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The objective of the study was to record Laryngeal Motor Evoked Potentials (LMEPs) in Vagus Nerve Stimulation (VNS)-implanted patients suffering from Drug-Resistant Epilepsy (DRE). Based on these recordings, LMEPs characteristics were evaluated and compared between responders (R) and non-responders (NR). Finally, possible under- or over-stimulation was assessed based on a physiological indicator of fiber engagement. Methods: Mean dose–response curves were compared between R and NR. A Support Vector Machine (SVM) model was built based on both LMEP and dose–response curves features, to discriminate R from NR. For the exploration of possible under- or over-stimulation, a ratio between the clinically applied stimulation intensity and the intensity yielding to LMEP saturation was computed for each patient. Results: A trend towards a greater excitability of the nerve was observed in R compared to NR. The SVM classifier discriminated R and NR with an accuracy of 80%. An ineffective attempt to overstimulate at current levels above what is usually necessary to obtain clinical benefits was suggested in NR. Conclusions: The SVM model built emphasizes a possible link between vagus nerve recruitment characteristics and treatment effectiveness. Most of the clinically responding patients receive VNS at a stimulation intensity 1-fold and 2-fold the intensity inducing LMEP saturation. Significance: LMEP saturation could be a practical help in guiding the titration of the stimulation parameters using a physiological indicator of fiber engagement.

The finding of white matter damage on brain magnetic resonance imaging may correspond to a wide variety of etiologies. The differential diagnosis may be particularly difficultin immunocompromised patients with a specific autoimmune disease or who are receiving medications after a solid-organ transplant. Herein, we describe the case of a 22-year-old woman who developed serious neurological complications after an acute rejection of a kidney graft that she had received a few months previous to treat a systemic lupus erythematosus-related nephritis.We discuss the possible hypotheses underlying the development of acute leukoencephalopathy in this setting.

Background. The optimal duration of antithrombotic therapy (ATT) after patent foramen ovale (PFO) closure remains under debate. This study sought to compare the clinical outcome of patients receiving antithrombotic agents for a short (6 months) versus extended (>6 months) period after the procedure. Methods. This was a retrospective cohort study using a propensity score matching analysis on 259 consecutive patients (131 males, 43 ± 10 years) undergoing PFO closure due to cryptogenic stroke, with complete follow-up (median duration of 10 [4–13] years). The outcome was compared between patients receiving short-term (Group short, N = 88) versus extended ATT (Group long, N = 171). Results. The PFO closure device was successfully implanted in all cases, with 3% of minor complications. After propensity score matching, there were no differences between Groups short and long in the rate of stroke (0.3 vs. 0.4% patient-year, p = 1.00 ), bleeding (2 vs. 2% patient-year, p = 0.17 ), and device thrombosis (0.3 vs. 0.1% patient-year; p = 0.60 ). Univariate analysis showed that short-term ATT was not associated with an increased risk of recurrent stroke (HR: 1.271 [95% CI: 0.247–6.551], p = 0.775 ) or prosthesis thrombus (HR: 0.50 [95% CI: 0.070–3.548], p = 0.72 ). Kaplan–Meier analysis revealed similar overall survival in Group short and long (100 vs. 99 ± 1%, respectively; p = 0.25 ). Conclusions. Short-term (6 months) ATT after PFO closure did not impair the clinical outcome, with a preserved low rate of recurrent stroke (0.3% patient-year) and device thrombosis (0.2% patient-year) at 10-year follow-up.

Background: Anxiety and depression are psychopathological states frequently co-occurring with severe alcohol use disorder (SAUD). These symptoms generally disappear with abstinence but may persist in some patients, increasing the relapse risk. Methods: The cerebral cortex thickness of 94 male patients with SAUD was correlated with symptoms of depression and anxiety, both measured at the end (2–3 weeks)of the detoxification treatment. Cortical measures were obtained using surface-based morphometry implemented with Freesurfer. Results: Depressive symptoms were associated with reduced cortical thickness in the superior temporal gyrus of the right hemisphere. Anxiety level was correlated with lower cortical thickness in the rostral middle frontal region, inferior temporal region, and supramarginal, postcentral, superior temporal, and transverse temporal regions of the left hemisphere, as well as with a large cluster in the middle temporal region of the right hemisphere. Conclusions: At the end of the detoxification stage, the intensity of depressive and anxiety symptoms is inversely associated with the cortical thickness of regions involved in emotions-related processes, and the persistence of the symptoms could be explained by these brain deficits.

This scientific commentary refers to ‘Medial temporal tau predicts memory decline in cognitively unimpaired elderly’, by Kwan et al. (https://doi.org/10.1093/braincomms/fcac325).

Visuospatial impairments have long been reported in Severe Alcohol Use Disorder but remain poorly understood, notably regarding the involvement of magnocellular (MC) and parvocellular (PC) pathways. This empirical gap hampers the understanding of the implications of these visual changes, especially since the MC and PC pathways are thought to sustain central bottom-up and top-down processes during cognitive processing. They thus influence our ability to efficiently monitor our environment and make the most effective decisions. To overcome this limitation, we measured PC-inferred spatial and MC-inferred temporal resolution in 35 individuals with SAUD and 30 healthy controls. We used Landolt circles displaying small apertures outside the sensitivity range of MC cells or flickering at a temporal frequency exceeding PC sensitivity. We found evidence of preserved PC spatial resolution combined with impaired MC temporal resolution in SAUD. We also measured how spatial and temporal sensitivity is influenced by the prior presentation of fearful faces – as emotional content could favor MC processing over PC one – but found no evidence of emotional modulation in either group. This spatio-temporal dissociation implies that individuals with SAUD may process visual details efficiently but perceive rapidly updating visual information at a slower pace. This deficit has implications for the tracking of rapidly changing stimuli in experimental tasks, but also for the decoding of crucial everyday visual incentives such as faces, whose micro-expressions vary continuously. Future studies should further specify the visual profile of individuals with SAUD to incorporate disparate findings within a theoretically grounded model of vision.

Network analyses have become increasingly common within the field of psychology, and temporal network analyses in particular are quickly gaining traction, with many of the initial articles earning substantial interest. However, substantial heterogeneity exists within the study designs and methodology, rendering it difficult to form a comprehensive view of its application in psychology research. Since the field is quickly growing and since there have been many study-to-study variations in terms of choices made by researchers when collecting, processing, and analyzing data, we saw the need to audit this field and formulate a comprehensive view of current temporal network analyses. To systematically chart researchers' practices when conducting temporal network analyses, we reviewed articles conducting temporal network analyses on psychological variables (published until March 2021) in the framework of a scoping review. We identified 43 articles and present the detailed results of how researchers are currently conducting temporal network analyses. A commonality across results concerns the wide variety of data collection and analytical practices, along with a lack of consistency between articles about what is reported. We use these results, along with relevant literature from the fields of ecological momentary assessment and network analysis, to formulate recommendations on what type of data is suited for temporal network analyses as well as optimal methods to preprocess and analyze data. As the field is new, we also discuss key future steps to help usher the field's progress forward and offer a reporting checklist to help researchers navigate conducting and reporting temporal network analyses.

Background and ObjectivesAlzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find the right test to optimize cognitive outcome measures for clinical trials. We sought to identify cognitive measures associated with the earliest detectable signs of emerging Aβ and tau pathology.MethodsOne hundred twelve clinically normal adults with longitudinal Pittsburgh compound B (PiB)-PET, 18F-flortaucipir (FTP)-PET, and cognitive data for ≥7 years were included from the Harvard Aging Brain Study (HABS). Analyses assessed those initially classified as PiB− (less than Centiloid [CL] 20) and then expanded to include PiB+ individuals up to CL40, the approximate threshold beyond which neocortical tau proliferation begins. Separate linear mixed-effects models assessed the effects of emerging global Aβ (PiB slope) and tau (baseline FTP level and FTP slope) in the entorhinal and inferior temporal (IT) cortices on multiple cognitive tasks and the Preclinical Alzheimer's Cognitive Composite (PACC) over time.ResultsSteeper PiB slopes were associated with declining processing speed (Digit Symbol Substitution Test [DSST], Trail Making Test Part A) in those CL40).DiscussionEarly, Aβ-mediated cognitive slowing was detected for processing speed measures, while early memory retrieval declines were associated with emerging Aβ and tau pathology. Composites of these measures may help determine whether anti-Aβ or anti-tau therapies administered at the first signs of pathology might preserve cognitive function.Classification of EvidenceThis study provides Class I evidence that in clinically normal older adults, emerging PET-detected AD pathology is associated with declining processing speeds and memory retrieval.

Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

Vagus nerve stimulation (VNS) is an adjunctive therapy for drug-resistant epilepsy. Noninvasive evoked potential recordings in laryngeal muscles (LMEPs) innervated by vagal branches may provide a marker to assess effective vagal nerve fiber activation. We investigated VNS-induced LMEPs in patients with epilepsy in acute and chronic settings.A total of 17 of 25 patients underwent LMEP recordings at initiation of therapy (acute group); 15 of 25 patients after one year of VNS (chronic group); and 7 of 25 patients were tested at both time points (acute + chronic group). VNS-induced LMEPs were recorded following different pulse widths and output currents using six surface laryngeal EMG electrodes to calculate input/output curves and estimate LMEP latency, threshold current for minimal (IVNS-induced LMEPs were present in all patients. INoninvasive VNS-induced LMEP recording is feasible both at initiation of VNS therapy and after one year. Low output currents (0.25-1.00 mA) may be sufficient to activate vagal Aα-motor fibers. Maximal LMEP amplitudes seemed to decrease after chronic VNS therapy in patients.

Posterior staphyloma, typically found in highly myopic eyes, may rarely be present in the absence of high myopia, in the context of various inherited degenerative diseases such as rod-cone dystrophy, Leber’s congenital amaurosis or retinitis pigmentosa. However, to our knowledge, the association between posterior staphyloma without high myopia and congenital stationary night blindness (CSNB) has never been described in the literature. CSNB is a genetically and clinically heterogenous retinal disorder, and it can be inherited in an autosomal dominant (AD), recessive (AR) or X-linked (XL) mode. Over 360 variants involving 17 genes, which affects signal processing within photoreceptors, retinoid recycling in the retinal pigment epithelium (RPE) and signal transmission via retinal bipolar cells have been associated with CSNB. CSNB is characterized by a nonprogressive nyctalopia, not always described (notably in children), a variable decrease in visual acuity (especially in the autosomal recessive and X-linked modes), and myopia. In addition, in autosomal recessive and X-linked forms, CSNB is also often associated with strabismus and nystagmus. Furthermore, CSNB is classified as being complete or incomplete, depending on the extent to which an electronegative electroretinogram is observed. This electro-physiologic presentation, as well as the mode of inheritance, are associated with specific mutated genes. For instance, the TRPM1 gene, which is mutated in this case, is affected in the autosomal recessive complete CSNB. This case aims at describing the clinical presentation of the homozygous variant c.1730A > T in the TRPM1 gene. To the best of our knowledge, this is the first description in the literature of this variant.

There are no specific guidelines regarding best treatment for focal, distant metastasis in ependymoma in the context of a well-controlled primary site. A combination using maximal safe resection and adjuvant radiotherapy is usually advised. As wound healing might be hindered by repeated radiotherapy, and delay future radiation treatment if needed, there is a growing interest in less invasive surgeries to reduce post-operative pain and wound healing complications. Those approaches have been extensively used and studied in adult but never in the pediatric population. Here, we present a pediatric case of a 12-year-old boy known for a posterior fossa ependymoma completely resected 18 months earlier who presented with a dual lumbosacral intradural ependymoma metastasis. A single-stage complete resection was achieved using a fixed tubular retractor with no complication. Post-operative course was favorable with rapid healing and discharge, minimal post-operative pain, and a rapid return to normal activities. Re-irradiation could be performed 2 weeks later without any problem. To our knowledge, this is the first report of the use of minimally invasive techniques to achieve complete resection of dual intradural metastasis of an ependymoma in the pediatric population. We demonstrate its feasibility and safety as well as its advantages. Keywords Ependymoma · Minimally invasive · Complete resection · Posterior · Single stage

The brainstem is among the first regions to accumulate Alzheimer’s disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainstem volumes and tau deposition. Our results support the hypothesis that lower brainstem volumes are associated with initial AD-related processes and may signal preclinical AD pathology.

BackgroundGraves’ orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves’ Orbitopathy (EUGOGO) tertiary referral centres and initial management over time.MethodsProspective observational multicentre study. All new referrals with diagnosis of GO within September–December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012.ResultsBesides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; pConclusionGO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

BACKGROUND: Ectopic ACTH pituitary adenomas (EAPA), located outside the sella turcica and deriving from cellular remnants of Rathke's pouch are a very rare cause of Cushing's syndrome (CS). The diagnosis is often difficult and delayed, even after comprehensive work-up. To our knowledge, we report for the first time an ectopic corticotroph tumor of the posterior wall of the sphenoid sinus, leading to false positive results of bilateral inferior petrosal sinus sampling (BIPPS) and which was finally localized by a co-registered11 C Methionine PET/MR imaging. CASE PRESENTATION: A 48-year-old woman was referred for a high clinical suspicion of ACTH-dependent CS. Biological testing comprising low dose dexamethasone suppression and CRH stimulation tests were indicative of pituitary Cushing's disease, but comprehensive pituitary MRI did not reveal any pituitary adenoma. BIPSS confirmed however a central origin of ACTH secretion (central-to-peripheral ACTH ratio > 100) and revealed a significant right-to-left gradient (6.2), leading to a first right-sided exploratory hypophysectomy, that did not cure the patient. BIPSS images were reviewed and revealed preferential drainage of the left pituitary to the right petrosal sinus, leading us to a left sided exploratory hypophysectomy, which was again unsuccessful. A11 C Methionine PET/MRI was performed and revealed a hypermetabolic lesion adjacent to the posterior wall of the sphenoidal sinus. After surgical resection, this polypoid mass was identified as an ectopic ATCH-secreting pituitary adenoma expressing ACTH and T-Pit and complete remission of hypercortisolism was observed. CONCLUSIONS: In conclusion, we report a case of ACTH-dependent Cushing's syndrome, caused by an ectopic corticotroph adenoma located in the sphenoidal sinus, which perfectly mimicked the biological features of a classical pituitary ACTH adenoma on a comprehensive hormonal evaluation including BIPPS, and the features of a benign naso-sinusal polyp at MRI. We report for the first time a key role of11 C Methionine PET co-registered to high resolution MRI for localizing ectopic adenomas, efficiently guiding surgical removal and leading to complete remission of hypercortisolism.

Paramagnetic Rim Lesions (PRL) in Multiple Sclerosis (MS) are associated with increased disability and axonal damage. In this work, we explored PRL's microstructure using Track Density Imaging (TDI) and four diffusion MRI (dMRI) models, including Microstructure Fingerprinting (MF). When compared to non-PRL, PRL showed larger size, higher T1-values, lower neurite density index and fibre volume fraction on dMRI (p < 0.001) and reduced track density on TDI (p < 0.0001), suggesting impaired axonal density/integrity in PRL. Results obtained with the novel MF model are in line with those obtained with other dMRI models, indicating its potential for studying MS lesion pathology.

Innovations dans la prise en charge de l’adénocarcinome pancréatique « limite résécable » ou « localement avancé », en 2022 : que retenir ? L’année 2022 a été riche en innovations dans la prise en charge de l’adénocarcinome du pancréas borderline ou localement avancé et offre de nouvelles opportunités de traitements multimodaux aux Cliniques universitaires Saint-Luc. Nous vous illustrons ici par deux histoires cliniques, l’importance de la prise en charge pluridisciplinaire pour ce type de patients. Nous vous détaillons ensuite, par spécialité, les innovations et spécificités propres à chacun, dont l’expertise est capitale au sein du groupe.

Objective For patients with drug-resistant epilepsy who are not candidates for epilepsy surgery, Vagus Nerve Stimulation (VNS) is the most widely available neuromodulation option and has been available in some countries for over 25 years. Given its broad availability and extended history on the market, many healthcare providers (HCPs) have developed individualized practice habits regarding the titration and dosing of VNS. This work describes the extent to which VNS management differs between providers and discusses how such idiosyncrasies may impact patient outcomes. Methods In this work, the evolution of practice habits regarding the titration and dosing of VNS was explored through a survey of HCPs as well as an examination of programming history data collected as part of routine product surveillance by the manufacturer. Results Programming history data revealed a decades long trend toward lower VNS doses from the late 1990s until the late 2010s that recently started to reverse (since 2017). Examination of programming history data from the past 5 years suggests that this increase in VNS dose post 2017 may be associated with the use of the automated titration using “Scheduled Programming” available on the newest VNS models. The global survey revealed significant idiosyncrasy in dosing and titration habits. Providers reported a wide range of initial/maximum target doses and time-to-dose, even if the population averages approximated guidance from professional societies and the manufacturer’s labeling. Idiosyncratic dosing and titration was reflected in varied perception of how long it takes to realize the clinical benefits of VNS. Conclusions Our results suggest VNS providers would benefit from continued training on the use of VNS and the use of the scheduled programming feature in order to enhance consistency of VNS management between providers.

Objective For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. Methods The EUSCREEN Questionnaire, conducted in 2017–2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow-up, were reappraised with an additional questionnaire. Results The practice of data collection in vision screening was reported in 36% (N = 42) of countries and in hearing screening in 81% (N = 43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. Conclusions Data collection is insufficient in hearing screening and even more so in vision screening: data essential for cost-effectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency.

Purpose: Visual function is typically evaluated in clinical settings with visual acuity (VA), a test requiring to behaviorally match or name optotypes such as tumbling E or Snellen letters. The ability to recognize these symbols has little in common with the automatic and rapid visual recognition of socially important stimuli in real life. Here we use sweep visual evoked potentials to assess spatial resolution objectively based on the recognition of human faces and written words. Methods: To this end, we tested unfamiliar face individuation1 and visual word recognition2 in 15 normally sighted adult volunteers with a 68-electrode electroencephalogram system. Results: Unlike previous measures of low-level visual function including VA, the most sensitive electrode was found at an electrode different from Oz in a majority of participants. Thresholds until which faces and words could be recognized were evaluated at the most sensitive electrode defined individually for each participant. Word recognition thresholds corresponded with the VA level expected from normally sighted participants, and even a VA significantly higher than expected from normally sighted individuals for a few participants. Conclusions: Spatial resolution can be evaluated based on high-level stimuli encountered in day-to-day life, such as faces or written words with sweep visual evoked potentials.

Objective The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pituitary adenoma within Endo-ERN. Design and Methods Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by reference centers on their current surgical practice. Results A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6-represented countries published 48 articles. Remission rates were 50% (95% CI: 42–59) for patients with acromegaly, 68% (95% CI: 60–75) for Cushing’s disease, and 53% (95% CI: 39–66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37–61%) of patients and visual improvement in 78% (95% CI: 68–87). Mortality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11–23), transient diabetes insipidus in 12% (95% CI: 6–21), permanent diabetes insipidus in 4% (95% CI: 3–6), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5–14), severe epistaxis in 2% (95% CI: 0–4), and cerebrospinal fluid leak in 4% (95% CI: 2–6). Thirty-five (81%) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. Conclusion The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the heterogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries.

Pour l'année 2022, le service d'Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale s'est concentré sur le bien-être de nos patients dans toutes les disciplines de notre spécialité. Tout d'abord, nous avons eu le plaisir d'obtenir le remboursement des produits biologiques tant attendus pour le traitement des patients atteints d’une rhinosinusite chronique avec des polypes nasaux. Ces nouvelles thérapies sont capables d'aider un nombre substantiel de patients dont la maladie ne peut être contrôlée par les traitements médicaux et chirurgicaux habituels. Ensuite, nous avons pu analyser une série de plus de 250 patients qui ont été opérés d'une parotidectomie avec un neuromonitoring peropératoire. Nous avons constaté que la préservation de la fonction du nerf facial était significativement meilleure par rapport aux données précédemment rapportées sur les parotidectomies sans neuromonitoring. Enfin, dans le domaine de l'implantation cochléaire pour les patients atteints d’une déficience auditive sévère, nous préparons l'avenir. De nouvelles techniques ont été développées pour préserver l'audition résiduelle lors de l'introduction de l'implant dans la cochlée, comme la chirurgie robotique et l'électrocochléographie peropératoire. Ces techniques nous permettront d'augmenter les indications de l'implantation, ce qui conduira à un plus grand nombre de patients qui seront aidés par cette technologie qui change la vie.

Tau protein aggregates in several neurodegenerative disorders, referred to as tauopathies. The tau isoforms observed in post mortem human brain aggregates is used to classify tauopathies. However, distinguishing tauopathies ante mortem remains challenging, potentially due to differences between insoluble tau in aggregates and soluble tau in body fluids. Here, we demonstrated that tau isoforms differ between tauopathies in insoluble aggregates, but not in soluble brain extracts. We therefore characterized post-translational modifications of both the aggregated and the soluble tau protein obtained from post mortem human brain tissue of patients with Alzheimer's disease, cortico-basal degeneration, Pick's disease, and frontotemporal lobe degeneration. We found specific soluble signatures for each tauopathy and its specific aggregated tau isoforms: including ubiquitination on Lysine 369 for cortico-basal degeneration and acetylation on Lysine 311 for Pick's disease. These findings provide potential targets for future development of fluid-based biomarker assays able to distinguish tauopathies in vivo.

6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [18F]MK6240 can be used to provide a surrogate index of cerebral perfusion. Methods: Forty-nine subjects who were cognitively normal (CN), had mild cognitive impairment (MCI), or had Alzheimer's disease (AD) underwent paired dynamic [18F]MK6240 and [11C]Pittsburgh compound B (PiB) PET, as well as structural MRI to obtain anatomic information. Arterial blood samples were collected in a subset of 24 subjects for [18F]MK6240 scans to derive metabolite-corrected arterial input functions. Regional time-activity curves were extracted using atlases available in the Montreal Neurologic Institute template space and using FreeSurfer. The early phase of brain time-activity curves was analyzed using a 1-tissue-compartment model to obtain a robust estimate of the rate of transfer from plasma to brain tissue, K 1 (mL⋅cm-3⋅min-1), and the simplified reference tissue model 2 was investigated for noninvasive estimation of the relative delivery rate, R 1 (unitless). A head-to-head comparison with R 1 derived from [11C]PiB scans was performed. Grouped differences in R 1 were evaluated among CN, MCI, and AD subjects. Results: Regional K 1 values suggested a relatively high extraction fraction. R 1 estimated noninvasively from simplified reference tissue model 2 agreed well with R 1 calculated indirectly from the blood-based compartment modeling (r = 0.99; mean difference, 0.024 ± 0.027), suggesting that robust estimates were obtained. R 1 measurements obtained with [18F]MK6240 correlated strongly and overall agreed well with those obtained from [11C]PiB (r = 0.93; mean difference, -0.001 ± 0.068). Statistically significant differences were observed in regional R 1 measurements among CN, MCI, and AD subjects, notably in the temporal and parietal cortices. Conclusion: Our results provide evidence that the early phase of [18F]MK6240 images may be used to derive a useful index of cerebral perfusion. The early and late phases of a [18F]MK6240 dynamic acquisition may thus offer complementary information about the pathophysiologic mechanisms of the disease.

L’année 2022 nous aura vu acquérir un bras robotisé neuronavigué (Stealth Autoguide de Medtronic) pour l’implantation des électrodes d’EEG invasif. Tel qu’estimé, celui-ci nous a permis de largement améliorer la précision de nos implantations et d’amener une meilleure sécurité pour nos patients.

Contains fulltext : 288062.pdf (Publisher’s version ) (Closed access) There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

Recent advances in MRI technology have enabled richer multi-shell sequences to be implemented in diffusion MRI, allowing the investigation of both the microscopic and macroscopic organization of the brain white matter and its complex network of neural fibers. The emergence of advanced diffusion models has enabled a more detailed analysis of brain microstructure by estimating the signal received from a voxel as the combination of responses from multiple fiber populations. However, disentangling the individual microstructural properties of different macroscopic white matter tracts where those pathways intersect remains a challenge. Several approaches have been developed to assign microstructural properties to macroscopic streamlines, but often present shortcomings. ROI-based heuristics rely on averages that are not tract-specific. Global methods solve a computationally-intensive global optimization but prevent the use of microstructural properties not included in the model and often require restrictive hypotheses. Other methods use atlases that might not be adequate in population studies where the shape of white matter tracts varies significantly between patients. We introduce UNRAVEL, a framework combining the microscopic and macroscopic scales to unravel multi-fixel microstructure by utilizing tractography. The framework includes commonly-used heuristics as well as a new algorithm, estimating the microstructure of a specific white matter tract with angular weighting. Our framework grants considerable freedom as the inputs required, a set of streamlines defining a tract and a multi-fixel diffusion model estimated in each voxel, can be defined by the user. We validate our approach on synthetic data and in vivo data, including a repeated scan of a subject and a population study of children with dyslexia. In each case, we compare the estimation of microstructural properties obtained with angular weighting to other commonly-used approaches. Our framework provides estimations of the microstructure at the streamline level, volumetric maps for visualization and mean microstructural values for the whole tract. The angular weighting algorithm shows increased accuracy, robustness to uncertainties in its inputs and maintains similar or better reproducibility compared to commonly-used analysis approaches. UNRAVEL will provide researchers with a flexible and open-source tool enabling them to study the microstructure of specific white matter pathways with their diffusion model of choice.

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF) as part of their participation in DIAN were included in this study. Linear mixed effects models were used to determine differences in clinical, cognitive, and biomarker measures between the NC, TM, and CY groups. While both the CY and TM groups were found to have similarly elevated Aβ compared to NC, TM carriers had greater cognitive impairment, smaller hippocampal volume, and elevated phosphorylated tau levels across the spectrum of pre-symptomatic and symptomatic phases of disease as compared to CY, using both cross-sectional and longitudinal data. As distinct portions of PSEN1 are differentially involved in APP processing by γ-secretase and the generation of toxic β-amyloid species, these results have important implications for understanding the pathobiology of ADAD and accounting for a substantial portion of the interindividual heterogeneity in ongoing ADAD clinical trials.

Short association fibers in the subcortical white matter, also known as U-fibers, represent the connections between neighboring gyri. Due to the geometry of the cortical folds and the sharp turns along the cortical surface, tractography of U-fibers remains a challenge since increasing the maximum angle between tractography steps also increases the occurence of false positive streamlines. We propose to replace the fixed maximum angle value in tractography algorithms by an angular map, allowing higher angles at the interface between grey and white matter. This enables a more accurate tracking of U-fibers, while keeping a low number of false positive streamlines.

IntroductionStroke causes multiple deficits including motor, sensitive and cognitive impairments, affecting also individual’s social participation and independence in activities of daily living (ADL) impacting their quality of life. It has been widely recommended to use goal-oriented interventions with a high amount of task-specific repetitions. These interventions are generally focused only on the upper or lower extremities separately, despite the impairments are observed at the whole-body level and ADL are both frequently bimanual and may require moving around. This highlights the need for interventions targeting both upper and lower extremities. This protocol presents the first adaptation of Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for adults with acquired hemiparesis.Methods and analysisThis randomised controlled trial will include 48 adults with chronic stroke, aged ≥40 years. This study will compare the effect of 50 hours of HABIT-ILE against usual motor activity and regular rehabilitation. HABIT-ILE will be provided in a 2-week, adult’s day-camp setting, promoting functional tasks and structured activities. These tasks will continuously progress by increasing their difficulty. Assessed at baseline, 3 weeks after and at 3 months, the primary outcome will be the adults-assisting-hand-assessment stroke; secondary outcomes include behavioural assessments for hand strength and dexterity, a motor learning robotic medical device for quality of bimanual motor control, walking endurance, questionnaires of ADL, stroke impact on participation and self-determined patient-relevant goals, besides neuroimaging measures.Ethics and disseminationThis study has full ethical approval from theComité d’éthique Hospitalo-Facultaire/Université catholique de Louvain, Brussels (reference number: 2013/01MAR/069) and the local medical Ethical Committee of the CHU UCL Namur-site Godinne. Recommendations of the ethical board and the Belgian law of 7 May 2004, concerning human experiments will be followed. Participants will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.Trial registration numberNCT04664673.

Liver disease, occurring during pediatric or adult age, is often of undetermined cause. Some cases are probably related to undiagnosed inherited metabolic disorders. Hepatic disorders associated with fructose-1,6-bisphosphatase deficiency, a gluconeogenesis defect, are not reported in the literature. These symptoms are mainly described during acute crises, and many reports do not mention them because hypoglycemia and hyperlactatemia are more frequently in the forefront. Herein, the liver manifestations of 18 patients affected with fructose-1,6-bisphosphatase deficiency are described and the corresponding literature is reviewed. Interestingly, all 18 patients had liver abnormalities either during follow-up (hepatomegaly [n = 8/18], elevation of transaminases [n = 6/15], bright liver [n = 7/11]) or during acute crises (hepatomegaly [n = 10/17], elevation of transaminases [n = 13/16], acute liver failure [n = 6/14], bright liver [n = 4/14]). Initial reports described cases of liver steatosis, when liver biopsy was necessary to confirm the diagnosis by an enzymatic study. There is no clear pathophysiological basis for this fatty liver disease but we postulate that endoplasmic reticulum stress and de novo lipogenesis activation could be key factors, as observed in FBP1 knockout mice. Liver steatosis may expose patients to severe long-term liver complications. As hypoglycemia becomes less frequent with age, most adult patients are no longer monitored by hepatologist. Signs of fructose-1,6-bisphosphatase deficiency may be subtle and can be missed in childhood. We suggest that fructose-1,6-bisphosphatase deficiency should be considered as an etiology of hepatic steatosis, and a liver monitoring protocol should be set up for these patients, during lifelong follow-up.

The COVID-19 pandemic has put healthcare workers under important psychological pressure. Concerns have been raised regarding the mental health and psychological status of healthcare workers and have underlined the need for institutions to develop long-term interventions to support their resilience. The current case study presents the way a large university hospital in Brussels, Belgium, has evolved to deal with this health crisis and support its workers. Initiatives were multiple and complementary, as it was decided to combine different forms of clinical interventions that were developed by psychologists, psychiatrists, and human resources, to an empirical approach including a large survey that permitted to reach a much larger audience (the results of the study have been published previously). We describe the initially proposed measures of psychological support, including the creation of a telephone hotline, the presence of psychologists among teams of dedicated COVID-19 units, discussion groups, and individualized follow-ups, and their consequences on healthcare workers. Second, we address how these initial measures of support were modified to tailor in the best way possible the needs of healthcare workers, using a research action project that used a survey to measure and address the psychological distress of healthcare workers. We explain how, through different objectives (screening of distress, adaptation of initial measures based on reported needs, active reinforcement of individual and collective resilience, reminder of availability of help, and normalization of distress), a research action project can be a form of support and is an effective way for an institution to show its pre-occupation for the mental health of its teams. The current case study highlights how an institution can provide support and the importance of the use of a combined strategy to limit the consequences of a major health crisis on the mental health of its healthcare workers. Improving the resilience of healthcare workers both in the short and long term is of the essence to maintain optimal care of patients.

BackgroundDuchenne muscular dystrophy (DMD) is the most common inherited human myopathy. Typically, the secondary process involving severe inflammation and necrosis exacerbate disease progression. Previously, we reported that the NLRP3 inflammasome complex plays a crucial role in this disorder. Moreover, pyroptosis, a form of programmed necrotic cell death, is triggered by NLRP3 via gasdermin D (GSDMD). So far, pyroptosis has never been described either in healthy muscle or in dystrophic muscle. The aim of this study was to unravel the role of NLRP3 inflammasome in DMD and explore a potentially promising treatment with MCC950 that selectively inhibits NLRP3.MethodsFour‐week‐old mdx mice (n=6 per group) were orally treated for 2 months with MCC950 (mdx‐T), a highly potent, specific, small-molecule inhibitor of NLRP3, and compared with untreated (mdx) and wild-type (WT) mice. In vivo functional tests were carried out to measure the global force and endurance of mice. Ex vivo biochemical and molecular analyses were performed to evaluate the pathophysiology of the skeletal muscle. Finally, in vitro tests were conducted on primary cultures of DMD human myotubes.ResultsAfter MCC950 treatment, mdx mice exhibited a significant reduction of inflammation, macrophage infiltration and oxidative stress (-20 to -65%, Pvs untreated mdx). Mdx‐T mice displayed considerably less myonecrosis (-54%, Pvs mdx) and fibrosis (-75%, Pvs mdx). Moreover, a more mature myofibre phenotype, characterized by larger-sized fibres and higher expression of mature myosin heavy chains 1 and 7 was observed. Mdx-T also exhibited enhanced force and resistance to fatigue (+20 to 60%, PP=0.075) and cleaved gasdermin D (N-GSDMD) (-42% in medium-sized-fibres, PConclusionSpecific inhibition of the NLRP3 inflammasome can significantly attenuate the dystrophic phenotype. A novel finding of this study is the overactivation of GSDMD, which is hampered by MCC950. This ultimately leads to less inflammation and pyroptosis and to a better muscle maturation and function. Targeting NLRP3 might lead to an effective therapeutic approach for a better management of DMD.

Margaretha B Breebaart,1,2 Lies Saerens,3 Jordi Branders,2 Sari Casaer,3 Luc Sermeus,4 Patrick Van Houwe3 1Department of Medicine and Healthcare Sciences, University of Antwerp, Wilrijk, Belgium; 2Department of Anesthesia, Antwerp University Hospital, Edegem, Belgium; 3Department of Anesthesia, GZA Hospitals, Wilrijk, Belgium; 4Department of Anesthesia, Université Catholique de Louvain, Brussel, BelgiumCorrespondence: Margaretha B Breebaart Email margaretha.breebaart@uza.bePurpose: Chloroprocaine provides spinal anesthesia for day-case surgery lasting up to 40 minutes. Intravenous and spinal dexmedetomidine can prolong spinal anesthesia, but no data are available for the combination with chloroprocaine. This double-blind randomized controlled trial compares chloroprocaine with spinal or intravenous dexmedetomidine regarding block characteristics, micturition, and discharge times.Patients and Methods: After ethical approval and informed consent, 135 patients scheduled for knee arthroscopy were randomized to receive either 40mg spinal chloroprocaine (Chloro-group), 40mg chloroprocaine with 5 mcg spinal dexmedetomidine (Spinal Dex-group) or 40mg chloroprocaine with 0.5 mcg/kg IV dexmedetomidine (IV DEXgroup). Block characteristics, hemodynamic variables and the use of analgesics were registered. Voiding and discharge times were noted. A scoring system was used for micturition problems and sedation. Transient neurological symptoms (TNS) and other late side effects were evaluated after one week.Results: Demographic data were similar between groups. Block onset times and intensity of motor block were comparable between groups. The time to L2 and Bromage 1 regression was prolonged in the SpinalDEx-group by approximately 30 minutes compared to the other groups (p < 0.01). First voiding as well as discharge from the hospital was prolonged in the Spinal Dex-group by approximately 40 minutes p < 0.01. There was no significant difference between groups regarding treatment of hypotension, sedation, micturition problems or the use of postoperative analgesics (P > 0.8). One patient experienced TNS.Conclusion: Intrathecal but not intravenous (0.5 mcg/kg) dexmedetomidine can prolong chloroprocaine (40mg) spinal anesthesia when surgery is expected to last over 40 minutes. Despite a similar incidence of adverse effects, this also led to a postponed hospital discharge time.Keywords: ambulatory surgery, bladder function, chloroprocaine, dexmedetomidine, knee arthroscopy, spinal anesthesia

Neural desynchronization was shown as a key mechanism of vagus nerve stimulation (VNS) action in epilepsy, and EEG synchronization measures are explored as possible response biomarkers. Since brain functional organization in sleep shows different synchrony and network properties compared to wakefulness, we aimed to explore the effects of acute VNS on EEG-derived measures in the two different states of vigilance. EEG epochs were retrospectively analyzed from twenty-four VNS-treated epileptic patients (11 responders, 13 non-responders) in calm wakefulness and stage N2 sleep. Weighted Phase Lag Index (wPLI) was computed as connectivity measure of synchronization, for VNS OFF and VNS ON conditions. Global efficiency (GE) was computed as a network measure of integration. Ratios OFF/ON were obtained as desynchronization/de-integration index. Values were compared between responders and non-responders, and between EEG states. ROC curve and area-under-the-curve (AUC) analysis was performed for response classification. In responders, stronger VNS-induced theta desynchronization (p < 0.05) and decreased GE (p < 0.05) were found in sleep, but not in wakefulness. Theta sleep wPLI Ratio OFF/ON yielded an AUC of 0.825, and 79% accuracy as a response biomarker if a cut-off value is set at 1.05. Considering all patients, the VNS-induced GE decrease was significantly more important in sleep compared to awake EEG state (p < 0.01). In conclusion, stronger sleep EEG desynchronization in theta band distinguishes responders to VNS therapy from non-responders. VNS-induced reduction of network integration occurs significantly more in sleep than in wakefulness., SCOPUS: ar.j, info:eu-repo/semantics/published

OBJECTIVES To compare the effects of Narrow band CE-Chirps (NB CE-Chirps) and tone bursts (TBs) at 500 Hz and 1000 Hz on the amplitudes and latencies in cervical vestibular evoked myogenic potentials (cVEMPs). DESIGN Thirty-one healthy adult volunteers of varying ages were tested by air conduction at 95 dB nHL. Recording conditions were randomized for each participant and each modality was tested twice. RESULTS NB CE-Chirps showed larger corrected amplitudes than TBs at 500 Hz (p < 0.001) which were themselves larger than NB CE-Chirps and TBs at 1000 Hz (p < 0.001). In older volunteers, NB CE-Chirps 500 and 1000 Hz had significantly higher response rates than TBs 500 Hz (p = 0.039). A negative correlation was observed between the corrected amplitudes and the age of the participants regardless of the stimulus and the frequency studied. The p13 and n23 latencies were not correlated with the age of the subjects. CONCLUSIONS NB CE-Chirps at 500 Hz improved the corrected amplitudes of waveforms in cVEMPs as a result of a better frequency specificity compared with TBs. In the elderly, eliciting cVEMPs at a frequency of 1000 Hz might not be necessary to improve response rates with NB CE-Chirps. Additional studies including a higher number of healthy participants and patients with vestibular disorders are required to confirm these observations.

BACKGROUND: Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts. OBJECTIVE: This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis. METHODS: The study population included HC (n = 90), subjective cognitive decline (SCD, n = 93), mild cognitive impairment (MCI, n = 357), and ADD (n = 280) patients. Through automated volumetric analyses of global, cortical, and subcortical brain structures on clinical brain MRI T1w (n = 820) images from a retrospective, multi-center study (REMEMBER), icobrain dm's (v.4.4.0) ability to differentiate disease stages via ROC analysis was compared to FreeSurfer (v.6.0). Stepwise backward regression models were constructed to investigate if combined brain volumes can differentiate between AD stages. RESULTS: icobrain dm outperformed FreeSurfer in processing time (15-30 min versus 9-32 h), robustness (0 versus 67 failures), and diagnostic performance for whole brain, hippocampal volumes, and lateral ventricles between HC and ADD patients. Stepwise backward regression showed improved diagnostic accuracy for pairwise group differentiations, with highest performance obtained for distinguishing HC from ADD (AUC = 0.914; Specificity 83.0%; Sensitivity 86.3%). CONCLUSION: Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that combined brain volumes improve diagnostic accuracy, using real-world imaging data from a clinical setting. ispartof: JOURNAL OF ALZHEIMERS DISEASE vol:83 issue:2 pages:623-639 ispartof: location:Netherlands status: published

Despite the widespread use of intraoperative electrocorticography (iECoG) during resective epilepsy surgery, there is conflicting data on its overall efficacy and inability to predict benefit per pathology. Given the heterogeneity of iECoG use in resective epilepsy surgery, it is important to assess the utility of interictal-based iECoG. This individual patient data (IPD) meta-analysis seeks to identify the benefit of iECoG during resective epilepsy surgery in achieving seizure freedom for various pathologies. Embase, Scopus and PubMed were searched from inception to January 31st, 2021 using the following topics: ‘ecog’, ‘electrocorticography’, ‘epilepsy’. Articles were included if they reported seizure freedom ≥ 12-month follow-up in cohorts with and without iECoG for epilepsy surgery. Non-English, non-comparative iECoG cohorts or less than 10% iECoG use were excluded. This meta-analysis followed the PRISMA 2020 guidelines. The primary outcome was seizure freedom at last follow-up and time to seizure recurrence, if applicable. Forest plots with random effects modeling assessed the relationship between iECoG use and seizure freedom. Cox regression of IPD was performed to identify predictors of longer duration of seizure freedom. Kaplan-Meier curves with log-rank test were created to visualize differences in time to seizure recurrence. Of 7,504 articles identified, 18 were included for study-level analysis. IECoG was not associated with higher seizure freedom at the study level (RR=1.09 95% CI: 0.96-1.23, p=0.19, I2=64%), but on IPD (n= 7 studies, 231 patients) iECoG use was independently associated with more favorable seizure outcomes (HR=0.47, 95% CI: 0.23-0.95, p=0.037). In Kaplan-Meier analysis of specific pathologies, iECoG use was significantly associated with longer seizure freedom only for FCD (p

Summary A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia. Conventional imaging was unremarkable. Selective pancreatic arterial calcium stimulation and hepatic venous sampling showed a maximum calcium-stimulated insulin concentration from several pancreatic areas, mainly the proximal splenic artery and the proximal gastroduodenal artery, suggesting the presence of one or more occult insulinoma(s) in the region of the pancreatic body. 68Ga-DOTA-exendin-4 PET/CT showed however generalized increased uptake in the pancreas and a diagnosis of nesidioblastosis was therefore suspected. The patient has been since successfully treated with dietetic measures and diazoxide. Treatment efficacy was confirmed by a flash glucose monitoring system with a follow-up of 7 months. Learning points Adult nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia. The distinction between insulinoma and nesidioblastosis is essential since the therapeutic strategies are different. 68Ga-DOTA-exendin-4 PET/CT emerges as a new noninvasive diagnostic tool for the localization of an endogenous source of hyperinsulinemic hypoglycemia. Medical management with dietetic measures and diazoxide need to be considered as a valuable option to treat patients with adult nesidioblastosis. Flash glucose monitoring system is helpful for the evaluation of treatment efficacy.

Patients with disorders of consciousness (DoC) are a challenging population prone to misdiagnosis with limited effective treatment options. Among neuromodulation techniques, transcutaneous auricular vagal nerve stimulation (taVNS) may act through a bottom-up manner to modulate thalamo-cortical connectivity and promote patients' recovery. In this clinical trial, we aim to (1) assess the therapeutic clinical effects of taVNS in patients with DoC; (2) investigate the neural mechanisms underlying the effects of its action; (3) assess the feasibility and safety of the procedure in this challenging population; (4) define the phenotype of clinical responders; and (5) assess the long-term efficacy of taVNS in terms of functional outcomes.We will conduct a prospective parallel randomized controlled double-blind clinical trial investigating the effects of taVNS as a treatment in DoC patients. Forty-four patients in the early period post-injury (7 to 90 days following the injury) will randomly receive 5 days of either active bilateral vagal stimulation (45 min duration with 30s alternative episodes of active/rest periods; 3mA; 200-300μs current width, 25Hz.) or sham stimulation. Behavioural (i.e., Coma Recovery Scale-Revised, CRS-R) and neurophysiological (i.e., high-density electroencephalography, hd-EEG) measures will be collected at baseline and at the end of the 5-day treatment. Analyses will seek for changes in the CRS-R and the EEG metrics (e.g., alpha band power spectrum, functional connectivity) at the group and individual (i.e., responders) levels.These results will allow us to investigate the vagal afferent network and will contribute towards a definition of the role of taVNS for the treatment of patients with DoC. We aim to identify the neural correlates of its action and pave the way to novel targeted therapeutic strategies.Clinicaltrials.gov n° NCT04065386.

This work describes the fabrication of a lab-made cuff electrode intended for rat vagus nerve electroneurography. The cuff electrode is built around 50 µm platinum wires contacts in tripolar configuration, 4mm contact spacing. The body is made of silicone rubber and four surgical threads. In vivo validation allowed to record respiration and cardiac related activity from the vagus nerve. The results show that our electrodes are a suitable low-cost alternative for our preclinical studies.

Background/Purpose: Brain function changes with Alzheimer’s disease (AD) progression. Evaluating those changes longitudinally is important to understand the complex relationships between brain pathologies and cognition. We aimed (1) to identify longitudinal changes in functional connectivity in patients with mild cognitive impairment (MCI) characterized for amyloid-b (Ab) status and (2) to relate these functional changes to clinical progression. Methods: Forty-four patients with MCI were followed using serial functional magnetic resonance imaging (fMRI) over 1.2 years (three sessions) and cognitive testing over 3.1 years (five sessions). Intra and inter-network connectivities were computed to assess changes in brain connectivity using a network atlas adapted for late adulthood. Sixteen low-Ab clinically normal older adults underwent a single fMRI session for group comparisons at baseline. Linear mixed-effects models with random intercept and slope were used to predict changes in connectivity based on Ab status and progression to dementia. Results: At baseline, intra and inter-network resting-state fMRI connectivities did not differ by baseline clinical diagnosis, Ab status, or clinical progression to dementia. At the final imaging session, progressive MCI had significantly higher connectivity compared with stable MCI, specifically within the default-mode network (DMN). Longitudinally, progressive MCI had increasing intra-DMN connectivity over time compared with stable MCI, and the rate of changes in connectivity was significantly associated with the rate of cognitive decline. Conclusions: Intra-DMN connectivity increases in MCI patients progressing toward dementia, suggesting aberrant synchronization in the symptomatic stages of AD.

Depression is associated with reduced executive functioning. Still, we lack a more detailed understanding of the factors explaining this association. Addressing several limitations in the previous literature, we examine whether poor executive functioning is associated with specific depression symptoms using a network approach. The sample consisted of currently depressed, previously depressed, and never-depressed individuals (n ​= ​289; 67% female; M age ​= ​37.4 years). Associations between poor executive functioning and nine depression symptoms were estimated using regularized Gaussian graphical modelling. Results showed associations between poor executive functioning and fatigue/energy loss, interest/pleasure loss, appetite changes, sleep problems, and concentration difficulties. Fatigue/energy loss was the most important symptom bridging depression with poor executive functioning. There were no direct associations between executive functions and core negative affect symptoms. Findings are discussed in the context of motivational impairments, and potential mechanisms such as immunological- and stress-related processes are considered.

Objective: During the presurgical evaluation, manual electrical source imaging (ESI) provides clinically useful information in one-third of the patients but it is time-consuming and requires specific expertise. This prospective study aims to assess the clinical added value of a fully automated ESI analysis in a cohort of patients with MRI-negative epilepsy and describe its diagnostic performance, by evaluating sublobar concordance with stereo-electroencephalography (SEEG) results and surgical resection and outcome. Methods: All consecutive patients referred to the Center for Refractory Epilepsy (CRE) of St-Luc University Hospital (Brussels, Belgium) for presurgical evaluation between 15/01/2019 and 31/12/2020 meeting the inclusion criteria, were recruited to the study. Interictal ESI was realized on low-density long-term EEG monitoring (LD-ESI) and, whenever available, high-density EEG (HD-ESI), using a fully automated analysis (Epilog PreOp, Epilog NV, Ghent, Belgium). The multidisciplinary team (MDT) was asked to formulate hypotheses about the epileptogenic zone (EZ) location at sublobar level and make a decision on further management for each patient at two distinct moments: i) blinded to ESI and ii) after the presentation and clinical interpretation of ESI. Results leading to a change in clinical management were considered contributive. Patients were followed up to assess whether these changes lead to concordant results on stereo-EEG (SEEG) or successful epilepsy surgery. Results: Data from all included 29 patients were analyzed. ESI led to a change in the management plan in 12/29 patients (41%). In 9/12 (75%), modifications were related to a change in the plan of the invasive recording. In 8/9 patients, invasive recording was performed. In 6/8 (75%), the intracranial EEG recording confirmed the localization of the ESI at a sublobar level. So far, 5/12 patients, for whom the management plan was changed after ESI, were operated on and have at least one-year postoperative follow-up. In all cases, the EZ identified by ESI was included in the resection zone. Among these patients, 4/5 (80%) are seizure-free (ILAE 1) and one patient experienced a seizure reduction of more than 50% (ILAE 4). Conclusions: In this single-center prospective study, we demonstrated the added value of automated ESI in the presurgical evaluation of MRI-negative cases, especially in helping to plan the implantation of depth electrodes for SEEG, provided that ESI results are integrated into the whole multimodal evaluation and clinically interpreted.

Introduction Impaired self-awareness of memory function, a.k.a. anosognosia, is a common symptom in Alzheimer’s disease (AD); however, its pathological correlates remain unclear. Here, we investigated the impact of amyloid and tau on memory self-awareness. Methods Two hundred thirty-six clinically normal (N) and 102 impaired (I) participants from the ADNI cohort were included. Amyloid (global) and tau burden (in entorhinal and inferior temporal cortices) were assessed using positron emission tomography (PET). Self-awareness of memory was assessed using discrepancy indexes of subjective participant-informant ratings, as well as participant-objective scores of memory performance. Subjective and objective values were derived from the Everyday Cognition memory questionnaire and Logical Memory (delayed recall). Results Lower awareness (both methods) of memory function was associated with higher levels of pathology in the I group as compared to N. There was a significant effect of tauopathy, but not amyloidosis, on individual complaint, such that higher levels of tau associated with lower awareness. Discussion Impaired self-awareness appears progressively in the evolution of the disease related to AD biomarkers. Discordant subjective and objective measures may be important for clinical consideration.

Resume Dans cet article, les auteurs detaillent, au vu des donnees de la litterature medicale scientifique, les points techniques clefs, les erreurs a eviter, ainsi que les principaux resultats et limitations de la thyroplastie de type I avec implant de Montgomery® dans les immobilites laryngees unilaterales.

Paranoid beliefs have been conceptualized as a central psychological process linked to schizophrenia and many mental disorders. Research on paranoia has indicated that it is pivotal to consider not only levels but also dynamics aspects of incriminated related-mechanisms over time. In the present study, we conceptualized paranoia as a system of interacting elements. To do so, we used temporal network analysis to unfold the temporal dynamics between core psychological paranoia-related mechanisms, such as self-esteem, sadness, feeling close to others, and experiential avoidance. Time-series data of 23 participants with high scores in paranoia and/or interpersonal sensitivity were collected via experience sampling methodology (ESM). We applied a multilevel vector autoregressive (mlVAR) model approach and computed three distinct and complementary network models (i.e., contemporaneous, temporal, and between-subject) to disentangle associations between paranoia-related mechanisms in three different time frames. The contemporaneous model indicated that paranoia and sadness co-occurred within the same time frame, while sadness was associated with both low self-esteem and lack of closeness to others. The temporal model highlighted the importance of feeling close to others in predicting low paranoia levels in the next time frame. Finally, the between-subject model largely replicated association found in both contemporaneous and temporal models. The current study reveals that the network approach offers a viable data-driven methodology for elucidating how paranoia-related mechanisms fluctuate over time and may determine its severity. Moreover, this novel perspective may open up new directions towards identifying potential targets for prevention and treatment of paranoia-related problems.

While the impact of the gut microbiota on brain and behavior is increasingly recognized, human studies examining this question are still scarce. The primary objective of the current study was to explore the potential relationships between the gut microbiota composition, motor cortical excitability at rest and during inhibitory control, as well as behavioral inhibition, in healthy volunteers and in patients suffering from alcohol use disorder. Motor cortical excitability was examined using a range of transcranial magnetic stimulation (TMS) measures probed at rest, including the recruitment curve, short and long intracortical inhibition, and intracortical facilitation within the primary motor cortex. Moreover, TMS was applied during a choice reaction time task to assess changes in motor excitability associated with inhibitory control. Finally, behavioral inhibition was investigated using a neuropsychological task (anti-saccade). Overall, our results highlight several interesting correlations between microbial composition and brain measures. Hence, higher bacterial diversity, as well as higher relative abundances of UGC-002 and Christensenellaceae R-7 group were correlated with stronger changes in motor excitability associated with inhibitory control. Also, higher abundance of Anaerostipes was associated with higher level of corticospinal excitability. Finally, relative abundances of Bifidobacterium and Faecalibacterium were positively related to performance in the neuropsychological task, suggesting that they might have a positive impact on behavioral inhibition. Although correlation is not causation, the present study suggests that excitatory and inhibitory brain processes might be related to gut microbiota composition.

This review covers the broad topic of brain surgery in the treatment of pediatric intractable epilepsy. The authors review the latest advancements in the presurgical workup as well as the mandatory tests needed to explore the epilepsy workup in these children. They describe the different types of epilepsy from a surgical standpoint (temporal, extratemporal, multifocal, and hemispheric epilepsies) and various surgical procedures that can be proposed depending on the clinical scenario: lesionectomies, lobectomies, hemispherectomies, neuromodulation, and palliative surgeries. They also describe the key differences of the pediatric patient as compared with the adult patient in such pathologic conditions. Keywords: Epilepsy surgery; Medically intractable epilepsy; Outcomes; Resection; Surgical selection.