Cerebrovascular Reserve (CVR) and Stages of Hemodynamic Compromise.

The concept of hemodynamic compromise (HC) is used to detect brain regions under ischemic stress by impaired ability to dilate in response to a vasodilatory challenge for cerebrovascular reserve (CVR). The vasodilatory challenges are either inhaled CO2 or a carbonic anhydrase inhibitor acetazolamide (AZ) with measurements of cerebral blood flow (CBF) before and during the challenge. The rationale for CVR is that the brain under ischemic stress is vasodilated and the increase in CBF is attenuated. However, regional oxygen extraction fraction (OEF) by positron emission tomography (PET) is the gold standard for measurement of HC. We showed a strong correlation between CVR and OEF and the OEF response (OEFR) before and after vasodilation in patients with acute ischemic stroke. These observations suggest that CVR measurements alone identify brain regions under ischemic stress without the need for expensive, time consuming and difficult PET OEF.

Unifying theory of carotid plaque disruption based on structural phenotypes and forces expressed at the lumen/wall interface.

OBJECTIVES: To integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption. MATERIALS AND METHODS: First, we analysed the phenotypes of carotid endarterectomy specimens in a photographic dataset A, and matched them with the likelihood of preoperative stroke. Second, laser angioscopy was used to further define the phenotypes in intact specimens (dataset B) and benchmark with histology. Third, representative vascular geometries for each structural phenotype were analysed with Computational Fluid Dynamics (CFD), and the mechanical strength of the complicated atheroma to resist penetrating forces was quantified (n=14). RESULTS: In dataset A (n=345), ulceration (fibrous cap disruption) was observed in 82% of all plaques, intraplaque haemorrhage in 68% (93% subjacent to an ulcer) and false luminal formation in 48%. At least one of these 'rupture' phenotypes was found in 97% of symptomatic patients (n=69) compared with 61% in asymptomatic patients. In dataset B (n=30), laser angioscopy redemonstrated the structural phenotypes with near-perfect agreement with histology. In CFD, haemodynamic stress showed a large pulse magnitude, highest upstream to the point of maximal stenosis and on ulceration the inflow stream excavates the necrotic core cranially and then recirculates into the true lumen. Based on mechanical testing (n=14), the necrotic core is mechanically weak and penetrated by the blood on fibrous cap disruption. CONCLUSIONS: Fibrous cap ulceration, plaque haemorrhage and excavation are sequential phenotypes of plaque disruption resulting from the chiselling effect of haemodynamic forces over unmatched mechanical tissue strength. This chain of events may result in thromboembolic events independently of the degree of stenosis.

MicroRNA Analysis of Human Stroke Brain Tissue Resected during Decompressive Craniectomy/Stroke-Ectomy Surgery.

BACKGROUND: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first time, we investigated miRNA expression signatures in freshly removed human stroke brain tissue. METHODS: Human brain samples were obtained during craniectomy and brain tissue resection in severe stroke patients with life-threatening brain swelling. The tissue samples were subjected to histopathological and immunofluorescence microscopy evaluation, next generation miRNA sequencing (NGS), and bioinformatic analysis. RESULTS: miRNA NGS analysis detected 34 miRNAs with significantly aberrant expression in stroke tissue, as compared to non-stroke samples. Of these miRNAs, 19 were previously identified in stroke patient blood and CSF, while dysregulation of 15 miRNAs was newly detected in this study. miRNA direct target gene analysis and bioinformatics approach demonstrated a strong association of the identified miRNAs with stroke-related biological processes and signaling pathways. CONCLUSIONS: Dysregulated miRNAs detected in our study could be regarded as potential candidates for biomarkers and/or targets for therapeutic intervention. The results described herein further our understanding of the molecular basis of stroke and provide valuable information for the future functional studies in the experimental models of stroke.

MRI-Guided High-Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A Review.

Stroke, either ischemic or hemorrhagic, accounts for significantly high morbidity and mortality rates around the globe effecting millions of lives annually. For the past few decades, ultrasound has been extensively investigated to promote clot lysis for the treatment of stroke, myocardial infarction, and acute peripheral arterial occlusions, with or without the use of tPA or contrast agents. In the age of modern minimal invasive techniques, magnetic resonance imaging-guided high-intensity focused ultrasound is a new emerging modality that seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke. High-intensity focused ultrasound causes thermal heating as the tissue absorbs the mechanical energy transmitted by the ultrasonic waves leading to tissue denaturation and coagulation. Several in-vitro and in-vivo studies have demonstrated the viability of this technology for sonothrombolysis in both types of stroke and have warranted clinical trials. Apart from safety and efficacy, initiation of trials would further enable answers regarding its practical application in a clinical setup. Though this technology has been under study for treatment of various brain diseases for some decades now, relatively very few neurologists and even neurosurgeons seem to be acquainted with it. The aim of this review is to provide basic understanding of this powerful technology and discuss its clinical application and potential role as an emerging viable therapeutic option for the future management of stroke.

Emerging Pharmacologic Targets in Cerebral Cavernous Malformation and Potential Strategies to Alter the Natural History of a Difficult Disease: A Review.

Importance: Cerebral cavernous malformations (CCMs) are vascular lesions of the brain that may lead to hemorrhage, seizures, and neurologic deficits. Most are linked to loss-of-function mutations in 1 of 3 genes, namely CCM1 (originally called KRIT1), CCM2 (MGC4607), or CCM3 (PDCD10), that can either occur as sporadic events or are inherited in an autosomal dominant pattern with incomplete penetrance. Familial forms originate from germline mutations, often have multiple intracranial lesions that grow in size and number over time, and cause an earlier and more severe presentation. Despite active preclinical research on a few pharmacologic agents, clinical translation has been slow. Open surgery and, in some cases, stereotactic radiosurgery remain the only effective treatments, but these options are limited by lesion accessibility and are associated with nonnegligible rates of morbidity and mortality. Observations: We discuss the limits of CCM management and introduce findings from in vitro and in vivo studies that provide insight into CCM pathogenesis and indicate molecular mechanisms as potential therapeutic targets. These studies report dysregulated cellular pathways shared between CCM, cardiovascular diseases, and cancer. They also suggest the potential effectiveness of proper drug repurposing in association with, or as an alternative to, targeted interventions. Conclusions and Relevance: We propose methods to exploit specific molecular pathways to design patient-tailored therapeutic approaches in CCM, with the aim to alter its natural progression. In this scenario, the lack of effective pharmacologic options remains a critical barrier that poses an unfulfilled and urgent medical need.

ACCESS to Better Health and Clear Skies: Telemedicine and Greenhouse Gas Reduction.

Introduction: This study estimates the reduction in greenhouse gas (GHG) emissions resulting from 2,020 neuro-emergent telemedicine consultations. We then estimate potential GHG reduction if the program was expanded nationwide. Materials and Methods: Travel distances in miles were calculated for each avoided patient transfer using hospital location data and ArcGIS® tools. Potential GHG reductions from program expansion were calculated based on state and national stroke Diagnosis-Related Groups (DRGs). Along with average flight distance from a rural hospital to closest level one trauma center. Results: Participation in the Access to Critical Cerebral Emergent Support Services (ACCESS) from May 2015 to July 2017 resulted in 2,020 consultations. Of these consultations, there was a 70% (1,414) reduction in patient transfers. Emission reduction totaled 618,772 kg of carbon dioxide equivalents (CO2e) (618.77 metric tons) or 0.306 metric tons of CO2e per patient. Expanding the program across New Mexico and similar U.S. areas resulted in potential reductions of 4,307 (IQR 3,386-5,274) and 213,279 (IQR 169,320-263,570) metric tons of CO2e. Conclusion: Transport accounts for 26% of global CO2 emissions and is one of the few industrial sectors where emissions are still growing. What makes this study more impactful is that aviation's emissions are not part of the Kyoto Protocol and little is being done in this sector. GHG reduction was not the main intention of the ACCESS program, but it has shown to be a significant by-product.

Middle Cerebral Artery Aneurysm "Neck Overhang": Decreased Postclipping Residual Using the Intersecting Clipping Technique.

BACKGROUND: Middle cerebral artery (MCA) aneurysms continue to be viewed by many as primarily surgical entities. OBJECTIVE: To introduce a new, easily measurable dimension termed "neck overhang," defined as the amount of the aneurysm that extends proximal to the 2 dimensionally defined "neck" and to evaluate the utility of the intersecting clipping technique (use of straight clip and intersecting fenestrated clip) to adapt to this overhanging segment's specific dimensions and achieve better obliteration of the MCA aneurysms. METHODS: We reviewed retrospectively 100 MCA aneurysms treated surgically over the last 10 yr at our institution. We identified the clipping technique that was performed (intersecting vs "standard" technique) and we evaluated the presence of a postoperative remnant. We then correlated these with the aneurysm's overhanging neck length. RESULTS: Forty-three aneurysms were treated with the intersecting clipping technique. The overall rate of remnant was 16%. In the standard group, the rate of remnant was 23%, whereas with intersecting clipping that was 7% (P = .029). Within the standard clipping group, we found that the optimum threshold for length of the neck overhang was ≥1.9 mm in order to predict the occurrence of residual. Applying this threshold to the intersecting clipping technique group resulted in a reduction in remnant from 35% in the standard group to 9%. CONCLUSION: Neck overhang >1.9 mm is associated with a higher chance of postclipping residual aneurysm in MCA aneurysms. The intersecting clipping technique is a versatile technique that can conform to various aneurysms' geometry and can reduce the rate of post clipping residual for aneurysms with high neck overhang.

Cost-effectiveness of Access to Critical Cerebral Emergency Support Services (ACCESS): a neuro-emergent telemedicine consultation program.

AIMS: Access to Critical Cerebral Emergency Support Services (ACCESS) was developed as a low-cost solution to providing neuro-emergent consultations to rural hospitals in New Mexico that do not offer comprehensive stroke care. ACCESS is a two-way audio-visual program linking remote emergency department physicians and their patients to stroke specialists. ACCESS also has an education component in which hospitals receive training from stroke specialists on the triage and treatment of patients. This study assessed the clinical and economic outcomes of the ACCESS program in providing services to rural New Mexico from a healthcare payer perspective. METHODS: A decision tree model was constructed using findings from the ACCESS program and existing literature, the likelihood that a patient will receive a tissue plasminogen activator (tPA), cost of care, and resulting quality adjusted life years (QALYs). Data from the ACCESS program includes emergency room patients in rural New Mexico from May 2015 to August 2016. Outcomes and costs have been estimated for patients who were taken to a hospital providing neurological telecare and patients who were not. RESULTS: The use of ACCESS decreased neuro-emergent stroke patient transfers from rural hospitals to urban settings from 85% to 5% (no tPA) and 90% to 23% (tPA), while stroke specialist reading of patient CT/MRI imaging within 3 h of onset of stroke symptoms increased from 2% to 22%. Results indicate that use of ACCESS has the potential to save $4,241 ($3,952-$4,438) per patient and increase QALYs by 0.20 (0.14-0.22). This increase in QALYs equates to ∼73 more days of life at full health. The cost savings and QALYs are expected to increase when moving from a 90-day model to a lifetime model. CONCLUSION: The analysis demonstrates potential savings and improved quality-of-life associated with the use of ACCESS for patients presenting to rural hospitals with acute ischemic stroke (AIS).

An Innovative Model for Naloxone Use Within an OTP Setting: A Prospective Cohort Study.

OBJECTIVES: Unintentional opioid overdose deaths are a public health crisis, and naloxone is the most effective harm reduction tool to curb many of these deaths. There is growing evidence that take-home naloxone can prevent opioid overdose in targeted populations. The goal of this study is to measure the opioid overdose reversal rate with take-home naloxone among participants with a diagnosis of opioid use disorder (OUD) in an opioid treatment program (OTP) setting. METHODS: Patients enrolled in an outpatient OTP program were eligible for this prospective cohort study between April 4, 2016 and July 4, 2016. Two hundred forty-four study participants received overdose education, instruction on how to use naloxone, and were provided with 2 doses of a take-home naloxone auto-injector kit. They were subsequently followed for 3 months. RESULTS: Thirty-one study participants reported overdose reversals using naloxone auto-injector kits on 38 community members. All overdose reversals were heroin-related. Eighty-seven per cent of the community members reversed with naloxone were friends or relatives of the study participants. CONCLUSIONS: This study validates that naloxone is not commonly used on the index study participant, but is often used on a secondary target among people who inject drugs. The large number of overdose reversals reported in this prospective study suggests that this novel model for naloxone use may be replicated at other OTP settings to reduce opioid overdose deaths.

Microsurgical Vascular Manipulation in Aneurysm Surgery and Delayed Ischemic Injury.

BACKGROUND: The role of aggressive surgical manipulation with clot evacuation, arachnoid dissection, and papaverine-guided adventitial dissection of large vessels during ruptured aneurysm surgery in reducing vasospasm is controversial. Here we describe a single-institution experience in aneurysm surgery outcomes with and without aggressive surgery. METHODS: We performed retrospective analysis of all patients >18 years of age with subarachnoid hemorrhage (SAH) from anterior circulation aneurysms between 2008 and 2013 at the University of New Mexico Hospital. Vasospasm was characterized on days 3 through 14 after SAH based on: (1) angiography, (2) vasospasm requiring angiographic intervention, (3) development of delayed ischemic neurologic deficit (DIND), and (4) radiological appearance of new strokes. RESULTS: Of 159 patients, 114 (71.6%) had "aggressive" and 45 (28.3%) had standard microsurgery. More than 60% of patients presented with a Hunt and Hess score of ≥3 and a Fisher grade (FG) of 4. Compared with standard surgery, there was a statistically significant decrease in the incidence of DIND in patients undergoing aggressive surgery (18.4% vs 37.8%, p=0.01). Moreover, there was a reduction in the number of new strokes by 30% in the aggressive surgery group with moderate or higher degrees of vasospasm (46.0% vs 76.5%, p=0.06). In the same group with FG 4 SAH, however, this difference was more than 50% (30% vs 64.7%, p=0.02). CONCLUSIONS: We conclude that aggressive surgical manipulation during aneurysm surgery results in lower incidence of DIND and new strokes. This effect is most pronounced in patients with FG 4 SAH.

Effect of Cerebrospinal Fluid Drainage on Brain Tissue Oxygenation in Traumatic Brain Injury.

The effectiveness of cerebrospinal fluid (CSF) drainage in lowering high intracranial pressure (ICP) is well established in severe traumatic brain injury (TBI). Recently, however, the use of external ventricular drains (EVDs) and ICP monitors in TBI has come under question. The aim of this retrospective study was to investigate the effect of CSF drainage on brain tissue oxygenation (PbtO2). Using a multi-modality monitoring system, we continuously monitored PbtO2 and parenchymal ICP during CSF drainage events via a ventriculostomy in 40 patients with severe TBI. Measurements were time-locked continuous recordings on a Component Neuromonitoring System in a neuroscience intensive care unit. We further selected for therapeutic CSF drainage events initiated at ICP values above 25 mm Hg and analyzed the 4-min periods before and after drainage for the physiologic variables ICP, cerebral perfusion pressure (CPP), and PbtO2. We retrospectively identified 204 CSF drainage events for ICP EVD-opening values greater than 25 mm Hg in 23 patients. During the 4 min of opened EVD, ICP decreased by 5.7 ± 0.6 mm Hg, CPP increased by 4.1 ± 1.2 mm Hg, and PbtO2 increased by 1.15 ± 0.26 mm Hg. ICP, CPP, and PbtO2 all improved with CSF drainage at ICP EVD-opening values above 25 mm Hg. Although the average PbtO2 changes were small, a clinically significant change in PbtO2 of 5 mm Hg or greater occurred in 12% of CSF drainage events, which was correlated with larger decreases in ICP, displaying a complex relationship between ICP and PbtO2 that warrants further studies.

Complicated Mild Traumatic Brain Injury and the Need for Imaging Surveillance.

OBJECTIVE: To evaluate the need for repeat head computed tomography (CT) in patients with complicated mild traumatic brain injury (TBI) determined nonoperative after the first head CT. METHODS: A total of 380 patients with mild TBI and a positive head CT not needing surgery were included. Changes between first and second head CT were categorized as decreased, increased, or stable. RESULTS: Three patients required neurosurgical intervention (0.8%) after the second CT. There were no significant differences in demographics including age, gender, alcohol consumption, anticoagulation status, time between first and second CT, Glasgow Coma Scale score at admission and discharge, and incidence of subarachnoid hemorrhage, epidural hematoma, contusion, or skull fractures between the operated and nonoperated groups. All patients in the operated group had subdural hematoma compared with 40.8% in the nonoperated group (P = 0.07). All operated patients showed symptoms of neurologic worsening after initial head CT, compared with 2.7% in the nonoperated group (P < 0.001). Moreover, patients who showed neurologic worsening were more likely to show increased intracranial bleeding on repeat head CT, whereas patients who did not show neurologic worsening were more likely to show decreased or stable intracranial bleeding (P = 0.04). CONCLUSIONS: Routine repeat head CT in patients with complicated mild TBI is very low yield to predict need for delayed surgical intervention. Instead, serial neurologic examination and observation over the first 8 hours after the injury is recommended. A second CT scan should be obtained only in patients who have neurologic worsening.

Cortical spreading depression occurs during elective neurosurgical procedures.

OBJECTIVE Cortical spreading depression (CSD) has been observed with relatively high frequency in the period following human brain injury, including traumatic brain injury and ischemic/hemorrhagic stroke. These events are characterized by loss of ionic gradients through massive cellular depolarization, neuronal dysfunction (depression of electrocorticographic [ECoG] activity) and slow spread (2-5 mm/min) across the cortical surface. Previous data obtained in animals have suggested that even in the absence of underlying injury, neurosurgical manipulation can induce CSD and could potentially be a modifiable factor in neurosurgical injury. The authors report their initial experience with direct intraoperative ECoG monitoring for CSD. METHODS The authors prospectively enrolled patients undergoing elective craniotomy for supratentorial lesions in cases in which the surgical procedure was expected to last > 2 hours. These patients were monitored for CSD from the time of dural opening through the time of dural closure, using a standard 1 × 6 platinum electrode coupled with an AC or full-spectrum DC amplifier. The data were processed using standard techniques to evaluate for slow potential changes coupled with suppression of high-frequency ECoG propagating across the electrodes. Data were compared with CSD validated in previous intensive care unit (ICU) studies, to evaluate recording conditions most likely to permit CSD detection, and identify likely events during the course of neurosurgical procedures using standard criteria. RESULTS Eleven patients underwent ECoG monitoring during elective neurosurgical procedures. During the periods of monitoring, 2 definite CSDs were observed to occur in 1 patient and 8 suspicious events were detected in 4 patients. In other patients, either no events were observed or artifact limited interpretation of the data. The DC-coupled amplifier system represented an improvement in stability of data compared with AC-coupled systems. Compared with more widely used postoperative ICU monitoring, there were additional challenges with artifact from saturation during bipolar cautery as well as additional noise peaks detected. CONCLUSIONS CSD can occur during elective neurosurgical procedures even in brain regions distant from the immediate operative site. ECoG monitoring with a DC-coupled full-spectrum amplifier seemed to provide the most stable signal despite significant challenges to the operating room environment. CSD may be responsible for some cases of secondary surgical injury. Though further studies on outcome related to the occurrence of these events is needed, efforts to decrease the occurrence of CSD by modification of anesthetic regimen may represent a novel target for study to increase the safety of neurosurgical procedures.

The Utility of Cerebral Blood Flow Assessment in TBI.

Over the past few decades, intracranial monitoring technologies focused on treating and preempting secondary injury after traumatic brain injury (TBI) have experienced considerable growth. A physiological measure fundamental to the management of these patients is cerebral blood flow (CBF), which may be determined directly or indirectly. Direct measurement has proven difficult previously; however, invasive and non-invasive CBF monitors are now available. This article reviews the history of CBF measurements in TBI as well as the role of CBF in pathologies associated with TBI, such as cerebral autoregulation, hyperemia, and cortical spreading depression. The limitations of various CBF monitors are reviewed in order to better understand their role in TBI management.

Co-prescription of naloxone as a Universal Precautions model for patients on chronic opioid therapy-Observational study.

BACKGROUND: The epidemic of lethal prescription opioid overdose is one of the most pressing public health problems in the United States. In an ambulatory clinic setting, current practice guidelines suggest that health care providers should screen patient's aberrant drug-related behaviors. Given the difficulty of predicting which patients on chronic opioid therapy (COT) will experience opioid overdose, a new paradigm of harm reduction is called for. In previous studies, naloxone, an opioid antagonist, was given only to high-risk patients. However, if naloxone is co-prescribed in a Universal Precautions manner for all patients receiving COT, this may have a significant impact on intentional and unintentional opioid overdose deaths. METHODS: Adult patients treated with COT for chronic noncancer pain are eligible study participants at the University of New Mexico Pain Center. The primary goal of this 1-year study was to develop an efficient Universal Precautions model for co-prescribing of naloxone with COT in the ambulatory clinic setting. Outcome measures included demographic data, detailed medical and substance use history, current morphine equivalent dose (MED), other "high-risk" medications used, and opioid misuse risk. RESULTS: One hundred and sixty-four patients were enrolled in this study. All subjects were educated about the risks of opioid overdose and provided naloxone rescue kits. No overdoses occurred in the study population. Follow-up data illustrated that approximately 57% of the cohort had depressive disorder, the median MED was 90 mg/day, and the median Current Opioid Misuse Measure score (COMM) was 5.0. CONCLUSIONS: The ambulatory co-prescribing of naloxone in a Universal Precautions model for all patients prescribed COT can be adopted as a useful public health intervention. This study illustrates a model that can be used to educate patients, caregivers, and an interdisciplinary team of health care professionals in an academic medical center.

Near-Complete Resolution of Clinical and Radiographic Findings After Endovascular Embolization of a Giant Serpentine A1 Aneurysm.

BACKGROUND: Giant serpentine aneurysms are complex intracranial lesions, associated with a poor prognosis if left untreated. Treatment usually involves surgical trapping of the aneurysm with arterio-arterial anastomosis; however, recent endovascular management has been implemented for the management of such aneurysms. CASE DESCRIPTION: We report the unique case of a 71-year-old woman who presented with visual deficits due to the mass effect of a giant serpentine aneurysm arising from the A1 segment of the anterior cerebral artery. Because of its location proximal to a widely patent anterior communicating artery, angiographic cure was achieved with sacrifice of the A1 segment. Clinical and radiographic follow-up demonstrated resolution of the presenting symptoms and near-complete obliteration of the aneurysm. CONCLUSIONS: Thrombosed giant serpentine aneurysms can show dramatic resolution of mass effect with endovascular treatment.

A Consensus-Based Interpretation of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure Trial.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Comparison of parenchymal and ventricular intracranial pressure readings utilizing a novel multi-parameter intracranial access system.

INTRODUCTION: Both ventricular and parenchymal devices are available for measurement of intracranial pressure (ICP). The Hummingbird(®) Synergy Ventricular System is a novel device allowing multi-parametric neurological monitoring, including both ventricular and parenchymal ICP. The purpose of this study is to compare the congruence of the device's ventricular and parenchymal ICP readings. METHODS: This single-center, quantitative, interventional study compared parenchymal and ventricular ICP readings from 35 patients with the Hummingbird(®) System. If a difference of > ± 3 mmHg existed between an individual patient's parenchymal and ventricular values, progressive intervention strategies were applied to correct identified issues. RESULTS: From a total of 2,259 observations, statistical analysis revealed congruence (within ±0-3 mmHg) of 93% of readings comparing parenchymal and ventricular ICP. Of the observations requiring intervention, 58% involved the parenchymal component, 30% involved the ventricular component, and 12% involved both components. Following prescribed interventions, 98% of readings became congruent (within ±0-3 mmHg). The adjusted mean difference between the two methods was -0.95 (95% CI: -0.97,-0.93) mmHg and all mean ICP readings fell between -2 and 2 mmHg. CONCLUSION: The Hummingbird(®) Synergy Ventricular System demonstrates congruence between ventricular and parenchymal ICP measurements within accepted parameters. Interventions required to realign parenchymal and ventricular readings serve as reminders to clinicians to be vigilant with catheter/cable connections and to maintain appropriate positioning of the ventricular drainage system. The results of this study support the recommendation to use the parenchymal ICP component for routine ICP monitoring, allowing dedication of the ventricular catheter to drainage of cerebrospinal fluid (CSF).

Enhancement of neurogenesis and memory by a neurotrophic peptide in mild to moderate traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a risk factor for Alzheimer disease (AD), a neurocognitive disorder with similar cellular abnormalities. We recently discovered a small molecule (Peptide 6) corresponding to an active region of human ciliary neurotrophic factor, with neurogenic and neurotrophic properties in mouse models of AD and Down syndrome. OBJECTIVE: To describe hippocampal abnormalities in a mouse model of mild to moderate TBI and their reversal by Peptide 6. METHODS: TBI was induced in adult C57Bl6 mice using controlled cortical impact with 1.5 mm of cortical penetration. The animals were treated with 50 nmol/d of Peptide 6 or saline solution for 30 days. Dentate gyrus neurogenesis, dendritic and synaptic density, and AD biomarkers were quantitatively analyzed, and behavioral tests were performed. RESULTS: Ipsilateral neuronal loss in CA1 and the parietal cortex and increase in Alzheimer-type hyperphosphorylated tau and A-ß were seen in TBI mice. Compared with saline solution, Peptide 6 treatment increased the number of newborn neurons, but not uncommitted progenitor cells, in dentate gyrus by 80%. Peptide 6 treatment also reversed TBI-induced dendritic and synaptic density loss while increasing activity in tri-synaptic hippocampal circuitry, ultimately leading to improvement in memory recall on behavioral testing. CONCLUSION: Long-term treatment with Peptide 6 enhances the pool of newborn neurons in the dentate gyrus, prevents neuronal loss in CA1 and parietal cortex, preserves the dendritic and synaptic architecture in the hippocampus, and improves performance on a hippocampus-dependent memory task in TBI mice. These findings necessitate further inquiry into the therapeutic potential of small molecules based on neurotrophic factors.