Predicting Outcome of Acquired Brain Injury by the Evolution of Paroxysmal Sympathetic Hyperactivity Signs.

In this multi-center study, we provide a systematic evaluation of the clinical variability associated with paroxysmal sympathetic hyperactivity (PSH) in patients with acquired brain injury (ABI) to determine how these signs can impact outcomes. A total of 156 ABI patients with a disorder of consciousness (DoC) were admitted to neurorehabilitation subacute units (intensive rehabilitation unit; IRU) and evaluated at baseline (T0), after 4 months from event (T1), and at discharge (T2). The outcome measure was the Glasgow Outcome Scale-Extended, whereas age, sex, etiology, Coma Recovery Scale-Revised (CRS-r), Rancho Los Amigos Scale (RLAS), Early Rehabilitation Barthel Index (ERBI), PSH-Assessment Measure (PSH-AM) scores and other clinical features were considered as predictive factors. A machine learning (ML) approach was used to identify the best predictive model of clinical outcomes. The etiology was predominantly vascular (50.8%), followed by traumatic (36.2%). At admission, prevalence of PSH was 31.3%, which decreased to 16.6% and 4.4% at T1 and T2, respectively. At T2, 2.8% were dead and 61.1% had a full recovery of consciousness, whereas 36.1% remained in VS or MCS. A support vector machine (SVM)-based ML approach provides the best model with 82% accuracy in predicting outcomes. Analysis of variable importance shows that the most important clinical factors influencing the outcome are the PSH-AM scores measured at T0 and T1, together with neurological diagnosis, CRS-r, and RLAS scores measured at T0. This joint multi-center effort provides a comprehensive picture of the clinical impact of PSH signs in ABI patients, demonstrating its predictive value in comparison with other well-known clinical measurements.

Consciousness and the Dimensionality of DOC Patients via the Generalized Ising Model.

The data from patients with severe brain injuries show complex brain functions. Due to the difficulties associated with these complex data, computational modeling is an especially useful tool to examine the structure-function relationship in these populations. By using computational modeling for patients with a disorder of consciousness (DoC), not only we can understand the changes of information transfer, but we also can test changes to different states of consciousness by hypothetically changing the anatomical structure. The generalized Ising model (GIM), which specializes in using structural connectivity to simulate functional connectivity, has been proven to effectively capture the relationship between anatomical structures and the spontaneous fluctuations of healthy controls (HCs). In the present study we implemented the GIM in 25 HCs as well as in 13 DoC patients diagnosed at three different states of consciousness. Simulated data were analyzed and the criticality and dimensionality were calculated for both groups; together, those values capture the level of information transfer in the brain. Ratifying previous studies, criticality was observed in simulations of HCs. We were also able to observe criticality for DoC patients, concluding that the GIM is generalizable for DoC patients. Furthermore, dimensionality increased for the DoC group as compared to healthy controls, and could distinguish different diagnostic groups of DoC patients.

Multimodal Neuroimaging Approach to Variability of Functional Connectivity in Disorders of Consciousness: A PET/MRI Pilot Study.

Behavioral assessments could not suffice to provide accurate diagnostic information in individuals with disorders of consciousness (DoC). Multimodal neuroimaging markers have been developed to support clinical assessments of these patients. Here we present findings obtained by hybrid fludeoxyglucose (FDG-)PET/MR imaging in three severely brain-injured patients, one in an unresponsive wakefulness syndrome (UWS), one in a minimally conscious state (MCS), and one patient emerged from MCS (EMCS). Repeated behavioral assessment by means of Coma Recovery Scale-Revised and neurophysiological evaluation were performed in the two weeks before and after neuroimaging acquisition, to ascertain that clinical diagnosis was stable. The three patients underwent one imaging session, during which two resting-state fMRI (rs-fMRI) blocks were run with a temporal gap of about 30 min. rs-fMRI data were analyzed with a graph theory approach applied to nine independent networks. We also analyzed the benefits of concatenating the two acquisitions for each patient or to select for each network the graph strength map with a higher ratio of fitness. Finally, as for clinical assessment, we considered the best functional connectivity pattern for each network and correlated graph strength maps to FDG uptake. Functional connectivity analysis showed several differences between the two rs-fMRI acquisitions, affecting in a different way each network and with a different variability for the three patients, as assessed by ratio of fitness. Moreover, combined PET/fMRI analysis demonstrated a higher functional/metabolic correlation for patients in EMCS and MCS compared to UWS. In conclusion, we observed for the first time, through a test-retest approach, a variability in the appearance and temporal/spatial patterns of resting-state networks in severely brain-injured patients, proposing a new method to select the most informative connectivity pattern.

Selegiline in Patients With Disorder of Consciousness: An Open Pilot Study.

This open study investigated the clinical effects of 10-week selegiline administration in six patients in vegetative state and in four patients in a minimally conscious state, at least 6 months after onset. Clinical outcome was assessed by Coma Recovery Scale-Revised once a week during selegiline administration and 1 month later. Three patients stopped treatment because of possible side effects. After treatment and at 1 month of follow-up, four patients showed improvements in clinical diagnosis, and three patients showed an increase in arousal level only. Selegiline might represent a relatively safe option to enhance arousal and promote recovery in brain-injured patients with disorders of consciousness.

Visual pursuit of one's own face in disorders of consciousness: a quantitative analysis.

BACKGROUND: Eye behaviour is important to distinguish minimally conscious state (MCS) from vegetative state (VS). OBJECTIVE: To search for conditions most suitable to characterize patients in MCS and in VS on quantitative assessment of visual tracking. DESIGN: This is a cross-sectional study. PARTICIPANTS: In total, 20 patients in VS, 13 in MCS plus and 11 in MCS minus participated in this study. SETTING: Neurorehabilitation Unit. METHODS: Evaluation of eye behaviour was performed by infrared system; stimuli were represented by a red circle, a picture of a patient's own face and a picture of an unfamiliar face, slowly moving on a personal computer (PC) monitor. Visual tracking on the horizontal and vertical axes was compared. MAIN OUTCOME MEASURES: The main outcome measures were proportion of on-target fixations and mean fixation duration. RESULTS: The proportion of on-target fixations differed as a function of the stimulus in patients in MCS plus but not in other groups. Own face and unfamiliar face elicited a similar proportion of on-target fixations. Tracking along the horizontal axis was more accurate than that along the vertical axis in patients in both MCS plus and MCS minus. Fixation duration did not differ among the three groups. CONCLUSIONS: Horizontal visual tracking of salient stimuli seems particularly suitable for eliciting on-target fixations. Quantitative assessment of visual tracking can complement clinical evaluation for reducing diagnostic uncertainty between patients in MCS or VS.

Do Medical Complications Impact Long-Term Outcomes in Prolonged Disorders of Consciousness?

OBJECTIVE: To investigate medical complications (MCs) occurring within 6 months postinjury in brain-injured patients with prolonged disorders of consciousness (DoC) and to evaluate impact of MC on mortality and long-term clinical outcomes. DESIGN: Prospective observational cohort study. SETTING: Rehabilitation unit for acquired DoC. PARTICIPANTS: Patients (N=194) with DoC (142 in vegetative state [VS], 52 in minimally conscious state; traumatic etiology 43, anoxic 69, vascular 82) consecutively admitted to a neurorehabilitation unit within 1-3 months postonset. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mortality and improvements in clinical diagnosis and functional disability level (assessed by Coma Recovery Scale-Revised [CRS-R] and Disability Rating Scale) at 12, 24, and 36 months postonset. RESULTS: Within 6 months postinjury, 188 of 194 patients (>95%) developed at least 1 MC and 142 of them (73%) showed at least 1 severe MC. Respiratory and musculoskeletal-cutaneous MCs were the most frequent, followed by endocrino-metabolic abnormalities. Follow-up, complete in 189 of 194 patients, showed that male sex and endocrine-metabolic MCs were associated with higher risk of mortality at all timepoints. Old age, anoxic etiology, lower CRS-R total scores, and diagnosis of VS at study entry predicted no clinical and functional improvements at most timepoints; however, epilepsy predicted no improvement in diagnosis at 24 months postonset only. CONCLUSIONS: MCs are very frequent in patients with DoC within at least 6 months after brain injury, regardless of clinical diagnosis, etiology, and age. Endocrino-metabolic MCs are independent predictors of mortality at all timepoints; however,epilepsy predicted poor long-term outcome. Occurrence and severity of MCs in patients with DoC call for long-term appropriate levels of care after the postacute phase.

Family caregivers' opinions about interaction with the environment in consciousness disorders.

OBJECTIVES: To assess family caregivers' opinions about level of interaction with the environment in their relatives with disorders of consciousness (DOCs) and to explore psychological features of caregivers whose opinions diverge from clinicians' diagnosis. METHOD: Forty-five family caregivers of 38 DOC inpatients without communication abilities answered 2 questions assessing their opinion about level of interaction with the environment in their relatives. Self-report questionnaires were used to evaluate caregivers' depression, anxiety, psychophysiological disturbances, prolonged grief disorder, coping strategies, quality of perceived needs and social support. RESULTS: Fifteen caregivers (5 relatives of patients in vegetative state and 10 of patients in minimally conscious state) considered their relatives able to communicate, in contrast with clinical diagnosis. These caregivers had significantly higher depressive symptoms, and higher worries about possible death of their relatives with respect to the remaining caregivers. CONCLUSIONS: Caregivers of DOC patients detected some interaction with the environment in their relatives more often than care professionals. This is likely related to caregivers' beliefs and expectations, but is also based on observations closer and longer than those possible for physicians. These considerations are important to build a therapeutic alliance with caregivers and to involve them in the diagnostic process and rehabilitative program. (PsycINFO Database Record

Repeated transcranial direct current stimulation in prolonged disorders of consciousness: A double-blind cross-over study.

OBJECTIVE: To evaluate effects of 5 sessions of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex in patients with prolonged disorders of consciousness (DOC). METHODS: Seven patients in vegetative state (VS) and 6 in minimally conscious state (MCS), at ≥3months after brain injury, were randomized into two groups: group 1 received one week of active tDCS and 1week of sham stimulation, separated by 1 resting week; group 2 received active and sham stimulation in reverse order. We performed clinical and EEG evaluations before and after the first stimulation session, two hours after the last weekly stimulation, twice during the resting week, and during a 3-month follow-up. RESULTS: We observed small changes of patients' conditions after the first tDCS session and immediately after the 5 active stimulations. Substantial clinical and EEG changes were observed in 5/13 patients (3 in MCS and 2 in VS) starting after entire (active and sham) stimulation protocol and further progressing during the next months. No baseline features distinguished patients who improved from patients who did not improve. CONCLUSIONS: Repeated tDCS did not exert remarkable short-term clinical and EEG effects in patients with prolonged DOC. Further studies should ascertain whether tDCS might promote clinical recovery in the long-term period.