Incidence of biomarkers in high-grade gliomas and their impact on survival in a diverse SouthEast Asian cohort - a population-based study.

BACKGROUND: Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS: Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS: 181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS: The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

Effects of surgery on neurocognitive function in patients with glioma: a meta-analysis of immediate post-operative and long-term follow-up neurocognitive outcomes.

PURPOSE: This study aims to identify the neuropsychological tests commonly used for assessment in each neurocognitive domain, and quantify the post-operative changes in neurocognitive function in the immediate post-operation and follow-up. METHODS: With the use of the PubMed, a comprehensive search of the English literature was performed following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. There were 1021 publications identified for screening. Standardized mean differences (SMD) in neuropsychological task performance were calculated both for immediate post-operation (up to 1 week) and follow-up (up to 6 months). RESULTS: Out of 12 studies which met the inclusion criteria, 11 studies were analyzed in this meta-analysis, with a total of 313 patients (age range 18-82, 50% males) with intracranial gliomas (45% high-grade, 55% low-grade). Complex attention, language and executive function were the most frequently tested neurocognitive domains. Surgery had a positive impact in the domains of complex attention, language, learning and memory tasks in the immediate post-operative period and sustained improvement at follow-up. In contrast, surgery was found to negatively impact performance for executive function in the immediate post-operative period with sustained decline in performance in the long term. CONCLUSIONS: This meta-analysis suggests that surgery for glioma confers a benefit for the domains of complex attention, language, learning and memory, while negatively affecting executive function, in the periods immediately after surgery and at 6 months follow-up. In addition, awake surgery seemed to confer a beneficial effect on neurocognitive functions. Future research should attempt to standardize a battery of neuropsychological tests for patients undergoing surgical resection for glioma, perhaps with a particular focus on executive function.

External Validation of Hematoma Expansion Scores in Spontaneous Intracerebral Hemorrhage in an Asian Patient Cohort.

BACKGROUND: Hematoma expansion (HE) occurs in approximately one-third of patients with intracerebral hemorrhage (ICH) and is known to be a strong predictor of neurological deterioration as well as poor functional outcome. This study aims to externally validate three risk prediction models of HE (PREDICT, 9-point, and BRAIN scores) in an Asian population. METHODS: A prospective cohort of 123 spontaneous ICH patients admitted to a tertiary hospital (certified stroke center) in Singapore was recruited. Logistic recalibrations were performed to obtain updated calibration slopes and intercepts for all models. The discrimination (c-statistic), calibration (Hosmer-Lemeshow test, le Cessie-van Houwelingen-Copas-Hosmer test, Akaike information criterion), overall performance (Brier score, R2), and clinical usefulness (decision curve analysis) of the risk prediction models were examined. RESULTS: Overall, the recalibrated PREDICT performed best among the three models in our study cohort based on the novel matrix comprising of Akaike information criterion and c-statistic. The PREDICT model had the highest R2 (0.26) and lowest Brier score (0.14). Decision curve analyses showed that recalibrated PREDICT was more clinically useful than 9-point and BRAIN models over the greatest range of threshold probabilities. The two scores (PREDICT and 9-point) which incorporated computed tomography (CT) angiography spot sign outperformed the one without (BRAIN). CONCLUSIONS: To our knowledge, this is the first study to validate HE scores, namely PREDICT, 9-Point and BRAIN, in a multi-ethnic Asian ICH patient population. The PREDICT score was the best performing model in our study cohort, based on the performance metrics employed in this study. Our findings also showed support for CT angiography spot sign as a predictor of outcome after ICH. Although the models assessed are sufficient for risk stratification, the discrimination and calibration are at best moderate and could be improved.

Incidence of Recurrent Intracerebral Hemorrhages in a Multiethnic South Asian Population.

INTRODUCTION: Spontaneous primary intracerebral hemorrhage (ICH) accounts for approximately 25% of all strokes in Singapore. Incidence of recurrent ICH is not well studied, and previous studies have reported inconsistent findings in the rate and risk factors associated with ICH recurrences. We aimed to study the incidence of recurrent ICHs in Singapore and to identify the associated risk factors as well as pattern of ICH recurrence. METHODS: A retrospective review of all consecutive admissions for intracerebral hemorrhage at the National Neuroscience Institute between January 2006 and November 2013 was performed. Imaging and computerized clinical records were reviewed. The demographic, clinical, and radiological characteristics of index and recurrent ICH were compared. Univariate analysis was performed using chi-square and Student's t-test, and logistic regression was used to analyze the predictors of ICH recurrence. RESULTS: In total, 1708 patients who survived the index ICH beyond 14 days were followed up for 6398 person-years. Sixty patients developed 68 recurrences of ICH, giving rise to an annual incidence rate of ICH recurrence of 1.1%. A history of previous ischemic stroke (P = .001) and index lobar location of ICH (P = .004) were significantly associated with the occurrence of ICH recurrences on multivariate analysis. The most common pattern on ICH recurrence was ganglionic-ganglionic (44.1%), followed by lobar-lobar (17.6%). Overall mortality of recurrent ICH was 17.6%. CONCLUSION: The average annual incidence rate of primary ICH recurrence in Singapore is 1.1%, and is associated with previous ischemic stroke and lobar location of index ICH.

Effect of prior statin use on outcome after severe traumatic brain injury in a South-East Asian population.

INTRODUCTION: Traumatic brain injury (TBI) is a global concern associated with high mortality and morbidity. Costs to individuals and society are extensive due to poor recovery, long-term disability and the young age group affected. Statins have emerged as potential therapeutic agents in TBI. This study aimed to investigate the protective effect of statins in severe TBI. METHODS: This case-control study included adults with severe TBI. A sliding dichotomy approach was used to dichotomize mortality at 14-days and Glasgow Outcome Score (GOS) at 6 months. Logistic regression analysis was used to calculate the odds ratios (OR) for 14-day mortality and 6-month GOS. RESULTS: Equivalent cohorts of 59 age- and sex-matched statin and non-statin users were selected, resulting in population of 118 (mean age = 70.2 years, SD = 10.3), with a median Glasgow Coma Score of 5. Statins did not reduce the likelihood of mortality at 14 days (adjusted OR = 1.23, p = 0.68) or unfavourable outcome at 6 months (adjusted OR = 1.19, p = 0.78). CONCLUSIONS: Despite increasing evidence for benefit of statins in TBI, this study in an Asian population does not support this association, demonstrating no significant improvement in outcome for statin users. Further research is required to understand the mechanisms and impact of statins in TBI.

Genome-based analysis of the nonhuman primate Macaca fascicularis as a model for drug safety assessment.

The long-tailed macaque, also referred to as cynomolgus monkey (Macaca fascicularis), is one of the most important nonhuman primate animal models in basic and applied biomedical research. To improve the predictive power of primate experiments for humans, we determined the genome sequence of a Macaca fascicularis female of Mauritian origin using a whole-genome shotgun sequencing approach. We applied a template switch strategy that uses either the rhesus or the human genome to assemble sequence reads. The sixfold sequence coverage of the draft genome sequence enabled discovery of about 2.1 million potential single-nucleotide polymorphisms based on occurrence of a dimorphic nucleotide at a given position in the genome sequence. Homology-based annotation allowed us to identify 17,387 orthologs of human protein-coding genes in the M. fascicularis draft genome, and the predicted transcripts enabled the design of a M. fascicularis-specific gene expression microarray. Using liver samples from 36 individuals of different geographic origin we identified 718 genes with highly variable expression in liver, whereas the majority of the transcriptome shows relatively stable and comparable expression. Knowledge of the M. fascicularis draft genome is an important contribution to both the use of this animal in disease models and the safety assessment of drugs and their metabolites. In particular, this information allows high-resolution genotyping and microarray-based gene-expression profiling for animal stratification, thereby allowing the use of well-characterized animals for safety testing. Finally, the genome sequence presented here is a significant contribution to the global "3R" animal welfare initiative, which has the goal to reduce, refine, and replace animal experiments.

Identifying risk factors of intracerebral hemorrhage stability using explainable attention model.

Segmentation of intracerebral hemorrhage (ICH) helps improve the quality of diagnosis, draft the desired treatment methods, and clinically observe the variations with healthy patients. The clinical utilization of various ICH progression scoring systems has limitations due to the systems' modest predictive value. This paper proposes a single pipeline of a multi-task model for end-to-end hemorrhage segmentation and risk estimation. We introduce a 3D spatial attention unit and integrate it into the state-of-the-art segmentation architecture, UNet, to enhance the accuracy by bootstrapping the global spatial representation. We further extract the geometric features from the segmented hemorrhage volume and fuse them with clinical features such as CT angiography (CTA) spot, Glasgow Coma Scale (GCS), and age to predict the ICH stability. Several state-of-the-art machine learning techniques such as multilayer perceptron (MLP), support vector machine (SVM), gradient boosting, and random forests are applied to train stability estimation and to compare the performances. To align clinical intuition with model learning, we determine the shapely values (SHAP) and explain the most significant features for the ICH risk scoring system. A total of 79 patients are included, of which 20 are found in critical condition. Our proposed single pipeline model achieves a segmentation accuracy of 86.3%, stability prediction accuracy of 78.3%, and precision of 82.9%; the mean square error of exact expansion rate regression is observed to be 0.46. The SHAP analysis reveals that CTA spot sign, age, solidity, location, and length of the first axis of the ICH volume are the most critical characteristics that help define the stability of the stroke lesion. We also show that integrating significant geometric features with clinical features can improve the ICH progression scoring by predicting long-term outcomes. Graphical abstract Overview of our proposed method comprising of spatial attention and feature extraction mechanisms. The architecture is trained on the input CT images, and the first step output is the predicted segmentation of the hemorrhagic region. The output is fed into a geometric feature extractor and is fused with clinical features to estimate ICH stability using a multilayer perceptron (MLP).

Calmin expression in embryos and the adult brain, and its regulation by all-trans retinoic acid.

The vitamin A metabolite, all-trans retinoic acid (atRA), is a regulator of nervous system development. Using a subtracted cDNA library constructed from neuroblastoma cells, the atRA-responsive gene calmin (Clmn) was identified (Merrill et al. [2004] Biol Chem 385:605-614). The Clmn transcript is detected very early in rat embryonic development and is sensitive to retinoid status. In vitamin A-deficient embryos, Clmn mRNA is dramatically down-regulated in the neuroepithelium adjacent to the somites, and this expression can be rescued with the addition of atRA. In embryonic day 18.5 embryos, CLMN is detected in regions where newly differentiated neurons are found, including the neural retina and the cortical plate; and in the adult brain, CLMN is most highly expressed in the neuron cell bodies of the hippocampus, cerebellum, and olfactory bulb. Thus, Clmn is sensitive to retinoid status during early gestational stages, and its expression is relegated to postmitotic neuronal cells in the adult rat brain.

The temporal requirement for vitamin A in the developing eye: mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina.

Mammalian eye development requires vitamin A (retinol, ROL). The role of vitamin A at specific times during eye development was studied in rat fetuses made vitamin A deficient (VAD) after embryonic day (E) 10.5 (late VAD). The optic fissure does not close in late VAD embryos, and severe folding and collapse of the retina is observed at E18.5. Pitx2, a gene required for normal optic fissure closure, is dramatically downregulated in the periocular mesenchyme in late VAD embryos, and dissolution of the basal lamina does not occur at the optic fissure margin. The addition of ROL to late VAD embryos by E12.5 restores Pitx2 expression, supports dissolution of the basal lamina, and prevents coloboma, whereas supplementation at E13.5 does not. Surprisingly, ROL given as late as E13.5 completely prevents folding of the retina despite the presence of an open fetal fissure, showing that coloboma and retinal folding represent distinct VAD-dependent defects. Retinal folding due to VAD is preceded by an overall reduction in the percentage of cyclin D1 positive cells in the developing retina, (initially resulting in retinal thinning), as well as a dramatic reduction in the cell adhesion-related molecules, N-cadherin and beta-catenin. Reduction of retinal cell number combined with a loss of the normal cell-cell adhesion proteins may contribute to the collapse and folding of the retina that occurs in late VAD fetuses.

Longitudinal medication profile and cost savings in Parkinson's disease patients after bilateral subthalamic nucleus deep brain stimulation.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus (STN DBS) has been shown to reduce antiparkinsonian medication in Parkinson's disease. We aimed to investigate the changes in long-term medication profile with STN DBS. METHODS: Antiparkinsonian medication data for 56 patients were collected from as early as 3 years before STN DBS up to 10 years after. Cost spending on medication changes was analyzed. Mean levodopa equivalent daily dose (LEDD) was projected 10 years into the future based on preoperative data to create a comparator group wherein the patients did not undergo STN DBS. Use of neuroleptics and antidepressants was also recorded. RESULTS: LEDD requirement was significantly reduced by a mean of 31 ± 2% over 10 years after DBS, from 1049 ± 381 mg at pre-DBS baseline, to 713 ± 392 mg at 1 year post-DBS, and 712 ± 385 mg at 10 years post-DBS. This was associated with a mean reduction of 35 ± 3% in medicine cost. Modeled LEDD requirements for not having STN DBS were in the range of 1489 mg to 2721 mg at 10 years post-DBS (109-282% higher than the observed mean LEDD in DBS cohort). The proportion of patients increased from 5% before STN DBS to 14% at 10 year post-DBS for neuroleptics, and 11-23% for antidepressants. CONCLUSION: STN DBS led to LEDD reduction and antiparkinsonian medication cost savings in our South-East Asian cohort. Medication reduction with STN DBS in our cohort over the 10-year period was comparable to those reported in Western populations.

Survey on Willingness to Pay for Life-Saving Treatment, Functional Recovery, and Cosmesis in a Neuroscience Outpatient Clinic Setting in Singapore.

BACKGROUND: Neurologic disorders impose a heavy burden on healthcare in Singapore. To date, no data on the willingness to pay (WTP) for neurologic treatments has been reported in the local population. OBJECTIVES: We aimed to quantify the value of various health domains to neuroscience patients and their caregivers by comparing their WTP for different types of treatments. METHODS: A questionnaire using a mixed open-ended and closed-ended contingent valuation method was developed to elicit WTP and self-administered by 112 visitors to a neuroscience outpatient clinic. The WTP for treatments in 3 health domains (advanced restoration of function, life extension, and cosmesis) was evaluated and compared. Subgroup regression analysis was performed to investigate the impact of demographic and socioeconomic factors. RESULTS: Treatment that improved cosmesis had the highest median WTP of Singapore dollar (SGD) 35 000, followed by treatment that provided 1 year of life extension (SGD 20 000) and 1 year of advanced restored function (SGD 10 000; P < .001). Respondents with a university education were willing to pay as much as 2 to 3 times of those without across all health domains. CONCLUSION: This is the first study to provide data on how different health domains are valued by neuroscience patients and caregivers in our population. Respondents valued treatment that restored or improved their physical appearances the most. These findings could contribute to future policies on the improvement of neuroscience care.

An open label randomized trial to assess the efficacy of tranexamic acid in reducing post-operative recurrence of chronic subdural haemorrhage.

Chronic subdural haemorrhage (CSDH) is a common neurosurgical entity with complex pathophysiological pathways. The generally favourable surgical outcome may be affected by its associated risks including recurrence rates. We performed a prospective randomized multi-center clinical trial comparing the addition of tranexamic acid (TXA) to standard neurosurgical procedures for patients with symptomatic CSDH. The primary endpoint was CSDH requiring repeat surgery within 6-month post-operatively. Secondary endpoints were comparison of post-operative volumes between the treatment arms and safety evaluation of the dosing regime. 90 patients were analyzed with 49 patients in the observation arm and 41 patients in the TXA arm. The observation arm had five (10.2%) recurrences compared to two (4.8%, p = 0.221) in the TXA arm. Patients in the TXA arm demonstrated a greater reduction of their CSDH volume at 6 weeks follow up (36.6%) compared to the observation arm (23.3%, p = 0.6648). There were no reportable serious adverse events recorded in the observation arm, compared to 4 (9.8%) patients in the TXA arm. The addition of TXA treatment to standard surgical drainage of CSH did not significantly reduce symptomatic post-operative recurrence. Patients in the TXA arm had a delay in the CSDH recurrence with a comparative reduction of residual hematoma volume at the 6-week follow up although the effect was unsustained. Larger randomized trials with dose adjustments should be considered to investigate subgroups of patients that may benefit from this medical adjunct.

A nutritional model of late embryonic vitamin A deficiency produces defects in organogenesis at a high penetrance and reveals new roles for the vitamin in skeletal development.

Vitamin A plays an essential role in vertebrate embryogenesis. In the present study, pregnant vitamin A-deficient (VAD) rats were maintained during early pregnancy on the short half-life vitamin A metabolite, all-trans retinoic acid (atRA), in an amount sufficient to support normal development to E10.5, with a higher level of atRA (250 microg atRA/g diet) provided from embryonic day (E) 8.5-10.5 to prevent mid-gestational resorption. When limiting amounts of atRA (1.5 or 12 microg/g diet) were provided after E10.5, a highly reproducible and penetrant state of late fetal vitamin A deficiency (late VAD) was induced in the organs of developing fetuses. In addition, late VAD fetuses displayed both anteriorization of cervical regions and novel posteriorization events at the thoracic and sacral levels of the skeleton, and showed sternal and pelvic malformations not previously observed in early VAD or genetic models. The expression of several Hox genes (Hoxd3 and Hoxb4) was altered in late VAD embryos, with a reduction in Hoxd3 noted as early as 1 day after instituting deficiency. All late VAD-induced malformations were prevented by the addition of retinol starting at E10.5, whereas provision of a high level of atRA throughout pregnancy improved but could not completely rescue the development of all organ systems. This work defines a nutritional model in which vitamin A deficiency can be induced during fetal development, and reveals new functions for the vitamin in the development of the axial and appendicular skeleton.

Effects of anticoagulant and antiplatelet agents in severe traumatic brain injury in an asian population - A matched case-control study.

The use of anticoagulation and antiplatelet agents (ACAP) has steadily increased over recent years. However, the effects of ACAP on traumatic brain injuries (TBI) are not well investigated. The aim of this study was to investigate the effects of pre-injury ACAP use on clinical outcome and mortality in severe TBI. A retrospective case-control study was performed for all patients who presented with severe TBI (GCS < 8) to the National Neuroscience Institute, Singapore, between 2006 and 2009. Patients with pre-injury ACAP use were compared to matched controls. Outcome measures were mortality at 14 days and 6 months, and Glasgow Outcome Score (GOS) at 6 months using a sliding dichotomy approach. Univariate analysis was performed using Chi-square and student's t-test and logistic regression was used to model the effect of ACAP on mortality rate. Forty-five patients with pre-injury use of ACAP were compared with matched controls. The mortality at 14 days (OR = 0.5, 95% CI 0.2-1.4) and 6 months (OR = 0.7, 95% CI 0.2-1.9) were not significantly different between the 2 groups. Using the sliding dichotomy approach, there was no difference in the odds for unfavorable functional outcomes at 6 months (OR = 1.2, 95% CI 0.4-3.7). In this case-control study, the use of ACAP did not have a significant effect on mortality and adverse outcomes in patients with severe TBI. This would suggest that in severe TBI, ACAP use may not contribute significantly to the overall prognosis.

Bioadhesives in neurosurgery: a review.

OBJECTIVE: Neurosurgery presents unique surgical challenges arising from delicate neural structures, limited accessibility, and the risk of CSF leakage that can lead to CNS infections. Sutures and staples may have limited applicability in the complex anatomical constraints of cranial and spinal surgeries, especially in trauma settings when time is of the essence. Surgical bioadhesives are emerging as attractive alternatives because they avoid traumatic application methods, provide a stress-distributed fixation, and provide good cosmesis and outcomes. This article presents the history of the development of surgical bioadhesives, and is also a review of current applications of commercial surgical bioadhesives within neurosurgical procedures and the unmet clinical needs that should be addressed in bioadhesives technologies. METHODS: A PubMed literature search was performed using the terms "(glue OR bioadhesive OR fibrin OR tisseel OR evicel OR tachosil OR cyanoacrylate OR duraseal OR bioglue) AND (neurosurgery OR spine OR spinal OR dural OR microvascular decompression OR transsphenoidal OR endovascular)." Of 2433 records screened, 168 studies were identified that described the use of bioadhesives in neurosurgical procedures. RESULTS: The greatest number of studies describing the use of bioadhesives in neurosurgery were identified for endovascular embolization, followed by dural closure and transsphenoidal surgeries. Other common areas of application were for microvascular decompression, skin closure, peripheral nerve repair, and other novel uses. Numerous case reports were also identified describing complications associated with bioadhesive use. CONCLUSIONS: Despite the paucity of approved indications, surgical bioadhesive use in neurosurgical procedures is prevalent. However, current bioadhesives still each have their own limitations and research is intense in the development of novel solutions.

Detection of Subthalamic Nucleus using Time-Frequency Features of Microelectrode recordings and Random Forest Classifier.

Accurate localization of subthalamic nucleus (STN) is a key prior in deep brain stimulation (DBS) surgery for the patients with advanced Parkinson's disease (PD). Microelectrode recordings (MERs) along with preplanned trajectories are often employed for the STN localization and it remains challenging task. These MER signals are nonstationary and multicomponent in nature. In this study, we propose a system based on time-frequency features of MERs to differentiate the STN and non-STN regions. We assessed the system with 50 MER trajectories from 26 PD patients who have undergone DBS surgery. The signals are pre-processed and subjected to six-level wavelet decomposition. Then, the entropy is computed from the detailed and approximate coefficients. These features are fed to the random forest classifier and the model is evaluated by leave one patient out cross-validation. The results show that entropy associated with detailed wavelet coefficients (D1and D2) are higher in STN where as it is lower in other wavelet scales. All extracted features except entropy from approximate coefficients are found to have significant difference between non-STN and STN (p<; 0.05). The random forest classifier achieves about 83% accuracy and 87% precision in differentiating the STN and non-STN regions.

A review on microelectrode recording selection of features for machine learning in deep brain stimulation surgery for Parkinson's disease.

OBJECTIVE: This study seeks to systematically review the selection of features and algorithms for machine learning and automation in deep brain stimulation surgery (DBS) for Parkinson's disease. This will assist in consolidating current knowledge and accuracy levels to allow greater understanding and research to be performed in automating this process, which could lead to improved clinical outcomes. METHODS: A systematic literature review search was conducted for all studies that utilized machine learning and DBS in Parkinson's disease. RESULTS: Ten studies were identified from 2006 utilizing machine learning in DBS surgery for Parkinson's disease. Different combinations of both spike independent and spike dependent features have been utilized with different machine learning algorithms to attempt to delineate the subthalamic nucleus (STN) and its surrounding structures. CONCLUSION: The state-of-the-art algorithms achieve good accuracy and error rates with relatively short computing time, however, the currently achievable accuracy is not sufficiently robust enough for clinical practice. Moreover, further research is required for identifying subterritories of the STN. SIGNIFICANCE: This is a comprehensive summary of current machine learning algorithms that discriminate the STN and its adjacent structures for DBS surgery in Parkinson's disease.

Validation of Prognostic Models to Predict Early Mortality in Spontaneous Intracerebral Hemorrhage: A Cross-Sectional Evaluation of a Singapore Stroke Database.

OBJECTIVE: Numerous scores have been developed for prognostication of outcomes in intracerebral hemorrhage (ICH). Prediction models must be validated internally and externally before they are considered widely applicable. We aim to independently externally validate and compare 3 prediction models (ICH score, ICH grading scale [ICH-GS], and simplified ICH [sICH]) in our population, which has not been previously done. METHODS: We reviewed 1338 patients with spontaneous ICH consecutively admitted to the National Neuroscience Institute, Singapore, between January 2009 and November 2013. We analyzed prospectively collected data of admission characteristics (clinical, neuroimaging, and laboratory findings). All 3 scores prognosticated 30-day mortality. Validation was based on calibration, goodness-of-fit tests, and discrimination (area under receiver operating characteristic curve [AUC]). Akaike information criterion (AIC) and decision curve analysis (DCA) were used to directly compare the scores. RESULTS: All 3 models showed good calibration and both the Hosmer-Lemeshow and the le Cessie-van Houwelingen-Copas goodness-of-fit test showed P values >0.05. AUCs ranged from 0.86 to 0.90, indicating good discriminative ability, with the ICH-GS performing the best with the highest AUC, lowest AIC (849), and overall highest net benefit in the DCA. CONCLUSIONS: This study successfully independently validates the ICH score, ICH-GS, and sICH score in a large patient cohort with spontaneous ICH, which has not been previously done in this non-Western population. We recommend the use of the ICH-GS as a prognostication tool in our patients instead of the widely used ICH score.

Long-term recovery profile of patients with severe disability or in vegetative states following severe primary intracerebral hemorrhage.

PURPOSE: We conducted a single-center retrospective review to investigate the long-term recovery of patients who were severely disabled or vegetative secondary to primary intracerebral hemorrhage upon discharge from hospital from January 2009 to November 2013. METHODS: Patients were categorized into two groups based on their Glasgow outcome scale (GOS) scores at discharge, namely vegetative state (GOS 2; n = 91) and severely disabled (GOS 3; n = 278). Long-term outcomes at three years post discharge were defined as death, stable, deterioration and improvement from discharge to follow-up. RESULTS: Lower mortality (29% versus 69%) and higher neurological improvement rates at three years (33% versus 10%) were observed in the SD compared to VS group (both p = .0001). Age was a significant predictor of survival in the VS group (p = .03) and the SD group (p = .012). Age was also the only predictor of neurological improvement in the SD group (p = .01). CONCLUSIONS: Neurological status at discharge from hospital was not truly indicative of long-term prognosis for patients who were severely disabled or vegetative. Patients in both groups can potentially improve in the long term and may benefit from prolonged rehabilitation programmes to maximize their recovery potential.

Awake Craniotomy for Resection of Brain Metastases: A Systematic Review.

BACKGROUND: Surgery for brain metastases aims to reduce mass effect and achieve local control through maximizing resection. There is increasing recognition that awake craniotomy (AC) is especially relevant for resection of brain metastases in eloquent areas. This study seeks to examine the neurologic outcomes of using AC for brain metastases resection. METHODS: A systematic search for studies examining the role of AC in patients with brain metastases was conducted via PubMed without limitations on the year of publication, language, or study design, using the following search terms: (cerebral OR brain) and (metastases OR tumor) and (awake OR intraoperative OR eloquent OR supramarginal). Studies were included if patients underwent AC for resection of brain metastases and data on pre- and postoperative neurologic function were available. RESULTS: Seven studies published between 2001 and 2017 with 104 patients who underwent 107 ACs were identified. Gross total resection was achieved in 61% of patients, supramarginal resection was achieved in 32%, and subtotal resection was achieved in 7%. Immediately after operation, 73% of patients experienced no change or improvement in neurologic outcomes, whereas 27% experienced worsening. In the long term, 96% of those with postoperative worsening of function experienced improvements in neurologic function. CONCLUSIONS: Most patients experienced improvements in neurologic function immediately after AC, and most patients that experienced short-term worsening of neurologic function after the procedure showed excellent recovery. AC should be considered as a technique to optimize outcomes in brain metastases in eloquent areas.