Application of digital health for improving medication adherence in MS patients

Review question / Objective: The aim of this study is to evaluate the efficacy of digital health interventions in monitoring and improving medication adherence in Multiple Sclerosis patients. Condition being studied: Multiple sclerosis (MS) is the most prevalent chronic inflammatory disease of the central nervous system (CNS), which leads to focal lesions in the white matter, characterized by selective primary demyelination with partial preservation of axons and reactive astrocytic gliosis. The disease is thought to be due to a complex interaction between different genetic and environmental factors. The prevalence of MS is rising all over the world, due on one hand to earlier diagnosis and prolonged survival, and on the other to a true increase in incidence of the disease. The diagnosis of MS remains clinical despite recent advances in diagnostics and relies on demonstrating dissemination in space and time while excluding alternative diagnoses.

Diseases of the peripheral nerves

This chapter first describes normal physiology, then principles of pathology, typical clinical symptoms and phenotypic subtypes. Lesions of a single nerve (mononeuropathy) include carpal tunnel syndrome, ulnar neuropathy at the elbow and many less commonly affected nerves. Polyneuropathy (generalised abnormality in proportion to nerve length) characteristically causes predominantly distal sensory loss and weakness, and has a large number of possible causes. These include diabetes mellitus, toxins including alcohol, malnutrition especially vitamin B12 deficiency, autoimmune inflammatory demyelination, vasculitis, and genetic neuropathies (Charcot-Marie-Tooth disease), although many patients remain idiopathic despite investigation. Only some causes are treatable. The disease process usually primarily affects the axon, but less commonly there is primary demyelination, neuronopathy or interstitial infiltration.

Serum CXCL13 reflects local B-cell mediated inflammatory demyelinating peripheral neuropathy

Immune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. The serum levels of CXCL13 were also higher in inflammatory demyelinating neuropathic patients but not in acute motor axonal neuropathy or a hereditary demyelinating neuropathy, Charcot-Marie-Tooth disease type 1a. In addition, CXCL13-expressing macrophages were not observed in the sciatic nerves after axonal injury, which causes the activation of innate immunity and Wallerian demyelination. Our findings indicate that the detection of serum CXCL13 will be useful to specifically recognize inflammatory demyelinating neuropathies in human.

Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

This chapter describes the basic neuropathology of multiple sclerosis and other inflammatory demyelinating diseases. It specifically addresses the nature of multiple sclerosis lesions, characterized by inflammation, selective primary demyelination with partial preservation of axons, remyelination, and reactive astroglial scar formation. Attention is paid to the importance of demyelinated lesions in the gray matter, and it discusses the differences of the pathology between the relapsing and the progressive stage of the disease. Finally, it summarizes the similarities and differences between multiple sclerosis and other inflammatory demyelinating diseases, such as acute multiple sclerosis, Baló concentric sclerosis, neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease and acute disseminated encephalomyelitis.

Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

ABSTRACT Recent studies have demonstrated that curcumin (Cur) has antioxidant, anti-inflammatory and anti-fibrotic effects. Ethidium bromide (EB) injections into the central nervous system (CNS) are known to induce local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Peripheral astrogliosis is seen around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). This investigation aimed to evaluate the effect of Cur administration on astrocytic response following gliotoxic injury. Wistar rats were injected with EB into the cisterna pontis and treated, or not, with Cur (100 mg/kg/day, intraperitoneal route) during the experimental period. Brainstem sections were collected at 15, 21 and 31 days after EB injection and processed for GFAP immunohistochemical staining. Astrocytic reactivity was measured in a computerized system for image analysis. In Cur-treated rats, the GFAP-stained area around the lesion was significantly smaller in all periods after EB injection compared to untreated animals, showing that Cur reduces glial scar development following injury.

Propentofylline reduces glial scar development following gliotoxic damage in the rat brainstem

ABSTRACT Propentofylline is a xanthine derivative that depresses activation of glial cells, whose responses contribute to neural tissue damage during inflammation. Ethidium bromide injection into the central nervous system induces local oligodendroglial and astrocytic loss, resulting in primary demyelination, neuroinflammation and blood-brain barrier disruption. Surviving astrocytes present a vigorous reaction around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). Objective This study aimed to evaluate the effect of propentofylline administration on astrocytic response following gliotoxic injury. Method Wistar rats were injected with ethidium bromide into the cisterna pontis and treated or not with propentofylline (12.5mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from 15 to 31 days after gliotoxic injection and processed for GFAP immunohistochemistry. Results and Conclusion Results demonstrate that propentofylline decreased astrocytic activation until the 21st day, suggesting that this drug may have a role in reducing glial scar development following injury.

Vestibular test findings in individuals with auditory neuropathy: review

Background:The vestibulocochlear nerve is a sensory nerve that serves the organs of hearing and equilibrium. Neuropathies of the nerve, particularly auditory neuropathy, may be caused by primary demyelination or axonal disease. Cochlear amplification function is normal in cases of auditory neuropathy, but afferent neural conduction in the auditory pathway is disordered. It is highly probable that the vestibular nerve has some involvement in disorders affecting the cochlear nerve.Objective:To provide an overview of vestibular test findings in individuals with auditory neuropathy.Method:A structured literature search was carried out, with no restrictions to the dates searched.Conclusion:Auditory neuropathy implicated the vestibular branch of the VIIIth cranial nerve as well as the cochlear nerve. However, there was variability in terms of vestibular test findings.