Performance and usability of pre-operative prediction models for 30-day peri-operative mortality risk: a systematic review.

Estimating pre-operative mortality risk may inform clinical decision-making for peri-operative care. However, pre-operative mortality risk prediction models are rarely implemented in routine clinical practice. High predictive accuracy and clinical usability are essential for acceptance and clinical implementation. In this systematic review, we identified and appraised prediction models for 30-day postoperative mortality in non-cardiac surgical cohorts. PubMed and Embase were searched up to December 2022 for studies investigating pre-operative prediction models for 30-day mortality. We assessed predictive performance in terms of discrimination and calibration. Risk of bias was evaluated using a tool to assess the risk of bias and applicability of prediction model studies. To further inform potential adoption, we also assessed clinical usability for selected models. In all, 15 studies evaluating 10 prediction models were included. Discrimination ranged from a c-statistic of 0.82 (MySurgeryRisk) to 0.96 (extreme gradient boosting machine learning model). Calibration was reported in only six studies. Model performance was highest for the surgical outcome risk tool (SORT) and its external validations. Clinical usability was highest for the surgical risk pre-operative assessment system. The SORT and risk quantification index also scored high on clinical usability. We found unclear or high risk of bias in the development of all models. The SORT showed the best combination of predictive performance and clinical usability and has been externally validated in several heterogeneous cohorts. To improve clinical uptake, full integration of reliable models with sufficient face validity within the electronic health record is imperative.

Malnutrition in early life and its neurodevelopmental and cognitive consequences: a scoping review.

The negative impact of stunting and severe underweight on cognitive neurodevelopment of children is well documented; however, the effect of overweight/obesity is still unclear. The 2018 Global Nutrition Report reported that stunting and overweight concurrently affect 189 million children worldwide. As existing reviews discuss undernutrition and overweight/obesity separately, this scoping review aims to document the impact of mild/moderate and severe underweight, stunting, and overweight/obesity among children aged 0-60 months on their cognitive neurodevelopmental trajectories. Twenty-six articles were analysed to extract significant information from literature retrieved from PubMed and Cochrane databases published from 1 January 2009 to 31 October 2019. Length gain is associated with cognitive neurodevelopment in normo-nourished and stunted children aged under 24 months. Among stunted children, it seems that cognitive and neurodevelopmental deficits can potentially be recovered before 8 years of age, particularly in those whose nutritional status has improved. The impact of overweight/obesity on cognitive neurodevelopment appears to be limited to attention, gross motor skills and executive control. Parental education level, birth weight/length, breastfeeding duration, and sanitation level are some identifiable factors that modify the impact of undernutrition and overweight/obesity on cognitive and neurodevelopment. In conclusion, underweight, stunting and overweight/obesity have a significant impact on cognitive neurodevelopment. Multidimensional approaches with various stakeholders should address all issues simultaneously, such as improving sanitation levels, assuring parental job security and adequate social welfare, and providing access to adequate nutrients for catch-up growth among underweight or stunted children and to affordable healthy foods for those who are overweight/obese and from low socio-economic status.

NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.

BACKGROUND: Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. OBJECTIVES: We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults. METHODS: A randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly. RESULTS: Following supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342]. CONCLUSIONS: Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.

Predicting clinical progression in multiple sclerosis after 6 and 12 years.

BACKGROUND AND PURPOSE: To predict disability and cognition in multiple sclerosis (MS) after 6 and 12 years, using early clinical and imaging measures. METHODS: A total of 115 patients with MS were selected and followed up after 2 and 6 years, with 79 patients also being followed up after 12 years. Disability was measured using the Expanded Disability Status Scale (EDSS); cognition was measured only at follow-up using neuropsychological testing. Predictors of interest included EDSS score, baseline brain and lesion volumes and their changes over 2 years, baseline age, clinical phenotype, sex and educational level. RESULTS: Higher 6-year EDSS score was predicted by early EDSS score and whole-brain volume changes and baseline diagnosis of primary progressive MS (adjusted R2  = 0.56). Predictors for 12-year EDSS score included larger EDSS score changes and higher T1-hypointense lesion volumes (adjusted R2  = 0.38). Year 6 cognition was predicted by primary progressive MS phenotype, lower educational level, male sex and early whole-brain atrophy (adjusted R2  = 0.26); year 12 predictors included male sex, lower educational level and higher baseline T1-hypointense lesion volumes (adjusted R2  = 0.14). CONCLUSIONS: Patients with early signs of neurodegeneration and a progressive disease onset were more prone to develop both disability progression and cognitive dysfunction. Male sex and lower educational level only affected cognitive dysfunction, which remains difficult to predict and probably needs more advanced imaging measures.

rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). METHODS: 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. RESULTS: N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. CONCLUSIONS: In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients' brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.

Treatment strategies for chronic osteomyelitis in low- and middle-income countries: systematic review.

OBJECTIVES: To identify a standard treatment regime or highly successful procedure for chronic osteomyelitis in low- and middle-income countries. METHODS: Systematic review following PRISMA guidelines. RESULTS: The initial search resulted in 102 studies of which nine met the inclusion criteria and were analysed qualitatively. The included studies involved 1173 patients from Africa and Asia. All patients were diagnosed with chronic osteomyelitis. Surgical and antibiotic treatment regimens differed substantially. No better judgement than moderate risk of selection bias could be made due to the study designs. CONCLUSIONS: The evidence is not sufficiently robust to identify the most effective treatment, or to even allow a recommendation of the best suitable treatment of chronic osteomyelitis in low-income countries.

[Multidisciplinary treatment of orofacial pain]. / Multidisciplinaire behandeling van aangezichtspijn.

The diagnosis and treatment of orofacial pain can be complex. The differential diagnosis is very extensive. Therefore, multidisciplinary diagnosis and treatment are often indicated. The diagnosis of chronic pain also entails the investigation of psychological factors. This is because psychological problems can play a role in the chronification of pain, but they can also be a consequence of chronic pain. Patients with persistent orofacial complaints should be seen by a medical team consisting of an oral and maxillofacial surgeon, a neurologist, an anaesthesiologist/pain specialist, a dentist-gnathologist, an orofacial physical therapist, and a psychologist or psychiatrist specialising in orofacial pain. Treatment options should be discussed, taking into account literature concerning their effectiveness. The general conclusion is that much research remains to be done into the causes of, and treatments for, orofacial pain.

Multicolor flow cytometry-based cellular phenotyping identifies osteoprogenitors and inflammatory cells in the osteoarthritic subchondral bone marrow compartment.

PURPOSE: The cellular component of subchondral bone is thought to be responsible for aberrant bone remodeling in osteoarthritis (OA). Direct phenotypical analysis of the cellular compartment is critical to better understand the OA disease process. This study provides proof-of-principle for flow cytometry-based phenotyping of isolated subchondral trabecular bone (STB) marrow cells without prior use of cell culture techniques. METHODS: Tibial plateaus were obtained from OA patients undergoing total knee arthroplasty. Subchondral bone chips were digested with collagenase IA and single cell suspensions were directly phenotyped using flow cytometry. Cells were analyzed for the expression of alkaline phosphatase (ALP) as osteoblast/osteoprogenitor marker and monocyte/macrophage markers (CD14, CD68, HLA-DR, CD115). RESULTS: MTT staining revealed abundant viable cells in the bone marrow compartment of STB prior to digestion, which were efficiently released by collagenase. Within the CD45-negative cell fraction, approximately 20% of the cells were positive for the early osteoblast/osteoprogenitor marker ALP. Within the CD45+ hematopoietic cell fraction, the majority of cells were of monocytic origin (>80%) displaying strong surface expression of CD14. Discreet macrophage populations (CD14+/HLA-DR+/CD68+) and putative osteoclast progenitors (CD45+/HLA-DR-/CD115+) were unequivocally identified. Osteoblast, macrophage and osteoclast progenitor presence in the subchondral bone unit (SBU) was confirmed by (immuno)histochemical staining for osteocalcin, CD68 and tartrate-resistant acid phosphatase, respectively. CONCLUSIONS: Flow cytometric analysis is a valuable methodology to study the cellular compartment of STB marrow. This method provides a proof of principle that the whole resident cell population can be directly phenotypically characterized without the prior use of cell culture techniques.

What drives MRI-measured cortical atrophy in multiple sclerosis?

BACKGROUND: Cortical atrophy, assessed with magnetic resonance imaging (MRI), is an important outcome measure in multiple sclerosis (MS) studies. However, the underlying histopathology of cortical volume measures is unknown. OBJECTIVE: We investigated the histopathological substrate of MRI-measured cortical volume in MS using combined post-mortem imaging and histopathology. METHODS: MS brain donors underwent post-mortem whole-brain in-situ MRI imaging. After MRI, tissue blocks were systematically sampled from the superior and inferior frontal gyrus, anterior cingulate gyrus, inferior parietal lobule, and superior temporal gyrus. Histopathological markers included neuronal, axonal, synapse, astrocyte, dendrite, myelin, and oligodendrocyte densities. Matched cortical volumes from the aforementioned anatomical regions were measured on the MRI, and used as outcomes in a nested prediction model. RESULTS: Forty-five tissue blocks were sampled from 11 MS brain donors. Mean age at death was 68±12 years, post-mortem interval 4±1 hours, and disease duration 35±15 years. MRI-measured regional cortical volumes varied depending on anatomical region. Neuronal density, neuronal size, and axonal density were significant predictors of GM volume. CONCLUSIONS: In patients with long-standing disease, neuronal and axonal pathology are the predominant pathological substrates of MRI-measured cortical volume in chronic MS.

Perivascular spaces in MS patients at 7 Tesla MRI: a marker of neurodegeneration?

BACKGROUND: Virchow-Robin spaces (VRS) are associated with vascular and neurodegenerative disease. In multiple sclerosis (MS), VRS have been associated with neuroinflammation. Ultra-high field imaging may be used to gain insight in these contradictory findings. OBJECTIVE: The objective of this paper is to analyze VRS in MS patients using high-resolution 7 Tesla (T) MRI. Additionally, we investigated whether the widening of VRS is related to inflammatory or neurodegenerative aspects of MS. METHODS: Thirty-four MS patients and 11 healthy controls were examined at 7T. Number and size of VRS were measured on three-dimensional (3D) T1-weighted images, and 3D fluid-attenuated inversion recovery (FLAIR) images were used for MS lesion detection. Brain atrophy was quantified by computing supratentorial brain volume fraction (sBVF). VRS counts were correlated with clinical variables, lesion count and sBVF. RESULTS: MS patients displayed more VRS (median 11) than healthy controls (median four), p = 0.001. VRS size did not differ between both groups. VRS count in MS patients was associated with sBVF (rho = -0.40, p = 0.02), but not with lesion count (p = 0.22). CONCLUSIONS: The 7T MRI reveals increased numbers of VRS in MS. The finding that VRS are associated with supratentorial brain atrophy, but not with lesion count, suggests that VRS might rather serve as a neurodegenerative than an inflammatory marker in MS.

Functional brain network analysis using minimum spanning trees in Multiple Sclerosis: an MEG source-space study.

Cognitive dysfunction in Multiple Sclerosis (MS) is closely related to altered functional brain network topology. Conventional network analyses to compare groups are hampered by differences in network size, density and suffer from normalization problems. We therefore computed the Minimum Spanning Tree (MST), a sub-graph of the original network, to counter these problems. We hypothesize that functional network changes analysed with MSTs are important for understanding cognitive changes in MS and that changes in MST topology also represent changes in the critical backbone of the original brain networks. Here, resting-state magnetoencephalography (MEG) recordings from 21 early MS patients and 17 age-, gender-, and education-matched controls were projected onto atlas-based regions-of-interest (ROIs) using beamforming. The phase lag index was applied to compute functional connectivity between regions, from which a graph and subsequently the MST was constructed. Results showed lower global integration in the alpha2 (10-13Hz) and beta (13-30Hz) bands in MS patients, whereas higher global integration was found in the theta band. Changes were most pronounced in the alpha2 band where a loss of hierarchical structure was observed, which was associated with poorer cognitive performance. Finally, the MST in MS patients as well as in healthy controls may represent the critical backbone of the original network. Together, these findings indicate that MST network analyses are able to detect network changes in MS patients, which may correspond to changes in the core of functional brain networks. Moreover, these changes, such as a loss of hierarchical structure, are related to cognitive performance in MS.

Suris tetrons: possible spectroscopic evidence for four-particle optical excitations of a two-dimensional electron gas.

The excitations of a two-dimensional electron gas in quantum wells with intermediate carrier density (ne∼1011 cm-2), i.e., between the exciton-trion and the Fermi-sea range, are so far poorly understood. We report on an approach to bridge this gap by a magnetophotoluminescence study of modulation-doped (Cd,Mn)Te quantum well structures. Employing their enhanced spin splitting, we analyzed the characteristic magnetic-field behavior of the individual photoluminescence features. Based on these results and earlier findings by other authors, we present a new approach for understanding the optical transitions at intermediate densities in terms of four-particle excitations, the Suris tetrons, which were up to now only predicted theoretically. All characteristic photoluminescence features are attributed to emission from these quasiparticles when attaining different final states.

Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration.

BACKGROUND: Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease. OBJECTIVES: The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS. METHODS: Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups). RESULTS: In the binary model, UCCA (p < 0.01) and T2LV (p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA (p < 0.01), T2LV (p = 0.02) and GMF (p = 0.04) were independently associated with disability. CONCLUSIONS: Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

The effect of post-traumatic long bone non-unions on health-related quality of life.

BACKGROUND: Fracture non-unions have a detrimental effect on patients due to reduced mobility and severe pain. Current literature on the quality of life in non-unions is limited, hence the purpose of this study, to quantify the health-related quality of life (HRQoL) among patients with post-traumatic long bone non-unions. It was hypothesized that the HRQoL of these patients is lower than the Dutch population standard as well as for multiple chronic diseases and musculoskeletal disorders. PATIENTS AND METHODS: From January 2020 to December 2021, this study included consecutive patients who were referred to a multidisciplinary (trauma, orthopedic and plastic surgery), non-union clinic at the Maastricht UMC+. All non-unions were evaluated using the Non-Union Scoring System (NUSS) questionnaire. Patient reported HRQoL outcomes were acquired using the EQ-5D-5L questionnaire and the Lower Extremity Functional Scale (LEFS). RESULTS: 50 patients were included, 18 females and 32 males, with a mean age of 55 years (± 15.5 SD). Eighteen patients presented with an open fracture, nine non-unions were infected and 39 patients had a lower extremity non-union. The mean NUSS score was 39.61 (± 14.6 SD). The mean EQ-5D-5L index score was 0.490 (± 0.261 SD), where patients experienced most problems with mobility. The mean EQ-5D-5L VAS was 61.4 (± 19.6 SD). The patients had a mean LEFS score of 28.7 (± 16.4 SD). The health-related quality of life was well below the age-corrected normative score of the Dutch population (EQ-5D-5L 0.857(p < 0.001); LEFS 77(p < 0.001)). This cohort's HRQoL was significantly lower than the HRQoL of multiple chronic and musculoskeletal disorders, including different forms of cancer and osteoarthritis. CONCLUSIONS: This study has quantified the detrimental effect of post-traumatic long bone non-unions on patient's health-related quality of life, being significantly lower than the HRQoL of the Dutch population as well as for multiple chronic and musculoskeletal medical conditions. This cohort demonstrates a patient population in need of more specialized care with a low health-related quality of life.

Comparing individual and group-level simulated neurophysiological brain connectivity using the Jansen and Rit neural mass model.

Computational models are often used to assess how functional connectivity (FC) patterns emerge from neuronal population dynamics and anatomical brain connections. It remains unclear whether the commonly used group-averaged data can predict individual FC patterns. The Jansen and Rit neural mass model was employed, where masses were coupled using individual structural connectivity (SC). Simulated FC was correlated to individual magnetoencephalography-derived empirical FC. FC was estimated using phase-based (phase lag index (PLI), phase locking value (PLV)), and amplitude-based (amplitude envelope correlation (AEC)) metrics to analyze their goodness of fit for individual predictions. Individual FC predictions were compared against group-averaged FC predictions, and we tested whether SC of a different participant could equally well predict participants' FC patterns. The AEC provided a better match between individually simulated and empirical FC than phase-based metrics. Correlations between simulated and empirical FC were higher using individual SC compared to group-averaged SC. Using SC from other participants resulted in similar correlations between simulated and empirical FC compared to using participants' own SC. This work underlines the added value of FC simulations using individual instead of group-averaged SC for this particular computational model and could aid in a better understanding of mechanisms underlying individual functional network trajectories.

Treatment of infected tibial non-unions using a BMAC and S53P4 BAG combination for reconstruction of segmental bone defects: A clinical case series.

INTRODUCTION: Treatment of infected non-unions of the tibia is a challenging problem. The cornerstones of optimal infected non-union treatment consist of extensive debridement, fracture fixation, antimicrobial therapy and creation of an optimal local biological bone healing environment. The combination of S53P4 bioactive glass (BAG), as osteostimulative antibacterial bone graft substitute, and bone marrow aspirate concentrate (BMAC) for the implantation of mesenchymal stem cells and growth factors might be a promising combination. In this paper, preliminary results of a new treatment algorithm for infected non-unions of the tibia is presented. METHODS: In this retrospective case series patients with infected non-unions of the tibia are treated according to a new treatment algorithm. Patients are treated with extensive debridement surgery, replacement of the osteosynthesis and implantation of S53P4 BAG and BMAC in a one-stage or two-stage procedure based on non-union severity. Subsequently patients are treated with culture based antibiotic therapy and followed until union and infection eradication. RESULTS: Five patients with an infected non-union were treated, mean age was 55, average NUSS-score was 44 and the average segmental bone defect was 4.6cm. One patient was treated in a one-stage procedure and four patients in a two-stage induced membrane-, or "Masquelet"-procedure. On average, 23 ml S53P4 BAG and 6.2 ml BMAC was implanted. The mean follow-up period was 13.6 months and at the end of follow-up all patients had clinical consolidation with an average RUST-score of 7.8 and complete eradication of infection. DISCUSSION: These early data on the combined implantation of S53P4 BAG and BMAC in treatment of infected non-unions shows promising results. These fracture healing results and eradication rates resulted in promising functional recovery of the patients. To substantiate these results, larger and higher quality studies should be performed.

Dorsal attention network centrality increases during recovery from acute stress exposure.

Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress.

Impaired saccadic eye movements in multiple sclerosis are related to altered functional connectivity of the oculomotor brain network.

BACKGROUND: Impaired eye movements in multiple sclerosis (MS) are common and could represent a non-invasive and accurate measure of (dys)functioning of interconnected areas within the complex brain network. The aim of this study was to test whether altered saccadic eye movements are related to changes in functional connectivity (FC) in patients with MS. METHODS: Cross-sectional eye movement (pro-saccades and anti-saccades) and magnetoencephalography (MEG) data from the Amsterdam MS cohort were included from 176 MS patients and 33 healthy controls. FC was calculated between all regions of the Brainnetome atlas in six conventional frequency bands. Cognitive function and disability were evaluated by previously validated measures. The relationships between saccadic parameters and both FC and clinical scores in MS patients were analysed using multivariate linear regression models. RESULTS: In MS pro- and anti-saccades were abnormal compared to healthy controls A relationship of saccadic eye movements was found with FC of the oculomotor network, which was stronger for regional than global FC. In general, abnormal eye movements were related to higher delta and theta FC but lower beta FC. Strongest associations were found for pro-saccadic latency and FC of the precuneus (beta band ß = -0.23, p = .006), peak velocity and FC of the parietal eye field (theta band ß = -0.25, p = .005) and gain and FC of the inferior frontal eye field (theta band ß = -0.25, p = .003). Pro-saccadic latency was also strongly associated with disability scores and cognitive dysfunction. CONCLUSIONS: Impaired saccadic eye movements were related to functional connectivity of the oculomotor network and clinical performance in MS. This study also showed that, in addition to global network connectivity, studying regional changes in MEG studies could yield stronger correlations.

Non-invasively measured brain activity and radiological progression in diffuse glioma.

Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoencephalography (MEG) was recorded in 45 diffuse glioma patients. Brain activity was estimated using three measures (absolute broadband power, offset and slope) calculated at three spatial levels: global average, averaged across the peritumoral areas, and averaged across the homologues of these peritumoral areas in the contralateral hemisphere. Tumors were segmented on MRI. Changes in tumor volume between the two scans surrounding the MEG were calculated and correlated with brain activity. Brain activity was compared between patient groups classified into having increasing or stable tumor volume. Results show that brain activity was significantly increased in the tumor hemisphere in general, and in peritumoral regions specifically. However, none of the measures and spatial levels of brain activity correlated with changes in tumor volume, nor did they differ between patients with increasing versus stable tumor volumes. Longitudinal studies in more homogeneous subgroups of glioma patients are necessary to further explore the clinical potential of non-invasively measured brain activity.

Acute severe memory impairment as a presenting symptom of multiple sclerosis: a clinical case study with 3D double inversion recovery MR imaging.

We present the case of a 21-year-old woman with acute memory impairment. It was initially not recognized as organic in nature. Repeated neuropsychological testing confirmed severely disturbed encoding and recall. Three-dimensional double inversion recovery (3D-DIR) MRI confirmed hippocampal and cortical lesions. Further clinical symptoms, visual evoked potential and MRI suggested a diagnosis of multiple sclerosis (MS). The amnestic syndrome has remained for 5 years. This case illustrates that MS can present with acute cortical symptoms which can be difficult to recognize. The hippocampus can be acutely affected and DIR MRI imaging can help to demonstrate cortical lesions that explain the clinical picture.