Demyelinating Disorders of the Central Nervous System

Critical Care Management ◽

Demyelinating Disorders

Patients with central nervous system (CNS) inflammatory demyelinating disease (IDD) usually have acute relapses of neurologic symptoms that frequently remit spontaneously or after corticosteroid administration; they may also present with a progressive neurodegenerative condition, either de novo or after 1 or more acute relapses. Most patients with acute relapses of demyelinating disease do not have severe disability and can be treated as outpatients. Most hospitalizations for patients with multiple sclerosis (MS), for instance, are for reasons unrelated to MS, such as infection. However, patients with CNS IDD occasionally present with serious, emergent complications caused directly by CNS inflammation or indirectly by secondary complications, either of which can require critical care management.

Demyelinating disorders of the central nervous system

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0591 ◽

2020 ◽

pp. 6026-6042

Author(s):

Alasdair Coles ◽

Siddharthan Chandran

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Demyelinating Disease ◽

Demyelinating Diseases ◽

System P ◽

Industrialized Nations ◽

Distinct Disease ◽

Demyelinating Disorders

The common feature of all of the demyelinating diseases is that, initially at least, the oligodendrocyte-myelin unit is the primary target, with the axon comparatively spared. There are a range of causes, both acquired and inherited, which this chapter explores. Multiple sclerosis, the prototypic demyelinating disorder of the central nervous system, is the leading causing of neurological disability among young adults in many industrialized nations. In the last two decades therapies have been licensed with increasing capacity to suppress the inflammation which underlies the condition, leading to durable benefits to patients. The next most prevalent demyelinating disease is neuromyelitis optica. Originally thought to be a variant of multiple sclerosis, it is now recognized to be a distinct disease whose treatment is radically different from multiple sclerosis.

Demyelinating disorders of the central nervous system

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.0241002_update_001 ◽

2010 ◽

pp. 4948-4963

Author(s):

Siddharthan Chandran ◽

Alastair Compston

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Acute Disseminated Encephalomyelitis ◽

Demyelinating Diseases ◽

Demyelinating Disorder ◽

System P ◽

Demyelinating Disorders ◽

Brain And Spinal Cord

Clinicians suspect demyelination when episodes reflecting damage to white matter tracts within the central nervous system occur in young adults. The paucity of specific biological markers of discrete demyelinating syndromes places an emphasis on clinical phenotype—temporal and spatial patterns—when classifying demyelinating disorders. The diagnosis of multiple sclerosis, the most common demyelinating disorder, becomes probable when these symptoms and signs recur, involving different parts of the brain and spinal cord. Other important demyelinating diseases include post-infectious neurological disorders (acute disseminated encephalomyelitis), demyelination resulting from metabolic derangements (central pontine myelinosis), and inherited leucodystrophies that may present in children or in adults. Accepting differences in mechanism, presentation, and treatment, two observations can usefully be made when classifying demyelinating disorders. These are the presence or absence of inflammation, and the extent of focal vs. diffuse demyelination. Multiple sclerosis is prototypic for the former, whereas dysmyelinating disorders, such as leucodystrophies are representative of the latter....

Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate

Neurotherapeutics ◽

10.1007/s13311-020-00855-0 ◽

2020 ◽

Vol 17 (3) ◽

pp. 1142-1152 ◽

Cited By ~ 1

Author(s):

Karl E. Carlström ◽

Praveen K. Chinthakindi ◽

Belén Espinosa ◽

Faiez Al Nimer ◽

Elias S. J. Arnér ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

De Novo ◽

Dimethyl Fumarate ◽

The Novel ◽

Demyelinating Disorders ◽

Target Effects

Abstract The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1–CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NFκB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.

The 2016 revision of the WHO classification of tumours of the central nervous system

10.1093/med/9780199651870.003.0001 ◽

2017 ◽

Author(s):

Paul Kleihues ◽

Elisabeth Rushing ◽

Hiroko Ohgaki

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Who Classification ◽

De Novo ◽

Genetic Profiling ◽

Primary Glioblastoma ◽

System P ◽

Significant Step ◽

The revised fourth edition of the WHO classification of Tumours of the Central Nervous System, published in 2016, comprises several newly recognized tumour entities, and a significant restructuring of the classification, mainly based on genetic profiling. Glioblastomas are now classified into two major types. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (primary glioblastoma IDH-wildtype) develops rapidly de novo without a recognizable precursor lesion. IDH-mutant glioblastoma (secondary glioblastoma IDH-mutant) develops more slowly through malignant progression from diffuse or anaplastic astrocytoma. Medulloblastomas are now defined by combining histological patterns (classic, desmoplastic/nodular, extensive nodularity, anaplastic) and genetic hallmarks (WNT-activated; SHH-activated, TP53-mutant; SHH-activated, TP53-wildtype; non-WNT/non-SHH). Other newly recognized tumour entities include diffuse midline glioma, H3 K27M-mutant; ependymoma, RELA fusion-positive; and embryonal tumour with multilayered rosettes. The new classification is a significant step forward and will facilitate the development of novel targeted therapies of brain tumours.

Myricetin alleviates cuprizone-induced behavioral dysfunction and demyelination in mice by Nrf2 pathway

Food & Function ◽

10.1039/c6fo00825a ◽

2016 ◽

Vol 7 (10) ◽

pp. 4332-4342 ◽

Cited By ~ 16

Author(s):

Qianying Zhang ◽

Zhike Li ◽

Shuangchan Wu ◽

Xiaofei Li ◽

Ying Sang ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Demyelinating Disease ◽

Nrf2 Pathway ◽

Behavioral Dysfunction ◽

System P ◽

Multiple sclerosis (MS) is a demyelinating disease occurring in the central nervous system.

Detection of anti MOG antibodies in Demyelinating disorders of the central nervous system (CNS)

10.26226/morressier.59a3e8b3d462b8028d8940fa ◽

2017 ◽

Author(s):

Arianna Sala

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mog Antibodies ◽

Demyelinating Disorders

Acute Disseminated Encephalomyelitis (ADEM): A Demyelinating Disease with Specific Morphological Features

International Journal of Surgical Pathology ◽

10.1177/1066896921993562 ◽

2021 ◽

pp. 106689692199356

Author(s):

Fleur Cordier ◽

Lars Velthof ◽

David Creytens ◽

Jo Van Dorpe

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Differential Diagnosis ◽

Clinical Case ◽

Demyelinating Disease ◽

Acute Disseminated Encephalomyelitis ◽

Demyelinating Diseases ◽

Demyelinating Disorder ◽

Immune Mediated ◽

Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory and demyelinating disorder of the central nervous system. Its characteristic perivenular demyelination and inflammation aid in the differential diagnosis with other inflammatory demyelinating diseases. Here, we present a clinical case of ADEM, summarize its histological hallmarks, and discuss pitfalls concerning the most important neuropathological differential diagnoses.

Biology of the repair of central nervous system demyelinated lesions: an appraisal

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1996000200026 ◽

1996 ◽

Vol 54 (2) ◽

pp. 331-334 ◽

Cited By ~ 3

Author(s):

L. A. V Peireira ◽

M. A. Cruz-Höfling ◽

M. S. J. Dertkigil ◽

D. L. Graça

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Schwann Cells ◽

Demyelinating Disease ◽

Experimental Models ◽

Primitive Cell ◽

Marked Influence ◽

Myelin Sheaths ◽

Human Material ◽

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.