Reducing inequities in preventable neural tube defects: the critical and underutilized role of neurosurgical advocacy for folate fortification.

Neural tube defects (NTDs) are one of the greatest causes of childhood mortality and disability-adjusted life years worldwide. Global prevalence at birth is approximately 18.6 per 10,000 live births, with more than 300,000 infants with NTDs born every year. Substantial strides have been made in understanding the genetics, pathophysiology, and surgical treatment of NTDs, yet the natural history remains one of high morbidity and profound impairment of quality of life. Direct and indirect costs of care are enormous, which ensures profound inequities and disparities in the burden of disease in countries of low and moderate resources. All indices of disease burden are higher for NTDs in developing countries. The great tragedy is that the majority of NTDs can be prevented with folate fortification of commercially produced food. Unequivocal evidence of the effectiveness of folate to reduce the incidence of NTDs has existed for more than 25 years. Yet, the most comprehensive surveys of effectiveness of implementation strategies show that more than 100 countries fail to fortify, and consequently only 13% of folate-preventable spina bifida is actually prevented. Neurosurgeons harbor a disproportionate, central, and fundamental role in the management of NTDs and enjoy high standing in society. No organized group in medicine can speak as authoritatively or convincingly. As a result, neurosurgeons and organized neurosurgery harbor disproportionate potential to advocate for more comprehensive folate fortification, and thereby prevent the most common and severe birth defect to impact the human nervous system. Assertive, proactive, informed advocacy for folate fortification should be a central and integral part of the neurosurgical approach to NTDs. Only by making the prevention of dysraphism a priority can we best address the inequities often observed worldwide.

Neurosurgical applications of viscoelastic hemostatic assays.

Patients taking antithrombotic agents are very common in neurosurgical practice. The perioperative management of these patients can be extremely challenging especially as newer agents, with poorly defined laboratory monitoring and reversal strategies, become more prevalent. This is especially true with emergent cases in which rapid reversal of anticoagulation is required and the patient's exact medical history is not available. With an aging patient population and the associated increase in diseases such as atrial fibrillation, it is expected that the use of these agents will continue to rise in coming years. Furthermore, thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and myocardial infarction are common complications of major surgery. These trends, in conjunction with a growing understanding of the hemostatic process and its contribution to the pathophysiology of disease, stress the importance of the complete evaluation of a patient's hemostatic profile in guiding management decisions. Viscoelastic hemostatic assays (VHAs), such as thromboelastography and rotational thromboelastometry, are global assessments of coagulation that account for the cellular and plasma components of coagulation. This FDA-approved technology has been available for decades and has been widely used in cardiac surgery and liver transplantation. Although VHAs were cumbersome in the past, advances in software and design have made them more accurate, reliable, and accessible to the neurosurgeon. VHAs have demonstrated utility in guiding intraoperative blood product transfusion, identifying coagulopathy in trauma, and managing postoperative thromboprophylaxis. The first half of this review aims to evaluate and assess VHAs, while the latter half seeks to appraise the evidence supporting their use in neurosurgical populations.

Lessons for the pathogenesis of vasospasm from a patient with sickle cell disease, moyamoya disease, subarachnoid hemorrhage, and 1 month of persistent vasospasm: illustrative case.

BACKGROUND: The mechanism of vasospasm post-subarachnoid hemorrhage (post-SAH) is a poorly understood yet devastating complication that can result in delayed ischemic neurological damage. High concentrations of free hemoglobin present in hemolytic conditions reduce nitric oxide (NO) availability which may disrupt vascular dynamics and contribute to the extent of vasospasm. OBSERVATIONS: The authors describe the clinical course of a sickle cell disease (SCD) patient with spontaneous SAH who suffered an abnormally long duration of vasospasm. The authors then present a focused review of the pathology of intravascular hemolysis and discuss the potential key role of intravascular hemolysis in the pathogenesis of cerebral vasospasm as illustrated in this case lesson. LESSONS: Abnormally prolonged and severe vasospasm in SCD with SAH may provide clues regarding the mechanisms of vasospasm. Intravascular hemolysis limits NO availability and may contribute to the development of vasospasm following SAH.

The underestimated incidence of an orbital angioleiomyoma is possibly associated with an orbital cavernous hemangioma: illustrative case.

BACKGROUND: Orbital angioleiomyoma is generally considered a rare tumor; approximately 40 cases have been reported. However, after their experience with 6 consecutive cases in their single institution during 3 years, the authors speculate that the incidence of orbital angioleiomyomas is possibly underestimated. OBSERVATIONS: A 34-year-old female presented with progressive exophthalmos of 2 years' duration. Orbital computed tomography and magnetic resonance imaging revealed a well-circumscribed orbital tumor with partial and heterogeneous gadolinium enhancement. Technetium-99m red blood cell single-photon emission computed tomography showed positive perfusion in the late blood-pool phase, which was exactly consistent with the finding of a cavernous hemangioma. Under the impression of a cavernous hemangioma, the authors accessed the mass with an endoscopic endonasal approach and completely removed it without neurological deficit. Pathological examination revealed that the final diagnosis was an angioleiomyoma with positive immunostaining results for smooth muscle actin (SMA). LESSONS: The incidence of orbital angioleiomyomas may not be very low, as these lesions have possibly been misdiagnosed as orbital cavernous hemangiomas because of their histological similarity. Preoperative presumption and differentiation from cavernous hemangiomas are very challenging because of the rarity of orbital angioleiomyoma and similar radiological findings. SMA immunostaining may be critical to differentiate orbital angioleiomyomas from cavernous hemangiomas.

Risk factors associated with conversion of an Ommaya reservoir to a permanent cerebrospinal fluid shunt in preterm posthemorrhagic hydrocephalus.

OBJECTIVE: A considerable percentage of preterm infants with posthemorrhagic hydrocephalus initially managed with an Ommaya reservoir require a permanent CSF shunt. The objective of the study was to analyze possible risk factors associated with the need for converting an Ommaya reservoir to a permanent shunt. METHODS: The authors retrospectively reviewed the clinical records of premature infants weighing 1500 g or less with posthemorrhagic hydrocephalus (Papile grades III and IV) managed with an Ommaya reservoir at their institution between 2002 and 2017. RESULTS: Forty-six patients received an Ommaya reservoir. Five patients (10.9%) were excluded due to intraventricular infection during management with an Ommaya reservoir. Average gestational age and weight for the remaining 41 patients was 27 ± 1.8 weeks and 987 ± 209 grams, respectively. Thirty patients required a permanent shunt and 11 patients did not require a permanent shunt. The conversion rate from an Ommaya reservoir to a permanent shunt was 76.1%. Symptomatic persistent ductus arteriosus (PDA) was more frequent in the nonpermanent shunt group than in the shunt group (88.9% vs 50%, p = 0.04). The need for extraction of more than 10 ml/kg per day of CSF through the Ommaya reservoir was lower in the nonpermanent shunt group than in the shunt group (9.1% vs 51.7%, p = 0.015). CSF lactate was lower in the nonpermanent group than in the shunt group (mean 2.48 mg/dl vs 3.19 mg/dl; p = 0.004). A cutoff value of ≥ 2.8 mg/dl CSF lactate predicted the need for a permanent shunt with sensitivity and specificity of 82.4% and 80%, respectively. There were no significant differences in gestational age, sex, weight, Papile grade, ventricular index, or other biochemical markers. After the multivariate analysis, only CSF lactate ≥ 2.8 mg/dl was associated with a higher conversion rate to a permanent shunt. CONCLUSIONS: This study showed that a high level of CSF lactate, absence of symptomatic PDA, and a higher CSF extraction requirement were associated with a higher likelihood of implanting a permanent CSF shunt. The authors believe these findings should be considered in future studies.

Sex-related differences in wall remodeling and intraluminal thrombus resolution in a rat saccular aneurysm model.

OBJECTIVE: Intracranial aneurysms (IAs) are more often diagnosed in women. Hormones and vessel geometry, which influences wall shear stress, may affect pathophysiological processes of the arterial wall. Here, the authors investigated sex-related differences in the remodeling of the aneurysm wall and in intraluminal thrombus resolution. METHODS: A well-characterized surgical side-wall aneurysm model was used in female, male, and ovariectomized rats. Decellularized grafts were used to model highly degenerated and decellularized IA walls and native grafts to model healthy IA walls. Aneurysm growth and thrombus composition were analyzed at 1, 7, 14, and 28 days. Sex-related differences in vessel wall remodeling were compared with human IA dome samples of men and pre- and postmenopausal women. RESULTS: At 28 days, more aneurysm growth was observed in ovariectomized rats than in males or non-ovariectomized female rats. The parent artery size was larger in male rats than in female or ovariectomized rats, as expected. Wall inflammation increased over time in all groups and was most severe in the decellularized female and ovariectomized groups at 28 days compared with the male group. Likewise, in these groups the most elastin fragmentation was seen at 28 days. In female rats, on days 1, 7, and 14, the intraluminal thrombus was mainly composed of red blood cells and fibrin. On days 14 and 28, macrophage and smooth muscle cell invasion inside the thrombus was shown, leading to the removal of red blood cells and deposition of collagen and elastin. On days 14 and 28, similar profiles of thrombus reorganization were observed in male and ovariectomized female rats. However, collagen content in thrombi and vessel wall macrophage content were higher in aneurysms of male rats at 28 days than in those of female rats. On day 28, thrombus coverage by endothelial cells was lower in ovariectomized than in female or male rats. Finally, analysis of human IA domes showed that endothelial cell coverage was lower in men and postmenopausal women than in younger women. CONCLUSIONS: Aneurysm growth and intraluminal thrombus resolution show sex-dependent differences. While certain processes (endothelial cell coverage and collagen deposition) point to a strong hormonal dependence, others (wall inflammation and aneurysm growth) seem to be influenced by both hormones and parent artery size.

Preoperative laboratory testing before pediatric neurosurgery: an NSQIP-Pediatrics analysis.

OBJECTIVES: The goal of this study was to evaluate clinical predictors of abnormal preoperative laboratory values in pediatric neurosurgical patients. METHODS: Data obtained in children who underwent a neurosurgical operation were extracted from the prospective National Surgical Quality Improvement Program-Pediatrics (NSQIP-P, 2012-2013) registry. Multivariable logistic regression evaluated predictors of preoperative laboratory values that might require further evaluation (white blood cell count < 2000/µl, hematocrit < 24%, platelet count < 100,000/µl, international normalized ratio > 1.4, or partial thromboplastin time > 45 seconds) or a preoperative transfusion (within 48 hours prior to surgery). Variables screened included patient demographics; American Society of Anesthesiologists (ASA) physical designation classification; comorbidities; recent steroid use, chemotherapy, or radiation therapy; and admission type. Predictive score validation was performed using the NSQIP-P 2014 data. RESULTS: Of the 6556 patients aged greater than 2 years, 68.9% (n = 5089) underwent laboratory testing, but only 1.9% (n = 125) had a critical laboratory value. Predictors of a laboratory abnormality were ASA class III-V; diabetes mellitus; hematological, hypothrombotic, or oncological comorbidities; nutritional support; recent chemotherapy; systemic inflammatory response syndrome; and a nonelective hospital admission. These 9 variables were used to create a predictive score, with a single point assigned for each predictor. The prevalence of critical values in the validation population (NSQIP-P 2014) of patients greater than 2 years of age was 0.3% with a score of 0, 1.0% in those with a score of 1, 1.6% in those with a score of 2, and 6.2% in those with a score ≥ 3. Higher score was predictive of a critical value (OR 2.33, 95% CI 1.91-2.83, p < 0.001, C-statistic 0.76) and with the requirement of a perioperative transfusion (intraoperatively or within 72 hours postoperatively; OR 1.42, 95% CI 1.22-1.67, p < 0.001) in the validation population. Moreover, when the same score was applied to children aged 2 years or younger, a greater score was predictive of a critical value (OR 2.47, 95% CI 2.15-2.84, p < 0.001, C-statistic 0.76). CONCLUSIONS: Critical laboratory values in pediatric neurosurgical patients are largely predicted by clinical characteristics, and abnormal preoperative laboratory results are rare in patients older than 2 years of age without comorbidities who are undergoing elective surgery. The NSQIP-P critical preoperative laboratory value scale is proposed to indicate patients with the highest odds of an abnormal value. The scale can assist with triaging preoperative testing based on the surgical risk, as determined by the treating surgeon and anesthesiologist.

Direct visualization of microcirculation impairment after acute subdural hemorrhage in a novel animal model.

OBJECTIVE: Direct brain compression and secondary injury due to increased intracranial pressure are believed to be the pathognomic causes of a grave outcome in acute subdural hemorrhage (aSDH). However, ischemic damage from aSDH has received limited attention. The authors hypothesized that cerebral microcirculation is altered after aSDH. Direct visualization of microcirculation was conducted in a novel rat model. METHODS: A craniectomy was performed on each of the 18 experimental adult Wistar rats, followed by superfusion of autologous arterial blood onto the cortical surface. Changes in microcirculation were recorded by capillary videoscopy. Blood flow and the partial pressure of oxygen in the brain tissue (PbtO2) were measured at various depths from the cortex. The brain was then sectioned for pathological examination. The effects of aspirin pretreatment were also examined. RESULTS: Instantaneous vasospasm of small cortical arteries after aSDH was observed; thrombosis also developed 120 minutes after aSDH. Reductions in blood flow and PbtO2 were found at depths of 2-4 mm. Blood-brain barrier disruption and thrombi formation were confirmed using immunohistochemical staining, while aspirin pretreatment reduced thrombosis and the impairment of microcirculation. CONCLUSIONS: Microcirculation impairment was demonstrated in this aSDH model. Aspirin pretreatment prevented the diffuse thrombosis of cortical and subcortical vessels after aSDH.

Timing and risks of chemoprophylaxis after spinal surgery: a single-center experience with 6869 consecutive patients.

OBJECTIVE Venous thromboembolism (VTE) after spinal surgery is a major cause of morbidity, but chemoprophylactic anticoagulation can prevent it. However, there is variability in the timing and use of chemoprophylactic anticoagulation after spine surgery, particularly given surgeons' concerns for spinal epidural hematomas. The goal of this study was to provide insight into the safety, efficacy, and timing of anticoagulation therapy after spinal surgery. METHODS The authors retrospectively examined records from 6869 consecutive spinal surgeries performed in their departments at Northwestern University. Data on patient demographics, surgery, hospital course, timing of chemoprophylaxis, and complications, including deep venous thrombosis (DVT), pulmonary embolism (PE), and spinal epidural hematomas requiring evacuation, were collected. Data from the patients who received chemoprophylaxis (n = 1904) were compared with those of patients who did not (n = 4965). The timing of chemoprophylaxis, the rate of VTEs, and the incidence of spinal epidural hematomas were analyzed. RESULTS The chemoprophylaxis group had more risk factors, including greater age (59.70 vs 51.86 years, respectively; p < 0.001), longer surgery (278.59 vs 145.66 minutes, respectively; p < 0.001), higher estimated blood loss (995 vs 448 ml, respectively; p < 0.001), more comorbid diagnoses (2.69 vs 1.89, respectively; p < 0.001), history of VTE (5.8% vs 2.1%, respectively; p < 0.001), and a higher number were undergoing fusion surgery (46.1% vs 24.7%, respectively; p < 0.001). The prevalence of VTE was higher in the chemoprophylaxis group (3.62% vs 2.03%, respectively; p < 0.001). The median time to VTE occurrence was shorter in the nonchemoprophylaxis group (3.6 vs 6.8 days, respectively; p = 0.0003, log-rank test; hazard ratio 0.685 [0.505-0.926]), and the peak prevalence of VTE occurred in the first 3 postoperative days in the nonchemoprophylaxis group. The average time of initiation of chemoprophylaxis was 1.46 days after surgery. The rates of epidural hematoma were 0.20% (n = 4) in the chemoprophylaxis group and 0.18% (n = 9) in the nonchemoprophylaxis group (p = 0.622). CONCLUSIONS The risks of spinal epidural hematoma among patients who receive chemoprophylaxis and those who do not are low and equivalent. Administering anticoagulation therapy from 1 day before to 3 days after surgery is safe for patients at high risk for VTE.

Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage.

OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor-κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH. CONCLUSIONS This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

Increased blood cell phosphatidylserine exposure and circulating microparticles contribute to procoagulant activity after carotid artery stenting.

OBJECTIVE Phosphatidylserine (PS) is a major component of the inner leaflet of membrane bilayers. During cell activation or apoptosis, PS is externalized to the outer membrane, providing an important physiological signal necessary for the release of the microparticles (MPs) that are generated through the budding of cellular membranes. MPs express PS and membrane antigens that reflect their cellular origin. PS exposure on the cell surface and the release of MPs provide binding sites for factor Xa and prothrombinase complexes that promote thrombin formation. Relatively little is known about the role of PS exposure on blood cells and MPs in patients with internal carotid artery (ICA) stenosis who have undergone carotid artery stenting (CAS). The authors aimed to investigate the extent of PS exposure on blood cells and MPs and to define its role in procoagulant activity (PCA) in the 7 days following CAS. METHODS The study included patients with ICA stenosis who had undergone CAS (n = 70), matched patients who had undergone catheter angiography only (n = 30), and healthy controls (n = 30). Blood samples were collected from all patients just before the procedure after an overnight fast and at 2, 6, 24, 48, and 72 hours and 7 days after the CAS procedure. Blood was collected from healthy controls after an overnight fast. Phosphatidylserine-positive (PS+) MPs and blood cells were analyzed by flow cytometry, while PCA was assessed with clotting time analysis, purified coagulation complex assays, and fibrin formation assays. RESULTS The authors found that levels of PS+ blood cells and PS+ blood cell-derived MPs (platelets and platelet-derived MPs [PMPs], neutrophils and neutrophil-derived MPs [NMPs], monocytes and monocyte-derived MPs [MMPs], erythrocytes and erythrocyte-derived MPs [RMPs], and endothelial cells and endothelial cell-derived MPs [EMPs]) were increased in the 7 days following the CAS procedure. Specifically, elevation of PS exposure on platelets/PMPs, neutrophils/NMPs, and monocytes/MMPs was detected within 2 hours of CAS, whereas PS exposure was delayed on erythrocytes/RMPs and EMPs, with an increase detected 24 hours after CAS. In addition, PS+ platelets/PMPs peaked at 2 hours, while PS+ neutrophils/NMPs, monocytes/MMPs, and erythrocytes/RMPs peaked at 48 hours. After their peak, all persisted at levels above baseline for 7 days post-CAS. Moreover, the level of PS+ blood cells/MPs was correlated with shortened coagulation time and significantly increased intrinsic and extrinsic Xase, thrombin generation, and fibrin formation. Pretreatment of blood cells with lactadherin at their peak time point after CAS blocked PS, resulting in prolonged coagulation times, decreased procoagulant enzyme activation, and fibrin production. CONCLUSIONS The results of this study suggest that increased exposure of PS on blood cells and MPs may contribute to enhanced PCA in patients with ICA stenosis who have undergone CAS, explaining the risk of perioperative thromboembolic complications in these patients. PS on blood cells and MPs may serve as an important biomarker for predicting, and as a pivotal target for monitoring and treating, acute postoperative complications after CAS. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: prospective cohort trial; evidence: Class I.

Superficial siderosis of the central nervous system associated with incomplete dural closure following posterior fossa surgery: report of 3 cases.

This report reviews a series of 3 patients who developed superficial siderosis following posterior fossa operations in which dural closure was incomplete. In all 3 patients, revision surgery and complete duraplasty was performed to halt the progression of superficial siderosis. Following surgery, 2 patients experienced resolution of their CSF xanthochromia while 1 patient had reduced CSF xanthochromia. In this paper the authors also review the etiology, pathophysiology, diagnosis, and treatment of this condition. The authors suggest that posterior fossa dural patency and pseudomeningocele are risk factors for the latent development of superficial siderosis and recommend that revision duraplasty be performed in patients with posterior fossa pseudomeningoceles and superficial siderosis to prevent progression of the disease.

Comparison of minimally invasive surgery with standard open surgery for vertebral thoracic metastases causing acute myelopathy in patients with short- or mid-term life expectancy: surgical technique and early clinical results.

OBJECT Spinal metastasis is common in patients with cancer. About 70% of symptomatic lesions are found in the thoracic region of the spine, and cord compression presents as the initial symptom in 5%-10% of patients. Minimally invasive spine surgery (MISS) has recently been advocated as a useful approach for spinal metastases, with the aim of decreasing the morbidity associated with more traditional open spine surgery; furthermore, the recovery time is reduced after MISS, such that postoperative chemotherapy and radiotherapy can begin sooner. METHODS Two series of oncological patients, who presented with acute myelopathy due to vertebral thoracic metastases, were compared in this study. Patients with complete paraplegia for more than 24 hours and with a modified Bauer score greater than 2 were excluded from the study. The first group (n = 23) comprised patients who were prospectively enrolled from May 2010 to September 2013, and who were treated with minimally invasive laminotomy/laminectomy and percutaneous stabilization. The second group (n = 19) comprised patients from whom data were retrospectively collected before May 2010, and who had been treated with laminectomy and stabilization with traditional open surgery. Patient groups were similar regarding general characteristics and neurological impairment. Results were analyzed in terms of neurological recovery (American Spinal Injury Association grade), complications, pain relief (visual analog scale), and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and EORTC QLQ-BM22 scales) at the 30-day follow-up. Operation time, postoperative duration of bed rest, duration of hospitalization, intraoperative blood loss, and the need and length of postoperative opioid administration were also evaluated. RESULTS There were no significant differences between the 2 groups in terms of neurological recovery and complications. Nevertheless, the MISS group showed a clear and significant improvement in terms of blood loss, operation time, and bed rest length, which is associated with a more rapid functional recovery and discharge from the hospital. Postoperative pain and the need for opioid administration were also significantly less pronounced in the MISS group. Results from the EORTC QLQ-C30 and QLQ-BM22 scales showed a more pronounced improvement in quality of life at follow-up in the MISS group. CONCLUSIONS In the authors' opinion, MISS techniques should be considered the first choice for the treatment for patients with spinal metastasis and myelopathy. MISS is as safe and effective for spinal cord decompression and spine fixation as traditional surgery, and it also reduces the impact of surgery in critical patients. However, further studies are needed to confirm these findings.

Increases in microvascular perfusion and tissue oxygenation via pulsed electromagnetic fields in the healthy rat brain.

OBJECT: High-frequency pulsed electromagnetic field stimulation is an emerging noninvasive therapy being used clinically to facilitate bone and cutaneous wound healing. Although the mechanisms of action of pulsed electromagnetic fields (PEMF) are unknown, some studies suggest that its effects are mediated by increased nitric oxide (NO), a well-known vasodilator. The authors hypothesized that in the brain, PEMF increase NO, which induces vasodilation, enhances microvascular perfusion and tissue oxygenation, and may be a useful adjunct therapy in stroke and traumatic brain injury. To test this hypothesis, they studied the effect of PEMF on a healthy rat brain with and without NO synthase (NOS) inhibition. METHODS: In vivo two-photon laser scanning microscopy (2PLSM) was used on the parietal cortex of rat brains to measure microvascular tone and red blood cell (RBC) flow velocity in microvessels with diameters ranging from 3 to 50 µm, which includes capillaries, arterioles, and venules. Tissue oxygenation (reduced nicotinamide adenine dinucleotide [NADH] fluorescence) was also measured before and for 3 hours after PEMF treatment using the FDA-cleared SofPulse device (Ivivi Health Sciences, LLC). To test NO involvement, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) was intravenously injected (10 mg/kg). In a time control group, PEMF were not used. Doppler flux (0.8-mm probe diameter), brain and rectal temperatures, arterial blood pressure, blood gases, hematocrit, and electrolytes were monitored. RESULTS: Pulsed electromagnetic field stimulation significantly dilated cerebral arterioles from a baseline average diameter of 26.4 ± 0.84 µm to 29.1 ± 0.91 µm (11 rats, p < 0.01). Increased blood volume flow through dilated arterioles enhanced capillary flow with an average increase in RBC flow velocity by 5.5% ± 1.3% (p < 0.01). Enhanced microvascular flow increased tissue oxygenation as reflected by a decrease in NADH autofluorescence to 94.7% ± 1.6% of baseline (p < 0.05). Nitric oxide synthase inhibition by L-NAME prevented PEMF-induced changes in arteriolar diameter, microvascular perfusion, and tissue oxygenation (7 rats). No changes in measured parameters were observed throughout the study in the untreated time controls (5 rats). CONCLUSIONS: This is the first demonstration of the acute effects of PEMF on cerebral cortical microvascular perfusion and metabolism. Thirty minutes of PEMF treatment induced cerebral arteriolar dilation leading to an increase in microvascular blood flow and tissue oxygenation that persisted for at least 3 hours. The effects of PEMF were mediated by NO, as we have shown in NOS inhibition experiments. These results suggest that PEMF may be an effective treatment for patients after traumatic or ischemic brain injury. Studies on the effect of PEMF on the injured brain are in progress.

Use of a cyanoacrylate skin adhesive to reduce external ventricular drain infection rates.

UNLABELLED: OBJECT.: Ventriculitis related to external ventricular drain (EVD) placement is a significant source of morbidity in neurological intensive care patients. Current rates of EVD-related infections range from 2% to 45% in the literature. The authors sought to determine if a 2-octyl cyanoacrylate adhesive would result in lower infection rate than standard semiocclusive dressings. METHODS: The authors tracked ventriculitis rates via CSF cultures among 259 patients whose EVD sites were dressed with sterile semiocclusive dressings and underwent routine sterile dressing exchanges every 48 hours. They analyzed data obtained in an additional 113 patients whose EVD sites were dressed one time with a surgical adhesive, 2-octyl cyanoacrylate. RESULTS: Ventriculitis rate in patients with standard bioocclusive dressings and wound care was 15.1%, whereas that in patients with a 2-octyl cyanoacrylate dressing was 3.54% (p = 0.002). Staphylococcus genus accounted for 79.5% of instances of ventriculitis among patients with bioocclusive dressings and routine wound care, whereas it accounted for 25.0% of the instances of ventriculitis among patients with a liquid polymer sealant dressing. A 90% reduction in Staphylococcus infection completely accounts for the observed effect (p = 0.04). CONCLUSIONS: The one-time application of 2-octyl cyanoacrylate to EVD wounds and exit sites provided superior protection against EVD-related ventriculitis compared to conventional EVD-site wound care. Likely this protection results from a barrier to the entry of gram-positive skin flora along the EVD exit tract. The results should be validated in a randomized trial.

Low risk for subsequent subarachnoid hemorrhage for emergency department patients with headache, bloody cerebrospinal fluid, and negative findings on cerebrovascular imaging.

UNLABELLED: OBJECT.: When patients present to the emergency department (ED) with acute headache concerning for subarachnoid hemorrhage (SAH) and a lumbar puncture (LP) shows blood in the CSF, it is difficult to distinguish the results of a traumatic LP from those of SAH. CT angiography (CTA) is often performed, but the long-term outcome for patients with a positive LP and normal neurovascular imaging remains uncertain. The primary objective of this study was to determine whether patients who presented to the ED with acute headache and had red blood cells (RBCs) in their CSF on LP but negative cerebrovascular imaging suffered subsequent SAH. METHODS: A case series study of consecutive adult ED patients who incurred charges for LP between 2001 and 2009 was performed from 2010 through 2011. Inclusion criteria were: headache, > 5 RBCs/mm(3) in CSF, noncontrast head CT with no evidence of hemorrhage, and cerebrovascular CTA or MRA without aneurysm or vascular lesion within 2 weeks of the ED visit. Patients with less than 6 months of available follow-up were excluded. The primary outcomes were 1) subsequent nontraumatic SAH and 2) new vascular lesion. Secondary outcomes were complications related to SAH, or LP or angiography. RESULTS: Of 4641 ED patients billed for an LP, 181 patients (mean age 42 years) were included in this study. Over a median follow-up of 53 months, 0 (0%) of 181 patients (95% CI 0%-2.0%) had a subsequent SAH or new vascular lesion identified. Although not the primary outcome, there was 1 patient who was ultimately diagnosed with vasculitis. Eighteen (9.9%) of 181 patients (95% CI 6.0%-15.3%) had an LP-related complication and 0 (0%) of 181 patients (95% CI 0%-2.0%) had an angiography-related complication. CONCLUSIONS: Patients who present to the ED with acute headache concerning for SAH and have a finding of bloody CSF on LP but negative findings on cerebrovascular imaging are at low risk for subsequent SAH and thus are likely to be safe for discharge. Replacement of the CT/LP with a CT/CTA diagnostic algorithm merits further investigation.