Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Current Neurologic Assessment and Neuroprotective Strategies in Cardiac Anesthesia: A Survey to the Membership of the Society of Cardiovascular Anesthesiologists.

BACKGROUND: Neurologic injury and cognitive disorder after cardiac surgery are associated with morbidity and mortality. Variability in the application of neuroprotective strategies likely exists during cardiac surgery. The Society of Cardiovascular Anesthesiologists (SCA) conducted a survey among its members on common perioperative neuroprotective strategies: assessment of aortic atheromatous burden, management of intraoperative blood pressure, and use of cerebral oximetry. METHODS: A 15-item survey was developed by 3 members of the SCA Continuous Practice Improvement - Cerebral Protection Working Group. The questionnaire was then circulated among all working group members, adapted, and tested for face validity. On March 26, 2018, the survey was sent to members of the SCA via e-mail using the Research Electronic Data Capture system. Responses were recorded until April 16, 2018. RESULTS: Of the 3645 surveys e-mailed, 526 members responded (14.4%). Most responders worked in academic institutions (58.3%), followed by private practices (38.7%). Epiaortic ultrasound for the assessment of aortic atheromatous burden was most commonly utilized at the surgeon's request (46.5%). Cerebral oximetry was most commonly used in patients with increased perioperative risk of cerebral injury (41.4%). Epiaortic ultrasound (1.9%) and cerebral oximetry (5.2%) were rarely part of a standardized monitoring approach. A majority of respondents (52.0%) reported no standardized management strategies for neuroprotection during cardiac surgery at their institution. A total of 55.3% stated that no standardized institutional guidelines were in place for managing a patient's blood pressure intraoperatively or during cardiopulmonary bypass. When asked about patients at risk for postoperative cerebral injury, 41.3% targeted a blood pressure goal >65 mmHg during cardiopulmonary bypass. The majority of responders (60.4%) who had access to institutional rates of postoperative stroke/cerebral injury had standard neuroprotective strategies in place. CONCLUSIONS: Our data indicate that approximately half of the respondents to this SCA survey do not use standardized guidelines/standard operating procedures for perioperative cerebral protection. The lack of standardized neuroprotective strategies during cardiac surgery may impact postoperative neurologic outcomes. Further investigations are warranted and should assess the association of standardized neuroprotective approaches and postoperative neurological outcomes.

Association of health insurance with post-resuscitation care and neurological outcomes after return of spontaneous circulation in out-of-hospital cardiac arrest patients in Korea.

BACKGROUND: We investigated the association of health insurance status with post-resuscitation care and neurological recovery in out-of-hospital cardiac arrest (OHCA) and whether the effects changed with age or gender. METHODS: Adult OHCAs with presumed cardiac etiology who had sustained ROSC from 2013 to 2016 were enrolled from the nationwide OHCA registry of Korea. Insurance status was categorized into 2 groups: National Health Insurance (NHI) and Medical Aid (MA). The endpoints were post-resuscitation coronary reperfusion therapy (CRT), targeted temperature management (TTM), and good neurological recovery (cerebral performance category of 1 or 2). Multivariable logistic regression models and interaction analyses (insurance × age and insurance × gender) were conducted for adjusted odds ratios (aORs) and 95% confidence intervals (CI). RESULTS: Of a total of 19,865 eligible OHCA patients, 18,119 (91.2%) were covered by NHI and 1746 (8.8%) by MA. The MA group was less likely to receive post-resuscitation CRT and TTM (aOR (95% CI): 0.75 (0.59-0.96) for CRT; 0.71 (0.57-0.89) for TTM) and had worse neurological outcomes (0.71 (0.57-0.89)) compared with the NHI group. In the interaction analyses, MA was associated with less CRT and good neurological recovery in the 45-64 year old group (0.54 (0.37-0.77) for CRT; 0.70 (0.51-0.95) for neurological outcome) and in the male group (0.69 (0.52-0.91) for CRT; 0.77 (0.61-0.97) for TTM; 0.70 (0.53-0.92)) for neurological outcome). CONCLUSIONS: There were disparities in post-resuscitation care and substantial neurological recovery by health insurance status, and the disparities were prominent in middle-aged adults and males. Increasing health insurance coverage for post-resuscitation care should be considered.

Treatment with normobaric or hyperbaric oxygen and its effect on neuropsychometric dysfunction after carbon monoxide poisoning: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning. METHODS: We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning. RESULTS: Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR] = 0.83, 95% CI = 0.38-1.80), memory impairment (18.2% vs 23.8%, RR = 0.80, 95% CI = 0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI = 0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59-1.39). Two sessions of HBO treatment exhibited no advantage over one session. CONCLUSIONS: The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.

Effect of reduced use of organic solvents on disability pension in painters.

OBJECTIVE: To investigate whether the decreased use of paints based on organic solvents has caused a decreased risk for neuropsychiatric disorders in painters by studying their incidence in disability pensions. METHODS: The incidence of disability pension in Swedish painters who had participated in health examinations between 1971 and 1993 was studied through linkage with Swedish registers of disability pension over 1971-2010 and compared with the incidence in other construction workers as woodworkers, concrete workers and platers. When phasing out began in the 1970s, about 40% of paints were based on organic solvents and it had decreased to 4% in 1990s. The analysis was adjusted for age, time period, body mass index and smoking. RESULTS: The painters (n=23 065) had an increased risk of disability pension due to neurological diagnosis (n=285, relative risk (RR) 1.92, 95% CI 1.67 to 2.20) and psychiatric diagnosis (n=632, RR=1.61, 95 % CI 1.42 to 1.82). For neurological disorders there was a time trend with a continuously decreasing risk from 1980 onwards, but there was no such trend for psychiatric disorders. CONCLUSIONS: High exposure to organic solvents increased the risk for disability pension in neurological disorders, and the risk decreased when the use of organic solvents decreased. The painters also had an increased risk of disability pension due to psychiatric disorders, but the causes have to be further investigated.

Incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case-control study.

OBJECTIVE: To describe the incidence, risk factors, management and outcomes of amniotic-fluid embolism (AFE) over time. DESIGN: A population-based cohort and nested case-control study using the UK Obstetric Surveillance System (UKOSS). SETTING: All UK hospitals with obstetrician-led maternity units. POPULATION: All women diagnosed with AFE in the UK between February 2005 and January 2014 (n = 120) and 3839 control women. METHODS: Prospective case and control identification through UKOSS monthly mailing. MAIN OUTCOME MEASURES: Amniotic-fluid embolism, maternal death or permanent neurological injury. RESULTS: The total and fatal incidence of AFE, estimated as 1.7 and 0.3 per 100 000, respectively, showed no significant temporal trend over the study period and there was no notable temporal change in risk factors for AFE. Twenty-three women died (case fatality 19%) and seven (7%) of the surviving women had permanent neurological injury. Women who died or had permanent neurological injury were more likely to present with cardiac arrest (83% versus 33%, P < 0.001), be from ethnic-minority groups (adjusted odds ratio [OR] 2.85, 95% confidence interval [95% CI] 1.02-8.00), have had a hysterectomy (unadjusted OR 2.49, 95% CI 1.02-6.06), had a shorter time interval between the AFE event and when the hysterectomy was performed (median interval 77 minutes versus 248 minutes, P = 0.0315), and were less likely to receive cryoprecipitate (unadjusted OR 0.30, 95% CI 0.11-0.80). CONCLUSION: There is no evidence of a temporal change in the incidence of or risk factors for AFE. Further investigation is needed to establish whether earlier treatments can reverse the cascade of deterioration leading to severe outcomes.

Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion during deep hypothermic circulatory arrest in aortic surgery: a meta-analysis of 7023 patients.

In aortic arch surgery, deep hypothermic circulatory arrest (DHCA) combined with cerebral perfusion is employed worldwide as a routine practice. Even though antegrade cerebral perfusion (ACP) is more widely used than retrograde cerebral perfusion (RCP), the difference in benefit and risk between ACP and RCP during DHCA is uncertain. The purpose of this meta-analysis is to compare neurologic outcomes and early mortality between ACP and RCP in patients who underwent aortic surgery during DHCA. PubMed, EMBASE, and the Cochrane Library were searched using the key words "antegrade," "retrograde," "cerebral perfusion," "cardiopulmonary bypass," "extracorporeal circulation," and "cardiac surgery" for studies reporting on clinical endpoints including early mortality, stroke, temporary neurologic dysfunction (TND), and permanent neurologic dysfunction (PND) in aortic surgery requiring DHCA with ACP or RCP. Heterogeneity was analyzed with the Cochrane Q statistic and I(2) statistic. Publication bias was tested with Begg's funnel plot and Egger's test. Thirty-four studies were included in this meta-analysis, with 4262 patients undergoing DHCA + ACP and 2761 undergoing DHCA + RCP. The overall pooled relative risk for TND was 0.722 (95% CI = [0.579, 0.900]), and the z-score for overall effect was 2.9 (P = 0.004). There was low heterogeneity (I(2) = 18.7%). The analysis showed that patients undergoing DHCA + ACP had better outcomes than those undergoing DHCA + RCP in terms of TND, while there were no significant differences between groups in terms of PND, stroke, and early mortality. This meta-analysis indicates that DHCA + ACP has an advantage over DHCA + RCP in terms of TND, while the two methods show similar results in terms of PND, early mortality, and stroke.

Appropriateness of clopidogrel use according to current recommendations.

BACKGROUND: Clopidogrel is widely used in cardiovascular prevention. However, the prescription of clopidogrel in clinical practice does not match the recommendations concerning its indication and treatment duration. OBJECTIVE: To assess the appropriateness of clopidogrel prescription according to the accepted indications. METHODS: We undertook a retrospective observational analytical audit of the electronic clinical records in the region of Valencia, Spain (5 million inhabitants), selecting those patients on treatment with clopidogrel between 2007 and 2010. The primary outcome measure was the duration of the treatment. RESULTS: A total of 45721 patients started clopidogrel treatment during the study period. Treatment was for cardiologic disorders (CD) in 56.85% of the patients, neurologic disorders (ND) in 37.06% and peripheral arterial disease in 6.08%. Treatment duration was longer than that expected from clinical recommendations in 38.8% of the CD patients and 87.8% of the ND patients. The estimated avoidable cost ranged from 2 to 4.4 million Euros per year, according to whether a cheaper generic clopidogrel or a more expensive version was considered. CONCLUSIONS: Almost 40% of the cardiologic patients and 90% of the neurologic patients received excess treatment. Adjustment of treatment duration to international recommendations would result in savings of between 80.1 and 176.3 Euros per year and per patient treated.

The impact of arterial cannulation strategy on operative outcomes in aortic surgery: evidence from a comprehensive meta-analysis of comparative studies on 4476 patients.

OBJECTIVES: There is a growing perception that peripheral cannulation through the femoral artery, by reversing the flow in the thoracoabdominal aorta, may increase the risk of retrograde brain embolization in aortic surgery. Central cannulation sites, including the right axillary artery, have been reported to improve operative outcomes by allowing antegrade blood flow. However, peripheral cannulation still remains largely used because a consensus for the routine use of central cannulation approaches has not been reached. METHODS: A meta-analysis of comparative studies reporting operative outcomes using central cannulation versus peripheral cannulation was performed. Pooled weighted incidence rates for end points of interest were obtained using an inverse variance model. RESULTS: A total of 4476 patients were included in the final analysis. Central cannulation was used in 2797 patients, and peripheral cannulation was used in 1679 patients. Central cannulation showed a protective effect on in-hospital mortality (risk ratio, 0.59; 95% confidence interval, 0.48-0.7; P < .001) and permanent neurologic deficit (risk ratio, 0.71; 95% confidence interval, 0.55-0.90; P = .005) when compared with peripheral cannulation. A trend toward an increased benefit in terms of reduced in-hospital mortality was observed when only the right axillary artery was used as the central cannulation approach (risk ratio, 0.35; 95% confidence interval, 0.22-0.55; P < .001; I(2) = 0%). CONCLUSIONS: Central cannulation was superior to peripheral cannulation in reducing in-hospital mortality and the incidence of permanent neurologic deficit. This superiority was particularly evident when the axillary artery was used for central cannulation.

Survival and neurologic outcome after out-of-hospital cardiac arrest: results one year after regionalization of post-cardiac arrest care in a large metropolitan area.

BACKGROUND: Post-resuscitation care of cardiac arrest patients at specialized centers may improve outcome after out-of-hospital cardiac arrest (OOHCA). This study describes experience with regionalized care of resuscitated patients. METHODS: Los Angeles (LA) County established regionalized cardiac care in 2006. Since 2010, protocols mandate transport of nontraumatic OOHCA patients with field return of spontaneous circulation (ROSC) to a STEMI Receiving Center (SRC) with a hypothermia protocol. All SRC report outcomes to a registry maintained by the LA County Emergency Medical Services (EMS) Agency. We report the first year's data. The primary outcome was survival with good neurologic outcome, defined by a Cerebral Performance Category (CPC) score of 1 or 2. RESULTS: The SRC treated 927 patients from April 2011 through March 2012 with median age 67; 38% were female. There were 342 patients (37%) who survived to hospital discharge. CPC scores were unknown in 47 patients. Of the 880 patients with known CPC scores, 197 (22%) survived to hospital discharge with a CPC score of 1 or 2. The initial rhythm was VF/VT in 311 (34%) patients, of whom 275 (88%) were witnessed. For patients with an initial shockable rhythm, 183 (59%) survived to hospital discharge and 120 (41%) had survival with good neurologic outcome. Excluding patients who were alert or died in the ED, 165 (71%) patients with shockable rhythms received therapeutic hypothermia (TH), of whom 67 (42%) had survival with good neurologic outcome. Overall, 387 patients (42%) received TH. In the TH group, the adjusted OR for CPC 1 or 2 was 2.0 (95%CI 1.2-3.5, p = 0.01), compared with no TH. In contrast, the proportion of survival with good neurologic outcome in the City of LA in 2001 for all witnessed arrests (irrespective of field ROSC) with a shockable rhythm was 6%. CONCLUSION: We found higher rates of neurologically intact survival from OOHCA in our system after regionalization of post-resuscitation care as compared to historical data.

Diffusion tensor tractography and neuropsychological assessment in patients with vitamin B12 deficiency.

INTRODUCTION: Structural imaging of the brain does not demonstrate any changes in a vast majority of patients with vitamin B12 deficiency, even in advanced stages. In this study, we aimed to assess and correlate the functional integrity of the brain fiber tracts using diffusion tensor tractography with neuropsychological examination in patients with vitamin B12 deficiency. METHODS: The study was conducted at two tertiary care centers. Thirty-two patients with vitamin B12 deficiency were enrolled and subjected to diffusion tensor tractography, as an extension of diffusion tensor imaging, and neuropsychological assessment. Tests of significance were done to detect changes, pre- and post-vitamin B12 supplementation in the diffusivity parameters (fractional anisotropy and mean diffusivity) and the neuropsychological test scores. RESULTS: Statistically significant changes were observed in the diffusivity parameters and the neuropsychological test scores between the controls and the patients with vitamin B12deficiency in the pre- and post-treatment phases. CONCLUSIONS: This is the first study to evaluate the diffusion tensor tractography (DTT) parameters in the light of clinical neuropsychological assessment in patients with vitamin B12 deficiency. Utilization of DTT parameters may antedate structural changes and may quantify the neurocognitive deficits.

Why our patients (and we) need basic science research.

In times of fiscal austerity, the tendency is to seek instant, inexpensive gratification. In the case of biomedical research, this means the shortest path to practical clinical implementation. But fueling the translational pipeline with discovery depends critically on allowing the biomedical research community to follow their science where it takes them. Fiscal constraints carry with them the risk of squelching creativity and forfeiting the power of serendipity to provide the substrate for the translational engine in the future.

Regional variability in survival outcomes of out-of-hospital cardiac arrest: the All-Japan Utstein Registry.

OBJECTIVE: There is a paucity of studies on the degree of regional variability in out-of-hospital cardiac arrest (OHCA) outcomes, particularly in neurological outcome. This study aimed to determine whether there is a significant regional variation in survival outcomes of OHCA across Japan. METHODS: We analyzed a prospective, nation-wide, population-based database (All-Japan Utstein Registry) involving all Japanese individuals who had non-traumatic OHCA resuscitated by emergency responders from January 2005 through December 2010. The primary study endpoint was favourable neurological survival at 1 month, defined as Cerebral Performance Category 1 or 2. We compared unadjusted and multivariable-adjusted rates of the outcome among seven geographic regions. RESULTS: In the total catchment population of 128 million, there were 539,641 non-traumatic OHCA patients. Unadjusted neurologically favourable survival varied across regions from 1.9% to 3.1% (rate difference, 1.2%; 95%CI, 1.0-1.3%); the Northeast region had a significantly lower rate compared to the Midwest region (unadjusted rate ratio, 0.62; 95%CI, 0.60-0.64). This disparity became larger after adjusting for patient- and prehospital-level confounders (adjusted rate ratio, 0.52; 95%CI, 0.51-0.54). Among 35,153 OHCA patients with return of spontaneous circulation, unadjusted neurologically favourable survival varied from 26.4% to 34.7% (rate difference, 8.3%; 95%CI, 6.6-10.1%); the East region had a significantly lower rate compared to the Midwest region (adjusted rate ratio, 0.72; 95%CI, 0.68-0.76). CONCLUSION: In this prospective, nation-wide, population-based study in Japan, we found a two-fold regional difference in neurologically favourable survival after OHCA, suggesting regional disparities in prehospital care and in-hospital post-resuscitation care.

DL-3-n-Butylphthalide, an anti-oxidant agent, prevents neurological deficits and cerebral injury following stroke per functional analysis, magnetic resonance imaging and histological assessment.

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

[Risk management in regional anesthesia: preface and comments].

The benefits of regional anesthesia for surgical procedures, when compared with general anesthesia and/or systemic analgesia, include improved postoperative analgesia, an associated decrease in postoperative pain medication use, decreased nausea and vomiting, and quicker recovery and discharge from the hospital. Neurologic complications associated with regional anesthesia are extremely rare. Although rare, these complications may be reduced with new regional techniques such as the use of ultrasound or fluoroscopy, but further detailed research is needed. In regional anesthesia, rare but serious complications make it necessary to always consider the risk-benefit ratio. The articles discuss these issues and give advice on its effective and safe conduct.

[Risk management in regional anesthesia: spinal epidural hematoma].

Spinal epidural hematoma following neuraxial anesthesia is a rare condition that usually presents with acute and, if any, progressive neurological symptoms including pain, sensory/motor impairment, and bladder/ rectal disturbance. Although possible pathogenesis is mainly considered to be a direct injury of Batson's venous plexus, preoperative coagulation status and anticoagulant therapy also play some role in its development. Therefore, to prevent such a disastrous complication, one must choose an appropriate anesthetic technique and monitor neurological function of the patient at a regular time interval. In addition, it is highly recommended to carefully follow the recently revised regional anesthesia guideline for the patient receiving antithrombotic or thrombolytic therapy, although we still need further understanding and investigation of the complexity around this issue.

[Risk management in epidural anesthesia].

Epidural anesthesia has many advantages, including block of surgical stress, postoperative pain management and prevention of postoperative complications. Therefore, we should use epidural anesthesia when indicated. However, patients with preexisting spinal stenosis or lumbar radiculopathy have higher incidence of neurologic complications after epidural anesthesia. Epidural abscesses caused by epidural anesthesia are rare. However, epidural abscesses are serious complications in patients. Knowing the risk factor of epidural abscesses is important to prevent epidural abscesses, and early diagnosis and early treatment are needed when suspected. It is important to have measures for safety in performing epidural anesthesia at every hospital. Recently, we have many anesthetic techniques, including epidural anesthesia, remifentanil infusion, ultrasound-guided peripheral nerve blocks and intravenous PCA. Therefore, we should choose an anesthesia method based on the careful evaluation of the benefit and risk balance for the patient's safety to reduce the incidence of complications.