-
Experimental Neurology Sep 2016There is an increasing number of neurologic disorders found to be associated with loss and/or dysfunction of the CNS myelin sheath, ranging from the classic... (Review)
Review
There is an increasing number of neurologic disorders found to be associated with loss and/or dysfunction of the CNS myelin sheath, ranging from the classic demyelinating disease, multiple sclerosis, through CNS injury, to neuropsychiatric diseases. The disabling burden of these diseases has sparked a growing interest in gaining a better understanding of the molecular mechanisms regulating the differentiation of the myelinating cells of the CNS, oligodendrocytes (OLGs), and the process of (re)myelination. In this context, the importance of the extracellular milieu is becoming increasingly recognized. Under pathological conditions, changes in inhibitory as well as permissive/promotional cues are thought to lead to an overall extracellular environment that is obstructive for the regeneration of the myelin sheath. Given the general view that remyelination is, even though limited in human, a natural response to demyelination, targeting pathologically 'dysregulated' extracellular cues and their downstream pathways is regarded as a promising approach toward the enhancement of remyelination by endogenous (or if necessary transplanted) OLG progenitor cells. In this review, we will introduce the extracellular cues that have been implicated in the modulation of (re)myelination. These cues can be soluble, part of the extracellular matrix (ECM) or mediators of cell-cell interactions. Their inhibitory and permissive/promotional roles with regard to remyelination as well as their potential for therapeutic intervention will be discussed.
Topics: Animals; Cell Differentiation; Demyelinating Diseases; Extracellular Matrix; Humans; Nerve Regeneration; Oligodendroglia; Stem Cells
PubMed: 27016069
DOI: 10.1016/j.expneurol.2016.03.019 -
Nature Reviews. Neurology Aug 2019Microglia are resident macrophages of the CNS that are involved in its development, homeostasis and response to infection and damage. Microglial activation is a common... (Review)
Review
Microglia are resident macrophages of the CNS that are involved in its development, homeostasis and response to infection and damage. Microglial activation is a common feature of neurological disorders, and although in some instances this activation can be damaging, protective and regenerative functions of microglia have been revealed. The most prominent example of the regenerative functions is a role for microglia in supporting regeneration of myelin after injury, a process that is critical for axonal health and relevant to numerous disorders in which loss of myelin integrity is a prevalent feature, such as multiple sclerosis, Alzheimer disease and motor neuron disease. Although drugs that are intended to promote remyelination are entering clinical trials, the mechanisms by which remyelination is controlled and how microglia are involved are not completely understood. In this Review, we discuss work that has identified novel regulators of microglial activation - including molecular drivers, population heterogeneity and turnover - that might influence their pro-remyelination capacity. We also discuss therapeutic targeting of microglia as a potential approach to promoting remyelination.
Topics: Aging; Animals; Central Nervous System; Demyelinating Diseases; Homeostasis; Humans; Macrophage Activation; Microglia; Remyelination
PubMed: 31256193
DOI: 10.1038/s41582-019-0184-2 -
Revista Brasileira de Reumatologia 2017Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and...
INTRODUCTION
Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population.
OBJECTIVE
To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients.
METHOD
22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies.
RESULTS
Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases.
CONCLUSION
Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults.
Topics: Adolescent; Autoimmune Diseases; Child; Cross-Sectional Studies; Female; Humans; Male; Multiple Sclerosis; Neuromyelitis Optica; Prevalence; Retrospective Studies; Rheumatic Diseases; Risk Factors
PubMed: 28535894
DOI: 10.1016/j.rbre.2016.09.016 -
Genes Jun 2023Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous... (Review)
Review
Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.
Topics: Humans; Multiple Sclerosis; Neuromyelitis Optica; Central Nervous System; Myelin Sheath; Diagnosis, Differential
PubMed: 37510224
DOI: 10.3390/genes14071319 -
Seminars in Neurology Dec 2015Fulminant demyelinating diseases of the central nervous system include acute disseminated encephalomyelitis, the related acute hemorrhagic leukoencephalitis, multiple... (Review)
Review
Fulminant demyelinating diseases of the central nervous system include acute disseminated encephalomyelitis, the related acute hemorrhagic leukoencephalitis, multiple sclerosis variants, neuromyelitis optica spectrum disorders, and idiopathic transverse myelitis. These syndromes are often managed with similar acute treatments including high-dose corticosteroids and plasmapheresis; however, long-term management varies. Although the prognosis of fulminant demyelinating disease was historically poor, outcomes today may be improved due to earlier diagnosis, rapid implementation of anti-inflammatory therapies such as high-dose corticosteroids and plasmapheresis, and improved supportive care.
Topics: Adrenal Cortex Hormones; Demyelinating Diseases; Diagnosis, Differential; Disease Management; Humans; Plasmapheresis; Prognosis
PubMed: 26595866
DOI: 10.1055/s-0035-1564682 -
Acta Neuropathologica Communications Nov 2018Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by massive infiltration of immune cells, demyelination, and axonal loss. Active... (Review)
Review
Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by massive infiltration of immune cells, demyelination, and axonal loss. Active MS lesions mainly consist of macrophages and microglia containing abundant intracellular myelin remnants. Initial studies showed that these foamy phagocytes primarily promote MS disease progression by internalizing myelin debris, presenting brain-derived autoantigens, and adopting an inflammatory phenotype. However, more recent studies indicate that phagocytes can also adopt a beneficial phenotype upon myelin internalization. In this review, we summarize and discuss the current knowledge on the spatiotemporal physiology of foamy phagocytes in MS lesions, and elaborate on extrinsic and intrinsic factors regulating their behavior. In addition, we discuss and link the physiology of myelin-containing phagocytes to that of foamy macrophages in other disorders such atherosclerosis.
Topics: Animals; Demyelinating Diseases; Humans; Macrophages; Microglia; Multiple Sclerosis; Myelin Sheath; Phagocytes
PubMed: 30454040
DOI: 10.1186/s40478-018-0628-8 -
Nature Reviews. Neurology Jun 2020
Topics: Demyelinating Diseases; Humans; Oligodendroglia; Remyelination
PubMed: 32203392
DOI: 10.1038/s41582-020-0341-7 -
Child Neuropsychology : a Journal on... Jul 2018Immune-mediated central nervous system (CNS) demyelinating diseases impact various areas of the brain, optic nerves, and/or spinal cord and can result in a wide range of... (Review)
Review
Immune-mediated central nervous system (CNS) demyelinating diseases impact various areas of the brain, optic nerves, and/or spinal cord and can result in a wide range of neurologic symptoms including adverse cognitive outcomes. Neuropsychological outcomes in adult multiple sclerosis (MS) are well documented, while literature on such outcomes in pediatric cohorts is more limited. Furthermore, literature on neuropsychological outcomes in pediatric acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and transverse myelitis (TM) is even more limited. This paper is the first to review what is known about neuropsychological outcomes associated with immune-mediated CNS demyelinating diseases, with a focus on pediatric MS, ADEM, NMO, and TM. Additionally, this review illuminates the need to clarify differences in neuropsychological sequelae between conditions, characterize longitudinal cognitive outcomes, and investigate neuropsychological outcomes in relation to clinical variables (e.g., age of onset, disease duration, number of relapses) and psychosocial variables (e.g., fatigue, emotional problems, behavioral functioning) to better understand neuropsychological outcomes associated with these conditions.
Topics: Child; Demyelinating Diseases; Female; Humans; Male; Multiple Sclerosis; Neuropsychiatry
PubMed: 28637379
DOI: 10.1080/09297049.2017.1339785 -
Molecular Genetics and Metabolism Apr 2015Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have...
Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms associated with leukodystrophies has allowed clinicians and researchers to prioritize treatment strategies and advance research in therapies for specific disorders, some of which are on the verge of pilot or Phase I/II clinical trials. This shifts the care of leukodystrophy patients from the management of the complex array of symptoms and sequelae alone to targeted therapeutics. The unmet needs of leukodystrophy patients still remain an overwhelming burden. While the overwhelming consensus is that these disorders collectively are symptomatically treatable, leukodystrophy patients are in need of advanced therapies and if possible, a cure.
Topics: Brain Diseases; Demyelinating Diseases; Hereditary Central Nervous System Demyelinating Diseases; Humans; Leukodystrophy, Metachromatic; Leukoencephalopathies
PubMed: 25684057
DOI: 10.1016/j.ymgme.2015.01.014 -
Italian Journal of Pediatrics Jan 2021Post-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to...
BACKGROUND
Post-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to the absence of any recognized guidelines and a univocal definition.
AIM OF THE STUDY
To elaborate a diagnostic guide for PINS.
MATERIALS AND METHODS
We retrospectively analysed patients younger than 14 years old admitted to Bambino Gesù Children's Hospital in Rome for PINS from December 2005 to March 2018. Scientific literature using PubMed as research platform was analysed: the key words "Post-Infectious Neurological Syndromes" were used.
RESULTS
A polysymptomatic presentation occurred in a percentage of 88% of the children. Motor signs and visual disturbances the most observed symptoms/signs were the most detached, followed by fever, speech disturbances, sleepiness, headache and bradipsychism. Blood investigations are compatible with inflammation, as a prodromal illnesses was documented in most cases. Normal cerebral spinal fluid (CSF) characteristics has been found in the majority of the study population. Magnetic resonance imaging (MRI) was positive for demyelinating lesions. Antibiotics, acyclovir and steroids have been given as treatment.
DISCUSSION
We suggest diagnostic criteria for diagnosis of PINS, considering the following parameters: neurological symptoms, timing of disease onset, blood and CSF laboratory tests, MRI imaging.
CONCLUSIONS
We propose criteria to guide clinician to diagnose PINS as definitive, probable or possible. Further studies are required to validate diagnostic criteria.
Topics: Adolescent; Anti-Infective Agents; Biomarkers; Child; Demyelinating Diseases; Diagnosis, Differential; Humans; Infections; Magnetic Resonance Imaging; Male; Retrospective Studies; Steroids; Syndrome
PubMed: 33494818
DOI: 10.1186/s13052-021-00968-y