Expert level of detection of interictal discharges with a deep neural network.

Objective: Deep learning methods have shown potential in automating the detection of interictal epileptiform discharges (IEDs) in electroencephalography (EEG). We compared IED detection using our previously trained deep neural network with a group of experts to assess its potential applicability.

Methods: First, we performed clinical validation on an internal data set.

Healthcare utilisation prior to the diagnosis of inflammatory bowel diseases and the influence of livestock exposure: A longitudinal case-control study.

An increased prevalence of the inflammatory bowel diseases, ulcerative colitis and Crohn's disease, was found amongst residents in a livestock dense area. We hypothesised that exposure to livestock farms might be a substantial environmental factor that contributes to the development of these diseases and that in the lead up to inflammatory bowel diseases potential risk factors can be identified. This study aimed to investigate the contribution of livestock exposure to the development of these diseases and the clinical events prior to the diagnosis.

Neurofilament light as an immune target for pathogenic antibodies.

Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunization with neuronal antigens such as neurofilament light (NF-L), a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, although antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease.

Comorbidity and coexisting symptoms and infections presented in general practice by COPD patients: Does livestock density in the residential environment play a role?

Objectives: Patients with chronic obstructive pulmonary disease (COPD) constitute a potentially susceptible group towards environmental exposures such as livestock farm emissions, given their compromised respiratory health status. The primary aim of this study was to examine the association between livestock exposure and comorbidities and coexisting symptoms and infections in COPD patients.

Methods: Data were collected from 1828 COPD patients (without co-occurring asthma) registered in 23 general practices and living in a rural area with a high livestock density.

Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

Background: Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS).

Objective: To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS.

Methods: The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26).

Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis.

Background: Neurofilament (NF) proteins detection in biological fluids as a by-product of axonal loss is technically challenging and to date relies mostly on cerebrospinal fluid (CSF) measurements. Plasma antibodies against NF proteins and particularly to their soluble light chain (NF-L) could be a more practical surrogate marker for disease staging in amyotrophic lateral sclerosis (ALS), an invariably fatal and clinically heterogeneous neuromuscular disorder.

Methodology: We have used a recombinant neurofilament light chain (NF-L) protein for the ELISA detection of antibodies against NF proteins in plasma samples from a well-characterised cohort of ALS individuals (n:73).

Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis.

Background: Autoimmunity to neuronal proteins occurs in several neurological syndromes, where cellular and humoral responses are directed to surface as well as intracellular antigens. Similar to myelin autoimmunity, pathogenic immune response to neuroaxonal components such as neurofilaments may contribute to neurodegeneration in multiple sclerosis.

Methods: We studied the immune response to the axonal protein neurofilament light (NF-L) in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis.

In vitro and in vivo models of multiple sclerosis.

Multiple sclerosis (MS) is widely considered to be the result of an aggressive autoreactive T cell attack on myelin. How these autoimmune responses arise in MS is unclear, but they could result from virus infections. Thus, viral and autoimmune diseases in animals have been used to investigate the possible pathogenic mechanisms operating in MS.

Experimental in vivo and in vitro models of multiple sclerosis: EAE and beyond.

Although the primary cause of multiple sclerosis (MS) is unknown, the widely accepted view is that aberrant (auto)immune responses possibly arising following infection(s) are responsible for the destructive inflammatory demyelination and neurodegeneration in the central nervous system (CNS). This notion, and the limited access of human brain tissue early in the course of MS, has led to the development of autoimmune, viral and toxin-induced demyelination animal models as well as the development of human CNS cell and organotypic brain slice cultures in an attempt to understand events in MS. The autoimmune models, collectively known as experimental autoimmune encephalomyelitis (EAE), and viral models have shaped ideas of how environmental factors may trigger inflammation, demyelination and neurodegeneration in the CNS.

Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis.

Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and blood-borne macrophages, whereas the fate of degenerating or damaged axons is unclear.