Permanent Neurologic Injury Research Articles

A review of medical malpractice cases in congenital cardiac surgery in the Westlaw database in the United States from 1994 to 2019

Medical malpractice litigations are common for cardiac surgeons, and congenital cardiac surgeons are uniquely held accountable by patients, who are minors, and their families. Therefore, it is imperative for physicians to be cognizant of clinically effective and legally tenable practices. The Westlaw legal research service was utilized to collect medical malpractice litigations from 1994 to 2019 pertaining to congenital cardiac surgery, inclusive, in the United States. Court documents were manually screened, with 177 litigations satisfying criteria for inclusion. Data collection included patient demographics, verdict and litigation characteristics, and clinical data. Fisher's exact test was used to assess the significance of association. Across the 177 litigations, 44% had defendant verdicts, 30% had plaintiff verdicts, and 26% had settlements. The average plaintiff award was $9,363,710, and the average settlement was $4,141,825. Patient mortality occurred in 87 cases (49.2%), and wrongful death claims were argued in 71 cases (40%). The most common reason for litigation were procedural errors (79 cases, 45%). The most frequent clinical event was cardiac arrest (95 cases, 54%). California recorded the most litigations (34 cases, 19.2%). Defendant verdicts were significantly associated with cardiac arrest, procedural errors, and permanent neurological injury (p < .05). Defendant's verdicts were more common in cases with patient mortality, which had lower average plaintiff awards and settlements, since future healthcare expenses are inapplicable to this cohort. Future litigations can be minimized with an emphasis on reducing procedural errors, treating and diagnosing patients timely, and monitoring patients sufficiently.

The Protective Effects of Juglanin in Cerebral Ischemia Reduce Blood-Brain Barrier Permeability via Inhibition of VEGF/VEGFR2 Signaling.

IntroductionIschemic brain injury due to stroke or other pathologies is a major contributor to disability and mortality worldwide. Upon the occurrence of stroke, neuronal cells undergo apoptosis due to the deprivation of oxygen and nutrients and failure of the blood–brain barrier (BBB). In the moments immediately following a stroke, widespread perfusion resulting from hyperpermeability is accompanied by an acute inflammatory response, which induces neovascularization and often permanent neurological injury. Vascular endothelial growth factor (VEGF) and its receptor VEGF receptor 2 (VEGFR2) have been targeted to suppress cerebral ischemia. Recently, natural products including flavonoids, such as juglanin, have been receiving increasing attention for their impressive physiological effects.MethodsTwenty mg/kg body weight juglanin was administrated for 3 weeks before inducing middle cerebral artery occlusion (MCAO) in mice. The animal brain infarction volume, neurological deficit score, blood–brain barrier permeability, and the expression of tight junction proteins were evaluated. Endothelial permeability and tight junction protein expression were also assessed in brain microvascular endothelial cells (HMBVECs) exposed to oxygen–glucose deprivation/reperfusion (OGD/R).ResultsJuglanin significantly reduced occlusion-induced infarct volume and improved neurological score by suppressing BBB hyperpermeability. Juglanin inhibited both the mRNA and protein expression of VEGF and VEGFR2 and restored the normal expression of occludin and zonula occludens-1 (ZO-1), two important tight junction proteins, in MCAO mice. Meanwhile, the results of in vitro experiments show that the protective effects of juglanin against increased BBB permeability and reduced tight junction functionality are dependent on the VEGF/VEGFR2 signaling pathway, as evidenced by the capacity of exogenous VEGF-A to abolish the effects of juglanin.ConclusionOur findings indicate a potent ability of juglanin to prevent neuronal injury resulting from cerebral ischemia by modulating the VEGF/VEGFR2 signaling pathway. Further research will help elucidate the exact mechanisms behind the protective effects of juglanin.

Anticancer Drugs and the Nervous System.

This article reviews the clinical features, prognosis, and treatment of neurotoxicity from anticancer drugs, including conventional cytotoxic chemotherapy, biologics, and targeted therapies, with a focus on the newer immunotherapies (immune checkpoint inhibitors and chimeric antigen receptor T cells). Whereas neurologic complications from traditional chemotherapy are widely recognized, newer cancer therapies, in particular immunotherapies, have unique and distinct patterns of neurologic adverse effects. Anticancer drugs may cause central or peripheral nervous system complications. Neurologic complications of therapy are being seen with increasing frequency as patients with cancer are living longer and receiving multiple courses of anticancer regimens, with novel agents, combinations, and longer duration. Neurologists must know how to recognize treatment-related neurologic toxicity since discontinuation of the offending agent or dose adjustment may prevent further or permanent neurologic injury. It is also imperative to differentiate neurologic complications of therapy from cancer progression into the nervous system and from comorbid neurologic disorders that do not require treatment dose reduction or discontinuation. Neurotoxicity from cancer therapy is common, with effects seen on both the central and peripheral nervous systems. Immune checkpoint inhibitor therapy and chimeric antigen receptor T-cell therapy are new cancer treatments with distinct patterns of neurologic complications. Early recognition and appropriate management are essential to help prevent further neurologic injury and optimize oncologic management.

Analysis of Chest-Compression Depth and Full Recoil in Two Infant Chest-Compression Techniques Performed by a Single Rescuer: Systematic Review and Meta-Analysis.

Pediatric cardiac arrest is associated with high mortality and permanent neurological injury. We aimed to compare the effects of the two-thumb (TT) and two-finger (TF) techniques in infant cardiopulmonary resuscitation (CPR) performed by a single rescuer. We searched PubMed, EMBASE, and CENTRAL for randomized control trials published before December 2019. Studies comparing the TT and TF techniques in infant CPR were included for meta-analysis. Relevant information was extracted for methodological assessment. Twelve studies were included. The TT technique was associated with deeper chest-compression depth (mean difference: 4.71 mm; 95% confidence interval: 3.61 to 5.81; p < 0.001) compared with the TF technique. The TF technique was better in terms of the proportion of complete chest recoil (mean difference: −11.73%; 95% confidence interval: −20.29 to −3.17; p = 0.007). CPR was performed on a manikin model, and the application of the results to real human beings may be limited. The TT technique was superior to the TF technique in terms of chest-compression depth, but with inferior chest full recoil. Future investigations should focus on modifying the conventional TT technique to generate greater compression depth and achieve complete chest recoil.

The prediction of intraoperative cervical cord function changes by different motor evoked potentials phenotypes in cervical myelopathy patients

BackgroundSurgery is usually the treatment of choice for patients with cervical compressive myelopathy (CCM). Motor evoked potential (MEP) has proved to be helpful tool in evaluating intraoperative cervical spinal cord function change of those patients. This study aims to describe and evaluate different MEP baseline phenotypes for predicting MEP changes during CCM surgery.MethodsA total of 105 consecutive CCM patients underwent posterior cervical spine decompression were prospectively collected between December 2012 and November 2016. All intraoperative MEP baselines recorded before spinal cord decompression were classified into 5 types (I to V) that were carefully designed according to the different MEP parameters. The postoperative neurologic status of each patient was assessed immediately after surgery.ResultsThe mean intraoperative MEP changes range were 10.2% ± 5.8, 14.7% ± 9.2, 54.8% ± 31.9, 74.1% ± 24.3, and 110% ± 40 in Type I, II, III, IV, and V, respectively. There was a significant correlation of the intraoperative MEP change rate with different MEP baseline phenotypes (r = 0.84, P < 0.01). Postoperative transient new spinal deficits were found 0/31 case in Type I, 0/21 in Type II, 1/14 in Type III, 2/24 in Type IV, and 4/15 in Type V. No permanent neurological injury was found in our cases series.ConclusionsThe MEP baselines categories for predicting intraoperative cervical cord function change is proposed through this work. The more serious the MEP baseline abnormality, the higher the probability of intraoperative MEP changes, which is beneficial to early warning for the cervical cord injury.

Spinal Tranexamic Acid—A New Killer in Town

(Anaesthesia. 2019;74:831–833) Tranexamic acid has become an important component in the management of postpartum hemorrhage since the WOMAN trial was published in 2017. A recent article by Patel and colleagues identified 21 case reports of accidental spinal administration of tranexamic acid, with several occurring in women receiving spinal anesthesia for cesarean delivery. These drug errors resulted in a mortality rate &gt;50% and permanent neurological injuries in many survivors.

Challenges to Neurosurgery During the Coronavirus Disease 2019 (COVID-19) Pandemic

The coronavirus disease 2019 pandemic has presented a massive burden to most health care systems across the globe. The demand for intensive care unit capacity in particular has increased significantly, and hospitals in most affected regions have struggled to cope. The focus of health care activity has shifted to the pandemic, with a negative impact on the management of other conditions.Neurosurgery, like most specialties, has been drastically affected but, arguably, warrants special considerations because many of the treatments required are time-critical. Lack or delay of appropriate intervention may lead, for an individual patient, to permanent neurologic injury and a significant decline in function and quality of life, or even death.In this report, we consider the challenges that neurosurgeons currently face in relation to the pandemic and are likely to face in the foreseeable future. The challenges are multifaceted with practical, ethical, legal, and other implications. These include re-deployment of staff to areas outside neurosurgery, treatment priority setting, ethical decision-making and risk of moral injury, as well as medicolegal risks, financial uncertainties and implications for training, research, and global health work. As well as patients, these challenges will affect neurosurgeons as doctors and as humans. The international neurosurgical community has a moral duty to contribute to the global response to the COVID-19 crisis, but also to retain a duty to care for individual patients.

Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389.

Congenital hyperinsulinism (CHI) is a significant cause of hypoglycaemia in neonates and infants with the potential for permanent neurologic injury. Accurate calculations of the incidence of rare diseases such as CHI are important as they inform health care planning and can aid interpretation of genetic testing results when assessing the frequency of variants in large-scale, unselected sequencing databases. Whilst minimal incidence rates have been calculated for four European countries, the incidence of CHI in the UK is not known. In this study we have used referral rates to a central laboratory for genetic testing and annual birth rates from census data to calculate the minimal incidence of CHI within the UK from 2007 to 2016. CHI was diagnosed in 278 individuals based on inappropriately detectable insulin and/or C-peptide measurements at the time of hypoglycaemia which persisted beyond 6 months of age. From these data, we have calculated a minimum incidence of 1 in 28,389 live births for CHI in the UK. This is comparable to estimates from other outbred populations and provides an accurate estimate that will aid both health care provision and interpretation of genetic results, which will help advance our understanding of CHI.

Prospective audit of sedation/anesthesia practices for children undergoing computerized tomography in a tertiary care institute.

Background and Aims:The aim of the study was to enumerate the sedative drugs used, assess the efficacy of sedative drugs, and determine the incidence of adverse events.Material and Methods:A prospective audit of children sedated for computerized tomography (CT) by anesthesiology team was conducted for a period of 4 months. The data included patient demographic variables, fasting period, medications administered, adequacy of sedation, imaging characteristics, adverse events, and requirement for escalated care.Results:A total of 331 children were enrolled for sedation by the anesthesia team. The drugs used for sedation were propofol, ketamine, and midazolam. Twenty-two percent children received one sedative drug, 60% children were administered two drugs, and 5% children required a combination of all three drugs for successful sedation. Sedation was effective for successful conduct of CT scan in 95.8% patients without the requirement of a repeat scan. Twelve (5%) children experienced adverse events during the study period. However, none of the adverse events necessitated prolonged postprocedural hospitalization or resulted in permanent neurologic injury or death.Conclusions:The current practice of sedation with propofol, ketamine, and midazolam, either single or in combination was efficacious in a high percentage of patients. The incidence of adverse events during the study period was low.

Uncertainty of somatosensory evoked potentials during neurosurgical procedure

The objective of measurement of bio-signals in measurement uncertainty is not to determine the true value as closely as possible, but to determine a measured value and to assign the interval of the value. The measurement uncertainty is estimated by type A and B evaluations, depending on whether they are evaluated by statistics or the mathematical probability theory. Intraoperative neurophysiologic monitoring is used often for early detection of inherent risk relevant to neurosurgical procedures leading to permanent neurological injury, while it is still potentially reversible. In this study, we evaluated the uncertainties in somatosensory evoked potentials (SSEPs), which are used for monitoring sensory neural pathways. In a 45-year-old man who underwent cervical laminectomy, SSEPs were monitored using the ISIS IOM SYSTEM (Inomed, Emendingen, Germany) to evaluate the uncertainties. Expanded uncertainty were 0.88 mV and 1.22 ms, for amplitude and latency, respectively. Measured values and corresponding uncertainties of amplitude and latency were 2.78 ± 0.88 mV and 24.02 ± 1.22 ms, respectively. The expanded uncertainty (0.88 mV) of the amplitude was approximately 30% of the mean value (2.78 mV). A reasonable explanation for this would be the effects of variables such as electromagnetic waves (diathermy and warming blankets), temperature, blood pressure, sex and body mass index on SSEPs. Careful attention is required in interpreting SSEPs.

Risk factors, management, and outcomes of amniotic fluid embolism: A multicountry, population-based cohort and nested case-control study.

BackgroundAmniotic fluid embolism (AFE) remains one of the principal reported causes of direct maternal mortality in high-income countries. However, obtaining robust information about the condition is challenging because of its rarity and its difficulty to diagnose. This study aimed to pool data from multiple countries in order to describe risk factors, management, and outcomes of AFE and to explore the impact on the findings of considering United Kingdom, international, and United States AFE case definitions.Methods and findingsA population-based cohort and nested case-control study was conducted using the International Network of Obstetric Survey Systems (INOSS). Secondary data on women with AFE (n = 99–218, depending on case definition) collected prospectively in population-based studies conducted in Australia, France, the Netherlands, Slovakia, and the UK were pooled along with secondary data on a sample of control women (n = 4,938) collected in Australia and the UK. Risk factors for AFE were investigated by comparing the women with AFE in Australia and the UK with the control women identified in these countries using logistic regression. Factors associated with poor maternal outcomes (fatality and composite of fatality or permanent neurological injury) amongst women with AFE from each of the countries were investigated using logistic regression or Wilcoxon rank–sum test. The estimated incidence of AFE ranged from 0.8–1.8 per 100,000 maternities, and the proportion of women with AFE who died or had permanent neurological injury ranged from 30%–41%, depending on the case definition. However, applying different case definitions did not materially alter findings regarding risk factors for AFE and factors associated with poor maternal outcomes amongst women with AFE. Using the most liberal case definition (UK) and adjusting for the severity of presentation when appropriate, women who died were more likely than those who survived to present with cardiac arrest (89% versus 40%, adjusted odds ratio [aOR] 10.58, 95% confidence interval [CI] 3.93–28.48, p < 0.001) and less likely to have a source of concentrated fibrinogen (40% versus 56%, aOR 0.44, 95% CI 0.21–0.92, p = 0.029) or platelets given (24% versus 49%, aOR 0.23, 95% CI 0.10–0.52, p < 0.001). They also had a lower dose of tranexamic acid (median dose 0.7 g versus 2 g, p = 0.035) and were less likely to have had an obstetrician and/or anaesthetist present at the time of the AFE (61% versus 75%, aOR 0.38, 95% CI 0.16–0.90, p = 0.027). Limitations of the study include limited statistical power to examine factors associated with poor maternal outcome and the potential for residual confounding or confounding by indication.ConclusionsThe findings of our study suggest that when an AFE is suspected, initial supportive obstetric care is important, but having an obstetrician and/or anaesthetist present at the time of the AFE event and use of interventions to correct coagulopathy, including the administration of an adequate dose of tranexamic acid, may be important to improve maternal outcome. Future research should focus on early detection of the coagulation deficiencies seen in AFE alongside the role of tranexamic acid and other coagulopathy management strategies.

NIMG-08. 2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN BRAINSTEM TUMOR PATIENTS IN VIVO

Abstract Evaluation of 2-hydroxyglutarate (2HG) by magnetic resonance spectroscopy (MRS) has significant application in assessing the isocitrate dehydrogenase (IDH) mutational status in brain tumor patients noninvasively. This clinical role of 2HG MRS may be demonstrated most clearly in patients with brainstem lesions, where surgical biopsy presents high risk of permanent neurological injury. We conducted 2HG MRS in 20 subjects with a radiographically identified brainstem tumor (13 male and 7 female, age 20 - 73, median age 38). Proton MRS data was acquired from the T2-FLAIR volume using a 2HG-tailored MRS protocol (PRESS TE 97 ms). The millimolar concentration of 2HG was estimated with reference to water. Excluding data with unacceptable quality, data from 16 patients were included in subsequent analysis. The 16 patients were clearly divided into two groups in terms of 2HG level. The tumors in 5 patients showed a clearly discernible 2HG signal (2.25 ppm) while those in 11 patients did not. The 2HG estimation ranged from 2.1 to 6.3 mM in the 5 patients (IDH mutation) and from 0 to 0.7 mM in the 11 patients (most likely IDH wildtype). The mean concentration of 2HG differed significantly between the groups (p=3.3×10−6). One tumor was confirmed to be IDH mutated from autopsy. A representative case for 2HG MRS utility was a patient in whom 2HG was estimated to be 5.3 mM in the first MRS scan and the clinical decision was made to follow with 2HG MRS without surgery and chemoradiation therapy. The patients had 22 follow-up MRS scans for 5.4 years (scan intervals ~3 months), during which the tumor was stable clinically and radiographically. The present study demonstrates the clinical utility of 2HG MRS in brainstem tumors. 2HG MRS provides reliable estimation of 2HG and can be utilized for evaluating the IDH mutation status in brainstem lesion noninvasively.

Safe Injectate Choice, Visualization, and Delivery for Lumbar Transforaminal Epidural Steroid Injections: Evolving Literature and Considerations

Lumbar transforaminal epidural steroid injection (TFESI) is a widely used treatment for lumbar radicular pain refractory to conservative care. However, rare but serious risks exist. This article summarizes the recent literature regarding considerations relevant to safe performance of TFESIs. We collated recent case report reporting of permanent neurologic injury after TFESI, which has been theorized to occur as a result of disrupted radiculomedullary arterial blood flow to the spinal cord. We also review how injectate selection, visualization methods, and delivery techniques may impact the safety considerations of these injections. While TFESIs are safe, there is continued need to optimize injectate selection, visualization methods, and delivery techniques to minimize the possibility of complications while maintaining clinical effectiveness.

ASIPP Guidelines for Sedation and Fasting Status of Patients Undergoing Interventional Pain Management Procedures

Many of the patients undergoing interventional procedures have daily regimens of medications including analgesics, muscle relaxants, and other drugs that can have significant additive/synergistic effects during the perioperative period. Further, many patients also present with comorbid states, including obesity, cardiovascular, and pulmonary disease. Consequently, in the perioperative period, a significant number of patients have suffered permanent neurologic injury, hypoxic brain injury, and even death as a result of over sedation, hypoventilation, and spinal cord injury. In addition, physicians are concerned about aspiration, subsequent complications, and as a result, they ask patients to fast for several hours prior to the procedures. Based on extensive literature and consensus, a minimum fasting period is established as 2 hours before a procedure for clear liquids and 4 hours before procedure for light meals, rather than having all patients fast for 8 hours or even fasting beginning at midnight the night before the procedure. Gastrointestinal stimulants, gastric acid secretion blockers, and antacids may be used, even though not routinely recommended. Due to the nature of chronic pain and anxiety, many patients undergoing interventional techniques may require mild to moderate sedation. Deep sedation and/or general anesthesia for most interventional procedures is considered as unsafe, since the patient cannot communicate acute changes in symptoms, thus, resulting in morbidity and mortality, as well as creating compliance issues. We are adapting the published standards of the American Society of Anesthesiologists for monitoring patients under sedation, regardless of the location of the procedure, either office-based, in a surgery center, or a hospital outpatient department. These standards include monitoring of blood pressure, cardiac rhythm, temperature, pulse oximetry, and continuous quantitative end tidal CO2 monitoring. Sedation must be provided either by qualified anesthesia or non-anesthesia providers, with appropriate understanding of the medications, drug interactions, and resuscitative protocols. Key words: Guidelines, sedation, fasting status, monitoring, neurological complications

Multimodality Intraoperative Neuromonitoring in Severe Thoracic Deformity Posterior Vertebral Column Resection Correction

Multimodal intraoperative neuromonitoring (IONM) has been proposed as an effective way to reduce permanent neurologic injury during spinal deformity surgery. However, few studies have reported evoked potential changes at different surgical stages of thoracic posterior vertebral column resection (PVCR). A total of 82 cases with severe thoracic deformity (Yang's A type) treated by PVCR in a single institution between January 2010 and March 2015 were reviewed. Multimodal IONM including somatosensory evoked potential, motor evoked potential, and descending neurogenic evoked potential was performed for real-time assessment of spinal cord function during surgery. The risk factors of neuromonitoring events at different surgical stages were documented and analyzed. Multimodal IONM was successfully performed in all 82 cases. Thirty-nine neuromonitoring events presented in 27 (32.9%) cases. Neurologic monitoring events were more likely to occur in patients with larger scoliosis and kyphosis, longer osteotomy closure distance, more Halo gravity traction, more screw insertion, and higher PVCR segments. The reasons for monitoring changes included 6 events during screw insertion, 20 during osteotomy, 9 during osteotomy gap closure, and 4 during deformity correction. New postoperative neurologic deficits were observed in 11 (13.4%) cases including 1 incomplete paraplegia, 8 transient cord deficits, and 2 nerve root injuries. Multimodal IONM can effectively identify neurologic deficits throughout surgery. Osteotomy and osteotomy gap closure are the surgical stages with the highest neurologic risks during PVCR procedures. It is imperative to improve dexterity since the majority of neuromonitoring events are caused by surgical techniques.

Selective versus standard cerebro-myocardial perfusion in neonates undergoing aortic arch repair: A multi-center study.

The results of neonatal aortic arch surgery using cerebro-myocardial perfusion were analyzed. Selective cerebral and myocardial perfusion, using two separate pump rotors, was compared with standard perfusion, using a single pump rotor with an arterial line Y-connector. Between May 2008 and May 2016, 69 consecutive neonates underwent arch repair using either selective cerebro-myocardial perfusion (Group A, n=34) or standard perfusion (Group B, n=35). The groups were similar for age, weight, BSA, prevalence of one-stage or staged repair, and single ventricle palliation; male gender was more frequent in Group A. The duration of the cerebro-myocardial perfusion was comparable (27±8 vs. 28±7 min, P=0.9), with higher flows in Group A (57±27 vs. 39±19 mL/kg/min, P=0.01). Although cardioplegic arrest was more common in Group B (13/34 vs. 23/35, P=0.03), the duration of myocardial ischemia was longer in Group A (64±41 vs. 44±14 min, P=0.04). There was 1 hospital death in each group, with no permanent neurological injury in either group. Cardiac morbidity (1/34 vs. 7/35, P=0.02) was more common in Group B, while extracardiac morbidity was similar in both the groups. During follow-up (3.2±2.4 years), 5 late deaths occurred with a comparable 5-year survival rate (75±17% vs. 88±6%, P=0.7) and freedom from arch reintervention (86±6% vs. 84±7%, P=0.6). Risk of cardiac morbidity was greater with standard cerebro-myocardial perfusion (OR=5.2, CI 3.3-6.8, P=0.001) and with perfusion flows less than 50 mL/kg/min (OR 3.7, CI 1.87-5.95, P=0.04). Cerebro-myocardial perfusion is a safe and effective strategy to protect the brain and heart in neonates undergoing arch repair. Selective techniques using higher perfusion flows may further attenuate cardiac morbidity.

Intraoperative neurophysiological monitoring during spinal surgery

Intraoperative neurophysiological monitoring (IOM) is a technique that may contribute to avoiding permanent neurological injury during spine surgery procedure, especially in patients undergoing scoliosis correction. In the last 12 months 26 patients underwent spinal procedures for scoliosis and kyphosis, spinal (cervical or lumbar) stenosis, degenerative disc disease; a patient with posttraumatic L1 fracture and a patient with intradural extramedullary neurinoma were monitored too. TIVA-TCI anesthesia was used in all patients while muscle relaxants were limited only during some patient’s intubation. SEPs (median and tibial nerve) and MEPs (ADM and TA-AH muscles and in cervical surgery also deltoid and ECD muscles) were attempted in all patients. Spontaneous EMG activity was also recorded from multiple muscles. Only in two cases we had significant prolonged alterations of IOM: during a D3 neurinoma surgery we observed the loss of MEPs from a leg with return at normality after a stop and change of neurosurgery procedures; in a decompression/stabilization D10-S1 cortical SEPs and MEPs of right leg slowly reduced progressively until the end of surgery (with a slight transitory paresis). The use of IOM in spine surgery affects positively the neurological outcome so that it has to become a routine procedure.

Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury

Fifteen million babies are born preterm every year and a significant number suffer from permanent neurological injuries linked to white matter injury (WMI). A chief cause of preterm birth itself and predictor of the severity of WMI is exposure to maternal-fetal infection-inflammation such as chorioamnionitis. There are no neurotherapeutics for this WMI. To affect this healthcare need, the repurposing of drugs with efficacy in other white matter injury models is an attractive strategy. As such, we tested the efficacy of GSK247246, an H3R antagonist/inverse agonist, in a model of inflammation-mediated WMI of the preterm born infant recapitulating the main clinical hallmarks of human brain injury, which are oligodendrocyte maturation arrest, microglial reactivity, and hypomyelination. WMI is induced by mimicking the effects of maternal-fetal infection-inflammation and setting up neuroinflammation. We induce this process at the time in the mouse when brain development is equivalent to the human third trimester; postnatal day (P)1 through to P5 with i.p. interleukin-1β (IL-1β) injections. We initiated GSK247246 treatment (i.p at 7 mg/kg or 20 mg/kg) after neuroinflammation was well established (on P6) and it was administered twice daily through to P10. Outcomes were assessed at P10 and P30 with gene and protein analysis. A low dose of GSK247246 (7 mg/kg) lead to a recovery in protein expression of markers of myelin (density of Myelin Basic Protein, MBP & Proteolipid Proteins, PLP) and a reduction in macro- and microgliosis (density of ionising adaptor protein, IBA1 & glial fibrillary acid protein, GFAP). Our results confirm the neurotherapeutic efficacy of targeting the H3R for WMI seen in a cuprizone model of multiple sclerosis and a recently reported clinical trial in relapsing-remitting multiple sclerosis patients. Further work is needed to develop a slow release strategy for this agent and test its efficacy in large animal models of preterm infant WMI.

Intraoperative Neuromonitoring During Thyroid Surgery: The Effect of Surgical Positioning.

Intraoperative neuromonitoring during thyroid surgery has been used to successfully prevent permanent neurological injury by early identification of anatomical variants. Proper interpretation of neuromonitoring data requires knowledge of what factors might affect the data. In this study, we examined the effect of surgical positioning on the latency and amplitude of neural recordings made from the vocalis muscle during thyroid surgery. A retrospective review was performed of 145 patients who underwent thyroid surgery. Eighty-three had open cervical procedures, and 62 had robotic-assisted transaxillary procedures. Intraoperative neuromonitoring recordings were made by stimulation of the vagus and recurrent laryngeal nerves for both groups. Ultrasound measurements were made of a subset of the transaxillary patients immediately before and after arm positioning. Groups differed only on right-sided recordings. Patients with transaxillary surgeries had significantly shorter latencies evoked from the vagus nerve. We found that vagus nerve-evoked latencies were also correlated to ultrasound measurements of the nerves. Surgical positioning during thyroid surgery is a factor that may affect intraoperative neuromonitoring data and should be taken into account by the surgeon during interpretation.

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: achieving lumbar interbody fusion: 199. Use of motor evoked potentials during lateral lumbar interbody fusion reduces postoperative deficits

BACKGROUND CONTEXT Intraoperative neurophysiological monitoring (IONM) has gained rather wide-spread acceptance as a method to mitigate risk to the lumbar plexus during Lateral Lumbar Interbody Fusion (LLIF) surgery. The most common approach to IONM involves using only electromyography (EMG) monitoring, and the rate of postoperative deficit remains unacceptably high. Other test modalities, such as transcranial electric motor-evoked potentials (tcMEPs) and somatosensory-evoked potentials (SSEPs), may be more suitable for monitoring neural integrity but they have not been widely adopted during LLIF. Recent studies have begun to examine their utility in monitoring LLIF surgery with favorable results. PURPOSE To evaluate the efficacy of different IONM paradigms in the prevention of iatrogenic neurologic sequelae during LLIFand to specifically evaluate the utility of including tcMEPs in an IONM strategy for LLIF surgery. STUDY DESIGN/SETTING Nonrandomized, retrospective analysis of 479 LLIF procedures at a single institution over a 4-year period. During the study epoch, three different IONM strategies were employed for LLIF procedures: (1) Surgeon-directed T-EMG monitoring (“SD-EMG”), (2) neurophysiologist-controlled T-EMG monitoring (“NC-EMG”), and (3) neurophysiologist-controlled T-EMG monitoring supplemented with MEP monitoring (“NC-MEP”). PATIENT SAMPLE The patient population was comprised of 254 males (53.5%) and 221 females (46.5%). Patient age ranged from a minimum of 21 years to a maximum of 89 years, with a mean of 56.6 years. OUTCOME MEASURES Physician-documented physiologic measures included manual muscle test (MMT) grading of hip-flexion, hip-adduction, or knee-extension, as well as hypo- or hyperesthesia of the groin and/or anterolateral thigh on the surgical side. Self-reported measures included numbness or tingling in the groin and/or anterolateral thigh on the surgical side. METHODS Patient progress notes were reviewed from the postoperative period up to 12 months after surgery. The rates of postoperative sensory and/or motor deficit consistent with lumbar plexopathy or peripheral nerve palsy on the surgical side were compared between the three cohorts. RESULTS Using the dependent measure of neurologic deficit, whether motor and/or sensory, patients with NC-MEP monitoring had the lowest rate of immediate postoperative deficit (22.3%), compared to NC-EMG monitoring (37.1%) and SD-EMG monitoring (40.4%). This result extended to sensory deficits consistent with lumbar plexopathy (pure motor deficits being excluded); patients with NC-MEP monitoring had the lowest rate (20.5%) compared to NC-EMG monitoring (34.3%) and SD-EMG monitoring (36.9%). Additionally, evaluation of postoperative motor deficits consistent with peripheral nerve palsy (pure sensory deficits being excluded), the NC-MEP group had the lowest rate (5.7%) of motor deficit compared to the SD-EMG (17.0%) and NC-EMG (17.1%) cohorts. Finally, when assessing only those patients whose last follow-up was greater than or equal to 12 months (n=251), the rate of unresolved motor deficits was significantly lower in the NC-MEP group (0.9%), as compared to NC-EMG (6.9%) and SD-EMG (11.0%). Comparison of the NC-MEP versus NC-EMG and SD-EMG groups, both independently and combined, was statistically significant (>95% confidence level) for all analyses. CONCLUSIONS The results of the present study indicate that preservation of tcMEPs from the adductor longus, quadriceps, and tibialis anterior muscles are of paramount importance for limiting iatrogenic sensory and motor injuries during LLIF surgery. In this regard, the inclusion of tcMEPs serves to compliment EMG and allows for the periodic, functional assessment of at-risk nerves during these procedures. Thus, tcMEPs appear to be the most effective modality for the prevention of both transient and permanent neurologic injury during LLIF surgery. We propose that the standard paradigm for protecting the nervous system during LLIF be adapted to include tcMEPs.