Management of Epileptic Seizures in Disorders of Consciousness: An International Survey.

peer reviewedEpileptic seizures/post-traumatic epilepsy (ES/PTE) are frequent in persons with brain injuries, particularly for patients with more severe injuries including ones that result in disorders of consciousness (DoC). Surprisingly, there are currently no best practice guidelines for assessment or management of ES in persons with DoC. This study aimed to identify clinician attitudes toward epilepsy prophylaxis, diagnosis and treatment in patients with DoC as well as current practice in regards to the use of amantadine in these individuals. A cross-sectional online survey was sent to members of the International Brain Injury Association (IBIA). Fifty physician responses were included in the final analysis. Withdrawal of antiepileptic drug/anti-seizure medications (AED/ASM) therapy was guided by the absence of evidence of clinical seizure whether or not the AED/ASM was given prophylactically or for actual seizure/epilepsy treatment. Standard EEG was the most frequent diagnostic method utilized. The majority of respondents ordered an EEG if there were concerns regarding lack of neurological progress. AED/ASM prescription was reported to be triggered by the first clinically evident seizure with levetiracetam being the AED/ASM of choice. Amantadine was frequently prescribed although less so in patients with epilepsy and/or EEG based epileptic abnormalities. A minority of respondents reported an association between amantadine and seizure. Longitudinal studies on epilepsy management, epilepsy impact on neurologic prognosis, as well as potential drug effects on seizure risk in persons with DoC appear warranted with the goal of pushing guideline development forward and improving clinical assessment and management of seizures in this unique, albeit challenging, population

Care pathways models and clinical outcomes in disorders of consciousness

Objective: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care path-way for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients’ clinical outcomes. Materials and Methods: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by ask-ing 90 patients’ caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received.Results: Seventy- three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diag-nosis. In long- term care units, the diagnosis at admission and the number of caregivers available for each patient (median value=3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non- Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. Conclusion: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and ac-tions are needed to guarantee equity and standardization of the care process in all European countries

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

SUpporting well-being through PEeR-Befriending (SUPERB) trial: an exploration of fidelity in peer-befriending for people with aphasia

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the most reliable diagnostic tool is currently the Coma Recovery Scale-Revised. The CRS-R distinguishes patients with unresponsive wakefulness syndrome (UWS) from patients in minimally conscious state (MCS) and patients who have emerged from MCS (EMCS). This international multi-centric study aims to validate a phone outcome questionnaire (POQ) based on the CRS-R and compare it to the CRS-R performed at the bedside and to the GOS-E which evaluates the level of disability and assigns patient’s in outcomes categories. The POQ will allow clinicians to probe the evolution of patient’s state of consciousness based on caregivers feedback. This research project is part of the International Brain Injury Association, Disorders of Consciousness-Special Interest Group (DOCSIG) and DOCMA consortium

'Less is more': validation with Rasch analysis of five short-forms for the Brain Injury Rehabilitation Trust Personality Questionnaires (BIRT-PQs).

Background: Previous analyses demonstrated a lack of unidimensionality, item redundancy, and substantial administrative burden for the Brain Injury Rehabilitation Trust Personality Questionnaires (BIRT-PQs). Objective: To use Rasch Analysis to calibrate five short-forms of the BIRT-PQs, satisfying the Rasch model requirements. Methods: BIRT-PQs data from 154 patients with severe Acquired Brain Injury (s-ABI) and their caregivers (total sample = 308) underwent Rasch analysis to examine their internal construct validity and reliability according to the Rasch model. Results: The base Rasch analyses did not show sufficient internal construct validity according to the Rasch model for all five BIRT-PQs. After rescoring 18 items, and deleting 75 of 150 items, adequate internal construct validity was achieved for all five BIRT-PQs short forms (model chi-square p-values ranging from 0.0053 to 0.6675), with reliability values compatible with individual measurements. Conclusions: After extensive modifications, including a 48% reduction of the item load, we obtained five short forms of the BIRT-PQs satisfying the strict measurement requirements of the Rasch model. The ordinal-to-interval measurement conversion tables allow measuring on the same metric the perception of the neurobehavioral disability for both patients with s-ABI and their caregivers

Multicenter prospective study on predictors of short-term outcome in disorders of consciousness

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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

Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study.

peer reviewedBACKGROUND AND PURPOSE: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality. METHODS: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury. RESULTS: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors. CONCLUSIONS: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC

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

peer reviewed[en] BACKGROUND AND OBJECTIVES: Comprehensive guidelines for diagnosis, prognosis, and treatments of disorders of consciousness (DoCs) in pediatric patients have not yet been released. We aim to summarize available evidence for DoCs with >14 days duration, to support the future development of guidelines for children aged 6 months to 18 years. METHODS: This scoping review was reported based on PRISMA-ScR 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, 2167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the last 5 years. Overall, 2161 individuals met the inclusion criteria; female patients were 527 of 1554 (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. Electroencephalography, event related potentials, structural computerized tomography and Magnetic Resonance Imaging were the most frequently used instrumental techniques. In 29/53 (54.7%) cases DoC improvement was observed, which was associated to 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 diagnosis, prognosis and treatment of pediatric DoCs