One of the key conditions for achieving the desirable result during botulinum toxin therapy for muscular dystonia, spasticity, and other diseases accompanied by spasm, pain, and autonomic dysfunction (dystonias, spasticity, etc.) is the proper administration of the agent into the muscles directly involved in the pathological process. The exact entry of botulinum toxin into the target muscles is essential for successful and safe treatment because its injection into a normal muscle may cause side effects. The most common errors are the incorrect depth and incorrect direction of a needle on insertion. Therefore, the exact injection of the agent particularly into the shallow and deep muscles is a difficult task even for an experienced specialist and requires the use of controlling methods.

The European Consensus on Botulinum Toxin Therapy points out that various injection techniques are needed for the better identification of necessary muscles. However, there are currently no reports on the clear advantage of any technique. In our country, injections using palpation and anatomical landmarks have been widely used in routine practice so far; electromyographic monitoring and electrostimulation have been less frequently applied. In recent years, the new method ultrasound-guided injection has continued to grow more popular. This effective, accessible, and easy-to-use method makes it possible to manage a real-time injection process and to ensure the exact entry of the agent into the muscle. This paper is dedicated to a comparative analysis of different injection methods and to a description of the ultrasound-guided technique and its advantages over others. 

Chronic pain syndromes as a cause of suffering, short-term or persistent disability, and social losses greatly worsen quality of life. The mechanisms leading to the occurrence and maintenance of chronic pain are traditionally of interest for in-depth study since each of them is potentially a target for pharmacotherapy. Peripheral and central sensitizations, as well as disinhibition make different contributions to the development of chronic pain. The fact that cyclooxygenase-2 (COX-2) inhibitors may affect at both the peripheral and central, spinal levels, by modulating such a phenomenon as central sensitization, has been recently discussed. There are theoretical prerequisites for a discussion of this action of COX-2 inhibitors; however, clinical findings supporting this hypothesis have been scarce so far. In this connection, of interest is the clinical trial published in 2016, which may suggest to a high degree of accuracy that some analgesic effect of the selective COX-2 inhibitor etoricoxib is realized through the central mechanisms of pain modulation. 

Objective: to evaluate the efficacy of Tanakan® (EGB761®) used in young and middle-aged patients with mixed cognitive impairments (CI) and emotional diseases.

Patients and methods. An open-label observational study of the efficacy of Tanakan® was conducted in 54 patients aged 18–4 years with CI and psychoemotional disorders. Tanakan® was administered at a daily dose of 120 mg (40 mg t.i.d) for 3 months.

Results. Tanakan® therapy resulted in health improvement, as shown by the HAM (Health, Activity, Mood) questionnaire; the mean score of the latter increased from 3.86 at baseline to 4.84 after 3 months of treatment. There were improvements in three HAM questionnaire items: the mean score of the item «Health» increased from 3.69 to 4.79; that of the item «Activity» from 3.65 to 4.58, and that the item «Mood» from 4.25 to 5.14 after the completion of the investigation.

Tanakan® therapy also demonstrated improvements in memory (the mean number of correctly repeated words increased from 5.7 to 6.7 at the beginning of a visit and from 4.2 to 5.8 at its end) and in attention (the mean symbol-digit coding test score increased from 48.1 to 55.7%. There were no clinically relevant differences between patients with higher and secondary education in the efficacy of Tanakan®.

Conclusion. Tanakan® had a very good safety profile; no adverse drug events were recorded during the investigation. Almost all the 53 (98.1%) of the 54 patients were satisfied with Tanakan® therapy results after 3 months of treatment. 

Objective: to evaluate the efficacy of prolonged-release melatonin used in routine practice to improve sleep quality in Russian patients over 55 years of age.

Patients and methods. The results of the multicenter open-label observational study of Circadin (prolonged-release melatonin) efficiency for treatment of insomnia in 36 patients older than 55 yeare presented. The drug was administered at a dose of 2 mg one-two hours before bedtime for 3 weeks.

Results. Treatment with Circadin resulted in statistically significant (p<0.0001) according to pared t-test (95% CI: 4.8; 7.3) improvement of the sleep quality: the mean value of the modified subjective sleep characteristics scale increased from 11.8±2.6 points at baseline to 17.8±2.3 points after 3 weeks of treatment. The modified Questionnaire Scoring Subjective Characteristics of Sleep was grade from 0 (very bad) to 20 (very good) taking into account: the amount of time required to fall asleep, the sleep duration, the number of night awakenings and the general well-being in the morning. An increase of 6 points on a scale from 0 to 20 was considered as clinically relevant. A greater effect was observed in patients with severely impaired sleep quality as well as with low level of depression and anxiety and absence of cognitive impairment. Upon completion of Circadin treatment there were statistically significant improvement (p<0.0001) of attention (the mean value of the symbol-digit coding test increased from 34.2±9.7 to 37.3±10.6 points) and memory (the median value of the short-term verbal memory test increased from 4 points at baseline to 5 points at the study end, p=0.0069).

The drug had a good safety profile; only one adverse event related to study medication (allergic rush) was registered in the study. The absolute majority (91.7%) of the study patients considered Circadin treatment as either effective or very effective.

Conclusion. Taking into consideration the good safety profile of this drug, confirmed in the present study, as well as the ability of the drug to improve cognitive functions, Circadin may be beneficial in patients from 55 years with insomnia complaint.

Objective: to investigate the frequency of anosognosia (a deficit of self-awareness), its anatomic correlates associated with other neuropsychological and neurological disorders in acute hemispheric ischemic stroke (IS).

Patients and methods 150 patients (83 men and 67 women; mean age, 63.0±9.3 years) with acute hemispheric IS were examined. All the patients underwent neurological, neuroimaging, and neuropsychological (by the procedure described by A.R. Luria) examinations. neuropsychological investigations. Anosognosia was diagnosed using the Dysexecutive Questionnaire (DEX) and the authors' procedure involving a scale to measure impaired self-rating of motor abilities and a scale to measure impaired self-rating of cognitive abilities in everyday life.

Results and discussion. In the acute period of hemispheric IS, reduced self-awareness of motor and cognitive abilities was noted in 14% of the patients and unawareness of only cognitive abilities was recorded in 15%. Patients with anosognosia and cognitive dysfunction (ACD) and those with anosognosia and motor dysfunction (AMD) had right-sided hemispheric IS more frequently (76%) while this was not found in patients with isolated ACD. The development of anosognosia for paralysis and paresis was favored by the large sizes of an ischemic focus that involved a few lobes in the posterior regions of the brain although no lesions were found in the anosognosia-specific anatomical regions. ACD and AMD proved to be associated with unilateral spatial and tactile neglect and obvious regulatory dysfunction. 

Objective: to evaluate the efficiency and safety of different therapy regimens for depression in relation to the clinical type of bipolar affective disorders (BAD) and to choose optimal treatment regimens for depression in BAD type I (BADI) and BAD type II (BADII).

Patients and methods. A total of 65 depressive patients, including 25 with BADI and 37 with BADII, were examined. 212 depressive episodes were analyzed in BAD patients, of them there were 74 with BADI and 138 with BADII. The patients with BADI took a combination of an antidepressant (AD) and a normothymic (NT), NT and a neuroleptic (NL), AD, NT and NL. Those with BADII received monotherapy with AD or NL, a combination of AD + NT, AD + NL. The patients' status was clinically evaluated using a specially designed questionnaire and the MADRS and CGI psychometric scales at baseline and then at the end of 1, 2, 4, and 8 weeks of therapy.

Results. The AD-containing regimens used to treat patients with BADI proved to be more effective; this therapy led to a more marked reduction in depressive symptoms (55.73% in the AD + NT-treated patients; 54.07% in the AD + NT + NL group versus 33.64% in the NT + NL-treated patients), a higher response to therapy, and a larger number of remissions by the end of the investigation (80.0, 72.7, and 33.3%, respectively). Moreover, the incidence of transient hypomanic symptoms did not significantly differ in these groups (20.0, 27.3, and 8.3%, respectively). The depressive patients with BADII generally responded better to different therapy regimens (the reduction in depressive symptoms was 52.08, 58.82, 58.40, and 53.98% in the AD, NL, AD + NT, and AD + NL groups; the remission index by the end of the investigation was 60.6, 92.9, 77.8, and 69.2%, respectively); these patients were seen to have less frequently symptoms of an antipole during their treatment (18.2, 7.1, 0.0, and 15.4%, respectively).

Conclusion. The incorporation of AD into a therapy regimen in BAD patients accelerates emergence from any depression severity and considerably enhances the efficiency of treatment. According to the clinical picture of depression, both AD monotherapy (BADII) and a combination of AD + NT and/or NL (BADI, BADII) may be used. The incorporation of AD into a therapy regimen does not significantly increase a risk for developing an inverse phase. 

Etifoxine modulates GABAergic transmission and is used as an anxiolytic (anti-anxiety) medication. The indications for etifoxine use are anxiety, fear and inner tension.

Objective: to simulate the biological properties of etifoxine. This simulation has been carried out for the first time.

Material and methods. Reliable estimates of more than 2,500 biological activities were obtained for this molecule, which were compared with the reference drug lorazepam (benzodiazepine).

Results and discussion. The data obtained from chemoreactome simulation may suggest that there are significant differences between the pharmacological effects of etifoxine and benzodiazepine in: 1) the selectivity of binding to various neurotransmitter receptors; 2) anti-inflammatory activity; 3) the effect on hemodynamics and vascular walls; 4) negative side effects and 5) pharmacokinetic parameters.

Conclusion. The findings are consistent with the available experimental and clinical data and are indicative of promising clinical applications of etifoxine. 

Psychogenic dizziness is one of the most common types of vertigo. To diagnose psychogenic dizziness is a complex task since it requires a thorough patient examination and exclusion of possible organic causes of dizziness. The paper describes the clinical case of a female patient with phobic postural vertigo, which demonstrates the efficiency of the early diagnosis and adequate therapy of this disease. Combination therapy for psychogenic dizziness, which encompasses different psychotherapeutic procedures, vestibular rehabilitation, and drug therapy, is most effective. Among the medications, vinpocetine is effective in treating patients with cerebrovascular disease. Inappropriate treatment may lead to the progression of psychogenic dizziness, to a considerable deterioration in quality of life, and to obvious social disadaptation. There is a worse treatment prognosis with a longer interval between of disease onset and diagnosis. 

To establish the exact cause of cognitive impairment (CI) is of great importance for appropriate patient management and disease prognosis. The paper describes a patient with moderate CI, with respect of whom both vascular and neurodegenerative pathology may be discussed. A specific example is used to consider the currently accepted approaches to the differential diagnosis of the most common nosological entities of cognitive impairment, including an analysis of its clinical neurological and neuropsychological symptoms and the results of instrumental and neuroradiological examinations. The present-day ideas on mixed (vascular and degenerative) CIs are set forth. The specific features of patient management in relation to the etiology of CI, as well as the place of neurometabolic therapy in the treatment of these impairments are discussed. 

The article describes a clinical case of psychogenic movement disorder appearing as fixed dystonia without pain. Over 5 years, a patient has had the right fingers being permanently clenched into a fist position at rest, which increased when fulfilling any motor task; carpal pain was absent. When he was 18 years old, the patient sustained a blast injury with concussion. A leather glove was used to reduce clenching and a makeshift device was applied to move the fingers apart. Motor function of the hand persisted; its atrophy was absent; muscle tone in the hand was sufficient; reflexes were symmetrical; sensitivity was not impaired. His gait, voice, speech were not changed. When writing, there was increased pencil grasp (not writer's cramp); his handwriting was smooth and legible. The patient uses the voluntary compensatory movements of the right hand (holding a thing with one hand in a supine position) and fingers (crossing the third finger over the fourth and conversely), which reduce the manifestations of movement disorder. He refused psychiatric examination and to take any medications. 

The paper describes a clinical case demonstrating the possibilities of using computed tomography (CT) in the diagnosis and treatment of botulinum toxin type A (BTA) treatment of mixed cervical dystonia (CD). The poor result of initial treatment is due to the fact that the abnormally active deep muscles of the neck were beyond the reach of injection. Routine clinical examination cannot identify a concurrence of the caput and collis types of CD in most cases, which occurred in our patient. Objective examination revealed displacement of the larynx to the left from the incisura thyroidea superior, which was characteristic of the left-sided rotational caput type of CD; however, CT detected mixed CD (a concurrence of torticollis and torticaput in the left). Cervical spine CT could visualize not only the superficial, but also deep dystonic muscles of the neck, specify a botulinum toxin therapy regimen, and estimate a difference in the volumes of the normal or dystonic inferior oblique muscle of the head with further intramuscular administration of botulinum toxin. The evaluation of the efficiency and safety of BTA therapy for this disease, as well as practical guidelines for the use of CT in the diagnosis and treatment of mixed CD are given.

Mesial temporal sclerosis (MTS) is the most common histopathology occurring in patients with drug-resistant temporal lobe epilepsy. Over the past decades, there have been various attempts to classify the variants of hippocampal neuronal cell loss in relation to postoperative outcome. However, no consensus on the common international definition and classification of MTS has been reached. The article describes the modern histological classification based on a semiquantitative hippocampal cell loss model. The publications dealing with the histological classification of mesial temporal sclerosis are reviewed. 

Ischemic stroke (IS) is characterized by high prevalence, mortality, and disability rates. Therapy aimed to correct one biochemical or molecular stage of ischemic cell injury fails to treat stroke, suggesting that it is necessary to study multimodality therapy affecting several related pathophysiological components.

The paper gives the January 2016 results of the randomized placebo-controlled multicenter study CARS that demonstrates the positive effect of cerebrolysin versus placebo according to the primary efficiency criterion, the Action Research Arm Test (ARAT) scale, and total outcome 90 days after disease onset. The investigation enrolled mainly patients with moderate or severe IS (the mean National Institutes of Health Stroke Scale score was 9 at baseline).

The specific features of the CARS study versus those of other clinical trials of neuroprotectors were the initial planning of narrower end criteria of efficiency (arm motor function recovery whereas the major goal of many investigations was to reduce mortality rates), as well as a standardized rehabilitation program in both treatment groups. Such investigations did not previously take into account the nature and volume of rehabilitation measures although the latter may have a substantial impact on the outcome of stroke.

The CARS study is the first among the previously conducted clinical trials of neuroprotectors, which has attained the primary objective (to restore motor function), which opens up fresh opportunities for the medical support of rehabilitation measures in patients with IS.

Some recovery of impaired neurological functions (a stroke recovery period) is almost always observed within the first 6–24 months after ischemic stroke (IS). The paper discusses the mechanisms responsible for this process (neurogenesis, neuroplasticity, and readaptation) and possible approaches to the drug support of cerebral reparative processes. It presents data on the rate and etiology of poststroke cognitive impairments (CI) that are one of the important factors that negatively influence the outcome of rehabilitation measures. The results obtained from a recent study of the efficacy of the neurometabolic agent citicoline in the recovery period of IS are given. The use of citicoline is shown to cause a significant regression of CI and to improve quality of life in patients who have sustained IS for the first time. 

Valproic acid (VA) is used in epileptology for the basic and additional control of simple and complex focal seizures, absences, generalized tonicclonic seizures, and myoclonus. Information has been recently stored on cases of chronic overdosage of VA due to its blood accumulation. These conditions are described in the use of both high and average therapeutic doses of VA preparations in patients with a genetically determined delay in metabolism. The paper presents current methods for clinical and laboratory diagnosis and correction of chronic intoxication when valproic acid preparations are administered during the prehospital, hospital and rehabilitation phases of treatment. The authors note that a personalized approach is of importance for dose adjustment and prediction of unwanted adverse drug reactions associated with the use of VA preparations. 

Cognitive impairments (CIs) are common in poststroke patients. The basis for this condition is frequently a neurodegenerative process and most often Alzheimer's disease (AD). Stroke may promote the manifestation of clinically asymptomatic AD, worsen prestroke cognitive deficit or merely manifest prestroke CIs.

The paper discusses the epidemiology, risk factors, and pathogenesis of poststroke CIs, current methods for its diagnosis, as well as symptomatic and pathogenetic treatment. The most informative method for the diagnosis of poststroke CIs is neuropsychological examination that should be made in the early poststroke period (if the patient's consciousness is clear). The most common screening tests include mini-mental state examination (the most sensitive to evaluate cognitive dysfunction in Alzheimer type dementias) and the Montreal cognitive assessment. Magnetic resonance imaging of the brain, positron emission tomography, cerebrospinal fluid examination, and genetic testing are used to reveal AD at its preclinical stages. Preventive measures include regular physical activity, a balanced diet, and sufficient mental workload. The prevention of stroke and other cardiovascular diseases are also important.

The major groups of drugs used to treat AD and vascular CIs are acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. It is expedient to use glutamatergic and acetylcholinergic therapy earlier in patients with obvious CIs that are unassociated with emotional problems and disturbance of consciousness. Akatinol memantine is a drug that can be regarded not only as a symptomatic but also pathogenetic agent. 

The paper presents a concise review of investigations into the role of impaired frontal-subcortical circuits in the development of obsessive-compulsive disorder (OCD). It gives data on the frequency of neurosis-like symptoms of the OCD spectrum in neurological diseases.

The development of OCD is associated with an imbalance between the activity of the direct (activating) and indirect (inhibitory) pathways of the cortico-striatal-thalamo-cortical feedback loop. These data are confirmed by the results of neuroimaging and neuropsychological studies in patients with OCD. The frequency of OCD symptoms is high in organic brain lesions. OCP may be a manifestation of neurological diseases so their timely detection is an important aspect of a neurologist's work. The treatment of patients with neurosis-like disorders of the OCD spectrum within neurological diseases requires a multidisciplinary approach with the participation of a neurologist, a psychiatrist/psychotherapist, and a psychologist. It is necessary to combine pathogenetic treatment of the underlying disease and its neurosis-like manifestations. 

The article considers the mechanisms of chronic low back pain. Three pathophysiological mechanisms: nociceptive, neurogenic (neuropathic), and psychogenic are noted to be involved in the development of pain syndrome. The role of cellular and molecular changes in the posterior horn and in the somatosensory dysregulated mechanism of neuropathic pain is shown. Immunological processes, including neurohumoral (serotoninergic) and hormonal (sex hormones and specific proteins) ones, play an important role in the development of pain. The generalization and further study of these mechanisms are embodied in approaches to therapy for pain syndromes and hence these require analysis and further investigation. 

Multiple sclerosis (MS) is a demyelinating disease of the CNS, which affects mainly young able-bodied people; in this connection the problem of MS treatment assumes particular relevance. The paper reviews the main GALA (Glatiramer Acetate Low-frequency Administration) and GLACIER (Glatiramer Acetate low frequenCy safety and patient ExpeRience) clinical studies of subcutaneous glatiramer acetate (GA) 40 mg/ml three times per week (TIW).

The results of the Phase III GALA multicenter randomized placebo-controlled parallel-group study of GA 40 mg injections administered less frequently (TIW) were published in 2013. The study involved 142 centers from 17 countries, including 17 Russian centers. The GALA study proved the efficacy, safety, and good tolerability of GA 40 mg TIW in patients with relapsing-remitting MS (RRMS). The safety profile of GA 40 mg was completely consistent with the well-known profile of GA 20 mg.

The new GLACIER study was initiated to evaluate the efficiency and tolerability of treatment with GA 40 mg TIW versus GA 20 mg every day. This study confirmed that the tolerability profile of therapy with GA 40 mg TIW was better than that of GA 20 mg every day in patients with RRMS. GA 40 mg/ml TIW was approved for use in the USA, the United Kingdom, and a number of European countries for the treatment of patients with RRMS. In the Russian Federation, GA 40 mg was approved for use in September 2015.