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To identify novel technologies pertinent to the prevention, diagnosis, treatment, and rehabilitation of ischemic stroke, and recommend the technologies that show the most promise in advancing ischemic stroke care. A systematic literature search on PubMed and Medscape was performed. Articles were assessed based on pre-determined criteria. Included journal articles were evaluated for specific characteristics and reviewed according to a structured paradigm. A search on www.clinicaltrials.gov was performed to identify pre-clinical ischemic stroke technological interventions. All clinical trial results were included. An additional search on PubMed was conducted to identify studies on robotic neuroendovascular procedures. Thirty journal articles and five clinical trials were analyzed. Articles were categorized as follows: six studies pertinent to pre-morbidity and prevention of ischemic stroke, three studies relevant to the diagnosis of ischemic stroke, 16 studies about post-ischemic stroke rehabilitation, and five studies on robotic neuroendovascular interventions. Novel technologies across the spectrum of ischemic stroke care were identified, and the ones that appear to have the most clinical utility are recommended. Future investigation of the feasibility and long-term efficacy of the recommended technologies in clinical settings is warranted.

Statins, drugs known for lipid lowering capabilities and reduction of cardiovascular disease, have demonstrated neuroprotective effects following ischemic stroke in retrospective clinical and animal studies. However, dosing (methods, time, type of statin, and quantity) varies across studies, limiting the clinical applicability of these findings. Furthermore, a comprehensive review of statins in edema and blood-brain barrier (BBB) breakdown is needed to provide insight on diverse, less explored neuroprotective effects. In the present study, we conduct a meta-analysis of publications evaluating statin administration in animal models of ischemic stroke. We review statins' most effective dosing regimen in four outcomes-infarct, edema, BBB breakdown, and functional outcome-to characterize several parameters of benefit associated with statin administration. A search term was constructed to identify experimental murine studies exploring statin use after transient middle cerebral artery occlusion (tMCAO) in PubMed, Web of Science, and Embase. Extracted data included statin type, dose, time and method of administration, and the four predetermined outcomes (functional outcome, edema, BBB breakdown, and infarction). A meta-analysis and stratified meta-regression were conducted using the standardized mean difference (SMD) method for continuous measurements. Included publications were assessed for bias using SYRCLE's RoB tool for animal studies. A total of 24 studies were included. Statin administration significantly reduced infarct volume (p < 0.0001), edema volume (p < 0.002), and neurological deficit (p < 0.0001). Simvastatin and pravastatin were most effective in reducing infarct volume when compared with atorvastatin (p = 0.0475, p = 0.0004) and rosuvastatin (p = 0.0036, p < 0.0001). Pravastatin outperformed all others in functional outcome. Subcutaneous (SC) injection was most effective in all outcomes. Statin therapy reduced BBB breakdown according to our systematic review. Mean study quality was 4.6/10. While statin therapy evidently improves neurological outcome following ischemic stroke, this analysis adds to our understanding of dosing and statins' effects on edema and BBB breakdown. These findings will aid the design of future studies investigating statin use and have larger implications for the clinical care of ischemic stroke patients.

OBJECTIVEPostoperative surgical site infections (SSIs) in neurosurgical patients carry a significant risk of increased morbidity and mortality. With SSIs accounting for approximately 20% of nosocomial infections and costing approximately $1.6 billion USD annually, there is a need for additional prophylaxis to improve current standards of care. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. A randomized controlled trial assessing its efficacy in the general neurosurgical population is currently underway. Here, the authors report their initial impressions of topical vancomycin safety among patients enrolled during the 1st year of the trial.METHODSThis prospective, multicenter, patient-blinded, randomized controlled trial will enroll 2632 patients over 5 years. Here, the authors report the incidence of adverse events, the degree of systemic vancomycin absorption in treated patients, and pattern changes of antibiotic-resistant profiles of Staphylococcus aureus flora among patients enrolled during the 1st year.RESULTSThe topical vancomycin treatment group comprised 257 patients (514 total enrolled patients), of whom 2 exhibited weakly positive serum levels of vancomycin (> 3.0 mg/dl). S. aureus was detected preoperatively in the anterior nares of 35 (18.1%) patients and the skin near the surgical site of 9 (4.7%). Colonization in the nares remained for many patients (71.4%) through postoperative day 30. The authors found a significant association between preoperative S. aureus colonization and postoperative colonization. Seven methicillin-resistant isolates were detected among 6 different patients. Two isolates were detected preoperatively, and 5 were de novo postoperative colonization. No adverse responses to treatment have been reported to date.CONCLUSIONSThe authors’ data indicate that the use of topical vancomycin is safe with no significant adverse effects and minimal systemic absorption, and no development of vancomycin-resistant microorganisms.Clinical trial registration no.: NCT02284126 (clinicaltrials.gov)

Introduction: For elderly adults in the United States, stroke is the fifth leading cause of death of which ischemic strokes comprise a vast majority. Optimal pharmacological management of elderly ischemic stroke patients involves both reperfusion and supportive care. Recent research into pharmacological management has focused on vascular, immunomodulatory, cytoprotective, and alternative agents, some of which have shown limited success in clinical trials. However, no treatments have been established as a reliable mode for management of cerebral ischemia for elderly adults beyond acute thrombolysis.Areas covered: The authors conducted a literature search for ischemic stroke management in the elderly and a search for human drug studies for managing ischemic stroke on clinicaltrials.gov. Here, they describe recent progress in the pharmacological management of cerebral ischemia in the elderly.Expert opinion: Many drug classes (antihypertensive, cytoprotective and immunomodulatory, and alternative agents) have been explored with limited success in managing ischemic stroke, though some have shown preventative benefits. We generally observed a broad gap in evidence on elderly patients from studies across all drug classes, necessitating further studies to gain an understanding of effective management of ischemic stroke in this large demographic of patients.

Carotid endarterectomy (CEA) is associated with perioperative stroke and mortality in a minority of cases. The aim of this systematic review and meta-analysis was to investigate the effect of pre-operative statins on perioperative outcomes in patients undergoing CEA for internal carotid artery (ICA) stenosis. A systematic review of PubMed, Medline, and the Cochrane Database of Systematic Reviews was performed. Studies were included which reported perioperative stroke and/or survival outcomes following CEA for ICA stenosis and compared patients who were and were not taking pre-operative statins. Relevant data were extracted and pooled using meta-analysis. Seven studies met the inclusion criteria, comprising 21,387 patients. A total of 68.9% (14,976) were administered statins and 31.1% (6657) were statin-free. Pre-operative statin use was higher in patients with a history of cardiac disease (12.2 vs. 23.6% in the statin-free group), diabetes (31.6 vs. 25.1% in the statin-free group), and hypertension (83.5 vs. 72.2% in the statin-free group), while a greater proportion of statin-free patients had symptomatic disease (44.9 vs. 55.5% in the statin-free group). Statins were associated with reduced perioperative stroke in all patients (OR 0.57; 95% CI 0.34–0.95; p = 0.03) and in symptomatic patients (OR 0.57; 95% CI 0.35–0.93; p = 0.03). A trend towards lower perioperative mortality (OR 0.54; 95% CI 0.29, 1.03; p = 0.06) and significantly improved overall survival was observed in the statin group (HR 0.69; 95% CI 0.59–0.81; p

Surgical-site infections (SSIs) account for 20% of all healthcare-associated infections, are the most common nosocomial infection among surgical patients, and are a focus of quality improvement initiatives. Despite implementation of many quality care measures (e.g. prophylactic antibiotics), SSIs remain a significant cause of morbidity, mortality, and economic burden, particularly in the field of neurosurgery. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. However, a randomized controlled trial assessing its efficacy in the general neurosurgical population has yet to be done. The principle aim of "Topical Vancomycin for Neurosurgery Wound Prophylaxis" (NCT02284126) is to determine whether prophylactic, topical vancomycin reduces the risk of SSIs in the adult neurosurgical population. This prospective, multicenter, patient-blinded, randomized controlled trial will enroll patients to receive the standard of care plus topical vancomycin, or the standard of care alone. The primary endpoint of this study is a SSI by postoperative day (POD) 30. Patients must be over 18years of age. Patients are excluded for renal insufficiency, vancomycin allergy, and some ineligible procedures. Univariate analysis and logistic regression will determine the effect of topical vancomycin on SSIs at 30days. A randomized controlled trial is needed to determine the efficacy of this treatment. Results of this trial are expected to directly influence the standard of care and prevention of SSIs in neurosurgical patients.

Background Intracerebral hemorrhage (ICH) is associated with neurological decline and poor prognosis. Although many etiologic models have been explored, secondary damage caused by continued inflammation and iron exposure from red blood cell lysis may explain poor outcomes at distant follow-up. Examining serum samples of patients with ICH for biomarkers of iron physiology may yield relationships between iron exposure and functional outcomes. Methods The following study retrospectively evaluated 41 patient serum samples obtained 1 day and 7 days post-ictus for CD163, ferritin, and hepcidin concentrations. Functional outcomes, using the modified Rankin Scale, were dichotomized into good (0-3) and poor (4-6). Correlation analysis and logistic regression were used to explore relationships between biomarker values, clinical metrics (such as ICH Score), and functional outcomes at 3 and 12 months. Results Clinical metrics (Acute Physiology and Chronic Health Evaluation II score, ICH Score, and National Institutes of Health Stroke Scale) were correlated with elevated ferritin levels 7 days post-ictus. Furthermore, it was found that mean CD163 levels on day 1 were significantly associated with functional outcomes at 3 and 12 months; mean serum ferritin concentrations on days 1 and 7 were elevated in those with poor outcomes at 3 months, and day 7 levels were independently correlated with 12-month outcomes. Conclusion Although this study serves to contribute to a growing body of evidence that CD163 and ferritin are biomarkers of functional outcomes, prospective cohort studies may clarify the role of iron-related inflammatory biomarkers as they pertain to neurological decline in patients with ICH.

Background Intracerebral hemorrhage (ICH) remains a devastating diagnosis. While the ICH Score continues to be used in the clinical setting to prognosticate outcomes, contemporary improvements in management have reduced mortality rates for each scoring tier. The aims of this study were to examine mortality rates within ICH Score strata and examine if these findings are stable when major disability is included in categorizing poor outcomes. Methods From a single-institution cohort built between 2009 and 2016, 582 patients were extracted based on the criteria for complete ICH Score, discharge mortality, and functional status for survivors. Mortality rates were stratified by ICH Score and compared with both historical and similar contemporary cohorts. Poor outcome was defined as severe disability (modified Rankin Scale score 5) in addition to death, stratified by ICH Score, and compared. A secondary analysis of patients with ICH Score of 2 was performed in light of the primary results. Results Mortality rates stratified by ICH Score were notably lower than expected for low- and moderate-grade ICH compared with the original cohort. However, when defining a poor outcome as including severe disability (modified Rankin Scale score 5) in addition to death, the rates for poor outcomes were higher for patients with ICH Score of 2 (51.16% vs. 26%, P = 0.017) and no different for any other score group compared with the original cohort. Conclusions Though the original ICH Score overestimates mortality for low-grade and moderate-grade hemorrhages, it may underpredict severe disability.

Stroke is a leading cause of death and disability worldwide and an increasing number of ischemic stroke patients are undergoing pharmacological and mechanical reperfusion. Both human and experimental models of reperfused ischemic stroke have implicated the complement cascade in secondary tissue injury. Most data point to the lectin and alternative pathways as key to activation, and C3a and C5a binding of their receptors as critical effectors of injury. During periods of thrombolysis use to treat stroke, acute experimental complement cascade blockade has been found to rescue tissue and improves functional outcome. Blockade of the complement cascade during the period of tissue reorganization, repair, and recovery is by contrast not helpful and in fact is likely to be deleterious with emerging data suggesting downstream upregulation of the cascade might even facilitate recovery. Successful clinical translation will require the right clinical setting and pharmacologic strategies that are capable of targeting the key effectors early while not inhibiting delayed repair. Early reports in a variety of disease states suggest that such pharmacologic strategies appear to have a favorable risk profile and offer substantial hope for patients.

OBJECTIVEDelayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH.METHODSIn this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH.RESULTSOf the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm.CONCLUSIONSThe power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov)

After heart disease and combined forms of cancer, stroke is the leading cause of death in the United States. Currently, tissue-plasminogen activator (tPA) thrombolysis is the only thrombolytic therapy that has been shown to improve patient outcome. Presently, the only antithrombotic drug treatment that has proven effective at improving acute ischemic stroke patient outcome is aspirin administration. Despite these studies, no clinical trials have yet demonstrated a reliably effective pharmacological treatment. Areas covered: We conducted a search of recent drug studies for ischemic stroke on clinicaltrials.gov in addition to a literature search for acute ischemic stroke therapy using PubMed. This review details our findings of recent advancements in the pharmacological treatment of acute ischemic stroke. Expert commentary: We concluded that recent attempts to establish new pharmacological treatment protocols for acute ischemic stroke have had limited success, but many Phase III and Phase IV clinical trials demonstrate promise. Moreover, several studies have demonstrated the efficacy of dual-antiplatelet therapies at reducing risk of secondary stroke. Studies for novel therapeutic targets for neuroprotection have been largely unsuccessful. Some trials had positive results; however, there is much room for improvement and other studies show promise in their preliminary stages.

Background The morbidity, mortality, and monetary cost associated with intracerebral hemorrhage (ICH) is devastatingly high. Several scoring systems have been proposed to prognosticate outcomes after ICH, although the original ICH Score is still the most widely used. However, recent research suggests that systemic physiologic factors, such as those included in the Acute Physiology and Chronic Health Evaluation II score, may also influence outcome. In addition, no scoring systems to date have included premorbid functional status. Therefore, we propose a scoring system that incorporates these factors to prognosticate 3-month and 12-month functional outcomes. Methods We used the Random Forest machine-learning technique to identify factors from a dataset of more than 200 data points per patient that were most strongly affiliated with functional outcome. We then used linear regression to create an initial model based on these factors and modified weightings to improve accuracy. Our scoring system was compared with the ICH Score for prognosticating functional outcomes. Results Two separate scoring systems (Intracerebral Hemorrhage Outcomes Project 3 [ICHOP3] and ICHOP12) were developed for 3-month and 12-month functional outcomes using Glasgow Coma Scale, National Institutes of Health Stroke Scale, Acute Physiology and Chronic Health Evaluation II, premorbid modified Rankin Scale (mRS), and hematoma volume (3-month only). Patient outcomes were dichotomized into good (mRS score, 0–3) and poor (mRS score, 4–6) categories based on functional status. Areas under the curve in the derivation cohort for predicting mRS score were 0.89 (3-month) and 0.87 (12-month); both were significantly more discriminatory than the original ICH Score. Conclusions The ICHOP scores may provide more comprehensive evaluation of a patient's long-term functional prognosis by taking into account systemic physiologic factors as well as premorbid functional status.

Despite a recent decline in mortality,1 cerebrovascular disease (stroke) remains the fifth leading cause of death in the United States and the leading preventable cause of disability.2 Furthermore, quality of life (QOL) after stroke depends on more than retention of physical functioning and ability.3 Psychological health and well-being are known to associate with QOL outcomes,4 for example, an estimated 30% of stroke survivors develop depression.5 Although poststroke depression (PSD) is a well-researched and established phenomenon,6–8 far less is known about the development of poststroke post-traumatic stress disorder (PTSD).9 Researchers have hypothesized that acute medical conditions such as asthma attack10 and myocardial infarction11 can precipitate PTSD, but PTSD specifically after a stroke has only been formally conceptualized for

Digital analysis of writing and drawing has become a valuable research and clinical tool for the study of upper limb motor dysfunction in patients with essential tremor, Parkinson's disease, dystonia, and related disorders. We developed a validated method of computerized spiral analysis of hand-drawn Archimedean spirals that provides insight into movement dynamics beyond subjective visual assessment using a Wacom graphics tablet. While the Wacom tablet method provides robust data, more widely available mobile technology platforms exist.We introduce a novel adaptation of the Wacom-based method for the collection of hand-drawn kinematic data using an Apple iPad. This iPad-based system is stand-alone, easy-to-use, can capture drawing data with either a finger or capacitive stylus, is precise, and potentially ubiquitous.The iPad-based system acquires position and time data that is fully compatible with our original spiral analysis program. All of the important indices including degree of severity, speed, presence of tremor, tremor amplitude, tremor frequency, variability of pressure, and tightness are calculated from the digital spiral data, which the application is able to transmit.While the iPad method is limited by current touch screen technology, it does collect data with acceptable congruence compared to the current Wacom-based method while providing the advantages of accessibility and ease of use.The iPad is capable of capturing precise digital spiral data for analysis of motor dysfunction while also providing a convenient, easy-to-use modality in clinics and potentially at home.

Three-dimensional (3D) printers are a developing technology penetrating a variety of markets, including the medical sector. Since its introduction to the medical field in the late 1980s, 3D printers have constructed a range of devices, such as dentures, hearing aids, and prosthetics. With the ultimate goals of decreasing healthcare costs and improving patient care and outcomes, neurosurgeons are utilizing this dynamic technology, as well. Digital Imaging and Communication in Medicine (DICOM) can be translated into Stereolithography (STL) files, which are then read and methodically built by 3D Printers. Vessels, tumors, and skulls are just a few of the anatomical structures created in a variety of materials, which enable surgeons to conduct research, educate surgeons in training, and improve pre-operative planning without risk to patients. Due to the infancy of the field and a wide range of technologies with varying advantages and disadvantages, there is currently no standard 3D printing process for patient care and medical research. In an effort to enable clinicians to optimize the use of additive manufacturing (AM) technologies, we outline the most suitable 3D printing models and computer-aided design (CAD) software for 3D printing in neurosurgery, their applications, and the limitations that need to be overcome if 3D printers are to become common practice in the neurosurgical field.