OS14.4.A The Neuroplastic Potential of the Human Brain before and After Glioma Surgery: Towards “Interventional Neurorehabilitation

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
A Poologaindran ◽  
R Romero-Garcia ◽  
M Hart ◽  
I Young ◽  
T Santarius ◽  
...  
Keyword(s):  
Human Brain ◽  
Safety Profile ◽  
Brain Networks ◽  
Low Grade ◽  
Healthy Individuals ◽  
Glioma Surgery ◽  
Post Surgery ◽  
Post Operative Period ◽  
Cognitive Data

Abstract INTRODUCTION The human brain is a highly neuroplastic ‘complex’ network: it self-organises without a hard blueprint, adapts to evolving circumstances, and can withstand insults. However, similar to other naturally occurring networks, brain networks can only endure a finite amount of damage before cognitive processes are affected. In this study, we first sought to establish the brain networks governing domain-general cognition (DGC) in healthy individuals across the lifespan. We then sought to map, track, and potentially rehabilitate networks governing DGC through connectomics and non-invasive brain stimulation (NIBS) when damaged by low-grade gliomas (LGG) and surgical oncology. METHODS Using MRI and cognitive data from n=629 individuals (aged 18–88, Female= 51%), we assessed the structural, functional, and topological relevance of the spatially-distributed multiple-demand (MD) system for DGC. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectomic and cognitive data at multiple time points: pre-surgery and post-surgery Day 1, Month 3, Month 12. In an independent cohort of n=34 patients, we sought to establish the safety profile for “interventional neurorehabilitation”: connectome-driven NIBS in the acute post-operative period to accelerate cognitive recovery. RESULTS In healthy individuals, the MD system across multiple scales of biological organisation was positively associated with higher-order cognition (Catell’s fluid intelligence). In our patients, pre-operative LGG infiltration into the structural MD system was negatively associated with the number of long-term cognitive deficits, suggesting a functional reorganisation. Mixed-effects modelling demonstrated the resilience of the functional MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed increased perioperative modularity can distinguish patients with long-term cognitive improvements at one-year follow-up. Finally, NIBS within two weeks post-craniotomy had a 90% (n=31/34) recruitment rate into the trial. There were no seizures or serious complications due to NIBS in this patient population. Transient headaches and tingling were reported in a minority of patients. CONCLUSION For the first time, we elucidate long-term cognitive and network trajectories following LGG surgery while establishing a positive safety-profile for NIBS in the acute post-operative period. We argue that “mesoscale” brain mapping serves as a robust biomarker for intervention-related plasticity for future clinical trials. While we performed these experiments in the context of neurosurgery, connectomics and NIBS could be adopted across diverse neuro-oncological care pathways (i.e. chemotherapy/radiation).

scholarly journals Longitudinal Connectome Analyses following Low-Grade Glioma Neurosurgery: Implications for Cognitive Rehabilitation

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv8-iv8
Author(s):  
Anujan Poologaindran ◽  
Mike Hart ◽  
Tom Santarius ◽  
Stephen Price ◽  
Rohit Sinha ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Cognitive Rehabilitation ◽  
Fluid Intelligence ◽  
Higher Order ◽  
Optimal Time ◽  
Single Subject ◽  
Low Grade ◽  
Post Surgery ◽  
Cognitive Data

Abstract Aims Low-grade gliomas (LGG) slowly grow and infiltrate the brain's network architecture (the connectome). Unlike strokes that acutely damage the connectome, LGGs intricately remodel it, leading to varying deficits in executive function (i.e. attention, concentration, working memory). By longitudinally mapping the “mesoscale” architecture of the connectome, we may begin to systematically accelerate domain-general cognitive rehabilitation in LGG patients. In this study, we pursued the following aims: 1) track cognitive and connectome trajectories following LGG surgery, 2) determine optimal time period for cognitive rehabilitation, and 3) distinguish patients with perioperative predictors of long-term cognitive deficits (>1 year). Method With MRI and cognitive data from n=629 individuals across the lifespan, we first validated the structural, functional, and topological relevance of the multiple demand (MD) system for higher-order cognition. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectome and cognitive data: pre-surgery, post-surgery Day 1, Month 3, & 12. We assessed how glioma infiltration, surgery, and rehabilitation affected MD system trajectories at the single-subject level. Deploying transcriptomic and graph theoretical analyses, we tested if perioperative connectome modularity can accurately distinguish long-term cognitive trajectories. Results Controlling for age and sex, the MD system’s multi-scale architecture in health was positively associated with higher-order cognition (Catell’s fluid intelligence). Pre-operative glioma infiltration into the MD system was negatively associated with the number of long-term cognitive deficits (OCS-Bridge cognitive battery), suggesting its functional reorganisation. Mixed-effects modelling demonstrated the resilience of the MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed perioperative modularity can distinguish patients with long-term cognitive deficits at one-year follow-up. Transcriptomic analyses of inter-module connector hubs revealed increased gene expression for mitochondrial metabolism and synaptic plasticity. Conclusion This is the first serial functional mapping of LGG patient trajectories for domain-general cognition. By assessing the mesoscale architecture, we demonstrate how connectomics can help overcome the intrinsic heterogeneity in LGG patients and predict long-term rehabilitation trajectories. We discuss how to identify neurobiologically-grounded personalised targets for 'interventional neurorehabilitation' following LGG surgery.

scholarly journals Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
◽  
Heli Julkunen ◽  
Anna Cichońska ◽  
P Eline Slagboom ◽  
Peter Würtz
Keyword(s):  
General Population ◽  
Disease Onset ◽  
Severe Pneumonia ◽  
Blood Sampling ◽  
Low Grade ◽  
Healthy Individuals ◽  
Metabolic Biomarkers ◽  
Low Grade Inflammation ◽  
Increased Susceptibility

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

scholarly journals How early damage to the dorsomedial prefrontal hub in human brain networks affects long term cognitive, behavioral, and neuroanatomical outcomes.

2020 ◽  
Vol 13 (3) ◽  
pp. 245-256
Author(s):  
Katrina L. Okerstrom-Jezewski ◽  
Amanda Grafft ◽  
Natalie L. Denburg ◽  
Joel Bruss ◽  
Carolina Deifelt Streese ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Networks ◽  
Cognitive Behavioral ◽  
Early Damage

scholarly journals NCMP-05. THE INCIDENCE AND IMPACT OF POST-OPERATIVE STROKE IN SURGERY FOR LGG

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi180-vi180
Author(s):  
Asaf Berger ◽  
Garry Tzarfati ◽  
Mathias Costa ◽  
Marga Serafimova ◽  
Akiva Korn ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Performance Status ◽  
Tumor Resection ◽  
Neurological Deficits ◽  
Functional Improvement ◽  
Motor Deficit ◽  
Low Grade ◽  
Post Surgery ◽  
One Year

Abstract BACKGROUND Postoperative neurological deficits may outweigh the benefit conferred by maximal resection of gliomas. We evaluated the incidence of ischemic events in patients undergoing surgery for low-grade gliomas (LGG) and the long-term neurological and cognitive sequelae. METHODS Between 2013–2017, 168 patients underwent surgical resection or biopsy for LGG at our center. A full dataset, including pre- and postoperative magnetic resonance imaging (MRI) and long-term clinical evaluation findings, was available for 82 patients (study group). Ischemic complications, overall and progression-free survival, and functional and neurocognitive outcomes were evaluated. RESULTS The immediate postoperative MRI revealed an acute ischemic stroke adjacent to the tumor resection cavity in 19 patients (23%), 13 of whom developed new neurological deficits due to the ischemic event. Infarcts were more common in patients with recurrent tumors, especially those involving the Sylvian fissure (p< 0.05). Surgery for insular gliomas had the strongest association with postoperative infarcts. Survival of patients w/wo a postoperative infarct was the same. The median Karnofsky-Performance Status was lower for the infarct group vs. the non-infarct group at 3 months post-surgery (p=0.016), with a gradual significant improvement for the former over one year (p=0.04). Immediately after surgery, 27% of the patients without infarcts and 58% of those with infarcts experienced a new motor deficit (p=0.037), decreasing to 16% (p=0.028) and 37% (p=0.001), respectively, at one year. Neurocognitive analysis findings before and 3 months after surgery were unchanged, but patients with an infarct had a significant decrease in naming (p=0.04). Confusion during awake craniotomy was a strong predictor of an ischemic stroke. CONCLUSIONS Intraoperative strokes are more prevalent among patients who undergo recurrent surgeries, especially in the insula. Although they do not affect survival, these strokes negatively impact the patients’ activity and performance status, especially during the first 3 postoperative months, with gradual functional improvement over one year.

scholarly journals Contribution of combined intraoperative electrophysiological investigation with 3-T intraoperative MRI for awake cerebral glioma surgery: comprehensive review of the clinical implications and radiological outcomes

2016 ◽  
Vol 40 (3) ◽  
pp. E14 ◽  
Author(s):  
Diana Ghinda ◽  
Nan Zhang ◽  
Junfeng Lu ◽  
Cheng-Jun Yao ◽  
Shiwen Yuan ◽  
...  
Keyword(s):  
Learning Curve ◽  
High Grade Glioma ◽  
Awake Craniotomy ◽  
Low Grade ◽  
High Grade ◽  
Short Term ◽  
Glioma Surgery ◽  
Eloquent Area ◽  
Short And Long Term

OBJECTIVE This study aimed to assess the clinical efficiency of combined awake craniotomy with 3-T intraoperative MRI (iMRI)–guided resection of gliomas adjacent to eloquent cortex performed at a single center. It also sought to explore the contribution of iMRI to surgeons' learning process of maximal safe resection of gliomas. METHODS All patients who underwent an awake craniotomy and iMRI for resection of eloquent area glioma during the 53 months between January 2011 and June 2015 were included. The cases were analyzed for short- and long-term neurological outcome, progression-free survival (PFS), overall survival (OS), and extent of resection (EOR). The learning curve was assessed after dividing the cohort into Group A (first 27 months) and Group B (last 26 months). Statistical analyses included univariate logistic regression analysis on clinical and radiological variables. Kaplan-Meier and Cox regression models were used for further analysis of OS and PFS. A p value < 0.05 was considered statistically significant. RESULTS One hundred six patients were included in the study. Over an average follow-up period of 24.8 months, short- and long-term worsening of the neurological function was noted in 48 (46.2%) and 9 (8.7%) cases, respectively. The median and mean EOR were 100% and 92%, respectively, and complete radiographic resection was achieved in 64 (60.4%) patients. The rate of gross-total resection (GTR) in the patients with low-grade glioma (89.06% ± 19.6%) was significantly lower than that in patients with high-grade glioma (96.4% ± 9.1%) (p = 0.026). Thirty (28.3%) patients underwent further resection after initial iMRI scanning, with a 10.1% increase of the mean EOR. Multivariate Cox proportional hazards modeling demonstrated that the final EOR was a significant predictor of PFS (HR 0.225, 95% CI 0.070–0.723, p = 0.012). For patients with high-grade glioma, the GTR (p = 0.033), the presence of short-term motor deficit (p = 0.027), and the WHO grade (p = 0.005) were independent prognostic factors of OS. Performing further resection after the iMRI (p = 0.083) and achieving GTR (p = 0.05) demonstrated a PFS benefit trend for the patients affected by a low-grade glioma. Over time, the rate of performing further resection after an iMRI decreased by 26.1% (p = 0.005). A nonsignificant decrease in the rate of short-term (p = 0.101) and long-term (p = 0.132) neurological deficits was equally noted. CONCLUSIONS Combined awake craniotomy and iMRI is a safe and efficient technique allowing maximal safe resection of eloquent area gliomas with possible subsequent OS and PFS benefits. Although there is a learning curve for applying this technique, it can also improve the surgeon's ability in eloquent glioma surgery.

The Stability of the WHO Reference Thromboplastin NIBS & C 67/40

1979 ◽  
Vol 42 (04) ◽  
pp. 1135-1140 ◽  
Author(s):  
G I C Ingram
Keyword(s):  
Human Brain ◽  
Collaborative Study ◽  
Calibration Constant ◽  
Long Term Stability ◽  
Freeze Dried ◽  
Show Evidence ◽  
Human Material ◽  
Reference Preparation ◽  
The Stability

SummaryThe International Reference Preparation of human brain thromboplastin coded 67/40 has been thought to show evidence of instability. The evidence is discussed and is not thought to be strong; but it is suggested that it would be wise to replace 67/40 with a new preparation of human brain, both for this reason and because 67/40 is in a form (like Thrombotest) in which few workers seem to use human brain. A �plain� preparation would be more appropriate; and a freeze-dried sample of BCT is recommended as the successor preparation. The opportunity should be taken also to replace the corresponding ox and rabbit preparations. In the collaborative study which would be required it would then be desirable to test in parallel the three old and the three new preparations. The relative sensitivities of the old preparations could be compared with those found in earlier studies to obtain further evidence on the stability of 67/40; if stability were confirmed, the new preparations should be calibrated against it, but if not, the new human material should receive a calibration constant of 1.0 and the new ox and rabbit materials calibrated against that.The types of evidence available for monitoring the long-term stability of a thromboplastin are discussed.

Efficient Co-Harvesting of Solar Energy and Low-Grade Heat by Molecular Photoswitches for High Energy Density, Long-Term Stable Solar Thermal Battery

2019 ◽  
Author(s):  
Zhao-Yang Zhang ◽  
Tao LI
Keyword(s):  
Energy Density ◽  
Solar Energy ◽  
High Performance ◽  
High Energy ◽  
Solar Thermal ◽  
High Energy Density ◽  
Low Grade ◽  
Thermal Battery ◽  
Low Grade Heat

Solar energy and ambient heat are two inexhaustible energy sources for addressing the global challenge of energy and sustainability. Solar thermal battery based on molecular switches that can store solar energy and release it as heat has recently attracted great interest, but its development is severely limited by both low energy density and short storage stability. On the other hand, the efficient recovery and upgrading of low-grade heat, especially that of the ambient heat, has been a great challenge. Here we report that solar energy and ambient heat can be simultaneously harvested and stored, which is enabled by room-temperature photochemical crystal-to-liquid transitions of small-molecule photoswitches. The two forms of energy are released together to produce high-temperature heat during the reverse photochemical phase change. This strategy, combined with molecular design, provides high energy density of 320-370 J/g and long-term storage stability (half-life of about 3 months). On this basis, we fabricate high-performance, flexible film devices of solar thermal battery, which can be readily recharged at room temperature with good cycling ability, show fast rate of heat release, and produce high-temperature heat that is >20<sup> o</sup>C higher than the ambient temperature. Our work opens up a new avenue to harvest ambient heat, and demonstrate a feasible strategy to develop high-performance solar thermal battery.

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