Minimally Conscious State Research Articles

The use of amantadine in patients with unresponsive wakefulness syndrome after severe cerebral hemorrhage

ABSTRACT Background Amantadine is currently recommended for use in patients of post-traumatic brain injury with unresponsive wakefulness syndrome (UWS). However, the application of amantadine in UWS after cerebral hemorrhage has only been rarely reported. This allows for a further exploration of the role of amantadine in the treatment of UWS resulting from a severe cerebral hemorrhage. Methods We observed the changes of seven patients with UWS of intracerebral hemorrhage after taking amantadine. We also carried out a detailed neurological examination of the patient with disorders of consciousness to include or exclude subjects for the study. CRS-R score was used to evaluate the neurological recovery. Results An improvement in consciousness was observed within 3–6 days after the start of amantadine administration in all seven cases (n = 7/7; 100%). Five patients recovered conscious and left aphasia, hemiplegia and other sequelae, and two patients recovered from UWS to minimally conscious state (MCS). Conclusions In this study, amantadine administration showed substantial positive effects on recovery following severe cerebral hemorrhage. We recommend further randomized controlled studies to determine the efficacy of amantadine.

Clinical application of Chinese Nanjing persistent vegetative state scale

BackgroundIt is a challenge to characterize the consciousness level of patients with severe disturbance of consciousness and predict their prognosis effectively for Chinese doctors. We aimed to investigate the psychometric property and the diagnostic practicality of severe disturbance of consciousness by Chinese Nanjing persistent vegetative state scale (CNPVSS) which was first set up in 1996 and modified in 2001 and 2011.MethodsThe concurrent validity, inter-rater consistency and diagnostic accuracy of CNPVSS and Chinese version of coma recovery scale-revised (CRS-R) were investigated by assessment of 380 patients with severe disorders of consciousness.ResultsTotal scores of the CNPVSS were correlated significantly with that of the CRS-R, indicating acceptable concurrent validity. Sub-scale analysis showed moderate to high inter-rater reliability and test-retest reliability. CNPVSS was superior to CRS-R on the diagnosis sensitivity. The CNPVSS was able to distinguish 65 patients in emergence from minimal consciousness state who were misclassified as in minimal consciousness state (MCS) by the CRS-R, and it could also distinguish two patients in MCS who were misclassified as in vegetative state by the CRS-R.ConclusionThe CNPVSS is an appropriate measurement and is sensitive to distinguish the MCS patients from the VS patients.

Serum BDNF Levels Are Reduced in Patients with Disorders of Consciousness and Are Not Modified by Verticalization with Robot-Assisted Lower-Limb Training.

Little is known about plastic changes occurring in the brains of patients with severe disorders of consciousness (DOCs) caused by acute brain injuries at rest and during rehabilitative treatment. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity whose production is powerfully modulated by physical exercise. In this study, we compared serum BDNF levels in 18 patients with unresponsive wakefulness syndrome (UWS) and in a minimally conscious state (MCS) with those in 16 sex- and age-matched healthy controls. In 12 patients, serum BDNF levels before and after verticalization with ErigoPro robot-assisted lower-limb training were compared. Serum BDNF levels were significantly lower in patients (median, 1141 pg/ml; 25th and 75th percentiles, 1016 and 1704 pg/ml) than in controls (median, 2450 pg/ml; 25th and 75th percentiles, 2100 and 2875 pg/ml; p < 0.001). BDNF levels measured before and after verticalization with robot-assisted lower-limb training did not change (p = 0.5). Moreover, BDNF levels did not differ between patients with UWS and MCS (p = 0.2), or between patients with traumatic and nontraumatic brain injuries (p = 0.6). BDNF level correlated positively with the time since brain injury (p = 0.025). In conclusion, serum BDNF levels are reduced in patients with UWS and MCS and cannot be improved by verticalization associated with passive lower-limb training. Additional studies are needed to better understand the mechanisms underlying BDNF reduction in patients with DOCs and to determine the best rehabilitative strategies to promote restorative plastic changes in these patients.

Neurobehavioral recovery in patients who emerged from prolonged disorder of consciousness: a retrospective study

BackgroundWe investigated the clinical course of patients with prolonged disorders of consciousness (PDoC), predictors of emergence from PDoC (EDoC), and the temporal dynamics of six neurobehavior domains based on the JFK Coma Recovery Scale-Revised (CRS-R) during the recovery.MethodsA total of 50 traumatic and non-traumatic patients with PDoC were enrolled between October 2014 and February 2017. A retrospective analysis of the clinical findings and neurobehavioral signs was conducted using standardized methodology such as CRS-R. The findings were used to investigate the incidence and predictors of EDoC and determine the cumulative pattern of neurobehavioral recovery at 6 months, 1 year, and 2 years post-injury.ResultsThe results showed that 46% of the subjects emerged from PDoC after 200 median days (64–1197 days) of injury onset. The significant predictors of EDoC included minimally conscious state (MCS) (vs. vegetative state), higher auditory, communication, arousal, total CRS-R scores, shorter lag time post-injury, and the absence of intra-axial lesions. In terms of cumulative recovery of motor and communication signs in patients who emerged from PDoC, 39 and 32% showed EDoC at 6 months post-injury, and 88 and 93% exhibited EDoC at 2 years post-injury, respectively.ConclusionsNearly half of the patients with PDoC recovered consciousness during inpatient rehabilitation. MCS, shorter lag time, the absence of intra-axial lesions, higher auditory, communication, arousal, and total CRS-R scores were important predictors for EDoC. Motor scores in the early stage of recovery and communication scores after prolonged intervals contributed to the higher levels of cumulative EDoC.

Effects of comprehensive rehabilitation on complications and long-term prognoses of patients in vegetative and minimal consciousness states.

To understand the clinical characteristics, prognoses, and prognostic factors of vegetative state (VS) and minimal consciousness state (MCS) patients hospitalized for comprehensive rehabilitation. The data of VS and MCS patients admitted in the past six years were retrospectively analyzed. Age of onset, etiology, course of disease, complications, and retention of tracheal intubation, gastric tube, and urethral catheter were recorded. All patients were followed for one year after onset, and their Glasgow Outcome Scale (GOS) scores were assessed. Long-term prognostic factors were analyzed using logistic regression. The proportion of patients with traumatic brain injuries in the MCS group was higher than in the VS group (p<0.05), while hypoxic-ischemic encephalopathy accounted for a higher proportion in the VS group; the differences were statistically significant between the two groups. The occurrence of infection was the highest in both groups, followed by spasticity and epilepsy. The occurrence of other complications was slightly different between the two groups but did not reach statistical significance (p>0.05). Age, etiology, and consciousness at admission had a significant impact on the long-term prognoses of VS or MCS patients (p<0.05), and the age of onset was the most important factor (the highest OR). Infection, spasticity, and epilepsy are common complications in both VS and MCS patients. Recovery of consciousness after one year was shown to be affected by age, etiology, and consciousness at admission.

Orthostatic Hemodynamic Changes in Brain Damage

Aim: to study orthostatic hemodynamic changes in patients with chronic disorders of consciousness after critical brain damage.Materials and methods. We studied 30 patients (10 women and 20 men) with chronic disorders of consciousness after severe brain damage aged 45±7 years, 10 of which were in the vegetative state (VS) and 20 had the minimally conscious state (MCS). The main causes of brain damage were traumatic brain injury (53% of patients) and cerebrovascular accidents (CVA) (23.3%). The rest of the patients had posthypoxic encephalopathy or were after brain tumor removal surgery. Passive orthostatic test (POT) 0° to 60° to 0° was performed using an electrically driven tilt table (Vario Line). Hemodynamic monitoring during the verticalization was done using a non-invasive oscillometric recording of blood pressure on the brachial artery, stroke volume (SV) and cardiac minute output (CMO) were measured by impedance cardiography with the multifunctional «Task Force Monitor 3010i» (CNSystem, Austria). Data were statistically analyzed using the Statistica 10 software package.Results. Orthostatic hemodynamic stability was found in 26 out of 30 patients with chronic disorders of consciousness after critical brain damage. It was manifested by stable systolic blood pressure (SBP) in tilted orthostatic and horizontal position (120.7±2.2 and 121.1±3.6 mmHg, respectively, P&gt;0.05). Orthostatic hypotension was observed in 3 patients and postural tachycardia syndrome (PTS) in one patient. We compared orthostatic hemodynamic changes in the studied cohort versus published data on orthostatic hemodynamic changes uncluding POT revealed in patients with severe brain damage examined before and after brain death.Conclusion. Orthostatic stability of blood circulation can be maintained for a short period of time in patients surviving after critical diffuse brain damage associated with chronic disorders of consciousness. Critical brain damage resulting in brain death associates with a significant reduction of all hemodynamic parameters and severe orthostatic hypotension with restoration of initial blood pressure values when the patient is returned to the horizontal position.

Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness

Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

Influence of Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Oxidative Stress Intensity in Minimally Conscious State Patients.

Neurological disorders, including minimally conscious state (MCS), may be associated with the presence of high concentrations of reactive oxygen species within the central nervous system. Regarding the documented role of mesenchymal stem cells (MSCs) in oxidative stress neutralization, the aim of this study is to evaluate the effect of bone marrow-derived MSC (BM-MSC) transplantation on selected markers of oxidative stress in MCS patients. Antioxidant capacity was measured in cerebrospinal fluid (CSF) and plasma collected from nine patients aged between 19 and 45 years, remaining in MCS for 3 to 14 months. Total antioxidant capacity, ascorbic acid and ascorbate concentrations, superoxide dismutase, catalase, and peroxidase activity were analyzed and the presence of tested antioxidants in the CSF and plasma was confirmed. Higher ascorbic acid (AA) content and catalase (CAT) activity were noted in CSF relative to plasma, whereas superoxide dismutase (SOD) activity and total antioxidant capacity were higher in plasma relative to CSF. Total antioxidant capacity measured in CSF was greater after BM-MSC transplantations. The content of ascorbates was lower and CAT activity was higher both in CSF and plasma after the administration of BM-MSC. The above results suggest that MSCs modulate oxidative stress intensity in MCS patients, mainly via ascorbates and CAT activity.

Peri-Personal Space Tracing by Hand-Blink Reflex Modulation in Patients with Chronic Disorders of Consciousness

The assessment of awareness in patients with chronic Disorders of Consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. The level of awareness impairment may depend on the degree of deterioration of the large-scale cortical-thalamo-cortical networks induced by brain injury. Electrophysiological approaches may shed light on awareness presence in patients with DoC by estimating cortical functions related to the cortical-thalamo-cortical networks including, for example, the cortico-subcortical processes generating motor responses to the perturbation of the peri-personal space (PPS). We measured the amplitude, latency, and duration of the hand-blink reflex (HBR) responses by recording electromyography (EMG) signals from both the orbicularis oculi muscles while electrically stimulating the median nerve at the wrist. Such a BR is thought to be mediated by a neural circuit at the brainstem level. Despite its defensive-response nature, HBR can be modulated by the distance between the stimulated hand and the face. This suggests a functional top-down control of HBR as reflected by HBR features changes (latency, amplitude, and magnitude). We therefore estimated HBR responses in a sample of patients with DoC (8 MCS and 12 UWS, compared to 15 healthy controls −HC) while performing a motor task targeting the PPS. This consisted of passive movements in which the hand of the subject was positioned at different distances from the participant’s face. We aimed at demonstrating a residual top-down modulation of HBR properties, which could be useful to differentiate patients with DoC and, potentially, demonstrate awareness preservation. We found a decrease in latency, and an increase in duration and magnitude of HBR responses, which were all inversely related to the hand-to-face distance in HC and patients with MCS, but not in individuals with UWS. Our data suggest that only patients with MCS have preserved, residual, top-down modulation of the processes related to the PPS from higher-order cortical areas to sensory-motor integration network. Although the sample size was relatively small, being thus our data preliminary, HBR assessment seems a rapid, easy, and first-level tool to differentiate patients with MCS from those with UWS. We may also hypothesize that such a HBR modulation suggests awareness preservation.

Brain Metabolism but Not Gray Matter Volume Underlies the Presence of Language Function in the Minimally Conscious State (MCS): MCS+ Versus MCS− Neuroimaging Differences

Background. The minimally conscious state (MCS) is subcategorized into MCS− and MCS+, depending on the absence or presence, respectively, of high-level behavioral responses such as command-following. Objective. We aim to investigate the functional and structural neuroanatomy underlying the presence of these responses in MCS− and MCS+ patients. Methods. In this cross-sectional retrospective study, chronic MCS patients were diagnosed using repeated Coma Recovery Scale–Revised assessments. Fluorodeoxyglucose-positron emission tomography data were acquired on 57 patients (16 MCS−; 41 MCS+) and magnetic resonance imaging with voxel-based morphometry analysis was performed on 66 patients (17 MCS−; 49 MCS+). Brain glucose metabolism and gray matter integrity were compared between patient groups and control groups. A metabolic functional connectivity analysis testing the hypothesis of preserved language network in MCS+ compared with MCS− was also done. Results. Patients in MCS+ presented higher metabolism mainly in the left middle temporal cortex, known to be important for semantic processing, compared with the MCS− group. The left angular gyrus was also functionally disconnected from the left prefrontal cortex in MCS− compared with MCS+ group. No significant differences were found in gray matter volume between patient groups. Conclusions. The clinical subcategorization of MCS is supported by differences in brain metabolism but not in gray matter structure, suggesting that brain function in the language network is the main support for recovery of command-following, intelligible verbalization and/or intentional communication in the MCS. Better characterizing the neural correlates of residual cognitive abilities of MCS patients contributes to reduce their misdiagnosis and to adapt therapeutic approaches.

How Does Functional Neurodiagnostics Inform Surrogate Decision-Making for Patients with Disorders of Consciousness? A Qualitative Interview Study with Patients’ Next of Kin

Functional neurodiagnostics could allow researchers and clinicians to distinguish more accurately between the unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS). It remains unclear how it informs surrogate decision-making. To explore how the next of kin of patients with disorders of consciousness (DOC) interpret the results of a functional neurodiagnostics measure and how/why their interpretations influence their attitudes towards medical decisions. We conducted problem-centered interviews with seven next of kin of patients with DOC who had undergone a functional HD-EEG examination at a neurological rehabilitation center in Germany. The examination included an auditory oddball paradigm and a motor imagery task to detect hidden awareness. We analyzed the interview transcripts using structuring qualitative content analysis. Regardless of the diagnostic results, all participants were optimistic of the patients’ meaningful recovery. We hypothesize, that participants deal with the results of examinations according to their belief system. Thus, an unfavorable evaluation of the patient’s state (e.g., a “negative” HD-EEG-result) had the potential to destabilize the participant’s belief system. To re-stabilize or to prevent the destabilization of their belief system, participants used different strategies. Participants accepted a “positive” HD-EEG result since it stabilized their belief system. We hypothesize, that a group of next of kin of patients with DOC deals with functional neurodiagnostics results on the basis of the result’s value and their high hope that the patient will recover meaningfully. A psychological mechanism seems to moderate the impact of functional neurodiagnostics on surrogate treatment decisions.

Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology.

The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including advanced EEG analyses, can allow achieving a more reliable diagnosis, that is, discovering residual traces of awareness in patients with UWS (namely, functional Locked-In Syndrome (fLIS)). These approaches aim at capturing the residual brain network models, at rest or that may be activated in response to relevant stimuli, which may be appropriate for awareness to emerge (despite their insufficiency to generate purposeful motor behaviors). For this, different brain network models have been studied in patients with DoC by using sensory stimuli (i.e., passive tasks), probing response to commands (i.e., active tasks), and during resting-state. Since it can be difficult for patients with DoC to perform even simple active tasks, this scoping review aims at summarizing the current, innovative neurophysiological examination methods in resting state/passive modality to differentiate and prognosticate patients with DoC. We conclude that the electrophysiologically-based diagnostic procedures represent an important resource for diagnosis, prognosis, and, therefore, management of patients with DoC, using advance passive and resting state paradigm analyses for the patients who lie in the “greyzones” between MCS, UWS, and fLIS.

Constructing a Consciousness Meter Based on the Combination of Non-Linear Measurements and Genetic Algorithm-Based Support Vector Machine.

Constructing a framework to evaluate consciousness is an important issue in neuroscience research and clinical practice. However, there is still no systematic framework for quantifying altered consciousness along the dimensions of both level and content. This study builds a framework to differentiate the following states: coma, general anesthesia, minimally conscious state (MCS), and normal wakefulness. This study analyzed electroencephalography (EEG) recorded from frontal channels in patients with disorders of consciousness (either coma or MCS), patients under general anesthesia, and healthy participants in normal waking consciousness (NWC). Four non-linear methods-permutation entropy (PE), sample entropy (SampEn), permutation Lempel-Ziv complexity (PLZC), and detrended fluctuation analysis (DFA)-as well as relative power (RP), extracted features from the EEG recordings. A genetic algorithm-based support vector machine (GA-SVM) classified the states of consciousness based on the extracted features. A multivariable linear regression model then built EEG indices for level and content of consciousness. The PE differentiated all four states of consciousness (p<0.001). Altered contents of consciousness for NWC, MCS, coma, and general anesthesia were best differentiated by the SampEn, and PLZC. In contrast, the levels of consciousness for these four states were best differentiated by RP of Gamma and PE. A multi-dimensional index, combined with the GA-SVM, showed that the integration of PE, PLZC, SampEn, and DFA had the highest classification accuracy (92.3%). The GA-SVM was better than random forest and neural networks at differentiating these four states. The 'coordinate value' in the dimensions of level and content were constructed by the multivariable linear regression model and the non-linear measures PE, PLZC, SampEn, and DFA. Multi-dimensional measurements, especially the PE, SampEn, PLZC, and DFA, when combined with GA-SVM, are promising methods for constructing a framework to quantify consciousness.

Impaired Frontoparietal Connectivity in Traumatic Individuals with Disorders of Consciousness: A Dynamic Brain Network Analysis.

Recent advances in neuroimaging have demonstrated that patients with disorders of consciousness (DOC) may retain residual consciousness through activation of a complex functional brain network. However, an understanding of the hierarchy of residual consciousness and dynamic network connectivity in DOC patients is lacking. This study aimed to investigate residual consciousness and the dynamics of neural processing in DOC patients. We included 42 patients with DOC, categorized by aetiology. Event-related potentials combined with time-varying electroencephalography networks were used to probe affective consciousness in DOC and examine the related network mechanisms. The results showed an obvious frontal P3a component among patients in minimally conscious state (MCS), while a prominent N1 was observed in unresponsive wakefulness syndrome (UWS). No late positive potential (LPP) was detected in these patients. Next, we divided the results by aetiology. Patients with nontraumatic injury presented an obvious frontal P3a response compared to those with traumatic injury. With respect to the dynamic network mechanism, patients with UWS, both with and without trauma, exhibited impaired frontoparietal network connectivity during the middle to late emotion processing period (P3a and LPP). Surprisingly, unconscious post-traumatic patients had an evident deficit in top-down connectivity. This, it appears that early automatic sensory identification is preserved in UWS and that exogenous attention was preserved even in MCS. However, high-level cognitive abilities were severely attenuated in unconscious patients. We also speculate that reduced frontoparietal connectivity may be useful as a biomarker to distinguish patients in an MCS from those with UWS given the same aetiology.

Behavioral and electrophysiological effects of network-based frontoparietal tDCS in patients with severe brain injury: A randomized controlled trial

BackgroundTranscranial direct current stimulation (tDCS) may promote the recovery of severely brain-injured patients with disorders of consciousness (DOC). Prior tDCS studies targeted single brain regions rather than brain networks critical for consciousness recovery. ObjectiveInvestigate the behavioral and electrophysiological effects of multifocal tDCS applied over the frontoparietal external awareness network in patients with chronic acquired DOC. MethodsForty-six patients were included in this randomized double-blind sham-controlled crossover trial (median [interquartile range]: 46 [35 – 59] years old; 12 [5 – 47] months post injury; 17 unresponsive wakefulness syndrome, 23 minimally conscious state (MCS) and 6 emerged from the MCS). Multifocal tDCS was applied for 20 min using 4 anodes and 4 cathodes with 1 mA per electrode. Coma Recovery Scale-Revised (CRS-R) assessment and 10 min of resting state electroencephalogram (EEG) recordings were acquired before and after the active and sham sessions. ResultsAt the group level, there was no tDCS behavioral treatment effect. However, following active tDCS, the EEG complexity significantly increased in low frequency bands (1–8 Hz). CRS-R total score improvement was associated with decreased baseline complexity in those bands. At the individual level, after active tDCS, new behaviors consistent with conscious awareness emerged in 5 patients. Conversely, 3 patients lost behaviors consistent with conscious awareness. ConclusionThe behavioral effect of multifocal frontoparietal tDCS varies across patients with DOC. Electrophysiological changes were observed in low frequency bands but not translated into behavioral changes at the group level.

Application of brain perfusion SPECT in the evaluation of response to zolpidem therapy in consciousness disorder due to traumatic brain injury

Background:Traumatic brain injury (TBI) is a critical health problem with various comorbidities and socioeconomic consequences. Tending to increase in recent decades, TBI results in more cases of consciousness disorders including vegetative state (VS)/minimally conscious state (MCS). However, no definite or effective treatment still exists for these conditions. The aim of this article is to study the effects of zolpidem in patients with VS caused by TBI by using brain perfusion single-photon emission computed tomography (SPECT).Materials and Methods:This was a prospective clinical trial on a cohort of patients with VS. We evaluated the TBI database to find VS/MCS patients, between the ages of 20 and 65 years. We received written consent from their family members prior to enrollment and compared their clinical status and brain perfusion SPECT prior and after 2 weeks of zolpidem therapy.Results:Among the 12 patients included in this study, six patients changed to MCS after 2 weeks. Comparison of their motor score, revealed a statistically significant difference (2.08 vs. 3.75, P = 0.007, respectively). None of the quantitative or qualitative brain perfusion parameters showed any differences after zolpidem therapy. However, the perfusion pattern, with focal or multifocal cortical defects, was significantly more prevalent in the responder group (five patients vs. one patient, P = 0.015).Conclusion:Zolpidem therapy may improve consciousness levels and motor function in a considerable portion of VS patients with TBI. This study showed that the presence of focal brain perfusion defect can predict response to zolpidem.

Transcranial magnetic stimulation-evoked connectivity reveals modulation effects of repetitive transcranial magnetic stimulation on patients with disorders of consciousness.

Several studies have investigated possible role of repetitive transcranial magnetic stimulation (rTMS) in patients with disorder of consciousness (DOC). But the details of patients' brain responses to the rTMS are yet to be disclosed. The aim of the study is to explore the neural electrical responses of DOC patients to rTMS modulation. DOC Patients [14 vegetative state, seven minimally conscious state (MCS)] and healthy subjects were enrolled and received one session of rTMS. The TMS-electroencephalogram was recorded at before and immediately after rTMS stimulation. TMS-evoked potentials as well as TMS-evoked connectivity were proposed to capture the effective connectivity alteration induced by rTMS. Significant changes of TMS-evoked potential were found in the healthy group but not in DOC patients. TMS-evoked connectivity was significantly enhanced by the rTMS in healthy and MCS groups. In addition, the enhancement was positively correlated with patients' Coma Recovery Scale-Revised scores. Global synchrony of the TMS-evoked connectivity matrix significantly enhanced by rTMS in the control and MCS groups but not in vegetative state patients. Furthermore, after rTMS stimulation, the similarity of TMS-evoked connectivity patterns between pairwise patients was significantly raised in MCS patients. But no significant changes were found in vegetative state patients. TMS-evoked connectivity reveals that rTMS can effectively modulate effective connectivity of MCS patients, but no evidence of changes in vegetative state patients.

Spinal cord stimulation modulates complexity of neural activities in patients with disorders of consciousness

Objective: Spinal cord stimulation (SCS) is a valuable treatment for patients with disorders of consciousness (DOC). This study used permutation entropy (PeEn) of neural activities to quantify brain responses to SCS.Method: We recruited 14 patients with DOC, including seven patients in minimally conscious state (MCS) and seven patients in vegetative state/unawareness state (VS/UWS). All patients received a single session of 20 min’ continuous SCS. We recorded resting state EEG before, during and after SCS. In this study, PeEn was first calculated to describe overall neural activities changes in SCS. The brain was then divided into frontal, central, parietal and occipital regions to explore spatial SCS modulation effects. Finally, a correlation analysis was conducted between CRS-R values and changes in PeEn on each of the four regions.Results: SCS was associated with short-term changes in neural activities in DOC. When SCS was on, PeEn increased as compared to the baseline. When SCS was shut off, PeEn decreased. The PeEn of all patients after SCS was higher than before SCS, and changes of PeEn for MCS were more significant than those for VS, especially in the frontal region.Conclusion: PeEn from EEG data could be used to evaluate SCS modulation effects, and EEG complexity might be a critical index to describe brain responses to SCS in DOC.

Unedited pathological recurrent association of palmomental and rooting archaic reflexes in a young woman with severe traumatic brain lesions – case presentation and physiopathological considerations

Introduction. Archaic reflexes are present in infancy, disappear as the brain matures, but reappear in pathological conditions. Case report. A 29-years-old woman has suffered a severe traumatic brain injury. She was admitted to neurorehabilitation 6 months after neurosurgical interventions (ventriculoperitoneal shunt for traumatic hydrocephalus, emerged after decompressive craniectomy). Neurological examination revealed a minimal conscious state, spastic tetraparesis, trismus, central facial palsy, nystagmus, bilateral palm-chin reflex, and a “mitigated” variant of the rooting reflex. The left corneal, snout and glabellar reflexes were absent. Osteotendinous reflexes were brisk, Babinski sign was bilaterally present, palmar and plantar grasp reflexes were absent. The trismus has persisted and chewing remained severely disabled after botulinum toxin injected in the left temporalis muscle and bilaterally in the masseter. The patient was fed by percutaneous endoscopic gastrostomy tube. Neurologic evolution remained stationary after two months of rehabilitative nursing. Discussion. The palmomental reflex described by Marinescu and Radovici, is elicited by scratching the thenar eminence of the palm, and consists of an ipsilateral twitch of the mentalis muscle. Baby rooting for milk is a primitive trigemino-facial reflex found in newborn infants. The lower lip is lowered, and the tongue is moved in the direction where the cheek near the corner of the mouth is brushed. The lockjaw has “mitigated” the classical pattern of clinical response. Repeated stimulation causes a unilateral mentalis muscle response, similar to the palm-chin reflex. The severe traumatic brain lesions have induced pathological reappearance of the palmomental and rooting archaic reflexes, in a unique, unedited pathological association. Key words: palmomental reflex (Marinescu Radovici reflex); rooting reflex; archaic reflexes; botulinum toxin; traumatic brain injury; minimal conscious state,

Prolonged disorders of consciousness after an acute brain injury

Only a fraction of patients in coma secondary to a primary acute brain injury develop a vegetative state (VS). At least 20% of patients show late transitions to a minimally conscious states (MCS). They are particularly common in young adults with traumatic brain injury. The main problems faced by clinicians are the diagnostic accuracy of VS and MCS as well as the usefulness of sophisticated paraclinical investigations. Specific therapies are of limited effectiveness. This population is vulnerable to misdiagnosis and limited access to medical care and rehabilitation, thus generating ethical problems.