[Metabolic disorders of chronically critically ill patients caused by consequences of traumatic brain injury].

The problem of chronic critical illness therapy is relevant all over the world. Revealing the metabolic function in patients in chronic critical condition is an important link in the development of adequate treatment and rehabilitation tactics. The aim - identification of metabolic features in chronic critical patients after brain injury in the first 3 days from the moment of admission to the rehabilitation center. Material and methods. Single-center observational study included a group of 25 patients with chronic critical illness, aged 38.7±14.0 years with body mass index 20.8± 4.3 kg/m2 (min 14.5; max 29.7), who were on independent breathing through a tracheostomy tube, and who have pronounced neurological disorders in the form of depression of minimally conscious state, FOUR scale from 12 to 16 points, as well as bedsores 1-2 stage and polysegmental pneumonia. The patients underwent indirect calorimetry and analysis of biochemical parameters of protein, carbohydrate, fat and mineral metabolism, as well as the level of nitrogen excretion with urine. Results and discussion. The data obtained indicate that chronic critical ill patients with the consequences of traumatic brain injury had pronounced metabolic disorders, mainly of a protein component. Total protein level decreased up to 61.0±9.4 g/l (min 39.1; max 83.1), albumin up to 30.2±6.0 g/l (min 17.4; max 37.8), prealbumin up to 0.13± 0.06 g/l (min 0.04; max 0.23) and transferrin up to 147.7±37.7 mg/dl (min 84.0; max 209.0). The patients' requirement in protein was 106.4±38.5 g/day (min 57.1; max 160.5) or 1.55±0.46 g/kg/day (min 0.75; max 2.22). The level of resting energy expenditure measured by indirect calorimetry was 1549.1±421.8 kcal/day (min 673.0; max 2430.0) or in terms of body weight 24.8±7.6 kcal/kg/day (min 12.4; max 45.8). Conclusion. The data obtained indicate a continuing catabolic phase in patients more than 30 days after the primary injury, which led to their chronic critical condition.

Transcranial parenchymal sonography in patients with Chronic Disorders of Consciousness: Association with neuroimaging data, and beyond.

Differential diagnosis of patients with Chronic Disorders of Consciousness (DoC) is rather challenging, owing to the lack of objective approaches highlighting residual awareness. Sophisticated functional neuroimaging have provided high diagnostic value, but their application in the clinical setting is limited due to their relative complexity, cost, availability and poor collaboration of persons with DoC. By using a specific ultrasound-based methodology, namely Transcranial B-mode Parenchymal Sonography (TCS), it is possible to obtain images of the main parenchymal brain structures. We assessed the TCS abnormalities in three patients with DoC, demonstrating widespread alterations of brain parenchyma morphology that matched to MRI findings and were associated with the degree of consciousness disorders. Thus, TCS might represent a valuable tool for routine assessment and follow-up of brain structures functioning of patients with DoC, potentially helping in differential diagnosis and prognosis.

Could autonomic system assessment be helpful in disorders of consciousness diagnosis? A neurophysiological study.

Although patients with chronic disorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), show a limited repertoire of awareness signs, owing to a large-scale cortico-thalamo-cortical functional disconnectivity, an activation of some cortical areas in response to relevant stimuli has been described by means of electrophysiological and functional neuroimaging approaches. In addition, cognitive processes associated with autonomic nervous system (ANS) responses elicited by nociceptive stimuli have been identified in some DOC patients. In an attempt to identify ANS functionality markers that could be useful in differentiating UWS and MCS individuals, we measured the amplitude, latency and γ-band power (γPOW) of ultra-late laser-evoked potentials (CLEPs) and skin reflex (SR), which both express some aspects of cognitive processes related to ANS functionality, besides other ANS parameters either during a 24(hh)-polygraphy or following a solid-state laser repetitive nociceptive stimulation. MCS showed physiological modification of vital signs (O2 saturation, hearth rate, hearth rate variability) throughout the night and a preservation of SR-γPOW, whereas UWS did not show significant variations. Following repetitive nociceptive stimulation, MCS patients had a significant increase in CLEP-γPOW, O2 saturation, hearth rate, and hearth rate variability, whereas UWS individuals did not show any significant change (but two patients, who reached high Coma Recovery Scale-Revised scores). Hence, our work suggests that a wide-spectrum electrophysiological evaluation of ANS functionality may support DOC differential diagnosis. Interestingly, the two above-mentioned UWS patients showed MCS-like vital sign modifications and electrophysiological pain responsiveness. It is therefore hypothesizable that our approach could be helpful in identifying residual aware autonomic system-related cognitive processes even in some UWS patients. Such issue draws the attention to either DOC clinical diagnosis or adequate pain treatment in DOC patients.

Posttraumatic epilepsy in chronic disorders of consciousness due to severe traumatic brain injury after traffic accidents.

PURPOSE: To evaluate the clinical state of posttraumatic epilepsy (PTE) in patients with chronic disorders of consciousness (CDC) due to severe traumatic brain injury (STBI) after traffic accidents and clarify the risk factors for seizure occurrence in such patients. METHODS: Two hundred ninety-three patients with CDC due to STBI (mean age at admission [±standard deviation]: 36.4 ± 17.9 years; men: 71.7 %; mean duration of injury to admission: 416 ± 732 days; mean hospitalization time: 899 ± 319 days) were enrolled in this study. We retrospectively investigated the relationship between seizure conditions (type and frequency) and clinical data, including age, sex, pathological types of brain injury, with/without surgical intervention, degree of CDC, and administration of antiseizure medications (ASMs). RESULTS: Overall, 52.9 % (n = 155/293) and 64.2 % of the patients (n = 183/of 285 patients surviving at discharge) were administered ASMs at admission and discharge, respectively. One hundred thirty-two patients (45.1 %) experienced epileptic seizures during hospitalization, and the mean seizure frequency was 4.0 ± 0.4 times per year. In multivariate analysis, significant and independent risk factors of seizure occurrence were revealed to be male sex, high National Agency for Automotive Safety and Victims' Aid score, hypoxic encephalopathy, and history of the neurosurgical operations. CONCLUSION: The high prevalence of PTE in patients with CDC due to STBI, and the significant and independent risk factors for seizure occurrence in the chronic clinical phase were revealed. We expect that this study will aid toward improving clinical assessment and management of epileptic seizures in the population.

Clinical Outcome After Epidural Spinal Cord Stimulation in Patients With Severe Traumatic Brain Injury.

INTRODUCTION:  Epidural spinal cord stimulation is a minimally invasive procedure with a growing list of indications. It has a good safety profile and analgesic effect, reduces the severity of spasticity, and activates various brain regions. The purpose of this study is to evaluate the clinical outcome of epidural spinal cord stimulation in patients with spastic syndrome and chronic disorders of consciousness resulting from severe traumatic brain injury (sTBI). METHODS: Between 2021 and 2023, an epidural spinal cord stimulation test was performed in 34 patients with central paresis, severe hypertonia, and chronically altered consciousness following sTBI. The severity of spastic syndrome was assessed using a modified Ashworth scale. All patients underwent implantation of a cylindrical eight-contact test epidural electrode at C3-C5 cervical level, followed by neurostimulation and selection of individual modes. Tonic stimulation at a frequency of 60 Hz, "burst" mode, or a combination of the two was used. RESULTS:  Epidural spinal cord stimulation was administered for an average of 4 ± 1.5 days, with tonic stimulation mode applied in 15 (44.1%) patients, "burst" mode in 10 (29.4%), and a combination of two in nine (26.5%) patients. A reduction in spasticity with clinical improvement was observed in 21 patients (61.8%). The Ashworth scale scores for distal and proximal upper extremities decreased from 3 points to 2.5 points and from 3 points to 2 points, respectively. This was significant in the right upper limbs (p = 0.0152 distally and p = 0.0164 proximally). Significant improvements were also seen in the lower extremities. Active movements in paretic limbs increased or appeared in 12 patients (35.3%), while a heightened level of consciousness was observed in six patients (17.6%). Permanent neurostimulator implantation was performed in 12 patients (35.3%), with no reported surgical complications. CONCLUSION:  Epidural spinal cord stimulation shows promise as an invasive rehabilitation method for patients with sTBI sequelae. Its use reduced the severity of spastic syndrome in over half of patients and increased active movements in paretic limbs in over a third. Notably, neuromodulation at the cervical level yielded pronounced effects on the upper extremities, both proximally and distally. Findings regarding consciousness level improvement are particularly intriguing but warrant further validation through randomized trials.

Brainstem volume, diffusion, and metabolism are associated with chronic consciousness disorders after traumatic brain injury.

BACKGROUND AND PURPOSE: We aimed to identify reliable neuroradiological features of the brainstem reflecting the neurological symptoms of patients with chronic disorders of consciousness (DOCs) due to severe traumatic brain injury (TBI). METHODS: We retrospectively examined 86 patients with chronic DOCs due to severe TBI caused by automobile accidents. We studied the relationships among (1) neurological symptoms, including consciousness level, (2) integrated cognitive/physical condition, and (3) neuroradiological features of the brainstem (brainstem volume on MRI, fractional anisotropy [FA] value in the brainstem, and standardized uptake value [SUV] of 18F-fluorodeoxyglucose [FDG] on positron emission tomography in the brainstem). RESULTS: Brainstem volume was significantly larger and FA values were significantly higher in patients with a better level of consciousness. However, brainstem volumes were significantly decreased and the maximum SUV (SUVmax ) of FDG significantly increased at 2 years following admission regardless of the level of consciousness at admission. The brainstem volume was significantly larger and the FA value and SUVmax of FDG were significantly higher in patients with better National Agency for Automotive Safety and Victims' Aid (NASVA) scores at admission. The decrease in the brainstem volume was significantly minimized and the SUVmax of FDG significantly increased in patients with more improvement in the NASVA score 2 years after admission. CONCLUSIONS: The volume, FA value, and SUVmax of FDG of the brainstem are important neuroradiological features associated with the neurological conditions of patients with chronic DOCs due to severe TBI.

Metabolic Abnormalities in Patients with Chronic Disorders of Consciousness.

The vegetative state (VS) and minimally conscious state (MCS) are two major types of chronic disorders of consciousness (DoC). The assessment of these two consciousness states generally relies on the Coma Recovery Scale-Revised (CRS-R) score, but a high misdiagnosis rate limits the generalized use of this score. To identify metabolites in human plasma that can accurately distinguish VS from MCS patients, comprehensive plasma metabolic profiles were obtained with targeted metabolomics analysis and untargeted and targeted lipidomics analysis. Univariate and multivariate analyses were used to assess the significance of differences. Compared with healthy controls (HCs), the DoC groups, Emerged from Minimally Conscious State (EMCS) group and Alzheimer's disease (AD) group had significantly different metabolic profiles. Purine metabolism pathway differed the most between the DoC (MCS and VS) and HC groups. In this pathway, adenosine, ADP, and AMP, which are the derived products of ATP degradation, were decreased in the MCS and VS groups compared to healthy controls. More importantly, we identified certain lipids for which the levels were enriched in the VS or MCS groups. Specifically, phosphatidylcholine, (38:5)-H (PC(38:5)-H), and arachidonic acid (AA) differed substantially between the VS and MCS groups and may be used to distinguish these two groups of patients. Together, our findings suggest that metabolic profiling is significantly altered in patients with chronic DoC.

The experience of family caregivers caring for a patient with chronic disorders of consciousness: a qualitative content analysis.

BACKGROUND: Management of a patient with chronic disorders of consciousness is a long-term and stressful situation for family caregivers. AIMS: The aim of this study was to describe the experiences of family caregivers of patients with chronic disorders of consciousness. METHODS: Purposeful sampling was used, data were collected through semi-structured, in-depth interviews at participants' homes. Data were analysed using qualitative content analysis. FINDINGS: Results indicated that family caregivers of patients with chronic disorders of consciousness face many difficulties in providing care to vegetative state (VS) and minimally conscious state (MCS) patients; they experience it as a challenging type of care, which influences their mental health. CONCLUSION: Family caregivers are faced with many challenges because of the high burden of care, round-the-clock concern, taking care of an alive but unresponsive patient without receiving enough support. They experience mental and inner turmoil because of social isolation and dealing with contradictory feelings in their daily life.

[Results of treatment with intravenous amantadine sulfate (PK-Merz) patients with chronic disorders of consciousness]. / Rezul'taty primeneniya amantadina sul'fata (PK-Merts) u patsientov s khronicheskim narusheniem soznaniya.

The article presents literature review of the recent publications devoted to the drugs with dopaminergic, antiglutamatergic and GABA-ergic effects in the treatment of patients with vegetative state/areactive wakefulness syndrome (VS/AWS). The authors analyzed their own results of the effects of intravenous form of amantadine sulfate (PK Merz) in 142 VS/AWS patients caused by different etiological factors. Depending on the dominant neurological symptoms, patients were divided into three main groups: areactive type of course (group 1 - 61 patients), predominance of primitive limbic reactions (group 2 - 35 patients) and predominance of extrapyramidal symptoms (group 3 - 46 patients). Therapy results were evaluated one month later by CRS-R scale, which showed that the most distinct positive dynamics was observed in group 3.

Towards New Diagnostic Approaches in Disorders of Consciousness: A Proof of Concept Study on the Promising Use of Imagery Visuomotor Task.

BACKGROUND: advanced paraclinical approaches using functional neuroimaging and electroencephalography (EEG) allow identifying patients who are covertly aware despite being diagnosed as unresponsive wakefulness syndrome (UWS). Bedside detection of covert awareness employing motor imagery tasks (MI), which is a universally accepted clinical indicator of awareness in the absence of overt behavior, may miss some of these patients, as they could still have a certain level of awareness. We aimed at assessing covert awareness in patients with UWS using a visuomotor-guided motor imagery task (VMI) during EEG recording. METHODS: nine patients in a minimally conscious state (MCS), 11 patients in a UWS, and 15 healthy individuals (control group-CG) were provided with an VMI (imagine dancing while watching a group dance video to command), a simple-MI (imagine squeezing their right hand to command), and an advanced-MI (imagine dancing without watching a group dance video to command) to detect command-following. We analyzed the command-specific EEG responses (event-related synchronization/desynchronization-ERS/ERD) of each patient, assessing whether these responses were appropriate, consistent, and statistically similar to those elicited in the CG, as reliable markers of motor imagery. RESULTS: All patients in MCS, all healthy individuals and one patient in UWS repeatedly and reliably generated appropriate EEG responses to distinct commands of motor imagery with a classification accuracy of 60-80%. CONCLUSIONS: VMI outperformed significantly MI tasks. Therefore, patients in UWS may be still misdiagnosed despite a rigorous clinical assessment and an appropriate MI assessment. It is thus possible to suggest that motor imagery tasks should be delivered to patients with chronic disorders of consciousness in visuomotor-aided modality (also in the rehabilitation setting) to greatly entrain patient's participation. In this regard, the EEG approach we described has the clear advantage of being cheap, portable, widely available, and objective. It may be thus considered as, at least, a screening tool to identify the patients who deserve further, advanced paraclinical approaches.

Feasibility of Non-Gaussian Diffusion Metrics in Chronic Disorders of Consciousness.

Diagnostic accuracy of different chronic disorders of consciousness (DOC) can be affected by the false negative errors in up to 40% cases. In the present study, we aimed to investigate the feasibility of a non-Gaussian diffusion approach in chronic DOC and to estimate a sensitivity of diffusion kurtosis imaging (DKI) metrics for the differentiation of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) from a healthy brain state. We acquired diffusion MRI data from 18 patients in chronic DOC (11 VS/UWS, 7 MCS) and 14 healthy controls. A quantitative comparison of the diffusion metrics for grey (GM) and white (WM) matter between the controls and patient group showed a significant (p < 0.05) difference in supratentorial WM and GM for all evaluated diffusion metrics, as well as for brainstem, corpus callosum, and thalamus. An intra-subject VS/UWS and MCS group comparison showed only kurtosis metrics and fractional anisotropy differences using tract-based spatial statistics, owing mainly to macrostructural differences on most severely lesioned hemispheres. As a result, we demonstrated an ability of DKI metrics to localise and detect changes in both WM and GM and showed their capability in order to distinguish patients with a different level of consciousness.

Novel Approaches to the Diagnosis of Chronic Disorders of Consciousness: Detecting Peripersonal Space by Using Ultrasonics.

The assessment of behavioral responsiveness in patients suffering from chronic disorders of consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. Even if a patient is unresponsive, he/she may be covertly aware in reason of a cognitive-motor dissociation, i.e., a preservation of cognitive functions despite a solely reflexive behavioral responsiveness. The approach of an external stimulus to the peripersonal space (PPS) modifies some biological measures (e.g., hand-blink reflex amplitude) to the purpose of defensive responses from threats. Such modulation depends on a top-down control of subcortical neural circuits, which can be explored through changes in cerebral blood flow velocity (CBFV), using functional transcranial Doppler (fTCD) and, thus, gaining useful, indirect information on brain connectivity. These data may be used for the DoC differential diagnosis. We evaluated the changes in CBFV by measuring the pulsatility index (PI) in 21 patients with DoC (10 patients with MCS and 11 with UWS) and 25 healthy controls (HC) during a passive movement and motor imagery (MI) task in which the hand of the subject approached and, then, moved away from the subject's face. In the passive movement task, the PI increased progressively in the HCs when the hand was moved toward the face and, then, it decreased when the hand was removed from the face. The PI increased when the hand was moved toward the face in patients with DoC, but then, it remained high when the hand was removed from the face and up to 30 s after the end of the movement in the patients with MCS (both MCS+ and MCS-) and 1 min in those with UWS, thus differentiating between patients with MCS and UWS. In the MI task, all the HCs, three out of four patients with MCS+, and one out of six patients with MCS- showed an increase-decrease PI change, whereas the remaining patients with MCS and all the patients with UWS showed no PI changes. Even though there is the possibility that our findings will not be replicated in all patients with DoC, we propose fTCD as a rapid and very easy tool to differentiate between patients with MCS and UWS, by identifying residual top-down modulation processes from higher-order cortical areas to sensory-motor integration networks related to the PPS, when using passive movement tasks.

Conventional Structural Magnetic Resonance Imaging in Differentiating Chronic Disorders of Consciousness.

Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.

Complement cascade on severe traumatic brain injury patients at the chronic unconscious stage: implication for pathogenesis.

BACKGROUND: Patients who awake from severely traumatic brain injury (TBI) may remain unconscious for many years. Although behavioral assessment and functional imaging are currently used as diagnostic tools, the molecular basis underlying chronic condition has yet to be explored. METHOD: Plasma samples were obtained at 3 time points (1, 3 and 6 months) from 18 patients with chronic disorders of consciousness who survived severe TBI, and 6 healthy volunteers. A coupled isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics approach was used to screen differentially expressed proteins (DEPs) between patients and controls. Potential molecular mechanisms were further discussed through bioinformatics analyses. RESULT: In total, 300 plasma proteins <1% false discovery rates were identified and 32 proteins were consistently altered between patients and controls. Biological pathway analysis revealed that the DEPs were predominantly involved in complement cascade. CONCLUSIONS: This study discussed potential mechanisms of complement cascade underlying chronic stage in severe TBI.

How far can we go in chronic disorders of consciousness differential diagnosis? The use of neuromodulation in detecting internal and external awareness.

Awareness generation and modulation may depend on a balanced information integration and differentiation across default mode network (DMN) and external awareness networks (EAN). Neuromodulation approaches, capable of shaping information processing, may highlight residual network activities supporting awareness, which are not detectable through active paradigms, thus allowing to differentiate chronic disorders of consciousness (DoC). We studied aftereffects of repetitive transcranial magnetic stimulation (rTMS) by applying graph theory within canonical frequency bands to compare the markers of these networks in the electroencephalographic data from 20 patients with DoC. We found that patients' high-frequency networks suffered from a large-scale connectivity breakdown, paralleled by a local hyperconnectivity, whereas low-frequency networks showed a preserved but dysfunctional large-scale connectivity. There was a correlation between metrics and the behavioral awareness. Interestingly, two persons with UWS showed a residual rTMS-induced modulation of the functional correlations between the DMN and the EAN, as observed in patients with MCS. Hence, we may hypothesize that the patients with UWS who demonstrate evidence of residual DMN-EAN functional correlation may be misdiagnosed, given that such residual network correlations could support covert consciousness.

Moving Toward Conscious Pain Processing Detection in Chronic Disorders of Consciousness: Anterior Cingulate Cortex Neuromodulation.

UNLABELLED: It has been assumed that patients with chronic disorders of consciousness (DOC) do not feel pain, but it is possible that some of them just cannot report it. Modulation of γ-band oscillatory activity (γBO) in centroparietal areas (considered as a marker of either subjective pain perception processes or pain-related motor behavior preparation) by part of the anterior cingulate cortex (ACC) has been proposed to be suggestive of conscious pain perception and could therefore be used to assess the maintenance of some level of conscious pain perception in patients with DOC. Hence, we used a repetitive transcranial magnetic stimulation (rTMS) approach in an attempt to trigger frontoparietal output. We enrolled 10 healthy participants (HC), 10 patients in a minimally conscious state (MCS), and 10 with unresponsive wakefulness syndrome (UWS), who underwent a 1-Hz rTMS protocol over ACC. Before and after the neurostimulation paradigm, we measured the pain-rating assessment (pVAS), γBO, latency, and the amplitude of cortical nociceptive potentials evoked by transcutaneous electric sinusoidal stimuli (EEP). In all the HC and MCS and in 2 of the UWS subjects, rTMS increased γBO and reduced the EEP amplitude, whereas pVAS scoring improved in the HC. Our findings provide some evidence about conscious pain processing even in patients with severe DOC and show that rTMS over ACC may be a useful approach to better investigate the level of conscious impairment. PERSPECTIVE: Patients with DOC may not be able to respond to pain stimuli, although they may feel it. The possibility of detecting residual pain perceptions by means of a noninvasive neuromodulation paradigm, studying the correlation between the ACC and centroparietal γBO, may help clinicians to better assess pain in such individuals.