[Autoimmune encephalitis: psychiatric aspects]. / Autoimmunnye entsefality: psikhiatricheskie aspekty.

Autoimmune encephalitis is a group of diseases researched by both neurologists and psychiatrists. Despite a large number of studies and practical recommendations, the differential diagnosis and early diagnostics still remains an important issue. The most difficult to diagnose are cases that debut as mental disorders and/or occur without neurological symptoms. The literature review presents the current state of the problem with an emphasis on the practice of a psychiatrist.

[Neuropsychiatric presentations of amyotrophic lateral sclerosis]. / Neiropsikhiatricheskie proyavleniya bokovogo amiotroficheskogo skleroza.

Neuropsychiatric presentations are observed in a substantial number of patients with amyotrophic lateral sclerosis (ALS). Severe behavioral disorders develop in ALS combined with frontotemporal dementia, which are considered to be a disease continuum. Psychiatric disorders in ALS with predominantly motor symptoms are less prominent and mostly presented with apathy. Psychiatric disorders in ALS by their origin could be psychogenic, reflecting the patients' reactions on severe disease, and organic, developing as a result of degeneration of central motor neurons and disconnection between fronto-subcortical and frontotemporal loops. An important role in the development of psychiatric disorders in ALS belongs to genetic factors, in particular to hexanucleotide expansion in the C9orf72 gene. During the first months after establishing the diagnosis of ALS, there is the high risk of developing depressive disorders, which in severe cases can lead to suicide. More research is needed in this area.

[Peripheral vertigo as onset of an immune-mediated disorder]. / Sistemnoe golovokruzhenie kak debyut immuno-oposredovannogo zabolevaniya.

In this article we present a clinical case of a female patient, 45 years old, with autoimmune encephalitis with antibodies to glutamate decarboxylase (GAD) beginning clinically with vertigo. According to high frequency of vestibular symptoms at the beginning and high frequency of admission to otoneurologist GAD-associated pathology should be included in differential diagnosis in complicated clinical cases with vertigo. These patients should be sent to neurologist.

[Autoimmune encephalitis in psychiatric institution (clinical case)]. / Autoimmunnyi entsefalit v praktike psikhiatra (klinicheskii sluchai).

Currently there is a new concept of «molecular neuropsychiatry¼ which aim is identification of biomarkers and biological substrates for mental disorders. Autoimmune encephalitis can start with psychiatric symptoms in 60% of cases. In this article we described a clinical case of a patient, 31 years old, with GABAb-associated AE started with acute polymorphic psychosis. AE was diagnosed and treated in time with a good clinical effect. According to the frequency of psychiatric symptoms in AE patients it should be reasonable to include antineuronal test in CSF and serum in patients with first acute psychosis if «red flags¼ or atypical course of the disease.

[Acute disseminated encephalomyelitis]. / Ostryi rasseyannyi entsefalomielit.

Acute disseminated encephalomyelitis (AEM) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS), usually single-phase. In WREM, multiple lesions of the central nervous system of an inflammatory-demyelinating nature accompanied by extremely polymorphic neurological disorders develop acutely or subacutely. The review considers the issues of epidemiology, trigger factors of the inflammatory process, clinical manifestations, differential and molecular diagnostics of WECM, and outlines the ways for further study of this pathology.

[Clinical case of levamisole-induced multifocal inflammatory leukoencephalopathy]. / Levamizol-indutsirovannaia vospalitel'naia leikoéntsefalopatiia.

Levamisole is an immunomodulatory drug which can trigger development of levamisole-induced multifocal inflammatory leukoencephalopathy (LIMIL) in patients treated for helminthic invasion, aphthous stomatitis, cancer, or cocaine users. LIMIL clinical case in patient 45 years old after single dose of levamisole (taken without any medical prescription) was described. We presented clinical history and clinical picture, MRI and laboratory data and treatment results during 1-year observation. According to similarity of LIMIL with acute disseminating encephalomyelitis or debut of multiple sclerosis and high frequency of levamisole usage in Russia (usually without medical prescription) LIMIL should be included in differential diagnosis in demyelinating disorders and treated according to current clinical recommendation.

[The Edinburgh Cognitive and Behavioral ALS Screen (ECAS): a Russian version.] / Édinburgskaia shkala otsenki stepeni narusheniia kognitivnykh funktsii i povedeniia u patsientov s bokovym amiotroficheskim sklerozom (ECAS) - russkoiazychnaia versiia.

AIM: To translate into Russian and adapt the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) for patients with amyotrophic lateral sclerosis (ALS). MATERIAL AND METHODS: Medical care for ALS patients requires participation of a multidisciplinary team. More than one third of patients with ALS suffer from cognitive and behavioral disturbances, and it influences decisions of the team, patients and family. The scale for measuring of these disturbances should be rapid and understandable for evaluation and take into account the specificity of cognitive and behavioral impairments in ALS. RESULTS AND CONCLUSION: ECAS met these criteria and allows screening examination of patients with ALS at different stages of movement impairment.

[Results of a randomized double blind parallel study on the efficacy and safety of tolpersione in patients with acute nonspecific low back pain]. / Rezul'taty randomizirovannogo dvoinogo slepogo parallel'nogo issledovaniia éffektivnosti i bezopasnosti primeneniia tolperizona u patsientov s ostroi nespetsificheskoi bol'iu v nizhnei chasti spiny.

AIM: To evaluate the efficacy and safety of tolpersione injection and oral formulations combined with NSAID over NSAID monotherapy in acute non-specific low back pain. MATERIAL AND METHODS: In this randomized double blind study 239 patients were included in the per protocol analysis. The first 5 days of treatment, patients received tolpersione or placebo injection which was followed by per os administration of tolpersione/placebo tablet up to 14 days. NSAID diclofenac tablet was used in both groups through the study. Functionality assessed by the Roland Morris Disability Questionnaire (RMDQ) at day 5 was the primary endpoint. Secondary endpoints were RMDQ at other time points, pain level change at rest and on movement assessed by the Visual Analogue Scale (VAS), the Clinical Global Impression of Improvement/Patient Global Impression of Improvement (CGI-I and PGI-I), change in the range of motion assessed by the distance from the fingertips to the floor, period of disability days, relative (%) changes in the daily dose of diclofenac from the 7th to the 14th day of therapy. RESULTS AND CONCLUSION: The primary and secondary endpoints clearly demonstrated the significant superiority of tolpersione added to NSAID monotherapy over NSAID monotherapy. The safety assessment revealed no statistically significant differences between the two groups. Based on the results, tolpersione injection and per os formulations can be considered an effective and safe drugs in the combined therapy for patients with acute nonspecific back pain.

[Experimental approach to the gene therapy of motor neuron disease with the use of genes hypoxia-inducible factors].

Motor neuron disease (MND), or amyotrophic lateral sclerosis, is a fatal neurodegenerative disorder characterized by a progressive loss of motor neurons in the spinal cord and the brain. Several angiogenic and neurogenic growth factors, such as the vascular endothelial growth factor (VEGF), angiogenin (ANG), insulin-like growth factor (IGF) and others, have been shown to promote survival of the spinal motor neurons during ischemia. We constructed recombinant vectors using human adenovirus 5 (Ad5) carrying the VEGF, ANG or IGF genes under the control of the cytomegalovirus promoter. As a model for MND, we employed a transgenic mice strain, B6SJL-Tg (SOD1*G93A)d11 Gur/J that develops a progressive degeneration of the spinal motor neurons caused by the expression of a mutated Cu/Zn superoxide dismutase gene SOD1. Delivery of the therapeutic genes to the spinal motor neurons was done using the effect of the retrograde axonal transport after multiple injections of the Ad5-VEGF, Ad5-ANG and Ad5-IGF vectors and their combinations into the limbs and back muscles of the SOD1(G93A) mice. Viral transgene expression in the spinal cord motor neurons was confirmed by immunocytochemistry and RT-RCR. We assessed the neurological status, motor activity and lifespan of experimental and control animal groups. We discovered that SOD1(G93A) mice injected with the Ad5-VEGF + Ad5-ANG combination showed a 2-3 week delay in manifestation of the disease, higher motor activity at the advanced stages of the disease, and at least a 10% increase in the lifespan compared to the control and other experimental groups. These results support the safety and therapeutic efficacy of the tested recombinant treatment. We propose that the developed experimental MND treatment based on viral delivery of VEGF + ANG can be used as a basis for gene therapy drug development and testing in the preclinical and clinical trials of the MND.

[Natalizumab in the treatment of patients with relapsing-remitting multiple sclerosis: the preliminary results of the observational program "Sovet"].

The post marketing observational program "Sovet" has been launched in 2011. Sixty-nine patients with relapsing-remitting multiple sclerosis (MS) treated with natalizumab (NZ), a second generation DMD, have been examined. NZ infusions were carried out during 1h every 4 weeks for 12 months. After treatment, there were a significant reduction in the frequency of relapses from 2.22±0.98 to 0.18±0.42 per year and a trend towards the decrease in EDSS scores from 3.69±1.00 to 3.37±1.17. Adverse effects were noted in 11 patients, with each patient having no more than one side-effect. One patient discontinued treatment due to a generalized allergic reaction. These findings are in line with literature results on the positive effect of NZ on the course and symptoms of MS. It has been concluded, that the strict selection of patients and their correct management during the treatment with NZ may provide the positive balance between advantages and potential risks.

Gene therapy of amyotrophic lateral sclerosis.

Two-year experiments were performed to evaluate the neurotrophic effect of hypoxia-inducible factors (vascular endothelial growth factor and angiogenin) expressed in recombinant human adenoviruses in amyotrophic lateral sclerosis. Randomized placebo-controlled trial demonstrated safety and good tolerability of the recombinant antiviral drugs. The life span of patients under conditions of hypoxia increased after treatment with the test drug, which was probably related to improved resistance of motoneurons. The presence of virus-neutralizing antibodies decreases the effectiveness of adenoviral vectors, which necessitates differential approach to the selection of patients and continuous monitoring of gene therapy.