Potential Impact of Amantadine on Aggression in Chronic Traumatic Brain Injury.

OBJECTIVE: To assess the effects of amantadine on anger and aggression among individuals with a chronic traumatic brain injury (TBI). METHODS: A cohort of 118 persons with chronic TBI (>6 months postinjury) and moderate-severe aggression selected from a larger cohort of 168 participants enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial of amantadine 100 mg twice daily (n = 82) versus placebo (n = 86) for treatment of irritability were studied. Anger and aggression were measured at treatment days 0, 28, and 60 using observer-rated and participant-rated State-Trait Anger Expression Inventory-2 (STAXI-2) and Neuropsychiatric Inventory-Agitation/Aggression domain (NPI-A) Most Problematic and Distress scores. RESULTS: Participant-rated day 60 NPI-A Most Problematic (adjusted P = .0118) and NPI-A Distress (adjusted P = .0118) were statistically significant between the 2 groups, but STAXI-2 differences were not significant after adjustment for multiple comparisons. Substantial improvements were noted in both amantadine and placebo groups (70% vs 56% improving at least 3 points on day 60 Observer NPI-A; P = .11). CONCLUSION: Amantadine 100 mg twice daily in this population with chronic TBI appears to be beneficial in decreasing aggression from the perspective of the individual with TBI. No beneficial impact on anger was found. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00779324; http://www.clinicaltrials.gov/ct2/show/NCT00779324?term=irritability&rank=6.

Does history of substance use disorder predict acute traumatic brain injury rehabilitation outcomes?

BACKGROUND/OBJECTIVE: The study explored whether premorbid substance use disorder (SUD) predicts acute traumatic brain injury (TBI) outcomes. METHODS: 143 participants with moderate (34.2%) and severe (65.8%) TBI were enrolled at two Level 1 trauma center inpatient brain injury rehabilitation units. Acute outcomes were measured with the Disability Rating Scale (DRS), the FIMTM; self and informant ratings of the Patient Competency Rating Scale (PCRS); self and family rating of the Frontal Systems Behavioral Scale (FrSBe), and the Neurobehavioral Rating Scale-Revised (NRS-R). RESULTS: Hierarchical linear modeling revealed that SUD history significantly predicted trajectories of PCRS clinician ratings, PCRS self-family and PCRS self-clinician discrepancy scores, and more negative FrSBE family ratings. These findings indicate comparatively greater post-injury executive functions (EF) impairments, particularly self-awareness (SA) of injury-related deficits, for those with SUD history. No significant SUD*time interaction effect was found for FIM or NRS-R scores. CONCLUSIONS: SUD history and TBI are associated with impaired SA and EF but their co-occurrence is not a consistent predictor of acute post-injury functional outcomes. Pre-morbid patient characteristics and rater expectations and biases may moderate associations between SA and recovery after TBI.

Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study.

This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons ≥6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale. Observer ratings between the two groups were not statistically significantly different at day 28 or 60; however, observers rated the majority in both groups as having improved at both intervals. Participant ratings for day 60 demonstrated improvements in both groups with greater improvement in the amantadine group on NPI-I Most Problematic (p<0.04) and NPI-I Distress (p<0.04). These results were not significant with correction for multiple comparisons. CGI demonstrated greater improvement for amantadine than the placebo group (p<0.04). Adverse event occurrence did not differ between the two groups. While observers in both groups reported large improvements, significant group differences were not found for the primary outcome (observer ratings) at either day 28 or 60. This large placebo or nonspecific effect may have masked detection of a treatment effect. The result of this study of amantadine 100 mg every morning and noon to reduce irritability was not positive from the observer perspective, although there are indications of improvement at day 60 from the perspective of persons with TBI and clinicians that may warrant further investigation.

Fully implantable peripheral nerve stimulation for the treatment of hemiplegic shoulder pain: a case report.

This case report describes the first participant treated with a fully implantable, single-lead peripheral nerve stimulation system for refractory hemiplegic shoulder pain. During the 6-wk trial stage, a temporary lead was placed percutaneously near the terminal branches of the axillary nerve to the deltoid. The primary outcome measure was the Brief Pain Inventory-Short Form Question 3, a 0-10 pain numeric rating scale. The participant experienced 75% pain reduction and proceeded to the implantation stage, where he received a single-lead, implantable pulse generator. After 3 wks, the participant became pain-free. However, 7 wks after implantation, the system was turned off because of an unrelated acute medical illness. Hemiplegic shoulder pain reemerged with a Brief Pain Inventory-Short Form Question 3 score of 9. After 11 wks of recovery, peripheral nerve stimulation was reinitiated and the participant became pain-free through the 9-mo follow-up. At 12 mos, Brief Pain Inventory-Short Form Question 3 score was 1. This case report demonstrates the feasibility of a single-lead, fully implantable peripheral nerve stimulation system for refractory hemiplegic shoulder pain.

Measures of injury severity and prediction of acute traumatic brain injury outcomes.

OBJECTIVE: To examine the comparative efficacy of 3 common measures of traumatic brain injury (TBI) severity for predicting inpatient outcomes upon hospital discharge. SETTING: Acute brain injury rehabilitation unit at level 1 trauma center. PARTICIPANTS: 100 patients with TBI. DESIGN: Retrospective analysis of injury severity, demographic, and outcome data. MAIN MEASURES: Glasgow Coma Scale (GCS) at admission, time to follow commands (TTC), duration of posttraumatic amnesia (PTA), and Functional Independence Measure at hospital discharge. RESULTS: A hierarchal multiple regression revealed that duration of PTA was a significant and powerful unique predictor of Functional Independence Measure scores at discharge (ß = -0.46, P = .001), while TTC (ß = 0.26, P = .056) and GCS (ß = 0.16, P = .143) were not. These effects were present even after controlling for age, gender, educational level, racial/ethnic minority status, cause of injury, history of substance abuse, and neurosurgical intervention. CONCLUSION: Although clinicians often use GCS scores and TTC when assessing acute TBI severity and during treatment formulation, this study provides evidence that duration of PTA may be a more meaningful predictor of patients' functional levels at discharge.