Advances in Cranial Surgery.

The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally invasive skull base approaches, SRS, laser interstitial thermal therapy and use of tubular retractors have revolutionized the management of intracerebral hemorrhages, deep seated tumors other intracranial pathologies. Introduction of these novel techniques is based on smaller incisions with maximal operative corridors, decreased blood loss, shorter hospital stays, decreased post-operative pain and cosmetically appealing scars that improves patient satisfaction and clinical outcomes. The sophisticated tools like neuroendoscopy have improved light source, and better visualization around the corners. Advanced navigated tools and channel-based retractors help us to target deeply seated lesions with increased precision and minimal disruption of the surrounding neurovascular tissues. Advent of stereotactic radiosurgery has provided us alternative feasible, safe and effective options for treatment of patients who are otherwise not medically stable to undergo complex cranial surgical interventions. This paper review advances in treatment of intracranial pathologies, and how the neurosurgeons and other medical providers at the University of Missouri-Columbia (UMC) are optimizing these treatments for their patients.

Preexisting Depression and Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. METHODS: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. RESULTS: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. CONCLUSIONS: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.

Red Blood Cell Transfusions and Risk of Postoperative Venous Thromboembolism.

INTRODUCTION: Postoperative venous thromboembolism (VTE) is a major risk for orthopaedic surgery and associated with notable morbidity and mortality. Knowing a patient's risk for VTE may help guide the choice of perioperative VTE prophylaxis. Recently, red blood cells (RBCs) have been implicated for their role in pathologic thrombosis. Therefore, we examine the association between perioperative RBC transfusion and postoperative VTE after orthopaedic surgery. METHODS: A retrospective cohort study was done by conducting a secondary analysis of data obtained from the 2016 American College of Surgeons National Surgical Quality Improvement Program database. Our population consisted of 234,608 adults who underwent orthopaedic surgery. The exposure was whether patients received a perioperative RBC transfusion. The primary outcome was postoperative VTE within 30 days of surgery that warranted therapeutic intervention, which was subsequently split into symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Odds ratios (ORs) were estimated using a multivariate logistic regression model. RESULTS: At baseline, 1,952 patients (0.83%) had postoperative VTE (DVT in 1,299 [0.55%], PE in 801 [0.34%], and both DVT and PE in 148 [0.06%]). Seven hundred ninety-five patients (0.3%) received preoperative RBC transfusions only, 11,587 patients (4.9%) received postoperative RBC transfusions only, and 848 patients (0.4%) received both preoperative and postoperative RBC transfusions. Postoperative RBC transfusion was associated with higher odds of VTE (adjusted OR [aOR], 1.47; 95% confidence interval [CI], 1.19-1.81), DVT (aOR, 1.40; 95% CI, 1.09-1.79), PE (aOR, 1.59; 95% CI, 1.14-2.22), and 30-day mortality (aOR, 1.21; 95% CI, 1.01-1.45) independent of various presumed risk factors. When creating subgroups within orthopaedics by Current Procedural Terminology codes, postoperative transfusions in spine (aOR, 2.03; 95% CI, 1.13-3.67) and trauma (aOR, 1.40; 95% CI, 1.06-1.86) were associated with higher odds of postoperative VTE. CONCLUSION: Our results suggest that postoperative RBC transfusion may be associated with an increased risk of postoperative VTE, both symptomatic DVT and life-threatening PE, independent of confounders. Additional prospective validation in cohort studies is necessary to confirm these findings. In addition, careful perioperative planning for patients deemed to be at high risk of requiring blood transfusion may reduce these postoperative complications in orthopaedic patients. LEVEL OF EVIDENCE: III.

The Role of Parenteral Dantrolene in the Contemporary Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

OBJECTIVE: Cerebral vasospasm remains a significant source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Dantrolene has shown promise in several animal studies in the treatment of cerebral vasospasm. The present study seeks to critically review the evidence of its use in human subjects, aiming to 1) describe the forms and dosages used, 2) describe its safety profile, and 3) describe its effectiveness in treating cerebral vasospasm. METHODS: A systematic review of intra-arterial dantrolene use in cerebral vasospasm was performed. A total of 86 articles were identified across all databases, 6 of which were ultimately included in the present study. Primary outcomes included a description of the form and dosage of dantrolene prescribed, the incidence of adverse effects after dantrolene use, and its efficacy for the treatment of cerebral vasospasm. RESULTS: Study designs included 2 randomized controlled trials (33.3%), 2 case series (33.3%), and 2 case reports (33.3%). Both the intra-arterial and intravenous administration of dantrolene has been performed with varying dose regimens. Although there exists limited clinical information regarding side effects, a case of liver toxicity was reported. All existing studies reported benefit in vasospasm measured either by transcranial Doppler or digital subtraction angiography. The level of evidence was low, consisting largely of retrospective studies that had a high likelihood of bias. CONCLUSIONS: Dantrolene is a promising new therapeutic agent in the treatment of cerebral vasospasm. Although existing reports of its use are encouraging, high-quality prospective randomized trials are necessary for recommendations pertaining to dose, route, indications, and efficacy.

Reassessing Diabetes and APOE Genotype as Potential Interacting Risk Factors for Alzheimer's Disease.

Objective: To assess whether diabetes alone or in association with Apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's Disease (AD) diagnosis. Methods: A retrospective cohort study of 33,456 participants from the National Alzheimer's Coordinating Center database. Results: Participants with one or two APOE ε4 alleles had 2.71 (CI:2.55-2.88) and 9.37 (CI:8.14-10.78) times higher odds of AD diagnosis, respectively, relative to those with zero ε4 alleles. In contrast, diabetic participants showed 1.07 (CI:0.96-1.18) times higher odds of AD relative to nondiabetics. Diabetes did not exacerbate the odds of AD in APOE ε4 carriers. APOE ε4 carriage was correlated with declines in long-term memory and verbal fluency, which were strongly correlated with conversion to AD. However, diabetes was correlated with working memory decline, which had a relatively weak correlation with AD. Conclusions: Unlike APOE ε4, there was little evidence that diabetes was a risk factor for AD.

Maximum intravenous alteplase dose for obese stroke patients is not associated with greater likelihood of worse outcomes.

BACKGROUND: IV alteplase is a primary treatment for acute ischemic stroke (AIS) at a weight-based dose (WBD) of 0.9 mg/kg and maximum dose (MD) of 90 mg. There are conflicting data regarding outcomes for those weighing ≥100 kg. There is also a paucity of data in Hispanics. The prevalence of adult obesity in the US has progressively increased; hence, the percentage of patients receiving the maximum dose also is expected to rise. We examined differences between patients treated with WBD vs. MD. METHODS: A retrospective review of our center's Get With The Guidelines-Stroke database was performed for IV alteplase cases between October 2013-February 2017. Selection criteria included age ≥18 years, IV alteplase administration, and a recorded measured weight. Patients were dichotomized into WBD group weighing <100 kg and MD group weighing ≥100 kg. Categorical variables were analyzed using Chi square tests and continuous variables were analyzed using independent samples t-tests. Multivariable logistic regression analysis was performed to determine whether MD in combination with other variables was associated with poor outcomes. RESULTS: There were 328 patients included in the study, 38 (11.6%) received MD. Proportions of younger, male, and non-Hispanic were higher in the MD group. There were no statistically significant differences for initial NIHSS, discharge modified Rankin Scale (mRS), 90-day mRS, symptomatic intracerebral hemorrhage (sICH), or systemic hemorrhage between groups. CONCLUSION: One in ten patients thrombolysed for the treatment of AIS received MD. In a predominantly Hispanic population, those who received MD and WBD had similar rates of sICH, discharge disposition, and functional outcome (mRS) at discharge and at 90 days. Limitations include small sample size and attrition for the 90-day mRS.

Intravenous cangrelor and oral ticagrelor as an alternative to clopidogrel in acute intervention.

BACKGROUND: Dual antiplatelet therapy (DAP) is necessary to prevent thromboembolic events during carotid stenting, stent-assisted coil embolization, and implant of flow diverters (FD). However, DAP in the acute phase may be challenging. An intravenous alternative, cangrelor, has rapid onset, short plasma half-life, and more reliable antiplatelet action for acute interventions. The study objective was to evaluate feasibility and safety of IV cangrelor during acute neuroendovascular surgery procedures. METHODS: We performed a retrospective analysis of our database of patients treated with stent-assisted coil embolization, FD placement for aneurysmal subarachnoid hemorrhage (aSAH), or stenting for acute internal carotid artery (ICA) occlusion where IV cangrelor was used. Morbidity, mortality, incidence of thromboembolic events, hemorrhages, and 90-day outcomes were reported. RESULTS: Ten patients were found in our database from June 2018 through January 2019. Four patients had aSAH, four had middle cerebral artery strokes with tandem lesions, one had an ICA occlusion, and one had a vertebral artery aneurysm. One of the ten patients experienced a thrombotic event. One patient developed new post-procedural bleeding and two had worsening intracranial hemorrhage. Five patients were discharged home in stable condition, two to acute rehabilitation, one to a nursing facility, and two others expired (likely the result of the severe and evolving strokes). Of the eight who were discharged, six (75%) had a good 90-day functional outcome (modified Rankin Scale 0-2). CONCLUSION: Acute administration of IV cangrelor with or without oral ticagrelor is a feasible antiplatelet treatment option for acute neuroendovascular procedures.

Hippocampal place cell dysfunction and the effects of muscarinic M1 receptor agonism in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease that disproportionately impacts memory and the hippocampus. However, it is unclear how AD pathology influences the activity of surviving neurons in the hippocampus to contribute to the memory symptoms in AD. One well-understood connection between spatial memory and neuronal activity in healthy brains is the activity of place cells, neurons in the hippocampus that fire preferentially in a specific location of a given environment (the place field of the place cell). In the present study, place cells were recorded from the hippocampus in a recently-developed rat model of AD (Tg-F344 AD) at an age (12-20 months) at which the AD rats showed marked spatial memory deficits. Place cells in the CA2 and CA3 pyramidal regions of the hippocampus in AD rats showed sharply reduced spatial fidelity relative to wild-type (WT) rats. In contrast, spiking activity of place cells recorded in region CA1 in AD rats showed good spatial fidelity that was similar to CA1 place cells in WT rats. Oral administration of the M1 muscarinic acetylcholine receptor agonist VU0364572 impacted place cell firing rates in CA1 and CA2/3 hippocampal regions, but did not improve the spatial fidelity of CA2/3 hippocampal place cells in AD rats. The results indicated that, to the extent the spatial memory impairment in AD rats was attributable to hippocampal dysfunction, the memory impairment was more attributable to dysfunction in hippocampal regions CA2 and CA3 rather than CA1.