Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Cortical responses to auditory stimulation predict the prognosis of patients with disorders of consciousness.

OBJECTIVE: This study aimed to assess the prognosis of patients with disorders of consciousness (DoC) using auditory stimulation with electroencephalogram (EEG) recordings. METHODS: We enrolled 72 patients with DoC in the study, which involved subjecting patients to auditory stimulation while EEG responses were recorded. Coma Recovery Scale-Revised (CRS-R) scores and Glasgow Outcome Scale (GOS) were determined for each patient and followed up for three months. A frequency spectrum analysis was performed on the EEG recordings. Finally, the power spectral density (PSD) index was used to predict the prognosis of patients with DoC based on a support vector machine (SVM) model. RESULTS: Power spectral analyses revealed that the cortical response to auditory stimulation showed a decreasing trend with decreasing consciousness levels. Auditory stimulation-induced changes in absolute PSD at the delta and theta bands were positively correlated with the CRS-R and GOS scores. Furthermore, these cortical responses to auditory stimulation had a good ability to discriminate between good and poor prognoses of patients with DoC. CONCLUSIONS: Auditory stimulation-induced changes in the PSD were highly predictive of DoC outcomes. SIGNIFICANCE: Our findings showed that cortical responses to auditory stimulation may be an important electrophysiological indicator of prognosis in patients with DoC.

[Implementation of a pediatric unit of acquired brain injury in subacute phase in the public health system. Epidemiological, clinical and initial evolution characteristics of the patients attended]. / Implantación de una unidad pediátrica de daño cerebral adquirido en fase subaguda en el sistema público de salud. Características epidemiológicas, clínicas y de evolución inicial de los pacientes atendidos.

INTRODUCTION: Acquired brain injury (ABI) is defined as a neurological injury, acutely occurred, at some point in life causing impairment or loss of functional capacity. In 2019, a specific document was created by the Ombudsman pointing out the relevance of attention to this entity in the pediatric age. PATIENTS AND METHOD: The process of creation and the casuistry of care of one of the first comprehensive care units for subacute ACD in pediatric age within the public health system is presented. RESULTS: Different clinical guidelines have been prepared on the admission and care process within the unit, both for patients and their relatives. Twenty-four patients ≤18 years old, admitted to the subacute phase ACD unit from November 2019 to July 2021, 12 coming from the Community of Madrid, were attended. The median age was 6.97 years. Traumatic mechanism was the most frequent, with iatrogenic causes predominating, followed by precipitation and vehicle-related accidents. On admission to the unit, 8 maintained a minimally conscious/vegetative state. The collaboration of up to 14 different specialists was required due to the complexity of the patients. The overall evolution was favorable in 23 cases, with sequelae in all of them. CONCLUSION: The creation of units specialized in pediatric ACD care with specific action protocols and coordinated trans- and multidisciplinary work is of vital importance.

Clinical and neurophysiological effects of central thalamic deep brain stimulation in the minimally conscious state after severe brain injury.

Deep brain stimulation (DBS) of the central thalamus is an experimental treatment for restoration of impaired consciousness in patients with severe acquired brain injury. Previous results of experimental DBS are heterogeneous, but significant improvements in consciousness have been reported. However, the mechanism of action of DBS remains unknown. We used magnetoencephalography to study the direct effects of DBS of the central thalamus on oscillatory activity and functional connectivity throughout the brain in a patient with a prolonged minimally conscious state. Different DBS settings were used to improve consciousness, including two different stimulation frequencies (50 Hz and 130 Hz) with different effective volumes of tissue activation within the central thalamus. While both types of DBS resulted in a direct increase in arousal, we found that DBS with a lower frequency (50 Hz) and larger volume of tissue activation was associated with a stronger increase in functional connectivity and neural variability throughout the brain. Moreover, this form of DBS was associated with improvements in visual pursuit, a reduction in spasticity, and improvement of swallowing, eight years after loss of consciousness. However, after DBS, all neurophysiological markers remained significantly lower than in healthy controls and objective increases in consciousness remained limited. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of DBS of the central thalamus in humans and suggest that DBS can re-activate dormant functional brain networks, but that the severely injured stimulated brain still lacks the ability to serve cognitive demands.

Animal presence modulates frontal brain activity of patients in a minimally conscious state: A pilot study.

Integrating animals into therapy is applied increasingly in patients in a minimally conscious state (MCS). This pilot study investigates the effect of animal presence on frontal brain activity in MCS patients compared to healthy subjects. O2HB, HHb and tHb of two MCS patients and two healthy adults was measured in frontal cortex using functional near-infrared spectroscopy during three sessions with a live animal and three sessions with a mechanical toy animal present. Each session had five phases: (1) baseline, (2) watching animal, (3) passive contact, (4) active contact, (5) neutral. Data were descriptively analysed. All participants showed the largest hemodynamic response during direct contact with the live or toy animal compared to "baseline" and "watching." During active contact, three of the four participants showed a stronger response when stroking the live compared to the toy animal. All participants showed an inverted signal with higher HHb than O2Hb concentrations while stroking the live or toy animal. Animal contact leads to a neurovascular reaction in both MCS patients and healthy subjects, indicating elevated neural activity in the frontal cortex. We conclude that while a toy animal can elicit attention processes, active contact to a living animal is combined with emotional processes.

Neural correlates of consciousness and related disorders: From phenotypic descriptors of behavioral and relative consciousness to cortico-subcortical circuitry.

We report a review of medical aspects of the consciousness. The behavioral dimension, phenotypic descriptors, relative consciousness and neural correlates of consciousness and related disorders were addressed successively in a holistic and chronological approach. Consciousness is relative, specific to each individual across time and space. Historically defined as the perception of the self and the environment, it cannot be separated from behaviors, entailing an idea of conscious behavior with metapractic and metagnostic aspects. Observation of spontaneous and evoked overt behavior distinguishes three main types of disorder of consciousness (DoC): coma, vegetative state or unresponsive wakefulness, and minimally conscious or relationally impoverished state. Modern functional exploration techniques, such as imaging, increase the understanding of DoCs and consciousness. Whether consciousness is a superior function and/or an instrumental function is discussed. Neural correlates can be subdivided into two wakefulness pathways (superior thalamic cholinergic and inferior extra-thalamic), and cortico-subcortical circuitry. The deep brain structures are those described in the well-known sensorimotor, associative and limbic loops, as illustrated in the mesolimbic model of DoC. The cortices can be segregated into several overlapping networks: (1) a global workspace including thalamo-cortical loops; (2) the default mode network (DMN) and related intrinsic connectivity networks (i.e., central executive, medial DMN and salience networks); (3) a 3-fold network comprising the fronto-parietal control system and its dorsal and ventral attentional sub-networks, the fronto-parietal executive control network, and the cingulo-opercular salience network; (4) the internal and external cortices, respectively medial, turned toward the self, and lateral, turned toward the environment. The network dynamics is the reflection of consciousness, notably anticorrelations such as the decrease in activity of the posterior cingulate-precuneus regions during attentional tasks. Thanks to recent advances in DoC pathophysiology, further significative therapeutic progress is expected, taking into account the societal context. This depends notably on the dissemination of medical knowledge and its transfer to a wider public.

[Xingnao Kaiqiao acupuncture on promoting wake-up of vegetative state after brain injury].

OBJECTIVE: To observe the clinical effect of Xingnao Kaiqiao acupuncture on promoting wake-up of vegetative state after brain injury on the basis of comprehensive rehabilitation training. METHODS: A total of 100 patients with vegetative state after brain injury were randomly divided into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases). Both groups were treated with routine clinical treatment. The patients in the control group were treated with rehabilitation and hyperbaric oxygen; on the basis of the control group treatment, the patients in the observation group were treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Chize (LU 5), Weizhong (BL 40), Hegu (LI 4) and Taichong (LR 3). The acupuncture was given once a day, 5 days per week, for continuous 30 days. The Glasgow coma scale (GCS) and coma recovery scale-revised (CRS-R) scores were observed before treatment and 10, 20 and 30 days into treatment. The wake-up rate of the two groups was compared after treatment. RESULTS: On 10, 20 and 30 days into treatment, the GCS and CRS-R scores in the two groups were higher than those before treatment (P<0.01), and the scores in the observation group were higher than those in the control group (P<0.01). After treatment, the wake-up rate was 16.7% (8/48) in the observation group, which was higher than 12.0% (6/50) in the control group (P<0.01). CONCLUSION: On the basis of comprehensive rehabilitation and wake-up promotion therapy, the Xingnao Kaiqiao acupuncture could promote the recovery of consciousness level in patients with vegetative state after brain injury.

An action-observation/motor-imagery based approach to differentiate disorders of consciousness: what is beneath the tip of the iceberg?

BACKGROUND: The evaluation of motor imagery in persons with prolonged Disorders of Consciousness (pDOC) is a practical approach to differentiate between patients with Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) and to identify residual awareness even in individuals with UWS. Investigating the influence of motor observation on motor imagery could be helpful in this regard. OBJECTIVE: In order to corroborate the clinical diagnosis and identify misdiagnosed individuals, we used EEG recordings, to assess the influence of the low-level perceptual and motoric mechanisms on motor observation on motor imagery, taking into account the role of the high-level cognitive mechanisms in patients with pDOC. METHODS: We assessed the influence of motor observation of walking in first-person or third-person view (by a video provision) on motor imagery of walking in the first-person view on the visual N190 (expression of motor observation processing), the readiness potential (RP) (expressing motor preparation), and the P3 component (high-level cognitive processes) in a sample of 10 persons with MCS, 10 with UWS, and 10 healthy controls (CG). Specifically, the video showed a first-view or third-view walk down the street while the participants were asked to imagine a first-view walking down the street. RESULTS: CG showed greater N190 response (low-level sensorimotor processing) in the non-matching than in the matching condition. Conversely, the P3 and RP responses (high-level sensorimotor processing) were greater in the matching than in the non-matching condition. Remarkably, 6 out of 10 patients with MCS showed the preservation of both high- and low-level sensorimotor processing. One UWS patient showed responses similar to those six patients, suggesting a preservation of cognitively-mediated sensorimotor processing despite a detrimental motor preparation process. The remaining patients with MCS did not show diversified EEG responses, suggesting limited cognitive functioning. CONCLUSIONS: Our study suggests that identifying the low-level visual and high-level motor preparation processes in response to a simple influence of motor observation of motor imagery tasks potentially supports the clinical differential diagnosis of with MCS and UWS. This might help identify UWS patients which were misdiagnosed and who deserve more sophisticated diagnoses.

The treatment of integrated traditional Chinese and Western medicine to cure severe immune thrombocytopenia in a patient in a minimally conscious state: a case report.

Immune thrombocytopenia is a common complication in patients in a minimally conscious state (MCS). MCS patients are prone to pulmonary infection for the reasons of long-term bed rest and tracheotomy etc., which leads to frequent immune thrombocytopenia. At present, there is no specific treatment for immune thrombocytopenia. Moreover, the cost of routine treatment is high, and clinicians need to consider different drug combinations, side effects, and the risk of drug dependence when selecting treatments. Here, we report a case of a patient in a MCS who developed immune thrombocytopenia after tracheotomy and long-term bed laying in October 2015. The patient's platelet count declined continuously, and by December 2015, she was in a critical condition, with a platelet count of less than 20×109/L. The patient firstly received routine treatment, however, this could only temporarily prevent the drop in platelets. Following a series of explorations, the patient was treated with a combination of traditional Chinese and Western medicine, which included treatment and preventive measures. For treatment, the patient was given roxithromycin dispersible administration tablets and a self-made preparation of peanut red skin, which could quickly cure the immune thrombocytopenia. Preventive measures included the addition of ursodeoxycholic acid capsules, silybin capsules, and a traditional Chinese medicine preparation. As shown by laboratory examination results, the patient's platelet count has stayed around a normal level since March 2016, and she now has normal liver and kidney function. This outcome evidence that combined traditional Chinese and Western medicine could effectively cure immune thrombocytopenia and prevent its recurrence. Moreover, the cost of the treatment was lower and there were fewer side effects than routine treatment, and at the same time, the method of treatment was simple and convenient. Our practical experience may provide a valuable clue for the treatment of immune thrombocytopenia.

Assessing the state of consciousness for individual patients using complex, statistical stimuli.

Patients with prolonged disorders of consciousness (PDOC) are often unable to communicate their state of consciousness. Determining the latter is essential for the patient's care and prospects of recovery. Auditory stimulation in combination with neural recordings is a promising technique towards an objective assessment of conscious awareness. Here, we investigated the potential of complex, acoustic stimuli to elicit EEG responses suitable for classifying multiple subject groups, from unconscious to responding. We presented naturalistic auditory textures with unexpectedly changing statistics to human listeners. Awake, active listeners were asked to indicate the change by button press, while all other groups (awake passive, asleep, minimally conscious state (MCS), and unresponsive wakefulness syndrome (UWS)) listened passively. We quantified the evoked potential at stimulus onset and change in stimulus statistics, as well as the complexity of neural response during the change of stimulus statistics. On the group level, onset and change potentials classified patients and healthy controls successfully but failed to differentiate between the UWS and MCS groups. Conversely, the Lempel-Ziv complexity of the scalp-level potential allowed reliable differentiation between UWS and MCS even for individual subjects, when compared with the clinical assessment aligned to the EEG measurements. The accuracy appears to improve further when taking the latest available clinical diagnosis into account. In summary, EEG signal complexity during onset and changes in complex acoustic stimuli provides an objective criterion for distinguishing states of consciousness in clinical patients. These results suggest EEG-recordings as a cost-effective tool to choose appropriate treatments for non-responsive PDOC patients.

Effect of acupuncture method of removing-stasisand resuscitating on the consciousness of patients with severe traumatic brain injury: A randomized clinical trial.

INTRODUCTION: With the development of social economy, transportation and various infrastructures have also developed, but it has objectively increased the number of patients with head injury. Although the current craniocerebral medicine technology continues to advance, long-term bed rest and other complications have led to an insignificant decrease in the mortality rate of coma patients. It is not uncommon for patients with disturbance of consciousness caused by head injury in major hospitals. METHODS/DESIGN: This will be a retrospective, single-blind clinical observational study. We will select 50 cases that meet the subject's selection criteria. According to whether they received acupuncture treatment or not, they will be randomly divided into 2 groups, namely treatment group and control group. The control group will be given conventional Western medicine treatment, and the treatment group will be given acupuncture method of removing-stasis and resuscitating treatment on the basis of the control group. DISCUSSION: Our purpose is to observe the role of acupuncture method of removing-stasis and resuscitating in promoting the recovery of patients with severe head injury. We aim to provide more evidence-based medical evidence for acupuncture treatment of this disease. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000034732, Registered on 19 July 2020.

[From Vegetative State to Participation: Amantadine As a Trigger of the Rehabilitation Program]. / Do Estado Vegetativo à Participação: A Amantadina Como Potenciadora do Programa de Reabilitação.

The use of amantadine in clinical practice still seems limited, despite its increasing evidence in the emergence of vegetative state after traumatic brain injury. We describe the case of an adolescent with severe traumatic brain injury after being run over by a car. After four months of hospitalization in a Central Hospital where he remained in a vegetative state, he was transferred to a Rehabilitation Center. He underwent a comprehensive rehabilitation program with physiotherapy, occupational therapy and speech therapy, including multisensory stimulation and intervention in the surrounding environment. He started amantadine, 50 mg/day, titrated up to 200 mg/day, with significant clinical and functional improvements, and emerged from vegetative state to minimally conscious state at week three and recovered consciousness at the sixth week of amantadine, maintaining progressive improvement, even after drug suspension. The case described underlines the importance of a holistic intervention and corroborates the literature in demonstrating the efficacy and safety of amantadine in the emergence from vegetative state.

A utilização da amantadina na prática clínica ainda parece pouco difundida, apesar da evidência crescente na emergência de alterações do estado de consciência após traumatismo cranioencefálico. Descrevemos o caso de um adolescente com traumatismo cranioencefálico grave por atropelamento. Após quatro meses de internamento num hospital central onde se manteve em estado vegetativo foi transferido para um centro de reabilitação. Iniciou um programa de reabilitação integral liderado por equipa médica, incluindo estimulação multissensorial e intervenção no meio envolvente. Iniciou amantadina, 50 mg/dia, titulada até 200 mg/dia, verificando-se melhoria clínica e funcional significativas, com emergência para estado de consciência mínima à terceira semana e recuperação da consciência à sexta semana de amantadina. Manteve melhoria progressiva mesmo após suspensão do fármaco. O caso descrito salienta a importância da intervenção holística e corrobora a literatura ao demonstrar a eficácia e segurança da amantadina na emergência do estado vegetativo.

Music Interventions for Disorders of Consciousness: A Systematic Review and Meta-analysis.

BACKGROUND: Quantitative evidence for the effects of music on patients with disorders of consciousness (DOCs) was presented. This study was based on available studies to summarize the effect estimates of music for DOC patients. METHODS: Three electronic databases were searched for studies that investigated the effects of music for DOC patients from start to July 2018. The summary results included functional scale, general physical indexes, electroencephalogram indexes, and favorable outcomes. The weighted mean difference and odds ratio with a corresponding 95% confidence interval were used to calculate continuous and frequency data using a random-effects model. This report adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Randomized controlled trials (3) and cohort studies (8) involving 201 DOC patients were included. Patients with DOCs receiving music interventions were associated with high levels of California Verbal Learning Test (P = .038) and persistent vegetative state (P < .001), whereas no significant differences were detected for agitated behavior scale (P = .982), Glasgow Coma Scale (P = .216), Mini-Mental State Examination (P = .215), music therapy in a vegetative or minimally conscious state (P = .590), and Stroop (P = 1.000). Furthermore, DOC patients receiving music intervention showed a significantly increased facial expression (P = .003) and reduced systolic blood pressure (P = .036), whereas no significant effects were observed on diastolic blood pressure (P = .777), heart rate (P = .666), oxygen saturation (P = .911), pulse (P = .899), respiratory frequency (P = .427), and temperature (P = .864). Moreover, music did not contribute significantly to electroencephalogram indexes including alpha (α), beta (ß), delta (δ), and theta (θ) in the left and right hemispheres (P > .050). Finally, DOC patients receiving music intervention showed an increased incidence of favorable outcomes (P = .015). CONCLUSION: This quantitative meta-analysis indicated that music might play a critical role on the functional scale, general physical indexes, and favorable outcomes for DOC patients. Music therapy can easily be provided at the bedside by nurses working with DOC patients.

Auditory steady-state response to chirp-modulated tones: A pilot study in patients with disorders of consciousness.

OBJECTIVE: Due to the problems with behavioral diagnosis of patients with prolonged DOC (disorders of consciousness), complementary approaches based on objective measurement of neural function are necessary. In this pilot study, we assessed the sensitivity of auditory chirp-evoked responses to the state of patients with severe brain injury as measured with CRS-R (Coma Recovery Scale - Revised). METHODS: A convenience sample of fifteen DOC patients was included in the study. Auditory stimuli, chirp-modulated at 1-120 Hz were used to evoke auditory steady-state response (ASSR). Phase-locking index (PLI) estimates within low gamma and high gamma windows were evaluated. RESULTS: The PLI estimates within a narrow low gamma 38-42 Hz window positively correlated with the CRS-R total score and with the scores of the Auditory and Visual Function subscales. In the same low gamma window, significant difference in the PLIs was found between minimally conscious (MCS) and vegetative state (VS) patients. We did not observe any between-group differences nor any significant correlations with CRS-R scores in the high gamma window (80-110 Hz). CONCLUSIONS: Our results support the notion that the activity around 40 Hz may serve as a possible marker of the integrity of thalamocortical networks in prolonged DOC patients. SIGNIFICANCE: Auditory steady-state responses at gamma-band frequencies highlight the role of upper parts of auditory system in evaluation of the level of consciousness in DOC patients.

Assessing the depth of language processing in patients with disorders of consciousness.

Assessing residual consciousness and cognitive abilities in unresponsive patients is a major clinical concern and a challenge for cognitive neuroscience. Although neuroimaging studies have demonstrated a potential for informing diagnosis and prognosis in unresponsive patients, these methods involve sophisticated brain imaging technologies, which limit their clinical application. In this study, we adopted a new language paradigm that elicited rhythmic brain responses tracking the single-word, phrase and sentence rhythms in speech, to examine whether bedside electroencephalography (EEG) recordings can help inform diagnosis and prognosis. EEG-derived neural signals, including both speech-tracking responses and temporal dynamics of global brain states, were associated with behavioral diagnosis of consciousness. Crucially, multiple EEG measures in the language paradigm were robust to predict future outcomes in individual patients. Thus, EEG-based language assessment provides a new and reliable approach to objectively characterize and predict states of consciousness and to longitudinally track individual patients' language processing abilities at the bedside.