Faculty Bibliography

There are no established biomarkers for mild traumatic brain injury (mTBI), in part because post-concussive symptoms (PCS) are subjective and conventional imaging is typically unremarkable. To test whether diffuse axonal abnormalities quantified with three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1H-MRSI) correlated with patients' PCS, we retrospectively studied 26 mTBI patients (mean Glasgow Coma Scale score of 14.7), 18-56 years old, 3 - 55 days post injury and 13 controls. All were scanned at 3 Tesla with T1-and T2-weighted MRI and 3D 1H-MRSI (480 voxels over 360 cm3, ~30% of the brain). On scan day patients completed a symptom questionnaire and those indicating at least one of the most common acute/subacute mTBI symptoms (headache, dizziness, sleep disturbance, memory deficits, blurred vision) were grouped as PCS-positive. Global gray- and white matter (GM/WM) absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) in the PCS-positive and PCS-negative patients were compared to age- and gender-matched controls using two-way analysis of variance. The results showed that the PCS-negative group (n=11) and controls (n=8) did not differ in any GM or WM metabolite level. The PCS-positive patients (n=15), however, had lower WM NAA than the controls (n=12): 7.0+/-0.6 mM (mean+/- standard deviation) versus 7.9+/-0.5mM (p=0.0007). Global WM NAA, therefore, showed sensitivity to the TBI sequelae associated with common PCS in individuals with mostly normal neuroimaging as well as GCS scores. This suggests a potential biomarker role in a patient population in which objective measures of injury and symptomatology are currently lacking.

Abstract Long-term mortality is increased after mild traumatic brain injury (mTBI). Central cardiovascular-autonomic dysregulation resulting from subtle, trauma-induced brain lesions might contribute to cardiovascular events and fatalities. We investigated whether there is cardiovascular-autonomic dysregulation after mTBI. In 20 mTBI patients (37+/-13 years, 5-43 months post-injury) and 20 healthy persons (26+/-9 years), we monitored respiration, RR intervals (RRI), blood pressures (BP), while supine and upon standing. We calculated the root mean square successive RRI differences (RMSSD) reflecting cardiovagal modulation, the ratio of maximal and minimal RRIs around the 30th and 15th RRI upon standing (30:15 ratio) reflecting baroreflex sensitivity (BRS), spectral powers of parasympathetic high-frequency (HF: 0.15-0.5 Hz) RRI oscillations, of mainly sympathetic low-frequency (LF: 0.04-0.15 Hz) RRI oscillations, of sympathetic LF-BP oscillations, RRI-LF/HF-ratios reflecting sympathovagal balance, and the gain between BP and RRI oscillations as additional BRS index (BRS(gain)). We compared supine and standing parameters of patients and controls (repeated measures analysis of variance; significance: p<0.05). While supine, patients had lower RRIs (874.2+/-157.8 vs. 1024.3+/-165.4 ms), RMSSDs (30.1+/-23.6 vs. 56.3+/-31.4 ms), RRI-HF powers (298.1+/-309.8 vs. 1507.2+/-1591.4 ms(2)), and BRS(gain) (8.1+/-4.4 vs. 12.5+/-8.1 ms.mmHg(-1)), but higher RRI-LF/HF-ratios (3.0+/-1.9 vs. 1.2+/-0.7) than controls. Upon standing, RMSSDs and RRI-HF-powers decreased significantly in controls, but not in patients; patients had lower RRI-30:15-ratios (1.3+/-0.3 vs. 1.6+/-0.3) and RRI-LF-powers (2450.0+/-2110.3 vs. 4805.9+/-3453.5 ms(2)) than controls. While supine, mTBI patients had reduced cardiovagal modulation and BRS. Upon standing, their BRS was still reduced, and patients did not withdraw parasympathetic or augment sympathetic modulation adequately. Impaired autonomic modulation probably contributes to cardiovascular irregularities post-mTBI

Rehabilitation following traumatic brain injury (TBI) is best provided by an interdisciplinary team of health care providers that takes advantage of the unique skills of multiple specialists, as well as their combined strengths that address problems that cut across disciplines. The setting where rehabilitation is provided is determined by the medical stability of patients, their ability to tolerate intensive therapies, and their likelihood of community reintegration within a reasonable period of time. Successful rehabilitation requires prompt recognition and treatment of TBI-related medical, cognitive, and behavioral problems to promote recovery and enhance community reintegration, using a combination of rehabilitation modalities and medications

OBJECTIVE: To examine the efficacy of sertraline in the treatment of depression after traumatic brain injury (TBI). DESIGN: Double-blind, randomized controlled trial. SETTING: Research center at a major urban medical center. PARTICIPANTS: Subjects were a referred and volunteer sample of 52 participants with TBI, a diagnosis of major depression disorder (MDD), and a score on the Hamilton Rating Scale for Depression (HAM-D) of 18 or greater. The majority of the sample was male (58%), had less than 14 years of education (73%), had incomes below $20,000 (82%), and were from minority backgrounds (75%). Approximately one third of the sample had mild brain injuries, and two thirds had moderate to severe brain injuries. The mean age was 47+/-11, and the mean time since injury was 17+/-14 years. One participant withdrew from the study because of side effects. INTERVENTION: Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg) or placebo for 10 weeks. MAIN OUTCOME MEASURES: The HAM-D, the Beck Anxiety Inventory, and the Life-3 quality of life (QOL). RESULTS: No statistically significant differences were found at baseline between drug and placebo groups on baseline measures of depression (24.8+/-7.3 vs 27.7+/-7.0), anxiety (16.4+/-12.3 vs 24.0+/-14.9), or QOL (2.96+/-1.0 vs 2.9+/-0.9). The income level of those receiving placebo was significantly lower than those participants receiving medication. Analyses of covariance revealed significant changes from preintervention to posttreatment for all 3 outcome measures (P<.001) but no group effects. Random-effects modeling did not find any significant difference in patterns of scores of the outcome measures between the placebo and medication groups. CONCLUSIONS: Both groups showed improvements in mood, anxiety, and QOL, with 59% of the experimental group and 32% of the placebo group responding to the treatment, defined as a reduction of a person's HAM-D score by 50%