Clinical diagnosis of patients with prolonged disorders of consciousness is very challenging. As spontaneous eye blink rate (EBR) is reliably correlated with cognitive activity in healthy ...individuals, we investigated whether EBR could serve as a marker of patients' level of consciousness. We assessed ten patients in prolonged Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS; three females; mean age = 50.3 ± 17.8 years) and fourteen patients in Minimally Conscious State (MCS; three females; mean age = 52.9 ± 17.5 years) at their admission to a rehabilitation unit after the acute phase. During two separate 3-min rest conditions, we recorded patients' EBR by integrating on-line visual and off-line electro-oculographic count. We also assessed EBR during two auditory oddball tasks, i.e. passive listening and active counting of target tones in a sub-group of patients. EBR was significantly higher in MCS than in VS/UWS; moreover, EBR positively correlated with a validated index of responsiveness derived from the Coma Recovery Scale-Revised. Patients' mean EBR showed no significant differences within sessions and across experimental conditions of the oddball task, in both VS/UWS and MCS. Our findings suggest that, at least in the post-acute phase, observing patients' EBR for 3 min at rest could help to discriminate between VS/UWS and MCS, improving accuracy of clinical diagnosis.
Abstract
Patients with severe acquired brain injury and prolonged disorders of consciousness (pDoC) are characterized by high clinical complexity and high risk to develop medical complications. The ...present multi-center longitudinal study aimed at investigating the impact of medical complications on the prediction of clinical outcome by means of machine learning models. Patients with pDoC were consecutively enrolled at admission in 23 intensive neurorehabilitation units (IRU) and followed-up at 6 months from onset via the Glasgow Outcome Scale—Extended (GOSE). Demographic and clinical data at study entry and medical complications developed within 3 months from admission were collected. Machine learning models were developed, targeting neurological outcomes at 6 months from brain injury using data collected at admission. Then, after concatenating predictions of such models to the medical complications collected within 3 months, a cascade model was developed. One hundred seventy six patients with pDoC (M: 123, median age 60.2 years) were included in the analysis. At admission, the best performing solution (k-Nearest Neighbors regression, KNN) resulted in a median validation error of 0.59 points IQR 0.14 and a classification accuracy of dichotomized GOS-E of 88.6%. Coherently, at 3 months, the best model resulted in a median validation error of 0.49 points IQR 0.11 and a classification accuracy of 92.6%. Interpreting the admission KNN showed how the negative effect of older age is strengthened when patients’ communication levels are high and ameliorated when no communication is present. The model trained at 3 months showed appropriate adaptation of the admission prediction according to the severity of the developed medical complexity in the first 3 months. In this work, we developed and cross-validated an interpretable decision support tool capable of distinguishing patients which will reach sufficient independence levels at 6 months (GOS-E > 4). Furthermore, we provide an updated prediction at 3 months, keeping in consideration the rehabilitative path and the risen medical complexity.
The number of patients in prolonged postanoxic vegetative state (VS) is increasing. However, little information is available about prognostic markers of long-term outcome in patients who remain in VS ...more than 1 month postonset. The present 2-year prospective clinical study aimed to identify prognostic markers, recorded in the chronic phase, that might be useful for predicting recovery of responsiveness in a cohort of postanoxic VS patients.
We enrolled 43 inpatients with prolonged anoxic VS (23 female; age range 12-83 years). We collected data about medical history, clinical findings, and neurophysiological assessments at study entry (1-6 months postonset), and assessed their relationships with outcome at 24 months postonset; for defining outcome, patients were classified as responsive or unresponsive on the basis of clinical criteria and on Coma Recovery Scale-Revised (CRS-R).
Nine patients had recovered responsiveness (but 2 of them died after awakening), whereas 12 patients remained in VS and 22 had died in VS. Functional abilities were severely affected in all responsive survivors. Responsive patients were significantly younger and showed higher CRS-R total score and lower Disability Rating Scale score at study entry than patients who did not recover. All responsive survivors had spared pupillary light reflex and nociceptive response, and paroxysmal sympathetic hyperactivity. Logistic regression analysis showed that the presence of median nerve somatosensory evoked potentials and CRS-R total score ≥ 6 were significant predictors of recovery of responsiveness.
Clinical features and evoked potentials are useful predictors of long-term recovery of responsiveness in patients with prolonged postanoxic VS.
Abstract
MicroRNAs (miRNAs) are involved in gene regulation and may affect secondary brain injury and recovery in patients with disorders of consciousness (DoC). This study investigated the role of ...five miRNAs (150-5p, 132-3p, 23b-3p, 451a, and 16-5p) in prolonged DoC. miRNA levels were assessed in serum samples from 30 patients with unresponsive wakefulness syndrome or minimally conscious state due to traumatic or hypoxic-ischemic brain injury (TBI, HIBI) at baseline (1–3 months) and 6 months post-injury. Patients’ diagnoses were determined using the Coma Recovery Scale revised, and functional outcomes were evaluated 6 months after injury with the Glasgow Outcome Scale Extended (GOSE) and the Functional Independence Measure (FIM). Compared to healthy controls, patients with TBI had lower levels of miRNAs 150-5p, 132-3p, and 23b-3p at baseline, while patients with HIBI had lower levels of miRNA 150-5p at baseline and 6 months post-injury and a reduction of miRNA 451a at baseline. Higher levels of miRNAs 132-3p and 23b-3p were associated with better outcomes in TBI patients as indicated by GOSE and FIM scores. This study highlights distinct miRNA dysregulated patterns in patients with prolonged DoC, dependent on etiology and post-injury time, and suggests that miRNAs 132-3p and 23b-3p may serve as prognostic biomarkers.
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.
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.
Objectives:
To report occurrence and identify patient’s features and risk factors of heterotopic ossifications in patients with severe acquired brain injury in intensive rehabilitation centres.
...Design:
Multicentre cross-sectional survey.
Setting:
A total of 48 severe acquired brain injury rehabilitation institutes.
Participants:
Traumatic and non-traumatic severe brain-injured patients (N = 689) in rehabilitation centres on 28 May 2016.
Main Outcome Measure:
Occurrence of heterotopic ossifications diagnosed by standard radiological and/or sonographic evaluation on the basis of clinical suspicion.
Results:
Heterotopic ossification occurred around one or more joints in 94/689 patients (13.6%) with a significantly higher prevalence in young males. Occurrence did not significantly differ in relation to aetiology (16.3% traumatic, 19.2% anoxic, 11.7% vascular and 11.5% other). Prevalence was significantly higher in patients with diffuse (23.3%) rather than focal brain lesions (12.4%) or unspecified lesions (11.2%; chi-square = 7.81, df = 2, P = 0.020); longer duration of coma (P = 0.0016) and ventilation support (P = 0.0145); paroxysmal sympathetic hyperactivity (22.6% versus 11.6%; chi-square = 10.81, df = 1, P = 0.001); and spasticity (22.7% versus 10.1%; chi-square = 18.63, df = 1, P < 0.0001). A longer interval between acute brain injury and admission to rehabilitation centre was significantly associated with higher frequency of heterotopic ossifications.
Conclusion:
Occurrence of heterotopic ossifications is frequent in patients with severe traumatic and non-traumatic brain-injury in rehabilitation centres. Our study confirms male gender, young age, paroxysmal sympathetic hyperactivity, spasticity, longer duration of coma and ventilation and longer interval between brain injury onset and admission to rehabilitation centre as possible risk factors. Further studies are necessary to investigate the role of early appropriate rehabilitation pathways to reduce occurrence of heterotopic ossifications.
Abstract Objective To report clinical conditions and neuropsychological functioning of patients with late recovery of responsiveness at least 5 years after injury. Design Patient series. Setting ...Patients discharged from an inpatient rehabilitation unit. Participants Patients (N=13) who recovered from a vegetative state 1 year after severe traumatic brain injury or 6 months after nontraumatic brain injury. Interventions Not applicable. Main Outcome Measures Coma Recovery Scale-Revised, Disability Rating Scale, and FIM. For patients who recovered full consciousness, neuropsychological tests specifically adapted for patients with very severe disabilities were used. Results After regaining responsiveness, 2 patients died because of severe clinical complications. Among the remaining 11 patients, 5 were still in a minimally conscious state at their last assessment, but 4 of them had recovered some complex behavioral responses to the environment (eg, they could follow simple commands, albeit inconsistently). Six patients had emerged from a minimally conscious state at the last evaluation. Severe functional disability was present in both patients who were conscious and patients who were minimally conscious. No patient was autonomous in common daily life activities or in transfers. All patients who were conscious showed variable cognitive impairments, and some of them also developed behavioral and psychological symptoms. However, such disturbances did not impede the patients' interaction with relatives and caregivers. Conclusions This study provides systematic data about the course of the disease in a cohort of patients that was previously considered as exceptional. Patients with late recovery show a variable degree of functional recovery, although they experience marked residual motor and cognitive disabilities. The present findings contribute to enhance the understanding of the course of the disease in patients with late recovery and might help clinicians optimize the levels of care and provide the patients' families with correct information.
Due to continuous advances in intensive care technology and neurosurgical procedures, the number of survivors from severe acquired brain injuries (sABIs) has increased considerably, raising several ...delicate ethical issues. The heterogeneity and complex nature of the neurological damage of sABIs make the detection of predictive factors of a better outcome very challenging. Identifying the profile of those patients with better prospects of recovery will facilitate clinical and family choices and allow to personalize rehabilitation. This paper describes a multicenter prospective study protocol, to investigate outcomes and baseline predictors or biomarkers of functional recovery, on a large Italian cohort of sABI survivors undergoing postacute rehabilitation.
All patients with a diagnosis of sABI admitted to four intensive rehabilitation units (IRUs) within 4 months from the acute event, aged above 18, and providing informed consent, will be enrolled. No additional exclusion criteria will be considered. Measures will be taken at admission (T0), at three (T1) and 6 months (T2) from T0, and follow-up at 12 and 24 months from onset, including clinical and functional data, neurophysiological results, and analysis of neurogenetic biomarkers.
Advanced machine learning algorithms will be cross validated to achieve data-driven prediction models. To assess the clinical applicability of the solutions obtained, the prediction of recovery milestones will be compared to the evaluation of a multiprofessional, interdisciplinary rehabilitation team, performed within 2 weeks from admission.
Identifying the profiles of patients with a favorable prognosis would allow customization of rehabilitation strategies, to provide accurate information to the caregivers and, possibly, to optimize rehabilitation outcomes.
The application and validation of machine learning algorithms on a comprehensive pool of clinical, genetic, and neurophysiological data can pave the way toward the implementation of tools in support of the clinical prognosis for the rehabilitation pathways of patients after sABI.
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