Prognostic value of motor and extramotor involvement in ALS.

Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder resulting in upper and lower motor neuron loss. ALS often has a focal onset of weakness, which subsequently spreads to other body regions. Survival is limited to two to five years after disease onset, often due to respiratory failure.

Differences in Cerebral Glucose Metabolism in ALS Patients with and without and Mutations.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons. In 10% of patients, the disorder runs in the family. Our aim was to study the impact of ALS-causing gene mutations on cerebral glucose metabolism.

Positive screens for mental disorders among healthcare professionals during the first covid19 wave in Belgium.

We examined the manifestation of major depressive disorder, generalized anxiety disorder, substance use disorder, post-traumatic stress disorder, and panic attacks among health care professionals during the first COVID-19 wave (n = 6409) by means of mental disorder screening instruments. Logistic regressions were used to gauge individual risk factors; population attributable risk proportions (PARP) were inferred to identify the most important risk factors at the societal level. Data were weighted to represent general profiles of Belgian health care professionals.

Barriers and Facilitators in Perioperative Antibiotic Prophylaxis: A Mixed-Methods Study in a Small Island Setting.

Few studies have addressed antibiotic guideline adherence in small island settings, such as Aruba. This study aimed to evaluate the appropriateness of perioperative antibiotic prophylaxis (PAP) and identify barriers for PAP guideline adherence. A mixed-methods study was carried out at the operating theatre (OT) in the Dr.

Altered perivascular fibroblast activity precedes ALS disease onset.

Apart from well-defined factors in neuronal cells, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia and blood vessels. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response.

Use of Multimodal Imaging and Clinical Biomarkers in Presymptomatic Carriers of C9orf72 Repeat Expansion.

Importance: During a time with the potential for novel treatment strategies, early detection of disease manifestations at an individual level in presymptomatic carriers of a hexanucleotide repeat expansion in the C9orf72 gene (preSxC9) is becoming increasingly relevant.

Objectives: To evaluate changes in glucose metabolism before symptom onset of amyotrophic lateral sclerosis or frontotemporal dementia in preSxC9 using simultaneous fluorine 18-labeled fluorodeoxyglucose ([18F]FDG positron emission tomographic (PET) and magnetic resonance imaging as well as the mutation's association with clinical and fluid biomarkers.

Design, Setting, And Participants: A prospective, case-control study enrolled 46 participants from November 30, 2015, until December 11, 2018.

Combined brain and spinal FDG PET allows differentiation between ALS and ALS mimics.

Purpose: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with on average a 1-year delay between symptom onset and diagnosis. Studies have demonstrated the value of [F]-FDG PET as a sensitive diagnostic biomarker, but the discriminatory potential to differentiate ALS from patients with symptoms mimicking ALS has not been investigated. We investigated the combination of brain and spine [F]-FDG PET-CT for differential diagnosis between ALS and ALS mimics in a real-life clinical diagnostic setting.

Moving Toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands.

Neuroinflammation has been implicated in amyotrophic lateral sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, TSPO radioligands have some challenges to overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (C-PBR28 and F-DPA714) is feasible, after validation of an established C-PBR28 PET pseudo reference analysis technique for F-DPA714.

TSPO Versus P2X7 as a Target for Neuroinflammation: An In Vitro and In Vivo Study.

Neuroinflammation is important in amyotrophic lateral sclerosis (ALS). The P2X7 receptor (P2X7R) is a promising target for neuroinflammation. The objective of this study was to compare F-DPA714, a second-generation translocator protein tracer, with C-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS.

Motor cortex metabolite alterations in amyotrophic lateral sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy.

Previous MRI and proton spectroscopy (H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n = 7) and healthy controls (n = 7).

Glucose metabolic brain patterns to discriminate amyotrophic lateral sclerosis from Parkinson plus syndromes.

Background: F-FDG brain PET measures metabolic changes in neurodegenerative disorders and may discriminate between different diseases even at an early stage. The objective of this study was to classify patients with amyotrophic lateral sclerosis (ALS) and Parkinson plus syndromes (PP). To this end, different approaches were evaluated using generalized linear models and corresponding glucose metabolic brain patterns.

Derivation of norms for the Dutch version of the Edinburgh cognitive and behavioral ALS screen.

Background: The Edinburgh cognitive and behavioral ALS screen (ECAS) was developed specifically to detect cognitive and behavioral changes in patients with amyotrophic lateral sclerosis (ALS). Differences with regard to normative data of different (language) versions of neuropsychological tests such as the ECAS exist.

Objective: To derive norms for the Dutch version of the ECAS.

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis.

Aims: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration.

Multicenter validation of [F]-FDG PET and support-vector machine discriminant analysis in automatically classifying patients with amyotrophic lateral sclerosis versus controls.

Objective: F-Fluorodeoxyglucose (F-FDG) positron emission tomography (PET) single-center studies using support vector machine (SVM) approach to differentiate amyotrophic lateral sclerosis (ALS) from controls have shown high overall accuracy on an individual patient basis using local a priori defined classifiers. The aim of the study was to validate the SVM accuracy on a multicentric level.

Methods: A previously defined Belgian (BE) group of 175 ALS patients (61.

Is there a glucose metabolic signature of spreading TDP-43 pathology in amyotrophic lateral sclerosis?

Background: Recently, four neuropathological stages of amyotrophic lateral sclerosis (ALS) with spreading of transactive response DNA-binding protein-43 pathology were described. Although 18F-FDG PET has been useful in diagnosis and prognosis of ALS patients, in-vivo disease staging using glucose metabolic patterns across the different ALS stages has not been attempted so far. In this study, we investigated whether the discriminant brain regions of the neuropathological stage model can be translated to metabolic patterns for in-vivo staging of ALS.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization.

Cervical spinal cord injuries in patients with refractory epilepsy.

The incidence of cervical spinal cord injuries (c-SCI) in patients with refractory epilepsy is 30-40 times higher than in the normal population. The injuries occur after seizure-related falls. Risk factors and pitfalls in diagnosis are discussed.