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Revista Medica Del Instituto Mexicano... Mar 2023Acute hemorrhagic leukoencephalitis (AHLE) is an inflammatory disease of the brain, with a fulminant course that leads to a hemorrhagic demyelination of the central... (Review)
Review
BACKGROUND
Acute hemorrhagic leukoencephalitis (AHLE) is an inflammatory disease of the brain, with a fulminant course that leads to a hemorrhagic demyelination of the central nervous system, having a poor prognosis and high mortality. Most of the times associated to crossed reactivity and molecular mimicry.
CLINICAL CASE
: We present a case report of a previously healthy young woman with an acute and multifocal clinical course, preceded by a viral respiratory tract infection, followed by a rapid disease progression and a delay in the diagnosis. The clinical, neuroimaging and cerebrospinal fluid featured suggested the diagnosis of AHLE, despite efforts and management with immunosuppression and intensive care, the response to treatment was poor leaving the patient with a severe neurological impairment.
CONCLUSION
There is little evidence regarding the clinical course and treatment of this disease, and more studies are needed to better characterize it and to provide further information about its prognosis and management. This paper gives a systematic review of the literature.
Topics: Female; Humans; Leukoencephalitis, Acute Hemorrhagic; Brain
PubMed: 37205605
DOI: No ID Found -
Aging and Disease May 2024In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of... (Review)
Review
In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process. Recent studies have shown that the voltage-gated proton channel Hv1 is selectively expressed in microglia in CNS, which regulates intracellular pH and is involved in the production of reactive oxygen species, underlying multifaceted roles in maintaining microglia function. This paper begins by examining the molecular mechanisms of demyelination and emphasizes the crucial role of the microenvironment in demyelination. It focuses specifically on the role of Hv1 in myelin repair and its therapeutic potential in CNS demyelinating diseases.
Topics: Humans; Microglia; Myelin Sheath; Animals; Demyelinating Diseases; Immunomodulation; Ion Channels; Remyelination; Reactive Oxygen Species
PubMed: 38029392
DOI: 10.14336/AD.2023.1107 -
Molecules (Basel, Switzerland) Aug 2021Multiple sclerosis (MS) belongs to demyelinating diseases, which are progressive and highly debilitating pathologies that imply a high burden both on individual patients... (Review)
Review
Multiple sclerosis (MS) belongs to demyelinating diseases, which are progressive and highly debilitating pathologies that imply a high burden both on individual patients and on society. Currently, several treatment strategies differ in the route of administration, adverse events, and possible risks. Side effects associated with multiple sclerosis medications range from mild symptoms, such as flu-like or irritation at the injection site, to serious ones, such as progressive multifocal leukoencephalopathy and other life-threatening events. Moreover, the agents so far available have proved incapable of fully preventing disease progression, mostly during the phases that consist of continuous, accumulating disability. Thus, new treatment strategies, able to halt or even reverse disease progression and specific for targeting solely the pathways that contribute to the disease pathogenesis, are highly desirable. Here, we provide an overview of the recent literature about peptide-based systems tested on experimental autoimmune encephalitis (EAE) models. Since peptides are considered a unique therapeutic niche and important elements in the pharmaceutical landscape, they could open up new therapeutic opportunities for the treatment of MS.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Humans; Multiple Sclerosis; Peptides
PubMed: 34500662
DOI: 10.3390/molecules26175227 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2022Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous... (Review)
Review
Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.
Topics: Demyelinating Diseases; High-Throughput Nucleotide Sequencing; Humans; Myelin Sheath; Neurodegenerative Diseases; Phenotype
PubMed: 35762440
DOI: 10.7499/j.issn.1008-8830.2202020 -
Glia Oct 2020Remyelination, namely, the formation of new myelin sheaths around denuded axons, counteracts axonal degeneration and restores neuronal function. Considerable advances... (Review)
Review
Remyelination, namely, the formation of new myelin sheaths around denuded axons, counteracts axonal degeneration and restores neuronal function. Considerable advances have been made in understanding this regenerative process that often fails in diseases like multiple sclerosis, leaving axons demyelinated and vulnerable to damage, thus contributing to disease progression. The identification of the membrane receptor GPR17 on a subset of oligodendrocyte precursor cells (OPCs), which mediate remyelination in the adult central nervous system (CNS), has led to a huge amount of evidence that validated this receptor as a new attractive target for remyelinating therapies. Here, we summarize the role of GPR17 in OPC function, myelination and remyelination, describing its atypical pharmacology, its downstream signaling, and the genetic and epigenetic factors modulating its activity. We also highlight crucial insights into GPR17 pathophysiology coming from the demonstration that oligodendrocyte injury, associated with inflammation in chronic neurodegenerative conditions, is invariably characterized by abnormal and persistent GPR17 upregulation, which, in turn, is accompanied by a block of OPCs at immature premyelinating stages. Finally, we discuss the current literature in light of the potential exploitment of GPR17 as a therapeutic target to promote remyelination.
Topics: Animals; Demyelinating Diseases; Epigenesis, Genetic; Humans; Myelin Sheath; Oligodendroglia; Receptors, G-Protein-Coupled; Remyelination; Signal Transduction
PubMed: 32086854
DOI: 10.1002/glia.23807 -
Pflugers Archiv : European Journal of... Dec 2022The cuprizone model is a widely used model to study the pathogenesis of multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is...
The cuprizone model is a widely used model to study the pathogenesis of multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is mainly being used to study demyelination and the mechanisms of remyelination, as well as the efficiency of compounds or therapeutics aiming at remyelination. Although early investigations using high dosages of cuprizone reported the occurrence of hydrocephalus, it has long been assumed that cuprizone feeding at lower dosages does not induce changes at the blood-brain barrier (BBB). Here, by analyzing BBB ultrastructure with high-resolution electron microscopy, we report changes at astrocytic endfeet surrounding vessels in the brain parenchyma. Particularly, edema formation around blood vessels and swollen astrocytic endfeet already occurred after feeding low dosages of cuprizone. These findings indicate changes in BBB function that will have an impact on the milieu of the central nervous system (CNS) in the cuprizone model and need to be considered when studying the mechanisms of de- and remyelination.
Topics: Animals; Mice; Cuprizone; Astrocytes; Demyelinating Diseases; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 36241864
DOI: 10.1007/s00424-022-02759-8 -
Frontiers in Immunology 2022Radiologically Isolated Syndrome (RIS) is characterized by MRI-typical brain lesions fulfilling the 2009 Okuda criteria, detected in patients without clinical conditions... (Review)
Review
Radiologically Isolated Syndrome (RIS) is characterized by MRI-typical brain lesions fulfilling the 2009 Okuda criteria, detected in patients without clinical conditions suggestive of MS. Half of all RIS patients convert to MS within 10 years. The individual course of the disease, however, is highly variable with 12% of RIS converting directly to progressive MS. Demographic and imaging markers have been associated with the risk of clinical MS in RIS: male sex, younger age, infra-tentorial, and spinal cord lesions on the index scan and gadolinium-enhancing lesions on index or follow-up scans. Although not considered as a distinct MS phenotype, RIS certainly shares common pathological features with early active and progressive MS. In this review, we specifically focus on biological markers that may help refine the risk stratification of clinical MS and disability for early treatment. Intrathecal B-cell activation with cerebrospinal fluid (CSF) oligoclonal bands, elevated kappa free light chains, and cytokine production is specific to MS, whereas neurofilament light chain (NfL) levels reflect disease activity associated with neuroaxonal injury. Specific microRNA profiles have been identified in RIS converters in both CSF and blood. CSF levels of chitinases and glial acidic fibrillary protein (GFAP) reflecting astrogliosis might help predict the evolution of RIS to progressive MS. Innovative genomic, proteomic, and metabolomic approaches have provided several new candidate biomarkers to be explored in RIS. Leveraging data from randomized controlled trials and large prospective RIS cohorts with extended follow-up to identify, as early as possible, biomarkers for predicting greater disease severity would be invaluable for counseling patients, managing treatment, and monitoring.
Topics: Biomarkers; Demyelinating Diseases; Humans; Immunoglobulin kappa-Chains; Male; Multiple Sclerosis; Prospective Studies; Proteomics
PubMed: 35572543
DOI: 10.3389/fimmu.2022.866092 -
European Review For Medical and... Feb 2022Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly... (Review)
Review
OBJECTIVE
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS.
PATIENTS AND METHODS
We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing).
RESULTS
There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS.
CONCLUSIONS
Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.
Topics: Animals; Bile Acids and Salts; Central Nervous System; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Multiple Sclerosis
PubMed: 35179760
DOI: 10.26355/eurrev_202202_28003 -
Journal of Neurology Jan 2022Optic neuritis (ON) is an inflammatory optic neuropathy that is often a harbinger of central nervous system (CNS) demyelinating disorders. ON is frequently misdiagnosed... (Review)
Review
Optic neuritis (ON) is an inflammatory optic neuropathy that is often a harbinger of central nervous system (CNS) demyelinating disorders. ON is frequently misdiagnosed in the clinical arena, leading to either inappropriate management or diagnostic delays. As a result, patients may fail to achieve optimal recovery. The treatment response to corticosteroids and long term risk of multiple sclerosis was established in the first clinical trials conducted roughly 30 years ago. Spontaneous resolution was observed in the vast majority of patients and intravenous high-dose corticosteroids hastened recovery; half of the patients eventually developed multiple sclerosis. Over the ensuing decades, the number of inflammatory conditions associated with ON has significantly expanded exposing substantial variability in the prognosis, treatment, and management of ON patients. ON subtypes can frequently be distinguished by distinct clinical, serological, and radiological profiles allowing expedited and specialized treatment. Guided by an increased understanding of the immunopathology underlying optic nerve and associated CNS injuries, novel disease management strategies are emerging to minimize vision loss, improve long-term surveillance strategies, and minimize CNS injury and disability. Knowledge regarding the clinical signs and symptoms of different ON subtypes is essential to guide acute therapy, prognosticate recovery, accurately identify underlying CNS inflammatory disorders, and facilitate study design for the next generation of clinical and translational trials.
Topics: Adrenal Cortex Hormones; Humans; Multiple Sclerosis; Optic Nerve Diseases; Optic Neuritis
PubMed: 33389032
DOI: 10.1007/s00415-020-10352-1 -
Brain : a Journal of Neurology Jun 2021Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple...
Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.
Topics: Aged; Brain; Demyelinating Diseases; Disability Evaluation; Disease Progression; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting
PubMed: 33880511
DOI: 10.1093/brain/awab033