An Initial miRNA Profile of Persons With Persisting Neurobehavioral Impairments and States of Disordered Consciousness After Severe Traumatic Brain Injury.

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.

Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: Results from a double-blind, placebo-controlled clinical pilot study.

BACKGROUND: Endocrinopathy, including hypogonadism, is common following traumatic brain injury (TBI). Prior evidence suggests hypogonadism is associated with poorer function. OBJECTIVE: Determine the feasibility, safety, and efficacy of testosterone (T) therapy in hypogonadal men following TBI in acute rehabilitation. DESIGN: Randomized, double blind, placebo-controlled pilot trial. SETTING: Inpatient rehabilitation brain injury unit. PARTICIPANTS: Men ages 18 -65, post moderate to severe TBI receiving inpatient rehabilitation. INTERVENTIONS: Transdermal T gel or placebo. MAIN OUTCOME MEASURES: Revised FIM™ score, strength, adverse events. RESULTS: Of 498 screened, 70 participants were enrolled, and 22 meeting all criteria were randomized into placebo (n = 10) or physiologic T therapy (n = 12). There was no significant difference between groups in rate of improvement on the FIM™ (intercepts t = -0.31, p = 0.7593, or slopes t = 0.61, p = 0.5472). The Treatment group demonstrated the greatest absolute improvement in FIM™ scores and grip strength compared to Placebo or Normal T groups. There was no difference in adverse events between groups. Percentage of time with agitation or aggression was highest in the Placebo group. CONCLUSIONS: Although there were no significant differences in rates of recovery, treatment group subjects showed greater absolute functional and strength improvement compared to the Placebo or Normal T groups.

Psychosis Following an Increase in Intrathecal Baclofen.

Baclofen is a commonly used medication to treat spasticity in neurologic disorders. In the traumatic brain injury (TBI) population, the intrathecal administration of baclofen is often preferred over oral administration due to cognitive side effects. Here we report on a case of a psychotic episode following an increase in intrathecal baclofen in a young man with a history of a TBI. Although intrathecal baclofen is commonly used and is generally well tolerated, this case highlights an important potential effect of intrathecal baclofen that has rarely been reported in the literature. LEVEL OF EVIDENCE: V.

Atomoxetine for attention deficits following traumatic brain injury: results from a randomized controlled trial.

OBJECTIVE: To determine if atomoxetine would improve attention impairment following traumatic brain injury (TBI). SETTING: Outpatients from a free-standing, private, not-for-profit rehabilitation hospital. POPULATION: Fifty-five adult participants with a history of a single moderate-to-severe TBI, who were at least 1 year from injury and with self-reported complaints of attention difficulties. INTERVENTION: Atomoxetine, a selective norepinephrine re-uptake inhibitor with a primary indication for attention dosed at 40 mg twice a day for 2 weeks, compared to placebo. DESIGN: Randomized double-blind placebo controlled trial, with placebo run-in. MEASURES: Cognitive Drug Research (CDR), Computerized Cognitive Assessment System, Stroop Color and Word Test, Adult ADHD Self-Report Scale (ASRS-v1.1), Neurobehavioural Functioning Inventory (NFI). RESULTS: Atomoxetine was well-tolerated by the subject sample. The use of atomoxetine by individuals with reported attention difficulty following TBI did not significantly improve scores on measures of attention, the CDR Power of Attention domain or the Stroop Interference score. In addition, no significant relationship was found between atomoxetine use and self-reported symptoms of attention or depression. CONCLUSION: Atomoxetine did not significantly improve performance on measures of attention among individuals post-TBI with difficulties with attention. This study follows a trend of other pharmacological studies not demonstrating significant results among those with a history of TBI. Various possibilities are discussed, including the need for a more sophisticated system of classification of TBI.

Predictors of sexual functioning and satisfaction 1 year following traumatic brain injury: a TBI model systems multicenter study.

OBJECTIVE: To investigate predictors of sexual functioning 1 year following traumatic brain injury (TBI). DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: A total of 255 persons with TBI (187 males; 68 females) who had been treated at 1 of 6 TBI Model Systems inpatient rehabilitation units and were living in the community. MAIN MEASURES: Derogatis Interview for Sexual Functioning-Self-Report (DISF-SR); Global Satisfaction With Sexual Functioning (Global Sexual Satisfaction Index); Participation Assessment With Recombined Tools-Objective; Patient Health Questionnaire-9. RESULTS: Older age, female gender, and more severe injury were associated with greater sexual dysfunction 1 year following injury. As age increased from 24 to 49 years, the odds of sexual impairment increased more than 3-fold (95% confidence interval: 1.82-5.88). Females had a 2.5 increase in odds of sexual impairment compared with males (95% confidence interval: 1.23-5.26). Greater social participation was predictive of better sexual functioning. Dissatisfaction with sexual functioning was predicted by older age and depression. CONCLUSIONS AND IMPLICATIONS: Older persons and females appear to be at greater risk for sexual dysfunction after TBI and may benefit from specialized assessment and treatment services. Relationships were identified between social participation and sexual function and between depression and sexual satisfaction that may serve as clinical indicators for further assessment and intervention. Further research is needed to elucidate these relationships and identify effective clinical approaches.

Are there cognitive and neurobehavioural correlates of hormonal neuroprotection for women after TBI?

This study examined possible cognitive correlates of hormonal neuroprotection following traumatic brain injury (TBI) using archival neuropsychological findings for 1563 individuals undergoing acute TBI rehabilitation between 1989 and 2002. Presumed age of menopause was based on the STRAW (Stages of Reproductive Aging) staging system (Soules, 2005; Soules et al., 2001) and general linear model (GLM) analysis of performance on neuropsychological testing by participants across gender and age groups (25-34, 35-44, 45-54, and 55-64) was performed. Hypotheses were (1) women with TBI in the oldest age group would have lower scores on neuropsychological tests and functional outcome measures than women in the younger groups, and (2) men in the oldest age group would have higher scores than women of the same age group. Analyses revealed that oldest females had significantly worse Trails B and SDMT written and oral scores than the youngest females. In addition, oldest females had significantly better Trails B, Rey AVLT and SDMT written scores than the oldest males. Possible cohort exposure to hormone replacement therapy, unknown hormonal status at time of testing, and sample-specific injury characteristics may have contributed to these findings.

The impact of female reproductive function on outcomes after traumatic brain injury.

OBJECTIVES: To determine the impact of traumatic brain injury (TBI) on female menstrual and reproductive functioning and to examine the relationships between severity of injury, duration of amenorrhea, and TBI outcomes. DESIGN: Retrospective cohort survey. SETTING: Telephone interview. PARTICIPANTS: Women (N=30; age range, 18-45y), between 1 and 3 years postinjury, who had completed inpatient rehabilitation for TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Data collected included menstrual and reproductive functioning pre- and postinjury, demographic, and injury characteristics. Outcome measures included the Glasgow Outcome Scale-Extended (GOS-E), the Mayo-Portland Adaptability Inventory-4 (MPAI-4), and the Medical Outcome Study 12-Item Short-Form Health Survey, Version 2 (SF-12v2). RESULTS: The median duration of amenorrhea was 61 days (range, 20-344d). Many subjects' menstrual function changed after TBI, reporting a significant increase in skipped menses postinjury (P<.001) and a trend toward more painful menses (P=.061). More severe TBI, as measured by the duration of posttraumatic amnesia, was significantly predictive of a longer duration of amenorrhea (P=.004). Subjects with a shorter duration of amenorrhea scored significantly better on the SF-12 physical component subscale (P=.004), the GOS-E (P=.05), and the MPAI-4 participation subscale (P=.05) after controlling for age, injury severity, and time postinjury. CONCLUSIONS: The severity of TBI was predictive of duration of amenorrhea and a shorter duration of amenorrhea was predictive of better ratings of global outcome, community participation, and health-related quality of life postinjury.

Relationships among premorbid alcohol use, acute intoxication, and early functional status after traumatic brain injury.

OBJECTIVE: To investigate the relationships among intoxication at time of injury, preinjury history of problem drinking, and early functional status in patients with traumatic brain injury (TBI). DESIGN: Prospective cohort study. SETTING: Acute inpatient TBI rehabilitation. PARTICIPANTS: Participants were 1748 persons with TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Blood alcohol levels (BALs) were obtained at admission to the emergency department, and a history of problem drinking was obtained through interview. Study outcomes, Disability Rating Scale (DRS), and FIM instrument scores were gathered at admission to inpatient rehabilitation. RESULTS: Multivariate regression analysis revealed that BAL and a history of binge drinking were predictive of DRS, but not FIM, scores. A higher BAL was associated with poorer functional status on the DRS. Paradoxically, a history of binge drinking was associated with more intact functional status on the DRS. CONCLUSIONS: The relationships among intoxication at time of injury, history of problem drinking, and early outcome after TBI were modest. Injury severity had a more significant association with TBI functional status.

The impact of diabetes mellitus on stroke acute rehabilitation outcomes.

OBJECTIVE: To examine the impact of diabetes mellitus (DM) on functional outcomes after acute rehabilitation for cerebrovascular accident (CVA). DESIGN: A retrospective research design was used to analyze outcomes in patients with a primary diagnosis of unilateral stroke (n = 367) admitted to an urban, acute rehabilitation center in the Southeastern United States. RESULTS: Multivariable hierarchical regression revealed that DM did not contribute statistically significant variance to stroke acute rehabilitation prediction models. Rehabilitation admission functioning scores, rehabilitation length of stay, age, and stroke type were significant predictors of poststroke rehabilitation motor outcomes (r2 = 0.603) and cognitive outcomes (r2 = 0.712). Diabetes also had no significant impact on acute stroke rehabilitation lengths of stay or rehabilitation discharge setting. CONCLUSIONS: Diabetes does not seem to significantly impact short-term acute rehabilitation outcomes after stroke. Persons with diabetes who suffer a stroke seem to benefit and improve during their acute rehabilitation stay at levels equivalent to peers who are not diagnosed with diabetes. Future research should examine the impact of diabetes subtypes and undiagnosed diabetes on short- and long-term outcomes.