[Multiple sclerosis vaccine: possibilities of the use of dendritic cells immunomodulatory potential].

For the first time we carried out a clinical assessment of the safety, tolerability and clinical efficacy course of repeated administration of experimental modified autologous vaccine interleykin (IL-10) dendritic cells in two patients with secondary-progressive multiple sclerosis patient and one with relapsing-remitting multiple sclerosis. In the course of treatment, we carried out clinical and immunological monitoring. It was found out that intradermal dose of 3 x 106 cells applied to spinal area 6-12. times did not cause any serious side effects. After the treatment with dendritic cells, the following results were observed: 1) a significant positive clinical effect in patients with secondary-progressive multiple sclerosis exacerbations; 2) moderate positive clinical effect in patients with relapsing-remitting multiple sclerosis, in a state of remission; 3) a complete absence of any clinical results in patients with secondary-progressive multiple sclerosis without exacerbations. The immune response was characterized by a significant absolute and relative increase of serum T-regulatory cells. Discovered distinct anti-inflammatory properties of dendritic cell therapy allow us to consider it as a promising area of personalized treatment based on an individual vaccination against multiple sclerosis.

[The complex of neurological symptoms of substance abuse].

Standard neurological examination was performed in 85 patients of military service age (the average age was 32,6±5,3 years - from 19 to 44 years) with a confirmed diagnosis of substance abuse, caused by the use of narcotic drugs and psychotropic substances: cocaine and amphetamine in 12 patients, opioids - in 73 patienls. Some symptoms of nervous system damage had statistically characteristic peculiarities for different forms of substance abuse. Mydriasis, signs a bilateral pyramidal insufficiency, hyperkinetic disorder are often characteristic for cocaine and amphetamine abuse. Opioid abuse is characterised by more severe symptoms of nervous system damage, disseminated neurologic symptomatic and polyneurotic disorders. Symptoms of neurasthenia and vegetative-vascular dystonia, which are usually accompanied by the; symptoms of organic lesions of the central and peripheral nervous system, were observed in all patients with substance abuse. In order to detect the symptoms of nervous system damage in patients, which are supposed to be conscribe, it is necessary to take medical history.

[Recovery of consciousness as manifestation of neuroplasticity].

Prolonged impairment of consciousness is one of the most fearsome syndromes during diseases and traumas of nervous system. Traumatic brain injury (TBI) is the cause of coma with outcome in vegetative state in approximately half of cases which allows considering this etiopathogenetic form of consciousness impairment as one of the models for studying its morphofunctional nature because the pathogenesis of TBI is mostly understood. Particularly, it has been showed that in the basis of clinical picture of TBI lie, on the one hand, morphological (diffuse axonal injury of subcortical white matter, necrotic changes in cortex, thalamus) and functional (diaschisis) disturbances and on the other--processes of sanogenesis occurring within the borders of neuroplasticity. The aim of our research was to investigate clinical and neurophysiological markers of consciousness recovery in patients with vegetative state (VS) after severe TBI by comparison of clinical changes dynamics and brain bioelectrical activity. In all patients we have evaluated neurological status, Glasgow coma scale, performed registration and spectral-coherent analysis of electroencephalography and also registration and analysis of somatosensory potentials, studied motor thresholds, amplitude-time characteristics of evoked motor potentials during transcranial magnetic stimulation, repeatedly conducted MRI or CT. The electroencephalography in most of the patients revealed theta- and delta-rhythm sometimes with signs of paroxysmal activity and interhemispheric asymmetry or low-amplitude EEG. It is estimated that reliable positive changes in amplitude-time characteristics of multimodal evoked potentials, reliable decrease of motor thresholds mostly in left hemisphere and increase of motor evoked potentials amplitude are in 5-7 preceded by clinical improvement in patients with TBI.

[Systematization of primary headache: current and future prospects].

The article is devoted to the current state of the problem of systematization of primary headaches and main clinical forms. The conceptual evolution of ideas about the classification of certain options of cephalgia and identified major trends for its improvement is given. Verification of types and subtypes of individual cephalgia can present a significant challenge even for experienced neurologists, neurosurgeons, and internists. In this regard in most European countries and the US. have set up specialized centers for the treatment of headaches. Concluded that in the short term in the national health care system, including. Including the Armed Forces, it is advisable to create such centers.

[Pathology of the nervous system in conscripts with drug abuse in past medical history: symptomatology, diagnostics methods].

Authors examined 60 female and male patients (average age 25.8±2.7 years) with confirmed diagnosis - drug abuse. Average duration of drug abuse was approximately 9±3.3 years. At the moment of examination patients had been fully in remission for 3 weeks. The following non-invasive procedures were undertaken: stimulation electroneuromyogrphy and brain MRI. Received results showed that drug abuse leads to diffuse lesion of the nervous system, which manifests itself as vegetative disorders, scattered neurological symptoms, polyneuropathy. Authors gave recommendations in the field of military examination with the aim of detection of nervous disorders caused by drug abuse.

[Comparative characteristics of neuropsychological and neurometabolic changes in patients with Alzheimer's disease and vascular cognitive impairment]. / Sravnitel'naya kharakteristika neiropsikhologicheskikh i neirometabolicheskikh pokazatelei u patsientov s bolezn'yu Al'tsgeimera i sosudistymi kognitivnymi rasstroistvami.

OBJECTIVE: To investigate the pattern and connections of neuropsychological and metabolic indices in patients with cognitive disorders of Alzheimer's and vascular (subcortical-cortical) types of different severity. MATERIAL AND METHODS: A total of 177 patients were examined, including 85 patients with Alzheimer's disease (AD) and 92 patients with vascular cognitive impairment (VCI). All patients underwent complex neuropsychological examination; 18F-FDG PET was performed in 17 patients with AD and 15 patients with VCI. RESULTS: The greatest changes in patients with AD were noted in the mnestic sphere, and the indicators significantly differed from the results of the study of patients with VCI already at the pre-dementia stage. Neurodynamic and dysregulatory disorders prevailed in patients with VCI. Patients with AD showed bilateral symmetrical reduction of metabolic activity in the cortex of parietal and temporal lobes, often in combination with marked hypometabolism in the hippocampal region. In patients with VCI, there were areas of decreased brain tissue metabolism of different localization and size, mainly in the projection of the basal ganglia and in the prefrontal and parietal cortex, as well as in the cingulate gyrus, which indirectly confirms the mechanism of disconnection of subcortical and cortical structures. In AD, impaired metabolic activity in the hippocampal region correlated with impaired temporal and spatial orientation (ρ=-0.54, p<0.05), memory impairment (ρ=-0.71, p<0.005). Hypometabolism of the parietal lobe cortex was associated with total MMSE score (ρ=-0.8, p<0.001), 10-word test (ρ=-0.89, p<0.001 and ρ=-0.82, p<0.001), visual-spatial impairment (ρ=-0.64, p<0.01), categorical association test (ρ=-0.73, p<0.005). In patients with VCI, dysregulatory disorders correlated with hypometabolism in the thalamic projection (ρ=-0.56, p<0.05), prefrontal cortex (ρ=-0.64, p<0.05) and in the cingulate gyrus (anterior regions) (ρ=-0.53, p<0.05). CONCLUSION: The results indicate the presence of differences in cognitive impairment and cerebral metabolism in patients with AD and VCI.

[Stages of formation and development of the national military neurology and psychiatry].

The article is devoted to the stages of formation and development of military neurology and psychiatry in Russia. Scholars of anxiety and mental disorders department of the Medical and Surgical Academy (Military Medical) made great contribution to development of scientific and organizational peculiarities of these medical disciplines and many other allied studies. Authors analyze the contribution of military psychiatrists and neurologists to the modern concept of mental care delivery in peace and wartime, research focus ares and prospects of its development.

[Early diagnosis of dementia with the help of MR-morphometry in patients with Parkinson's disease].

54 patients with idiopathic Parkinson's disease were examined. 1,5 Tesla MRI with T1 gradient-echo protocol and following calculating by FreeSurfer software was performed. Dementia was revealed in 23 patients. Significant changes of different zones of brain-cortex were revealed in patients with Parkinson's disease accompanied by dementia. Changes were revealed in the hemispheres, particularly in frontal, temporal and occipital lobes. Thickness of lingual medial occipitotemporal gyrus can be used as a criterion for dementia prognosis. Individual patient monitoring and cortex alteration evaluation allow prognosticating increasing risk of cognitive disorders development and prescribing proper therapy.

[Vladimir Mikhailovich Bekhterev--the founder of the clinical neuropsychiatry].

The article presents main milestones in the career of Vladimir Mikhailovitch Bekhterev. The research in anatomy and physiology of the brain performed by V.M. Bekhterev gave original data of worldwide priority. V.M. Bekhterev significantly improved methodology of neurological examination and differential diagnosis in clinical neuropsychiatry. The scientific heritage of V.M. Bekhterev proves his outstanding role in establishment and development of the neuropsychiatry.

[Analysis of frequency and structure of cerebrovascular diseases in servicemen during the military physician expertise].

Analysis of the results of medical inspection of soldiers under contract taken place in 2005-2009 is given. In 48.9% of cases was revealed diseases of blood circulatory system. In patients with cardiovascular events in 42.2% of cases different forms of cerebrovascular diseases were diagnosed. It shows high level of these diseases and its early progression among the servicemen. According to the authors, specific peculiarities of intensive military service provide the early progression of diseases. In such a case, presence of cerebrovascular diseases influences on expert decisions about professional suitability of servicemen for some military specialties including the level of suitability for military service.

[Complex therapy and rehabilitation approach patients with posttraumatic cognitive defects].

The craniocerebral trauma is one of the major problems of modern medicine. The significant amount of the patients who have had a trauma of the brain become invalids, this situation promotes their social and household disadaptation. The origin of the damage of the highest cortical functions which embarrass full reintegration of patients into different spheres of activity has a particular significance. In the article the philosophies of clinical diagnostic posttraumatic cognitive disorders are set up, the possible approaches to the rehabilitation of patients are showed, the different directions of the pathogenetic pharmacological therapy with allowance of the action drugs mechanism.

[The 1st native department of nervous and mental diseases].

In 1860 year in Medical-surgical academy in St. Petersburg was found the first department of nervous and mental diseases. With this department are aligned names of the greatest native neurologists and psychiatrists (Merzheevsky I.P., Bekhterev V.M., Blumenau L.V., Astvatsarov M.I., Dojnikov B.S., Triumfov A.V., Razdolsky I.Ya., Panov A.G. and etc.) who took the glory of Russian neurology. For 150 years the department was the base of neurological specialists for all medical institutes of the state. The department keeps the single educational and scientific institute, supplying systematic and high-qualified preparedness of military neurologists.

[Clinical and morphological risk factors for epilepsy in patients with glial and metastatic brain tumors]. / Kliniko-morfologicheskie faktory riska razvitiya epilepsii u bol'nykh s glial'nymi i metastaticheskimi opukholyami golovnogo mozga.

OBJECTIVES: To estimate the incidence of epileptic seizures in patients with glial and metastatic brain tumors and to identify clinical and morphological risk factors for epileptic seizures in patients with glial and metastatic brain tumors. MATERIAL AND METHODS: The study included 225 (88.6%) patients with glial brain tumors and 29 patients (11.4%) with metastatic tumors. RESULTS: Statistically significant differences in the incidence of epileptic seizures depending on age, histological characteristics of the tumor, degree of malignancy, tumor localization, involvement of the cerebral cortex, the presence of the midline shift were obtained. CONCLUSIONS: Epilepsy and epileptic seizures was found to develop in 51.11% and 24.14% of cases in glial and metastatic brain tumors, respectively. Risk factors for developing epileptic seizures include younger age (up to 57 years), histological characteristics corresponding to diffuse astrocytomas, anaplastic astrocytomas, oligodendrogliomas, oligoastrocytomas, grade I-III malignancy, lesion of the temporal lobe, involvement of the cerebral cortex. Factors that reduce the risk for attacks include age over 57, histological characteristics corresponding to glioblastomas and metastatic tumors, grade IV malignancy, subcortical localization of the tumor, damage to the occipital lobe, involvement of the commissural pathways, subtentorial localization of the tumor, the absence of lesions of the temporal and frontal lobes of the brain, the involvement of both brain hemispheres, damage to two or more brain lobes, the presence of a midline shift.

[First-string native neurohistologist and histopathologist (to the 130th anniversary of Doynikov B.S.)].

The article presents a biographic sketch, devoted to one of founders of histopathology of peripheral nervous system--Doynikov B.S. (1879-1948) - professor of Military-medical academy, author of fundamental monographies "General histology and histopathology of peripheral somatic nervous system" and "General histology and histopathology of peripheral vegetative nervous system".

[Characteristics of postoperative cerebral dysfunction depending on the type and position of the implanted prosthetic heart valve]. / Osobennosti posleoperatsionnoi mozgovoi disfunktsii v zavisimosti ot tipa i pozitsii implantiruemogo proteza klapana serdtsa.

AIM: To study the prevalence and structure of postoperative cerebral dysfunction depending on the type and position of the implanted prosthetic heart valve in patients who underwent surgery for the acquired heart valve disease. MATERIAL AND METHODS: The study included 115 patients (70 men and 45 women; 64 [56; 72] years old), who underwent elective replacement or repair surgery for the acquired heart valve disease. RESULTS AND CONCLUSION: The postoperative cerebral dysfunction was diagnosed in 40.9% patients, including replacement in the aortic position (45.5%), in the mitral position (55%), in several positions (20%). Replacement surgery was accompanied by three clinical types of postoperative cerebral dysfunction and repair surgery - by deferred cognitive impairment only. Postoperative cerebral dysfunction after the replacement in the mitral position was more common (odds ratio 4.47, 95% confidence interval 1.21-18.35, p=0.041), including its acute clinical types - perioperative stroke and symptomatic delirium of the early postoperative period (p=0.029), compared to that after the repair heart valve surgery. After the replacement in the aortic position, acute clinical types of postoperative cerebral dysfunction were more common (p=0.036). After the replacement with biological prosthesis, symptomatic delirium of the early postoperative period was more common (p=0.047). The occurrence of the deferred cognitive impairment didn't depend on the type and position of the implanted prosthetic heart valve.

[The efficacy and safety of siponimod in the Russian population of patients with secondary progressive multiple sclerosis]. / Éffektivnost' i bezopasnost' siponimoda u patsientov s vtorichno-progressiruiushchim rasseiannym sklerozom v rossiiskoi populiatsii.

AIM: To study the efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis (SPMS) in the Russian population of the EXPAND study. MATERIAL AND METHODS: Ninety-four patients with SPMS from Russia were included in the analysis. Sixty-three patients received siponimod and 31 patients received placebo. The primary endpoint of the study was time to 3-month confirmed disability progression (3m-CDP) events, other clinical and radiological endpoints were also evaluated. RESULTS: The siponimod group showed a 54% reduction in the risk of 3m-CDP compared with the placebo group (p=0.0334). Secondary endpoints also showed the advantage of the drug over placebo. In the siponimod group, mild adverse events associated with impaired liver function, as well as arterial hypertension, were more common. No patient left the study due to an adverse event. CONCLUSION: The use of siponimod in patients with SPMS in the Russian population reduced the risk of disability progression. Siponimod showed a favorable safety profile.

Efficacy and safety of galantamine (reminyl) for dementia in patients with Parkinson's disease (an open controlled trial).

An open controlled trial of the use of galantamine at a maximum dose of 16 mg/day included 41 patients with Parkinson's disease with dementia randomized to a galantamine treatment group (21 patients) and a control group (20 patients). Cognitive, neuropsychiatric, and motor symptoms were assessed clinically before the trial and at 4, 12, and 24 weeks, using the Mini Mental State Examination (MMSE), the cognitive Alzheimer's Disease Assessment Scale (ADAS-cog), the clock drawing test, the Frontal Assessment Battery (FAB), and the Neuropsychiatric Inventory (NPI) with assessment of distress in relatives. Patients treated with galantamine had better scores on the MMSE (p < 0.05),ADAS-cog (p < 0.05), the clock drawing test (p < 0.05), and the FAB (p < 0.01) at the end of the study period as compared with the control group. Changes in total point scores on the NPI-12 at the ends of weeks 12 and 24, as compared with the beginning of the trial, were in favor of the group treated with galantamine, with significant changes in the hallucinations (p = 0.0002), anxiety (p = 0.04), sleep disturbance (p = 0.04), and apathy (p = 0.006) sections. Galantamine treatment was accompanied by decreases in the level of distress in patients' relatives (p = 0.007) and improvements in daily activity (p = 0.003). Improvements in gait and decreases in freezing and falls were seen in the galantamine treatment group. However, two patients of this group showed minor increases in tremor. Side effects (drooling, postural hypotension, nausea, dysuria) occurred in seven patients (30%).

[Postoperative cerebral dysfunction]. / Posleoperatsionnaia mozgovaia disfunktsiia.

AIM: To study the structure, risk factors and methods of prevention of postoperative brain dysfunction on the example of coronary artery bypass surgery with cardiopulmonary bypass. MATERIAL AND METHODS: The study included 77 patients who undergone elective coronary artery bypass surgery at the beating heart (22 patients) or with cardiopulmonary bypass (55 patients, including 24 patients, who received cerebroprotective treatment with cytoflavin in the preoperative period). All patients underwent dynamic (pre- and postoperative) neurological, neuropsychological, instrumental examinations. RESULTS: The postoperative cerebral dysfunction was diagnosed in 34 (44,2%) patients. The frequency of the clinical types of postoperative cerebral dysfunction significantly differed: perioperative stroke - 3 (3,9%) cases, symptomatic delirium of the early postoperative period - 11 (14,3%) cases, delayed cognitive impairment - 28 (36,4%) cases. The risk factors of postoperative cerebral dysfunction after the coronary artery bypass surgery with cardiopulmonary bypass were identified. Preventive preoperative use of the neuroprotective drug cytoflavin reduces the severity of delayed cognitive impairment after the coronary artery bypass surgery with cardiopulmonary bypass and has a good safety profile. CONCLUSION: An analysis of the literature data and the results of our own studies show that postoperative cerebral dysfunction is the nosological entity with various etiological factors, pathogenetic mechanisms and the characteristic clinical types, which has an effect on the outcome of surgical treatment.

[Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study]. / Levodopa-karbidopa intestinal'nyi gel' v terapii bol'nykh s razvernutymi stadiyami bolezni Parkinsona: rezul'taty 12-mesyachnogo otkrytogo issledovaniya.

AIM: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. MATERIAL AND METHODS: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study. RESULTS: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. CONCLUSION: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

[New morphological data on multiple sclerosis].

The brain from 6 patients who died of multiple sclerosis was studied with MR tomography (MRT), macroscopy, light (CD 3, CD 20, LCA antigens) and electron microscopy (EM). Typical foci of demyelinization (plaques) were found in all cases. Alterations of brain arteries were found particularly in arteries of narrow lumen--with disturbance or even absence of elastin and muscle layer. Up to 30% of the vessels were surrounded by microcavities. Perivascular infiltrates consisting primarily of T lymphocytes were observed around the vessels (up to 70% of all vessels). This indicates the importance of vascular changes in the disease pathogenesis. Four variants of demyelinization (plaques) are distinguished depending on the degree of destruction of myelin, axons and glia. Two types of cells were found in the plaques with most pronounced changes: astrocytes and newly formed oligodendrocytes. Classification of plaques is suggested.