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Objective: To examine the merits of using microRNAs (miRNAs) as biomarkers of disorders of consciousness (DoC) due to traumatic brain injury (TBI). Settings: Acute and subacute beds. Participants: Patients remaining in vegetative and minimally conscious states (VS, MCS), an average of 1.5 years after TBI, and enrolled in a randomized clinical trial (n = 6). Persons without a diagnosed central nervous system disorder, neurotypical controls (n = 5). Design: Comparison of whole blood miRNA profiles between patients and age/gender-matched controls. For patients, correlational analyses between miRNA profiles and measures of neurobehavioral function. Main Measures: Baseline measures of whole blood miRNAs isolated from the cellular and fluid components of blood and measured using miRNA-seq and real-time polymerase chain reaction (RT-PCR). Baseline neurobehavioral measures derived from 7 tests. Results: For patients, relative to controls, 48 miRNA were significantly (P <.05)/differentially expressed. Cluster analysis showed that neurotypical controls were most similar to each other and with 2 patients (VS: n = 1; and MCS: n = 1). Three patients, all in MCS, clustered separately. The only female in the sample, also in MCS, formed an independent group. For the 48 miRNAs, the enriched pathways identified are implicated in secondary brain damage and 26 miRNAs were significantly (P <.05) correlated with measures of neurobehavioral function. Conclusions: Patients remaining in states of DoC an average of 1.5 years after TBI showed a different and reproducible pattern of miRNA expression relative to age/gender-matched neurotypical controls. The phenotypes, defined by miRNA profiles relative to persisting neurobehavioral impairments, provide the basis for future research to determine the miRNA profiles differentiating states of DoC and the basis for future research using miRNA to detect treatment effects, predict treatment responsiveness, and developing targeted interventions. If future research confirms and advances reported findings, then miRNA profiles will provide the foundation for patient-centric DoC neurorehabilitation. [ABSTRACT FROM AUTHOR]

Examine the psychometric properties of the World Health Organization Disability Assessment Schedule 2.0 among U.S. Iraq/Afghanistan Veterans with a combination of mild traumatic brain injury and behavioral health conditions using Rasch analysis. 307 Veterans were classified as either combat control (n = 141), or one of three clinical groups: mild traumatic brain injury (n = 10), behavioral health conditions (n = 24), or both (n = 128). Data from the three clinical groups were used to establish step and item calibrations serving as anchors when including the control group. Measurement precision was excellent (person separation reliability = 0.93). Ordering of item calibrations formed a logical hierarchy. Test items were off-target (too easy) for the clinical groups. Principal component analysis indicated unidimensionality although 4/36 items misfit the measurement model. No meaningful differential item functioning was detected. There was a moderate effect size (Hedge's g = 1.64) between the control and clinical groups. The World Health Organization Disability Assessment Schedule was suitable for our study sample, distinguishing 4 levels of functional ability. Although items may be easy for some Veterans with mild traumatic brain injury and/or behavioral health conditions, the World Health Organization Disability Assessment Schedule can be used to capture disability information for those with moderate to severe disability. Persistent functional disability is seen in military and civilian populations with mild traumatic brain injury which often co-occurs with behavioral health conditions. A comprehensive measure of disability is needed to distinguish between levels of disability to inform clinical decisions for individual patients and to detect treatment effects between groups in research. Results of this analysis indicate the World Health Organization Disability Assessment Schedule items are sufficiently unidimensional to evaluate level of disability in the moderate and severe range among persons with mild traumatic brain injury with and without behavioral health conditions. Further examination of the psychometric properties of the World Health Organization. Disability Assessment Schedule is necessary before measurement of disability is recommended for those with less than moderate levels of disability. [ABSTRACT FROM AUTHOR]

Background: Biomarkers that can advance precision neurorehabilitation of the traumatic brain injury (TBI) are needed. MicroRNAs (miRNAs) have biological properties that could make them well suited for playing key roles in differential diagnoses and prognoses and informing likelihood of responsiveness to specific treatments. Objective: To review the evidence of miRNA alterations after TBI and evaluate the state of science relative to potential neurorehabilitation applications of TBI-specific miRNAs. Methods: This scoping review includes 57 animal and human studies evaluating miRNAs after TBI. PubMed, Scopus, and Google Scholar search engines were used. Results: Gold standard analytic steps for miRNA biomarker assessment are presented. Published studies evaluating the evidence for miRNAs as potential biomarkers for TBI diagnosis, severity, natural recovery, and treatmentinduced outcomes were reviewed including statistical evaluation. Growing evidence for specific miRNAs, including miR21, as TBI biomarkers is presented. Conclusions: There is evidence of differential miRNA expression in TBI in both human and animal models; however, gaps need to be filled in terms of replication using rigorous, standardized methods to isolate a consistent set of miRNA changes. Longitudinal studies in TBI are needed to understand how miRNAs could be implemented as biomarkers in clinical practice. [ABSTRACT FROM AUTHOR]

For people with disordered consciousness (DoC) after traumatic brain injury (TBI), relationships between treatment-induced changes in neural connectivity and neurobehavioral recovery have not been explored. To begin building a body of evidence regarding the unique contributions of treatments to changes in neural network connectivity relative to neurobehavioral recovery, we conducted a pilot study to identify relationships meriting additional examination in future research. To address this objective, we examined previously unpublished neural connectivity data derived from a randomized clinical trial (RCT). We leveraged these data because treatment efficacy, in the RCT, was based on a comparison of a placebo control with a specific intervention, the familiar auditory sensory training (FAST) intervention, consisting of autobiographical auditory-linguistic stimuli. We selected a subgroup of RCT participants with high-quality imaging data (FAST n = 4 and placebo n = 4) to examine treatment-related changes in brain network connectivity and how and if these changes relate to neurobehavioral recovery. To discover promising relationships among the FAST intervention, changes in neural connectivity, and neurobehavioral recovery, we examined 26 brain regions and 19 white matter tracts associated with default mode, salience, attention, and language networks, as well as three neurobehavioral measures. Of the relationships discovered, the systematic filtering process yielded evidence supporting further investigation of the relationship among the FAST intervention, connectivity of the left inferior longitudinal fasciculus, and auditory-language skills. Evidence also suggests that future mechanistic research should focus on examining the possibility that the FAST supports connectivity changes by facilitating redistribution of brain resources. For a patient population with limited treatment options, the reported findings suggest that a simple, yet targeted, passive sensory stimulation treatment may have altered functional and structural connectivity. If replicated in future research, then these findings provide the foundation for characterizing the unique contributions of the FAST intervention and could inform development of new treatment strategies. For persons with severely damaged brain networks, this report represents a first step toward advancing understanding of the unique contributions of treatments to changing brain network connectivity and how these changes relate to neurobehavioral recovery for persons with DoC after TBI. Clinical Trial Registry: NCT00557076, The Efficacy of Familiar Voice Stimulation During Coma Recovery (http://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Objective: Repetitive Transcranial Magnetic Stimulation (rTMS) is emerging as a promising treatment for persons with disorder of consciousness (DoC) following traumatic brain injury (TBI). Clinically, however, there are concerns about rTMS exacerbating baseline seizure risk. To advance understanding of risks, this article reports evidence of DoC-TBI rTMS-related seizure risk., Setting: Acute and sub-acute hospitals., Participants: Persons in states of DoC 6.5 months to 15 years after TBI (n = 20) who received active rTMS (n = 17) or placebo rTMS (n = 3). After completing placebo procedures, placebo participants completed active rTMS procedures. These 3 participants are included in the active group., Design: Meta-analysis of data from 3 clinical trials; 2 within-subject, 1 double blind randomized placebo-controlled. Each trial used the same rTMS protocol, provided at least 30 rTMS sessions, and delivered rTMS to the dorsolateral prefrontal cortex., Main Measures: During each study's rTMS treatment phase, seizure occurrences were compared between active and placebo groups using logistic regression. After stratifying active group by presence/absence of seizure occurrences, sub-groups were compared using contingency chi-square tests of independence and relative risk (RR) ratios., Results: Two unique participants experienced seizures (1 active, 1 placebo). Post seizure, both participants returned to baseline neurobehavioral function. Both participants received antiepileptics during remaining rTMS sessions, which were completed without further seizures. rTMS-related seizure incidence rate is 59 per 1000 persons. Logistic regression revealed no difference in seizure occurrence by treatment condition (active vs placebo) or when examined with seizure risk factors (P > .1). Presence of ventriculoperitoneal shunt elevated seizure risk (RR = 2.0)., Conclusion: Collectively, findings indicate a low-likelihood that the specified rTMS protocol exacerbates baseline seizure rates in persons with DoC after TBI. In presence of VP shunts, however, rTMS likely elevates baseline seizure risk and mitigation of this increased risk with pharmacological seizure prophylaxis should be considered., Competing Interests: The views expressed do not necessarily reflect the position or policy of the United States Department of Veterans Affairs, Department of Defense, or the US Government. The authors have nothing to disclose and no conflicts of interest to report. The article mentions products, but this does not mean that the authors endorse these products. All authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)