Nociception Coma Scale-Revised with Personalized Painful Stimulus Versus Standard Stimulation in Persons with Disorders of Consciousness: An International Multicenter Study.

Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale-Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management.

Medicolegal issues and disorders of consciousness.

BACKGROUND: The tasks and responsibilities that come with clinician involvement in medicolegal proceedings can be daunting and particularly so in challenging areas such as provision of medicolegal opinions in cases involving disorders of consciousness (DoC). OBJECTIVE: The aim of this narrative review was to provide education and advice to healthcare practitioners who by choice or circumstance are asked and/or required to provide medicolegal opinions in cases involving patients with DoC. METHODS: A literature search was conducted using PubMed Central and MedlinePlus for articles dealing with clinician involvement in medicolegal cases involving persons with DoC. The information provided also integrates the authors' nearly 40 years of clinical experience, brain injury medicine practice and "trials and tribulations" associated with medicolegal involvement in such cases. RESULTS: The literature was found to be replete with articles on brain death and withdrawal/withholding of care (which are not the focus of this review). The extant medical literature in brain injury medicine on the other hand is currently lacking in practical information for clinicians working "in the trenches" regarding the challenges and caveats of medicolegal involvement in such cases. CONCLUSION: This review provides the reader with a big picture overview of the most pertinent medicolegal topics inherent in clinical work with patients with DOC including pertinent nomenclature, caveats regarding forensic consultation including independent medical examinations, testimony tips, discussion of life expectancy/median survival concepts, prognostication in a medicolegal context, documentation and record keeping as well as some of the specific challenges pertinent to these types of brain injury cases that are not per se relevant in less severe injuries.

International survey on the implementation of the European and American guidelines on disorders of consciousness.

Diagnostic, prognostic, and therapeutic procedures for patients with prolonged disorders of consciousness (pDoCs) vary significantly across countries and clinical settings, likely due to organizational factors (e.g., research vs. non-academic hospitals), expertise and availability of resources (e.g., financial and human). Two international guidelines, one from the European Academy of Neurology (EAN) and one from the American Academy of Neurology (AAN) in collaboration with the American Congress of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), were developed to facilitate consistent practice among professionals working with this challenging patient population. While the recommendations of both guidelines agree in principle, it remains an open issue how to implement them into clinical practice in the care pathway for patients with pDoCs. We conducted an online survey to explore health professional clinical practices related to the management of patients with pDoCs, and compare said practices with selected recommendations from both the guidelines. The survey revealed that while some recommendations are being followed, others are not and/or may require more honing/specificity to enhance their clinical utility. Particular attention should be given to the implementation of a multimodal assessment of residual consciousness, to the detection and treatment of pain, and to the impact of restrictions imposed by COVID-19 pandemics on the involvement of patients' families/representatives.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

Comparison of veterans affairs and NIDILRR traumatic brain injury model systems participants with disorders of consciousness.

OBJECTIVE: To characterize demographic, pre-injury, and outcome data within the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) and Veterans Affairs (VA) Traumatic Brain Injury Model Systems (TBIMS) cohorts with severe traumatic brain injury (TBI) with no command-following ability at time of admission to acute rehabilitation. DESIGN: Retrospective cohort. SETTING: NIDILRR and VA TBI Model Systems (TBIMS) centers. PARTICIPANTS: 396 NIDILRR and 72 VA participants without command-following ability who experienced TBI with subsequent Disorder of Consciousness (DoC). MAIN OUTCOME MEASURE: Pre-injury and injury characteristics, rehabilitation outcomes, and 1-year self-reported outcomes. RESULTS: VA TBIMS cohort included individuals who were active duty or had military service before their injury. The VA cohort were more likely to be re-hospitalized at 1-year follow-up or residing in a long-term care or rehab setting. The NIDILRR TBIMS cohort had higher FIM and DRS scores at rehabilitation discharge, while the VA participants saw longer lengths of stay and higher numbers of "violent" injury types. CONCLUSIONS: This study allows for a better understanding of the comparability between VA and NIDILRR DoC cohorts providing guidance on how veteran and civilian samples might be merged in future TBIMS studies to explore predictors of recovery from a DoC.

Neurorehabilitation for people with disorders of consciousness: an international survey of health-care structures and access to treatment, (Part 1).

AIMS: The provision of rehabilitation services for people with disorders of consciousness (DoC) may vary due to geographical, financial, and political factors. The extent of this variability and the implementation of treatment standards across countries is unknown. This study explored international neurorehabilitation systems for people with DoC. METHODS: An online survey (SurveyMonkey®) was disseminated to all members of the International Brain Injury Association (IBIA) DoC Special Interest Group (SIG) examining existing rehabilitation systems and access to them. RESULTS: Respondents (n = 35) were from 14 countries. Specialized neurorehabilitation was available with varying degrees of access and duration. Commencement of specialized neurorehabilitation averaged 3-4 weeks for traumatic brain injury (TBI) and 5-8 weeks for non-traumatic brain injury (nTBI) etiologies. Length of stay in inpatient rehabilitation was 1-3 months for TBI and 4-6 months for nTBI. There were major differences in access to services and funding across countries. The majority of respondents felt there were not enough resources in place to provide appropriate neurorehabilitation. CONCLUSIONS: There exists inter-country differences for DoC neurorehabilitation after severe acquired brain injury. Further work is needed to implement DoC treatment standards at an international level.

Pain in Persons with Disorders of Consciousness.

Pain and suffering in persons with disorders of consciousness (DoC) remain poorly understood, frequently unaddressed or inadequately addressed, and controversial on numerous levels. This narrative literature review will address a number of critical issues germane to pain and suffering in this challenging group of patients, providing an introductory overview of the topic, perspectives on current knowledge regarding pain pathoanatomy and pathophysiology, and a review of common pain generators and factors that can lead to the chronifcation of pain. Caveats on bedside pain assessment challenges, as well as electrophysiologic and neuroimaging findings in these patients, will also be explored. Pain management techniques, including non-pharmacological and pharmacological, will be reviewed. Ethical considerations in the context of pain and suffering in persons with disorders of consciousness will round out the review prior to our concluding comments.

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.

Prognosis 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 neurological music therapy on behavioural and emotional recovery after traumatic brain injury: A randomized controlled cross-over trial.

Traumatic brain injury (TBI) causes deficits in executive function (EF), as well as problems in behavioural and emotional self-regulation. Neurological music therapy may aid these aspects of recovery. We performed a cross-over randomized controlled trial where 40 persons with moderate-severe TBI received a 3-month neurological music therapy intervention (2 times/week, 60 min/session), either during the first (AB, n = 20) or second (BA, n = 20) half of a 6-month follow-up period. The evidence from this RCT previously demonstrated that music therapy enhanced general EF and set shifting. In the current study, outcome was assessed with self-report and caregiver-report questionnaires performed at baseline, 3-month, 6-month, and 18-month stages. The results showed that the self-reported Behavioural Regulation Index of the Behaviour Rating Inventory of Executive Function (BRIEF-A) improved more in the AB than BA group from baseline to 3-month stage and the effect was maintained in the 6-month follow-up. No changes in mood or quality of life questionnaires were observed. However, a qualitative content analysis of the feedback revealed that many participants experienced the intervention as helpful in terms of emotional well-being and activity. Our results suggest that music therapy has a positive effect on everyday behavioural regulation skills after TBI.

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

BACKGROUND 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.

Epilepsy in prolonged disorders of consciousness: a systematic review.

To date, no guideline exists for the management of epilepsy in patients with prolonged Disorders of Consciousness (DoC). This review aimed to assess the occurrence of epilepsy and epileptic abnormalities (EA) in these patients, to determine their impact on recovery; and to review the effect of antiepileptic drugs (AED) and therapeutic interventions on seizure occurrence and consciousness recovery. A structured search for studies on prolonged DoC and epilepsy was undertaken following PRISMA guidelines. From an initial search resulting in 5,775 titles, twelve studies met inclusion criteria. The occurrence of epilepsy and EA in DoC was poorly and inconsistently reported across studies. The results estimated a seizure prevalence of 27% in DoC. No conclusive data were found for the effects of AED on recovery nor on the influence of any therapeutic interventions on seizure occurrence. Given the scarcity of data, it is premature to make evidence-based recommendations on epilepsy in prolonged DoC. Based on this review and current clinical practices the following are recommended: (1) repeated standard EEG for detecting seizures and EA; (2) treating epilepsy while avoiding AEDs with sedating or cognitive side-effects. Future research should use standardized classification systems for seizures and EA.

Assessing the Severity of Traumatic Brain Injury-Time for a Change?

Traumatic brain injury (TBI) has been described to be man's most complex disease, in man's most complex organ. Despite this vast complexity, variability, and individuality, we still classify the severity of TBI based on non-specific, often unreliable, and pathophysiologically poorly understood measures. Current classifications are primarily based on clinical evaluations, which are non-specific and poorly predictive of long-term disability. Brain imaging results have also been used, yet there are multiple ways of doing brain imaging, at different timepoints in this very dynamic injury. Severity itself is a vague concept. All prediction models based on combining variables that can be assessed during the acute phase have reached only modest predictive values for later outcome. Yet, these early labels of severity often determine how the patient is treated by the healthcare system at large. This opinion paper examines the problems and provides caveats regarding the use of current severity labels and the many practical and scientific issues that arise from doing so. The objective of this paper is to show the causes and consequences of current practice and propose a new approach based on risk classification. A new approach based on multimodal quantifiable data (including imaging and biomarkers) and risk-labels would be of benefit both for the patients and for TBI clinical research and should be a priority for international efforts in the field.

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

Epileptic 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.

Functional Change from Five to Fifteen Years after Traumatic Brain Injury.

Few studies have assessed the long-term functional outcomes of traumatic brain injury (TBI) in large, well-characterized samples. Using the Traumatic Brain Injury Model Systems cohort, this study assessed the maintenance of independence between years 5 and 15 post-injury and risk factors for decline. The study sample included 1381 persons with TBI who received inpatient rehabilitation, survived to 15 years post-injury, and were available for data collection at 5 or 10 years and 15 years post-injury. The Functional Independence Measure (FIM) and Disability Rating Scale (DRS) were used to measure functional outcomes. The majority of participants had no changes during the 10-year time frame. For FIM, only 4.4% showed decline in Self-Care, 4.9% declined in Mobility, and 5.9% declined in Cognition. Overall, 10.4% showed decline in one or more FIM subscales. Decline was detected by DRS Level of Function (24% with >1-point change) and Employability (6% with >1-point change). Predictors of decline factors across all measures were age >25 years and, across most measures, having less than or equal to a high school education. Additional predictors of FIM decline included male sex (FIM Mobility and Self-Care) and longer rehabilitation length of stay (FIM Mobility and Cognition). In contrast to studies reporting change in the first 5 years post-TBI inpatient rehabilitation, a majority of those who survive to 15 years do not experience functional decline. Aging and cognitive reserve appear to be more important drivers of loss of function than original severity of the injury. Interventions to identify those at risk for decline may be needed to maintain or enhance functional status as persons age with a TBI.

Post-traumatic cephalalgia.

After traumatic brain injury (TBI), a host of symptoms of varying severity and associated functional impairment may occur. One of the most commonly encountered and challenging to treat are the post-traumatic cephalalgias. Post-traumatic cephalalgia (PTC) or headache is often conceptualized as a single entity as currently classified using the ICHD-3. Yet, the terminology applicable to the major primary, non-traumatic, headache disorders such as migraine, tension headache, and cervicogenic headache are often used to specify the specific type of headache the patients experiences seemingly disparate from the unitary definition of post-traumatic headache adopted by ICHD-3. More complex post-traumatic presentations attributable to brain injury as well as other headache conditions are important to consider as well as other causes such as medication overuse headache and medication induced headache. Treatment of any post-traumatic cephalalgia must be optimized by understanding that there may be more than one headache pain generator, that comorbid traumatic problems may contribute to the pain presentation and that pre-existing conditions could impact both symptom complaint, clinical presentation and recovery. Any treatment for PTC must harmonize with ongoing medical and psychosocial aspects of recovery.