[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[Mathematical analysis of EEG in consciousness recovery after traumatic brain injuries].

The clinical and EEG study of 20 patients with post-comatose consciousness disturbances caused by severe traumatic brain injuries (9 patients with autonomic state and 11 with Korsakoff syndrome), applying a statistical method of analysis of EEG spectrum and coherent connections developed by the authors, has revealed pathological features of the EEG interhemispheric connections. Patients with consciousness disturbances exhibited (1) total functional disconnections of hemispheres which was characteristic of the autonomic state and (2) disconnection in frontal areas of the brain in patients with Korsakoff syndrome as compared to the normal spatial distribution of coherence observed in 40 healthy people. Consciousness recovery has been accompanied by interhemispheric connections normalization, at first in the posterior regions of the hemispheres and then in the anterior ones as well as by transforming of coherence profile in the shape of "envelope" being most typical for the normal pattern of coherence distributation.

[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.

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.