NNS 2015 Abstract Book

African-American, 2 for work-related injury, 1 for dangerous mecha-

nism and 1 for other injury. Subjects with a HeadSMART30

7; 7 and

8; 9 and 10; and greater than 10 had a 1-month risk of incomplete

recovery of 0%, 27%, 71% and 86% respectively. This study provides

preliminary evidence that prognostication of mTBI outcome using

readily available clinical and demographic data is feasible.

Keywords: prognostic models, GOSE, TBI

S12-02

AN INITIAL EVALUATION OF THE NINDS PHENOTYPING

COMMON DATA ELEMENTS FOR TRAUMATIC BRAIN

INJURY

John Dsurney

, Shannon McNally

, Andre van der Merwe

Leighton

Chan

1,2

National Institutes of Health, Clinical Center, Bethesda, USA

Center for Neuroscience and Regenerative Medicine, Phenotyping

Core, Rockville, USA

Introduction:

In 2010, the NIH and other federal agencies identified a

list of Common Data Elements (CDE) that might be used in traumatic

brain injury (TBI) research. The selection of these instruments was not

empirically based, but was guided by their availability in the public

domain, the availability of alternate forms, and, most importantly,

expert opinion regarding the utility of the tests. The present study

undertakes an empirical examination of these instruments, comparing

their performance to other tests.

Methods:

A total of 111 (62% male) subjects who had sustained a

closed head injury were seen at 30, 90, 180 and/or 365 days post injury.

Subjects were administered eight of the ten original ‘‘core’’ neu-

ropsychological CDE’s, two ‘‘core’’ CDE’s were replaced by equiva-

lent ‘‘supplemental’’ measures. Subjects were also administered seven

additional ‘‘supplemental’’ CDE’s, as well as additional well validated,

commonly used neuropsychological tests. The percentage of individuals

classified as ‘‘impaired’’ (scoring less than one standard deviation be-

low the mean) was calculated for each time point and by severity.

Results:

Our cohort included 60 mild, 33 moderate, and 18 severe

patients with TBI. Of the original CDE’s, the Trail Making Tests

(TMT) A and B and California Verbal Learning Test (CVLT-2) were

the most sensitive, identifying impairment regardless of patient se-

verity or time since injury. Other original CDE tests, such the Wis-

consin Card Sort did not perform as well. In addition, some other tests,

such as the Booklet Category Test, Sea Shore Rhythm Test, Con-

trolled Oral Word Association Test, Grooved Pegboard, and Finger

Tapping Tests consistently identified impairment, outperformed the

original CDE’s.

Conclusions:

Only some of the current CDE’s were useful in our

cohort. These included: TMT A and B, BSI and CVLT-2. In addition,

a number of tests not included as original CDE’s demonstrated sen-

sitivity in the evaluation of TBI subjects and are recommended for use

in this population.

Keywords: Common Data Elements, Neuropsychological, Out-

comes, Phenotyping

S12-03

ADOLESCENT TRAUMATIC BRAIN INJURY INCREASES

ALCOHOL CONSUMPTION AND REWARD IN FEMALE

MICE

Zachary Weil

, Kate Karelina

, Kristopher Gaier

, Timothy

Corrigan

, John Corrigan

Ohio State University Wexner Medical Center, Department of Neu-

roscience, Columbus, USA

Ohio State University Wexner Medical Center, Department of Phy-

sical Medicine and Rehabilitation, Columbus, USA

Traumatic brain injury (TBI) is inextricably and bidirectionally linked

with alcohol use. Some estimates implicate alcohol intoxication in one-

third to one-half of all TBI cases. Alcohol use following injury can reduce

the efficacy of rehabilitation and greatly increase the chances for addi-

tional injury. Additionally, there is mounting evidence that TBI itself may

be a risk factor for the development of alcohol use disorders. Finally,

patients injured in childhood have poorer overall life outcomes and a

much greater likelihood of developing substance abuse disorders. We

used a standardized closed head injury to model mild traumatic brain

injuries. We found that mice injured during adolescence but not during

adulthood exhibited much greater alcohol self-administration in adult-

hood. Further, this phenomenon was limited to female mice as there was

no effect of injury in males. Using behavioral testing, we determined that

increased drinking behavior is mediated by alterations in the rewarding

properties of alcohol and not sensory deficits from TBI. Environmental

enrichment administered after injury reduced axonal degeneration and

prevented the increase in drinking behavior. Additionally, brain derived

neurotrophic factor gene expression, which was reduced by TBI, was

normalized by environmental enrichment. Finally, an analysis of human

data indicated that girls injured during early adolescence were muchmore

likely to misuse alcohol as adults than were girls injured during other

developmental epochs. Together these results suggest a novel model of

alterations in reward circuitry following trauma during development.

Keywords: Alcohol, Adolescent Injury, Environmental Enrichment,

BDNF, Inflammation, Concussion

S12-04

SINGLE EPISODE OF SEVERE AXONAL INJURY IN HU-

MANS IS ASSOCIATED WITH PATHOLOGY RESEMBLING

CHRONIC TRAUMATIC ENCEPHALOPATHY

Sarah Edgerton, Sharon Shively, Bao-Xi Qu, Diaz-Arrastia Ramon,

Dan Perl

USUHS, CNRM, Bethesda, USA

Chronic traumatic encephalopathy (CTE) is a neurodegenerative

disorder associated with repetitive mild traumatic brain injury (TBI).

In CTE, abnormal

tau

proteins aggregate in a distinctive pattern of

neurofibrillary tangles (NFTs) and astrocytic tangles favoring sulcal

depths, perivascular regions and superficial neocortical layers. It has

been suggested that these

tau

aggregates develop following axonal

damage and/or impact-related mechanical stresses.

We analyzed postmortem brains from six schizophrenic patients who

had undergone prefrontal leucotomy prior to 1953 and then lived at least

another 40 years. Because leucotomy involves severing axons of the

prefrontal cortex, this procedure represents a single TBI with severe

axonal injury and no external cortical impact. We examined cortical

tissues at the leucotomy sites, prefrontal and caudal frontal cortices and

hippocampi. We compared these specimens to brains of six age-matched,

non-leucotomized schizophrenics. We conducted immunohistochemis-

try using antibodies against abnormal

tau,

-amyloid and astrocytes. We

performed APOE genotyping for the six leucotomy patients.

In all six leucotomy cases, prefrontal lesion sites revealed severe white

matter damage. Abnormal

tau

(NFTs and astrocytic tangles) was de-

tected in cortex adjacent to leucotomy sites, involving depths of sulci,

perivascular regions and superficial neocortical layers, but not in pre-

frontal and caudal frontal cortices distant to the leucotomy lesions. Si-

milarly,

-amyloid plaques occupied the gray matter adjacent to the

A-14