Department of Physical Medicine and Rehabilitation

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Neurobiological mechanisms associated with facial affect recognition deficits after traumatic brain injury
(Springer, 2015-06) Neumann, Dawn; McDonald, Brenna C.; West, John; Keiski, Michelle A.; Wang, Yang; Department of Physical Medicine and Rehabilitation, IU School of Medicine
The neurobiological mechanisms that underlie facial affect recognition deficits after traumatic brain injury (TBI) have not yet been identified. Using functional magnetic resonance imaging (fMRI), study aims were to 1) determine if there are differences in brain activation during facial affect processing in people with TBI who have facial affect recognition impairments (TBI-I) relative to people with TBI and healthy controls who do not have facial affect recognition impairments (TBI-N and HC, respectively); and 2) identify relationships between neural activity and facial affect recognition performance. A facial affect recognition screening task performed outside the scanner was used to determine group classification; TBI patients who performed greater than one standard deviation below normal performance scores were classified as TBI-I, while TBI patients with normal scores were classified as TBI-N. An fMRI facial recognition paradigm was then performed within the 3T environment. Results from 35 participants are reported (TBI-I = 11, TBI-N = 12, and HC = 12). For the fMRI task, TBI-I and TBI-N groups scored significantly lower than the HC group. Blood oxygenation level-dependent (BOLD) signals for facial affect recognition compared to a baseline condition of viewing a scrambled face, revealed lower neural activation in the right fusiform gyrus (FG) in the TBI-I group than the HC group. Right fusiform gyrus activity correlated with accuracy on the facial affect recognition tasks (both within and outside the scanner). Decreased FG activity suggests facial affect recognition deficits after TBI may be the result of impaired holistic face processing. Future directions and clinical implications are discussed.
Exploration of a new tool for assessing emotional inferencing after traumatic brain injury
(Taylor and Francis, 2015-05) Zupan, Barbra; Neumann, Dawn; Babbage, Duncan R.; Willer, Barry; Department of Physical Medicine and Rehabilitation, IU School of Medicine
bjective: To explore validity of an assessment tool under development—the Emotional Inferencing from Stories Test (EIST). This measure is being designed to assess the ability of people with traumatic brain injury (TBI) to make inferences about the emotional state of others solely from contextual cues. Methods and procedures: Study 1: 25 stories were presented to 40 healthy young adults. From this data, two versions of the EIST (EIST-1; EIST-2) were created. Study 2: Each version was administered to a group of participants with moderate-to-severe TBI—EIST 1 group: 77 participants; EIST-2 group: 126 participants. Participants also completed a facial affect recognition (DANVA2-AF) test. Participants with facial affect recognition impairment returned 2 weeks later and were re-administered both tests. Main outcomes: Participants with TBI scored significantly lower than the healthy group mean for EIST-1, F(1,114) = 68.49, p < 0.001, and EIST-2, F(1,163) = 177.39, p < 0.001. EIST scores in the EIST-2 group were significantly lower than the EIST-1 group, t = 4.47, p < 0.001. DANVA2-AF scores significantly correlated with EIST scores, EIST-1: r = 0.50, p < 0.001; EIST-2: r = 0.31, p < 0.001. Test–re-test reliability scores for the EIST were adequate. Conclusions: Both versions of the EIST were found to be sensitive to deficits in emotional inferencing. After further development, the EIST may provide clinicians valuable information for intervention planning.
Amantadine effect on perceptions of irritability after traumatic brain injury: results of the amantadine irritability multisite study
(Mary Ann Liebert, Inc., 2015-08-15) Hammond, Flora M.; Sherer, Mark; Malec, James F.; Zafonte, Ross D.; Whitney, Marybeth; Bell, Kathleen; Dikmen, Sureyya; Bogner, Jennifer; Mysiw, Jerry; Pershad, Rashmi; Physical Medicine and Rehabilitation, School of Medicine
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.
Long-term survival after traumatic brain injury: a population-based analysis controlled for nonhead trauma
(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-01) Brown, Allen W.; Leibson, Cynthia L.; Mandrekar, Jay; Ransom, Jeanine E.; Malec, James F.; Department of Physical Medicine and Rehabilitation, IU School of Medicine
OBJECTIVE: To examine the contribution of co-occurring nonhead injuries to hazard of death after traumatic brain injury (TBI). PARTICIPANTS: A random sample of Olmsted County, Minnesota, residents with confirmed TBI from 1987 through 1999 was identified. DESIGN: Each case was assigned an age- and sex-matched, non-TBI "regular control" from the population. For "special cases" with accompanying nonhead injuries, 2 matched "special controls" with nonhead injuries of similar severity were assigned. MEASURES: Vital status was followed from baseline (ie, injury date for cases, comparable dates for controls) through 2008. Cases were compared first with regular controls and second with regular or special controls, depending on case type. RESULTS: In total, 1257 cases were identified (including 221 special cases). For both cases versus regular controls and cases versus regular or special controls, the hazard ratio was increased from baseline to 6 months (10.82 [2.86-40.89] and 7.13 [3.10-16.39], respectively) and from baseline through study end (2.92 [1.74-4.91] and 1.48 [1.09-2.02], respectively). Among 6-month survivors, the hazard ratio was increased for cases versus regular controls (1.43 [1.06-2.15]) but not for cases versus regular or special controls (1.05 [0.80-1.38]). CONCLUSIONS: Among 6-month survivors, accounting for nonhead injuries resulted in a nonsignificant effect of TBI on long-term mortality.
Dietary intake relative to cardiovascular disease risk factors in individuals with chronic spinal cord injury: a pilot study
(Thomas Land, 2014-04-11) Lieberman, Jesse; Goff, David Jr.; Hammond, Flora; Schreiner, Pamela; Norton, H. James; Dulin, Michael; Zhou, Xia; Steffan, Lyn; Department of Physical Medicine and Rehabilitation, School of Medicine
BACKGROUND: The relationship between cardiovascular disease (CVD) risk factors and dietary intake is unknown among individuals with spinal cord injury (SCI). OBJECTIVE: To investigate the relationship between consumption of selected food groups (dairy, whole grains, fruits, vegetables, and meat) and CVD risk factors in individuals with chronic SCI. METHODS: A cross-sectional substudy of individuals with SCI to assess CVD risk factors and dietary intake in comparison with age-, gender-, and race-matched able-bodied individuals enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary history, blood pressure, waist circumference (WC), fasting blood glucose, high-sensitivity C-reactive protein (hs-CRP), lipids, glucose, and insulin data were collected from 100 SCI participants who were 38 to 55 years old with SCI >1 year and compared to 100 matched control participants from the CARDIA study. RESULTS: Statistically significant differences between SCI and CARDIA participants were identified in WC (39.2 vs 36.2 in.; P < .001) and high-density lipoprotein cholesterol (HDL-C; 39.2 vs 47.5 mg/dL; P < .001). Blood pressure, total cholesterol, triglycerides, glucose, insulin, and hs-CRP were similar between SCI and CARDIA participants. No significant relation between CVD risk factors and selected food groups was seen in the SCI participants. CONCLUSION: SCI participants had adverse WC and HDL-C compared to controls. This study did not identify a relationship between consumption of selected food groups and CVD risk factors.
Dietary intake and adherence to the 2010 Dietary Guidelines for Americans among individuals with chronic spinal cord injury: a pilot study
(Maney Publishing, 2014-11) Lieberman, Jesse; Goff, David; Hammond, Flora; Schreiner, Pamela; Norton, H. James; Dulin, Michael; Zhou, Xia; Steffen, Lyn; Department of Physical Medicine and Rehabilitation, IU School of Medicine
OBJECTIVE: To investigate dietary intake and adherence to the 2010 Dietary Guidelines for Americans in individuals with chronic spinal cord injury (SCI) and able-bodied individuals. DESIGN: A pilot study of dietary intake among a sample of individuals with SCI >1 year ago from a single site compared with able-bodied individuals. PARTICIPANTS/METHODS: One hundred black or white adults aged 38-55 years old with SCI >1 year and 100 age-, sex-, and race-matched adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary intake was assessed by the CARDIA dietary history. Linear regression analysis was used to compare dietary intake between the subjects with SCI and those enrolled in the CARDIA study. Further, adherence to the 2010 Dietary Guidelines for dairy, fruits, and vegetables, and whole-grain foods was assessed. RESULTS: Compared with CARDIA participants, participants with SCI consumed fewer daily servings of dairy (2.10 vs. 5.0, P < 0.001), fruit (2.01 vs. 3.64, P = 0.002), and whole grain foods (1.20 vs. 2.44 P = 0.007). For each food group, fewer participants with SCI met the recommended servings compared with the CARDIA participants. Specifically, the participants with SCI and in CARDIA who met the guidelines were, respectively: dairy, 22% vs. 54% (P < 0.001), fruits and vegetables 39% vs. 70% (P = 0.001), and whole-grain foods 8% vs. 69.6% (P = 0.001). CONCLUSIONS: Compared with able-bodied individuals, SCI participants consumed fewer daily servings of fruit, dairy, and whole grain foods than proposed by the 2010 Dietary Guideline recommendations. Nutrition education for this population may be warranted.
Perspective training to treat anger problems after brain injury: Two case studies
(IOS, 2016-07) Winegardner, Jill; Keohane, Clare; Prince, Leyla; Neumann, Dawn; Department of Physical Medicine and Rehabilitation, IU School of Medicine
BACKGROUND: People with acquired brain injury (ABI) often show increased anger and aggression. Anger has been linked to attributions of hostile intent. The more intentional and hostile the judgments of other’s behaviours are, the angrier the responses tend to be. Some people with ABI tend to make harsher attributions than healthy controls (negative attribution bias). Poor perspective-taking may distort assessment of others’ intentions, thereby contributing to this bias and subsequent anger responses. OBJECTIVE: Examine changes in anger and perspective-taking after a Perspectives Group in two participants with ABI. METHODS: This study is a case report exploring observational changes in anger, hostility, verbal and physical aggression and perspective-taking in two males with ABI and severe emotion dysregulation. Participants and their spouses also provided qualitative feedback through a semi-structured interview following perspectives training. The six-week “Perspectives Group” used hypothetical and real-life situations to teach participants to consider the perspectives of others when determining their intentions. RESULTS: Both participants showed post-treatment declines in aggression. Although only minimal changes occurred on the perspective-taking measure, spouses described important behavioural changes in their partners that indicated both decreased aggression and better perspective taking. CONCLUSIONS: These preliminary findings support further investigation of perspectives training for reducing anger after ABI.
Preliminary Evaluation of a Measure for Reliable Assessment of Need for Constant Visual Observation in Adults with Traumatic Brain Injury
(Taylor & Francis, 2016) Moessner, Anne; Malec, James F.; Beveridge, Scott; Reddy, Cara Camiolo; Huffman, Tracy; Marton, Julia; Department of Physical Medicine and Rehabilitation, IU School of Medicine
Primary objective: To develop and provide initial validation of a measure for accurately determining the need for Constant Visual Observation (CVO) in patients with traumatic brain injury (TBI) admitted to inpatient rehabilitation. Research design: Rating scale development and evaluation through Rasch analysis and assessment of concurrent validity. Methods and procedures: One hundred and thirty-four individuals with moderate–severe TBI were studied in seven inpatient brain rehabilitation units associated with the National Institute for Disability, Independent Living and Rehabilitation Research (NIDILRR) TBI Model System. Participants were rated on the preliminary version of the CVO Needs Assessment scale (CVONA) and, by independent raters, on the Levels of Risk (LoR) and Supervision Rating Scale (SRS) at four time points during inpatient rehabilitation: admission, Days 2–3, Days 5–6 and Days 8–9. Outcomes and results: After pruning misfitting items, the CVONA showed satisfactory internal consistency (Person Reliability = 0.85–0.88) across time points. With reference to the LoR and SRS, low false negative rates (sensitivity > 90%) were associated with moderate-to-high false positive rates (29–56%). Conclusions: The CVONA may be a useful objective metric to complement clinical judgement regarding the need for CVO; however, further prospective study is desirable to further assess its utility in identifying at-risk patients, reducing adverse events and decreasing CVO costs.
PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury
(Springer (Biomed Central Ltd.), 2016-06-09) Hammond, Flora M.; Alexander, David N.; Cutler, Andrew J.; D’Amico, Stephen; Doody, Rachelle S.; Sauve, William; Zorowitz, Richard D.; Davis, Charles S.; Shin, Paul; Ledon, Fred; Yonan, Charles; Formella, Andrea E.; Siffert, Joao; Department of Physical Medicine and Rehabilitation, IU School of Medicine
BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013.
Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury
(Wiley, 2016-09) Ritter, Anne C.; Wagner, Amy K.; Szaflarski, Jerzy P.; Brooks, Maria M.; Zafonte, Ross D.; Pugh, Mary Jo; Fabio, Anthony; Hammond, Flora M.; Dreer, Laura E.; Bushnik, Tamara; Walker, William C.; Brown, Allen W.; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W.; Rosenthal, Joseph A.; Department of Physical Medicine and Rehabilitation, IU School of Medicine
Objective Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Methods Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011–2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). Results The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. Significance The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should externally validate models and determine clinical utility.

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