Primary External Ventricular Drainage Catheter Versus Intraparenchymal ICP Monitoring: Outcome Analysis.

BACKGROUND: Intracranial pressure (ICP) monitoring is central to the care of severe traumatic brain injury (TBI). External ventricular drains (EVD) allow ICP control via cerebrospinal fluid drainage, whereas intraparenchymal monitors (IPM) for ICP do not, but it is unclear whether EVD placement improves outcomes. To evaluate whether there exists a difference in patient outcomes with the use of EVD versus IPM in severe TBI patients, we conducted a retrospective cohort study using data from the Citicoline Brain Injury Treatment trial. METHODS: Adults with Glasgow Coma Score < 9 who had either an EVD or IPM placed within 6 h of study center arrival were included. We compared patients with EVD placement to those without on Glasgow Outcome Scale-Extended (GOS-E) and neuropsychological performance at 180 days, mortality, and intensive care unit length of stay. We used regression models with propensity score weighting for probability of EVD placement to test for association between EVD use and outcomes. Of 224 patients included, 45% received an EVD. RESULTS: EVD patients had lower GOS-E at 180 days [3.8 ± 2.2 vs 4.9 ± 2.2, p = 0.002; weighted difference - 0.97, 95% CI (- 1.58, - 0.37)], higher in-hospital mortality [23% vs 10%, p = 0.014; weighted OR 2.46, 95% CI (1.20, 5.05)], and did significantly worse on all 8 neuropsychological measures. Additional sensitivity analysis was performed to minimize confounding effects supported our initial results. CONCLUSIONS: Our retrospective data analysis suggests that early placement of EVDs in severe TBI is associated with worse functional and neuropsychological outcomes and higher mortality than IPMs and future prospective trials are needed to determine whether these results represent an important consideration for clinicians.

Structural imaging of mild traumatic brain injury may not be enough: overview of functional and metabolic imaging of mild traumatic brain injury.

A majority of patients with traumatic brain injury (TBI) present as mild injury with no findings on conventional clinical imaging methods. Due to this difficulty of imaging assessment on mild TBI patients, there has been much emphasis on the development of diffusion imaging modalities such as diffusion tensor imaging (DTI). However, basic science research in TBI shows that many of the functional and metabolic abnormalities in TBI may be present even in the absence of structural damage. Moreover, structural damage may be present at a microscopic and molecular level that is not detectable by structural imaging modality. The use of functional and metabolic imaging modalities can provide information on pathological changes in mild TBI patients that may not be detected by structural imaging. Although there are various differences in protocols of positron emission tomography (PET), single photon emission computed tomography (SPECT), functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and magnetoencephalography (MEG) methods, these may be important modalities to be used in conjunction with structural imaging in the future in order to detect and understand the pathophysiology of mild TBI. In this review, studies of mild TBI patients using these modalities that detect functional and metabolic state of the brain are discussed. Each modality's advantages and disadvantages are compared, and potential future applications of using combined modalities are explored.

Variation in PPP3CC Genotype Is Associated with Long-Term Recovery after Severe Brain Injury.

After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). The following tagging single nucleotide polymorphisms (tSNPs) in PPP3CC were genotyped: rs2443504, rs2461491, rs2469749, and rs10108011. The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.

The Effect of Hyponatremia and Sodium Variability on Outcomes in Adults with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hyponatremia is common in patients with subarachnoid hemorrhage, but its effect on outcomes remains contentious. Fluctuation in sodium has been reported to negatively affect perioperative outcomes in general surgical patients, but not specifically in patients with a subarachnoid hemorrhage. The primary aim was to describe the relationship between 1) hyponatremia and 2) sodium fluctuations during intensive care and neurologic outcome at hospital discharge. METHODS: Adults with aneurysmal subarachnoid hemorrhage between January 2012 and September 2013 were retrospectively reviewed. Data were collected for admission to day 14 of intensive care or death. Severity of illness was assessed by Hunt and Hess grade and simplified acute physiology score. Hyponatremia was defined as any measurement <135 mEq/L. Sodium variability was categorized as a maximum change of <6, 6-12, or >12 mEq/L during intensive care. Neurologic outcomes at discharge were assessed by modified Rankin Scale. The relationship between sodium and outcome was assessed by ordinal logistic regression. RESULTS: A total of 198 patients were included. After adjustment for Hunt and Hess grade, severity of systemic illness, patient age, surgical intervention, and whether or not the hyponatremia was treated with additional sodium, hyponatremia was not associated with worse neurologic outcomes. More patients with sodium variability of 6-12 and >12 mEq/L had cerebral infarction than those with variability <6 mEq/L and had modified Rankin Scale scores of 2-3 and 4-6, respectively (P = 0.001). CONCLUSIONS: Sodium fluctuation, not hyponatremia, is associated with worse neurologic outcome in patients with aneurysmal subarachnoid hemorrhage. This is in contradistinction to current teaching and warrants further examination.

Infra-Conus Single-Level Laminectomy for Selective Dorsal Rhizotomy: Technical Advance.

BACKGROUND/AIMS: Selective dorsal rhizotomy for spastic cerebral palsy is an effective and well-validated surgical approach. Multiple techniques have been described in the past including multiple laminectomies and a single-level laminectomy at the level of the conus. There is considerable technical challenge involved with a single-level laminectomy approach. METHODS: We report here a modification of the single-level laminectomy that selectively analyzes each individual nerve root with electromyography to separate dorsal and ventral nerve roots through comparison of stimulus responses. RESULTS: In 18 children with cerebral palsy who underwent this operation there was a mean improvement in the Modified Ashworth Scale of 2.0 with no reported incidence of muscle weakness, sensory loss, or neurogenic bladder. CONCLUSION: This approach allows for a modification of selective dorsal rhizotomy through a single-level laminectomy and tailors the selection of nerve root sectioning to the individual patient of interest while still maintaining its effectiveness.

Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Oral nimodipine is standard therapy for patients suffering an aneurysmal subarachnoid hemorrhage (aSAH). During a national drug shortage, nimodipine therapy was shortened from a 21-day course to a 14-day course at our institution. OBJECTIVE: The objective of this study was to compare neurological outcomes among patients who had previously received the standard duration of therapy compared with those who received a shortened duration as a result of the national drug shortage. METHODS: This retrospective cohort study evaluated adult patients receiving nimodipine for aSAH from January 2012 to August 2013. Neurological outcome, graded by Modified Rankin Scale (mRS) at hospital discharge, was compared between patients receiving a shortened course and those receiving the standard duration of nimodipine. RESULTS: A total of 199 aSAH patients were included in the analysis. There were 164 patients in the standard-duration and 35 patients in the shortened-duration group. Baseline patient severity of illness, assessed by SAPS II (Simplified Acute Physiology Score), and severity of aSAH, assessed by Fisher grade, and Hunt and Hess grade scores, did not differ between the treatment groups. A shortened duration of nimodipine was not associated with a higher risk of a poor neurological outcome defined by mRS (odds ratio = 1.85; 95% CI = 0.54-6.32; P = 0.32). Mortality rates were similar between the groups. CONCLUSIONS: A 14-day course of nimodipine therapy was not associated with worse neurological outcomes in aSAH patients at one institution. More studies are needed prior to recommending a shortened duration of nimodipine therapy in all aSAH patients.

Transanal presentation of a distal ventriculoperitoneal shunt catheter: Management of bowel perforation without laparotomy.

BACKGROUND: Bowel perforation is a serious but rare complication after a ventriculoperitoneal shunt (VPS) procedure. Prior studies have reported spontaneous bowel perforation after VPS placement in adults of up to 0.07%. Transanal catheter protrusion is a potential presentation of VPS bowel perforation and places a patient at risk for both peritonitis and ventriculitis/meningitis via retrograde migration of bacteria. This delayed complication can be fatal if unrecognized, with a 15% risk of mortality secondary to ventriculitis, peritonitis, or sepsis. CASE DESCRIPTION: We describe a unique case of a patient with distal VPS catheter protrusion from the anus whose bowel perforation did not cause clinical sequelae of infection. We were able to manage the patient without laparotomy. CONCLUSIONS: A subset of patients can be managed without laparotomy and only with externalization of the ventricular shunt with antibiotics until the cerebrospinal fluid cultures finalize without growth.

Reversible coma and Duret hemorrhage after intracranial hypotension from remote lumbar spine surgery: case report.

Intracranial hypotension is a rare condition caused by spontaneous or iatrogenic CSF leaks that alter normal CSF dynamics. Symptoms range from mild headaches to transtentorial herniation, coma, and death. Duret hemorrhages have been reported to occur in some patients with this condition and are traditionally believed to be associated with a poor neurological outcome. A 73-year-old man with a remote history of spinal fusion presented with syncope and was found to have small subdural hematomas on head CT studies. He was managed nonoperatively and discharged with a Glasgow Coma Scale score of 15, only to return 3 days later with obtundation, fixed downward gaze, anisocoria, and absent cranial nerve reflexes. A CT scan showed Duret hemorrhages and subtle enlargement of the subdural hematomas, though the hematomas remained too small to account for his poor clinical condition. Magnetic resonance imaging of the spine revealed a large lumbar pseudomeningocele in the area of prior fusion. His condition dramatically improved when he was placed in the Trendelenburg position and underwent repair of the pseudomeningocele. He was kept flat for 7 days and was ultimately discharged in good condition. On long-term follow-up, his only identifiable deficit was diplopia due to an internuclear ophthalmoplegia. Intracranial hypotension is a rare condition that can cause profound morbidity, including tonsillar herniation and brainstem hemorrhage. With proper identification and treatment of the CSF leak, patients can make functional recoveries.

The effect of environmental enrichment on substantia nigra gene expression after traumatic brain injury in rats.

Experimental investigations into the effects of traumatic brain injury (TBI) have demonstrated significant alterations in dopaminergic systems. Dopaminergic fibers originating within the substantia nigra and ventral tegmental area (VTA) are important for reward learning, addiction, movement, and behavior. However, little is known about the effect of TBI on substantia nigra and VTA function. Environmental enrichment (EE) has been shown to improve functional outcome after TBI, and a number of studies suggest that it may exert some benefits via dopaminergic signaling. To better understand the role of dopamine in chronic TBI pathophysiology and the effect of EE, we examined the mRNA expression profile within the substantia nigra and VTA at 4 weeks post-injury. Specifically, three comparisons were made: 1) TBI versus sham, 2) sham+EE versus sham+standard (STD) housing, and 3) TBI+EE versus TBI+STD. There were differential expressions of 25, 4, and 40 genes in these comparisons, respectively. Chronic alterations in genes post-injury within the substantia nigra and VTA included genes important for cellular membrane homeostasis and transcription. EE-induced gene alterations after TBI included genes important for signal transduction, in particular calcium signaling pathways, membrane homeostasis, and metabolism. Elucidation of these alterations in gene expression within the substantia nigra and VTA provides new insights into chronic changes in dopamine signaling post-TBI, and the potential role of EE in TBI rehabilitation.

Breastfeeding rates and factors related to cessation in a military population.

Evidence continues to accumulate showing the benefits of breastfeeding to infants, mothers, and society as a whole. However, breastfeeding success rates nationwide have consistently fallen short of recommendations set forth by the American Academy of Pediatrics. There are several potential barriers to successful breastfeeding, and many of these could be magnified in the demanding careers of military members and their families. We surveyed 254 women at a regional military medical facility, both active duty members and dependents of active duty members, regarding their ability to successfully breastfeed their infants. We found that American Academy of Pediatrics target goals in this population as a whole were indeed nearly met at this facility, but also found that active duty members and those who encountered military-related difficulty fell well short of these goals. These findings suggest potential barriers to breastfeeding success that warrant further study from the U.S. Department of Defense.

Swimming overuse injuries associated with triathlon training.

Most triathlon overuse injuries occur due to the running and cycling aspects of the sport. By nature of swimming being a non-weight-bearing sport, triathletes have a tendency to use swimming for rehabilitation and recovery. Swimming has a significantly lower injury rate than the other 2 disciplines in a triathlon. Most triathletes use the freestyle stroke, because it is typically the first stroke learned, it is for many the fastest stroke, and by lifting the head the freestyle stroke allows triathletes to sight their direction, which is important in open water swimming. During the freestyle stroke, the shoulder undergoes repetitive overhead motion, and shoulder pain is the most common and well-documented site of musculoskeletal pain in competitive swimmers. It is felt that the pathologic process is attributable to repetitive overhead motion causing microtrauma in the shoulder from either mechanical impingement or generalized laxity or both. Without sufficient rest and recovery, the development of inflammation and pain may result. Depending on the age of the triathlete and the exact etiology of the shoulder pain, treatment options range from nonsurgical to surgical in nature.

Training on a knife's edge: how to balance triathlon training to prevent overuse injuries.

The sport of triathlon offers athletes the chance to build and/or maintain cardiovascular fitness across 3 endurance disciplines. Swimming, biking, and running each have a host of overuse injuries that can occur as a result of overtraining. High running mileage, a history of previous injury, inadequate warm up or cool down, and an increase in the years of triathlon experience are a few of the factors that have been linked to triathlon overuse injuries. Early identification of overtraining symptoms and a corresponding reallocation of balance between each discipline, perhaps with an emphasis on increasing swimming, may help prevent many overuse injuries.

Triathlon: how to mentally prepare for the big race.

With the mastery of 3 sports required, a triathlon can be a daunting mental challenge. Some liken a triathlon to a physical game of chess. A triathlete must mentally assess their physical ability across 3 sports against their competitors, the environment, and, most of all, themselves. The mental preparation required for a triathlon is often minimized, but its importance should not be underestimated. Appropriate mental planning should be carried out during training. The need for nutrition, race planning, visualization, imaging, and possible changes in conditions should all be anticipated. Anxiousness at the start of the event is normal, but this energy needs to be channeled appropriately, or it can be detrimental. Athletes who arrive at race day with a sound mental strategy typically perform better.

The triathlon tips from the top: practical tips for racing and training for a triathlon.

Training for a triathlon is a very demanding pursuit. There are a multitude of problems, such as overuse injuries, overtraining, and inappropriate training that can derail even the best athlete. We present some of the symptoms to look for to avoid overtraining, some training tips to maximize your training time, and look at some popular myths that surround endurance training.

Evaluation for ulnar neuropathy at the elbow in Ironman triathletes: physical examination and electrodiagnostic evidence.

OBJECTIVE: Evaluation of the elbow in Ironman triathletes for ulnar compression neuropathy caused by aerobar use. DESIGN: Descriptive laboratory study. SETTING: Ironman California 70.3, Ironman Arizona, Ironman New Orleans 70.3, San Antonio, Texas. PARTICIPANTS: Study 1: (n = 712) Ironman California 70.3/Ironman Arizona participants. Study 2: (n = 54) Ironman New Orleans 70.3 finishers. Study 3: (n = 11) participants training for an Ironman triathlon. INTERVENTIONS: Pilot questionnaire (study 1). Pilot questionnaire and prerace and postrace physical examination (study 2). Pilot questionnaire and preride and postride (and postseason) physical examination, and electrodiagnostic testing (study 3). MAIN OUTCOME MEASURES: Participants with symptoms, physical examination findings, and electrodiagnostic findings (amplitude or conduction velocity decrease) (P < 0.05). RESULTS: In study 1, 20.8% reported a history of ulnar symptoms. In study 2, 35.2% reported a history of ulnar symptoms. Preevent physical examination testing of the elbow showed 39.5% with positive Tinel sign and 41.5% with positive flexion/compression test. Postevent testing showed 70.4% with positive Tinel sign and 75.9% with positive flexion/compression test. In study 3, 46% reported ulnar symptoms. Preride physical examination testing showed 4.5% with positive Tinel sign and 9% with positive flexion/compression test. Postride testing showed 95.5% with positive Tinel sign and 91% with positive flexion/compression test. Postseason testing showed 64% with positive Tinel sign and 82% with positive flexion/compression test. Electrodiagnostic testing comparing preride and postride showed that ulnar nerve latency increased in 82%, amplitude decreased in 50%, and conduction velocity slowed in 64%. Electrodiagnostic testing comparing preseason and postseason showed that ulnar nerve latency increased in 73%, amplitude decreased in 64%, and conduction velocity slowed in 82%. CONCLUSIONS: The findings support the hypothesis of an ulnar compression neuropathy at the elbow occurring at high rates in aerobar using Ironman triathletes.

The dopamine and cAMP regulated phosphoprotein, 32 kDa (DARPP-32) signaling pathway: a novel therapeutic target in traumatic brain injury.

Traumatic brain injury (TBI) causes persistent neurologic deficits. Current therapies, predominantly focused upon cortical and hippocampal cellular survival, have limited benefit on cognitive outcomes. Striatal damage is associated with deficits in executive function, learning, and memory. Dopamine and cAMP regulated phosphoprotein 32 (DARPP-32) is expressed within striatal medium spiny neurons and regulates striatal function. We found that controlled cortical impact injury in rats produces a chronic decrease in DARPP-32 phosphorylation at threonine-34 and an increase in protein phosphatase-1 activity. There is no effect of injury on threonine-75 phosphorylation or on DARPP-32 protein. Amantadine, shown to be efficacious in treating post-TBI cognitive deficits, given daily for two weeks is able to restore the loss of DARPP-32 phosphorylation and reduce protein phosphatase-1 activity. Amantadine also decreases the phosphorylation of threonine-75 consistent with activity as a partial N-methyl-D-aspartate (NMDA) receptor antagonist and partial dopamine agonist. These data demonstrate that targeting the DARPP-32 signaling cascade represents a promising novel therapeutic approach in the treatment of persistent deficits following a TBI.

Regional calcineurin subunit B isoform expression in rat hippocampus following a traumatic brain injury.

Calcineurin subunit isoforms are implicated in long term potentiation, long term depression, and structural plasticity. Calcineurin inhibitors benefit axonal damage, cellular dysfunction, and cognitive outcomes in animal models of traumatic brain injury (TBI). Distribution of the catalytic calcineurin A subunit is altered and calcineurin activity increased following fluid percussion injury. Alterations in calcineurin subunit A isoform distribution within the hippocampus also occur post controlled cortical impact (CCI) demonstrating a reduction in catalytic subunit distribution in CA1-2 dendritic fields. Furthermore the effect of TBI on the regulatory subunit, calcineurin B, is unknown. Understanding the role of both subunits is necessary to effectively target alterations in calcineurin signaling as current calcineurin inhibitors, such as cyclosporin A and FK-506, rely upon binding sites on both subunits for complete inhibition. The effect of moderate CCI on the expression and distribution of calcineurin B isoforms within the hippocampus was examined at 2h and 2weeks post injury. Calcineurin B isoforms showed increased expression throughout the CA1 and CA2 while there was a decrease in expression within the ipsilateral dentate gyrus. Alterations in CnB isoform expression within the CA1, CA1-2, and dentate gyrus have significant implications for persistent hippocampal dysfunction following TBI. Regional changes in regulatory subunit expression may alter the effect of calcineurin inhibitors regionally following a traumatic brain injury.

Targeting Dopamine in Acute Traumatic Brain Injury.

In addition to the initial mechanical damage, traumatic brain injury (TBI) induces a series of secondary insults, such as, but not limited to, excitotoxicity, metabolic disruption, and oxidative stress. Neuroprotective strategies after TBI have traditionally focused on cellular preservation as the measurable endpoint although multiple lines of evidence indicate that even with significant neuronal sparing deficits remain at both the cellular and behavioral level. As such, the development of therapies that can effectively confer both neuronal sparing and post-injury functional benefit is critical to providing the best treatment options for clinical TBI. Targeting dopaminergic signaling pathways is a novel approach in TBI that provides benefits to both neuronal survival and functional outcomes. Dopamine, like glutamate, can cause oxidative stress and significant cellular dysfunction when either depleted or over-expressed, and also plays an important role in central nervous system inflammation. The purpose of this review is to discuss dopamine in acute TBI and the role that dopaminergic therapies have as neuroprotective strategies.

Expression of protein phosphatase 2B (calcineurin) subunit A isoforms in rat hippocampus after traumatic brain injury.

Calcineurin (CaN) is a calcium/calmodulin-dependent phosphatase directly activated by calcium as a result of neuronal activation that is important for neuronal function. CaN subunit isoforms are implicated in long-term potentiation (LTP), long-term depression (LTD), and structural plasticity. CaN inhibitors are also beneficial to cognitive outcomes in animal models of traumatic brain injury (TBI). There are known changes in the CaN A (CnA) subunit following fluid percussion injury (FPI). The CnA subunit has two isoforms: CnAalpha and CnAbeta. The effect of moderate controlled cortical impact (CCI) on distribution of CnA isoforms was examined at 2 h and 2 weeks post-injury. CnA distribution was assayed by immunohistochemistry and graded for non-parametric analysis. Acutely CnA isoforms showed reduced immunoreactivity in stratum radiatum processes of the ipsilateral CA1 and CA1-2. There was also a significant alteration in the immunoreactivity of both CnA isoforms in the ipsilateral dentate gyrus, predominantly within the hidden blade. Alterations in CnA isoform regional distribution within the CA1, CA1-2, and dentate gyrus may have significant implications for persistent hippocampal dysfunction following TBI, including dysfunction in hippocampal plasticity. Understanding alterations in CnA isoform distribution may help improve the targeting of current therapeutic interventions and/or the development of new treatments for TBI.

Persistent cognitive dysfunction after traumatic brain injury: A dopamine hypothesis.

Traumatic brain injury (TBI) represents a significant cause of death and disability in industrialized countries. Of particular importance to patients the chronic effect that TBI has on cognitive function. Therapeutic strategies have been difficult to evaluate because of the complexity of injuries and variety of patient presentations within a TBI population. However, pharmacotherapies targeting dopamine (DA) have consistently shown benefits in attention, behavioral outcome, executive function, and memory. Still it remains unclear what aspect of TBI pathology is targeted by DA therapies and what time-course of treatment is most beneficial for patient outcomes. Fortunately, ongoing research in animal models has begun to elucidate the pathophysiology of DA alterations after TBI. The purpose of this review is to discuss clinical and experimental research examining DAergic therapies after TBI, which will in turn elucidate the importance of DA for cognitive function/dysfunction after TBI as well as highlight the areas that require further study.