CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord.

Ageing is a critical factor in spinal-cord-associated disorders1, yet the ageing-specific mechanisms underlying this relationship remain poorly understood. Here, to address this knowledge gap, we combined single-nucleus RNA-sequencing analysis with behavioural and neurophysiological analysis in non-human primates (NHPs). We identified motor neuron senescence and neuroinflammation with microglial hyperactivation as intertwined hallmarks of spinal cord ageing. As an underlying mechanism, we identified a neurotoxic microglial state demarcated by elevated expression of CHIT1 (a secreted mammalian chitinase) specific to the aged spinal cords in NHP and human biopsies. In the aged spinal cord, CHIT1-positive microglia preferentially localize around motor neurons, and they have the ability to trigger senescence, partly by activating SMAD signalling. We further validated the driving role of secreted CHIT1 on MN senescence using multimodal experiments both in vivo, using the NHP spinal cord as a model, and in vitro, using a sophisticated system modelling the human motor-neuron-microenvironment interplay. Moreover, we demonstrated that ascorbic acid, a geroprotective compound, counteracted the pro-senescent effect of CHIT1 and mitigated motor neuron senescence in aged monkeys. Our findings provide the single-cell resolution cellular and molecular landscape of the aged primate spinal cord and identify a new biomarker and intervention target for spinal cord degeneration.

Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions.

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

Integrative roles of human amygdala subdivisions: Insight from direct intracerebral stimulations via stereotactic EEG.

Substantial studies of human amygdala function have revealed its importance in processing emotional experience, autonomic regulation, and sensory information; however, the neural substrates and circuitry subserving functions have not been directly mapped at the level of the subnuclei in humans. We provide a useful overview of amygdala functional characterization by using direct electrical stimulation to various amygdala regions in 48 patients with drug-resistant epilepsy undergoing stereoelectroencephalography recordings. This stimulation extends beyond the anticipated emotional, neurovegetative, olfactory, and somatosensory responses to include visual, auditory, and vestibular sensations, which may be explained by the functional connectivity with cortical and subcortical regions due to evoked amygdala-cortical potentials. Among the physiological symptom categories for each subnucleus, the most frequently evoked neurovegetative symptoms were distributed in almost every subnucleus. Laterobasal subnuclei are mainly associated with emotional responses, somatosensory responses, and vestibular sensations. Superficial subnuclei are mainly associated with emotional responses and olfactory and visual hallucinations. Our findings contribute to a better understanding of the functional architecture of the human amygdala at the subnuclei level and as a mechanistic basis for the clinical practice of amygdala stimulation in treating patients with neuropsychiatric disorders.

The role of the orbitofrontal cortex and insula for prognosis of mesial temporal lobe epilepsy.

OBJECTIVE: We investigated the network between the medial temporal lobe (MTL) and extratemporal structures in patients with mesial temporal lobe epilepsy (MTLE) in order to explain the recurrence of MTLE after surgery. This study contributes to our current understanding of MTLE with stereotactic electroencephalography (SEEG). METHODS: We conducted a retrospective study of SEEG in 20 patients with MTLE in order to observe and analyze the intensity of interictal high-frequency oscillations (HFOs), as well as the dynamic course of coherence connectivity values of the MTL and extratemporal structures during the initial phase of the seizure. The results correlated with the patient prognosis. RESULTS: First, the presence of HFOs was observed during the interictal period in all 20 patients; these were localized to the MTL in 17 patients and the orbitofrontal cortex in seven patients and the insula in six patients. The better the prognosis, the greater the localization of the HFOs concentration in the MTL structures (p < 0.05). Second, significantly enhanced connectivity of MTL structures with the orbitofrontal cortex and insula was observed in most patients with MTLE, before and after the seizure onset (p < 0.05). Finally, the connectivity between extratemporal structures, such as the orbitofrontal cortex and insula, and MTL structures was significantly stronger in patients who had a worse prognosis than in other patients, before and after seizure onset (p < 0.05). INTERPRETATION: The epileptogenic network in recurrent MTLE is not limited to MTL structures but is also associated with the orbitofrontal cortex and insula. This can be used as a potential indicator for predicting the prognosis of patients after surgery, providing an important avenue for future clinical evaluation.

Real-time evaluation of the independent analgesic efficacy of dexmedetomidine.

BACKGROUND: Dexmedetomidine has analgesic properties, but the intraoperative analgesic effect of dexmedetomidine is often masked by the effects of other general anaesthetics. Therefore, the degree to which it reduces intraoperative pain intensity remains unclear. The objective of this double-blind, randomised controlled trial was to evaluate the independent intraoperative analgesic efficacy of dexmedetomidine in real-time. METHODS: This single-centre study enrolled 181 patients who were hospitalised for below-knee orthopaedic surgeries between 19 January 2021 to 3 August 2021 were eligible for this is single-centre study. Peripheral neural block was performed on patients scheduled for below-knee orthopaedic surgeries. Patients were randomly assigned to the dexmedetomidine or midazolam group and were intravenously administered with 1.5 µg kg-1 h-1 dexmedetomidine or 50 µg kg-1 h-1 midazolam, respectively. The analgesic efficacy was evaluated using the real-time non-invasive nociception monitoring. The primary endpoint was the attainment rate of the nociception index target. The secondary endpoints included the occurrence of intraoperative hypoxemia, haemodynamic parameters, the consciousness index, electromyography and patient outcomes. RESULTS: On Kaplan-Meier survival analysis, the defined nociception index target was attained in 95.45% and 40.91% of patients receiving dexmedetomidine and midazolam, respectively. Log-rank analysis revealed that the dexmedetomidine group attained the nociception index target significantly faster and the median attainment time of the nociception index target in the dexmedetomidine group was 15 min. Dexmedetomidine group was associated with a significantly lower incidence of hypoxemia. There was no significant difference in blood pressure between the dexmedetomidine and midazolam groups. Further, the dexmedetomidine group had a lower maximum visual analogue scale score and lower analgesic consumption postoperatively. CONCLUSIONS: Dexmedetomidine has independent analgesia and systemically administered as an adjuvant agent has better analgesic efficacy than midazolam without severe side effects. TRIAL REGISTRATION: clinicaltrial.gov Registry Identifier: NCT-04675372.Registered on 19/12 /2020.

Optimized SEEG-guided three-dimensional radiofrequency thermocoagulation for insular epilepsy.

PURPOSE: The high risk of resection surgery for drug-resistant insular epilepsy has driven interest in new treatment techniques. Stereo-electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) offers an alternative option. Herein, we present the detailed protocol and investigation of the efficacy and safety of a preliminary observational study. METHODS: From February 2017 to April 2021, ten patients diagnosed with insular epilepsy were enrolled in the study. They underwent implantation of a combination of SEEG electrodes to form a high-density focal stereo-array in insula, including oblique electrodes through the long axis of insula and orthogonal electrodes to widely cover the medial and lateral insula. SEEG-3D RFTC was performed between two contiguous contacts of the same electrode, or between two adjacent contacts of different electrodes. RESULTS: Surgical procedures were well tolerated, with no related long-term complications. Seizure-free outcome was achieved in seven patients (70%), including ILAE I in four and ILAE II in three. Two other (20%) patients had rare seizures (ILAE III). One (10%) patient experienced an ILAE IV outcome (follow-up = 12--63 months). The responder rate (including ILAE I-IV) was 100%. CONCLUSION: The optimized SEEG-3D RFTC is an effective and safe option for the treatment of drug-resistant insular epilepsy.

Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients: A Prospective Observational Cohort Study.

OBJECTIVE: To investigate gut microbiota and intestinal barrier function changes after orthopedic surgery in elderly patients with either normal cognition (NC) or a prodromal Alzheimer disease phenotype (pAD) comprising either subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI). BACKGROUND: Homeostatic disturbances induced by surgical trauma and/or stress can potentially alter the gut microbiota and intestinal barrier function in elderly patients before and after orthopedic surgery. METHODS: In this prospective cohort study, 135 patients were subject to preoperative neuropsychological assessment and then classified into: NC (n=40), SCD (n=58), or aMCI (n=37). Their gut microbiota, bacterial endotoxin (lipopolysaccharide), tight junction (TJ) protein, and inflammatory cytokines in blood were measured before surgery and on postsurgical day 1, 3, and 7 (or before discharge). RESULTS: The short-chain fatty acid (SCFA)-producing bacteria were lower while the gram-negative bacteria, lipopolysaccharide and TJ were higher preoperatively in both the SCD and aMCI (pAD) groups compared with the NC group. After surgery, a decrease in SCFA-producing bacteria, and an increase in both gram-negative bacteria and plasma claudin were significant in the pAD groups relative to the NC group. SCFA-producing bacteria were negatively correlated with TJ and cytokines in pAD patients on postsurgical day 7. Furthermore, surgery-induced perioperative metabolic stress and inflammatory responses were associated with gut microbiota alterations. CONCLUSIONS: Surgery exacerbates both preexisting microbiota dysbiosis and intestinal barrier dysfunction in pAD patients, all of which may be associated with systemic inflammation and, in turn, may lead to further cognitive deterioration.

Morphometric analysis program and quantitative positron emission tomography in presurgical localization in MRI-negative epilepsies: a simultaneous PET/MRI study.

PURPOSE: To evaluate morphometric analysis program (MAP) and quantitative positron emission tomography (QPET) in epileptogenic zone (EZ) identification using a simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) system in MRI-negative epilepsies. METHODS: Seventy-one localization-related MRI-negative epilepsies who underwent preoperative simultaneous PET/MRI examination and surgical resection were enrolled retrospectively. MAP was performed on a T1-weighted volumetric sequence, and QPET was analyzed using statistical parametric mapping (SPM) with comparison to age- and gender-matched normal controls. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MAP, QPET, MAP + QPET, and MAP/QPET in EZ localization were assessed. The correlations between surgical outcome and modalities concordant with cortical resection were analyzed. RESULTS: Forty-five (63.4%) patients had Engel I seizure outcomes. The sensitivity, specificity, PPV, and NPV of MAP were 64.4%, 69.2%, 78.3%, and 52.9%, respectively. The sensitivity, specificity, PPV, NPV of QPET were 73.3%, 65.4%, 78.6%, and 58.6%, respectively. MAP + QPET, defined as two tests concordant with cortical resection, had reduced sensitivity (53.3%) but increased specificity (88.5%) relative to individual tests. MAP/QPET, defined as one or both tests concordant with cortical resection, had increased sensitivity (86.7%) but reduced specificity (46.2%) relative to individual tests. The regions determined by MAP, QPET, MAP + QPET, or MAP/QPET concordant with cortical resection were significantly associated with the seizure-free outcome. CONCLUSION: QPET has a superior sensitivity than MAP, while the combined MAP + QPET obtained from a simultaneous PET/MRI scanner may improve the specificity of the diagnostic tests in EZ localization coupled with the preferable surgical outcome in MRI-negative epilepsies.

Delineating the Decussating Dentato-rubro-thalamic Tract and Its Connections in Humans Using Diffusion Spectrum Imaging Techniques.

The objective of this study was to identify the decussating dentato-rubro-thalamic tract (d-DRTT) and its afferent and efferent connections in healthy humans using diffusion spectrum imaging (DSI) techniques. In the present study, the trajectory and lateralization of the d-DRTT was explored using data from subjects in the Massachusetts General Hospital-Human Connectome Project adult diffusion dataset. The afferent and efferent networks that compose the cerebello-thalamo-cerebral pathways were also reconstructed. Correlation analysis was performed to identify interrelationships between subdivisions of the cerebello-dentato-rubro-thalamic and thalamo-cerebral connections. The d-DRTT was visualized bilaterally in 28 subjects. According to a normalized quantitative anisotropy and lateralization index evaluation, the left and right d-DRTT were relatively symmetric. Afferent regions were found mainly in the posterior cerebellum, especially the entire lobule VII (crus I, II and VIIb). Efferent fibers mainly are projected to the contralateral frontal cortex, including the motor and nonmotor regions. Correlations between cerebello-thalamic connections and thalamo-cerebral connections were positive, including the lobule VIIa (crus I and II) to the medial prefrontal cortex (MPFC) and the dorsolateral prefrontal cortex and lobules VI, VIIb, VIII, and IX, to the MPFC and motor and premotor areas. These results provide DSI-based tratographic evidence showing segregated and parallel cerebellar outputs to cerebral regions. The posterior cerebellum may play an important role in supporting and handling cognitive activities through d-DRTT. Future studies will allow for a more comprehensive understanding of cerebello-cerebral connections.

Individual [18F]FDG PET and functional MRI based on simultaneous PET/MRI may predict seizure recurrence after temporal lobe epilepsy surgery.

OBJECTIVES: To investigate the individual measures of brain glucose metabolism, neural activity obtained from simultaneous 18[F]FDG PET/MRI, and their association with surgical outcomes in medial temporal lobe epilepsy due to hippocampal sclerosis (mTLE-HS). METHODS: Thirty-nine unilateral mTLE-HS patients who underwent anterior temporal lobectomy were classified as having completely seizure-free (Engel class IA; n = 22) or non-seizure-free (Engel class IB-IV; n = 17) outcomes at 1 year after surgery. Preoperative [18F]FDG PET and functional MRI (fMRI) were obtained from a simultaneous PET/MRI scanner, and individual glucose metabolism and fractional amplitude of low-frequency fluctuation (fALFF) were evaluated by standardizing these with respect to healthy controls. These abnormality measures and clinical data from each patient were incorporated into a machine learning framework (gradient boosting decision tree and logistic regression analysis) to estimate seizure recurrence. The predictive values of features were evaluated by the receiver operating characteristic (ROC) curve in the training and test cohorts. RESULTS: The machine learning classification model showed [18F]FDG PET and fMRI variations in contralateral hippocampal network and age of onset identify unfavorable surgical outcomes effectively. In the validation dataset, the logistic regression model with [18F]FDG PET and fALFF obtained from simultaneous [18F]FDG PET/MRI gained the maximum area under the ROC curve of 0.905 for seizure recurrence, higher than 0.762 with 18[F]-FDG PET, and 0.810 with fALFF alone. CONCLUSION: Machine learning model suggests individual [18F]FDG PET and fMRI variations in contralateral hippocampal network based on 18[F]-FDG PET/MRI could serve as a potential biomarker of unfavorable surgical outcomes. KEY POINTS: • Individual [18F]FDG PET and fMRI obtained from preoperative [18F]FDG PET/MR were investigated. • Individual differences were further assessed based on a seizure propagation network. • Machine learning can classify surgical outcomes with 90.5% accuracy.

MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study.

OBJECTIVES: To investigate the effects of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status of gliomas on O-(2-18F-fluoroethyl)-L-tyrosine ([18F]FET) uptake and cerebral blood flow (CBF) of arterial spin labeling (ASL), evaluated by hybrid PET/MR. Stereotactic biopsy was used to validate the findings. METHODS: A set of whole tumor and reference volumes of interest (VOIs) based on PET/FLAIR imaging were delineated and transferred to the corresponding [18F]FET PET and CBF maps in 57 patients with newly diagnosed gliomas. The mean and max tumor-to-brain ratio (TBR) and normalized CBF (nCBF) were calculated. The predictive efficacy of [18F]FET PET and CBF in determining MGMT promoter methylation status of glioma were evaluated by whole tumor analysis and stereotactic biopsy. The correlation between PET/MR parameters and MGMT promoter methylation were analyzed using histological specimens acquired from multiple stereotactic biopsies. RESULTS: Based on the analysis of whole tumor volume and biopsy site, TBRmean, TBRmax, nCBFmean, and nCBFmax showed no statistically significant differences between gliomas with and without MGMT promoter methylation (all p > 0.05). Furthermore, stereotactic biopsy demonstrated that TBRmean, TBRmax, nCBFmean, and nCBFmax showed no correlation with MGMT promoter methylation (r = -0.117, p = 0.579; r = -0.161, p = 0.443; r = -0.271, p = 0.191; r = -0.300, p = 0.145; respectively). CONCLUSIONS: MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. Stereotactic biopsy validates it and further reveals there is no correlation of [18F]FET PET uptake and CBF with the percentages of MGMT promoter methylation. KEY POINTS: • Based on whole tumor VOI assessment, MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. • For WHO grade IV glioblastomas, [18F]FET PET and ASL parameters based on hybrid PET/MR fail to predict the MGMT promoter methylation status. • Stereotactic image-based histology reveals that there is no correlation of [18F]FET PET uptake and CBF with the status and percentages of MGMT promoter methylation in gliomas.

[18F]FDG PET/MRI and magnetoencephalography may improve presurgical localization of temporal lobe epilepsy.

OBJECTIVES: To evaluate the clinical value of the combination of [18F]FDG PET/MRI and magnetoencephalography (MEG) ([18F]FDG PET/MRI/MEG) in localizing the epileptogenic zone (EZ) in temporal lobe epilepsy (TLE) patients. METHODS: Seventy-three patients with localization-related TLE who underwent [18F]FDG PET/MRI and MEG were enrolled retrospectively. PET/MRI images were interpreted by two radiologists; the focal hypometabolism on PET was identified using statistical parametric mapping (SPM). MEG spike sources were co-registered onto T1-weighted sequence and analyzed by Neuromag software. The clinical value of [18F]FDG PET/MRI, MEG, and PET/MRI/MEG in locating the EZ was assessed using cortical resection and surgical outcomes as criteria. The correlations between surgical outcomes and modalities concordant or non-concordant with cortical resection were analyzed. RESULTS: For 46.6% (34/73) of patients, MRI showed definitely structural abnormality concordant with surgical resection. SPM results of [18F]FDG PET showed focal temporal lobe hypometabolism concordant with surgical resection in 67.1% (49/73) of patients, while the concordant cases increased to 82.2% (60/73) patients with simultaneous MRI co-registration. MEG was concordant with surgical resection in 71.2% (52/73) of patients. The lobar localization was defined in 94.5% (69/73) of patients by the [18F]FDG PET/MRI/MEG. The results of PET/MRI/MEG concordance with surgical resection were significantly higher than that of PET/MRI or MEG (χ2 = 13.948, p < 0.001; χ2 = 5.393, p = 0.020). The results of PET/MRI/MEG cortical resection concordance with surgical outcome were shown to be better than PET/MRI or MEG (χ2 = 6.695, p = 0.012; χ2 = 16.991, p < 0.0001). CONCLUSIONS: Presurgical evaluation by [18F]FDG PET/MRI/MEG could improve the identification of the EZ in TLE and may further guide surgical decision-making. KEY POINTS: • Lobar localization was defined in 94.5% of patients by the [18F]FDG PET/MRI/MEG. • The results of PET/MRI/MEG concordance with surgical resection were significantly higher than that of PET/MRI or MEG alone. • The results of PET/MRI/MEG cortical resection concordance with surgical outcome were shown to be better than that of PET/MRI or MEG alone.

Combined [18F]FDG-PET with MRI structural patterns in predicting post-surgical seizure outcomes in temporal lobe epilepsy patients.

OBJECTIVES: To integrate the glucose metabolism measured using [18F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy. METHODS: This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes. RESULTS: The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38-161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02-50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13-101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90-73.80, p = 0.001) and 12.01 (95% CI 2.91-49.65, p = 0.001), respectively. CONCLUSION: Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery. KEY POINTS: • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV.

Comprehensive geriatric assessment for older orthopedic patients and analysis of risk factors for postoperative complications.

BACKGROUND: The comprehensive geriatric assessment (CGA) has been proposed as a supplementary tool to reduce perioperative complications of geriatric patients, however there is no universally accepted standardization of CGA for orthopedic surgery. In this study, a novel CGA strategy was applied to evaluate the conditions of older patients undergoing orthopedic surgery from a broad view and to identify potential risk factors for postoperative complications. METHODS: A prospective cohort study was conducted from March 2019 to December 2020.The study enrolled patients (age > 75 years) for elective or confined orthopedic surgery. All patients were treated by a multidisciplinary team. A structured CGA was conducted to identify high-risk older patients and to facilitate coordinated multidisciplinary team care by a geriatric team. The basic patient characteristics, CGA results, postoperative complication and mortality rates were collected. Multivariate logistic regression analysis was used to identify risk factors for postoperative complications. RESULTS: A total of 214 patients with an age of 81.07 ± 4.78 (range, 75-100) years were prospectively enrolled in this study. In total, 66 (30.8%) complications were registered, including one death from myocardial infarction (mortality rate, 0.5%). Poor Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were accompanied by frailty, worse perioperative risk, pain, and nutritional status. Poor ADL was also associated with higher risks of falling, polypharmacy, and cardiac and respiration complications. Poor IADL was associated with a higher risk of cardiac and respiration complications. Higher stroke risk was accompanied by higher risks of cardiac complications, delirium, and hemorrhage. Worse American Society of Anesthesiologists (ASA) score was associated with worse ADL, IADL, frailty, and higher delirium risk. Multivariate logistic regression analysis showed that spinal fusion (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.65 to 0.83; p = 0.0214), blood loss(OR, 1.68; 95% CI, 1.31 to 2.01; p = 0.0168), ADL (severe dysfunction or worse) (OR, 1.45; 95% CI, 1.16 to 1.81; p = 0.0413), IADL (serious dependence) (OR, 1.08; 95% CI, 1.33 to 1.63; p = 0.0436), renal function (chronic kidney disease (CKD) ≥ stage 3a) (OR, 2.01; 95% CI, 1.54 to 2.55; p = 0.0133), and malnutrition(OR, 2.11; 95% CI, 1.74 to 2.56; p = 0.0101) were independent risk factors for postoperative complications. CONCLUSION: The CGA process reduces patient mortality and increases safety in older orthopedic surgery patients. Spinal fusion, blood loss, ADL (severe dysfunction or worse), IADL (serious dependence), renal function (CKD ≥ stage 3a) and nutrition mini nutritional assessment (MNA) (malnourished) were independent risk factors of postoperative complications following orthopaedic surgery in older patients.

Binaural processing deficit and cognitive impairment in Alzheimer's disease.

Speech comprehension in noisy environments depends on central auditory functions, which are vulnerable in Alzheimer's disease (AD). Binaural processing exploits two ear sounds to optimally process degraded sound information; its characteristics are poorly understood in AD. We studied behavioral and electrophysiological alterations in binaural processing among 121 participants (AD = 27; amnestic mild cognitive impairment [aMCI] = 33; subjective cognitive decline [SCD] = 30; cognitively normal [CN] = 31). We observed impairment of binaural processing in AD and aMCI, and detected a U-shaped curve change in phase synchrony (declining from CN to SCD and to aMCI, but increasing from aMCI to AD). This improvement in phase synchrony accompanying more severe cognitive stages could reflect neural adaptation for binaural processing. Moreover, increased phase synchrony is associated with worse memory during the stages when neural adaptation apparently occurs. These findings support a hypothesis that neural adaptation for binaural processing deficit may exacerbate cognitive impairment, which could help identify biomarkers and therapeutic targets in AD.

Assessment of localization accuracy and postsurgical prediction of simultaneous 18F-FDG PET/MRI in refractory epilepsy patients.

OBJECTIVES: To evaluate the accuracies of simultaneous 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) in preoperative localization and the postsurgical prediction. METHODS: This retrospective study was performed on ninety-eight patients diagnosed with refractory epilepsy whose presurgical evaluation included [18F]-FDG PET/MRI, with 1-year post-surgery follow-up between August 2016 and December 2018. PET/MRI images were interpreted by two radiologists and a nuclear medicine physician to localize the EOZ using standard visual analysis and asymmetry index based on standard uptake value (SUV). The localization accuracy and predictive performance of simultaneous 18F-FDG PET/MRI based on the surgial pathology and postsurgical outcome were evaluated. RESULTS: A total of 41.8% (41/98) patients were found to have a definitely structural abnormality on the MR portion of PET/MRI; 93.9% (92/98) were shown hypometabolism on the PET portion of the hybrid PET/MRI. PET/MRI identified 18 cases with subtle structural abnormalities on MRI re-read. Six percent (6/98) of patients PET/MRI were negative. A total of 65.3% (64/98) patients showed seizure-free at 1-year follow-up after epilepsy surgery. The sensitivity, specificity, and accuracy of [18F]-FDG PET/MRI was 95.3%, 8.8%, and 65.3% for seizure onset localization based on surgical pathology and postsurgical outcome, respectively. Multivariate regression analysis indicated that concordant of EOZ localization between PET/MRI and surgical resection range, which was a good positive predictor of seizure freedom (Engel I) (OR = 14.741, 95% CI 3.934-55.033, p < 0.001). CONCLUSIONS: [18F]-FDG PET/MRI used as two combined modalities providing additional sensitivity when detecting possible epileptic foci and will probably improve the surgical outcome. KEY POINTS: • Sensitivity, specificity, and accuracy of [18F]-FDG PET/MRI were 95.3%, 8.8%, and 65.3% for seizure onset localization based on surgical pathology and postsurgical outcome, respectively. • Concordance of EOZ localization between PET/MRI and surgical resection range was a good positive predictor of seizure freedom; presurgical [18F]-FDG PET/MRI will probably improve the surgical outcome.

Static 18F-FET PET and DSC-PWI based on hybrid PET/MR for the prediction of gliomas defined by IDH and 1p/19q status.

OBJECTIVES: To investigate the predictive value of static O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET) and cerebral blood volume (CBV) for glioma grading and determining isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status. METHODS: Fifty-two patients with newly diagnosed gliomas who underwent simultaneous 18F-FET PET and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) examinations on hybrid PET/MR were retrospectively enrolled. The mean and max tumor-to-brain ratio (TBR) and normalized CBV (nCBV) were calculated based on whole tumor volume segmentations with reference to PET/MR images. The predictive efficacy of FET PET and CBV in glioma according to the 2016 World Health Organization (WHO) classification was evaluated by receiver operating characteristic curve analyses with the area under the curve (AUC). RESULTS: TBRmean, TBRmax, nCBVmean, and nCBVmax differed between low- and high-grade gliomas, with the highest AUC of nCBVmean (0.920). TBRmax and nCBVmean showed significant differences between gliomas with and without IDH mutation (p = 0.032 and 0.010, respectively). Furthermore, TBRmean, TBRmax, and nCBVmean discriminated between IDH-wildtype glioblastomas and IDH-mutated astrocytomas (p = 0.049, 0.034 and 0.029, respectively). The combination of TBRmax and nCBVmean showed the best predictive performance (AUC, 0.903). Only nCBVmean differentiated IDH-mutated with 1p/19q codeletion oligodendrogliomas from IDH-wildtype glioblastomas (p < 0.001) (AUC, 0.829), but none of the parameters discriminated between oligodendrogliomas and astrocytomas. CONCLUSIONS: Both FET PET and DSC-PWI might be non-invasive predictors for glioma grades and IDH mutation status. FET PET combined with CBV could improve the differentiation of IDH-mutated astrocytomas and IDH-wildtype glioblastomas. However, FET PET and CBV might be limited for identifying oligodendrogliomas. KEY POINTS: • Static 18F-FET PET and DSC-PWI parameters differed between low- and high-grade gliomas, with the highest AUC of the mean value of normalized CBV. • Static 18F-FET PET and DSC-PWI parameters based on hybrid PET/MR showed predictive value in identifying glioma IDH mutation subtypes, which have gained importance for both determining the diagnosis and prognosis of gliomas according to the 2016 WHO classification. • Static 18F-FET PET and DSC-PWI parameters have limited potential in differentiating IDH-mutated with 1p/19q codeletion oligodendrogliomas from IDH-wildtype glioblastomas or IDH-mutated astrocytomas.

Detecting small conflicting drainages with contrast-enhanced magnetic resonance venography for surgical planning: a technical description and quantified analysis.

BACKGROUND: Recent studies have shown the challenges involved in detecting small conflicting vessels (1.0-1.5 mm) on contrast-enhanced (CE) T1 images during stereoelectroencephalography (SEEG) planning. Improving the resolution of non-invasive approaches to identify these vessels is possible and important. We present a superior sagittal sinus mapping-based CE-magnetic resonance venography (CE-MRV) protocol calibrated by craniotomies. METHOD: Seven patients with epileptic symptoms who received craniotomy were enrolled. CE-MRV was acquired with a bolus mapping of the superior sagittal sinus. Together with the T1 image, 3D veins and the brain surface were visualized. The resolution of the CE-MRV was quantified by measuring the diameter of superficial drainages after exposure of the brain surface during craniotomy. RESULTS: A total of 37 superficial drainages were exposed in the bone windows. CE-MRV visualized all these drainages. On average, one superficial drainage could be found in every 13.2 mm diameter of the bone window. The boundary resolution of the CE-MRV was 0.58-0.8 mm in vessel diameter, while drainages larger than 0.8 mm were visualized consistently. CONCLUSIONS: The resolution of the CE-MRV in the present study met the requirement for detection of small conflicting vessels during SEEG planning. The visualized venous landmarks could be used for visual guidance to the surgical zone. As a non-invasive approach, CE-MRV is practical to use in the clinical setting.

The effect of hypothermia during cardiopulmonary bypass on three electro-encephalographic indices assessing analgesia and hypnosis during anesthesia: consciousness index, nociception index, and bispectral index.

The depth of anesthesia is commonly assessed in clinical practice by the patient's clinical signs. However, during cardiopulmonary bypass and hypothermia, common symptoms of nociception such as tachycardia, hypertension, sweating, or movement have low sensitivity and specificity in the description of the patient nociception and hypnosis, in particular, detecting nociceptive stimuli. Better monitoring of the depth of analgesia during hypothermia under cardiopulmonary bypass will avoid underdosage or overdosage of analgesia, especially opioids. Induced hypothermia has a multifactorial effect on the level of analgesia and hypnosis. Thermoregulatory processes appear essential for the activation of analgesic mechanisms, ranging from a physiological strong negative affiliation between nerve conduction velocity and temperature, until significant repercussions on the pharmacological dynamics of the analgesic drugs, the latter decreasing the clearance rate with a subsequent increase in the effect-site concentrations. Under the hypothesis that deep hypothermia induces massive effects on the analgesia and hypnosis levels of the patient, we studied whether hypothermia effects were mirrored by several neuromonitoring indices: two hypnosis indices, consciousness index and bispectral index, and a novel nociception index designed to evaluate the analgesic depth. In this clinical trial, 39 patients were monitored during general anesthesia with coronary atherosclerosis cardiopathy who were elective for on-pump coronary artery bypass graft surgery under hypothermia. The changes and correlation between the consciousness index, bispectral index, and nociception index with respect to the temperature were compared in different timepoints at basic state, during cardiopulmonary bypass and after cardiopulmonary bypass. While the three neuromonitoring indices showed significant correlations with respect to the temperature, the nociception index and consciousness index showed the strongest sensitivities, indicating that these two indices could be an important means of intraoperative neuromonitoring during induced hypothermia under cardiopulmonary bypass.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.