Merging Clinical and EEG Biomarkers in an Elastic-Net Regression for Disorder of Consciousness Prognosis Prediction

Patients with Disorder of Consciousness (DoC) entering Intensive Rehabilitation Units after a severe Acquired Brain Injury have a highly variable evolution of the state of consciousness which is a complex aspect to predict. Besides clinical factors, electroencephalography has clearly shown its potential into the identification of prognostic biomarkers of consciousness recovery. In this retrospective study, with a dataset of 271 patients with DoC, we proposed three different Elastic-Net regressors trained on different datasets to predict the Coma Recovery Scale-Revised value at discharge based on data collected at admission. One dataset was completely EEG-based, one solely clinical data-based and the last was composed by the union of the two. Each model was optimized, validated and tested with a robust nested cross-validation pipeline. The best models resulted in a median absolute test error of 4.54 [IQR = 4.56], 3.39 [IQR = 4.36], 3.16 [IQR = 4.13] for respectively the EEG, clinical and hybrid model. Furthermore, the hybrid model for what concerns overcoming an unresponsive wakefulness state and exiting a DoC results in an AUC of 0.91 and 0.88 respectively. Small but useful improvements are added by the EEG dataset to the clinical model for what concerns overcoming an unresponsive wakefulness state. Data-driven techniques and namely, machine learning models are hereby shown to be capable of supporting the complex decision-making process the practitioners must face

Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index.

peer reviewedPrognosis of prolonged Disorders of Consciousness (pDoC) is influenced by patients' clinical diagnosis and Coma Recovery Scale-Revised (CRS-R) total score. We compared the prognostic accuracy of a novel Consciousness Domain Index (CDI) with that of clinical diagnosis and CRS-R total score, for recovery of full consciousness at 6-, 12-, and 24-months post-injury. The CDI was obtained by a combination of the six CRS-R subscales via an unsupervised machine learning technique. We retrospectively analyzed data on 143 patients with pDoC (75 in Minimally Conscious State; 102 males; median age = 53 years; IQR = 35; time post-injury = 1-3 months) due to different etiologies enrolled in an International Brain Injury Association Disorders of Consciousness Special Interest Group (IBIA DoC-SIG) multicenter longitudinal study. Univariate and multivariate analyses were utilized to assess the association between outcomes and the CDI, compared to clinical diagnosis and CRS-R. The CDI, the clinical diagnosis, and the CRS-R total score were significantly associated with a good outcome at 6, 12 and 24 months. The CDI showed the highest univariate prediction accuracy and sensitivity, and regression models including the CDI provided the highest values of explained variance. A combined scoring system of the CRS-R subscales by unsupervised machine learning may improve clinical ability to predict recovery of consciousness in patients with pDoC

Effects of control strategies on gait in robot-assisted post-stroke lower limb rehabilitation: a systematic review

Background Stroke related motor function deficits affect patients' likelihood of returning to professional activities, limit their participation in society and functionality in daily living. Hence, robot-aided gait rehabilitation needs to be fruitful and effective from a motor learning perspective. For this reason, optimal human–robot interaction strategies are necessary to foster neuroplastic shaping during therapy. Therefore, we performed a systematic search on the effects of different control algorithms on quantitative objective gait parameters of post-acute stroke patients. Methods We conducted a systematic search on four electronic databases using the Population Intervention Comparison and Outcome format. The heterogeneity of performance assessment, study designs and patients’ numerosity prevented the possibility to conduct a rigorous meta-analysis, thus, the results were presented through narrative synthesis. Results A total of 31 studies (out of 1036) met the inclusion criteria, without applying any temporal constraints. No controller preference with respect to gait parameters improvements was found. However, preferred solutions were encountered in the implementation of force control strategies mostly on rigid devices in therapeutic scenarios. Conversely, soft devices, which were all position-controlled, were found to be more commonly used in assistive scenarios. The effect of different controllers on gait could not be evaluated since conspicuous heterogeneity was found for both performance metrics and study designs. Conclusions Overall, due to the impossibility of performing a meta-analysis, this systematic review calls for an outcome standardisation in the evaluation of robot-aided gait rehabilitation. This could allow for the comparison of adaptive and human-dependent controllers with conventional ones, identifying the most suitable control strategies for specific pathologic gait patterns. This latter aspect could bolster individualized and personalized choices of control strategies during the therapeutic or assistive path

Effects of control strategies on gait in robot-assisted post-stroke lower limb rehabilitation: a systematic review

Background Stroke related motor function deficits affect patients' likelihood of returning to professional activities, limit their participation in society and functionality in daily living. Hence, robot-aided gait rehabilitation needs to be fruitful and effective from a motor learning perspective. For this reason, optimal human–robot interaction strategies are necessary to foster neuroplastic shaping during therapy. Therefore, we performed a systematic search on the effects of different control algorithms on quantitative objective gait parameters of post-acute stroke patients. Methods We conducted a systematic search on four electronic databases using the Population Intervention Comparison and Outcome format. The heterogeneity of performance assessment, study designs and patients’ numerosity prevented the possibility to conduct a rigorous meta-analysis, thus, the results were presented through narrative synthesis. Results A total of 31 studies (out of 1036) met the inclusion criteria, without applying any temporal constraints. No controller preference with respect to gait parameters improvements was found. However, preferred solutions were encountered in the implementation of force control strategies mostly on rigid devices in therapeutic scenarios. Conversely, soft devices, which were all position-controlled, were found to be more commonly used in assistive scenarios. The effect of different controllers on gait could not be evaluated since conspicuous heterogeneity was found for both performance metrics and study designs. Conclusions Overall, due to the impossibility of performing a meta-analysis, this systematic review calls for an outcome standardisation in the evaluation of robot-aided gait rehabilitation. This could allow for the comparison of adaptive and human-dependent controllers with conventional ones, identifying the most suitable control strategies for specific pathologic gait patterns. This latter aspect could bolster individualized and personalized choices of control strategies during the therapeutic or assistive path.ISSN:1743-000

Can Respiration Complexity Help the Diagnosis of Disorders of Consciousness in Rehabilitation?

Background: Autonomic Nervous System (ANS) activity, as cardiac, respiratory and electrodermal activity, has been shown to provide specific information on different consciousness states. Respiration rates (RRs) are considered indicators of ANS activity and breathing patterns are currently already included in the evaluation of patients in critical care. Objective: The aim of this work was to derive a proxy of autonomic functions via the RR variability and compare its diagnostic capability with known neurophysiological biomarkers of consciousness. Methods: In a cohort of sub-acute patients with brain injury during post-acute rehabilitation, polygraphy (ECG, EEG) recordings were collected. The EEG was labeled via descriptors based on American Clinical Neurophysiology Society terminology and the respiration variability was extracted by computing the Approximate Entropy (ApEN) of the ECG-derived respiration signal. Competing logistic regressions were applied to evaluate the improvement in model performances introduced by the RR ApEN. Results: Higher RR complexity was significantly associated with higher consciousness levels and improved diagnostic models’ performances in contrast to the ones built with only electroencephalographic descriptors. Conclusions: Adding a quantitative, instrumentally based complexity measure of RR variability to multimodal consciousness assessment protocols may improve diagnostic accuracy based only on electroencephalographic descriptors. Overall, this study promotes the integration of biomarkers derived from the central and the autonomous nervous system for the most comprehensive diagnosis of consciousness in a rehabilitation setting

Multiplexing Biosensor for the Detection of Extracellular Vesicles as Biomarkers of Tissue Damage and Recovery after Ischemic Stroke

The inflammatory, reparative and regenerative mechanisms activated in ischemic stroke patients immediately after the event cooperate in the response to injury, in the restoration of functions and in brain remodeling even weeks after the event and can be sustained by the rehabilitation treatment. Nonetheless, patients’ response to treatments is difficult to predict because of the lack of specific measurable markers of recovery, which could be complementary to clinical scales in the evaluation of patients. Considering that Extracellular Vesicles (EVs) are carriers of multiple molecules involved in the response to stroke injury, in the present study, we have identified a panel of EV-associated molecules that (i) confirm the crucial involvement of EVs in the processes that follow ischemic stroke, (ii) could possibly profile ischemic stroke patients at the beginning of the rehabilitation program, (iii) could be used in predicting patients’ response to treatment. By means of a multiplexing Surface Plasmon Resonance imaging biosensor, subacute ischemic stroke patients were proven to have increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) and translocator protein (TSPO) on the surface of small EVs in blood. Besides, microglia EVs and endothelial EVs were shown to be significantly involved in the intercellular communications that occur more than 10 days after ischemic stroke, thus being potential tools for the profiling of patients in the subacute phase after ischemic stroke and in the prediction of their recovery

Brain microstate spatio-temporal dynamics as a candidate endotype of consciousness

Consciousness can be defined as a phenomenological experience continuously evolving. Current research showed how conscious mental activity can be subdivided into a series of atomic brain states converging to a discrete spatiotemporal pattern of global neuronal firing. Using the high temporal resolution of EEG recordings in patients with a severe Acquired Brain Injury (sABI) admitted to an Intensive Rehabilitation Unit (IRU), we detected a novel endotype of consciousness from the spatiotemporal brain dynamics identified via microstate analysis. Also, we investigated whether microstate features were associated with common neurophysiological alterations. Finally, the prognostic information comprised in such descriptors was analysed in a sub-cohort of patients with prolonged Disorder of Consciousness (pDoC). Occurrence of frontally-oriented microstates (C microstate), likelihood of maintaining such brain state or transitioning to the C topography and complexity were found to be indicators of consciousness presence and levels. Features of left–right asymmetric microstates and transitions toward them were found to be negatively correlated with antero-posterior brain reorganization and EEG symmetry. Substantial differences in microstates’ sequence complexity and presence of C topography were found between groups of patients with alpha dominant background, cortical reactivity and antero-posterior gradient. Also, transitioning from left-right to antero-posterior microstates was found to be an independent predictor of consciousness recovery, stronger than consciousness levels at IRU’s admission. In conclusions, global brain dynamics measured with scale-free estimators can be considered an indicator of consciousness presence and a candidate marker of short-term recovery in patients with a pDoC

Machine learning based estimation of dynamic balance and gait adaptability in persons with neurological diseases using inertial sensors

Abstract Poor dynamic balance and impaired gait adaptation to different contexts are hallmarks of people with neurological disorders (PwND), leading to difficulties in daily life and increased fall risk. Frequent assessment of dynamic balance and gait adaptability is therefore essential for monitoring the evolution of these impairments and/or the long-term effects of rehabilitation. The modified dynamic gait index (mDGI) is a validated clinical test specifically devoted to evaluating gait facets in clinical settings under a physiotherapist’s supervision. The need of a clinical environment, consequently, limits the number of assessments. Wearable sensors are increasingly used to measure balance and locomotion in real-world contexts and may permit an increase in monitoring frequency. This study aims to provide a preliminary test of this opportunity by using nested cross-validated machine learning regressors to predict the mDGI scores of 95 PwND via inertial signals collected from short steady-state walking bouts derived from the 6-minute walk test. Four different models were compared, one for each pathology (multiple sclerosis, Parkinson’s disease, and stroke) and one for the pooled multipathological cohort. Model explanations were computed on the best-performing solution; the model trained on the multipathological cohort yielded a median (interquartile range) absolute test error of 3.58 (5.38) points. In total, 76% of the predictions were within the mDGI’s minimal detectable change of 5 points. These results confirm that steady-state walking measurements provide information about dynamic balance and gait adaptability and can help clinicians identify important features to improve upon during rehabilitation. Future developments will include training of the method using short steady-state walking bouts in real-world settings, analysing the feasibility of this solution to intensify performance monitoring, providing prompt detection of worsening/improvements, and complementing clinical assessments

Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index.

peer reviewedPrognosis of prolonged Disorders of Consciousness (pDoC) is influenced by patients' clinical diagnosis and Coma Recovery Scale-Revised (CRS-R) total score. We compared the prognostic accuracy of a novel Consciousness Domain Index (CDI) with that of clinical diagnosis and CRS-R total score, for recovery of full consciousness at 6-, 12-, and 24-months post-injury. The CDI was obtained by a combination of the six CRS-R subscales via an unsupervised machine learning technique. We retrospectively analyzed data on 143 patients with pDoC (75 in Minimally Conscious State; 102 males; median age = 53 years; IQR = 35; time post-injury = 1-3 months) due to different etiologies enrolled in an International Brain Injury Association Disorders of Consciousness Special Interest Group (IBIA DoC-SIG) multicenter longitudinal study. Univariate and multivariate analyses were utilized to assess the association between outcomes and the CDI, compared to clinical diagnosis and CRS-R. The CDI, the clinical diagnosis, and the CRS-R total score were significantly associated with a good outcome at 6, 12 and 24 months. The CDI showed the highest univariate prediction accuracy and sensitivity, and regression models including the CDI provided the highest values of explained variance. A combined scoring system of the CRS-R subscales by unsupervised machine learning may improve clinical ability to predict recovery of consciousness in patients with pDoC