The Prognostic Role of Candidate Serum Biomarkers in the Post-Acute and Chronic Phases of Disorder of Consciousness: A Preliminary Study.

INTRODUCTION: Serum biomarkers, such as Neurofilament Light (NF-L), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase (UCH-L1), and Total-tau (T-Tau) have been proposed for outcome prediction in the acute phase of severe traumatic brain injury, but they have been less investigated in patients with prolonged DoC (p-DoC). METHODS: We enrolled 25 p-DoC patients according to the Coma Recovery Scale-Revised (CRS-R). We identified different time points: injury onset (t0), first blood sampling at admission in Neurorehabilitation (t1), and second blood sampling at discharge (t2). Patients were split into improved (improved level of consciousness from t1 to t2) and not-improved (unchanged or worsened level of consciousness from t1 to t2). RESULTS: All biomarker levels decreased over time, even though each biomarker reveals typical features. Serum GFAP showed a weak correlation between t1 and t2 (p = 0.001), while no correlation was observed for serum NF-L (p = 0.955), UCH-L1 (p = 0.693), and T-Tau (p = 0.535) between t1 and t2. Improved patients showed a significant decrease in the level of NF-L (p = 0.0001), UCH-L1 (p = 0.001), and T-Tau (p = 0.002), but not for serum GFAP (p = 0.283). No significant statistical differences were observed in the not-improved group. CONCLUSIONS: A significant correlation was found between the level of consciousness improvement and decreased NF-L, UCH-L1, and T-Tau levels. Future studies on the association of serum biomarkers with neurophysiological and neuroimaging prognostic indicators are recommended.

Neuro-orthopaedic assessment and management in patients with prolonged disorders of consciousness: A review.

BACKGROUND: Following a severe acquired brain injury, neuro-orthopaedic disorders are commonplace. While these disorders can impact patients' functional recovery and quality of life, little is known regarding the assessment, management and treatment of neuro-orthopaedic disorders in patients with disorders of consciousness (DoC). OBJECTIVE: To describe neuro-orthopaedic disorders in the context of DoC and provide insights on their management and treatment. METHODS: A review of the literature was conducted focusing on neuro-orthopaedic disorders in patients with prolonged DoC. RESULTS: Few studies have investigated the prevalence of spastic paresis in patients with prolonged DoC, which is extremely high, as well as its correlation with pain. Pilot studies exploring the effects of pharmacological treatments and physical therapy show encouraging results yet have limited efficacy. Other neuro-orthopaedic disorders, such as heterotopic ossification, are still poorly investigated. CONCLUSION: The literature of neuro-orthopaedic disorders in patients with prolonged DoC remains scarce, mainly focusing on spastic paresis. We recommend treating neuro-orthopaedic disorders in their early phases to prevent complications such as pain and improve patients' recovery. Additionally, this approach could enhance patients' ability to behaviourally demonstrate signs of consciousness, especially in the context of covert awareness.

International survey on the implementation of the European and American guidelines on disorders of consciousness.

Diagnostic, prognostic, and therapeutic procedures for patients with prolonged disorders of consciousness (pDoCs) vary significantly across countries and clinical settings, likely due to organizational factors (e.g., research vs. non-academic hospitals), expertise and availability of resources (e.g., financial and human). Two international guidelines, one from the European Academy of Neurology (EAN) and one from the American Academy of Neurology (AAN) in collaboration with the American Congress of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), were developed to facilitate consistent practice among professionals working with this challenging patient population. While the recommendations of both guidelines agree in principle, it remains an open issue how to implement them into clinical practice in the care pathway for patients with pDoCs. We conducted an online survey to explore health professional clinical practices related to the management of patients with pDoCs, and compare said practices with selected recommendations from both the guidelines. The survey revealed that while some recommendations are being followed, others are not and/or may require more honing/specificity to enhance their clinical utility. Particular attention should be given to the implementation of a multimodal assessment of residual consciousness, to the detection and treatment of pain, and to the impact of restrictions imposed by COVID-19 pandemics on the involvement of patients' families/representatives.

Long-term risk of cardiovascular disease after traumatic brain injury: screening and prevention.

Traumatic brain injury (TBI) is highly prevalent among individuals participating in contact sports, military personnel, and in the general population. Although it is well known that brain injury can cause neurological and psychiatric complications, evidence from studies on individuals exposed to a single or repetitive brain injuries suggests an understudied association between TBI and the risk of developing chronic cardiovascular diseases and risk factors for cardiovascular disease. Several studies have shown that people without pre-existing comorbidities who sustain a TBI have a significantly higher risk of developing chronic cardiovascular disease, than people without TBI. Similar observations made in military and professional American-style football cohorts suggest causal pathways through which modifiable cardiovascular risk factors might mediate the relationship between brain injury and chronic neurological diseases. A better understanding of cardiovascular disease risk after TBI combined with a proactive, targeted screening programme might mitigate long-term morbidity and mortality in individuals with TBI, and improve their quality of life.

The structure of the Early Rehabilitation Barthel Index (ERBI) should be modified: evidence from a Rasch analysis study.

BACKGROUND: The Early Rehabilitation Barthel Index (ERBI) comprises seven items of the Early Rehabilitation Index and ten items of the Barthel Index. The ERBI is usually used to measure functional changes in patients with severe acquired brain injury (sABI), but its measurement properties have yet to be extensively assessed. AIM: To study the unidimensionality and internal construct validity (ICV) of the ERBI through Confirmatory Factor Analysis (CFA), Mokken Analysis (MA), and Rasch Analysis (RA). DESIGN: Multicenter prospective study. SETTING: Inpatients from five intensive rehabilitation centers. POPULATION: Two hundred and forty-seven subjects with sABI. METHODS: ERBI was administered on admission and discharge to study its unidimensionality through CFA and MA and its ICV, reliability, and targeting through RA. RESULTS: The preliminary analyses showed a lack of unidimensionality (RMSEA=0.460 >0.06; SRMR=0.176 >0.06; CFI=1.000 >0.950; TLI=1.000 >0.950). According to CFA, "Confusional state" and "Behavioral disturbance" items showed low factor loadings (<0.40), whereas these two items composed a separate scale within the MA. Furthermore, the baseline RA showed that three items misfitted ("Mechanical ventilation," "Confusional state," "Behavioral disturbances") and a lack of conformity of several ICV requirements. After deletion of three misfitting items and further non-structural modifications (i.e., testlets creation to absorb local dependence between items and item misfit), the solution obtained showed adequate ICV, adequate reliability for measurements at the individual level (PSI>0.85), although with a frank floor effect. This final solution was successfully replicated in a total sample of the subjects. After post-hoc modifications of the score structure of two out of three misfitting items, the subsequent CFA (RMSEA=0.044 <0.06; SRMR=0.056 <0.06; CFI=1.000 >0.950 TLI=1.000 >0.950) and MA showed the resolution of the unidimensional issues. CONCLUSIONS: Although the ERBI is a potentially valuable tool for measuring functioning in the coma-to-community continuum, our analyses suggested its lack of ICV, partly due to an incorrect scoring design of some items. A new perspective multicenter study is proposed to validate a modified version of the ERBI that overcomes the problems highlighted in this analysis. CLINICAL REHABILITATION IMPACT: Our results do not support the use of the original structure of the ERBI in clinical practice and research, as a lack of ICV was highlighted.

Sham-controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness.

BACKGROUND AND PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double-blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS. METHODS: Patients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months' follow-up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non-traumatic). Interim analyses were planned to continue or stop the trial. RESULTS: The trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post-injury, 18 women, 32 MCS, 39 non-traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months' follow-up revealed a significant improvement for patients in MCS and with traumatic aetiology. CONCLUSIONS: Transcranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.

Scoping Review on the Diagnosis, Prognosis, and Treatment of Pediatric Disorders of Consciousness.

BACKGROUND AND OBJECTIVES: Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to summarize available evidence for DoC with >14 days duration to support the future development of guidelines for children, adolescents and young adults aged 6 months-18 years. METHODS: This scoping review was reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses-extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3 blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated. RESULTS: On November 9, 2022, 2,167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the past 5 years. Overall, 2,161 individuals met the inclusion criteria; female patients were 527 of 1,554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%) and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near-Coma Scale, Level of Cognitive Functioning Assessment Scale, and Post-Acute Level of Consciousness scale. EEG, event-related potentials, structural CT, and MRI were the most frequently used instrumental techniques. In 29/53 (54.7%) cases, DoC improvement was observed, which was associated with treatment with amantadine. DISCUSSION: The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence and have limited validity and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to the diagnosis, prognosis, and treatment of pediatric DoC.

When the practice does not meet the theory: results from an Italian survey on the clinical and pathway management of inpatients with decompressive craniectomy or cranioplasty admitted to rehabilitation.

BACKGROUND: Cranioplasty (CP) is supposed to improve the functional outcome of severe acquired brain injury (sABI) patients with decompressive craniectomy (DC). However, ongoing controversies exist regarding its indications, optimum materials, timing, complications, and relationships with hydrocephalus (HC). For these reasons, an International Consensus Conference (ICC) on CP in traumatic brain injury (TBI) was held in June 2018 to issue some recommendations. AIM: The aims of this study were: to investigate cross-sectionally before the ICC the prevalence of DC/CP in sABI inpatients admitted to neurorehabilitation units in Italy; to assess the perception of Italian clinicians working in the sABI neurorehabilitation settings on the management of inpatients with DC/CP during their rehabilitation stay. DESIGN: Cross-sectional. SETTING AND POPULATION: Physiatrists or neurologists working in 38 Italian rehabilitation centers involved in the care of sABI, giving a pooled sample of 599 inpatients. METHODS: Survey questionnaire consisting of 21 closed-ended questions with multiple-choice answers. Sixteen questions regarded the respondents' opinions and experiences regarding the clinical and management aspects of patients. Survey data were collected via e-mail between April and May 2018. RESULTS: About 1/3 of the 599 inpatients had either a DC (18.9%) or a CP (13.5%). TBI and cerebral hemorrhage were strongly associated with DC/CP, although the association was much stronger for TBI. Significant discrepancies were uncovered between some of the recommendations of the ICC and the corresponding perceptions of the respondents, especially regarding the clinical management of patients (i.e., CP timing). Clear guidelines were perceived as the most crucial factor in improving clinical pathways. CONCLUSIONS: Early collaboration between the neurosurgical and the neurorehabilitation teams is crucial to optimize all clinical and organizational factors, which could expedite CP and minimize the risk of complications, such as infections and HC, to ensure the best possible outcome for DC patients, regardless of the etiology of the sABI. CLINICAL REHABILITATION IMPACT: There may be different attitudes and perceptions, if not controversies, between neurorehabilitation physicians and neurosurgeons regarding the optimal clinical and care pathway management of patients with DC/CP in Italy. Therefore, an Italian Consensus Conference involving all stakeholders on the clinical and management pathways of DC/CP patients admitted to neurorehabilitation is advocated.

Modeling outcome trajectories in patients with acquired brain injury using a non-linear dynamic evolution approach.

This study describes a dynamic non-linear mathematical approach for modeling the course of disease in acquired brain injury (ABI) patients. Data from a multicentric study were used to evaluate the reliability of the Michaelis-Menten (MM) model applied to well-known clinical variables that assess the outcome of ABI patients. The sample consisted of 156 ABI patients admitted to eight neurorehabilitation subacute units and evaluated at baseline (T0), 4 months after the event (T1) and at discharge (T2). The MM model was used to characterize the trend of the first Principal Component Analysis (PCA) dimension (represented by the variables: feeding modality, RLAS, ERBI-A, Tracheostomy, CRS-r and ERBI-B) in order to predict the most plausible outcome, in terms of positive or negative Glasgow outcome score (GOS) at discharge. Exploring the evolution of the PCA dimension 1 over time, after day 86 the MM model better differentiated between the time course for individuals with a positive and negative GOS (accuracy: 85%; sensitivity: 90.6%; specificity: 62.5%). The non-linear dynamic mathematical model can be used to provide more comprehensive trajectories of the clinical evolution of ABI patients during the rehabilitation period. Our model can be used to address patients for interventions designed for a specific outcome trajectory.

The Possible Role of Apathy on Conflict Monitoring: Preliminary Findings of a Behavioral Study on Severe Acquired Brain Injury Patients Using Flanker Tasks.

The diagnosis of apathy, one of the most common behavioral changes after acquired brain injury (ABI), is important for improving clinical understanding and treatment of persons with ABI. The main aim of this study was to determine the possible role of apathy in conflict monitoring, by using choice reaction time tasks. Methods: We examined behavioral responses of conflict monitoring during three different flanker tasks in 10 severe ABI patients with or without diagnosis of apathy (3 M, mean age = 56.60; 3 M, mean age ± SD = 58.60, respectively), and 15 healthy controls (9 M, mean age = 54.46) Reaction times (RTs), accuracy, and global index of performance (GIP) were analyzed for each task. Results: Only apathetic ABI patients showed a significant difference from healthy subjects (p-value ≤ 0.001), while the performance of patients without apathy was not significantly different from that of healthy controls (p-value = 0.351). Healthy participants had higher accuracy in comparison to both ABI patients with (p < 0.001) and without (p-value = 0.038) apathy, whilst slower RTs were shown by ABI patients without apathy in comparison to both healthy subjects (p-value = 0.045) and apathetic ABI patients (p-value = 0.022). Only patients with apathy exhibited a significantly higher number of missing trials (p-value = 0.001). Conclusions: Our results may suggest a potential link between apathy following severe ABI and conflict monitoring processes, even though further investigations with larger sample size are needed.

EEG-based Brain-Computer Interfaces for people with Disorders of Consciousness: Features and applications. A systematic review.

Background: Disorders of Consciousness (DoC) are clinical conditions following a severe acquired brain injury (ABI) characterized by absent or reduced awareness, known as coma, Vegetative State (VS)/Unresponsive Wakefulness Syndrome (VS/UWS), and Minimally Conscious State (MCS). Misdiagnosis rate between VS/UWS and MCS is attested around 40% due to the clinical and behavioral fluctuations of the patients during bedside consciousness assessments. Given the large body of evidence that some patients with DoC possess "covert" awareness, revealed by neuroimaging and neurophysiological techniques, they are candidates for intervention with brain-computer interfaces (BCIs). Objectives: The aims of the present work are (i) to describe the characteristics of BCI systems based on electroencephalography (EEG) performed on DoC patients, in terms of control signals adopted to control the system, characteristics of the paradigm implemented, classification algorithms and applications (ii) to evaluate the performance of DoC patients with BCI. Methods: The search was conducted on Pubmed, Web of Science, Scopus and Google Scholar. The PRISMA guidelines were followed in order to collect papers published in english, testing a BCI and including at least one DoC patient. Results: Among the 527 papers identified with the first run of the search, 27 papers were included in the systematic review. Characteristics of the sample of participants, behavioral assessment, control signals employed to control the BCI, the classification algorithms, the characteristics of the paradigm, the applications and performance of BCI were the data extracted from the study. Control signals employed to operate the BCI were: P300 (N = 19), P300 and Steady-State Visual Evoked Potentials (SSVEP; hybrid system, N = 4), sensorimotor rhythms (SMRs; N = 5) and brain rhythms elicited by an emotional task (N = 1), while assessment, communication, prognosis, and rehabilitation were the possible applications of BCI in DoC patients. Conclusion: Despite the BCI is a promising tool in the management of DoC patients, supporting diagnosis and prognosis evaluation, results are still preliminary, and no definitive conclusions may be drawn; even though neurophysiological methods, such as BCI, are more sensitive to covert cognition, it is suggested to adopt a multimodal approach and a repeated assessment strategy.

Neurorehabilitation of severe acquired brain injury in the time of COVID-19: impact of the absence of caregivers.

INTRODUCTION: During the COVID-19 pandemic, several restrictions were imposed to limit the circulation of the infection within communities. Hospitals denied access to the family and friends of inpatients, and thus to caregivers. This observational study evaluated the impact of the physical absence of caregivers during the lockdown period due to the COVID-19 emergency on the rehabilitation of inpatients with severe acquired brain injury (sABI). METHODS: The functional outcome at discharge was measured in 25 inpatients with sABI through the Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS), and Levels of Cognitive Functioning scale (LCF) after neuropsychological rehabilitation in an Adult Inpatient Neurorehabilitation Unit for Patients with sABI. Fourteen patients were directly assisted by their informal caregivers physically present in the neurorehabilitation ward. Eleven patients were indirectly supported via remote connection because during the lockdown period (from March to July 2020) caregivers could not be admitted to the rehabilitation hospital. The Caregiving Impact on Neuro-Rehabilitation Scale (CINRS) was also used to evaluate both the change since the admission and the impact of the caregiver from the perspective of the cognitive therapist. Demographic characteristics, time since injury, injury severity (duration of impaired consciousness measured by the time to follow commands), level of functioning at the beginning of the rehabilitation, and duration of the rehabilitation treatment were comparable between the groups. RESULTS: Both groups improved after the treatment; however, the improvement was consistently greater in the group directly assisted by the caregivers. The results showed that although the caregivers ensured their virtual presence at distance, their physical absence played a role in hindering the functional outcome of the patients. CONCLUSIONS: The role of the caregiver of patients with sABI is underlined in being not only a person handing out generic aid, cares, and affection, but also an integral part of the rehabilitation process.

Vestibular Rehabilitation Improves Gait Quality and Activities of Daily Living in People with Severe Traumatic Brain Injury: A Randomized Clinical Trial.

Neurorehabilitation research in patients with traumatic brain injury (TBI) showed how vestibular rehabilitation (VR) treatments positively affect concussion-related symptoms, but no studies have been carried out in patients with severe TBI (sTBI) during post-acute intensive neurorehabilitation. We aimed at testing this effect by combining sensor-based gait analysis and clinical scales assessment. We hypothesized that integrating VR in post-acute neurorehabilitation training might improve gait quality and activity of daily living (ADL) in sTBI patients. A two-arm, single-blind randomized controlled trial with 8 weeks of follow-up was performed including thirty sTBI inpatients that underwent an 8-week rehabilitation program including either a VR or a conventional program. Gait quality parameters were obtained using body-mounted magneto-inertial sensors during instrumented linear and curvilinear walking tests. A 4X2 mixed model ANOVA was used to investigate session−group interactions and main effects. Patients undergoing VR exhibited improvements in ADL, showing early improvements in clinical scores. Sensor-based assessment of curvilinear pathways highlighted significant VR-related improvements in gait smoothness over time (p < 0.05), whereas both treatments exhibited distinct improvements in gait quality. Integrating VR in conventional neurorehabilitation is a suitable strategy to improve gait smoothness and ADL in sTBI patients. Instrumented protocols are further promoted as an additional measure to quantify the efficacy of neurorehabilitation treatments.

Self-Awareness Multilevel Assessment Scale (SAMAS): psychometric analysis of inter-rater reliability.

BACKGROUND: Severe acquired brain injury (sABI) frequently causes impairment in self-awareness (ISA), leading to reduced patients' compliance to treatment, worse functional outcome, and high caregiver distress. Self-awareness (SA) is a multilevel and complex function that, as such, requires a specific and effective assessment. To date, many tools are available to evaluate the declarative, but not emergent and anticipatory levels of awareness, therefore the Self-Awareness Multilevel Assessment Scale (SAMAS) was recently proposed. The new tool proved to be useful to assess SA at different levels across all domains of functioning (motor, cognitive, psycho-behavioural, etc.) because it measures not only the declarative SA, but also emergent and anticipatory levels of SA, thus overcoming some important limits of other current assessment methods. AIM: This study evaluated the inter-rater reliability (IRR) of the SAMAS. METHODS: Four professionals blind to each other evaluated 12 patients with sABI. Each patient was rated by two professionals. RESULTS: Inter-rater reliability was moderate-to-excellent, adding evidence in support of the use of SAMAS to specifically diagnose ISA after sABI. CONCLUSIONS: The SAMAS can help to better address neurorehabilitation, as it allows assessing ISA as early as possible, at all possible levels of awareness and functional domains.

The Effect of Dual-Task Motor-Cognitive Training in Adults with Neurological Diseases Who Are at Risk of Falling.

Falls are common in patients with neurological diseases and can be very problematic. Recently, there has been an increase in fall prevention research in people with neurological diseases; however, these studies are usually condition-specific (e.g., only MS, PD or stroke). Here, our aim was to evaluate and compare the efficacy of an advanced and innovative dual-task, motor-cognitive rehabilitation program in individuals with different neurological diseases who are at risk of falling. We recruited 95 consecutive adults with neurological diseases who are at risk of falling and divided them into four groups: 31 with cerebrovascular disease (CVD), 20 with Parkinson's disease (PD), 23 with traumatic brain injury (TBI) and 21 with other neurological diseases (OND). Each patient completed a dual-task, motor-cognitive training program and underwent two test evaluations to assess balance, gait, fear of falling and walking performance at the pre-and post-intervention. We found that our experimental motor-cognitive, dual-task rehabilitation program was an effective method for improving walking balance, gait, walking endurance and speed, and fear of falling, and that it reduced the risk of falls in patients with different neurological diseases. This study presents an alternative approach for people with chronic neurological diseases and provides innovative data for managing this population.

What names for covert awareness? A systematic review.

Background: With the emergence of Brain Computer Interfaces (BCI), clinicians have been facing a new group of patients with severe acquired brain injury who are unable to show any behavioral sign of consciousness but respond to active neuroimaging or electrophysiological paradigms. However, even though well documented, there is still no consensus regarding the nomenclature for this clinical entity. Objectives: This systematic review aims to 1) identify the terms used to indicate the presence of this entity through the years, and 2) promote an informed discussion regarding the rationale for these names and the best candidates to name this fascinating disorder. Methods: The Disorders of Consciousness Special Interest Group (DoC SIG) of the International Brain Injury Association (IBIA) launched a search on Pubmed and Google scholar following PRISMA guidelines to collect peer-reviewed articles and reviews on human adults (>18 years) published in English between 2006 and 2021. Results: The search launched in January 2021 identified 4,089 potentially relevant titles. After screening, 1,126 abstracts were found relevant. Finally, 161 manuscripts were included in our analyses. Only 58% of the manuscripts used a specific name to discuss this clinical entity, among which 32% used several names interchangeably throughout the text. We found 25 different names given to this entity. The five following names were the ones the most frequently used: covert awareness, cognitive motor dissociation, functional locked-in, non-behavioral MCS (MCS*) and higher-order cortex motor dissociation. Conclusion: Since 2006, there has been no agreement regarding the taxonomy to use for unresponsive patients who are able to respond to active neuroimaging or electrophysiological paradigms. Developing a standard taxonomy is an important goal for future research studies and clinical translation. We recommend a Delphi study in order to build such a consensus.

Neurorehabilitation for people with disorders of consciousness: an international survey of health-care structures and access to treatment, (Part 1).

AIMS: The provision of rehabilitation services for people with disorders of consciousness (DoC) may vary due to geographical, financial, and political factors. The extent of this variability and the implementation of treatment standards across countries is unknown. This study explored international neurorehabilitation systems for people with DoC. METHODS: An online survey (SurveyMonkey®) was disseminated to all members of the International Brain Injury Association (IBIA) DoC Special Interest Group (SIG) examining existing rehabilitation systems and access to them. RESULTS: Respondents (n = 35) were from 14 countries. Specialized neurorehabilitation was available with varying degrees of access and duration. Commencement of specialized neurorehabilitation averaged 3-4 weeks for traumatic brain injury (TBI) and 5-8 weeks for non-traumatic brain injury (nTBI) etiologies. Length of stay in inpatient rehabilitation was 1-3 months for TBI and 4-6 months for nTBI. There were major differences in access to services and funding across countries. The majority of respondents felt there were not enough resources in place to provide appropriate neurorehabilitation. CONCLUSIONS: There exists inter-country differences for DoC neurorehabilitation after severe acquired brain injury. Further work is needed to implement DoC treatment standards at an international level.

Neural underpinnings of the slowness of information processing in patients with traumatic brain injury: insights from tract-based spatial statistics.

Slowness of information processing (SIP) is frequently reported after traumatic brain injury (TBI). Previous studies point toward a pivotal role of white matter damage on speed of information processing. However, little is known about the more comprehensive and ecological assessment of SIP in TBI. Here, we combined an ecological assessment of SIP with the use of tract-based spatial statistics (TBSS) on individuals' fractional anisotropy (FA) maps. Twenty-six moderate-to-severe patients with TBI (21 males and 5 females) participated in this study: 10 individuals were classified as not having SIP (SIP-) and 16 were classified as having SIP (SIP +). SIP + showed lower FA in bilateral anterior thalamic radiation, corticospinal tract, cingulum, and forceps, as well as in bilateral inferior fronto-occipital, inferior and superior longitudinal fasciculi and uncinate fasciculus. Overall, this result is consistent with and expands previous reports on information processing speed to a more comprehensive and ecological perspective on SIP in TBI.

Pain in Persons with Disorders of Consciousness.

Pain and suffering in persons with disorders of consciousness (DoC) remain poorly understood, frequently unaddressed or inadequately addressed, and controversial on numerous levels. This narrative literature review will address a number of critical issues germane to pain and suffering in this challenging group of patients, providing an introductory overview of the topic, perspectives on current knowledge regarding pain pathoanatomy and pathophysiology, and a review of common pain generators and factors that can lead to the chronifcation of pain. Caveats on bedside pain assessment challenges, as well as electrophysiologic and neuroimaging findings in these patients, will also be explored. Pain management techniques, including non-pharmacological and pharmacological, will be reviewed. Ethical considerations in the context of pain and suffering in persons with disorders of consciousness will round out the review prior to our concluding comments.