Iowa Plan for Brain Injury: Executive Summary, 2007-2010

Traumatic Brain Injury (TBI) impacts the lives of thousands of Iowans every year. TBI has been described as the “Silent Epidemic” because so often the scars are not visible to others. The affects of brain injury are cognitive, emotional, and social and can result in physical disability. In addition to the overwhelming challenges individuals with brain injury experience, families also face many difficulties in dealing with their loved one’s injury and in navigating a service delivery system that can be confusing and frustrating.

Traumatic Brain Injury in Iowa: An Analysis of Core Surveillance Data 2006-2008, July 15, 2011

Termed the “silent epidemic”, traumatic brain injury is the most debilitating outcome of injury characterized by the irreversibility of its damages, long-term effects on quality of life, and healthcare costs. The latest data available from the Centers for Disease Control and Prevention (CDC) estimate that nationally 50,000 people with traumatic brain injury (TBI) die each year; three times as many are hospitalized and more than twenty times as many are released from emergency room departments (ED) (CDC, 2008)1. The purpose of this report is to describe the epidemiology of TBI in Iowa to help guide policy and programming. TBI is a result of an external force which transfers energy to the brain. Stroke is caused by a disruption of blood flow in the brain that leads to brain injury. Though stroke is recognized as the 3rd leading cause of death nationally2, and is an injury that affects the brain it does not meet the definition a traumatic brain injury and is not included in this report.

Traumatic Brain Injury in Iowa Inpatient Hospital Data, 2003-2005

According to the Centers for Disease Control and Prevention, unintentional injury is the fifth leading cause of death for all age groups and the first leading cause of death for people from 1 to 44 years of age in the United States, while homicide remains the 2nd leading cause of death for 15 to 24 years old (CDC, 2006). In 2004, there were approximately 144,000 deaths due to unintentional injuries in the US; 53% of which represent people over 45 years of age (CDC, 2004). With 20,322 suicidal deaths and 13,170 homicidal deaths, intentional injury deaths affect mostly people under 45 years old. On average, there are 1,150 unintentional deaths per year in Iowa. In 2004, 37% of unintentional deaths were due to motor vehicle accidents (MTVCC) occurring across all age ranges and 30% were due to falls involving persons over 65 years of age 82% of the time (IDPH Health Stat Div., 2004). The most debilitating outcome of injury is traumatic brain injury, which is characterized by the irreversibility of its damages, long-term effects on quality of life, and healthcare costs. The latest data available from the CDC estimated that, nationally, 50,000 traumatic brain injured (TBI) people die each year; three times as many are hospitalized and more than twenty times as many are released from emergency room (ER) departments (CDC, 2006). Besides the TBI registry, brain injury data is also captured through three other data sources: 1) death certificates; 2) hospital inpatient data; and, 3) hospital outpatient data. The inpatient and outpatient hospital data are managed by the Iowa Hospital Association, which provides to Iowa Department of Public Health the hospital data without personal identifiers. (The hospitals send reports to the Agency of Health Care Research and Quality, which developed the Health Care Utilization Project and its product, the National Inpatient Sample).

Traumatic Brain Injury in Iowa: Iowa Brain Injury Resource Network Outcome Evaluation 2007-2009, August 2011

Termed the “silent epidemic,” traumatic brain injury (TBI) is the most debilitating outcome of injury, and is characterized by the irreversibility of its damages, long-term effects on quality of life and healthcare costs. The latest data available from the CDC estimate that nationally, 52,000 people die each year from TBI2. In Iowa, TBI is a major public health problem. The numbers and rates of hospitalizations and emergency department (ED) visits due to TBIs are steadily increasing. From 2006 to 2008, there were on average 545 injury deaths per year. Among the injured Iowans, TBI constituted nearly 30 percent (545) of all injury deaths, ten percent (1,591) of people hospitalized and seven percent (17,696) of ED visitors. 3 The state of Iowa has been supporting secondary prevention services to TBI survivors for several years. An Iowa organization that has made a significant effort in assisting TBI survivors is the Brain Injury Association of Iowa (BIAIA). The BIAIA administers the IBIRN program in cooperation with the Iowa Department of Public Health (IDPH) through HRSA TBI Implementation grant funding and state appropriations.

Brain injury program to ensure greater access to community-based services, July 11, 2006

More than 2,200 Iowans each year experience a traumatic brain injury that requires hospitalization. Of those, more than 750 will experience long-term disability as a result. According to a 2000 CDC report, there are an estimated 50,000 such individuals living in Iowa – a number similar to the population of Ames. As part of an enterprise-wide effort to ensure that all Iowans, including those with brain injuries, have access to quality healthcare, Governor Tom Vilsack signed the Brain Injury Services program bill on May 23. The bill will allow the Iowa Department of Public Health (IDPH) to implement a one-of-a-kind program to help those with brain injuries and their families in navigating and maximizing the Iowa community-based service system.

Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain.

Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain.

Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study.

OBJECTIVES: To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury. DESIGN: Retrospective analysis of a prospective observational cohort. SETTING: University hospital neurologic intensive care unit. PATIENTS: Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care. INTERVENTIONS: Intensive insulin therapy (systemic glucose target: 4.4-6.7 mmol/L [80-120 mg/dL]). MEASUREMENTS AND MAIN RESULTS: Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target "tight" (4.4-6.7 mmol/L [80-120 mg/dL]) vs. "intermediate" (6.8-10.0 mmol/L [121-180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10-1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04-1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 +/- 0.23 vs. 1.04 +/- 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37-39.51, p = 0.02). CONCLUSIONS: In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.

Free-breathing renal MR angiography with steady-state free-precession (SSFP) and slab-selective spin inversion: initial results.

BACKGROUND: The aim of our study was the investigation of a novel navigator-gated three-dimensional (3D) steady-state free-precession (SSFP) sequence for free-breathing renal magnetic resonance angiography (MRA) without contrast medium, and to examine the advantage of an additional inversion prepulse for improved contrast. METHODS: Eight healthy volunteers (mean age 29 years) and eight patients (mean age 53 years) were investigated on a 1.5 Tesla MR system (ACS-NT, Philips, Best, The Netherlands). Renal MRA was performed using three navigator-gated free-breathing cardiac-triggered 3D SSFP sequences [repetition time (TR) = 4.4 ms, echo time (TE) = 2.2 ms, flip angle 85 degrees, spatial resolution 1.25 x 1.25 x 4.0 mm(3), scanning time approximately 1 minute 30 seconds]. The same sequence was performed without magnetization preparation, with a non-slab selective and a slab-selective inversion prepulse. Signal-to-noise ratio (SNR), contrast-to-noise (CNR) vessel length, and subjective image quality were compared. RESULTS: Three-dimensional SSFP imaging combined with a slab-selective inversion prepulse enabled selective and high contrast visualization of the renal arteries, including the more distal branches. Standard SSFP imaging without magnetization preparation demonstrated overlay by veins and renal parenchyma. A non-slab-selective prepulse abolished vessel visualization. CNR in SSFP with slab-selective inversion was 43.6 versus 10.6 (SSFP without magnetization preparation) and 0.4 (SSFP with non-slab-selective inversion), P < 0.008. CONCLUSION: Navigator-gated free-breathing cardiac-triggered 3D SSFP imaging combined with a slab-selective inversion prepulse is a novel, fast renal MRA technique without the need for contrast media.

In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease.

In contrast to intact BALB/c mice, BALB/c mice rendered deficient in Vbeta4+ CD4+ T cells develop a Th1 response to infection with Leishmania major and are resistant. Vbeta4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in Vbeta4 Valpha8 CD4+ T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of Vbeta4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction with CD4+ T cells. In contrast to draining lymph node cells from BALB/c mice, cells from Vbeta4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to Vbeta4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R beta2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.

Brain Injury Quick Guide: Information and Resources for Teachers and School Staff, July 2013

The Brain Injury Quick Guide was developed as a resource tool for educators and school staff. Functional challenges (including social, physical, communication, and cognitive) are common following brain injury. This booklet serves as a resource outlining common challenges students may face in the classroom as well as strategies for addressing these challenges. Case studies outlining common challenges with possible strategies are provided with suggestions for IEP/504 plan accommodations. Basic brain anatomy and brain injury statistics are also reviewed.

Changes in cerebral compartmental compliances during mild hypocapnia in patients with traumatic brain injury.

The benefit of induced hyperventilation for intracranial pressure (ICP) control after severe traumatic brain injury (TBI) is controversial. In this study, we investigated the impact of early and sustained hyperventilation on compliances of the cerebral arteries and of the cerebrospinal (CSF) compartment during mild hyperventilation in severe TBI patients. We included 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom an increase in ventilation (20% increase in respiratory minute volume) was performed during 50 min as part of a standard clinical CO(2) reactivity test. Using a new mathematical model, cerebral arterial compliance (Ca) and CSF compartment compliance (Ci) were calculated based on the analysis of ICP, arterial blood pressure, and cerebral blood flow velocity waveforms. Hyperventilation initially induced a reduction in ICP (17.5 ± 6.6 vs. 13.9 ± 6.2 mmHg; p < 0.001), which correlated with an increase in Ci (r(2) = 0.213; p = 0.015). Concomitantly, the reduction in cerebral blood flow velocities (CBFV, 74.6 ± 27.0 vs. 62.9 ± 22.9 cm/sec; p < 0.001) marginally correlated with the reduction in Ca (r(2) = 0.209; p = 0.017). During sustained hyperventilation, ICP increased (13.9 ± 6.2 vs. 15.3 ± 6.4 mmHg; p < 0.001), which correlated with a reduction in Ci (r(2) = 0.297; p = 0.003), but no significant changes in Ca were found during that period. The early reduction in Ca persisted irrespective of the duration of hyperventilation, which may contribute to the lack of clinical benefit of hyperventilation after TBI. Further studies are needed to determine whether monitoring of arterial and CSF compartment compliances may detect and prevent an adverse ischemic event during hyperventilation.