndrome (GBS) is an acute autoimmune, inflammatory, demyelinating disease affecting the peripheral nervous system, responsible for a typical ascending flaccid paralysis with the classic albuminocytological dissociation in the cerebrospinal fluid. Its occurrence during pregnancy is a rare eventuality. Through the clinical observation of a 33-year-old pregnant woman who had GBS during third trimester and a literature review, we will study the clinical, diagnostic, therapeutic and maternal-fetal prognostic aspects of this pathology during pregnancy. 

The polymorphism of the clinical manifestations of coronavirus infection often creates great diagnostic difficulties for the practitioners, especially in patients with a predominance of neurological symptoms. Of the latter, cranial neuropathies take a particular place, as they may be either one of the first symptoms or appear during the disease progression. Impairment of smell and taste is considered an early manifestation of SARS-CoV2 infection. Similar to the involvement of the olfactory bulb, multiple cranial nerves involvement (for example, VII, VI, and III) has been described. Patients with COVID-19 associated multiple cranial neuropathies are more likely to experience partial recovery of impaired function. We present and discuss a rare case of COVID-19 associated multiple cranial neuropathies with a sequential involvement of the olfactory (I), right visual (II), frontal branch of the trigeminal (V), facial (VII), and hypoglossal (XII) nerves. Data on clinical manifestations and diagnostic criteria for this form of pathology are presented. 

Neurological symptoms could be a manifestation of cancer both with direct involvement of the nervous system (tumor invasion, metastasis, compression of nerve tissue by neoplasm) and its mediated damage in patients with paraneoplastic syndromes. Neurological manifestations in this syndrome are more likely to cause neoplasms that produce neuroendocrine proteins (small-cell lung cancer, neuroblastoma) or involve immune system organs (thymomas, lymphomas, plasmacytomas). The paraneoplastic syndrome can be observed ahead of tumor detection and verification in some cases, so cancer screening can be a successful evaluation tactic in patients with neurological symptoms of undetermined etiology.

To illustrate this diagnostic approach, we present the clinical case of a patient with multiple cranial neuropathies as a malignant thymoma manifestation. Symptoms of multiple neuropathies developed in the 20-year-old woman within two months prior to hospitalization. The differential diagnosis included infectious, autoimmune, vascular diseases, diseases manifested by hyperostosis of the skull bones, and oncological diseases. Magnetic resonance imaging of the brain with contrast revealed a pathological accumulation of contrast in the oculomotor, trigeminal, vestibulocochlear, and vagus nerves. Computed tomography of the thorax and abdomen showed signs of neoplasms of the mediastinum, right lung, liver, right adrenal gland, and left kidney. Antemortem pathology study of the material obtained by Video-assisted thoracoscopic biopsy from a mediastinal neoplasm revealed a malignant thymoma.

Patients with multiple cranial neuropathies are often encountered in neurological practice. However, establishing the cause of this condition is a complex medical task due to many diseases with which it will be necessary to conduct a differential diagnosis.

We present familial tuberous sclerosis (TS) case complicated by COVID-19. COVID-19 aggravates the course of TS and may lead to a fatal outcome. We review the role of mTORC1 (mechanistic/mammalian Target of Rapamycin Complex 1) in the development and functions of the nervous system and the pathogenesis of TS and COVID-19 with emphasis on the involvement of the brain and lungs. We observed that COVID-19 worsens the course of epilepsy in patients with TS. In TS patients, lymphangioleiomyomatosis may predispose to SARS-CoV-2 invasion into the respiratory system because of the increased expression of ACE2 and TMPRSS2 in type II pneumocytes and thus may worsen the prognosis. We also review the current data on the continuation/termination of everolimus administration in patients with TS associated with COVID-19. 

We present a description of a functional writer's cramp case. The disease manifested as pain and tension in the right hand when writing; thus, we suspected kinesigenic dystonia in the form of writer's cramp. However, the motor pattern and the presence of additional manifestations made it possible to assume the neurotic nature of hyperkinesis. A psychiatrist diagnosed a combined conversion motor and undifferentiated somatoform disorder as a part of personality dynamics of the dramatic cluster at the involutionary age. Treatment included cognitive-behavioral therapy and periciazine administration with a positive effect. We discuss the aspects of hyperkinesis and mental status, which help differentiate the kinesigenic form of dystonia (writer's cramp) and functional movement disorder.