Recent guidelines on disorders of consciousness (DoC) propose strategies to enhance care; however, an international survey reveals that many recommendations are inadequately implemented, and treatment structures are insufficient. Neurorehabilitation practices vary by region and are not applicable to countries with less stable healthcare systems. In Latin America (LA), there is a lack of information on current clinical practice and could be key to improve DoC management in the region.
The aim of this study was to explore the availability of treatment facilities and current clinical practices in LA regarding the neurorehabilitation of pediatrics and adults with DoC.

Methods: An online survey (RedCap) was completed by 103 health professionals from 11 countries in Latin America. It was distributed through scientific societies in 21 countries and included 42 closed questions on demographic data, knowledge, professional practice and access to rehabilitation treatment. Descriptive statistics were generated from the responses.

Results: The survey was primarily conducted in Spanish (90.6%) respondents. Mean age of 42 years (SD = 10), and 70.7% female. The mean experience was 10 years in DoC. Key countries represented were Argentina (58%), Mexico (17%), and Brazil (10%), with 52% being physicians.
54% of respondents treat patients with 3 to 12 months of injury and 39% treat them in rehabilitation centers. Familiarity with clinical practice guidelines was noted by 44%, and 80% implemented them fully or partially. About 39.4% had structured programs for treating DoC patients, while 16.8% were in the implementation phase.
35.4% responded that the length of stay in rehabilitation is 3-6 months. Diagnostic evaluations included clinical history reviews (87%), structural imaging (71%), standardized behavioral tests (78%), and general assessments (93%). The Coma Recovery Scale-Revised (CRS-R) was the most used standardized scale (54.5%).
Pharmacological interventions included medications for spasticity (76%), central nervous system stimulants (44%), pain control (58%), and wakefulness enhancers (52%). Non-pharmacological interventions were primarily physical therapy (89.1%), occupational therapy (75.2%), and speech therapy (81.2%). Professionals had access to both high-tech (40%) and low-tech technology devices (66%).
The most common discharge destination was home (75%), with 78% continuing rehabilitation at home or in outpatient settings. Follow-up care preferences included clinic visits (53%) and teleconsultations (9%). Assistive products commonly used were wheelchairs (89.1%) and personal care devices (73.3%).
Primary caregivers were often involved through educational sessions (73.3%), with 70% providing formal training. Family members mainly assumed caregiver roles (46%). Key challenges included resource shortages (69.3%) and limited access to specialized programs (57.4%).

Conclusions: This survey reveals significant gaps between clinical practice guidelines and actual rehabilitation of individuals with DoC in LA. Despite familiarity with these guidelines, resources and limited access to specialized programs impede effective treatment. Most patients return home after discharge, emphasizing the need for effective home-based rehabilitation strategies.

Disorders of consciousness (DoC) encompass several conditions, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), with limited treatment options. Current theories linking brain complexity to consciousness suggest that psychedelic drugs, such as Lysergic Acid Diethylamide (LSD) and psilocybin, hold potential as therapeutic agents for these disorders. Computational modelling offers an ethical precursor to experimental work which can guide future empirical research. In this study, we present a novel computational framework to simulate the effects of LSD and psilocybin in patients with DoC. Whole-brain computational models were constructed at the single-subject level, utilising patient-specific structural connectivity (SC), derived from diffusion-weighted imaging (DWI) tractography, and functional magnetic resonance imaging (fMRI) resting-state BOLD activity. We used previously acquired fMRI data from 52 DoC patients (23 UWS, 29 MCS), comprising 21 with traumatic brain injury and 25 with non-traumatic brain injury, as well as 12 HC after LSD/placebo and 15 HC after psilocybin/placebo. Each brain region's dynamics were modelled by Stuart-Landau oscillators, and model parameters were optimised to ensure the best fit between simulated and empirical fMRI connectivity. We then simulated the administration of LSD and psilocybin on patients with DoC, by applying the changes in parameters between the drug state and the non-drug state in healthy controls to patient models. We assessed simulated treatment effects by calculating the perturbation integration latency index (PILI) at both the baseline and the simulated drug state. The PILI is a modelling-based measure of brain dynamical instability which quantifies the recovery of a perturbed brain region to its basal state. Changes in PILI between baseline and drug-simulated states served as a proxy for potential treatment response. At baseline, PILI values were significantly higher in HC compared to UWS (z=3.60, p<0.001) and in MCS compared to UWS (z=2.34, p=0.02). Simulations of LSD on patient models led to significant PILI increases in MCS (z=4.13, p<0.001) and UWS (z=2.8, p<0.001) patients. Simulations of psilocybin on patient models also led to significant PILI increases in MCS (z=3.92, p<0.001) and UWS (z=3.71, p<0.001) patients. For MCS patients, simulated treatment-related PILI increases were correlated with functional connectivity (FC) (r=0.66, p<0.0001), whereas in UWS patients, PILI changes were associated with SC strength (r=0.67, p<0.001). The observed PILI increases during psychedelic simulations suggest that these treatments may shift the brains of DoC patients towards a more critical regime, enhancing sensitivity to perturbations—a foundational concept for this therapeutic approach. Importantly, we identified potential biomarkers for treatment efficacy: in MCS patients, higher baseline FC predicted larger treatment effects, while in UWS patients, SC strength was the key predictor. Here, we contributed to the burgeoning field of computational modelling for personalised medicine and provide an example of available avenues for testing emerging therapies in-silico.

Introduction: The duration and characteristics of the Post-traumatic Confusional State (PTCS) in patients that have emerged from a prolonged Disorders of Consciousness (DoC) has not been investigated yet. OBJECTIVES: To describe the frequency and attributes of PTCS in patients with prolonged DoC (ie., >28 days post-injury), as well as the factors predicting emergence from PTCS.

Methods: We retrospectively included patients from the database of a specialized neurorehabilitation service. Inclusion criteria were: patients (admitted January 2004 to October 2023) with a prolonged DoC caused by a traumatic brain injury (TBI), ≥ 16 years old, ≤ 6 months post-injury at admission, records of follow-up data for at least 3 months post-admission. Patients were assessed weekly with the Coma Recovery Scale-Revised (CRS-R) while in DoC; and with the Mississippi Aphasia Screening Test (MAST) and Galveston Orientation and Amnesia Test (GOAT) when they emerged from the minimally conscious state (eMCS). We conducted univariate analyses on sample characteristics and a multivariate logistic regression analysis on predictors of emerging from the PTCS.

Results: 88 patients (VS/UWS=40, MCS-=28; MCS+=20, on admission) met inclusion criteria. 47 of them emerged from the MCS (VS/UWS=11, MCS-=16; MCS+=20, on admission) with these characteristics on the CRS-R (N=16 emerged with functional object use, N=13 with functional communication, and N=18 with both). 25 out of the 47 patients who emerged (VS/UWS=4, MCS-=8, MCS+=13, on admission) overcame PTCS a mean of 98.5±60 days after emerging from MCS. A total of 13 patients required a modified GOAT due to global aphasia (N=5) or anarthria (N=8). None of the patients with global aphasia overcame PTCS, while 3 of the 8 patients with anarthria did. Of the 47 patients who emerged from MCS, those who emerged from PTCS were younger (p<0.05), had shorter time since injury (p<0.05), emerged from MCS earlier (p<0.01), showed functional communication upon emerging (p<0.05), and had higher scores on the CRS-R (p<0.01) and GOAT (p<0.01) at the time of MCS emergence. The multivariate regression analysis identified the initial GOAT score as the strongest predictor of PTCS emergence (p<0.01).

Conclusions: Even though diagnosis at admission is a known predictor of emergence from the MCS, it does not appear to play a role in emergence from the PTCS. The overall cognitive state at emergence from MCS (eg. initial GOAT score) and the communication level (eg. presence/absence of aphasia or anarthria) seem to be particularly relevant in establishing the odds of patients to emerge from the PTCS.

Acknowledgments: This work was supported by Conselleria d’Innovació, Universitats, Ciència i Societat Digital of Generalitat Valenciana (CIDEXG/2022/15), Ministerio de Ciencia e Innovación (PID2022-141498OA-I00), Fundació la Marató de la TV3 (60/2023), and European Commission (HORIZON-MSCA-2022-PF-01-10110814).

Introduction: Some patients who survive severe brain injuries may develop disorders of consciousness (DoC), such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). UWS is characterized by signs of arousal without self or environmental awareness, while MCS involves both arousal and awareness, demonstrated by non-reflexive behaviors or preserved language. Patients are considered to have emerged from MCS if they regain functional communication or object use. Although research on DoC diagnosis and prognosis is expanding, long-term clinical progress in patients emerging from MCS is less frequently studied, likely due to limited data. Yet, understanding the functional independence these patients can achieve is crucial for setting realistic expectations and improving care planning, resource allocation, and decision-making. Existing studies tend to be limited by small sample sizes, a focus on late recovery, specific etiologies, or the use of non-standardized or general measures. The aim of this study is to assess and describe the functional independence of patients who have emerged from MCS at six and twelve months post-emergence, overcoming the previous limitations.

Methods: The demographic and behavioral data of 267 patients with DOC, who were admitted to a long-term neurorehabilitation unit either in a state of UWS (n=125) or MCS (n=142), were retrospectively analyzed. The functional independence of those patients who emerged from MCS was evaluated at 6 and 12 months post-emergence using the Disability Rating Scale (DRS), the Barthel Index (BI), and the Functional Independence Measure+Functional Assessment Measure (FIM+FAM).

Results: 82 out of the 267 patients successfully emerged from MCS. Information of the functional independence was available for 75 patients at 6 months post-emergence and 57 patients at 12 months.
Six months after emergence, patients had mean DRS scores of 14.8±5.5, BI scores of 21.6±28.6, and FIM+FAM scores of 38.4±26.1. One year after emergence, patients had mean DRS scores of 13.1±6.1, BI scores of 34.1±32.8, and FIM+FAM scores of 47.0±29.0. Significant differences were found between the admission and 6 months post-emergence in the DRS; and between 6 and 12 months post-emergence in the DRS, BI, and FIM+FAM. Most patients required total or maximal assistance (> 6 hours of daily assistance) at 6 months (81.1 %) and 12 post-emergence (63.4 %).

Conclusions: Although certain improvement in functional independence can be expected after the emergence of MCS, the great majority of the patients are likely to have a very limited functional independence and require total or almost total assistance one year after emergence.

ACKNOWLEDGEMENTS: This work was supported by Conselleria d’Innovació, Universitats, Ciència i Societat Digital of Generalitat Valenciana (CIDEXG/2022/15), Ministerio de Ciencia e Innovación (PID2022-141498OA-I00), and Fundació la Marató de la TV3 (60/2023).

Background: The objective of our research study was to investigate outcomes of Disorders of Consciousness (DOC) patients with hypoxic-ischemic brain injuries (HIBIs) compared to those with traumatic brain injuries (TBIs). More robust literature exists with the moderate to severe traumatic brain injury (TBI) population, likely in part due to the TBI Model System database. However, the literature on those with DOC secondary to HIBI (DOC/HIBI) is sparse. Very little is known regarding the outcomes of individuals with HIBIs, and even less research is available comparing outcomes by etiology.

Methods: This was a retrospective chart review consisting of three inpatient rehabilitation hospitals (IRHs) in the Northeastern United States. A pre-existing DOC patient database was queried for demographics, etiology of brain injury, medical comorbidities, outcome measures, and neurological sequelae. A total of 98 patients were included for analysis including DOC/HIBI n=46, and DOC/TBI n=52.

Results: Overall demographic analysis revealed individuals with DOC/HIBI (n=46) compared with DOC/TBI (n=52) were older with a mean age of 42.9 years vs 36.9 years (p=0.037), had lower admission coma recovery scale-revised (CRS-R) scores (p=0.018), and were more likely to be in an unresponsive wakefulness state (UWS) on admission 80.4% when compared with DOC/TBI 57.5% (p=0.016). The DOC/HIBI group was 3.4 times more likely to be discharged in an UWS compared to TBI counterparts at 62.5% versus 35.3%, respectively (p=0.004). Additionally, HIBI/DOC were more likely to have myoclonus (p=0.001) and cortical blindness (p=0.020). There were no statistically significant differences between DOC/HIBI compared to TBI regarding spasticity (p=0.602), dysautonomia (p=0.294), or seizures (p=0.617).

Within the HIBI group, etiology was categorized by cardiac DOC/HIBI n=16 and non-cardiac DOC/HIBI n=30. Non-cardiac etiologies were composed of the following categories: substance/overdose (n=11), perioperative arrest (n=11), respiratory (n=6), and other (n=2). Patients with cardiac DOC/HIBI were significantly older at 53.1 years old versus 37.4 years (p<0.001). Regarding discharge outcomes, patients with DOC/HIBI secondary to cardiac outcomes were more likely to be discharged to an acute care hospital from IRH (p=0.017). Individuals with DOC/HIBI of a cardiac nature were more likely to be discharged to acute care but had no differences in the level of DOC or neurological sequelae, including myoclonus (p=0.757), cortical blindness (p=1.000), spasticity (p=0.216), dysautonomia (p=0.754), or seizures (p=0.283).

Conclusion: In conclusion, our research suggests individuals with DOC from HIBI origin were more likely to be discharged from IRH in UWS. Moreover, DOC/HIBI patients were more likely to experience myoclonus and cortical blindness compared to DOC/TBI counterparts. Regarding those with DOC/HIBI, cardiac etiologies were more likely to be discharged to acute care, but there were no differences in the level of DOC or neurological sequelae.

Background: Recent advancements in medical care have significantly improved survival rates for patients with severe brain injuries. Consequently, there has been an increase in the number of survivors with prolonged disorders of consciousness (PDOC). Literature suggests that early intensive neurorehabilitation (EIN) is crucial for achieving optimal outcomes in these patients.

Objectives: This study evaluates the frequency and extent of consciousness recovery, mortality rates, and complications during a nationwide EIN programme for PDOC-patients following acquired brain injury.

Methods: A prospective cohort study was conducted involving PDOC-patients aged 16 years and older, admitted to the EIN department centralized in a single rehabilitation centre in the Netherlands (Libra Rehabilitation & Audiology). The EIN program provides subacute medical care and rehabilitation for up to 14 weeks. The outcome measures included the level of consciousness (CRS-R), mortality, and the number of complications.

Results: Among the 104 participants:
• 68% reached a minimally conscious state with command-following or higher during EIN.
• 44% regained full consciousness.
• The mortality rate during EIN was 6%, with 50% of the deaths resulting from non-treatment decisions or withdrawal of life-sustaining treatment.
• Nearly all PDOC-patients experienced at least one medical complication, with 30% requiring hospital readmission.

Conclusions: During the EIN programme, many PDOC-patients achieved at least a minimally conscious state or even consciousness. These outcomes and the high incidence of medical complications emphasize the need for intensive specialized care for all PDOC-patients. The outcomes of this study can assist health professionals in providing better information about the short-term prognosis to the families of PDOC-patients.

Background: Following an acute brain injury, patients may develop prolonged disorders of consciousness (PDOC). While specialized Intensive Neurorehabilitation has been proven effective, its long-term impact on recovery of consciousness and independency in daily living is somewhat limited. The novel, nationwide chain of care for PDOC-patients in the Netherlands provides the opportunity of gathering this information about virtually all new cases in a single country. This chain of care includes 14 weeks of Early Intensive Neurorehabilitation (EIN), followed by Prolonged Intensive Neurorehabilitation (PIN) for those who do not regain consciousness during the initial 14 weeks of EIN.

Objective: To determine the long-term outcomes in PDOC-patients, in terms of both level of consciousness and level of functioning.

Methods: This research is a longitudinal prospective cohort study with a 2-year follow-up. It included all PDOC patients aged 16 and older admitted to a nationwide specialized PDOC chain of care, starting at a single rehabilitation center in the Netherlands. Outcomes were measured using the Coma Recovery Scale-Revised (CRS-R), the Disability Rating Scale (DRS), and the Functional Independence Measure (FIM) up to 2 years post-admission to the specialized rehabilitation center.

Results: Of 129 patients included, mean age of 38 years, 43% regained consciousness during the first 14 weeks of specialized treatment. An additional 20% regained consciousness after this period, with 10% within the first 6 months after admission. Functional independency (mean total FIM and DRS scores) improved over time, with the most significant gains observed between week 14 and 28 post-admission. Among conscious survivors, the rate of independent functioning (FIM total score ≥ 78) increased from 5% at week 14 to 47% at the 2-year follow-up.

Conclusion: PDOC-patients can show improvements in both level of consciousness and level of functioning beyond the early phases of specialized rehabilitation, up to 2 years post-injury. Most recovery occurs within the first 6 months after admission to rehabilitation, but meaningful progress is still possible even after one year in a context of continued specialized intensive rehabilitation. These findings highlight the importance of providing specialized care for PDOC-patients during the first 2 years following their injury.

Background: Even with the most careful behavioral assessment, willful brain activity might still be missed in patients with Disorders of Consciousness (DoC). Indeed, for the past two decades, clinicians have been facing a group of patients who are unable to show any behavioral sign of consciousness at the bedside but are able to respond to active neuroimaging or electrophysiological paradigms. Even though researchers and clinicians recognize its existence, there is still no wide consensus regarding the nomenclature for this clinical entity with various names used across the literature such as: covert awareness (CA), cognitive motor dissociation (CMD), functional locked-in (fLIS), and non-behavioral MCS (MCS*).

Objective: Using a Delphi method, this study aimed at looking at the level of agreement existing among international experts for these names and their related definition across the literature.

Methods: a Delphi method was used to investigate the level of consensus on names and related definition for CA, CMD, fLIS, and MCS*. Three hundred experts were contacted. REDCap was used as a platform to build and send electronically the survey to participants. The survey had 11 to 16 statements related to definitions and three to 4 questions related to name preferences. The survey duration was kept around 30 minutes. Consensus for agreement was defined as a median score of 5, an IQR ≤ 1, and ≥ 75% scoring 4 or 5.

Results: Of the 300 invited experts, 96 (32%) agreed to participate and fit our criteria for expertise. Seventy-five experts (78%) completed all rounds. Most experts were clinical scientists (71%) and worked in rehabilitation setting (63%). They were located in Europe/UK (49%), in USA (32%) and in other parts of the world (19%). This Delphi study included only 2 rounds since consensus was reached for more than two thirds of the statements on Round 2. A full consensus was reached on a definition for CA. Moreover, a consensus only for CA was reached when experts were asked which name they would agree upon (87%).

Conclusion: the general goal of our study was to inform future discussions on taxonomy for such state. In this first Delphi study, our large group of international experts mostly agreed upon “Covert Awareness” (CA) as the term of choice to call this peculiar entity. However, this study has limitations and further investigations involving international experts with various background but also non-experts should be performed.