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Developmental Medicine and Child... Nov 2019The last two decades witnessed significant advances in the treatment of acquired demyelinating disorders: thirteen new agents have been approved for the treatment of... (Review)
Review
The last two decades witnessed significant advances in the treatment of acquired demyelinating disorders: thirteen new agents have been approved for the treatment of multiple sclerosis in adults by the European Medicines Agency and US Food and Drug Administration in the last twenty years. Although the long-term efficacy and safety profiles of some new drugs are still being assessed in paediatric MS, clinicians may have to use them in the management of paediatric onset MS resistant to first-line medications, based on results obtained in adult-onset disease. This review summarizes the current approach to treatment in children with demyelinating syndromes. WHAT THIS PAPER ADDS: Serological markers affect management in paediatric demyelinating diseases. Antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein should be tested in children with acute demyelinating disease. New therapeutic agents currently in trial for pediatric disease should be used with close follow-up.
Topics: Aquaporin 4; Demyelinating Diseases; Humans; Myelin-Oligodendrocyte Glycoprotein; Risk Factors; Serologic Tests; Treatment Outcome
PubMed: 30993677
DOI: 10.1111/dmcn.14228 -
Brain Research. Brain Research Reviews Apr 2005Re-myelination in the adult CNS has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that re-myelination... (Review)
Review
Re-myelination in the adult CNS has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that re-myelination is effective in multiple sclerosis (MS), the most diffuse demyelinating disease. Moreover, chronic disabilities in MS are believed to be due to remyelination failure and consequent neuron damage and degeneration. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, reasons for remyelination failure are unknown. In this paper, we reviewed data from embryonic development and in vitro studies supporting the primary role of thyroid hormone in oligodendrocyte maturation. We also reviewed personal data on the possibility of promoting myelination in chronic experimental allergic encephalomyelitis (EAE), a widely used experimental model of MS, by recruiting progenitors and channeling them into oligodendroglial lineage through the administration of thyroid hormone.
Topics: Animals; Central Nervous System; Demyelinating Diseases; Humans; Inflammation; Models, Neurological; Myelin Sheath; Nerve Regeneration; Thyroid Hormones
PubMed: 15850672
DOI: 10.1016/j.brainresrev.2004.12.022 -
Multiple Sclerosis and Related Disorders Jun 2021Since March 2020, during the Coronavirus disease 2019 (COVID-19) pandemic, it has been observed that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has...
BACKGROUND
Since March 2020, during the Coronavirus disease 2019 (COVID-19) pandemic, it has been observed that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has neurological involvement with various clinical tables.
METHODS
We present 3 new cases admitted to our clinic with various neurological findings which were affected by SARS-CoV-2.
RESULTS
Imaging studies have shown that inflammatory/demyelinizing lesions appeared in different areas of the central nervous system which were accepted as an atypical demyelinating spectrum associated with Covid 19.
CONCLUSIONS
With increasing experience, it has been suggested that SARS-CoV-2 may also have a neurotrophic effect. The spectrum of neurological involvement is also expanding as the pandemic continues. These 3 cases suggest that the virus plays a role in the clinical onset of the inflammatory/demyelinating disease.
Topics: COVID-19; Central Nervous System; Demyelinating Diseases; Humans; Pandemics; SARS-CoV-2
PubMed: 33770573
DOI: 10.1016/j.msard.2021.102900 -
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 -
Wiener Medizinische Wochenschrift (1946) Jun 2017Adrenoleukodystrophy (ALD) is an X‑linked hereditary disorder due to mutations of the ABCD1 gene, which encodes a peroxisomal transport protein necessary for very... (Review)
Review
Adrenoleukodystrophy (ALD) is an X‑linked hereditary disorder due to mutations of the ABCD1 gene, which encodes a peroxisomal transport protein necessary for very long-chain fatty acid degradation (VLCFA). Toxic accumulation thereof is associated with a proinflammatory state and eventual cell death in multiple tissues. ALD may manifest either as a fatal, rapidly progressive demyelinating disease in boys and adult men, or as a slowly progressive adult-onset long-tract myelopathy along with peripheral neuropathy. Our understanding of manifold mechanisms implicated in the disease pathology is currently incomplete, as neither genotype-phenotype correlation nor the trigger for cerebral disease has been described. Therapy objectives are therefore broadly aimed at correcting either the gene mutation or downstream molecular effects, such as oxidative stress. Advancements in disease detection, including the newly implemented newborn screening in the US and imaging modalities, allow for more timely intervention in the form of hematopoietic stem cell transplantation (HSCT), which may only be performed in early cerebral disease states.
Topics: Adrenoleukodystrophy; Adult; Brain Diseases; Cell Death; Child; Chromosomes, Human, X; DNA Mutational Analysis; Demyelinating Diseases; Disease Progression; Hematopoietic Stem Cell Transplantation; Humans; Infant, Newborn; Male; Neonatal Screening
PubMed: 28493141
DOI: 10.1007/s10354-016-0534-2 -
Multiple Sclerosis (Houndmills,... Jun 2019Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of...
Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of the central nervous system during treatment with Pembrolizumab and discuss the evidence in the literature supporting its causative role. The patient had a good clinical recovery after intravenous steroids, plasma exchange and discontinuation of Pembrolizumab. Due to the expected increase in the importance of immune checkpoint inhibitors in cancer treatment, it is important to be aware of neurological adverse events, as early treatment usually leads to good clinical responses.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Demyelinating Diseases; Female; Humans; Melanoma; Middle Aged; Neoplasm Metastasis; Skin Neoplasms; White Matter
PubMed: 30311534
DOI: 10.1177/1352458518803724 -
Neurology(R) Neuroimmunology &... Jan 2019We sought to develop molecular biomarkers of intrathecal inflammation to assist neurologists in identifying patients most likely to benefit from a range of immune...
OBJECTIVE
We sought to develop molecular biomarkers of intrathecal inflammation to assist neurologists in identifying patients most likely to benefit from a range of immune therapies.
METHODS
We used Luminex technology and index determination to search for an inflammatory activity molecular signature (IAMS) in patients with inflammatory demyelinating disease (IDD), other neuroinflammatory diagnoses, and noninflammatory controls. We then followed the clinical characteristics of these patients to find how the presence of the signature might assist in diagnosis and prognosis.
RESULTS
A CSF molecular signature consisting of elevated CXCL13, elevated immunoglobulins, normal albumin CSF/serum ratio (Q), and minimal elevation of cytokines other than CXCL13 provided diagnostic and prognostic value; absence of the signature in IDD predicted lack of subsequent inflammatory events. The signature outperformed oligoclonal bands, which were frequently false positive for active neuroinflammation.
CONCLUSIONS
A CSF IAMS may prove useful in the diagnosis and management of patients with IDD and other neuroinflammatory syndromes.
CLASSIFICATION OF EVIDENCE
This study provides Class IV evidence that a CSF IAMS identifies patients with IDD.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albumins; Biomarkers; Chemokine CXCL13; Cytokines; Demyelinating Diseases; Encephalitis; Female; Humans; Immunoglobulins; Male; Middle Aged; Myelitis; Young Adult
PubMed: 30568998
DOI: 10.1212/NXI.0000000000000520 -
Autoimmunity Reviews Oct 2002The pathogenesis of multiple sclerosis (MS), a human demyelinating disease of the central nervous system (CNS), is currently unknown. It is widely thought that MS is an... (Review)
Review
The pathogenesis of multiple sclerosis (MS), a human demyelinating disease of the central nervous system (CNS), is currently unknown. It is widely thought that MS is an autoimmune disease which is supported by animal studies showing that myelin-specific CD4+ T cells can induce similar clinical disease in mice as observed in MS. However, the mechanism(s) of activation of these autoreactive CD4+ T cells are unknown. Although genetic susceptibility is important, other factors may be involved. Viral infections have long thought to be involved in the pathogenesis of MS although there exists little or no direct evidence implicating a role for a specific virus in MS pathogenesis. This review will discuss two models of virus-induced CNS autoimmunity, molecular mimicry and epitope spreading. These two mechanisms of activation of autoreactive T cells are presented in the context of MS.
Topics: Animals; Antigens, Viral; Autoimmunity; Cardiovirus Infections; Demyelinating Diseases; Disease Models, Animal; Epitopes; Humans; Mice; Models, Immunological; Molecular Mimicry; Multiple Sclerosis; Theilovirus
PubMed: 12848977
DOI: 10.1016/s1568-9972(02)00080-0 -
Molecular Psychiatry 2002
Review
Topics: Animals; Demyelinating Diseases; Humans; Nerve Regeneration; Tumor Necrosis Factor-alpha
PubMed: 12232770
DOI: 10.1038/sj.mp.4001120 -
Neuroimaging Clinics of North America May 2013
Topics: Brain; Child; Demyelinating Diseases; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Neuroimaging
PubMed: 23608695
DOI: 10.1016/j.nic.2013.02.001