[Neuromodulatory pharmacotherapy individualization in prolonged and chronic consciousness disorders after severe traumatic brain injury]. / K probleme individualizatsii neiromodulyatornoi farmakoterapii pri prolongirovannykh i khronicheskikh narusheniyakh soznaniya vsledstvie tyazheloi cherepno-mozgovoi travmy.

One of the most probable causes of effective therapy for post-comatose disorders of consciousness is the lack of individualization of drug prescriptions. In this observational study, we analyzed 48 courses of neuromodulatory therapy in 28 patients with prolonged and chronic disorders of consciousness following severe traumatic brain injury. Comparison of 24 effective and 24 ineffective courses demonstrated higher effectiveness of pharmacotherapy through its individualization, i.e. the choice of a drug whose neuromodulatory spectrum would correspond to neurological syndromes of neurotransmitter dysfunction. In this approach, 74% of therapy courses were effective while opposite management resulted only 34% of effective courses.

[Surgical treatment of drug-resistant epilepsy following hippocampal sclerosis]. / Khirurgicheskoe lechenie farmakorezistentnoi epilepsii pri skleroze gippokampa.

Surgery is an effective approach for drug-resistant temporal lobe epilepsy following hippocampal sclerosis. There is still no clear and unanimous opinion about advantages and disadvantages of certain surgical technique. MATERIAL AND METHODS: There were 103 surgical interventions in 101 patients. Females prevailed (1.45:1). Age of patients ranged from 16 to 56 years (median 28). Anteromedial temporal lobectomy and selective amygdaloghippocampectomy were performed in 49 (47.6%) and 54 (52.4%) patients, respectively. In the latter group, 30 patients were operated via a 14-mm burr hole-subtemporal approach. Postoperative outcomes were assessed using the Engel grading system. The follow-up period ranged from 2 to 8 years (median 4 years). RESULTS: By the 2nd year, Engel class I was observed in 74 (72%) patients, Engel II, III and IV - in 20 (19.4%), 6 (5.8%) and 3 (2.9%) patients, respectively. Engel class I was achieved after anteromedial temporal lobectomy in 68% of cases, selective amygdaloghippocampectomy via standard approaches in 75% of cases, amygdaloghippocampectomy via subtemporal burr hole approach - in 80% of cases. Neurocognitive impairments after anteromedial lobectomy and selective amygdaloghippocampectomy were similar. At the same time, mental disorders de novo prevailed in the group of anteromedial lobectomy (p<0.05). There were no severe visual field disorders after subtemporal burr-hole access. In other cases, these disorders occurred in 36.2% of patients (p<0.05). There were 8 (7.8%) postoperative complications: 5 (10.2%) - after anterior temporal lobectomy, 3 (5.5%) - after selective surgeries via standard approaches. There were no complications after burr-hole surgery. CONCLUSION: Selective amygdaloghippocampectomy is not inferior to anteromedial lobectomy. Moreover, this procedure is associated with a lower risk of complications and adverse events.

[Productive mental disorders in post-traumatic disturbances of consciousness].

Productive mental disorders (PMD) are the result of pathological mental activity. Alongside with deficient disorders PMD are the main characteristics of post-traumatic disturbances of consciousness. PMD can be represented by different types of excitation, mistaken judgments (including paranoidal ones, confabulations, false orientation), false perception (psychosensory, in particular, illusory and hallucinatory phenomena) and affective disorders. Occurrence and signs of PMD were studied in 417 patients with brain injuries and their consequences. It was found that occurrence of PMD in clear consciousness (in form of delirium, confusion etc) is often a sign of deterioration of cerebral and/or somatic situation and requires urgent diagnostic and therapeutic measures. In another situation with PMD being revealed during emergence from coma, they are regarded as a prognostically favorable sign and require some correction only in case of long-term (more than 1-3 weeks) course. It was determined that PMD are characterized by: (a) a gradual (after emergence from unconsciousness) aggravation and complications of clinical symptoms till achieved orientation in the surroundings with their possible partial or complete regress; (b) the highest frequency and intensity with prevailed signs of dysfunction of any of cerebral hemispheres and the lowest frequency in case of relatively symmetric bilateral and profound brain damage; b) a great variety and severity in adult patients (compared with children and elderly). Irritation of different brain structures and their disconnection as well as pathological neuroplasticity in prolonged forms--are considered the basis for PMD occurrence.

[The evidence-based neurointensive care: what's next?].

The work is devoted to the analysis of modern trends of process of cognition in neurointensive care. In particular, considered the emergence and development of the method of "evidence-based medicine" in the treatment of patients with diseases and injuries of the brain. Demonstrated the positive features of the method. However, the authors are focused on the limitations of evidence-based approach, the main of which are the lack of an individualized treatment plan and the paucity of information obtained from materials of randomized controlled trials. The authors propose to combine the "evidence" data and the "classical style" of treatment, which involves individual clinical judgment based on knowledge of the pathophysiology and pathomorphology, intelligent use of technology, retrospective analysis of the beneficial and adverse effects of certain methods, creation of a special data bank of "natural" course of events, the development of individual prognostic model. The authors believe that the use of standards is more appropriate during acute illness and trauma, and the classic style is better for chronic situation.

[Neurotransmitter basis of consciousness and uncosciousness states].

Plenty of different studies are dedicated to consciousness recovery problem, such as neuroanatomical, neurophysiological, neuropsychiatric, neurosurgical, neurological points of view. However, neurotransmitter dysfunction is one of the main difficulties for consciousness and other neurological functions recovery after brain trauma. There are a lot of pharmacological agents modulating brain neurotransmitter activity, but no one precise clinical indication. So, the neurotransmitter mechanisms of consciousness recovery in patients with brain pathologies are very actual for studying with updating methods. This review concerns to the current understanding of unconsciousness, neuroanatomical and neurotransmitter bases of the last one.

[EEG-correlates of consciousness recovery after traumatic brain injury].

The aim of studies of patients in long-term posttraumatic unconscious state (PUS) was to outline prognostically significant EEG-markers of consciousness condition and an assessment of its dynamics orientation. We analysed outcomes of dynamic (from days to 16 years after trauma) EEG studies in 196 patients in TBI-caused PUS and different degrees of mental recovery: from chronic unconscious state up to clear consciousness. These results were compared to clinical protocols and data of MRI. It is revealed that dynamic features of EEC pattern (with the analysis of equivalent dipolar sources of separate components) allow to characterize the severity of patient's current state, to reveal the brain structures with the most expressed dysfunction, to define a zone of local cortical damage, and also the general direction of development of a traumatic illness (as though dynamics of a homeostasis of a brain). Frequency characteristics of EEG power spectrum (average frequency--an effective frequency strip) in a background and at reactions find the greatest predictive importance, especially at their assessment in 2-3 months after a trauma. The background interhemispheric EEG coherence (first of all, frontal) as the integrative characteristic of system brain activity, and its change at reactions to external incentives most reflect degree of consciousness oppression, dynamics and potential of its restoration. It was shown the high informational of the researches EEG changes to indifferent and functionally significant signs for an assessment of CNS functionality, and also of PUS pathogenesis.

[Neuroanatomical basis for traumatic coma: clinical and magnetic resonance correlates].

In this paper, the relationship between brain lesion localization (verified by magnetic resonance imaging (MRI)) and the severity of traumatic brain injury (TBI) and its outcomes is presented. Magnetic resonance studies in different modes (T1, T2, FLAIR, DWI, DTI, T2 * GRE, SWAN) were performed in 162 patients with acute TBI. Statistical analysis was done using Statistica 6, 8 software and R programming language. A new advanced MRI-based classification of TBI was introduced implying the assessment of hemispheric and brainstem traumatic lesions level and localization. Statistically significant correlations were found between the Glasgow coma and outcome scales scores (p < 0.001), and the proposed MRI grading scale scores, which means a high prognostic value of the new classification. The knowledge of injured brain microanatomy coming from sensitive neuroimaging, in conjunction with the assessment of mechanisms, aggravating factors and clinical manifestation of brain trauma is the basis for the actual predictive model of TBI. The proposed advanced MRI classification contributes to this concept development.

[Prognostic value of ICP, CPP and regional blood flow monitoring in diffuse and focal traumatic cerebral lesions].

Forty patients with severe traumatic brain injury (GCS score 8 and less) aged 16-54 years treated in our clinic were analyzed. Correlations between clinical symptoms, CT signs of diffuse and focal traumatic lesions, intracranial hemorrhage, indices of cerebral blood flow (CBF) according to perfusion CT study, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were assessed. Main mechanism of injury in 27 of 40 (67.5%) patients was acceleration-deceleration due to traffic accidents which usually leads to diffuse axonal injury (DAI) of different severity. In the other 13 (32.5%) cases injury was associated with coup-countercoup mechanism which caused focal contusions mostly. Not only GCS score but CT-signs of DAI severity, intracranial hemorrhage and minimal levels of CPP had significant prognostic value. Results of perfusion CT studies demonstrated that in 37 of 40 (92.5%) patients cerebral blood flow decreased (below 28.6 ml/100 g/min) in one or more arterial blood distribution areas. Increase of CBF was registered in 9 cases (over 69 ml/100 g/min), in 6 of them elevation of CBF in one arterial distribution area was associated with reduction in the other. Generally, mean CBF values were higher in the middle cerebral artery circulation than in the other. The lowest CBF levels (16.3 +/- 6 ml/100 g/min) were observed in cortical and subcortical hemorrhagic foci while these values were significantly higher in the same contralateral intact zones (36.0 +/- 10.0 ml/100 g/min; p < 0.01). In 3 patients with DAI the CBF in the midbrain varied from 12.5 to 30.1 ml/100 g/min with the lowest levels in hemorrhagic focus in cerebral peduncle. It corresponded to cystic-atrophic alterations found on subsequent follow-up MRI. Thus, reduction of CBF and episodes of low CPP were the leading pathophysiological phenomena of diffuse and focal brain damages.

[Long-latency components (N100, N200 and P300) of acoustic evoked potentials in prediction of mental recovery in severe traumatic brain injury].

The authors analyzed correlations of amplitude and latency levels of N100, N200 and P300 components of acoustic evoked potentials (AEP) registered during sonic stimulation and counting of target-oriented stimuli in 22 patients in vegetative state and mutism as an outcome of traumatic brain injury. Results were analyzed with association of electrophysiological findings with data of diffusion-tensor MRI. 55 healthy volunteers were included into control group. It is described that patients in vegetative state with formal recovery to the level of clear consciousness develop all three components of AEP in response to target-oriented tone. The instruction "to counts" leads to their better development. Patients with restoration to minimal level of consciousness produce all components during audition of sounds and only N100 and N200 in response to standard tone after instruction "to count". It is discovered that levels of amplitude have bigger correlation according to Spearman's criterion with outcome in comparison to latency. There changes are more prominent in N100 and N200 components rather in P300. In addition, after instruction "to count sounds" the registered changes between stages of vegetative state and mutism are significant for leads of left hemisphere, and during audition of sounds--for sagittal leads. The study showed correspondence of acquired changes with MRI data. Chronic unconscious state is associated with changes in corpus callosum (degeneration fibers) and corticospinal tracts in the brainstem. The data are discussed in light of hypothesis of the role of morphofunctional disconnections (brainstem-thalamus and interhemispheric) in impairment of attention and in genesis of different forms of posttraumatic unconscious state.

[Dynamic assessment of corpus callosum and corticospinal tracts structure using diffusion-tensor MRI in diffuse axonal injury].

BACKGROUND: Diffuse axonal injury (DAI) causes neurodegenerative processes in brain which can last weeks and months after traumatic brain injury. Aim of this study was to assess structural changes of corpus callosum and corticospinal tracts in dynamics using diffusion-tensor magnetic resonance imaging (DT-MRI) in severe DAI. MATERIALS AND METHODS: 14 patients with severe DAI (GCS < or = 8 in acute period) were examined using DT-MRI. In 12 cases 1.5 Tesla device was used, in 2-3 Tesla tomography was applied. Initial studies were performed on 3rd-17th days after injury and control studies were done between 3 weeks and 33 months after injury. Outcomes were assessed using GOS 6 months after injury and later. RESULTS: MR-tractography demonstrated almost absolutely absent visualization of ascending fibers of corpus callosum 3-20 weeks after brain injury in 5 patients with poor outcomes (severe disability and persistent vegetative state). Raized asymmetry of corticospinal tracts was associated with hemiparesis or quadriparesis in the same patients. In 6 patients with severe disability partial loss and thinning of corpus callosum fibers were observed. In 2 patients with good recovery and moderate disability repeated studies showed no severe changes in structure of corpus callosum. CONCLUSION: DT-MRI presents new data about structural changes of white matter tracts in traumatic brain injury.

[Dynamics of P300 component of acoustic evoked potential in postraumatic unconsciousness].

In order to reveal features of the brain reactions to external stimuli in the course of consciousness recovery after a severe craniocerebral injury, component P300 of acoustic evoked potential was analyzed in 9 patients with chronic and 32 patients with reversible unconsciousness. In patients with chronic unconsciousness, P300 parameters displayed a linear correlation with the current functional state. However, this component remained significantly different from its normal shape and varied only in a narrow range. In patients with reversible unconsciousness, time course of changes in amplitude and latency between recovery stages was of linear character with a tendency to normalization. The findings suggest that, in reversible unconsciousness states, processing of sensory information at different recovery stages may be performed with various functional systems that determine varying quality of processing, whereas changes in chronic unconsciousness are caused by a decrease in the number of active elements within the same functional system.

[Clinical/encephalographic syndrome of dopamine deficiency in patients with depressed consciousness after severe brain injury].

OBJECTIVE: To determine electroencephalographic signs of dopamine deficiency syndrome during the recovery after severe brain injury (SBI). MATERIAL AND METHODS: We studied 35 patients with SBI (23 men and 12 women, mean age 29 ± 13 years). RESULTS AND CONCLUSION: We identified a set of neurological symptoms (increased muscular tone of extrapyramidal type, rest tremor, autonomic disorders, which were most characteristic of the autonomic state, and some forms of mutism associated, according to current conceptions, with the dopaminergic system deficiency syndrome. This clinical picture was accompanied by stable EEG changes: an increase in the severity of beta activity of 13-14 Hz, enhanced in the frontal and anterior temporal areas, synchronized with equivalent dipole source localization in subcortical and frontal/basal areas. Dopamine deficiency regression syndrome was accompanied by an increase in beta EEG activity (from 13 to 16 Hz), but with the persistent abnormal enhancement of coherent hemispheric relations, especially in the occipital-temporal areas.

Characteristics of brain bioelectrical activity in post-traumatic Korsakov's syndrome.

A total of 32 patients (21 with reversible and 11 with chronic Korsakov's syndrome of traumatic origin) and 20 healthy controls were studied. Visual and spectral coherence analysis was applied to EEG recordings and the three-dimensional localization of equivalent dipole sources of beta1 activity in the frequency range 13-20 Hz. Stable increases in the coherence of EEG beta1 activity generated by a limited number of sources (mostly frontobasal and brainstem locations) had negative prognostic significance in Korsakov's syndrome. Comparison with clinical data allow this EEG phenomenon to be linked to the inhibitory state of the corresponding cortical zones.

[The P300 component of the auditory evoked potential in the posttraumatic vegetative state]. / Komponent P300 akusticheskogo vyzvannogo potentsiala v posttravmaticheskom vegetativnom sostoianii.

The dynamic studies of P300 component of the acoustic evoked potential were conducted in 12 patients in posttraumatic state of the autonomic system. The amplitude and time parameters of P300 were analyzed, its spatial distribution over the cortex, and features of generation. The obtained results were compared with the normative data. Significant changes in P300 in comparison with the normal characteristics were revealed in patients with the absence of conscious mental activity. These changes were maximally expressed when the state of patients was irreversible. In case of patients' outcome from the studied state the amplitude-temporal and topographic response characteristics tended to normalization but did not reach it completely. The obtained results allow us to consider the P300 component as one of the most informative indices in consciousness recovery after severe brain injury.

[The effect of shunting operations on the psychopathological symptoms of posttraumatic hydrocephalus]. / Vliianie shuntiruiushchikh operatsii na psikhopatologicheskuiu simptomatiku posttravmaticheskoi gidrotsefalii.

A total number of 35 patients underwent CSF diversion procedures for posttraumatic hydrocephalus (HCP). To facilitate the analysis of correlation between the onset and clinical course of HCP and psychopathology, all patients were divided into 2 groups. Group 1 consisted of patients who developed HCP within the first 6 months after head injury interfering with the psychiatric recovery. Group 2 was formed by patients who developed HCP after being stable for more than 6 months after injury and having some sort of psychiatric condition (e.g., vegetable status, dementia) before HCP was evident. We considered surgery to be effective if patients had signs of postoperative psychiatric improvement. This was demonstrated in 68.8% of the cases. Mental changes were more prominent in Group 1 vs Group 2. Worsening of the condition was noted only in six patients, all from the second group. It was transient in 4 cases and progressive in 2 cases. All complications occurred due to intracranial infections.

[The age-related factor in the pathology of consciousness in craniocerebral trauma]. / Vozrastnoi faktor v patologii soznaniia pri cherepno-mozgovoi travme.

In children (n = 103), elderly and old persons (n = 42), abnormal consciousness was comparatively studied in the acute period of brain injury. The revealed clinical features were compared with the previously described syndromes of consciousness disorders in young and middle-aged patients. The authors consider it appropriate to identify quantitative (deafening, sopor, coma) and qualitative (obscure consciousness, confusion, and mixed types differing in the ratio of productive to deficiency symptoms). Depressed consciousness was found to be prevalent in children, obscure consciousness was most typical in adults, confusion was common in elderly and old patients. The low presentation of productive disorders and their low association mainly with brain injury in patients who are on the different poles of ontogenesis are explained in the context of the teaching of cerebral functional asymmetry.

[Visual evoked potentials and the P300 component in different courses of the posttraumatic vegetative state]. / Zritel'nye vyzvannye potentsialy i komponent P300 pri raznom techenii posttravmaticheskogo vegetativnogo sostoianiia.

The late latency components of visual evoked potentials (VEP) and the component P300 AEP were analyzed to evaluate their informative value in the process of mental function restoration in patient after long-term traumatic coma. VEP components with latencies of 70 to 320 msec were studied in 24 patients. Topographical mapping of the power of the study VEP components and components P300 was made by the peak amplitude. Long-term VEP components and component P300 were examined by the method of three-dimensional localization of equivalent dipole sources. In 16 patients with positive tendencies in the condition there was a stable localization of the maximum VEP power in the parietal, sagittal, and occipital regions, component P300 showed its maximum amplitude in the central and parietal regions in the left hemisphere. Eight patients with negative tendencies in the status had the maximum VEP and component P300 in the frontal and temporal regions, predominantly in the right hemisphere. The paper shows it important to evaluate not only time-amplitude parameters and analyzes the tomographic features of its formation in dynamics.

[An epileptic syndrome in patients with the sequelae of gunshot craniocerebral wounds]. / Epilepticheskii sindrom u bol'nykh s posledstviiami ognestrel'nykh cherepno-mozgovykh ranenii.

To study the specific features of the epileptic syndrome after present-day gunshot cranial wounds (GCW), as well as risk factors of its occurrence, 56 victims were examined prospectively (within at least a year after their admission). The epileptic syndrome developed in 18 (32.1%) patients within 1 to 15 months following GCW; there were prevalent generalized convulsive (in 13 of the 18 patients) and focal (in 12 of the 18 ones) seizures. One type of seizures was noted in 7 patients, two or three ones were in 11. The polymorphism of seizures and a disparity of their psychopathological structure to the side of brain lesion were typical for left-handers. As compared to other patients, epileptics were more commonly found to have: 1) frontoparietal lesion; 2) multiple bony defects of the vault of the skull; 3) enlargement of the lateral ventricle of the brain on CT scans; 4) primary coma for > 2 hours and other depressed consciousness syndromes for > 1 day; 5) signs of left-handedness. The findings suggest that there is a need for studies of the functional asymmetry of the brain to gain a better insight into the problem.

[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.

[Clinical and electroencephalographic effects of amantadine sulfate (PK-Merz) on consciousness disorders due to the severe traumatic brain injury].

It was carried out a complex clinical-neurological and electroencephalographic study of 12 patients with consequences of severe traumatic brain injury with changes in consciousness, motor deficit, higher tonus of voluntary muscles and cognitive disorders. The study was conducted before, during and after treatment with amantadine sulfate. There were correlations between changes in mental and neurological status of patients and basic EEG.