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Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies., Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival., Design, Setting, and Participants: This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023., Main Outcomes and Measures: Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies)., Results: Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable., Conclusions and Relevance: In this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.

Objectives: There is scarce data in the literature concerning the anti-GAD65 antibodies (GAD-Abs) autoimmunity in the Omani population., Methods: Retrospective cohort study included GAD-Abs positive patients ( n  = 444) presented to a tertiary referral center in Oman from January 2005 until January 2018, with a five-year follow-up to study the cancer association and mortality outcomes., Results: Out of 444 patients, 27 patients (6.1%) showed GAD-Abs related neurological disorders. Adult age group was significantly associated with more GAD-Abs related neurological manifestations compared to pediatric and adolescents age group ( p  = 0.045). There was no association between the presence or absence of neurological manifestations with diabetes mellitus nor the titer level of GAD-Abs. Refractory status epilepticus and stiff person syndrome were the main causes of death in patients with neurological manifestations over five years and none of them found to have associated cancer., Conclusion: The GAD-Abs autoimmunity represents a spectrum of neurological manifestations with variable severity and outcome among Omanis with positive GAD-Abs testing. The results of this study will serve as a platform for future studies to address the impact of GAD-Abs autoimmunity on the morbidity, mortality and treatment efficacy in the Omani population.

Objective: We examine whether the rise in neurological death rates over the 21st century are solely explained by the Gompertzian hypothesis., Study Design: We examine two data-sets. First, Office of National Statistics (ONS, 2022) for nineteen mortality categories in England/Wales, including Alzheimer's, Dementias and Parkinson's Disease. Secondly, WHO (2020) Combined Neurological Mortality (CNM), from WHO Global mortality categories, Nervous Disease Deaths, and Alzheimer's & Other Dementias., Methods: Based on ONS data we investigate trends in Age-Standardised Mortality Rates (ASMR) of CNM 2000-2022. Based on WHO data we examine rates of Early Deaths (55-74) and ASMR, for CNM between 2000 and 2015 in the ten Major 'Western' economies: Australia, Canada, France, Germany, Italy, Japan, Netherlands, Spain, UK, and the USA., Results: In England & Wales death rates have increased 348% for Alzheimer's, 235% for Dementias, and 105% for Parkinson's Disease in contrast with falls in most other cause mortality. Early Adults Deaths CNM rates increased in eight countries, an average of 19%. Neurological ASMR rose in every country, averaging 43%, the highest was the UK 95%., Conclusion: We reject the Gompertzian hypothesis as an all-encompassing explanation for these marked increases in ASMR. Increases in early adult neurological deaths suggests this cannot be solely explained by an aging population. Furthermore, increases in mortality could be related to an increased prevalence of neurological conditions in this age group. Action is urgently needed to investigate factors - whether environmental, lifestyle or health systems - that could explain these findings., Competing Interests: Declaration of competing interest No author has conflicts or vested interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Determining the frequency and outcomes of neurological disorders associated with coronavirus disease 2019 (COVID-19) is imperative for understanding risks and for recognition of emerging neurological disorders. We investigated the susceptibility and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among persons with premorbid neurological disorders, in addition to the post-infection incidence of neurological sequelae, in a case-control population-based cohort. Using health service data collected between 1 March 2020 and 30 June 2021, we constructed a cohort of SARS-CoV-2 RNA-positive (n = 177 892) and -negative (n = 177 800) adults who were age, sex and comorbidity matched and underwent RT-PCR testing at similar times. COVID-19-associated mortality rates were examined within the cohort. Neurological sequelae were analysed during the acute (<3 months) and the post-acute (3-9 months) phases post-infection. The risk of death was significantly greater in the SARS-CoV-2 RNA-positive (2140 per 100 000 person years) compared with RNA-negative (922 per 100 000 person years) over a follow-up of 9 months, particularly amongst those with premorbid neurological disorders: adjusted odds ratios (95% confidence interval) in persons with a prior history of parkinsonism, 1.65 (1.15-2.37); dementia, 1.30 (1.11-1.52); seizures, 1.91 (1.26-2.87); encephalopathy, 1.82 (1.02-3.23); and stroke, 1.74 (1.05-2.86). There was also a significantly increased risk for diagnosis of new neurological sequelae during the acute time phase after COVID-19, including encephalopathy, 2.0 (1.10-3.64); dementia, 1.36 (1.07-1.73); seizure, 1.77 (1.22-2.56); and brain fog, 1.96 (1.20-3.20). These risks persisted into the post-acute phase after COVID-19, during which inflammatory myopathy (2.57, 1.07-6.15) and coma (1.87, 1.22-2.87) also became significantly increased. Thus, persons with SARS-CoV-2 infection and premorbid neurological disorders are at greater risk of death, and SARS-CoV-2 infection was complicated by increased risk of new-onset neurological disorders in both the acute and post-acute phases of COVID-19., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Variation in the provision of care and outcomes in the last months of life by cancer and non-cancer conditions is poorly understood., Aims: (1) To describe patient conditions, symptom burden, practical problems, service use and dissatisfaction with end-of-life care for older adults based on the cause of death. (2) To explore factors related to these variables focussing on the causes of death., Design: Secondary analysis of pooled data using cross-sectional mortality follow-back surveys from three studies: QUALYCARE; OPTCare Elderly; and International Access, Right, and Empowerment 1., Setting/participants: Data reported by bereaved relatives of people aged ⩾75 years who died of cancer, cardiovascular disease, respiratory disease, dementia or neurological disease., Results: The pooled dataset contained 885 responses. Overall, service use and circumstances surrounding death differed significantly across causes of death. Bereaved relatives reported symptom severity from moderate to overwhelming in over 30% of cases for all causes of death. Across all causes of death, 28%-38% of bereaved relatives reported some level of dissatisfaction with care. Patients with cardiovascular disease and dementia experienced lower symptom burden and dissatisfaction than those with cancer. The absence of a reliable key health professional was consistently associated with higher symptom burden ( p  = 0.002), practical problems ( p  = 0.001) and dissatisfaction with care ( p  = 0.001)., Conclusions: We showed different trajectories towards death depending on cause. Improving symptom burden and satisfaction in patients at the end-of-life is challenging, and the presence of a reliable key health professional may be helpful., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Mortality rates for neurologic diseases are increasing in the United States, with large disparities across geographical areas and populations. Racial and ethnic populations, notably the non-Hispanic (NH) Black population, experience higher mortality rates for many causes of death, but the magnitude of the disparities for neurologic diseases is unclear. The objectives of this study were to calculate mortality rates for neurologic diseases by race and ethnicity and-to place this disparity in perspective-to estimate how many US deaths would have been averted in the past decade if the NH Black population experienced the same mortality rates as other groups., Methods: Mortality rates for deaths attributed to neurologic diseases, as defined by the International Classification of Diseases, were calculated for 2010 to 2019 using death and population data obtained from the Centers for Disease Control and Prevention and the US Census Bureau. Avertable deaths were calculated by indirect standardization: For each calendar year of the decade, age-specific death rates of NH White persons in 10 age groups were multiplied by the NH Black population in each age group. A secondary analysis used Hispanic and NH Asian populations as the reference groups., Results: In 2013, overall age-adjusted mortality rates for neurologic diseases began increasing, with the NH Black population experiencing higher rates than NH White, NH American Indian and Alaska Native, Hispanic, and NH Asian populations (in decreasing order). Other populations with higher mortality rates for neurologic diseases included older adults, the male population, and adults older than 25 years without a high school diploma. The gap in mortality rates for neurologic diseases between the NH Black and NH White populations widened from 4.2 individuals per 100,000 in 2011 to 7.0 per 100,000 in 2019. Over 2010 to 2019, had the NH Black population experienced the neurologic mortality rates of NH White, Hispanic, or NH Asian populations, 29,986, 88,407, or 117,519 deaths, respectively, would have been averted., Discussion: Death rates for neurologic diseases are increasing. Disproportionately higher neurologic mortality rates in the NH Black population are responsible for a large number of excess deaths, making research and policy efforts to address the systemic causes increasingly urgent., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging method of cardiopulmonary resuscitation to improve outcomes from cardiac arrest. This approach targets patients with out-of-hospital cardiac arrest previously unresponsive and refractory to standard treatment, combining approximately 1 h of standard CPR followed by venoarterial extracorporeal membrane oxygenation (VA-ECMO) and coronary artery revascularization. Despite its relatively new emergence for the treatment of cardiac arrest, the approach is grounded in a vast body of preclinical and clinical data that demonstrate significantly improved survival and neurological outcomes despite unprecedented, prolonged periods of CPR. In this review, we detail the principles behind VA-ECMO-facilitated resuscitation, contemporary clinical approaches with outcomes, and address the emerging new understanding of the process of death and capability for neurological recovery., (© 2021 New York Academy of Sciences.)

Background: Gastrostomy tube (G-tube) placement for children with neurologic impairment with dysphagia has been suggested for pneumonia prevention. However, prior studies demonstrated an association between G-tube placement and increased risk of pneumonia. We evaluate the association between timing of G-tube placement and death or severe pneumonia in children with neurologic impairment., Methods: We included all children enrolled in California Children's Services between July 1, 2009, and June 30, 2014, with neurologic impairment and 1 pneumonia hospitalization. Prior to analysis, children with new G-tubes and those without were 1:2 propensity score matched on sociodemographics, medical complexity, and severity of index hospitalization. We used a time-varying Cox proportional hazard model for subsequent death or composite outcome of death or severe pneumonia to compare those with new G-tubes vs those without, adjusting for covariates described above., Results: A total of 2490 children met eligibility criteria, of whom 219 (9%) died and 789 (32%) had severe pneumonia. Compared to children without G-tubes, children with new G-tubes had decreased risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.39-0.55) but increased risk of the composite outcome (HR 1.21, CI 1.14-1.27). Sensitivity analyses using varied time criteria for definitions of G-tube and outcome found that more recent G-tube placement had greater associated risk reduction for death but increased risk of severe pneumonia., Conclusion: Recent G-tube placement is associated with reduced risk of death but increased risk of severe pneumonia. Decisions to place G-tubes for pulmonary indications in children with neurologic impairment should weigh the impact of severe pneumonia on quality of life.

Objectives: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality., Design: Secondary analysis of three prospective, observational, multicenter studies., Setting: Cohort studies conducted in 2004, 2010, and 2016., Patients: Adult patients who received mechanical ventilation for more than 12 hours., Interventions: None., Measurements and Main Results: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma., Conclusions: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease., Competing Interests: Dr. Thille received funding from Fisher & Paykel, GE Healthcare, Maquet-Getinge, and Covidien. Dr. Amin received funding from CIPLA, Sanofi, and Fresenius. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Importance: The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome., Objective: To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19., Design, Setting, and Participants: This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation., Exposures: Clinically diagnosed or laboratory-confirmed COVID-19., Main Outcomes and Measures: Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality., Results: Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19., Conclusions and Relevance: In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19.

Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear., Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19., Setting, Design, and Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features., Exposures: Severe acute respiratory syndrome coronavirus 2., Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge., Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died., Conclusions and Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

Background: Prior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate., Objective: This WOVEN study assesses the 1-year follow-up from this cohort., Methods: Twelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis., Results: In the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up., Conclusions: The WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients., Competing Interests: Competing interests: MJA, AZ, RG, AEH, BWB, RCC and WY are scientific consultants for Stryker Neurovascular. No industry compensation was provided for this research or the production of this manuscript to any of the investigators., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cerebral infarction (CI) remains one of the most common and fatal complications of infective endocarditis (IE), and the timing of surgery for IE with neurologic complications is controversial. As outcomes beyond the perioperative period have not been assessed with a meta-analysis previously, we conducted a meta-analysis comparing mid- to long-term outcomes of early and late surgery in patients with IE and neurologic complications., Methods: All studies that investigated early and late surgery in patients with IE and neurologic complications were identified. The primary and secondary endpoints were all-cause mortality and recurrence, respectively. Hazard ratios (HRs) for all-cause mortality and recurrence were extracted from each study., Results: Our search identified five eligible studies, which were all observational studies consisting of a total of 624 patients with IE and neurologic complications. Pooled analyses demonstrated that all-cause mortality was similar between the early and late surgery groups (HR [95% confidence interval [CI]] = 0.90 [0.49-1.64]; P = 0.10; I 2  = 49%). Similarly, the recurrence rates were similar between both groups (HR [95% CI] = 1.86 [0.76-4.52]; P = 0.43; I 2  = 0%)., Conclusions: Our meta-analysis showed similar mortality and recurrent rates between the early and late surgery groups. The optimal timing of surgery should be individualized on a case-to-case basis.

Objective: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes., Methods: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders., Results: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, p < 0.001)., Conclusions: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness., (© 2020 American Academy of Neurology.)

To evaluate the impact of maternal hypertensive disorders of pregnancy (HDP) on mortality and neurological outcomes in extremely and very preterm infants using a nationwide neonatal database in Japan. This population-based retrospective study was based on an analysis of data collected by the Neonatal Research Network of Japan from 2003 to 2015 of neonates weighing 1,500 g or less at birth, between 22 and 31 weeks' gestation. A total of 21,659 infants were randomly divided into two groups, HDP (n = 4,584) and non-HDP (n = 4,584), at a ratio of 1:1 after stratification by four factors including maternal age, parity, weeks of gestation, and year of delivery. Short-term (neonatal period) and medium-term (3 years of age) mortality and neurological outcomes were compared between the two groups by logistic regression analyses. In univariate analysis, HDP was associated with an increased risk for in-hospital death (crude odds ratio [OR], 1.31; 95% confidence interval, 1.04-1.63) and a decreased risk for severe intraventricular haemorrhage (0.68; 0.53-0.87) and periventricular leukomalacia (0.60; 0.48-0.77). In multivariate analysis, HDP was significantly associated with a lower risk for in-hospital death (adjusted OR, 0.61; 0.47-0.80), severe intraventricular haemorrhage (0.47; 0.35-0.63), periventricular leukomalacia (0.59; 0.45-0.78), neonatal seizures (0.40; 0.28-0.57) and cerebral palsy (0.70; 0.52-0.95) at 3 years after adjustment for covariates including birth weight. These results were consistent with those of additional analyses, which excluded cases with histological chorioamnionitis and which divided the infants into two subgroups (22-27 gestational weeks and 28-31 gestational weeks). Maternal HDP was associated with an increased risk for in-hospital death without adjusting for covariates, but it was also associated with a lower risk for mortality and adverse neurological outcomes in extremely and very preterm infants if all covariates except HDP were identical.

Background: Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined., Methods: We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC)., Results: Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33μg/l [16-94] vs. 119μg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21μg/l [16-29] vs. 40μg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127μg/l [0.063-0.360] vs. 0.772μg/l [0.121-2.710], p<0.001 and 0.086μg/l [0.061-0.122] vs. 0.138μg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36μg/l for NSE and 0.128μg/l for S-100b could be determined; for poor neurological outcome 33μg/l (NSE) and 0.123μg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b., Conclusions: Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making., Competing Interests: AS received modest lecture fees from ZOLL Inc. regarding therapeutic hypothermia. All other authors have no conflict of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Emergency medical services (EMS) routinely face complex scenarios where decisions should be taken with limited clinical information. The development of fast, reliable and easy to perform warning biomarkers could help in such decision-making processes. The present study aims at characterizing the validity of point-of-care lactate (pLA) during prehospital tasks for predicting in-hospital mortality within two days after the EMS assistance., Materials and Methods: Prospective, multicentric, ambulance-based and controlled observational study without intervention, including six advanced life support and five hospitals. The pLA levels were recorded during EMS assistance of adult patients. The validity of pLA to determine the in-hospital mortality was assessed by the area under the curve (AUC) of the receiver operating curve (ROC)., Results: A total of 2997 patients were considered in the study, with a median of 69 years (IQR 54-81) and 41.4% of women. The median pLA value was 2.7 mmol/L (1.9-3.8) in survivors and 5.7 mmol/L (4.4-7.6) in nonsurvivors. The global discrimination level of pLA reached an AUC of 0.867, being 1.9 mmol/L and 4 mmol/L the cut-off point for low and high mortality. The discrimination value of pLA was not affected by sex, age or pathology., Conclusions: Our results highlight the clinical importance of prehospital pLA to determine the in-hospital risk of mortality. The incorporation of pLA into the EMS protocols could improve the early identification of risky patients, leading to a better care of such patients., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Importance: The safety and efficacy of intensive systolic blood pressure reduction in patients with intracerebral hemorrhage who present with systolic blood pressure greater than 220 mm Hg appears to be unknown., Objective: To evaluate the differential outcomes of intensive (goal, 110-139 mm Hg) vs standard (goal, 140-179 mm Hg) systolic blood pressure reduction in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more vs less than 220 mm Hg., Design, Setting, and Participants: This post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage-II trial was performed in November 2019 on data from the multicenter randomized clinical trial, which was conducted between May 2011 to September 2015. Patients with intracerebral hemorrhage and initial systolic blood pressure of 180 mm Hg or more, randomized within 4.5 hours after symptom onset, were included., Interventions: Intravenous nicardipine infusion titrated to goals., Main Outcomes and Measures: Neurological deterioration and hematoma expansion within 24 hours and death or severe disability at 90 days, plus kidney adverse events and serious adverse events until day 7 or hospital discharge., Results: A total of 8532 patients were screened, and 999 individuals (mean [SD] age, 62.0 [13.1] years; 620 men [62.0%]) underwent randomization and had an initial SBP value. Among 228 participants with initial systolic blood pressures of 220 mm Hg or more, the rate of neurological deterioration within 24 hours was higher in those who underwent intensive (vs standard) systolic blood pressure reduction (15.5% vs 6.8%; relative risk, 2.28 [95% CI, 1.03-5.07]; P = .04). The rate of death and severe disability (39.0% vs 38.4%; relative risk, 1.02 [95% CI, 0.73-1.78]; P = .92) was not significantly different between the 2 groups. There was a significantly higher rate of kidney adverse events in participants randomized to intensive systolic blood pressure reduction (13.6% vs 4.2%; relative risk, 3.22 [95% CI, 1.21-8.56]; P = .01), but no difference was observed in the rate of kidney serious adverse events., Conclusions and Relevance: The higher rate of neurological deterioration within 24 hours associated with intensive treatment in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more, without any benefit in reducing hematoma expansion at 24 hours or death or severe disability at 90 days, warrants caution against generalization of recommendations for intensive systolic blood pressure reduction.

Marked protein catabolism is common in critically ill patients. We hypothesized that optimal protein supplementation using nitrogen balance might be associated with better outcomes in the neurointensive care unit (NICU) patients. A total of 175 patients admitted to the NICU between July 2017 and December 2018 were included. Nitrogen balance was measured after NICU admission and measurements were repeated in 77 patients. The outcomes were compared according to initial nitrogen balance results and improvement of nitrogen balance on follow-up measurements. A total of 140 (80.0%) patients had a negative nitrogen balance on initial assessments. The negative balance group had more events of in-hospital mortality and poor functional outcome at three months. In follow-up measurement patients, 39 (50.6%) showed an improvement in nitrogen balance. The improvement group had fewer events of in-hospital mortality ( p = 0.047) and poor functional outcomes ( p = 0.046). Moreover, improvement of nitrogen balance was associated with a lower risk of poor functional outcomes (Odds ratio, 0.247; 95% confidence interval, 0.066-0.925, p = 0.038). This study demonstrated that a significant proportion of patients in the NICU were under protein hypercatabolism. Moreover, an improvement in protein balance was related to improved outcomes in neurocritically ill patients. Further studies are needed to confirm the relationship between protein balance and outcomes.

Background and Purpose: Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis., Methods: We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses ( P <0.05). Main outcomes were incidence of END, associated predictors of END, ordinal day-90 mRS, and day-90 mortality., Results: We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%-7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96-3.54], P <0.001), large vessel disease (LVD) with carotid stenosis (OR, 2.97 [95% CI, 2.45-3.61], P <0.001), other LVD (OR, 2.41 [95% CI, 2.03-2.88], P <0.001), and ischemic stroke versus transient ischemic attack (TIA)/stroke mimics (OR, 16.14 [95% CI, 3.99-65.3], P <0.001). END was associated with worse outcome on ordinal mRS: adjusted OR 2.48 (95% CI, 2.39-2.57, P <0.001) by day-90 compared with no END. The adjusted OR for day-90 mortality was 9.70 (95% CI, 8.36-11.26, P <0.001)., Conclusions: The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.

Introduction: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death., Methods: In this retrospective cohort study, we included 103 adult inpatients (aged ≥ 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients., Results: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer's dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age., Conclusions: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.

Objective: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19)., Methods: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period., Results: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, p = 0.009) on admission., Conclusions: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19., (© 2020 American Academy of Neurology.)

Background: There is still a paucity of information on the burden of neurological disorders particularly in low-resource settings such as sub-Saharan Africa. The objective of this study was to report the burden of neurological disorders, including morbidity and mortality, in adult patients at a Northwestern Nigerian tertiary hospital over a 2-year period., Materials and Methods: An audit of adult medical admissions from July 1, 2015, to June 30, 2017, was conducted. Anonymized data on medical admissions were retrieved from admission registries. Primary and secondary outcomes of interest were neurological diagnoses and clinical outcomes, respectively. The Pearson χ and independent t tests were used to test for differences between neurological and general medical proportions and outcomes with a 5% significance level set., Results: Over the 2-year period, 2772 adults were admitted. Neurological morbidity comprised almost a 10th of all adult medical admissions (9.1%), whereas neurological mortality accounted for more than a fifth of all deaths (22.2%). Stroke was the leading cause of neurological morbidity (62.9%) and mortality (79.8%). Infections of the nervous system and epilepsy were other frequent causes of neurological morbidity. Outcomes were poorer for neurological patients (fatality rates: neurological, 55.5%; medical, 19.5%, P<0.001)., Conclusions: Neurological disorders were a significant cause of adult medical morbidity and, to a greater extent, of mortality. Cerebrovascular disease and infections of the nervous system were major drivers of mortality. Cost-effective strategies appropriate for low-resource settings are required to prevent and reverse these negative outcomes.

Background: Neurologic complications are common complications encountered by patients with left ventricular assist devices (LVADs). This single-center retrospective study aims to identify the incidence and risk factors of neurologic complications and interventions in patients supported with LVADs and define the associated anticoagulation management., Methods: Between August 2009 and August 2017, 244 patients underwent LVAD implantation. Twenty-one patients were excluded for having neurologic complications before LVAD placement or for having previously undergone heart transplantation., Results: Fifty-six patients (25%) suffered 61 complications, and 11 (19.6%) died as a result. Gender, type of LVAD, or chronic medical comorbidities evaluated did not contribute to a difference in complication rate; in contrast, length of LVAD implantation was directly related to risk of neurologic complication. Eleven patients (19.6%) underwent 13 surgical interventions including 5 mechanical thrombectomies. Anticoagulation was reversed in 16 patients and held without complication. Anticoagulation was not held for ischemic complications, and no clinically significant hemorrhagic transformation occurred. Intravenous tissue plasminogen activator was also successfully administered to 3 patients without complication., Conclusions: Neurologic complications were observed in 25% of patients supported with LVADs, of which 20% required neurosurgical intervention. Anticoagulation can be safely withheld in patients with hemorrhagic complications. Patients with ischemic complications can continue to be anticoagulated with no significant risk of hemorrhagic transformation. Length of LVAD implantation was directly related to the risk of neurologic complication. Finally, our study adds to existing literature that mechanical thrombectomy and even intravenous tissue plasminogen activator are options for LVAD patients with ischemic complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objective: The global burden of chronic obstructive pulmonary disease (COPD) is increasing and COPD patients are at higher risk for all-cause mortality. We aimed to evaluate the impact of COPD on specific-cause mortality using national data., Methods: This was nationwide retrospective cohort study of 340, 767 adults aged 40-84 years who lacked COPD diagnosis at baseline between 1 January 2003 and 31 December 2013. Incident COPD was defined by reference to COPD claim codes and prescription of COPD medication at least twice annually. Cox proportional hazard ratio (HR) for each cause of death in the COPD group was compared to that of the non-COPD group, with other causes of death accounted as the competing risk., Results: All-cause mortality was higher in the COPD (2,978 per 100, 000 person-years) than the non-COPD group (629 per 100, 000 person-years) and adjusted HR was 1.41 (95% CI = 1.32, 1.50). The association was particularly strong for chronic lower airway disease (adjusted sub-HR = 9.67; 95% CI = 7.21, 12.96) and lung cancer (adjusted sub-HR = 3.16; 95% CI = 2.68, 3.71), and the association was stronger in those aged <60 years., Conclusion: In this large national cohort, COPD patients were at a statistically significant higher risk for all-cause mortality than those without COPD. They were more likely to die from chronic lower airway disease, lung cancer and pneumonia than subjects without COPD. The impact of COPD on specific mortalities was stronger in younger subjects., (© 2019 Asian Pacific Society of Respirology.)

Objective: Pediatric oncology patients admitted to the pediatric intensive care unit (PICU) are at high risk of mortality. This study aims to describe the epidemiology of and the risk factors for mortality in these patients., Study Design: This is a retrospective cohort study including all consecutive PICU oncology admissions from 2011 to 2017. Demographic and clinical risk factors between survivors and nonsurvivors were compared. Both univariate and multivariate Cox proportional hazard regression models were used to quantify the association between 60-day mortality and admission categories, accounting for other covariates (Pediatric Risk Of Mortality [PRISM] III score and previous bacteremia)., Main Outcome Measures: The primary outcome was 60-day mortality., Results: The median (interquartile range) age and PRISM III scores of pediatric oncology patients admitted to the PICU were 7 (3, 12) years and 3 (0, 5), respectively. The most common underlying oncological diagnoses were brain tumors (73/200 [36.5%]) and acute lymphoblastic leukemia (36/200 [18.0%]). Emergency admissions accounted for approximately half of all admissions (108/200 [54.0%]), including cardiovascular (24/108 [22.2%]), neurology (24/108 [22.2%]), respiratory (22/108 [20.4%]), and "other" indications (38/108 [35.2%]). The overall 60-day mortality was 35 of 200 (17.5%). Independent risk factors for mortality were emergency respiratory and neurology categories of admission (adjusted hazard ratio[aHR]: 5.62, 95% confidence interval [95% CI]: 1.57, 20.19; P = .008 and aHR: 6.96, 95% CI: 2.04, 23.75; P = .002, respectively) and previous bacteremia (aHR: 3.37, 95% CI: 1.57, 7.20; P = .002)., Conclusion: Emergency respiratory and neurology admissions and previous bacteremia were independent risk factors for 60-day mortality for pediatric oncological patients admitted to the PICU., (© 2020 Wiley Periodicals, Inc.)

Coronavirus disease 2019 (COVID-19), first reported in Wuhan, the capital of Hubei, China, has been associated to a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization declared the SARS-CoV-2 infection a global pandemic. Soon after, the number of cases soared dramatically, spreading across China and worldwide. Italy has had 12,462 confirmed cases according to the Italian National Institute of Health (ISS) as of March 11, and after the "lockdown" of the entire territory, by May 4, 209,254 cases of COVID-19 and 26,892 associated deaths have been reported. We performed a review to describe, in particular, the origin and the diffusion of COVID-19 in Italy, underlying how the geographical circulation has been heterogeneous and the importance of pathophysiology in the involvement of cardiovascular and neurological clinical manifestations.

Severe neurological complications following infective endocarditis remain a major problem with high mortality rate. The long-term neurological consequences following infective endocarditis remain uncertain. Otherwise, neurosurgeries could be performed after these complications; however, few clinical series have reported the results. Therefore, we utilized a large, nationwide database to unveil the long-term mortality and neurosurgical outcome following infective endocarditis. We included patients with a first-time discharge diagnosis of infective endocarditis between January 2001 and December 2013 during hospitalization. Patients were further divided into subgroups consisting of neurological complications under neurosurgical treatment and complications under non-neurosurgical treatment. Long-term result of symptomatic neurological complications after infective endocarditis and all-cause mortality after different kinds of neurosurgeries were analyzed. There were 16,495 patients with infective endocarditis included in this study. Symptomatic neurological complications occurred in 1,035 (6.27%) patients, of which 279 (26.96%) accepted neurosurgical procedures. Annual incidence of neurological complications gradually increased from 3.6% to 7.4% (P < 0.001). The mortality rate among these patients was higher than that among patients without complications (48.5% vs. 46.1%, P = 0.012, increased from 20% initially to nearly 50% over the 5-year follow-up). However, neurosurgery had no effect on the long-term mortality rate (50.9% vs. 47.6%, P = 0.451). Incidence of neurological complications post-infective endocarditis is increasing, and patients with these complications have higher mortality rates than patients without. Neurosurgery in these populations was not associated with higher long-term mortality. Therefore, it should not be ruled out as an option for those with neurological complications.

Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. In the past 30 years, the absolute numbers of deaths and people with disabilities owing to neurological diseases have risen substantially, particularly in low-income and middle-income countries, and further increases are expected globally as a result of population growth and ageing. This rise in absolute numbers of people affected suggests that advances in prevention and management of major neurological disorders are not sufficiently effective to counter global demographic changes. Urgent measures to reduce this burden are therefore needed. Because resources for health care and research are already overstretched, priorities need to be set to guide policy makers, governments, and funding organisations to develop and implement action plans for prevention, health care, and research to tackle the growing challenge of neurological disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: While the burden of neurologic illness in developing countries is increasing, less is known about mortality among patients admitted to sub-Saharan African hospitals with neurologic disease. We sought to characterize the rate and patient-level predictors of in-hospital mortality in a Ugandan Neurology ward.cc., Methods: Data was prospectively collected on 335 patients admitted to the Neurology ward of Mulago Hospital, Kampala, Uganda. Kaplan-Meier survival curves and multivariate COX proportional hazard modeling were used to assess survival., Results: Within our sample (n = 307), 35.8% received no diagnosis at time of hospital admission. Stroke (27.3%), head trauma (19.6%), and malaria (16.0%) were the most common diagnoses. Among the 56 (18.5%) patients who died during the index hospitalization, the most common diagnosis at admission and at death was stroke. Adjusted regression analysis showed that patients without a diagnosis at time of death (HR = 7.01 [2.42-20.35], p < .001) and those with diagnoses of infections (HR = 5.21 [2.16-12.58], p = <.001), stroke (HR = 2.69 [1.20-6.04], p = .017), or head trauma (HR = 3.39, [1.27-9.07], p = 0.15) had worse survival., Conclusions: In-hospital mortality affected nearly 20% of the cohort, with worse survival among those without a diagnosis and with infections, stroke, head trauma. Future work should identify reasons for increased mortality among these high-risk groups and implement targeted interventions.

Traumatic brain injury (TBI) is the leading cause of pediatric morbidity and mortality worldwide, and half of all fatalities occur in infants aged less than 1 year. We analyzed 129 infants diagnosed with TBI complicated with intracranial hemorrhage confirmed by brain computed tomography. We defined delta hemoglobin (ΔHB) as nadir HB - age specific mean HB, and the ratio of HB (%) as ΔHB/age specific mean HB x 100. Infants with poor neurologic outcomes had a lower admission HB and ΔHB (p < 0.05). The in-hospital mortality rate was 10.1% (13 infants), and the infants who died had a significantly lower ΔHB ratio compared to the survivors. The area under the receiving operating characteristic curve (AUC) of initial Glasgow Coma Score (GCS) in predicting neurologic outcomes was higher than that of ratio of ΔHB (0.881 v.s 0.859). In multivariate logistic regression analysis with the optimal cutoff ratio of ΔHB, it remained an independent predictor for in-hospital mortality and poor neurologic outcomes at discharge and at 6 months. AUC analysis for the ratio of ΔHB for poor neurologic outcomes in infants aged from 0-6 months was 0.85 and the optimal cutoff was -30.7% (sensitivity, 69%; specificity, 92%; positive likelihood ratio (LR + ), 8.24; negative likelihood ratio (LR - ), 0.34); the AUC was 0.88 in infants aged from 6-12 months and the optimal cutoff was -20.6% (sensitivity, 89%; specificity, 79%; LR + , 4.13; LR - , 0.15).

This paper dispenses an exhaustive review on deep learning techniques used in the prognosis of eight different neuropsychiatric and neurological disorders such as stroke, alzheimer, parkinson's, epilepsy, autism, migraine, cerebral palsy, and multiple sclerosis. These diseases are critical, life-threatening and in most of the cases may lead to other precarious human disorders. Deep learning techniques are emerging soft computing technique which has been lucratively used to unravel different real-life problems such as pattern recognition (Face, Emotion, and Speech), traffic management, drug discovery, disease diagnosis, and network intrusion detection. This study confers the discipline, frameworks, and methodologies used by different deep learning techniques to diagnose different human neurological disorders. Here, one hundred and thirty-six different articles related to neurological and neuropsychiatric disorders diagnosed using different deep learning techniques are studied. The morbidity and mortality rate of major neuropsychiatric and neurological disorders has also been delineated. The performance and publication trend of different deep learning techniques employed in the investigation of these diseases has been examined and analyzed. Different performance metrics like accuracy, specificity, and sensitivity have also been examined. The research implication, challenges and the future directions related to the study have also been highlighted. Eventually, the research breaches are identified and it is witnessed that there is more scope in the diagnosis of migraine, cerebral palsy and stroke using different deep learning models. Likewise, there is a potential opportunity to use and explore the performance of Restricted Boltzmann Machine, Deep Boltzmann Machine and Deep Belief Network for diagnosis of different human neuropsychiatric and neurological disorders.

Coronavirus is an enveloped, non-segmented, positive-polarity and single-stranded RNA virus. It has four types of genera that infect mammals and birds, with only alpha and beta types found to affect humans with varying severity. A specific clade of beta coronaviruses is reported as lethal zoonotic viruses and has created major epidemic troubles, starting with the severe acute respiratory syndrome (SARS) in 2002, then the Middle East respiratory syndrome (MERS) in 2012, and lastly Coronavirus Disease 2019 (COVID-19) in 2019. However, many neurological complications reported in COVID-19 patients have highlighted a critical pattern of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Awareness of such an association could create new insight to consider neurological manifestations as a COVID-19 differential diagnosis during the pandemic period of COVID-19 to avoid delayed diagnosis and prevent further transmission. This mini-review aims to collect the current knowledge regarding the mechanism behind the neuroinvasive capacity of SARS-CoV-2, to summarize the common documented neurological symptoms and associated complications in COVID-19 patients, and to review the impact of neurological manifestations on COVID-19 mortality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: There is paucity of literature on the prognostic value of tissue oxygen saturation (StO2) and regional cerebral oxygen saturation (rSO2) in neurological patients with sepsis. In this preliminary study, we investigated the prognostic value of StO2 and rSO2 in a group of neurological patients and correlated StO2 and rSO2 with hemodynamic and metabolic parameters., Materials and Methods: This preliminary, prospective observational study was conducted in 45 adult neurological patients admitted to intensive care unit. Once a diagnosis of sepsis or septic shock was established, parameters of oxygenation (StO2, rSO2, central venous oxygen saturation [ScvO2]), serum lactate, illness severity scores (Acute Physiology and Chronic Health Evaluation score, Sequential Organ Failure Assessment score, Glasgow Coma Scale) were recorded at 0, 6, 12, 24, 36, and 48 hours, and once daily thereafter. Outcomes were in-hospital mortality attributable to sepsis and the Glasgow outcome score at hospital discharge., Results: There was a moderately positive correlation between StO2 and rSO2 at baseline (r=0.599; P=0.001). StO2, illness severity scores and serum lactate, but not rSO2, were significantly different between survivors (n=29) and nonsurvivors (n=16) at baseline and during the first 48 hours. An rSO2 of 62.5% had a sensitivity of 83% and specificity of 67% to differentiate survivors and nonsurvivors of septic shock at 48 hours. StO2 had a higher correlation with ScvO2 and serum lactate than rSO2., Conclusions: StO2 prognosticates survival and favorable/unfavorable outcomes in neurological patients with sepsis. The role of rSO2 in predicting survival in milder form of sepsis is doubtful.

Background: Fetal environment has a substantial influence on an individual's health throughout their life course. Animal models of hypertensive disease of pregnancy have demonstrated adverse health outcomes among offspring exposed to hypertensive disease of pregnancy in utero. Although there are numerous descriptions of the neonatal, infant, and pediatric outcomes of human offspring affected by hypertensive disease of pregnancy, there are few data in US populations on later life outcomes, including mortality., Objective: To assess risk for early mortality among offspring of pregnancies complicated by hypertensive disease of pregnancy., Study Design: This is a retrospective cohort study of offspring born to women with singleton or twin pregnancies between 1947 and 1967 with birth certificate information in the Utah Population Database. We identified offspring from delivery diagnoses of gestational hypertension, preeclampsia, or eclampsia. Offspring from these pregnancies (exposed) were matched to offspring of pregnancies without hypertensive disease of pregnancy (unexposed) by maternal age at delivery, birth year, sex, and multiple gestation. We also identified unexposed siblings of exposed offspring for a separate sibling analysis. Mortality follow-up of all offspring continued through 2016, at which time they would have been 49-69 years old. Adjusted hazard ratios for cause-specific mortality comparing exposed with unexposed offspring were estimated using Cox proportional hazard models., Results: We compared mortality risks for 4050 exposed offspring and 6989 matched unexposed offspring from the general population and 7496 unexposed siblings. Mortality risks due to metabolic, respiratory, digestive, nervous, and external causes of death did not differ between exposed and unexposed groups. Mortality risks from cardiovascular disease were greater in exposed offspring compared with unexposed offspring (adjusted hazard ratio, 1.57; 95% confidence interval, 1.16-2.12). In sex-specific models among the general population, cardiovascular disease mortality was significantly associated with exposure among male patients (adjusted hazard ratio, 1.92; 95% confidence interval, 1.27-2.88) but not among female patients (adjusted hazard ratio, 0.97; 95% confidence interval, 0.81-1.94). An interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality was significant (P=.047), suggesting that the effect of hypertensive disease of pregnancy on cardiovascular disease mortality increased with higher birth order. Among siblings, the association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality was not significant (adjusted hazard ratio, 1.39; 95% confidence interval, 0.99-1.95), and this was also true for sex-specific analyses of males (adjusted hazard ratio, 1.26; 95% confidence interval, 0.81-1.94) and females (adjusted hazard ratio, 1.71; 95% confidence interval, 0.96-3.04). As in the general population, there was a significant interaction between hypertensive disease of pregnancy exposure and birth order on cardiovascular disease mortality (P=.011)., Conclusion: In a US population, overall mortality risks are greater for offspring of pregnancies complicated by hypertensive disease of pregnancy compared with unexposed offspring. Among siblings, there was not a significant association between hypertensive disease of pregnancy exposure and cardiovascular disease mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To explore the predictive value of serum creatinine (Cr) to cystatin C (CysC) ratio in neurocritically ill patients., Methods: We conducted a retrospectively observational study of adult patients admitted to a neurocritical care unit (NCU) between Jan 2013 and Jan 2017. Patients were excluded if <18 years old, required neurocritical care <72 hr, did operation during hospitalization, had premorbid disability or acute kidney injury (AKI) at admission. The Cr/CysC ratio was obtained at NCU admission. Primary end points were short-term (30-day) mortality and long-term (6-month) poor outcome, with the latter defined as modified Rankin Scale (mRS) of 4-6., Results: Of 538 eligible patients, the etiology included acute ischemic stroke (N = 193, 35.9%), intracranial hemorrhage (N = 116, 21.6%), encephalitis and/or meningitis (N = 85, 15.8%), and others (N = 144, 26.7%). Serum Cr/CysC ratio was significantly correlated with body mass index (BMI) (r = .161, p < .001), the length of NCU stay (r = -.161, p < .001), duration of mechanical ventilation (r = -.138, p = .001), and risk of tracheotomy (r = -.095, p = .028). During follow-up, 88 (16.4%), patients died within 30 days and 307 (57.1%) patients achieved good outcome at 6 months. In multivariate logistic regression analysis, we identified serum Cr/CysC ratio as an independent predictor of long-term functional outcome (OR: 0.989, 95% CI: 0.980-0.998, p = .015) but not 30-day mortality (p = .513)., Conclusions: Serum Cr/CysC ratio at admission could be used as a predictor of long-term poor prognosis in neurocritically ill patients., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

The serum lactate level is a useful predictor of mortality in critically ill patients. However, little is known about the association between the serum lactate level and mortality in patients admitted to neuro-intensive care units (NCUs). The present study aimed to investigate the association between the initial lactate level and 90-day mortality in NCU patients. This retrospective observational study was conducted by reviewing the medical records of adult (age ≥18 years) patients admitted to the NCU at a single tertiary care academic hospital during 2013-2017. The initial lactate level (mmol L -1 ) was defined as the serum lactate level measured within 6 h following NCU admission. The final analysis included 2737 patients, of whom 280 (10.2%) died within 90 days of NCU admission. In a receiver operating characteristic (ROC) analysis, the estimated area under the curve (AUC) for the initial lactate level in predicting overall 90-day mortality was 0.55 [95% confidence interval (CI): 0.52-0.59]. The corresponding values for neurologic and non-neurologic disease-related 90-day mortality were 0.76 (95% CI: 0.71-0.82) and 0.49 (95% CI: 0.45-0.53), respectively. In a multivariable Cox regression analysis, a 1-mmol L -1 increase in the initial lactate level was associated with 1.17- and 1.22-fold increases in overall and neurologic disease-related 90-day mortality, respectively, but not with non-neurological disease-related 90-day mortality (P = 0.422). Elevated lactate levels were related with an increase in overall 90-day mortality among NCU patients. This association was specifically attributed to neurologic disease-related 90-day mortality., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Right ventricular RV dysfunction among transplant recipients correlates with transplant outcome, but its frequency in donors is unknown. The purpose of this study was to describe the epidemiology of RV dysfunction in potential heart donors.", Methods: In a seven-year retrospective study of potential heart donors, we explored the incidence of RV dysfunction as observed on echocardiography and explored the association of four distinct factors with RV dysfunction: brain injury diagnosis, thoracic trauma, vasopressin infusion and left ventricular (LV) dysfunction., Results: All 123 potential heart donors underwent echocardiography: 55 had RV dysfunction (44.7%). Fourty-one (33.3%) had LV dysfunction. Isolated RV dysfunction was present in 27 subjects (22%). LV dysfunction was the only factor significantly associated with RV dysfunction (OR = 4.6 (95% CI 1.9-11.4)). We observed no difference in heart acceptance between subjects with or without RV dysfunction., Conclusion: We observed a high frequency of RV dysfunction in a sample of potential heart donors. However, the temporal evolution of RV dysfunction, the hemodynamic predictors of RV dysfunction, as well the link between donor RV dysfunction and recipient outcomes need to be assessed with further prospective studies., (Copyright © 2019. Published by Elsevier Inc.)

Background: Vitamin D deficiency is related to various cardiovascular diseases, including sudden cardiac arrest (SCA). This study investigated the association of vitamin D level with neurologic outcome and mortality after resuscitation from SCA., Patients and Methods: We enrolled patients who were successfully resuscitated from out-of-hospital cardiac arrest of presumed cardiac cause in Severance Cardiovascular Hospital as a prospective cohort registry. Baseline blood samples including pH, lactate, and vitamin D were obtained without fluid replacement just after hospital admission. Outcome was assessed by cerebral performance category (CPC) score at 1 month after SCA. Favorable outcome was defined as survival with CPC score of 1 or 2, whereas unfavorable one as death or survival with CPC scores of 3 through 5. Severe vitamin D deficiency was defined as 25(OH)D <10 ng/mL., Results: A total of 163 patients were included. Overall 96 (59%) patients had a favorable neurologic outcome, whereas 67 patients (41%) showed unfavorable outcome, including 37 (23%) mortality. Patients with unfavorable outcome were likely to be female and have initial non-shockable rhythm, longer arrest time, severe shock, diabetes, and baseline renal dysfunction. In multivariate analysis, severe vitamin D deficiency was one of the poor prognostic factors of both unfavorable neurologic outcome and mortality after SCA., Conclusions: Vitamin D deficiency is very prevalent and strongly associated with both unfavorable neurologic outcome and mortality in patients resuscitated from SCA.

Background: In patients with severe neurologic conditions, percutaneous endoscopic gastrostomy (PEG) is typically performed either alone or with a tracheostomy. The characteristics and outcomes of patients receiving PEG concomitantly with a tracheostomy (CTPEG) and those receiving delayed PEG (DPEG) after a tracheostomy were compared., Methods: Retrospective cohort study in a 24-bed neuroscience critical care unit (NCCU) at a tertiary care hospital. Consecutive patients admitted to the NCCU from April 2007 to July 2013 who underwent percutaneous tracheostomy and gastrostomy by the percutaneous tracheostomy team were included and grouped according to the timing of PEG placement: CTPEG versus DPEG., Results: Of the 290 patients, 234 (81%) received CTPEG. Demographic and clinical characteristics were similar among the 2 groups except for a lower median (interquartile range [IQR]) body mass index (BMI; 27 [22.67-31.60] versus 30.8 [24.55-40.06], P = .017) and lower rate of acute respiratory distress syndrome (3.85% vs 10.71%, P = .048) in the CTPEG cohort. Furthermore, 59% of CTPEG cohort were neurology patients while 63% of DPEG were neurosurgery patients, P = .004. Primary outcomes showed shorter mean NCCU length of stay (LOS; 25 [12] vs 33 [17] days, P < .001) and median hospital LOS (32 [25-43] vs 37 [31-56] days, P = .002) for the CTPEG cohort. Secondary outcomes showed higher predischarge prealbumin levels (15.6 [7.75] vs 11.58 [5.41], P = .021) and lower median overall hospital cost (US$123 860.20 [US$99 024-US$168 713.40] vs US$159 633.50 [US$121 312-US$240 213.10], P = .0003) in the CTPEG group. Anatomic contraindications were the most common reason for DPEG (30%)., Conclusions: Among institutions with a tracheostomy team, the practice of tracheostomy with concomitant PEG placement may be considered as feasible as delayed PEG in carefully selected neurocritically ill patients with possible advantages of overall shorter NCCU and hospital LOS, higher predischarge prealbumin, and lower hospital costs. These findings may aid in decisions regarding the timing of PEG placement in the NCCU. Further prospective studies are warranted.

Introduction: Delayed cerebral ischaemia (DCI) is one of the most frequent complications of aneurysmal subarachnoid haemorrhage (aSAH). The purpose of the present retrospective cohort study of patients with aSAH was to identify the association between DCI, functional outcome and 4-year mortality., Methods: Patients admitted to the Neurointensive Care Unit at Rigshospitalet, Copenhagen, with aSAH from 1 January 2010, through 31 December 2013 were registered. Patients were categorized into 3 groups: (a) those with DCI, defined as either a decline in consciousness or focal neurological deficits lasting ≥1 hour without any other detectable cause, (b) those without DCI, or (c) those who were unassessable for DCI. Functional neurological outcome after 6 months, as measured by the modified Rankin Scale (mRS), was dichotomized into good (mRS 0-2) and poor (mRS 3-6). Kaplan-Meier survival curves were constructed, and incidence risk rates were calculated both to determine the association between DCI and mortality., Results: Four hundred ninety-two cases of aSAH were recorded in the study period. DCI occurred in 23% of all patients, corresponding to 33% of assessable patients. Patients without DCI had the best functional outcome (mRS) compared to patients with DCI and patients who were unassessable; furthermore, the latter had worse outcomes than patients with DCI. Patients diagnosed with DCI had significantly higher mortality than those without DCI, even ignoring the first 14 days after admission., Conclusion: DCI may be associated with both short- and long-term morbidity and mortality in patients with aSAH., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: To investigate the effect of neutrophil-lymphocyte ratio (NLR) on survival and mortality in patients who were interned in the Neurology Intensive Care Unit (NICU)., Study Design: A cohort study., Place and Duration of Study: Tertiary referral hospital in Bolu, Turkey, between February 2016 and November 2017., Methodology: Demographic data, hemogram and other laboratory parameters of the patients who were treated in NICU were retrospectively recorded. The patients who had a history of hematologic disease and/or premorbid use of corticosteroids were excluded from the study. Patients were divided into two groups: surviving and dead patients. Mann- Whitney U-test, Independent sample t-test or Chi-square test was used to compare the data between the groups, including demographic parameters, NLR and other blood parameters., Results: A total of 120 patients were studied. There was no significant difference in age, gender, hemoglobin (Hb), platelet (PLT), and erythrocyte distribution width (RDW) between the two groups. On the other hand, The NLR values [(3.9 (0.9-48) vs. 11.9 (0.9-69, p <0.001))], C-reactive protein [CRP=(25.6 mg/dL (0.1-250) vs. 57.7 mg/dL (1.2-337, p <0.002)] and white blood cell [WBC=(8.9 μ/mm3 (3-59.8) vs. 12.4 μ/mm3 (5-41.3), p <0.002)] were significantly higher in dead patients compared to survived patients., Conclusion: Elevated NLR ratio in NICU patients may be considered as a poor prognostic factor. Clinicians should be more cautious in the follow-up of these patients.

Objective: Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (allo-HCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence, and impact on survival., Methods: We searched MEDLINE, COCHRANE, EMBASE through March 2019 for all types of primary studies. Two independent reviewers screened, extracted data, and assessed risk of bias (RoB)., Results: We identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case-control, 17 prospective, 86 retrospective cohort studies, 21 case series, and 425 case reports. RoB ranged from fair to high although case series were low-risk. The majority of studies traced infectious or drug-related neurologic manifestations. Infectious complications were present in 2.7% (95% CI 1.9-3.6) and 3.3% (95% CI 0.8-7.1) of patients in retrospective and prospective cohort studies, respectively. In retrospective studies, 3.4% (95% CI 2.1-4.9) of patients suffered from drug-related neurologic events. In prospective cohorts the equivalent incidence was 13% (95% CI 4.2-24.8). Neurologic complications had a detrimental impact on survival., Interpretation: Our study highlights the wide spectrum and significant impact of neurologic complications on survival post allo-HCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Objective: Neurologic injury complicating the presentation of acute type A aortic dissection remains a challenge for cardiac surgeons., Methods: This was a retrospective review of patients undergoing open repair of acute type A aortic dissection at our institution between January 2005 and December 2015. Evidence of neurologic injury at the time of presentation was abstracted from the medical record. Propensity-score matching was used to account for baseline differences between groups, and outcome analysis was performed using logistic regression and Kaplan-Meier analysis. Among patients with persistent neurologic deficits, a threshold for time-to-operation was evaluated using receiver operating characteristic curves., Results: There were 345 patients who underwent open repair for acute type A aortic dissection; 50 patients presented with neurologic injury. In the matched analysis, in-hospital mortality was greater among patients who presented with neurologic deficits (odds ratio, 4.42; 95% confidence interval, 1.15-16.97; P = .03). Among patients with persistent neurologic deficits at presentation, receiver operating characteristic curve analysis with cross-validation suggested that time-to-operation was a poor predictor of both neurologic outcome (area under the curve, 0.40) and death (area under the curve, 0.49)., Conclusions: Neurologic injury at the time of presentation with acute type A aortic dissection was associated with an increased risk of in-hospital mortality. Among patients with persistent neurological deficits, time-to-operation failed to predict either neurologic outcome or perioperative mortality suggesting that longer time from onset of symptoms of neurologic injury should not act as a contraindication to proceeding to the operating room for expedient repair., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Paying attention to men's health seems quite important for a variety of reasons. We evaluated the change of mortality rates due to various causes in Iranian men over the past decades., Study Design: A cross-sectional study., Methods: The mortality rates for deadliest causes of diseases among Iranian men during 1990-2016 were extracted from the Global Burden of Disease (GBD) study. Latent Growth Mixture Models (LGMM) were applied to determine subgroups' cause of death. In this way, the causes within each group showed similar trends of mortality rates over time., Results: The LGMM clustered causes into 4 classes. Diabetes mellitus, hypertensive heart disease and neurological disorders have had increasing trend. Causes in class 2, including diarrhea, lower respiratory and other common infectious diseases, ischemic heart disease, ischemic stroke, neonatal disorders, and other non-communicable diseases manifested a slow decreasing trend. Most causes were allocated to 3rd class with a slow increase in mortality rates over time. Finally, within the last class, transport injuries and unintentional injuries revealed a decreasing trend., Conclusion: Most factors have rising trend, despite the fact that some have shown a very slight downward trend. Consequently, according to the four distinguished clusters resulting from LGMM, it is essential to provide programs to attain the goal of access to prevention, treatment, and support for high-risk mortality factors.

Introduction: Background and aims: home enteral nutrition (HEN) is an established treatment for clinically stable patients. The objective of this study was to determine the frequency and the situation of patients in HEN, in the capital city in the south of Brazil. Methods: in this retrospective study, we recorded all new cases of HEN in adults in Curitiba, Brazil, from January 2006 to December 2015. Data were collected by a dietitian from medical records of patients attending public health settings. The following data were analyzed: clinical diagnosis, diet prescribed during hospitalization and at discharge, and feeding access types. Kaplan-Meier and Cox regression analyses were used to calculate survival. Results: a total of 1,231 patients were included. There was a 425% increase in the frequency of HEN over the years studied. The mean age was 66.7 years, and 54.4% were men. Neurological diseases were the most prevalent (46.4%), followed by cancer (33.6%). Eight hundred and one patients (65.1%) died during this period. Mean HEN duration was 180 days (95% CI 163.6-193.4), with a significant difference between neurological diseases (median: 180 days) and cancer (median: 210 days) (p < 0.05). Neurological disease was an independent risk factor for mortality in patients on HEN (HR: 1.17; CI: 1.08-1.27). Conclusions: the study shows an increase in HEN. Neurological diseases prevailed and presented a risk of mortality, and more than half of the patients with NED died in this period.