[Early predictive biomarkers of posttraumatic epilepsy]. / Rannie prediktivnye biomarkery posttravmaticheskoi epilepsii.

Traumatic brain injury (TBI) affects about 50 million people in the world every year. Posttraumatic epilepsy (PTE) is a significant complication of TBI of any severity. PTE occurs in 20% of patients with TBI. Treatment of patients with PTE is particularly difficult due to obvious tendency towards drug resistance. Currently, there are no validated predictive biomarkers for PTE. Development of a system of validated predictive markers would improve PTE prediction quality and therapeutic approach for these patients. This review is devoted to the current data on the most perspective predictive biomarkers of PTE for clinical practice.

[Clinical and MRI predictors of coma duration, intensive care and outcome of traumatic brain injury]. / Klinicheskie i magnitno-rezonansnye tomograficheskie prediktory dlitel'nosti komy, ob"ema intensivnoi terapii i iskhodov pri cherepno-mozgovoi travme.

OBJECTIVE: This research is aimed to study the clinical and MRI predictors of coma duration, the intensity of critical care, and outcome of traumatic brain injury (TBI). MATERIAL AND METHODS: The data from 309 patients with TBI of varying severity were included in the analysis, of whom 257 (86.7%) were treated in the intensive care unit (ICU), including 196 (63.4%) patients admitted in a comatose state lasting longer than 1 day. All patients underwent brain MRI within 21 days after the injury. MRI findings were classified according to MRI grading scale of brain damage level and localization proposed previously. RESULTS: The proposed MRI grading significantly correlated with the Glasgow coma (GCS, r=-0.67; p<0.0001) and Glasgow outcome (0.69; p<0.001) scores in the entire group. In a subgroup of comatose patients (GCS<9) it correlated with coma duration (r=0.52; p<0.0001). Spearman correlation analysis showed a significant relationship between the MRI classification and a number of parameters: ICU length of stay (r=0.62; p<0.0001), the duration of artificial ventilation (r=0.47; p<0.0001), the rate of artificial ventilation, sedatives, analgesics, mannitol, hypertonic saline and vasopressors usage (p<0.01). These data confirm the relationship between higher grades of MRI classification (deep brain damage) and the need for the escalation of intensive care main components. CONCLUSION: Our results support the hypothesis that the levels and localization of brain damage, estimated by the proposed MRI grading scale, might be predictors of coma duration, intensity and duration of intensive care, and TBI outcomes. A prognosis based on clinical and neuroimaging data comparison can be valuable for planning and efficient use of the hospital beds and ICU resources, for optimizing the patient flow and timing of patient transfer to neurorehabilitation facilities.

[Diffusion kurtosis imaging in diffuse axonal injury]. / Izmeneniia parametrov diffuzionno-kurtozisnoi MRT u patsientov s diffuznym aksonal'nym povrezhdeniem.

Diffuse axonal injury (DAI) is one of the most severe traumatic brain injuries. The availability of neuroimaging biomarkers for monitoring expansion of traumatic brain injury in vivo is a topical issue. PURPOSE: To evaluate novel neuroimaging biomarkers for monitoring brain injury using diffusion kurtosis imaging (DKI) in patients with severe diffuse axonal injury. MATERIAL AND METHODS: DKI data of 12 patients with severe DAI (11 patients with a Glasgow Coma Scale (GCS) score of ≤ 8 and 1 patient with a GCS score of 9) and 8 healthy volunteers (control group) were compared. MRI examination was performed 5 to 19 days after injury; 7 of the 12 patients underwent repeated MRI examinations. We assessed the following parameters: mean, axial, and radial kurtosis (MK, AK, RK, respectively) and kurtosis anisotropy (KA) of the white and gray matter; fractional anisotropy (FA), axonal water fraction (AWF), axial and radial extra-axonal diffusion (AxEAD and RadEAD, respectively), and tortuosity (TORT) of the extra-axonal space) of the white matter. Regions of interest (ROIs) were set bilaterally in the centrum semiovale, genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, putamen, thalamus, midbrain, and pons. RESULTS: A significant reduction in KA (p<0.05) in most of ROIs set on the white matter was revealed. AK was increased (p<0.05) not only in the white matter but also in the putamen and thalamus. A significant reduction in MK with time was observed when the first and second DKI data were compared. AWF was reduced in the centrum semiovale and peduncles. The TORT parameter was decreased (p<0.05) in the majority of ROIs in the white matter, with the most pronounced changes occurring in the genu and splenium of the corpus callosum. CONCLUSION: DKI provides novel data about microstructural injury in DAI and improves our knowledge of brain trauma pathophysiology. DKI parameters should be considered as potential biomarkers of brain injury and potential predictors of the outcome.

[CSF shunting surgery in patients with post-traumatic hydrocephalus in the vegetative status and minimally conscious state: analysis of its efficacy and safety]. / Likvoroshuntiruiushchie operatsii u patsientov s posttravmaticheskoi gidrotsefaliei v vegetativnom statuse i sostoianii minimal'nogo soznaniia: analiz éffektivnosti i bezopasnosti.

The development of post-traumatic hydrocephalus (PTH) after severe traumatic brain injury can cause, in some cases, severe impairment of consciousness and prevent rehabilitation of patients. The influence of cerebrospinal fluid (CSF) circulation disorders on processes of consciousness recovery is a fundamental problem that requires in-depth research. The issues of differential diagnosis, results of surgical treatment of PTH, and its complications in patients in the vegetative status (VS) and minimally conscious state (MCS) remain poorly covered. MATERIAL AND METHODS: We performed a retrospective analysis of the long-term outcomes of surgical treatment in 82 PTH patients in the VS (38 cases) and MCS (44 cases). RESULTS: A significant clinical improvement occurred in 60.6% of VS patients and in 65.9% of MCS patients. The rate of shunt infection was high and amounted to 21.05% in the group of VS patients and 20.4% in the group of MCS patients. The rate of shunt system dysfunction was 26.05% in the first group and 20.4% in the second group. Postoperative mortality (associated directly with treatment complications) was 3.6%. Total mortality was 10.9%. DISCUSSION: The positive effect of shunting surgery in patients with gross impairment of consciousness was associated with transition to higher levels of consciousness. The high rate of complications, especially infections, was due to a serious condition of patients and comorbidities, in particular chronic infection foci. Shunt system dysfunction was not a factor of the adverse outcome of surgical treatment because rarely led to irreversible consequences, but required repeated surgery. Mortality after shunting surgery was significantly higher in patients with gross impairment of consciousness than in other groups of patients. We found a correlation between deaths in VS patients and shunt infection in the postoperative period. CONCLUSION: CSF shunting surgery is an important step in surgical rehabilitation of PTH patients. To assess the contribution of various risk factors to the development of shunt infection and to develop measures reducing its rate, further prospective studies are needed.

[In search of an effective algorithm for rhythmic transcranial magnetic stimulation in neurorehabilitation after severe traumatic brain injury]. / V poiskakh éffektivnogo algoritma ritmicheskoi transkranial'noi magnitnoi stimuliatsii v neiroreabilitatsii posle tiazheloi cherepno-mozgovoi travmy.

Rehabilitation of patients with severe traumatic brain injury (sTBI) is a topical medical and social issue because this pathology is one of the main causes of mortality and disability in the young working age population [1]. The most common sTBI consequences include motor and cognitive impairment as well as depression of consciousness [2, 3]. Despite significant progress in treatment of the consequences of severe traumatic brain injury, there are no treatment and rehabilitation standards for these patients, and the used rehabilitation measures are not always effective. These circumstances substantiate the need for the development of additional methods of neurotherapy. Over the past decade, transcranial electrical and magnetic stimulation (TMS) has been increasingly used as neuromodulatory treatment in clinical practice [4-12]. The accumulated experience has shown that transcranial neurostimulation methods require a more individualized approach in terms of both careful selection of patients and choice of exposure parameters. This review is based on an analysis of the most significant publications and recommendations recognized in the scientific community, as well as on reports of domestic and foreign authors presented at dedicated congresses in comparison with experience of our own research on transcranial stimulation. The paper discusses the main problems of using this method in medical practice of sTMI and their possible solutions.

[Autoregulation of cerebral blood flow in severe diffuse axonal brain injury: the role of neuroanatomical factors]. / Autoreguliatsiia mozgovogo krovotoka pri tiazhelom diffuznom aksonal'nom povrezhdenii golovnogo mozga: rol' neiroanatomicheskikh faktorov.

Autoregulation of cerebral blood flow (ACBF) is a system of mechanisms for maintaining stable adequate perfusion of the brain despite changes in systemic arterial pressure. In recent years, new data on the numerous metabolic and systemic mechanisms of cerebral blood flow regulation have been obtained, but the role of neurogenic regulation has not yet been fully understood and, therefore, not considered in clinical practice. AIM: The study aim was to assess the effect of anatomical injuries to deep brain structures on the extent and duration of ACBF abnormalities in a model of severe diffuse axonal injury (DAI). RESULTS: The study demonstrated that brain injury in the projection of a dopaminergic structure (substantia nigra) and a cholinergic structure (nucleus basalis of Meynert region) was more common in patients with impaired ACBF and was associated with a longer duration of the impairment. CONCLUSION: The obtained data may indicate the presence of central (neurogenic) pathways of cerebral vessel tone regulation; traumatic injury of the pathways leads to a more severe and prolonged period of impaired ACBF. Probably, injury to these regulatory structures in some patients has an indirect effect on the course of intracranial hypertension. Further experimental and clinical studies in this direction are needed to elucidate all elements of neurogenic regulation of cerebral vessel tone and ACBF mechanisms.

[New opportunities of magnetic-resonance imaging: an algorithm of CSD-HARDI tractography in reconstruction of the brainstem reticular formation fibers]. / Novye vozmozhnosti magnitno-rezonansnoi tomografii: algoritm CSD-HARDI traktografii v postroenii volokon retikuliarnoi formatsii stvola.

The study purpose was to develop a technique for intravital visualization of the brainstem reticular formation fibers in healthy volunteers using magnetic resonance imaging (MRI). MATERIAL AND METHODS: The study included 21 subjects (13 males and 8 females) aged 21 to 62 years. The study was performed on a magnetic resonance imaging scanner with a magnetic field strength of 3 T in T1, T2, T2-FLAIR, DWI, and SWI modes. A CSD-HARDI algorithm was used to identify thin intersecting fibers of the reticular formatio. RESULTS: We developed a technique for reconstructing the reticular formation pathways, tested it in healthy volunteers, and obtained standard quantitative indicators (fractional anisotropy (FA), apparent diffusion coefficient (ACD), fiber length and density, and axial and radial diffusion). We performed a comparative analysis of these indicators in males and females. There was no difference between these groups and between indicators for the right and left brainstem. Our findings will enable comparative analysis of examination results in patients with brain pathology accompanied by brainstem injury, which may help predict the outcome. This work was supported by a grant of the Russian Foundation for Basic Research (#16-04-01472).

[Indicators of homeostasis, inflammation and homocysteine in ischemic stroke in the young age]. / Pokazateli gemostaza, vospaleniia i gomotsistein pri ishemicheskom insul'te v molodom vozraste.

AIM: To determine indicators of homeostasis, inflammation and homocysteine in the young-aged patients with ischemic stroke (IS) of different genesis in the subacute and chronic stages. MATERIAL AND METHODS: Out of 218 patients with IS (mean age 34.7±8.7 years), 55 had stroke due to dissection of the inner carotid or the spinal artery, 28 due to cardioembolia, 38 due to antiphospholipid syndrome (APS), 16 due to cerebral arteritis; 85 patients were classified as having cryptogenic stroke, including 23 with noncerebral thrombosis (coagulopathy of unknown etiology) and 62 with no thrombosis. The control group included 28 healthy people matched for age and sex. RESULTS: There were 1) an increase in von Willebrand factor and coagulation factor VIII as well as a decrease in plasminogen and an increase in plasmin-inhibitor in IS caused by thrombosis (APS, cardioembolia, coagulopathy of unknown etiology); 2) alterations in erythrocyte aggregation and deformity in cryptogenic stroke; 3) mild or moderate hyperhomocysteinemia, with the exception of patients with APS and arteritis. Linear regression analysis confirmed these relationships. Discriminant analysis identified the clusters of parameters characteristic of APS (an increase in (aPTT), plasminogen, blood sedimentation rate, C-reactive protein) and cardioembolia (decreased protein C and increased hematocrit). CONCLUSION: The laboratory markers associated with cerebral thrombosis can be used for identification of a prothrombotic state as a cause of IS in the young age. Moderate hyperhomocysteinemia is a risk factor but not a cause of IS. The increase of inflammatory markers in APS suggests a role of infection in its development.

[Navigation systems in neurosurgery]. / Navigatsionnye sistemy v neirokhirurgii.

When preparing the review, we analyzed publications available at the Medline database; a total of 1,083 publications related to the review's subject were analyzed. After more careful analysis, we selected 117 publications devoted to the development of neuronavigation in craniocerebral surgery, historical prerequisites of neuronavigation emergence, current trends, and future perspectives of the technique.

[Clinical syndromes of neurotransmitter system dysfunction in severe brain injury].

AIM: To explore neurotransmitter system dysfunctions involved in maintaining of consciousness and motor functions in patients with severe traumatic brain injury (TBI) and to assess their severity and predictive value. MATERIAL AND METHODS: Authors examined 100 patients (34 women and 66 men), aged 32.0 ± 13.0 years, with severe TBI. Eighty-eight patients (31 women and 57 men) were studied in the acute stage (1-15 days, mean 5.8 ± 3.7 days) and 70 patients (24 women and 46 men) in the subacute stage (18-70 days, mean 30.4 ± 12.7 days). Inclusion criteria were: severe TBI with depression of consciousness (≤ 7 scores on the Glasgow Coma Scale), admission to the hospital in acute and subacute stages. Outcome of TBI was evaluated using the Glasgow Outcome Scale. RESULTS AND CONCLUSION: The following clinical syndromes of neurotransmitter system dysfunction were singled out: excess or insufficiency of glutamate, cholinergic deficit, excess or insufficiency of dopamine. Their transformation during disease was identified. Predictive value of neurotransmitter dysfunctions for TBI is emphasized.

[The current state of the brain-computer interface problem].

It was only 40 years ago that the first PC appeared. Over this period, rather short in historical terms, we have witnessed the revolutionary changes in lives of individuals and the entire society. Computer technologies are tightly connected with any field, either directly or indirectly. We can currently claim that computers are manifold superior to a human mind in terms of a number of parameters; however, machines lack the key feature: they are incapable of independent thinking (like a human). However, the key to successful development of humankind is collaboration between the brain and the computer rather than competition. Such collaboration when a computer broadens, supplements, or replaces some brain functions is known as the brain-computer interface. Our review focuses on real-life implementation of this collaboration.

[Clinical and prognostic significance of genetic markers in craniocerebral injury (Part III)].

It is now becoming increasingly clear that the course and outcome of craniocerebral injury (CCI) are determined not only by its biomechanism, severity, patient's age, presence of premorbid factors, etc., but also by individual features of the genome of each patient, which puts traumatic brain injury among multifactorial diseases. The genome determines the presence or absence of«genetic predilection to the development of various complications and sequelae of CCI, which generally determines the progression of traumatic brain injury disease. The first part of the review by Potapov et al. (201 0) [2] was devoted to the role of apolipoprotein E (apoE) gene polymorphism in CCI, the second one [3]- to the role of inflammation and immune response genes in the course and outcome of CCI. The present (third) part will provide a review of modern data on the effect of genes underlying intracellular processes of oxidative stress, apoptosis, regeneration, and synthesis of neurotransmitters and their receptors.

[Connexin-43 antibodies in intraoperative diagnosis of experimental poorly differentiated gliomas].

Fluorescent diagnosis was first proposed in the early XX century and has been used in neurosurgery for about 15 years. The method relies on selective accumulation of strongly fluorescent protoporphyrin IX in tumor cells. Over the past years, the method of intraoperative fluorescence diagnosis has occupied its niche in many neurosurgical clinics around the world and is now used for fast intraoperative diagnosis in brain tumor surgery. However, the efficiency of fluorescent intraoperative diagnosis using 5-aminolevulinic acid is 80-90% and 58.8% for surgery of Grade III-IV and I-II gliomas, respectively. One of the methods to improve the efficiency of fluorescent diagnosis is to use vector systems for delivering fluorescent drugs into the tumor. This paper reports the results of an experimental study of systems for delivering fluorescent agents (protoporphyrin IX, Alexa 488, Alexa 660) using connexin-43 antibodies in rats with transplanted C6 glioma.

[Plasma catecholamines in consciousness recovery in patients with severe traumatic brain injury].

Changes in plasma noradrenalin (NA) and dopamine (DA) levels were evaluated in the stages of consciousness recovery in patients with severe traumatic brain injury with and without deep brain structure damage. Forty-eight patients (36 men and 12 women), aged from 12 to 56 (31,9±10,9) yeas, were enrolled in the study. Two variants of catecholamine (CA) changes were found: 1) a CA-dissociation that was oppositely directed to NA and DA changes was observed in unconsciousness; 2) a CA-dissociation (unidirectional NA and DA changes) that was observed after the restoration of consciousness. In patients with the damage of two frontal lobes and deep brain structures, CA-association periods were seen in the stage of mental confusion with psychomotor agitation or when the brain stem was damaged. The duration of CA-association was negatively correlated with the velocity, quality of consciousness recovery and outcomes evaluated by the Glasgow scale.

[Characteristics of work environment factors and health state of workers engaged in open mining of refractory clay and structural quartz sand]. / Kharakteristika faktorov proizvodstvennoi sredy i zdorov'ia rabochikh pri otkrytoi dobyche ogneupornoi gliny i stroitel'nykh kvartsevykh peskov.

This article covers evaluation of work conditions and health state in workers engaged into open-cast extraction of refractories and of building quartz sand in moderate climate of Voronezh region.

[Lymphotoxin production by human lymphocytes. I. Study of the supernatants of phytohemagglutinin stimulated human lymphocyte cultures]. / Produktsiia limfotoksina limfotsitami cheloveka. Soobshchenie I. Izuchenie supernatantov kul'tur limfotsitov cheloveka, stimulirovannykh fitogemaggliutininom.

Lymphotoxin was found to be present in supernatants from 22 human lymphocytes cultures stimulated with phytohemagglutinin in a dose of 5 and 10 microgram/ml. The lymphocytes were obtained from the peripheral blood of 6 apparently healthy persons. Lymphotoxin activity was determined by simple and objective method, i.e. by staining the target cells (mouse L-cells) monolayer with crystal violet, with the following determination of optic densities of the L-cells lysates at 570 nm in the spectrophotometer. As revealed, 1 : 5 dilutions of the supernatants from the lymphocyte cultures incubated for 48 hours inhibited the L-cells growth by from 40 to 60%. With further incubation of the cultures (up to 72 and 96 hours) the cytotoxicity of their supernatants for the target cells showed no increase, whereas the blasttransformation index reaches the maximal value by 72nd incubation hour. Supernatants from unstimulated lymphocyte cultures failed to produce any cytotoxic effect on L-cells.