[BRAIN NATRIURETIC PEPTIDE AS A MARKER OF SEVERITY OF PATIENT'S CONDITION AFTER SEVERE TRAUMATIC BRAIN INJURY].

The aim of the study was to assess the significance of NT-proBNP levels as a predictor of the severity of patients' condition after severe TBI and critical stress of the heart. In this prospective observational study 118 patients admitted on 1-4 day after severe TBI (GCS <8 points on admission) was supervised. The average age of patients was 32 +/- 16 years, 28 women and 90 men were in this group. 12 of the observed patients died within the first 10 days. NT-proBNP level was determined by immunochemiluminescent analyzer "Immulite 2000" (Siemens). Blood sampling was performed daily at 8:00 am during the acute period--an average for 7 days (5 to 10) from the date of admission. At the same time hemodynamic status was assessed by PiCCO. It has been shown that NT-proBNP level may be not only a marker of severity of condition and poor outcome in patients with severe TBI, but also can be used as a good predictor of exhaustion of compensatory myocardial capacity in these patients.

[SEPTIC SHOCK IN PATIENT WITH SEVERE HEAD TRAUMA].

The clinical observation illustrates the role of screening of inflammatory markers and advanced hemodynamic monitoring in optimization of the treatment of the patient with severe traumatic brain injury (sTBI). The level of consciousness by the Glasgow Coma Scale at admission was 5 points. From the first day of stay the patient suffered hyperthermia to 39,0° C° The diagnosis of the aspiration pneumonia was determined by radiological signs, bronchoscopy and inflammatory blood markers, C-reactive protein, leukocytosis. From the second day the constant infusion of norepinephrine was necessary to maintain mean ABP above 80 mmHg. On the 10th day the patient's condition deteriorated sharply. Developed hyperthermia to 40, 2° and cardiovascular collapse (in spite of the high level of norepinephrine support a sharp decline in ABP up to 49/20 mmHg). Invasive advanced hemodynamic PiCCO monitoring (transpulmonary thermodilution) was started Septic shock was suspected. Standard laboratory tests did not meet the criteria for septic shock. Witnessed a slight increase in CRP and procalcitonin (PCT) was within normal limits. Diagnostic search was supplemented by a study of interleukins (IL-6 and IL-2R) in the blood plasma. The significant increase in their values, was regarded as the initial manifestations of the systemic inflammatory response. Sepsis was confirmed. The extended antibiotic therapy started Continuous Veno-Venous hemofiltration was used as part of treatment of the inflammatory-toxic condition. In two days of the therapy the patient's condition has stabilized, the patient recovered consciousness in the form of opening the eyes, simple instructions. At discharge, the patient's condition according to the Glasgow outcome scale was estimated at 4 points.

[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.

[Analysis of thyroid homeostasis disorders in patients with severe traumatic brain injury].

Aim of the study was to investigate the status of thyroid homeostasis and the relationship between severe traumatic brain injury (TBI) and thyroid disorders. The study included 56 patients. Protocol of the study concluded: noninvasive and invasive hemodynamic monitoring, including PICCO, transcranial Doppler ultrasonography, measurement of intracranial pressure (ICP), indirect calorimetry, levels of thyroid stimulating hormone (TSH), T3, T4 and free fractions. Patients were divided into three groups. Group 1--with normal thyroid hormones (n = 20), Group 2--with the low T3 (n = 23) and Group 3 with the low T3 and T4 (n = 13). Correlation between the Glasgow Coma Scale (GCS) and thyroid hormone levels was obtained: the first group between GCS and T4 (r = 0.50), GCS, and free fraction T4 (r = 0.51); between the GCS and TSH (r = 0.51), T3 (r = 0.48) and T4 (r = 0.57) in the second group, and the third--with TSH (r = 0.67). Poor outcomes in the first group compound 15%, in the second group--39.2%, and in the third group--62.5% of patients. Doses of vasopressors were significantly higher in groups 2 and 3 compared with a first group. ICP was significantly higher in the group with the low T3 and T4. Development of intracranial hypertension correlated with the formation of thyroid insufficiency. Deficiency of thyroid hormones, especially the simultaneous reduction and T3, and T4 is associated with poor outcome in patients with severe TBI. Doses of sympathomimetic drugs used to optimize the parameters of systemic hemodynamics in acute severe head injury were higher in patients with deficiency of thyroid hormones.

[Clinical and prognostic value of inflammatory genetic markers in traumatic brain injury].

The paper analyses the published data about association of polymorphic gene markers of different bioactive agents (interleukins, angiotensin convertase, catechol-O-methyltransferase, dopamine receptors etc.) with traumatic brain injury. Analysis of the entire pool of data concerning clinical and experimental studies of association of different polymorphic markers of candidate genes with outcome of traumatic brain injury allows to conclude that IL 1alpha and IL 1beta, IL 6, catechol-O-methyltransferase, angiotensin convertase, D2 dopamine receptors in fact play important role in neuroinflammatory response to injury and recovery of the brain ant its functions. Moreover presence or absence of certain polymorphic gene markers differentially influence separate pathogenetic mechanisms of brain injury (e.g., severity of brain edema, cerebral blood flow, cognitive functions). Consequently each of the investigated genes contributes in outcome after traumatic brain injury.

[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.

[Comparative analysis of surgical and medical treatment of macroprolactinoma of different localization].

The authors performed comparative analysis of results of primary surgical and medical treatment of 306 patients with macroprolactinoma. The series included 178 male and 128 female patients. The tumor was endosellar in 48 cases, endosuprasellar in 94, invaded skull base in 164. The paper demonstrates that according to dynamics of visual function, neurological and hypopituitary symptoms, and probability of prolactin level normalization, treatment with cabergoline has significant advantages in comparison to surgery. Only surgical treatment of endosellar prolactinomas can compete with conservative treatment. After these operations no postoperative complications were observed, normalization of prolactin level was present in 67% of cases, and these results did not differ from results of medical treatment (71%). In case of extrasellar grown of macroprolactinoma, especially invading skull base, primary medical therapy is preferred.

[Selection of management tactics in treatment of giant prolactin-secreting pituitary adenomas].

Surgical treatment of giant pituitary adenomas is one of the most complicated problems of modern neurosurgery. Before introduction of dopamine agonists surgery was the dominating therapy. Advances in modern pharmacology allowed to approach the alternative way of management of giant prolactinomas (GP). The paper focuses on comparative analysis of results of surgical and conservative treatment of 57 patients with GP. 34 of them were operated and 23 received cabergolin as primary therapy. Assessment of neurological status, visual functions, hypopituitary disorders and prolactin level was performed. Dynamics of evaluated symptoms resulting from tumor shrinking showed that primary conservative treatment of GP is more preferable than surgical.

[Clinical presentation, diagnostics and results of primary conservative treatment of large and giant prolactin-secreting pituitary adenomas].

A prospective study of 55 patients with large and giant prolactin-secreting pituitary tumors receiving dopamine agonists as primary treatment was performed. Statistically significant data were obtained indicating decrease of prolactin level, improvement of vision, normalization of sexual function and shrinking of the tumor. Effectiveness and safety of dopamine agonists in patients with large and giant prolactinomas are proved. Also we discovered possibility of nasal CSF leak during conservative treatment.

[Cerebral low T3 syndrome]. / Mozgovoi sindrom nizkogo T3.

The authors studied the time course of changes in the parameters of the cerebral thyronergic system (total and free triiodthyronine (T3) and thyroxin (T4), thyroxine-binding globulin (TBG), thyroid-stimulating hormone (TSH) by radioimmunoassay (Immunotech, Czechia; CIS, France), proinflammatory cytokine of TNF-alpha by enzyme immunoassay (Innogenetic, Belgium) in the blood and cerebrospinal fluid (CSF) in 59 patients (37 males and 22 females whose age ranged from 21 to 64 years) in acute subarachnoidal hemorrhage due to arterial aneurysmal rupture. On admission, the condition of 47 (79.7%) was rated as grades III-VI according to the Hunt-Hess scale, which was responsible for high mortality rates (33.89% in the assessment of outcomes according to the Glasgow outcome scale). The causes of death were ischemic and hemorrhagic insults, edema of the brain, cerebral stem wedging. Laboratory findings were analyzed in relation to the clinical condition of patients, outcomes, and the degree of secondary vasospasm assessed by Doppler transcranial study by the average blood flow velocity in the middle cerebral artery. They revealed a significant depression of thyroidal metabolism with developed the total low T3 syndrome just before surgical treatment in patients with deterioration in the early postoperative period. The significant correlations found by the authors between the decreased blood T3 and TSH levels and 1) the severity of neurological disorders; 2) the degree of vasospasm, and 3) the outcome of disease, as well as negative correlations of elevated TNF-alpha levels not only in the blood, but also in CSF with the content of CT3, CT4 and with the severity of neurological symptomatology are indicative of the development of isolated syndrome in the brain, which is characterized by specific thyroidal metabolic disorders, which the author propose to call the cerebral low T3 syndrome (by taking into account the presence of the autonomic systems of thyroidal homeostatic provision).

[Involvement of thyroid hormones in mental recovery following severe craniocerebral trauma]. / Rol' tireoidnykh gormonov v protsesse vosstanovleniia psikhicheskoi deiatel'nosti posle tiazheloi cherepno-mozgovoi travmy.

To study a role of thyroid hormones in the recovery of mental performance, 71 patients (60 males, 11 females) aged 7 to 66 years (mean age 32.7 +/- 3.5) with severe brain injury (TBI). According to the stage of mental recovery (1--none; 2--elementary acts; 3--verbal contact; 4--spatial orientation; 5--intellectual and mnestic processes and emotional and personality traits), the study was divided into 5 series. Immunoradiometric assay of thyroid hormones (T3 and T4) and their free fractions (FT3 and FT4), thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG), and prolactin (P) revealed significant alterations in thyroid metabolism at stages 1 to 4, which appeared as low T3 syndrome. The thyrotropin-releasing hormone (TRH) test made in study series 3 to 5 suggests that the patients have neuroendocrine dysfunctions at the mentioned recovery stages of mental functions of the brain. There was a close relationship of clinical parameters (mental time course) to alterations in the thyroid status and metabolism and to morphological impairments of brain tissues in their traumatic damage, which is evidenced by a correlation of the levels of blood and spinal fluid markers (neurone-specific enolase--NSE and protein S-100) of brain injury with psychopathological disorders (r = -0.96 and -0.6, respectively; p < 0.05) and by the assessment of TBI outcomes (r = -0.65 and -0.62, respectively; p < 0.05). Thus, the findings clinically confirm the neurotransmitter role of thyroid hormones at the stages of mental recovery. In addition, the results show that measurement of blood T3, FT3, TSH, T4, TBH, and NSE should be included into neurochemical monitoring in SBI as prognostically significant criteria. They also may serve as a basis for timely correction of thyroid metabolism.

[Epidural anesthesia in surgical interventions on the spine and spinal cord. I. Comparative analysis of the effectiveness of anesthesiological protection under conditions of epidural anesthesia and neuroleptanalgesia in surgery of the spine and and spinal cord]. / Epidural'naia anesteziia pri operativnykh vmeshatel'stvakh na pozvonochnike i spinnom mozge. Chast' I. Sravnitel'nyi analiz adekvatnosti anesteziologicheskoi zashchity v usloviiakh épidural'noi anestezii i neiroleptanal'gezii pri operatsiiakh na pozvonochnike i spinnom mozge.

The study was carried out in 22 patients operated on for vertebral disk hernias and spinal tumors at lumbosacral level. The patients were divided in 2 groups depending on the type of anesthesia (epidural or neuroleptanalgesia-EA and NLA). In the test group all patients were operated under EA with local anesthetics combined with intravenous sedative drugs (diprivan + relanium) under conditions of spontaneous respiration and O2 inhalation through a mask. In the control group combined total intravenous anesthesia by myorelaxants and tracheal intubation were carried out (relanium + diprivan: induction dose 1.95 +/- 0.5 mg/kg, maintenance dose 5.3 +/- 0.4 mg/kg/h, and phentanyl). The purpose of the study was to compare the efficiency of anesthesiological protection under EA and traditional NLA in interventions on the spine, when surgical injury is inflicted in the immediate vicinity to the central structures responsible for pain impulsation. Only EA ensured adequate protection of the patients from surgical stress, as was seen from hemodynamic (arterial pressure and heart rate) and endocrine metabolic parameters (glucose, epinephrine, norepinephrine, hydrocortisone, and prolactin levels). Hence, EA fully demonstrated its protective properties during operations on the spine, and therefore can be regarded as a method of choice in this patient population.

Thyroid hormones in comatose patients with traumatic brain injury.

The objective was to study if thyroid hormones, cortisol, prolactin and brain injury marker levels were changed in traumatic brain injury (TBI) patients with changing levels of consciousness. We estimated the above named parameters in 32 patients (27 men and 5 women aged 11-55). Admission Glasgow Coma Score was < 8. Follow-up period--30 days. The length of coma was 3 to 25 days. There were significant decreases in TSH, TBG, FT3 and F_levels (p < 0.05, for each) and a T3 increase (as compared to very low preceding values) on day 1 before emergence from coma and considerable post-coma increase in TBG, FT3, TSH and F levels (p < 0.001 each) on days 1-3 in patients with diffuse axonal injury (DAI). In patients with contusions and epidural and subdural hematomas (CH) T3 and T4 levels continued to fall until 4-6 postcoma days. TSH values significantly increased up to average normal ranges (p < 0.05) on days "-" 2 and "-" 1 before emergence from coma and remained so. Significantly lower levels of TSH, F and PRL were found in patients with CH in the mostly remote period (on days "-" 12-"-" 8) before emergence from coma in comparison with DAI patients. In blood the following correlations of examined parameters were established: between NSE and T3 (r = -0.39), NSE and FT3 (r = -0.59), TNF alpha and TBG (r = -0.64), TNF alpha and T3 (r = -0.3) and S-100 and T3 (r = -0.3) (p < 0.05, for each). The results obtained confirmed a low T3 syndrome in comatose TBI patients. We demonstrated an objective and informative interdependence: the turning-point moment of the emergence from coma was accompanied by significant changes of examined hormone levels and brain injury marker levels. The results may serve as a base for recommending monitoring FT3 and T3 levels simultaneously with that of other injury markers and adequate T3 replacement therapy in the early posttraumatic period.

The plasma and CSF vasopressin levels in brain tumors with brain edema.

Vasopressin (VP) levels were evaluated by radioimmunoassay (RIA) in the arterial (A), peripheral (Vp) and jugular (Vj) vein blood and in CSF in 102 patients with brain tumors. In 60 cases the patients' state was complicated by brain edema (BE) and hemodynamic disturbances (HDD). The obtained data revealed significantly higher VP levels: 1) in A, Vp and CSF in patients with BE (Group A) in comparison with patients without BE (Group B), 2) in Vj in patients with HDD only (Group Bc) and 3) in Vp in patients with HDD and BE (Group Ac) in comparison with Group Bc (p < 0.05). There were marked extremely high VP levels in Vj in patients with severe haemorrhage, tachycardia and high blood pressure (BP) and in CSF in patients with tachycardia, high BP and cardiac arrest (p < 0.05 correspondingly in each of the cases). Our results on a clinical basis confirmed CSF VP influence on BE development. We also confirmed the neurohumoral (through blood) and neurotransmitter (possibly through CSF and/or vasopressinergic pathways) VP influences on cardiovascular regulation mechanisms. We content that this is a pathogenetic basis for application of VP direct or indirect antagonists for preventing and treating brain edema in neurosurgical patients.

The CSF aldosterone in brain tumors with brain edema.

The study of renin-angiotensin-aldosterone (RAA) and vasopressin (VP) systems in neurosurgical patients with brain tumors and brain edema (BE) had revealed an excessive activity of these systems with secondary hyperaldosteronism especially with BE that proves the pathogenetic role of these systems. Measurement of Aldosterone (Ald) in CSF may serve as a diagnostic test to help manage the patient's clinical condition. Mechanisms of Ald penetration in CSF assumed to be the result of blood-brain-barrier (BBB) destruction (especially in astrocytomas) and/or the mediation by neuropeptides (for example increasing activity of VP V1-receptors). Results serve as a basis for application of the neuropeptide and hormone antagonists and inhibitors on all stages of cascade reactions taking part in the water and sodium retention.

[Mechanisms of development of brain edema in neurosurgical pathology]. / Mekhanizmy razvitiia oteka mozga pri neirokhirurgicheskoi patologii.

As many as 120 neurosurgical patients were examined after the excision of hemispheric gliomas, basal and subtentorial tumors. Based on an the computer-aided analysis biochemical and clinical data, attempts have been made to unify the mechanisms responsible for brain edema development in patients with neurosurgical pathology. In the early postoperative period, brain edema occurs in 95% of neurosurgical patients. Edema development, spreading and intensity depend on the site and nature of the primary pathological focus as well as on traumatism of surgical interventions. It is proved that edema is an original, biologically expedient brain response to its injury. This response manifests in hyperhydration of all tissues, with the maximum intensity being concentrated in the focus of injury. Specific (neurogenic neurohumoral) and nonspecific (biochemical, autoimmune, mechanical, and so forth) factors of brain edema development may be distinguished. The differences in the neurogenic and neurohumoral mechanisms by which brain edema develops may be accounted for by the topography of the focus of injury. The closer the pathological focus is to the stem and diencephalic structures, the more remarkable the action of neurogenous and neurohumoral factors and the more distinct the tendency toward edema generalization are. At the diencephalic level of injury, damaged are the structures responsible for central regulation of metabolism and trophicity of nerve cells. The neurogenously precipitated diffuse impairment of permeability of the cells entails their hyperhydration, which marks cellular (cytotoxic) edema. The subtentorial process that affects the vasomotor centre of the stem triggers the neurogenic diffuse alterations in the vascular tone, manifesting in an increase of permeability for water and plasma proteins which is characteristic of vasogenic edema.(ABSTRACT TRUNCATED AT 250 WORDS)

[Brain edema as a cause of critical states in neurosurgical patients]. / Otek mozga kak prichina kriticheskikh sostoianii u neirokhirurgicheskikh bol'nykh.

The results of the studies in 120 patients after resection of tumours located in cranial fossa (40 cases), basal-diencephalic area (45 cases), hemispheres (35 cases) have shown the role of brain edema in the onset of critical conditions after neurosurgery (with consideration of a new concept concerning the mechanisms of brain edema development). It has been demonstrated that brain edema at its early stages is a biologically expedient adaptation response to any damage and is manifested in hyperhydration of all the tissues, most marked in the affected focus. Specific (neurogenic, neurohumoral) and non-specific (biochemical, autoimmune, mechanical, etc.) factors of brain edema onset have been identified. It turned out that the location of the affected focus determines the differences in neurogenic and neurohumoral mechanisms of the edema onset. The nearer the affected focus to the stem and diencephalic structures, the more marked the effect of neurogenic and neurohumoral factors and the more distinct the tendency towards edema generalization. Brain edema may be a cause of critical conditions and lethal outcomes only when it leads to dislocation and strangulation of them brain structures, and disturbances of brain metabolism and blood flow.

[The effect of anesthesia on the neurohumoral regulation system and water-electrolyte balance during aortocoronary bypass]. / Vliianie anestezii na sistemu neirogumoral'noi reguliatsii i vodno-élektrolitnyi obmen vo vremia aortokoronarnogo shuntirovaniia.

Two methods of multicomponent general anesthesia distinct in the analgetic agent used to ensure analgesia have been compared. In group I (6 patients) analgesia was ensured by fentanyl at a dose of 10 micrograms/(kg/min), in group II (7 patients) it was ensured by pyritramide (dipidolor) at a dose of 2 mg/kg for the whole operative period. The study has shown that during aortocoronary bypass surgery in patients with ischemic heart disease analgesia is better ensured by pyritramide than by fentanyl administration. The latter technique of analgesia should be improved, as the current modification causes almost twice as great stress-reaction as the one employing pyritramide.