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Background: While patient care often involves interprofessional collaboration, interprofessional teaching formats with participants from medical and physiotherapy fields are still rare. Furthermore, interprofessional education often takes place as separate courses and is not integrated into the clinical curriculum. Therefore, the goal of this project was to develop and implement interprofessional content into bedside teaching. Course development: The clinical subject of the course was "Parkinson's disease", as this condition allowed for the exemplary demonstration of interprofessional teamwork and different competencies. Through interprofessional bedside teaching and a specific clinical context, interprofessionalism was intended to be integrated and experienced as natural part of clinical practice. The bedside teaching was complemented with work in break-out groups and a lecture. Evaluation: The course was first conducted in the winter semester 2021/22. Participants were medical and physiotherapy students. Teaching teams were also interprofessional. A concurrent evaluation was carried out using the University of the West of England Interprofessional Questionnaire (UWE-IP) before and after course participation. UWE-IP scores in all sub-scales indicated a positive attitude, except for the "Interprofessional Learning" scale among physiotherapy students, which reflected a neutral attitude. Significant group differences were observed in the same scale at the pre-course time point between medical and physiotherapy students (p<0.01) and among medical students before and after course participation (p=0.02).Conclusion: The course proved to be well-suited for integrating interprofessional content into clinical education and can serve as a model for future teaching units. The evaluation reflected a positive attitude toward interprofessional learning., Hintergrund: Während Patientenversorgung häufig interprofessionell erfolgt, sind interprofessionelle Lehreinheiten mit teilnehmenden Personen aus Humanmedizin und Physiotherapie noch eine Seltenheit. Zudem findet interprofessionelle Lehre häufig immer noch in Form von gesonderten Veranstaltungen mit interprofessionellen Inhalten statt und sind nicht in das klinische Curriculum integriert. Ziel dieses Projekts war daher die Entwicklung und Implementierung eines interprofessionellen Unterrichts an Patient*innen (UaP).Kursentwicklung: Klinisches Thema des Kurses war "Morbus Parkinson", da sich anhand dieser Erkrankung interprofessionelle Teamarbeit und unterschiedliche Kompetenzen exemplarisch darstellen ließen. Anhand eines interprofessionellen UaP und konkretem klinischen Kontext sollte Interprofessionalität als selbstverständlicher Teil des klinischen Handelns integriert und erlebbar gemacht werden. Eine Ummantelung des UaP erfolgte mit einer Vorlesung und eigenverantwortlicher Kleingruppenarbeit. Evaluation: Der Kurs wurde erstmals im Wintersemester 2021/22 durchgeführt. Teilnehmende Personen waren Medizinstudierende und Physiotherapieschüler*innen, die Dozierendenteams waren ebenfalls interprofessionell. Eine begleitende Evaluation erfolgte mit Hilfe des University of the West of England Interprofessional Questionnaire (UWE-IP) vor und nach Kursteilnahme. Im UWE-IP ergaben sich in allen Subskalen Summenscores, die einer positiven Einstellung entsprachen. Einzige Ausnahme war die Skala "Interprofessionelles Lernen" bei Physiotherapieschüler*innen, die einer neutralen Einstellung entsprachen. Signifikante Gruppenunterschiede ergaben sich in derselben Skala zum Zeitpunkt vor Kursteilnahme zwischen Medizinstudierenden und Physiotherapieschüler*innen (p<0,01) sowie bei Medizinstudierenden vor und nach Kursteilnahme (p=0,02).Schlussfolgerung: Der Kurs erwies sich als gut geeignet, um interprofessionelle Lehrinhalte in die klinische Lehre zu integrieren und kann als Mode

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives: This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods: The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject. Results: MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p <.001) and BPAD (r = -0.26,p <.001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p =.014) and moderate (p =.040) drinkers. Conclusions: Brain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g. brain oximetry) and noninvasive monitoring (NIM) methods (e.g. transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. Methods: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. Results: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18–22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. Conclusions: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering, SCOPUS: ar.j, info:eu-repo/semantics/published

Conventional magnetoencephalography (MEG) requires cryogenic cooling of magnetic field sensors, which are positioned in a one-size-fits-all rigid helmet to maintain a thermal insulation space with the scalp. Optically pumped magnetometers (OPMs) are new sensors that do not require cryogenic cooling. Their placement directly on the scalp allows to perform on-scalp MEG recordings which benefit from a higher signal-to-noise ratio thanks to the reduced brain-tosensor distance. The advantages of on-scalp MEG based on OPMs make it a future promising diagnostic tool for the investigation of numerous neurological pathologies, such as epilepsy or Alzheimer's disease. On-scalp MEG also opens the way to a better understanding of the pathophysiological processes underlying these neurological diseases. This review reports the current knowledge acquired thanks to both cryogenic and on-scalp MEG in these two neurological pathologies and the perspectives raised by the advent of on-scalp MEG., SCOPUS: ar.j, info:eu-repo/semantics/published

The lumbosacral radicular syndrome or sciatica is a common neurological problem characterized by pain radiating into the leg, following one of the lumbosacral nerve roots. There are several treatment options including medication, physiotherapy, transforaminal epidural steroid injections (TESIs) and disc surgery. This thesis, that was aimed to contribute to best clinical practice during the acute stage of the lumbosacral radicular syndrome and was subdivided into three themes. Theme 1: Diagnosis and treatment of acute lumbosacral radicular syndrome This theme contains an historical overview and a survey among 124 physicians. The results of this survey showed that 40-60% of neurologists think that TESIs are effective in 40% of injected patients and that 23/44(52%) of anesthesiologists think that TESIs are effective in 60-80% of the injected patients. We also found that neurologists treat patients with lumbosacral radicular syndrome initially with pain medication and physiotherapy, followed by epidural steroid injections and referral for surgery Anesthesiologists treat patients with lumbosacral radicular syndrome with one or more steroid injections or may perform a selective nerve root block. Theme 2: Inflammation This theme contained a systematic review that answers the following two questions: What inflammatory biomarkers have been identified in patients with sciatica in the literature so far, and is there an association between the level of inflammatory activity and clinical symptoms? Based on the results of the systematic review, we concluded that there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies and that, taking into account the overall risk of bias, there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica. Theme 3 (Cost-)effectiveness of transforaminal epidural steroid injections in patients with acut

International guidelines on the treatment of myasthenia gravis (MG) have been published but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian MG experts for the practical management of MG in Belgium. It includes recommendations for treatment of adult patients with generalized myasthenia gravis (gMG) or ocular myasthenia gravis (oMG). Depending on the MG-related antibody a treatment sequence is suggested with therapies that can be added on if the treatment goal is not achieved. Selection of treatments was based on the level of evidence of efficacy, registration and reimbursement status in Belgium, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in February 2024. In addition to the treatment considerations, other relevant aspects in the management of MG are addressed, including comorbidities, drugs aggravating disease symptoms, pregnancy, and vaccination. As many new treatments might potentially come to market, a realistic future perspective on the impact of these treatments on clinical practice is given. In conclusion, these recommendations intend to be a guide for neurologists treating patients with MG in Belgium., SCOPUS: ar.j, info:eu-repo/semantics/published

Background and purpose: Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials. Methods: Muscle magnetic resonance imaging, patient-reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed-function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow-up. Results: Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32-item Motor Function Measurement (MFM-32) scale (−1.3%, p = 0.017), North Star Ambulatory Assessment (−1.3 points, p = 0.010) and patient-reported activity limitations scale (−0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6-min walk distance (−28.7 m, p = 0.042), 10-m walking test (−0.1 m/s, p = 0.032), time to climb four stairs test (−0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (−4.6 N m, p = 0.014) and hamstrings (−5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM-32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15). Discussion: It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow-up. Finally, significant changes are reported in a wide range of clinical and patient-reported outcome measures, of which the MFM-32 appeared to be the most sensitive to change in adults with BMD., SCOPUS: ar.j, info:eu-repo/semantics/published

Most auditory environments contain multiple sound waves that are mixed before reaching the ears. In such situations, listeners must disentangle individual sounds from the mixture, performing the auditory scene analysis. Analyzing complex auditory scenes relies on listeners ability to segregate acoustic events into different streams, and to selectively attend to the stream of interest. Both segregation and selective attention are known to be challenging for adults with normal hearing, and seem to be even more difficult for children. Here, we review the recent literature on the development of auditory scene analysis, presenting behavioral and neurophysiological results. In short, cognitive and neural mechanisms supporting stream segregation are functional from birth but keep developing until adolescence. Similarly, from 6 months of age, infants can orient their attention toward a target in the presence of distractors. However, selective auditory attention in the presence of interfering streams only reaches maturity in late childhood at the earliest. Methodological limitations are discussed, and a new paradigm is proposed to clarify the relationship between auditory scene analysis and speech perception in noise throughout development., SCOPUS: sh.j, info:eu-repo/semantics/published

Following cerebellar tumour surgery, children may suffer impairments of spontaneous language. Yet, the language processing deficits underlying these impairments are poorly understood. This study is the first to try to identify these deficits for four levels of language processing in cerebellar tumour survivors. The spontaneous language of twelve patients who underwent cerebellar tumour surgery (age range 3–24 years) was compared against his or her controls using individual case statistics. A distinction was made between patients who experienced postoperative cerebellar mutism syndrome (pCMS) and those who did not. Time since surgery ranged between 11 months and 12;3 years. In order to identify the impaired language processing levels at each processing level (i.e. lexical, semantic, phonological and/or morphosyntactic) nouns and verbs produced in the spontaneous language samples were rated for psycholinguistic variables (e.g. concreteness). Standard spontaneous language measures (e.g. type-token ratio) were calculated as well. First, inter-individual heterogeneity was observed in the spontaneous language outcomes in both groups. Nine out of twelve patients showed language processing deficits three of whom were diagnosed with pCMS. Results implied impairments across all levels of language processing. In the pCMS-group, the impairments observed were predominantly morphosyntactic and semantic, but the variability in nature of the spontaneous language impairments was larger in the non-pCMS-group. Patients treated with cerebellar tumour surgery may show long-term spontaneous language impairments irrespective of a previous pCMS diagnosis. Individualised and comprehensive postoperative language assessments seem necessary, given the inter-individual heterogeneity in the language outcomes., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective: New-onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%–50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well-phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers. Methods: Well-characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005–2019. Treating epileptologists reported on post-NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post-discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome. Results: Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow-up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes. Significance: Among survivors of cryptogenic NORSE, longer-term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. Methods: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. Discussion: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. Trial registration: NCT number: NCT05839418., SCOPUS: ar.j, info:eu-repo/semantics/published

Pathogenic variants in RAC3 cause a neurodevelopmental disorder with brain malformations and craniofacial dysmorphism, called NEDBAF. This gene encodes a small GTPase, which plays a critical role in neurogenesis and neuronal migration. We report a 31 weeks of gestation fetus with triventricular dilatation, and temporal and perisylvian polymicrogyria, without cerebellar, brainstem, or callosal anomalies. Trio whole exome sequencing identified a RAC3 (NM_005052.3, GRCh38) probably pathogenic de novo variant c.276 T>A p.(Asn92Lys). Eighteen patients harboring 13 different and essentially de novo missense RAC3 variants were previously reported. All the patients presented with corpus callosum malformations. Gyration disorders, ventriculomegaly (VM), and brainstem and cerebellar malformations have frequently been described. The only previous prenatal case associated with RAC3 variant presented with complex brain malformations, mainly consisting of midline and posterior fossa anomalies. We report the second prenatal case of NEDBAF presenting an undescribed pattern of cerebral anomalies, including VM and polymicrogyria, without callosal, cerebellar, or brainstem malformations. All neuroimaging data were reviewed to clarify the spectrum of cerebral malformations., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective: To assess the effects to functional connectivity (FC) caused by lesions related to spastic diplegic cerebral palsy (CP) in children and adolescents using multiple imaging modalities. Methods: We used resting state magnetoencephalography (MEG) envelope signals in alpha, beta and gamma ranges and resting state functional magnetic resonance imaging (fMRI) signals to quantify FC between selected sensorimotor regions of interest (ROIs) in 11 adolescents with spastic diplegic cerebral palsy and 24 typically developing controls. Motor performance of the hands was quantified with gross motor, fine motor and kinesthesia tests. Results: In fMRI, participants with CP showed enhanced FC within posterior parietal regions; in MEG, they showed enhanced interhemispheric FC between sensorimotor regions and posterior parietal regions both in alpha and lower beta bands. There was a correlation between the kinesthesia score and fronto-parietal connectivity in the control population. Conclusions: CP is associated with enhanced FC in sensorimotor network. This difference is not correlated with hand coordination performance. The effect of the lesion is likely not fully captured by temporal correlation of ROI signals. Significance: Brain lesions can show as increased temporal correlation of activity between remote brain areas. We suggest this effect is likely separate from typical physiological correlates of functional connectivity., SCOPUS: ar.j, info:eu-repo/semantics/published

The clinical phenotype of the so-called late-onset depression (LOD) affecting up to 30% of older adults and yielding heterogeneous manifestations concerning symptoms, severity and course has not been fully elucidated yet. This European, cross-sectional, non-interventional, naturalistic multicenter study systematically investigated socio-demographic and clinical correlates of early-onset depression (EOD) and LOD (age of onset ≥ 50 years) in 1410 adult in- and outpatients of both sexes receiving adequate psychopharmacotherapy. In a total of 1329 patients (94.3%) with known age of disease onset, LOD was identified in 23.2% and was associated with unemployment, an ongoing relationship, single major depressive episodes, lower current suicidal risk and higher occurrence of comorbid hypertension. In contrast, EOD was related to higher rates of comorbid migraine and additional psychotherapy. Although the applied study design does not allow to draw any causal conclusions, the present results reflect broad clinical settings and emphasize easily obtainable features which might be characteristic for EOD and LOD. A thoughtful consideration of age of onset might, hence, contribute to optimized diagnostic and therapeutic processes in terms of the globally intended precision medicine, ideally enabling early and adequate treatment allocations and implementation of respective prevention programs., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side. Objective: The present study aims to systematically review the literature on RS-VNS, assessing its effectiveness and safety. Methods: A systematic review following PRISMA guidelines was conducted: Pubmed/MEDLINE, The Cochrane Library, Scopus, Embase and Web of science databases were searched from inception to August 13th,2023. Gray literature was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy. Results: Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively). Conclusion: Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients., SCOPUS: re.j, info:eu-repo/semantics/published