Severe Neurological Morbidity Research Articles

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Abstract PO1-20-10: Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity

Abstract Wernicke encephalopathy (WE) is an acute medical syndrome that manifests as a clinical triad of encephalopathy, gait ataxia, and oculomotor dysfunction, requiring urgent treatment. Early recognition and treatment can prevent severe neurological morbidity and the chronic neurological consequence of WE, known as Korsakoff syndrome. Thiamine (vitamin B1) deficiency is the root cause of WE, which can occur due to several underlying conditions, including chronic alcoholism, hyperemesis of pregnancy, malnutrition, prolonged fasting, and malignancy. In cases of malignancy, WE is often undiagnosed or misdiagnosed because the presenting symptoms can be confused with several other complications of malignancy. We present the case of a 47-year-old woman with no significant medical history who was diagnosed with triple negative metastatic breast cancer and admitted to the hospital with confusion, memory loss, and progressive lower extremity weakness. During her breast cancer treatments, she experienced significant nausea and vomiting, leading to a prolonged state of nutritional imbalance. Patient underwent extensive infectious and neurological workup for encephalopathy including lumbar puncture which was negative for leptomeningeal disease or infection. MRI brain did not show any new metastatic lesions however revealed enhancement of mammillary bodies bilaterally. Mammillary body enhancement can be seen in WE but not always present on imaging. She was treated for WE with high dose of thiamine infusion for five days, resulting in an improvement of her neurological symptoms. Diagnosing WE in cancer patients is challenging, as there are various factors to consider, such as cerebral metastasis, infection, chemotherapy treatment, and electrolyte imbalances, that can cause neurological symptoms. Cancer patients are at high risk for development of WE due to chemotherapy or whole brain radiation induced nausea and vomiting that can lead to chronic malnutrition. The typical triad of symptoms is not present in many cases and presenting symptoms can be nonspecific which makes the diagnosis challenging. As a result, WE is often underdiagnosed in such patients, making it essential to educate the physician community about this acute neurological manifestation that can be easily treated. A high index of suspicion is necessary for early recognition, and prompt treatment can prevent Korsakoff syndrome, thereby enhancing the overall quality of life of patients with malignancy. Citation Format: Archit Patel, Arya Mariam Roy, Ronald Alberico, Shipra Gandhi. Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-10.

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study

BackgroundThe aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. MethodsThis was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000–2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests.Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. FindingsThe final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0·19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13·2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0·74%), with the highest rate (19·6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7·59% livebirths), with the peak incidence occurring in the <1st centile category (12·3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10–90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. InterpretationAlthough the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently “appropriately grown” (i.e., birthweight 10th - 90th centile). FundingNational Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women’s Health Foundation – Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

Five-minute Apgar score and risk of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity in term infants – an Australian population-based cohort study

The aim of this study was to ascertain risks of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity related to the 5-min Apgar score in early term (37+0-38+6 weeks), full term (39+0-40+6 weeks), late term (41+0-41+6 weeks), and post term (≥42+0 weeks) infants. This was a retrospective cohort study of 941,221 term singleton births between 2000 and 2018 in Queensland, Australia. Apgar scores at 5-min were categorized into five groups: Apgar 0 or 1, 2 or 3, 4-6, 7 or 8 and 9 or 10. Gestational age was stratified into 4 groups: Early term, full term, late term and post term. Three specific neonatal study outcomes were considered: 1) Neonatal mortality 2) Severe neurological morbidity and 3) Severe non-neurological morbidity. Poisson multivariable regression models were used to determine relative risk ratios for the effect of gestational age and Apgar scores on these severe neonatal outcomes. We hypothesized that a low Apgar score of <4 was significantly associated with increased risks of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity. Of the study cohort, 0.04% (345/941,221) were neonatal deaths, 0.70% (6627/941,221) were infants with severe neurological morbidity and 4.3% (40,693/941,221) had severe non-neurological morbidity. Infants with Apgar score <4 were more likely to birth at late term and post term gestations and have birthweights <3rd and <10th percentiles. The adjusted relative risk ratios (aRRR) for neonatal mortality and severe neurological morbidity were highest in the Apgar 0 or 1 cohort. For infants in the Apgar 0 or 1 group, neonatal mortality increased incrementally with advancing term gestation: early term (aRRR 860.16, 95% CI 560.96, 1318.94, p<0.001); full term (aRRR 1835.77, 95% CI 1279.48, 2633.91, p<0.001); late term (aRRR 1693.61, 95% CI 859.65, 3336.6, p<0.001) and post term (aRRR 2231.59, 95% CI 272.23, 18293.07, p<0.001) whilst severe neurological morbidity decreased as gestation progressed: early term (aRRR 158.48, 95% CI 118.74, 211.51, p<0.001); full term (aRRR 112.99, 95% CI 90.56, 140.98, p<0.001); late term (aRRR 87.94, 95% CI 67.09, 115.27, p<0.001) and post term (aRRR 52.07, 95% CI 15.17, 178.70, p<0.001). Severe non-neurological morbidity was greatest in the full term, Apgar 2-3 cohort (aRRR 7.36, 95% CI 6.2, 8.74, p<0.001). A 5-min Apgar score of <4 was prognostic of neonatal mortality, severe neurological morbidity, and severe non-neurological morbidity in infants born >37 weeks' gestation with the risk greatest in the early term cohort. National Health and Medical Research Council and Mater Foundation.

Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial

The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone. RATIO37 was a randomised, open-label, multicentre, pragmatic trial, conducted in low-risk pregnant women, recruited from nine hospitals over six countries. The eligibility criteria were designed to be broad; participants were required to be 18 years or older, with an ultrasound-dated confirmed singleton pregnancy in the first trimester, an alive fetus with no congenital malformations at the routine second-trimester ultrasound, an absence of adverse medical or obstetric history, and the capacity to give informed consent. Women were randomly assigned in a 1:1 ratio (block size 100) using a web-based system to either the concealed group or revealed group. In the revealed group, the cerebroplacental ratio value was known by clinicians, and if below the fifth centile, a planned delivery after 37 weeks was recommended. In the concealed group, women and clinicians were blinded to the cerebroplacental ratio value. All participants underwent ultrasound at 36 + 0 to 37 + 6 weeks of gestation with growth assessment and Doppler evaluation. In both groups, planned delivery was recommended when the estimated fetal weight was below the tenth centile. The primary outcome was perinatal mortality from 24 weeks' gestation to infant discharge. The study is registered at ClinicalTrials.gov (NCT02907242) and is now closed. Between July 29, 2016, and Aug 3, 2021, we enrolled 11 214 women, of whom 9492 (84·6%) completed the trial and were eligible for analysis (4774 in the concealed group and 4718 in the revealed group). Perinatal mortality occurred in 13 (0·3%) of 4774 pregnancies in the concealed group and 13 (0·3%) of 4718 in the revealed group (OR 1·45 [95% CI 0·76-2·76]; p=0·262). Overall, severe neonatal morbidity occurred in 35 (0·73%) newborns in the concealed group and 18 (0·38%) in the revealed group (OR 0·58 [95% CI 0·40-0·83]; p=0·003). Severe neurological morbidity occurred in 13 (0·27%) newborns in the concealed group and nine (0·19%) in the revealed group (OR 0·56 [95% CI 0·25-1·24]; p=0·153). Severe non-neurological morbidity occurred in 23 (0·48%) newborns in the concealed group and nine (0·19%) in the revealed group (0·58 [95% CI 0·39-0·87]; p=0·009). Maternal adverse events were not collected. Planned delivery at term based on ultrasound fetal growth assessment and cerebroplacental ratio at term was not followed by a reduction of perinatal mortality although significantly reduced severe neonatal morbidity compared with fetal growth assessment alone. La Caixa foundation, Cerebra Foundation for the Brain Injured Child, Agència per la Gestió d'Ajuts Universitaris i de Recerca, and Instituto de Salud Carlos III.

Transuterine Ultrasound-Guided Fetal Embolization of Vein of Galen Malformation, Eliminating Postnatal Pathophysiology.

Transuterine Ultrasound-Guided Fetal Embolization of Vein of Galen Malformation, Eliminating Postnatal Pathophysiology.

Retrospective Evaluation of Patients with Infantile Spasm Diagnosis

Introduction: Infantile spasm (West Syndrome) (IS) is an age-dependent epileptic encephalopathy clinic specific to the first two years of life. Infantile spasm is the most known epileptic syndrome of infancy with typical seizures in the form of spasm, psychomotor retardation and hypsarrhythmia on electroencephalography. Typical spasms are in the form of flexor/extensor contractions that last for about 2-5 seconds, which usually symmetrically involves all muscle groups in the body. Material and Method: In this study, the data of patients, who were followed up with the diagnosis of "infantile spasm" in the Pediatric Neurology Clinic of Mersin City Training and Research Hospital between 2020 and 2022, were retrospectively analyzed. Demographic characteristics, clinical, EEG and MRI findings of the patients were analyzed. Results: Eighteen patients were included in the study. Ten (55.5%) of our patients were male and 8 (44.5%) were female. The mean age of patients was ……. years. 11 (61.1%) patients were in the symptomatic group, 5 (27.7%) patients were in the cryptogenic group, and 2 (11.1%) patients were in the idiopathic group. At the time of diagnosis, there was flexor spasm, extensor spasm, mixt spasm, tonic seizure, myoclonic seizure in 5 (27,7%), 4 (22,2%), 4 (22,2%), 3 (16,6%), and 2 (11,1%) patients, respectively. Hypsarrhythmia, suppression-burst pattern, focal epileptic abnormality and generalized epileptic abnormality was observed in 8 (44,4%), 4 (22,2%), 3 (16,6%), and 3 (16,6%) patients, respectively. Of the 14 patients who were first diagnosed, 8 (57.1%) were treated with ACTH, 4 (28.6%) with phenobarbital, 2 (14.3%) with vigabatrin. Conclusion: Infantile spasm is an important age-related encephalopathy with severe neurological sequelae, resistant seizures, and high morbidity and mortality all over the world and in our country. Spasms cause further damage to the central nervous system, which continues to develop. For this reason, a positive contribution can be made in terms of prognosis with early and appropriate treatment.

Selective vs complete fetoscopic coagulation of vascular equator: a matched comparative study

Complete coagulation of the vascular equator (asin the Solomon technique) has been suggested to reduce postoperative complications such as twin anemia polycythemia syndrome and the recurrence of twin-twin transfusion syndrome following fetoscopic laser coagulation of chorionic vessels for twin-twin transfusion syndrome. We aimed to evaluate the benefit of this technique on perinatal outcomes compared with selective ablation of anastomoses. We conducted a monocentric retrospective study comparing selective laser coagulation of anastomoses to the Solomon technique from January 2006 to August 2020. To adjust for potential confounders, the cases operated by selective surgery were matched to the cases operated with the Solomon technique according to the gestational age at laser therapy, placental localization, and Quintero stage using propensity score matching. With a total of 994 cases, 399 matched pairs were included in the analysis. Compared with selective ablation, the Solomon technique was associated with significantly improved survival: the overall twin survival at delivery and discharge was 72% vs 79% (P=.003) and 69% vs 75% (P=.006), respectively; the double twin survival rate at discharge was 55% vs 65% (P=.02), respectively, and the rate of intrauterine death dropped from 18% to 12% (P=.003), respectively. The Solomon technique significantly reduced the rate of twin anemia polycythemia syndrome (10% vs 4%; P=.02), leading to fewer secondary rescue procedures (13% vs 7.3%; P=.01). However, the Solomon technique was associated with an increased risk of preterm rupture of membranes, especially at early gestational ages (3.8% vs 11%; P<.001 for preterm rupture of membranes <24 weeks). Among the survivors at delivery, both the groups had similar gestational ages at birth. Both neonatal mortality and severe neurologic morbidity were similar in both the groups. However, an increased risk of bronchopulmonary dysplasia was found in the Solomon group (4.5% vs 12%; P<.001). Although the risk of preterm premature rupture of membranes has increased, the introduction of the Solomon technique has significantly improved perinatal outcomes in pregnancies affected with twin-twin transfusion syndrome.

Outcomes of laser surgery for stage I twin-twin transfusion syndrome.

A recent randomized controlled trial (RCT) demonstrated no difference in 6month survival in expectantly managed stage I twin-twin transfusion syndrome (TTTS) patients and those undergoing immediate laser surgery. We aimed to describe outcomes following immediate laser surgery at a single fetal surgery center. A retrospective study of monochorionic diamniotic twins diagnosed with stage I TTTS who underwent laser surgery between 16 and 26 gestational weeks from 2006 to 2019. The primary outcome was 6month survivorship. Intact survival was also assessed. Secondarily, outcomes were compared to the RCT expectant management group. Of 126 consecutive stage I TTTS patients, 114 (90.5%) met inclusion criteria. Median (range) gestational age at delivery was 34.1 (20.6-39.4) weeks. At 6months, the proportion of patients with at-least-one survivor in the single-center-laser cohort was 97.4%, with 88.6% dual survivorship. Neurological morbidity outcomes were available in 110 pregnancies (220 fetuses). Severe neurological morbidity occurred in 2.7% (6/220), and 6month survival without severe neurological morbidity was 90.0%. Outcomes compared favorably with the RCT expectant management group. Given favorable survival and neurological outcomes, laser surgery is a reasonable treatment option for stage I TTTS at experienced fetal surgery centers. Further study is warranted to optimize treatment strategies.

Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

BackgroundHypoxic-ischemic brain damage (HIBD) significantly affects neurodevelopment in infants and is a leading cause of severe neurological morbidity and mortality in neonates. Our previous study found that photobiomodulation therapy (PBMT) improves the impaired spatial learning and memory of HIBD rat models. However, the neuroprotective mechanism conferred by PBMT in HIBD is unclear.MethodsIn the present study, HIBD model rats were treated with PBMT at 5 mW/cm2 per day in the dark for 14 days (10 min each day), and primary neural stem cells (NSCs) after oxygen-glucose deprivation (OGD) were treated with PBMT for 10 min at 1, 5, 10, and 20 mW/cm2 in the dark. PBMT promoted hippocampal neural stem cell (NSC) proliferation in vivo and in vitro.ResultsMechanistically, PBMT upregulated phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β), β-catenin, and cyclin D1 expression in vivo and in vitro, promoting NSC proliferation. Furthermore, both LY294002 (a PI3K inhibitor) and IWR-1 (a Wnt/β-catenin inhibitor) inhibited the PBMT promotion of NSC proliferation after OGD and suppressed β-catenin and cyclin D1 expression in vitro.ConclusionsPBMT improved the spatial learning and memory of HIBD rats and promoted hippocampal NSC proliferation through the AKT/GSK-3β/β-catenin pathway.

Perinatal outcome of pregnancy complicated by twin anemia-polycythemia sequence: systematic review and meta-analysis.

To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Intraoperative brain mapping during awake surgery in symptomatic supratentorial cavernomas

BackgroundComplete resection of symptomatic supratentorial cavernoma (SCA) and removal of the surrounding gliotic area is recommended to minimize the risk of persistent seizures or (re)bleeding. Surgery of SCA located in an eloquent area, can carry out severe postoperative neurological morbidity. We report a study aimed to assess feasibility, extent of resection and outcome after surgical removal of CA by cortico-subcortical intraoperative brain stimulation (ioBS) in the awake patient. MethodsSix patients diagnosed of symptomatic SCA located on an eloquent area and operated on while awake under local anaesthesia ioBS, were included. Preoperative planning included neuropsychologic assessment of language-related functions, sociocognitive functions and executive functions. Intraoperatively, we recorded the results achieved in the planned neuropsychological tasks when stimulation was applied (cortical and subcortical). Postoperative control 3D MRI was scheduled at 1 month after surgery to calculate extent of resection. Neuropsychological assessment at 6 months after surgery was performed in all cases. ResultsSix patients (5 females, 1 male) aged 24–48 years were included in our study. Locations of the lesions were right insular (n=1), left insular (n=1), left temporo-insular (n=1), left temporal (n=2) and left frontal (n=1). In all patients, positive findings were obtained during ioBS. In 5 patients, complete surgical resection was achieved. Two patients had postoperative transient neurological deficits, one case of hemiparesis, one case of dysnomia, both cleared over a 6-month period. Clinical follow-up revealed that all patients experienced complete recovery from preoperative symptoms within a year and five patients with seizures showed marked improvement and eventually quit antiepileptic drugs. Neuropsychological assessment at 6 months provided normal results compared to preoperative baseline in all domains. ConclusionsOur study suggests that ioBS in the awake surgery of symptomatic SCA located in eloquent areas, allows to increase the rate of complete resection, minimizing postoperative neurological and neuropsychological deficit, and improving postoperative seizures control.

Maternal near-miss attributable to haemorrhagic stroke in patients with hypertensive disorders of pregnancy in Japan: A national cohort study.

To investigate the epidemiologic and clinical characteristics of maternal near-misses attributable to haemorrhagic stroke (HS) occurring in patients with hypertensive disorders of pregnancy (HDP), with a focus on severe neurological morbidity. A national retrospective cohort study was conducted using the national database of health insurance claims for the period 2010 to 2017. The subjects were all insured women with a diagnosis of both HDP and HS. Severe neurological morbidity requiring rehabilitation, types of HDP, types of HS, and magnesium sulphate use were tabulated. The number of women with HDP who were diagnosed with HS was 3.4 per 100,000 deliveries between 2010 and 2017. Forty percent of HDP-related HS cases had neurological morbidities requiring rehabilitation (1.4 per 100,000 deliveries), and 4.4% were in a persistent vegetative state after HS. Of the HDP cases who developed HS, 69.2% were severe HDP, of which 55.6% were without eclampsia. The most common type of HS was intracerebral haemorrhage (2.5 per 100,000 deliveries), followed by subarachnoid haemorrhage due to cerebral aneurysm (1.2 per 100,000 deliveries). The frequency of magnesium sulphate use increased in all patients with HDP-related HS in the second half of the study period (2014-2017) compared with the first half (2010-2013) (p<0.0001). This was more evident in cases of HDP-related HS with eclampsia (31.9% to 83.8%) compared to those without eclampsia (25.0% to 42.9%). Of the maternal near-miss cases due to HDP-related HS, 40.0% were rehabilitated and 69.2% were HDP without either eclampsia or severe hypertension.

Does general comorbidity impact the postoperative outcomes after surgery for large and giant petroclival meningiomas?

We assessed the role of the general condition of the patient in addition to usual anatomical reasoning to improve the prediction of personalized surgical risk for patients harboring a large and giant petroclival meningiomas. Single-center, retrospective observational study including adult patients surgically treated for a large and giant petroclival meningioma between January 2002 and October 2019 in a French tertiary neurosurgical skull-base center by one Neurosurgeon. Inclusion criteria were as follows: (1) histopathologically proven meningioma; (2) larger than 3cm in diameter; (3) located within the upper two-thirds of the clivus, the inferior petrosal sinus, or the petrous apex around the trigeminal incisura, medial to the trigeminal nerve. Clinical and radiological characteristics were gathered preoperatively including ASA score, the modified frailty index, and the Charlson comorbidity index. Post-operative severe neurological and non-neurological complications were collected. A total of 102 patients harboring a large and giant petroclival meningioma were included. The rate of postoperative death was 3.0% related to a congestive heart failure (n = 1), a surgical site hematoma (n = 1), and an ischemic stroke (n = 1). A severe neurological impairment was found in 12.8% and a severe non-neurological morbidity was found in 4.0%. The overall rate of severe morbidity and mortality was 15.7% after large and giant petroclival meningioma surgery. The presence of brainstem peri-tumoral edema (adjusted OR, 4.83 [95% CI 1.84-7.52], p = 0.028) was independently associated with a history of postoperative severe neurological morbidity. Male gender (adjusted OR, 7.42 [95% CI 1.05-49.77], p = 0.044), major cardiovascular morbidity (adjusted OR, 9.5 [95% CI 1.05-86.72], p = 0.045), and an ASA score ≥ 2 (adjusted OR, 11.09 [95% CI 1.46-92.98], p = 0.038) were independently associated with a history of postoperative severe non-neurological morbidity. A modified frailty index ≥ 1 (adjusted OR, 3.13 [95% CI 1.07-9.93], p = 0.047) and a low neurosurgical experience (adjusted OR, 5.38 [95% CI 1.38-20.97], p = 0.007) were independently associated with a history of postoperative overall morbidity and mortality. Pre-operative cranial nerve deficits (adjusted OR, 4.77 [95% CI 1.02-23.31], p = 0.024) and gross total resection (adjusted OR, 10.72 [95% CI 1.72-66.90], p = 0.022) were independently associated with postoperative new cranial nerve deficits. This study suggests to add scores assessing the patient general condition in daily practice to improve the selection of patients eligible for surgery. Collaborative international multicenter studies will be necessary to confirm these results and allow their implementation in clinical routine.

Perinatal outcome of monochorionic diamniotic twin pregnancy complicated by selective intrauterine growth restriction according to umbilical artery Doppler flow pattern: single-center study using strict fetal surveillance protocol.

To determine the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective intrauterine growth restriction (sIUGR), which were classified according to the umbilical artery (UA) Doppler flow pattern of the IUGR twin. This was a retrospective cohort study of all MCDA twin pregnancies diagnosed with sIUGR and managed at a single tertiary referral center between 2012 and 2018. Cases were classified according to the UA Doppler flow pattern of the IUGR twin as Type I (positive end-diastolic flow), Type II (persistently absent/reversed end-diastolic flow) or Type III (intermittently absent/reversed end-diastolic flow). Patients with Type-II or -III sIUGR were hospitalized at 26-28 weeks of gestation for increased fetal surveillance. Perinatal and immediate and long-term neurodevelopmental outcomes were stratified according to the UA Doppler flow pattern at the final examination. Intact survival rate was defined as the number of infants surviving without neurological impairment, divided by the total number of fetuses. Composite adverse outcome, defined as any mortality, presence of severe brain lesions on postnatal transcranial ultrasound or severe neurological morbidity, was also assessed. Of 88 MCDA twin pregnancies with sIUGR included in the study, 28 underwent selective termination by cord occlusion using radiofrequency ablation, resulting in a perinatal survival rate of 89.3% and a median gestational age (GA) at delivery of 33.8 (interquartile range (IQR), 28.8-38.2) weeks for the large cotwin. Expectant management was employed in 60 cases. In 26 (43.3%) cases in the expectant-management group, the classification according to the UA Doppler flow pattern changed during gestation, resulting in 26 (43.3%) cases of Type-I, 22 (36.7%) cases of Type-II and 12 (20.0%) cases of Type-III sIUGR at the final examination. The perinatal survival rate of both twins with sIUGR Types I, II and III at the final examination was 100%, 81.8% and 75.0%, respectively (P = 0.04). Two cases of double fetal death and one case of single fetal death occurred 1-4 weeks after the Doppler pattern had changed from Type I or Type II to Type III. The median GA at delivery was 34.8 (IQR, 33.1-35.7) weeks in Type I, 30.3 (IQR, 28.6-32.1) weeks in Type II and 32.0 (IQR, 31.3-32.6) weeks in Type III (P < 0.01). The total intact survival rate was 100% for Type I, 77.3% for Type II and 75.0% for Type III (P < 0.001). Multivariate analysis demonstrated that early GA at diagnosis (odds ratio (OR), 0.83 (95% CI, 0.69-0.99); P = 0.04) and the presence of Type II or III vs Type I at the last examination (OR, 13.16 (95% CI, 1.53-113.32); P = 0.02) were associated with preterm birth < 32 weeks' gestation. Early GA at diagnosis was also associated with the composite adverse outcome (OR, 0.60 (95% CI, 0.36-0.99); P = 0.04). The classification system of MCDA pregnancy complicated by sIUGR, according to the UA Doppler flow pattern of the IUGR twin at final examination, is associated with perinatal outcome. Importantly, the UA Doppler flow pattern can change during gestation, which has an impact on the risk of fetal death. Nevertheless, under strict fetal surveillance, the perinatal outcome of these pregnancies is favorable. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Intrauterine fetoscopic laser surgery versus expectant management in stage 1 twin-to-twin transfusion syndrome: an international randomized trial

Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition. This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome. We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes. The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively). It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.

Intraoperative brain mapping during awake surgery in symptomatic supratentorial cavernomas.

Complete resection of symptomatic supratentorial cavernoma (SCA) and removal of the surrounding gliotic area is recommended to minimize the risk of persistent seizures or (re)bleeding. Surgery of SCA located in an eloquent area, can carry out severe postoperative neurological morbidity. We report a study aimed to assess feasibility, extent of resection and outcome after surgical removal of CA by cortico-subcortical intraoperative brain stimulation (ioBS) in the awake patient. Six patients diagnosed of symptomatic SCA located on an eloquent area and operated on while awake under local anaesthesia ioBS, were included. Preoperative planning included neuropsychologic assessment of language-related functions, sociocognitive functions and executive functions. Intraoperatively, we recorded the results achieved in the planned neuropsychological tasks when stimulation was applied (cortical and subcortical). Postoperative control 3D MRI was scheduled at 1 month after surgery to calculate extent of resection. Neuropsychological assessment at 6 months after surgery was performed in all cases. Six patients (5 females, 1 male) aged 24-48 years were included in our study. Locations of the lesions were right insular (n=1), left insular (n=1), left temporo-insular (n=1), left temporal (n=2) and left frontal (n=1). In all patients, positive findings were obtained during ioBS. In 5 patients, complete surgical resection was achieved. Two patients had postoperative transient neurological deficits, one case of hemiparesis, one case of dysnomia, both cleared over a 6-month period. Clinical follow-up revealed that all patients experienced complete recovery from preoperative symptoms within a year and five patients with seizures showed marked improvement and eventually quit antiepileptic drugs. Neuropsychological assessment at 6 months provided normal results compared to preoperative baseline in all domains. Our study suggests that ioBS in the awake surgery of symptomatic SCA located in eloquent areas, allows to increase the rate of complete resection, minimizing postoperative neurological and neuropsychological deficit, and improving postoperative seizures control.

Neonatal Morbidity of Monoamniotic Twin Pregnancies: A Systematic Review and Meta-analysis.

This study was aimed to report the incidence of neonatal morbidity in monochorionic monoamniotic (MCMA) twin pregnancies according to gestational age at birth and type of management adopted (inpatient or outpatient). Medline and Embase databases were searched. Inclusion criteria were nonanomalous MCMA twins. The primary outcome was a composite score of neonatal morbidity, defined as the occurrence of at least one of the following outcomes: respiratory morbidity, overall neurological morbidity, severe neurological morbidity, and infectious morbidity, necrotizing enterocolitis at different gestational age windows (24-30, 31-32, 33-34, and 35-36 weeks). Secondary outcomes were the individual components of the primary outcome and admission to neonatal intensive care unit (NICU). Subanalysis according to the type of surveillance strategy (inpatient compared with outpatient) was also performed. Random effect meta-analyses were used to analyze the data. A total of 14 studies including 685 MCMA twin pregnancies without fetal anomalies were included. At 24 to 30, 31 to 32, 33 to 34, and 35 to 36 weeks of gestation, the rate of composite morbidity was 75.4, 65.5, 37.6, and 18.5%, respectively, the rate of respiratory morbidity was 74.2, 59.1, 35.5, and 12.2%, respectively, while overall neurological morbidity occurred in 15.3, 10.2, 4.3, and 0% of the cases, respectively. Infectious morbidity complicated 13, 4.2, 3.1, and 0% of newborns while 92.1, 81.6, 58.7, and 0% of cases required admission to NICU. Morbidity in pregnancies delivered between 35 and 36 weeks of gestation was affected by the very small sample size of cases included. When comparing the occurrence of overall morbidity according to the type of management (inpatient or outpatient), there was no difference between the two surveillance strategies (p = 0.114). MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity that gradually decreases with increasing gestational age at delivery with a significant reduction for pregnancies delivered between 33 and 34 weeks. We found no difference in the occurrence of neonatal morbidity between pregnancies managed as inpatient or outpatient. · MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity.. · Neonatal morbidity gradually decreases with increasing GA at delivery, mostly between 33 and 34 weeks.. · There is no difference in the occurrence of neonatal morbidity between in- or outpatient management..

Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats.

Hypoxic-ischemic (HI) brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. Autophagy is involved in the pathogenesis of HIBD. This study aims to investigate the effect of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on HIBD and to validate whether autophagy is involved in this process. A HIBD model in rat pups and a HI model in rat primary cerebrocortical neurons were established. Autophagy was evaluated by western blot. The HIBD in rats was evaluated by hematoxylin and eosin staining, TUNEL staining, triphenyl tetrazolium chloride staining, and morris water maze test. The HI injury in vitro was evaluated by determining cell viability and apoptosis. The results showed that CRNDE expression was time-dependently increased in the brain after HIBD. Administration with CRNDE shRNA-expressing lentiviruses alleviated pathological injury and apoptosis in rat hippocampus, decreased infarct volume, and improved behavior performance of rats subjected to HIBD. Furthermore, CRNDE silencing promoted cell viability and inhibited cell apoptosis in neurons exposed to HI. Moreover, CRNDE silencing promoted autophagy and the autophagy inhibitor 3-methyladenine counteracted the neuroprotective effect of CRNDE silencing on HI-induced neuronal injury both in vivo and in vitro. Collectively, CRNDE silencing alleviates HIBD, at least partially, through promoting autophagy.

Cost-Effectiveness of Implantable Cardioverter-Defibrillators in Children with Cardiac Conditions Associated with Risk for Sudden Cardiac Death.

Children at high risk for sudden cardiac death (SCD) receive implantable cardioverter-defibrillators (ICD) for prevention, but the cost effectiveness of ICDs in children at intermediate risk is unclear. Our objective was to create a cost-effectiveness model to compare costs and outcomes in children at risk of SCD, with and without ICD. Utilizing hypertrophic cardiomyopathy as the proxy disease, a theoretical cohort of 8150 children was followed for 69years. Model inputs were derived from the literature, with an incremental cost-effectiveness ratio (ICER) willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY) used to delineate cost effectiveness. Outcomes included prevalence of severe neurological morbidity (SNM), SCD, cost, and QALYs. In children at intermediate risk of SCD (4-6% over 5years), ICD resulted in 56 fewer cases of SNM, 2686 fewer deaths. In children at high risk (> 6% over 5years), ICD placement resulted in 74 fewer cases of SNM and 3663 fewer deaths from cardiac causes. The costs of ICD were higher, but placement was cost effective with an ICER of $3009 per QALY in intermediate risk children, but ICD therapy was a dominant strategy in high-risk children. Sensitivity analysis demonstrated ICD placement was cost-effective until the annual probability of SCD was < 0.22%. The model was robust over a wide range of values. For children at risk of SCD, prophylactic ICD implantation is cost effective, resulting in improved outcomes and increased QALYs, despite increased costs. These findings highlight the economic benefits of ICD utilization in this population.