Review and Updates on the Treatment of Refractory and Super Refractory Status Epilepticus.

Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent neurological damage and reduce morbidity and mortality. RSE is defined as status epilepticus that persists despite administering at least two appropriately dosed parenteral medications, including a benzodiazepine. SRSE is status epilepticus that persists at least 24 h after adding at least one appropriately dosed continuous anesthetic (i.e., midazolam, propofol, pentobarbital, and ketamine). Other therapeutic interventions include immunotherapy, neuromodulation, ketogenic diet, or even surgical intervention in certain cases. Continuous electroencephalogram is an essential monitoring tool for diagnosis and treatment. In this review, we focus on the diagnosis and treatment of RSE and SRSE.

How Well Do Neurochecks Perform After Stroke?

BACKGROUND: In the certification of stroke centers, the performance of serial nursing neurological assessments and reassessments, commonly known as neurochecks, is often cited as one of the most problematic standards. The role of neurochecks is to readily detect neurological change, but it is surprising that this practice has undergone relatively little scientific study. Their effectiveness in detecting worsening in acute ischemic stroke patients has not been well studied. Our objective was to investigate the sensitivity of neurochecks to detect neurological deterioration after acute ischemic stroke. We performed a retrospective chart review of patients with acute ischemic stroke who were admitted to a comprehensive stroke center over a 2-year period and who received intravenous thrombolysis. The incidence, reasons, and detection rates for neurological deterioration by neurochecks were collected during the first 72 hours of admission. RESULTS: A total of 231 patient records were reviewed. Over the first 72 hours of admission, each patient had a mean of 63±15 neurochecks. Neurological worsening as determined by a stroke neurologist was found in 62 (27%) patients. This deterioration was first detected by a scheduled neurocheck in 28 (45%) patients and was discovered by the nurse outside of a scheduled neurocheck in 16 (26%) patients. In 18 out of 62 (29%) patients, the worsening was not detected. CONCLUSIONS: Although neurochecks detected neurological deterioration in almost half of patients with acute stroke, a significant proportion of deteriorations were found outside scheduled assessments or remained undetected. This suggests that novel monitoring strategies are needed to readily identify worsening neurological status in acute stroke.

Graft dural closure is associated with a reduction in CSF leak and hydrocephalus in pediatric patients undergoing posterior fossa brain tumor resection.

OBJECTIVE: The authors aimed to evaluate clinical, radiological, and surgical factors associated with posterior fossa tumor resection (PFTR)-related outcomes, including postoperative complications related to dural augmentation (CSF leak and wound infection), persistent hydrocephalus ultimately requiring permanent CSF diversion after PFTR, and 90-day readmission rate. METHODS: Pediatric patients (0-17 years old) undergoing PFTR between 2000 and 2016 at Monroe Carell Jr. Children's Hospital of Vanderbilt University were retrospectively reviewed. Descriptive statistics included the Wilcoxon signed-rank test to compare means that were nonnormally distributed and the chi-square test for categorical variables. Variables that were nominally associated (p < 0.05) with each outcome by univariate analysis were included as covariates in multivariate linear regression models. Statistical significance was set a priori at p < 0.05. RESULTS: The cohort consisted of 186 patients with a median age at surgery of 6.62 years (range 3.37-11.78 years), 55% male, 83% Caucasian, and average length of follow-up of 3.87 ± 0.25 years. By multivariate logistic regression, the variables primary dural closure (PDC; odds ratio [OR] 8.33, 95% confidence interval [CI] 1.07-100, p = 0.04), pseudomeningocele (OR 7.43, 95% CI 2.23-23.76, p = 0.0007), and hydrocephalus ultimately requiring permanent CSF diversion within 90 days of PFTR (OR 9.25, 95% CI 2.74-31.2, p = 0.0003) were independently associated with CSF leak. PDC versus graft dural closure (GDC; 35% vs 7%, OR 5.88, 95% CI 2.94-50.0, p = 0.03) and hydrocephalus ultimately requiring permanent CSF diversion (OR 3.30, 95% CI 1.07-10.19, p = 0.0007) were associated with wound infection requiring surgical debridement. By multivariate logistic regression, GDC versus PDC (23% vs 37%, OR 0.13, 95% CI 0.02-0.87, p = 0.04) was associated with persistent hydrocephalus ultimately requiring permanent CSF diversion, whereas pre- or post-PFTR ventricular size, placement of peri- or intraoperative extraventricular drain (EVD), and radiation therapy were not. Furthermore, the addition of perioperative EVD placement and dural closure method to a previously validated predictive model of post-PFTR hydrocephalus improved its performance from area under the receiver operating characteristic curve of 0.69 to 0.74. Lastly, the authors found that autologous (vs synthetic) grafts may be protective against persistent hydrocephalus (p = 0.02), but not CSF leak, pseudomeningocele, or wound infection. CONCLUSIONS: These results suggest that GDC, independent of potential confounding factors, may be protective against CSF leak, wound infection, and hydrocephalus in patients undergoing PFTR. Additional studies are warranted to further evaluate clinical and surgical factors impacting PFTR-associated complications.

Social determinants of health affecting treatment of pediatric brain tumors.

OBJECTIVE: Little is understood about the role that health disparities play in the treatment and management of brain tumors in children. The purpose of this study was to determine if health disparities impact the timing of initial and follow-up care of patients, as well as overall survival. METHODS: The authors conducted a retrospective study of pediatric patients (< 18 years of age) previously diagnosed with, and initially treated for, a primary CNS tumor between 2005 and 2012 at Monroe Carell Jr. Children's Hospital at Vanderbilt. Primary outcomes included time from symptom presentation to initial neurosurgery consultation and percentage of missed follow-up visits for ancillary or core services (defined as no-show visits). Core services were defined as healthcare interactions directly involved with CNS tumor management, whereas ancillary services were appointments that might be related to overall care of the patient but not directly focused on treatment of the tumor. Statistical analysis included Pearson's chi-square test, nonparametric univariable tests, and multivariable linear regression. Statistical significance was set a priori at p < 0.05. RESULTS: The analysis included 198 patients. The median time from symptom onset to initial presentation was 30.0 days. A mean of 7.45% of all core visits were missed. When comparing African American and Caucasian patients, there was no significant difference in age at diagnosis, timing of initial symptoms, or tumor grade. African American patients missed significantly more core visits than Caucasian patients (p = 0.007); this became even more significant when controlling for other factors in the multivariable analysis (p < 0.001). African American patients were more likely to have public insurance, while Caucasian patients were more likely to have private insurance (p = 0.025). When evaluating survival, no health disparities were identified. CONCLUSIONS: No significant health disparities were identified when evaluating the timing of presentation and survival. A racial disparity was noted when evaluating missed follow-up visits. Future work should focus on identifying reasons for differences and whether social determinants of health affect other aspects of treatment.

Circulating Troponin I Level in Patients with Acute Ischemic Stroke.

PURPOSE OF REVIEW: Cardiac troponin levels in the blood are an important biomarker of acute coronary events, but may also be elevated in the context of acute ischemic stroke without an obvious concurrent myocardial insult. The objective of this study and systematic review is to determine how high the circulating troponin I level can rise due to ischemic stroke. RECENT FINDINGS: Anonymized medical records from Vanderbilt University Medical Center were reviewed identifying 151,972 unique acute ischemic stroke events, of which 1226 met criteria for inclusion in this study. Included patients had at least one measurement of troponin I level documented during the hospital visit when an acute ischemic stroke was diagnosed and were free of known cardiac/coronary disease, renal impairment, sepsis, or other confounders. In this group, 20.6% had a circulating troponin I level elevated over the reference range, but 99% were below 2.13 ng/mL. This is significantly lower than the distribution observed in a cohort of 89,423 unique cases of acute coronary syndrome (p < 2.2-16). A systematic review of published literature further supported the conclusion that troponin I level may increase due to an acute ischemic stroke, but rarely rises above 2 ng/mL. Because of the shared risk factors between stroke and coronary artery disease, clinicians caring for patients with acute ischemic stroke should always have a high index of suspicion for comorbid cardiac and cardiovascular disease. In general, troponin I levels greater than 2 ng/mL should not be attributed to an acute ischemic stroke, but should prompt a thorough evaluation for coronary artery disease.

Atomic layer deposition of nano-TiO2 thin films with enhanced biocompatibility and antimicrobial activity for orthopedic implants.

Titanium (Ti) and its alloys have been extensively used as implant materials in orthopedic applications. Nevertheless, implants may fail due to a lack of osseointegration and/or infection. The aim of this in vitro study was to endow an implant surface with favorable biological properties by the dual modification of surface chemistry and nanostructured topography. The application of a nanostructured titanium dioxide (TiO2) coating on Ti-based implants has been proposed as a potential way to enhance tissue-implant interactions while inhibiting bacterial colonization simultaneously due to its chemical stability, biocompatibility, and antimicrobial properties. In this paper, temperature-controlled atomic layer deposition (ALD) was introduced for the first time to provide unique nanostructured TiO2 coatings on Ti substrates. The effect of nano-TiO2 coatings with different morphology and structure on human osteoblast and fibroblast functions and bacterial activities was investigated. In vitro results indicated that the TiO2 coating stimulated osteoblast adhesion and proliferation while suppressing fibroblast adhesion and proliferation compared to uncoated materials. In addition, the introduction of nano-TiO2 coatings was shown to inhibit gram-positive bacteria (Staphylococcus aureus), gram-negative bacteria (Escherichia coli), and antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus), all without resorting to the use of antibiotics. Our results suggest that the increase in nanoscale roughness and greater surface hydrophilicity (surface energy) together could contribute to increased protein adsorption selectively, which may affect the cellular and bacterial activities. It was found that ALD-grown TiO2-coated samples with a moderate surface energy at 38.79 mJ/m2 showed relatively promising antibacterial properties and desirable cellular functions. The ALD technique provides a novel and effective strategy to produce TiO2 coatings with delicate control of surface nanotopography and surface energy to enhance the interfacial biocompatibility and mitigate bacterial infection, and could potentially be used for improving numerous orthopedic implants.

Implementation of an institution-wide acute stroke algorithm: Improving stroke quality metrics.

BACKGROUND: In May 2012, an updated stroke algorithm was implemented at Vanderbilt University Medical Center. The current study objectives were to: (1) describe the process of implementing a new stroke algorithm and (2) compare pre- and post-algorithm quality improvement (QI) metrics, specificaly door to computed tomography time (DTCT), door to neurology time (DTN), and door to tPA administration time (DTT). METHODS: Our institutional stroke algorithm underwent extensive revision, with a focus on removing variability, streamlining care, and improving time delays. The updated stroke algorithm was implemented in May 2012. Three primary stroke QI metrics were evaluated over four separate 3-month time points, one pre- and three post-algorithm periods. RESULTS: The following data points improved after algorithm implementation: average DTCT decreased from 39.9 to 12.8 min (P < 0.001); average DTN decreased from 34.1 to 8.2 min (P ≤ 0.001), and average DTT decreased from 62.5 to 43.5 min (P = 0.17). CONCLUSION: A new stroke protocol that prioritized neurointervention at our institution resulted in significant lowering in the DTCT and DTN, with a nonsignificant improvement in DTT.

Prospective series of two hours supine rest after 4fr sheath-based diagnostic cerebral angiography: Outcomes, productivity and cost.

There is no standard of care for catheter size or post-procedure supine time in cerebral angiography. Catheter sizes range from 4-Fr to 6-Fr with supine times ranging from two to over six hours. The objective of our study was to establish the efficacy, safety, and cost savings of two-hour supine time after 4-Fr elective cerebral angiography. A prospective, single arm study was performed on 107 patients undergoing elective cerebral angiography. All cerebral angiograms were performed with a 4-Fr sheath-based system without closure devices. Ten minutes of manual compression was applied to the femoral access site, with further compression held as clinically indicated. Patients were then monitored in a nursing unit for two hours supine and subsequently mobilized. Nursing discretion was allowed for earlier mobilization. Patients were called the next day to assess delayed hematoma and bleeding. Estimates of cost savings and productivity increases are provided. All patients ambulated in two hours or less. There were no strokes or vessel dissections. Five patients (4.7%) experienced a palpable hematoma, three patients (2.8%) experienced bleeding immediately following the procedure requiring further compression, and one patient (0.9%) experienced minor groin oozing at home. No patient required transfusion, thrombin injection, or endovascular/surgical management of a groin complication. A two-hour post-procedure supine time resulted in cost savings of $952 per angiogram and a total of $101,864. 4-Fr sheath based cerebral angiography with two-hour post-procedure supine time is safe and effective, and allows for a considerable increase in patient satisfaction, cost savings and productivity.

Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar.

UNLABELLED: The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier, and its resultant spare capacity requires substantial blockade to increase the uptake of avid substrates, blunting the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined 2 P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and 2 routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate (11)C-N-desmethyl-loperamide (dLop) while avoiding side effects associated with high doses of tariquidar. METHODS: Forty-two (11)C-dLop PET scans were obtained from 37 healthy volunteers. PET was performed with (11)C-dLop under the following 5 conditions: injected under baseline conditions without P-gp inhibition, injected 1 h after intravenous tariquidar infusion, injected during intravenous tariquidar infusion, injected after oral tariquidar, and injected after disulfiram. (11)C-dLop uptake was quantified with kinetic modeling using metabolite-corrected arterial input function or by measuring the area under the time-activity curve in the brain from 10 to 30 min. RESULTS: Neither oral tariquidar nor oral disulfiram increased brain uptake of (11)C-dLop. Injecting (11)C-dLop during tariquidar infusion, when plasma tariquidar concentrations reach their peak, resulted in a brain uptake of the radioligand approximately 5-fold greater than baseline. Brain uptake was similar with 2 and 4 mg of intravenous tariquidar per kilogram; however, the lower dose was better tolerated. Injecting (11)C-dLop after tariquidar infusion also increased brain uptake, though higher doses (up to 6 mg/kg) were required. Brain uptake of (11)C-dLop increased fairly linearly with increasing plasma tariquidar concentrations, but we are uncertain whether maximal uptake was achieved. CONCLUSION: We sought to increase the dynamic range of P-gp function measured after blockade. Performing (11)C-dLop PET during peak plasma concentrations of tariquidar, achieved with concurrent administration of intravenous tariquidar, resulted in greater P-gp inhibition at the human blood-brain barrier than delayed administration and allowed the use of a lower, more tolerable dose of tariquidar. On the basis of prior monkey studies, we suspect that plasma concentrations of tariquidar did not fully block P-gp; however, higher doses of tariquidar would likely be associated with unacceptable side effects.

Olecranon fractures: factors influencing re-operation.

PURPOSE: We evaluated factors influencing re-operation in tension band and plating of isolated olecranon fractures. METHODS: Four hundred eighty-nine patients with isolated olecranon fractures who underwent tension band (TB) or open reduction internal fixation (ORIF) from 2003 to 2013 were identified at an urban level 1 trauma centre. Medical records were reviewed for patient information and complications, including infection, nonunion, malunion, loss of function or hardware complication requiring an unplanned surgical intervention. Electronic radiographs of these patients were reviewed to identify Orthopaedic Trauma Association (OTA) fracture classification and patients who underwent TB or ORIF. RESULTS: One hundred seventy-seven patients met inclusion criteria of isolated olecranon fractures. TB was used for fixation in 43 patients and ORIF in 134. No statistical significance was found when comparing complication rates in open versus closed olecranon fractures. In a multivariate analysis, the key factor in outcome was method of fixation. Overall, there were higher rates of infection and hardware removal in the TB compared with the ORIF group. CONCLUSIONS: Our results demonstrate that the dominant factor driving re-operation in isolated olecranon fractures is type of fixation. When controlling for all variables, there is an increased chance of re-operation in patients with TB fixation.

Outcomes in pediatric patients with Chiari malformation Type I followed up without surgery.

OBJECT: The natural history of untreated Chiari malformation Type I (CM-I) is poorly defined. The object of this study was to investigate outcomes in pediatric patients with CM-I who were followed up without surgical intervention. METHODS: The authors retrospectively reviewed 124 cases involving patients with CM-I who presented between July 1999 and July 2008 and were followed up without surgery. The patients ranged in age from 0.9 to 19.8 years (mean 7 years). The duration of follow-up ranged from 1.0 to 8.6 years (mean 2.83 years). Imaging findings, symptoms, and findings on neurological examinations were noted at presentation and for the duration of follow-up. RESULTS: The mean extent of tonsillar herniation at presentation was 8.35 mm (range 5-22 mm). Seven patients had a syrinx at presentation. The syrinx size did not change in these patients on follow-up imaging studies. No new syrinxes developed in the remaining patients who underwent subsequent imaging. The total number of patients with presenting symptoms was 81. Of those 81 patients, 67 demonstrated symptoms that were not typical of CM-I. Of the 14 patients with symptoms attributed to CM-I, 9 had symptoms that were not severe or frequent enough to warrant surgery, and surgery was recommended in the remaining 5 patients. Chiari malformation Type I was also diagnosed in 43 asymptomatic patients who had imaging studies performed for various reasons. No new neurological deficits were noted in any patient for the duration of follow-up. CONCLUSIONS: The majority of patients with CM-I who are followed up without surgery do not progress clinically or radiologically. Longer follow-up of this cohort will be required to determine if symptoms or new neurological findings develop over the course of many years.