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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]

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.)