Identification of Demographic and Clinical Prognostic Factors in Traumatic Intraventricular Hemorrhage

BackgroundThe presence of traumatic intraventricular hemorrhage (tIVH) following traumatic brain injury (TBI) is associated with worse neurological outcome. The mechanisms by which patients with tIVH have worse outcome are not fully understood and research is ongoing, but foundational studies that explore prognostic factors within tIVH populations are also lacking. This study aimed to further identify and characterize demographic and clinical variables within a subset of patients with TBI and tIVH that may be implicated in tIVH outcome.MethodsIn this observational study, we reviewed a large prospective TBI database to determine variables present on admission that predicted neurological outcome 6 months after injury. A review of 7,129 patients revealed 211 patients with tIVH on admission and 6-month outcome data. Hypothesized risk factors were tested in univariate analyses with significant variables (p < 0.05) included in logistic and linear regression models. Following the addition of either the Rotterdam computed tomography or Glasgow Coma Scale (GCS) score, we employed a backward selection process to determine significant variables in each multivariate model.ResultsOur study found that that hypotension (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.13-0.94, p = 0.04) and the hemoglobin level (OR = 1.33, 95% CI = 1.09-1.63, p = 0.006) were significant predictors in the Rotterdam model, whereas only the hemoglobin level (OR = 1.29, 95% CI = 1.06-1.56, p = 0.01) was a significant predictor in the GCS model.ConclusionsThis study represents one of the largest investigations into prognostic factors for patients with tIVH and demonstrates that admission hemoglobin level and hypotension are associated with outcomes in this patient population. These findings add value to established prognostic scales, could inform future predictive modeling studies, and may provide potential direction in early medical management of patients with tIVH

Early Intervention via Stimulation of the Medial Septal Nucleus Improves Cognition and Alters Markers of Epileptogenesis in Pilocarpine-Induced Epilepsy

Over one-third of patients with temporal lobe epilepsy are refractory to medication. In addition, anti-epileptic drugs often exacerbate cognitive comorbidities. Neuromodulation is an FDA treatment for refractory epilepsy, but patients often wait >20 years for a surgical referral for resection or neuromodulation. Using a rodent model, we test the hypothesis that 2 weeks of theta stimulation of the medial septum acutely following exposure to pilocarpine will alter the course of epileptogenesis resulting in persistent behavioral improvements. Electrodes were implanted in the medial septum, dorsal and ventral hippocampus, and the pre-frontal cortex of pilocarpine-treated rats. Rats received 30 min/day of 7.7 Hz or theta burst frequency on days 4–16 post-pilocarpine, prior to the development of spontaneous seizures. Seizure threshold, spikes, and oscillatory activity, as well as spatial and object-based learning, were assessed in the weeks following stimulation. Non-stimulated pilocarpine animals exhibited significantly decreased seizure threshold, increased spikes, and cognitive impairments as compared to vehicle controls. Furthermore, decreased ventral hippocampal power (6–10 Hz) correlated with both the development of spikes and impaired cognition. Measures of spikes, seizure threshold, and cognitive performance in both acute 7.7 Hz and theta burst stimulated animals were statistically similar to vehicle controls when tested during the chronic phase of epilepsy, weeks after stimulation was terminated. These data indicate that modulation of the septohippocampal circuit early after pilocarpine treatment alters the progression of epileptic activity, resulting in elevated seizure thresholds, fewer spikes, and improved cognitive outcome. Results from this study support that septal theta stimulation has the potential to serve in combination or as an alternative to high frequency thalamic stimulation in refractory cases and that further research into early intervention is critical. © Copyright © 2021 Izadi, Schedlbauer, Ondek, Disse, Ekstrom, Cowen, Shahlaie and Gurkoff.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Recovery of Theta Frequency Oscillations in Rats Following Lateral Fluid Percussion Corresponds With a Mild Cognitive Phenotype

Whether from a fall, sports concussion, or even combat injury, there is a critical need to identify when an individual is able to return to play or work following traumatic brain injury (TBI). Electroencephalogram (EEG) and local field potentials (LFP) represent potential tools to monitor circuit-level abnormalities related to learning and memory: specifically, theta oscillations can be readily observed and play a critical role in cognition. Following moderate traumatic brain injury in the rat, lasting changes in theta oscillations coincide with deficits in spatial learning. We hypothesized, therefore, that theta oscillations can be used as an objective biomarker of recovery, with a return of oscillatory activity corresponding with improved spatial learning. In the current study, LFP were recorded from dorsal hippocampus and anterior cingulate in awake, behaving adult Sprague Dawley rats in both a novel environment on post-injury days 3 and 7, and Barnes maze spatial navigation on post-injury days 8–11. Theta oscillations, as measured by power, theta-delta ratio, peak theta frequency, and phase coherence, were significantly altered on day 3, but had largely recovered by day 7 post-injury. Injured rats had a mild behavioral phenotype and were not different from shams on the Barnes maze, as measured by escape latency. Injured rats did use suboptimal search strategies. Combined with our previous findings that demonstrated a correlation between persistent alterations in theta oscillations and spatial learning deficits, these new data suggest that neural oscillations, and particularly theta oscillations, have potential as a biomarker to monitor recovery of brain function following TBI. Specifically, we now demonstrate that oscillations are depressed following injury, but as oscillations recover, so does behavior. © Copyright © 2020 Ondek, Pevzner, Tercovich, Schedlbauer, Izadi, Ekstrom, Cowen, Shahlaie and Gurkoff.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Derivation of a Clinical Decision Instrument to Identify Adult Patients With Mild Traumatic Intracranial Hemorrhage at Low Risk for Requiring ICU Admission

Study objectiveThe objective of this study is to derive a clinical decision instrument with a sensitivity of at least 95% (with upper and lower bounds of the 95% confidence intervals [CIs] within a 5% range) to identify adult emergency department patients with mild traumatic intracranial hemorrhage who are at low risk for requiring critical care resources during hospitalization and thus may not need admission to the ICU.MethodsThis was a prospective, observational study of adult patients with mild traumatic intracranial hemorrhage (initial Glasgow Coma Scale [GCS] score 13 to 15, with traumatic intracranial hemorrhage) presenting to a Level I trauma center from July 2009 to February 2013. The need for ICU admission was defined as the presence of an acute critical care intervention (intubation, neurosurgical intervention, blood product transfusion, vasopressor or inotrope administration, invasive monitoring for hemodynamic instability, urgent treatment for arrhythmia or cardiopulmonary resuscitation, and therapeutic angiography). We derived the clinical decision instrument with binary recursive partitioning (with a misclassification cost of 20 to 1). The accuracy of the decision instrument was compared with the treating physician's (emergency medicine faculty) clinical impression.ResultsA total of 600 patients with mild traumatic intracranial hemorrhage were enrolled; 116 patients (19%) had a critical care intervention. The derived instrument consisted of 4 predictor variables: admission GCS score less than 15, nonisolated head injury, aged 65 years or older, and evidence of swelling or shift on initial cranial computed tomography scan. The decision instrument identified 114 of 116 patients requiring an acute critical care intervention (sensitivity 98.3%; 95% CI 93.9% to 99.5%) if at least 1 variable was present and 192 of 484 patients who did not have an acute critical care intervention (specificity 39.7%; 95% CI 35.4% to 44.1%) if no variables were present. Physician clinical impression was slightly less sensitive (90.1%; 95% CI 83.1% to 94.4%) but overall similar to the clinical decision instrument.ConclusionWe derived a clinical decision instrument that identifies a subset of patients with mild traumatic intracranial hemorrhage who are at low risk for acute critical care intervention and thus may not require ICU admission. Physician clinical impression had test characteristics similar to those of the decision instrument. Because the results are based on single-center data without a validation cohort, external validation is required