Small subdural hemorrhages: Does size of intracranial hemorrhage impact symptoms after discharge?

INTRO: Patients with small intracranial hemorrhage at initial presentation (ICHi) have a relatively uneventful hospital course, as compared with larger ICHi. In this study, we tested the null hypothesis that ICHi does not impact the symptom profile of patients with traumatic brain injury (TBI) after discharge. METHODS: In this retrospective study, TBI patients over 18 years of age with a head CT at initial presentation and at least one follow-up visit between 2015 and 2018 were included. Those with vascular risk factors, major psychiatric comorbidities, neurologic disorders, and TBI / CT evidence of ICH within five years were excluded. Patients were stratified based on the presence or absence of ICHi. Symptom profiles were characterized during early (0-3 months post-TBI) and late follow up (4-12 months post-TBI). An adapted 15-question Post-Concussion Symptom Scale and a vestibulo-oculomotor (VOM) exam were assessed by a TBI specialist. We compared the age adjusted clinical symptom profiles between those with and without ICHi. RESULTS: 69 patients met inclusion/exclusion criteria. 26 (37.8%) had ICHi and 43 (62.32%) did not have ICH. The severity of measured symptoms or VOM findings were not more severe in those with ICHi. Age-adjusted analyses did not show any effect on these outcomes. CONCLUSION: ICHi does not impact the symptom profile of patients with TBI in either short or long term.

Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria.

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.

The dissociation of temporal processing behavior in concussion patients: Stable motor and dynamic perceptual timing.

Temporal processing is an integral aspect of human cognition and perception. Recent studies have suggested that patients suffering from concussion exhibit a deficit in temporal processing, characterized by poor performance on a variety of timing tasks. However, the majority of studies focusing on temporal processing deficits in concussion have focused on visual timing mechanisms. As temporal processing may be dominant for auditory-based processing, and so less susceptible to noise, we investigated patients with TBI and compared them to normal healthy controls on a battery of temporal processing tasks, including paced finger tapping and temporal bisection with sub-second intervals. The results of our investigation found that traumatic brain patients were unimpaired on the paced finger tapping task, suggesting that temporal processing deficits do not extend into motor timing and rhythmicity domain. In the temporal bisection task, TBI patients maintained precision but had a significantly higher bisection point, characterized by a greater propensity to judge stimuli as "short" and were significantly slower than controls. Analysis with a drift-diffusion model of perceptual decision-making revealed that TBI patients were specifically impaired in evidence accumulation, suggesting a smaller signal to noise ratio. Specifically, it demonstrated that patients had higher decision threshold and slower drift rates for accumulating evidence in order to arrive at a decision. Patients had to surmount higher evidence thresholds to reach a decision and were slower than controls in their rate of evidence accumulation. These results suggest specific deficits in temporal perceptual decision-making may predict the neural temporal pathways that may be compromised or unaffected, paving the way for designing targeted therapies to address these impairments.

Diffusion tensor imaging in mild traumatic brain injury litigation.

A growing body of literature addresses the application of diffusion tensor imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity, and their diagnosis and prognosis are often challenging. These challenges may be exacerbated in medicolegal contexts, where plaintiffs seek to present objective evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits quantification of white matter integrity and because TBI frequently involves white matter injury, DTI represents a conceptually appealing method of demonstrating white matter pathology attributable to mTBI. However, alterations in white matter integrity are not specific to TBI, and their presence does not necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the literature describing DTI findings in mTBI and related neuropsychiatric disorders. Based on this review, we suggest that expert testimony regarding DTI findings will seldom be appropriate in legal proceedings focused on mTBI.

Verbal learning strategy following mild traumatic brain injury.

That learning and memory deficits persist many years following mild traumatic brain injury (mTBI) is controversial due to inconsistent objective evidence supporting subjective complaints. Our prior work demonstrated significant reductions in performance on the initial trial of a verbal learning task and overall slower rate of learning in well-motivated mTBI participants relative to demographically matched controls. In our previous work, we speculated that differences in strategy use could explain the differences in rate of learning. The current study serves to test this hypothesis by examining strategy use on the California Verbal Learning Test-Second Edition. Our present findings support the primary hypothesis that mTBI participants under-utilize semantic clustering strategies during list-learning relative to control participants. Despite achieving comparable total learning scores, we posit that the persisting learning and memory difficulties reported by some mTBI patients may be related to reduced usage of efficient internally driven strategies that facilitate learning. Given that strategy training has demonstrated improvements in learning and memory in educational and occupational settings, we offer that these findings have translational value in offering an additional approach in remediation of learning and memory complaints reported by some following mTBI.

Procedural learning impairments identified via predictive saccades in chronic traumatic brain injury.

OBJECTIVE: To characterize integrity of fronto-striatal circuitry in chronic traumatic brain injury (TBI). BACKGROUND: Due to both direct and indirect effects, TBI is hypothesized to affect frontal and striatal function. On the basis of elegant animal, lesion, and neuroimaging literatures, oculomotor testing can provide a useful tool for in vivo assessments of neurophysiologic function. The predictive saccade paradigm in oculomotor function is well established to provide assessment of this fronto-striatal circuit. METHODS: Sixty patients with a history of chronic TBI completed 2 specific tests of oculomotor function, including a test of reflexive visually guided saccades to assess basic oculomotor function and a predictive saccade test to assess procedural learning. RESULTS: TBI (mild and moderate/severe) was associated with a decrease in rates of procedural learning, with degree of impairment increasing with injury severity. This was observed as a decrease in the proportion of anticipatory saccades (primary measure of learning). CONCLUSIONS: This abnormal oculomotor performance supports the hypothesis that TBI results in chronic impairment of frontal-striatal functions proportionally to injury severity and demonstrate that oculomotor testing is sensitive to all severities of closed-head injury.

Verbal learning differences in chronic mild traumatic brain injury.

Following mild traumatic brain injury (TBI), a percentage of individuals report chronic memory and attention difficulties. Traditional neuropsychological assessments often fail to find evidence for such complaints. We hypothesized that mild TBI patients may, in fact, experience subtle cognitive deficits that reflect diminished initial acquisition that can be explained by changes in cerebral white matter microstructure. In the data presented here, a sample of nonlitigating and gainfully employed mild TBI patients demonstrated statistically significant differences from age and education matched control participants in performance on the first trial of a verbal learning task. Performance on this trial was associated with reduced fractional anisotropy in the uncinate fasciculus and the superior longitudinal fasciculus providing an anatomical correlate for the cognitive findings. Mild TBI patients were not impaired relative to control participants on total learning or memory composite variables. Performance on the first learning trial was not related to any psychological variables including mood. We concluded that patients with mild TBI demonstrate diminished verbal learning that is not often interpreted in standard neuropsychological assessment.

Neuroimaging of hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury (HI-BI) is a common cause of neurological morbidity in children and adults. Recent developments in neuroimaging techniques may permit in vivo identification of the structural and functional anatomy of HI-BI, and offer opportunities for the development of neuroimaging-guided prognosis. This article provides an update on the types and possible roles of currently-available neuroimaging techniques. The applications and limitations of these techniques to the study and clinical evaluation of persons with HI-BI are discussed, and the need of further research is highlighted.

Review of adjunctive glutamate antagonist therapy in the treatment of catatonic syndromes.

Catatonia is a common neuropsychiatric syndrome which may arise from GABA-A hypoactivity, dopamine (D2) hypoactivity,and possibly glutamate NMDA hyperactivity. Amantadine and memantine have been reported as effective treatments for catatonia in selected cases, and probably mediate the presence of catatonic signs and symptoms through complex pathways involving glutamate antagonism. The authors identified 25 cases of catatonia treated with either agent. This article provides indirect evidence that glutamate antagonists may improve catatonic signs in some patients who fail to respond to established treatment, including lorazepam or electroconvulsive therapy. Further study of glutamate antagonists in the treatment of catatonia is needed.

White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study.

Traumatic brain injury (TBI) is a serious public health problem. Even injuries classified as mild, the most common, can result in persistent neurobehavioural impairment. Diffuse axonal injury is a common finding after TBI, and is presumed to contribute to outcomes, but may not always be apparent using standard neuroimaging. Diffusion tensor imaging (DTI) is a more recent method of assessing axonal integrity in vivo. The primary objective of the current investigation was to characterize white matter integrity utilizing DTI across the spectrum of chronic TBI of all severities. A secondary objective was to examine the relationship between white matter integrity and cognition. Twenty mild, 17 moderate to severe TBI and 18 controls underwent DTI and neuropsychological testing. Fractional anisotropy, axial diffusivity and radial diffusivity were calculated from the DTI data. Fractional anisotropy was the primary measure of white matter integrity. Region of interest analysis included anterior and posterior corona radiata, cortico-spinal tracts, cingulum fibre bundles, external capsule, forceps minor and major, genu, body and splenium of the corpus callosum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and sagittal stratum. Cognitive domain scores were calculated from executive, attention and memory testing. Decreased fractional anisotropy was found in all 13 regions of interest for the moderate to severe TBI group, but only in the cortico-spinal tract, sagittal stratum and superior longitudinal fasciculus for the mild TBI group. White Matter Load (a measure of the total number of regions with reduced FA) was negatively correlated with all cognitive domains. Analysis of radial and axial diffusivity values suggested that all severities of TBI can result in a degree of axonal damage, while irreversible myelin damage was only apparent for moderate to severe TBI. The present data emphasize that white matter changes exist on a spectrum, including mild TBI. An index of global white matter neuropathology (White Matter Load) was related to cognitive function, such that greater white matter pathology predicted greater cognitive deficits. Mechanistically, mild TBI white matter changes may be primarily due to axonal damage as opposed to myelin damage. The more severe injuries impact both. DTI provides an objective means for determining the relationship of cognitive deficits to TBI, even in cases where the injury was sustained years prior to the evaluation.

Oculomotor function in chronic traumatic brain injury.

OBJECTIVE: To characterize oculomotor function using visually guided saccade and antisaccade (AS) tasks in chronic traumatic brain injury (TBI) and assess the relationship to neuropsychologic testing. BACKGROUND: TBI causes dysfunction of prefrontal cortex, in part by disrupting cortical and subcortical pathways, resulting in specific cognitive impairments. Oculomotor function tests provide a method of assessing the integrity of these pathways. METHODS: Twenty mild TBI (MTBI), 17 moderate to severe TBI (M/STBI), and 19 healthy controls underwent oculomotor and neuropsychologic testing. RESULTS: On the visually guided saccade task, the M/STBI showed longer latencies and reduced accuracy. On the AS task, which is more dependent on prefrontal cortex function, both patient groups committed more prosaccade errors than controls. On neuropsychologic testing, only the M/STBI patients were significantly impaired. Correlations were found between AS and neuropsychologic performance. CONCLUSIONS: The M/STBI group was impaired on both oculomotor tasks and neuropsychologic testing, consistent with more global neuropathology. The MTBI group showed impaired performance primarily on the AS task, consistent with prefrontal system dysfunction. Hence, oculomotor testing is sensitive to the range of neuropathology in chronic TBI, and importantly, may be more sensitive to neuropathology in MTBI.

Relationship between apoE4 allele and excitatory amino acid levels after traumatic brain injury.

OBJECTIVE: Apolipoprotein E isoform (E4) has been posited to affect outcomes after central nervous system injury. This project sought to determine the relationship between the apoE4 allele and the recovery of amino acid neurotransmitters (aspartate, glutamate, and lactate/pyruvate ratio [L/P]) following a traumatic brain injury (TBI) after controlling for patient characteristics. DESIGN: This prospective clinical study examined neurotransmitters and L/P within the cerebrospinal fluid and compared the trends by apoE genotypes. SETTING: Adults with TBI were recruited from a neurotrauma intensive care unit within a trauma I university medical center. PATIENTS: Ninety-one patients were enrolled into the study after a severe TBI (Glasgow Coma Scale [GCS] score,

Amantadine improves water maze performance without affecting motor behavior following traumatic brain injury in rats.

Amantadine, a dopamine agonist, is reported to have beneficial effects on the neurobehavioral sequelae of clinical brain injury. However, there are currently no published laboratory reports on its use in the assessment of functional or histopathological outcome following experimental traumatic brain injury (TBI). To this end, we examined the effects of daily amantadine treatment on functional recovery (motor and Morris water maze performance) and hippocampal neuronal survival following controlled cortical impact (CCI) injury (4 meters/sec, 2.7 mm tissue deformation). Male Sprague-Dawley rats were pretrained on motor performance tasks (beam balance and beam walking) one day prior to injury and tested on post-operative days 1-5. Additionally, all subjects were trained on the Morris water maze on post-operative days 14-18. Beginning one day after CCI injury or sham surgery, animals were injected once daily for 18 days with either amantadine (10 mg/kg, i.p.) or saline. The amantadine treatment regimen was ineffective in promoting motor recovery and increasing survival of hippocampal neurons in both the CA1 and CA3 regions following TBI, but did show improved swim latencies during the five days of water maze testing (Day 14 vs. Day 18, p < 0.01) when compared to saline controls. Mean (+/- SE) swim latencies on Day 18 were 15.12 +/- 2.8, 13.25 +/- 4.18, 70.83 +/- 11.1, and 38.5 +/- 3.55 sec for the sham/saline, sham/amantadine, injured/saline, and injured/amantadine treatment groups, respectively. Thus, while the daily administration of amantadine exhibited a neutral effect on motor behavior, it produced a modest attenuation of water maze performance deficits. This latter finding is consistent with published clinical data suggesting a beneficial effect on functional outcome with amantadine therapy.