Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Behavioral scales variability in patients with prolonged disorders of consciousness.

BACKGROUND: The principal conditions differentiating disorders of consciousness (DOC) patients are the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS). Many individuals who suffer from sudden-onset severe brain injury move through stages of UWS/VS and MCS before regaining full awareness. In some patients, the DOC condition is protracted for years (PDOC). In this study, we observed PDOC patients for 6 months to assess possible changes in their level of consciousness. METHODS: We enrolled 40 PDOC patients, 23 UWS/VS and 17 MCS hosted in a dedicated unit for long-term brain injury care. The time from injury was 472 ± 533 days for UWS/VS and 1090 ± 1079 days for MCS. The Wessex Head Injury Matrix (WHIM), Coma Recovery Scale-R (CRS-R), and Nociception Coma Scale were administered monthly for 6 months. RESULTS: During the period of assessment, the percentage of UWS/VS shifted from 58 to 45%, while for the MCS, from 42 to 55%. A positive correlation was found for the UWS/VS patients between the months of observation with the CRS-R total score and WHIM total numbers of behaviors (TNB). In the UWS/VS group, the CRS-R auditive and visual subscales correlated positively with the observation time. During the whole period of observation, 8 patients had constant CRS-R total scores while the WHIM TNB changed in 7 of them. CONCLUSION: Our findings demonstrated that the monthly assessment of PDOC by means of the CRS-R and WHIM was able to detect also subtle changes in consciousness level.

Machine learning and network analysis for diagnosis and prediction in disorders of consciousness.

BACKGROUND: Prolonged Disorders of Consciousness (PDOC) resulting from severe acquired brain injury can lead to complex disabilities that make diagnosis challenging. The role of machine learning (ML) in diagnosing PDOC states and identifying intervention strategies is relatively under-explored, having focused on predicting mortality and poor outcome. This study aims to: (a) apply ML techniques to predict PDOC diagnostic states from variables obtained from two non-invasive neurobehavior assessment tools; and (b) apply network analysis for guiding possible intervention strategies. METHODS: The Coma Recovery Scale-Revised (CRS-R) is a well-established tool for assessing patients with PDOC. More recently, music has been found to be a useful medium for assessment of coma patients, leading to the standardization of a music-based assessment of awareness: Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC). CRS-R and MATADOC data were collected from 74 PDOC patients aged 16-70 years at three specialist centers in the USA, UK and Ireland. The data were analyzed by three ML techniques (neural networks, decision trees and cluster analysis) as well as modelled through system-level network analysis. RESULTS: PDOC diagnostic state can be predicted to a relatively high level of accuracy that sets a benchmark for future ML analysis using neurobehavioral data only. The outcomes of this study may also have implications for understanding the role of music therapy in interdisciplinary rehabilitation to help patients move from one coma state to another. CONCLUSIONS: This study has shown how ML can derive rules for diagnosis of PDOC with data from two neurobehavioral tools without the need to harvest large clinical and imaging datasets. Network analysis using the measures obtained from these two non-invasive tools provides novel, system-level ways of interpreting possible transitions between PDOC states, leading to possible use in novel, next-generation decision-support systems for PDOC.

Regional Homogeneity Alterations in Patients with Impaired Consciousness. An Observational Resting-State fMRI Study.

PURPOSE: It is always challenging to correctly differentiate between minimally conscious state (MCS) and vegetative state/unresponsive wakefulness syndrome (VS/UWS) among disorders of consciousness (DOC) patients. However, the underlying neural mechanisms of awareness identification remain incompletely understood. METHODS: Using regional homogeneity (ReHo) analysis, we evaluated how regional connectivity of brain regions is disrupted in MCS and VS/UWS patients. Resting-state functional magnetic resonance imaging was conducted in 14 MCS patients, 25 VS/UWS patients, and 30 age-matched healthy individuals. RESULTS: We found that MCS and VS/UWS patients demonstrated DOC-dependent reduced ReHo within widespread brain regions including posterior cingulate cortices (PCC), medial prefrontal cortices (mPFC), and bilateral fronto-parieto-temporal cortices and showed increased ReHo in limbic structures. Moreover, a positive correlation between Coma Recovery Scale-Revised (CRS-R) total scores and reduced ReHo in the left precuneus was observed in VS/UWS patients, despite the linear trend was not found in MCS patients. In addition, ReHo were also observed reduced in three mainly intrinsic connectivity networks (ICNs), including default mode network (DMN), executive control network (ECN), and salience network (SN). Notably, as the clinical symptoms of consciousness disorders worsen from MCS to VS/UWS, ReHo in dorsal DMN, left ECN, and posterior SN became significantly reduced. CONCLUSION: These findings make a further understanding of the underlying neural mechanism of regional connectivity among DOC patients and provide additional neuroimaging-based biomarkers for the clinical diagnosis of MCS and VS/UWS patients.

The influence of the CRS-R score on functional outcome in patients with severe brain injury receiving early rehabilitation.

BACKGROUND: The aim of the study was to determine the role of the Coma Recovery Scale-Revised (CRS-R) in the prediction of functional status at the end of neurological early rehabilitative treatment. METHODS: Patients consecutively admitted to intensive or intermediate care units of a neurological rehabilitation center were enrolled in the study. Consciousness and functional status were assessed with the Coma Recovery Scale-Revised (CRS-R) and the Early Rehabilitation Barthel Index (ERBI), respectively. Both assessments were carried out weekly within the first month and at the end of early rehabilitation. Patient and clinical data were entered into a binary logistic regression model to predict functional status at discharge. RESULTS: 327 patients (112 females, 215 males) with a median age of 63 years (IQR = 53-75) and a median disease duration of 18 days (IQR = 12-28) were included. Most patients suffered from stroke (59 %), followed by traumatic brain injury (31 %), and hypoxic ischemic encephalopathy (10 %). Upon admission, 12 % were diagnosed as comatose, 31 % as unresponsive wakefulness syndrome (UWS), 35 % as minimally conscious state (MCS) and 22 % already emerged from MCS (eMCS). Of all patients undergoing complete early rehabilitative treatment (n = 180), 72 % showed improvements in level of consciousness (LOC). In this group, age, initial CRS-R score and gains in CRS-R score after four weeks independently predicted functional outcome at discharge. CONCLUSIONS: The study confirms the relevance of the CRS-R score for functional outcome prediction. High CRS-R scores and young age facilitate functional improvements and increase the probability to continue treatment in subsequent rehabilitation phases. Moreover, results indicate that recovery might occur over a period of time that extends beyond acute care.

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.

Diagnostic accuracy of the CRS-R index in patients with disorders of consciousness.

Objective: To obtain a CRS-R index suitable for diagnosis of patients with disorders of consciousness (DOC) and compare it to other CRS-R based scores to evaluate its potential for clinics and research. Design: We evaluated the diagnostic accuracy of several CRS-R-based scores in 124 patients with DOC. ROC analysis of the CRS-R total score, the Rasch-based CRS-R score, CRS-R-MS and the CRS-R index evaluated the diagnostic accuracy for patients with the Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS). Correlations were computed between the CRS-R-MS, CRS-R index, the Rasch-based score and the CRS-R total score. Results: Both the CRS-R-MS and CRS-R index ranged from 0 to 100, with a cut-off of 8.315 that perfectly distinguishes between patients with UWS and MCS. The CRS-R total score and Rasch-based score did not provide a cut-off score for patients with UWS and MCS. The proposed CRS-R index correlated with the CRS-R total score, Rasch-based score and the CRS-R-MS. Conclusion: The CRS-R index is reliable to diagnose patients with UWS and MCS and can be used in compliance with the CRS-R scoring guidelines. The obtained index offers the opportunity to improve the interpretation of clinical assessment and can be used in (longitudinal) research protocols. Abbreviations: CRS-R: Coma Recovery Scale-Revised; CRS-R-MS: Coma Recovery Scale-Revised Modified Score; DOC: Disorders of Consciousness; MCS: Minimally Conscious State; UWS: Unresponsive Wakefulness Syndrome; ROC: Receiver Operating Characteristic; AUC: Area Under the Curve; IRT: Item Response Theory.

Longitudinal recovery of local neuronal activity and consciousness level in acquired brain injury.

Decreased brain activity in the default mode network, particularly in the precuneus (PCU), has been consistently shown in acquired brain injury (ABI) patients. However, it is unclear whether resting-state brain activity recovers longitudinally in ABI patients and whether functional activity restoration is associated with improvements in consciousness level. Here, resting-state fMRI data were acquired from 23 ABI patients and 30 age- and gender-matched controls with two longitudinal observations for each participant. The fMRI data were analyzed using amplitude of low-frequency fluctuation (ALFF) to measure the fluctuation strength of local spontaneous activity, and seed-based functional connectivity was used to measure functional relationship with the seed region in the whole brain. The level of consciousness was assessed using the Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) on both scanning days of the patients. Interaction effect between the two groups and two scans in ALFF was observed in the PCU, which was driven by restored ALFF in the ABI, while a stable ALFF in the control group. Moreover, restoration of ALFF in the PCU correlated with improvements in both the CRS-R and GCS. Specifically, recovery of ALFF in the PCU primarily reflected the signals of the slow-4 frequency band (0.027-0.073 Hz). Based on the functional connectivity maps of the PCU, we observed a nonsignificant interaction effect or correlation with consciousness level. These findings suggest local activity in the PCU but possibly not its functional connectivity, is related to the longitudinal changes in behavioral responsiveness in ABI. Hum Brain Mapp 38:3579-3591, 2017. © 2017 Wiley Periodicals, Inc.

Transcranial direct current stimulation effects in disorders of consciousness.

OBJECTIVE: To assess the efficacy of transcranial direct current stimulation (tDCS) on improving consciousness in patients with persistent unresponsive wakefulness syndrome (UWS) (previously termed persistent vegetative state [PVS]) or in a minimally conscious state (MCS). DESIGN: Prospective, case series trial with follow-up at 12 months. SETTING: General and research hospital. PARTICIPANTS: Inpatients in a PVS/UWS or MCS (N=10; 7 men, 3 women; age range, 19-62y; etiology: traumatic brain injury, n=5; anoxia, n=4; postoperative infarct, n=1; duration of PVS/UWS or MCS range, 6mo-10y). No participant withdrew because of adverse effects. INTERVENTION: All patients received sham tDCS for 20 minutes per day, 5 days per week, for 1 week, and real tDCS for 20 minutes per day, 5 days per week, for 2 weeks. An anodal electrode was placed over the left primary sensorimotor cortex or the left dorsolateral prefrontal cortex, with cathodal stimulation over the right eyebrow. One patient in an MCS received a second round of 10 tDCS sessions 3 months after initial participation. MAIN OUTCOME MEASURE: JFK Coma Recovery Scale-Revised. RESULTS: All patients in an MCS showed clinical improvement immediately after treatment. The patient who received a second round of tDCS 3 months after initial participation showed further improvement and emergence into consciousness after stimulation, with no change between treatments. One patient who was in an MCS for <1 year before treatment (postoperative infarct) showed further improvement and emergence into consciousness at 12-month follow-up. No patient showed improvement before stimulation. No patient in a PVS/UWS showed immediate improvement after stimulation, but 1 patient who was in a PVS/UWS for 6 years before treatment showed improvement and change of status to an MCS at 12-month follow-up. CONCLUSIONS: tDCS seems promising for the rehabilitation of patients with severe disorders of consciousness. Severity and duration of pathology may be related to the degree of tDCS' beneficial effects.

Long-term HD-tDCS modulates dynamic changes of brain activity on patients with disorders of consciousness: A resting-state EEG study.

OBJECTIVE: High-definition transcranial direct current stimulation (HD-tDCS) has been an effective neurostimulation method in the treatment of disorders of consciousness (DOC). However, the effects and mechanism of HD-tDCS are still unclear. METHODS: This study recruited 8 DOC patients and applied 20-min sessions of 2 mA HD-tDCS (central anode electrode at Pz) for 14 consecutive days. We record DOC patients' EEG data and Coma Recovery Scale-Revised (CRS-R) values at four time point: baseline (T0), after 1 day's and 7,14 days' parietal HD-tDCS treatment (T1, T2, T3). Power spectral density (PSD), relative power (RP), spectral entropy and spectral exponent were calculated to evaluate the EEG dynamic changes of DOC patients during long-term parietal HD-tDCS. At last, we calculated the correlation between changes of EEG features and changes of CRS-R values. RESULT: After 1 day's parietal HD-tDCS, DOC patients' CRS-R value had not changed (8.25 ± 1.91). HD-tDCS improved DOC patients' CRS-R value at T2 (9.75 ± 1.91, p < 0.05) and at T3 (11.38 ± 2.77, p < 0.05), compared with that at T0 (8.25 ± 1.91). As the treatment time increased, the EEG PSD decayed more slowly. Specifically, the delta frequency band RP decreased, while the alpha, beta, and gamma frequency bands RP increased. EEG oscillation characteristics changed but not significant at T1 (p > 0.05), and showed significant changes at T2 and T3 (p < 0.05). The spectral entropy continuously increased and the spectral exponent continuously decreased from T0 to T3. Specifically, the spectral entropy and spectral exponent of the parietal and occipital regions were significantly higher at T2 and T3 than that at T0 (p < 0.05). In addition, The changes in EEG features of the parietal and occipital lobes were correlated with changes in CRS-R value, especially between T2 and T0. CONCLUSION: Long-term parietal HD-tDCS can improve the consciousness level and brain activity in DOC patients. Resting-state EEG can evaluate the dynamic changes of brain activity in DOC patients during HD-tDCS. EEG oscillation and non-oscillatory activity might be used to explain the mechanism of HD-tDCS on DOC patients.

EEG connectivity and network analyses predict outcome in patients with disorders of consciousness - A systematic review and meta-analysis.

Outcome prediction in prolonged disorders of consciousness (DOC) remains challenging. This can result in either inappropriate withdrawal of treatment or unnecessary prolongation of treatment. Electroencephalography (EEG) is a cheap, portable, and non-invasive device with various opportunities for complex signal analysis. Computational EEG measures, such as EEG connectivity and network metrics, might be ideal candidates for the investigation of DOC, but their capacity in prognostication is still undisclosed. We conducted a meta-analysis aiming to compare the prognostic power of the widely used clinical scale, Coma Recovery Scale-Revised - CRS-R and EEG connectivity and network metrics. We found that the prognostic power of the CRS-R scale was moderate (AUC: 0.67 (0.60-0.75)), but EEG connectivity and network metrics predicted outcome with significantly (p = 0.0071) higher accuracy (AUC:0.78 (0.70-0.86)). We also estimated the prognostic capacity of EEG spectral power, which was not significantly (p = 0.3943) inferior to that of the EEG connectivity and graph-theory measures (AUC:0.75 (0.70-0.80)). Multivariate automated outcome prediction tools seemed to outperform clinical and EEG markers.

Corticomotor facilitation in vegetative state: results of a pilot study.

OBJECTIVE: To investigate whether corticomotor facilitation induced by transcranial magnetic stimulation (TMS-CF) could evoke a simple purposeful motor behavior in patients with a diagnosis of vegetative state. DESIGN: Cross-sectional survey. SETTING: Post-coma and rehabilitation care unit. PARTICIPANTS: Patients (N=6) with a diagnosis of vegetative state. INTERVENTIONS: A cascade of consecutive motor-evoked potentials (MEPs) was elicited under 3 different conditions: in the first condition, patients were at rest (Rest); in the second, they were asked to open and close the right hand (Execution); in the third, the examiner modeled a movement of abduction of the thumb in front of the patient who was encouraged in advance to imitate the action (Observation to Imitate). MAIN OUTCOME MEASURES: Changes in MEP values from the abductor pollicis brevis muscle and improvement in scores on the Coma Recovery Scale-Revised. RESULTS: TMS-CF alone or combined with verbal instructions did not yield any change; only the combination with imitation caused changes in MEPs (shorter latency and increased amplitude) associated with behavioral improvement in 4 patients. CONCLUSIONS: Encouraging observation to imitate may favor the transformation of some perceived actions into motor images and performances, probably depending on the activation of mirror motor neurons. In our opinion, combining visual input with TMS-CF might have reinforced the coupling between movement planning and execution, promoting the recovery of elementary motor activities in some patients. The proposed protocol may contribute to unmasking signs of preserved consciousness in patients with latent capacities for recovery.

Integration of intensive care treatment and neurorehabilitation in patients with disorders of consciousness: a program description and case report.

Severe brain injuries frequently result in disorders of consciousness, requiring intensive care unit treatment. We present a rehabilitative system that integrates neurorehabilitation into intensive care treatment. The system will be described using the case report of a young man who was in a vegetative state after a severe traumatic brain injury that resulted in major medical problems and complications. Despite these challenges, interdisciplinary therapies can be applied throughout the rehabilitative process. The patient in our case report showed significant improvements and functional gains during the course of treatment. Additional data from other patients support the feasibility of this system and show that integrating neurorehabilitation into intensive care treatment is possible and can lead to improved outcomes in this patient population. We will discuss the advantages, special features, and limitations of the system. Additional studies are needed to further demonstrate the efficacy of this approach compared with standard treatment.

Medical complications during inpatient rehabilitation among patients with traumatic disorders of consciousness.

OBJECTIVE: To assess the incidence of medical complications in patients with recent traumatic disorders of consciousness (DOCs). DESIGN: Data on adverse events in a placebo controlled trial of amantadine hydrochloride revealed no group difference, which allowed these events to be reanalyzed descriptively as medical complications experienced by the 2 groups collectively. SETTING: Eleven clinical facilities in the United States, Denmark, and Germany with specialty rehabilitation programs for patients with DOCs. PARTICIPANTS: Patients (N=184) with nonpenetrating traumatic brain injury enrolled from acute inpatient rehabilitation programs between 4 and 16 weeks postinjury. INTERVENTIONS: Participants were randomized to receive 200 to 400mg of amantadine hydrochloride or placebo daily for 4 weeks, and followed for an additional 2 weeks. Adverse events were recorded and categorized with respect to their nature, timing, and severity. MAIN OUTCOME MEASURE: Number, type, and severity of medical complications occurring during the 6-week study interval. RESULTS: A total of 468 medical complications were documented among the patients (.40 events per week per patient). More than 80% of patients experienced at least 1 medical complication, and 41 of these were defined as serious adverse events. New medical complications declined over time in rehabilitation and were not dependent on time since injury. Hypertonia, agitation/aggression, urinary tract infection, and sleep disturbance were the most commonly reported problems. Hydrocephalus, pneumonia, gastrointestinal problems, and paroxysmal sympathetic hyperactivity were the most likely to be severe. CONCLUSIONS: Patients with DOCs have a high rate of medical complications early after injury. Many of these complications require brain injury expertise for optimal management. Active medical management appears to contribute to the reduction in new complications. An optimal system of care for DOC patients must provide expert medical management in the early weeks after injury.

Can mental imagery functional magnetic resonance imaging predict recovery in patients with disorders of consciousness?

OBJECTIVE: To determine the potential prognostic value of using functional magnetic resonance imaging (fMRI) to identify patients with disorders of consciousness, who show potential for recovery. DESIGN: Observational study. SETTING: Unit for acute rehabilitation care. PARTICIPANTS: Patients (N=22) in a vegetative state (VS; n=10) and minimally conscious state (MCS; n=12) during the first 200 days after the initial incident. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Further course on the Coma Recovery Scale-Revised. RESULTS: Participants performed a mental imagery fMRI paradigm. They were asked to alternately imagine playing tennis and navigating through their home. In 14 of the 22 examined patients (VS, n=5; MCS, n=9), a significant activation of the regions of interest (ROIs) of the mental imagery paradigm could be found. All 5 patients with activation of a significant blood oxygen level dependent signal, who were in a VS at the time of the fMRI examination, reached at least an MCS at the end of the observation period. In contrast, 5 participants in a VS who failed to show activation in ROIs, did not (sensitivity 100%, specificity 100%). Six of 9 patients in an MCS with activation in ROIs emerged from an MCS. Of 3 patients in an MCS who did not show activation, 2 patients stayed in an MCS and 1 patient emerged from the MCS (sensitivity 85%, specificity 40%). CONCLUSIONS: The fMRI paradigm mental imagery displays a high concordance with the further clinical course of patients in a VS. All 5 patients in a VS who showed significant activation of ROIs had a favorable further course until the end of the observation period. We therefore propose the term "functional minimally conscious state" for these patients. They may benefit from rehabilitation treatment. In cases where no significant activation was seen, the method has no prognostic value. Prediction of the clinical course of patients in an MCS by fMRI was considerably less accurate than in patients in a VS.

Descriptive characteristics and rehabilitation outcomes in active duty military personnel and veterans with disorders of consciousness with combat- and noncombat-related brain injury.

OBJECTIVE: To report the injury and demographic characteristics, medical course, and rehabilitation outcome for a consecutive series of veterans and active duty military personnel with combat- and noncombat-related brain injury and disorder of consciousness (DOC) at the time of rehabilitation admission. DESIGN: Retrospective study. SETTING: Rehabilitation center. PARTICIPANTS: From January 2004 to October 2009, persons (N=1654) were admitted to the Polytrauma Rehabilitation System of Care. This study focused on the N=122 persons admitted with a DOC. Participants with a DOC were primarily men (96%), on active duty (82%), ≥12 years of education, and a median age of 25. Brain injury etiologies included mixed blast trauma (24%), penetrating (8%), other trauma (56%), and nontrauma (13%). Median initial Glasgow Coma Scale score was 3, and rehabilitation admission Glasgow Coma Scale score was 8. Individuals were admitted for acute neurorehabilitation approximately 51 days postinjury with a median rehabilitation length of stay of 132 days. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Recovery of consciousness and the FIM instrument. RESULTS: Most participants emerged to regain consciousness during neurorehabilitation (64%). Average gains ± SD on the FIM cognitive and motor subscales were 19 ± 25 and 7 ± 8, respectively. Common medical complications included spasticity (70%), dysautonomia (34%), seizure occurrence (30%), and intracranial infection (22%). Differential outcomes were observed across etiologies, particularly for those with blast-related brain injury etiology. CONCLUSIONS: Despite complex comorbidities, optimistic outcomes were observed. Individuals with severe head injury because of blast-related etiologies have different outcomes and comorbidities observed. Health-services research with a focus on prevention of comorbidities is needed to inform optimal models of care, particularly for combat injured soldiers with blast-related injuries.

Rationale and design of the prospective German registry of outcome in patients with severe disorders of consciousness after acute brain injury.

OBJECTIVE: To describe the rationale and design of a new patient registry (Koma Outcome von Patienten der Frührehabilitation-Register [KOPF-R; Registry for Coma Outcome in Patients Undergoing Acute Rehabilitation]) that has the scope to examine determinants of long-term outcome and functioning of patients with severe disorders of consciousness (DOC). DESIGN: Prospective multicenter neurologic rehabilitation registry. SETTING: Five specialized neurologic rehabilitation facilities. PARTICIPANTS: Patients (N=42) with DOC in vegetative state or minimally conscious state (MCS) as defined by the Coma Recovery Scale-Revised (CRS-R) after brain injury. Patients are being continuously enrolled. The data presented here cover the enrollment period from August 2011 to January 2012. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: CRS-R, FIM, and emergence from MCS. RESULTS: The registry was set up in 5 facilities across the state of Bavaria/Germany with a special expertise in the rehabilitation of acquired brain injury. Inclusion of patients started in August 2011. Measures include sociodemographic and clinical characteristics, course of acute therapy, electrophysiologic measures (evoked potentials, electroencephalogram), neuron-specific enolase, current medication, functioning, cognition, participation, quality of life, quantity and characteristics of rehabilitation therapy, caregiver burden, and attitudes toward end-of-life decisions. Main diagnoses were traumatic brain injury (24%), intracerebral or subarachnoid hemorrhage (31%), and anoxic-ischemic encephalopathy (45%). Mean CRS-R score ± SD at admission to rehabilitation was 5.9 ± 3.3, and mean FIM score ± SD at admission was 18 ± 0.4. CONCLUSIONS: The KOPF-R aspires to contribute prospective data on prognosis in severe DOC.

Specialized early treatment for persons with disorders of consciousness: program components and outcomes.

OBJECTIVES: To describe a specialized early treatment program for persons with disorders of consciousness (DOC) that includes family education; to identify rates of secondary conditions, imaging used, and selected interventions; and to evaluate outcomes. DESIGN: A single-center, retrospective, pre-post design using electronic medical record data. SETTING: A Commission on Accreditation of Rehabilitation Facilities-accredited, long-term acute care hospital that provides acute medical and inpatient rehabilitation levels of care for people with catastrophic injuries. PARTICIPANTS: Persons (N=210) aged 14 to 69 years with DOC of primarily traumatic etiology admitted at a mean ± SD of 41.0 ± 27.2 days postinjury; 2% were in coma, 41% were in the vegetative state, and 57% were in the minimally conscious state. INTERVENTIONS: An acute medical level of care with ≥90 minutes of daily interdisciplinary rehabilitation and didactic and hands-on caretaking education for families. MAIN OUTCOME MEASURES: Coma Recovery Scale-Revised, Modified Ashworth Scale, and discharge disposition. RESULTS: Program admission medical acuity included dysautonomia (15%), airway modifications (79%), infections (eg, pneumonia, 16%; urinary tract infection, 14%; blood, 11%), deep vein thrombosis (17%), pressure ulcers (14%), and marked hypertonia (30% in each limb). There were 168 program interruptions (ie, 139 surgeries, 29 nonsurgical intensive care unit transfers). Mean length of stay ± SD was 39.1 ± 29.4 days (range, 6-204d). Patients showed improved consciousness and respiratory function and reduced presence or severity of pressure ulcers and upper extremity hypertonia. At discharge, 54% showed sufficient emergence from a minimally conscious state to transition to mainstream inpatient rehabilitation, and 29% did not emerge but were discharged home to family with ongoing programmatic support; only 13% did not emerge and were institutionalized. CONCLUSIONS: Persons with DOC resulting primarily from a traumatic etiology who receive specialized early treatment that includes acute medical care and ≥90 minutes of daily rehabilitation are likely to show improved consciousness and body function; more than half may transition to mainstream inpatient rehabilitation. Families who receive comprehensive education and hands-on training with ongoing follow-up support may be twice as likely to provide care for medically stable persons with DOC in their homes versus nursing facility placement.

Evaluating the effect of spinal cord stimulation on patient with disorders of consciousness: A TMS-EEG study.

OBJECTIVE: The application of spinal cord stimulation (SCS) in the treatment of disorders of consciousness (DOC) has attracted attention, but its effect on brain activity is still unknown. Transcranial magnetic stimulation combined with EEG (TMS-EEG) can measure cortical activity, which can evaluate the effect of SCS on DOC. METHODS: We record 20 DOC patients' CRS-R values and TMS-EEG data before and after one-session SCS (Pre-SCS and Post-SCS). 20 DOC patients including 10 patients with unresponsive wakefulness syndrome (UWS) and 10 patients with minimally conscious states (MCS). TMS evoked potential (TEP) was used to measure the changes of cortical activity in DOC patients between Pre-SCS and Post-SCS. Firstly, we used the global mean field potential (GMFP) and fast perturbational complexity index (PCIst) to compare the temporal changes of patients' cortical activity. Then, we obtained the frequency feature (natural frequency, NF) based on the TEP time-frequency analysis, and compared the changes of natural frequency between Pre-SCS and Post-SCS. Finally, the study explored the relationship between the patient's baseline CRS-R values and changes of TMS evoked cortical activity in time and frequency domains. RESULTS: After SCS, MCS and UWS groups almost have no changes of CRS-R values (MCS: 9.9 ± 1.52 at Pre-SCS, 10.2 ± 1.48 at Post-SCS; UWS: 5.6 ± 1.26 at Pre-SCS, 5.7 ± 1.34 at Post-SCS). MCS group showed significant increases of GMFP amplitude (around 100 ms and 300 ms) and PCIst values at Post-SCS (p < 0.05). UWS group had no significant changes (p > 0.05). Besides, SCS induced the significant increases of natural frequency for MCS group(p < 0.05), but not for UWS group. At last, the study found that all patient's baseline CRS-R values were significantly correlated with ΔPCIst (r = 0.67, p < 0.005), and ΔNF (r = 0.72, p < 0.001). CONCLUSIONS: SCS can modulate cortical activity of DOC patient, including temporal complexity and natural frequency. The changes of cortical activity caused by SCS are related to patients' consciousness level. TMS-EEG can evaluate the effect of SCS on DOC patients.

Deep brain stimulation improves electroencephalogram functional connectivity of patients with minimally conscious state.

AIM: Deep brain stimulation (DBS) is a potential neuromodulatory therapy that enhances recovery from disorders of consciousness, especially minimally conscious state (MCS). This study measured the effects of DBS on the brain and explored the underlying mechanisms of DBS on MCS. METHODS: Nine patients with MCS were recruited for this study. The neuromodulation effects of 100 Hz DBS were explored via cross-control experiments. Coma Recovery Scale-Revised (CRS-R) and EEG were recorded, and corresponding functional connectivity and network parameters were calculated. RESULTS: Our results showed that 100 Hz DBS could improve the functional connectivity of the whole, local and local-local brain regions, while no significant change in EEG functional connectivity was observed in sham DBS. The whole brain's network parameters (clustering coefficient, path length, and small world characteristic) were significantly improved. In addition, a significant increase in the CRS-R and functional connectivity of three MCS patients who received 100 Hz DBS for 6 months were observed. CONCLUSION: This study showed that DBS improved EEG functional connectivity and brain networks, indicating that the long-term use of DBS could improve the level of consciousness of MCS patients.