Pathological Heterogeneity of Idiopathic Central Nervous System Inflammatory Demyelinating Disorders

The spectrum of central nervous system demyelinating disorders is vast and heterogeneous and, often, with overlapping clinical presentations. Misdiagnosis might occur in some cases with serious therapeutic repercussions. However, introduction of several new biomarkers such as aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG has made distinction between diseases such as multiple sclerosis and myelin oligodendrocyte glycoprotein antibody-associated disorder easier. Here, we report a case of a 15-year-old male patient with subacute multifocal neurological presentation without encephalopathy, eventually diagnosed as myelin oligodendrocyte glycoprotein antibody-associated disorder.

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Clinical spectrum of inflammatory central nervous system demyelinating disorders associated with antibodies against myelin oligodendrocyte glycoprotein

Neurochemistry International ◽

10.1016/j.neuint.2018.10.016 ◽

2019 ◽

Vol 130 ◽

pp. 104319 ◽

Cited By ~ 5

Author(s):

Tetsuya Akaishi ◽

Douglas Kazutoshi Sato ◽

Toshiyuki Takahashi ◽

Ichiro Nakashima

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Myelin Oligodendrocyte Glycoprotein ◽

Clinical Spectrum ◽

Demyelinating Disorders

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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 ◽

The Central Nervous System ◽

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....

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International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions

Multiple Sclerosis Journal ◽

10.1177/1352458513484547 ◽

2013 ◽

Vol 19 (10) ◽

pp. 1261-1267 ◽

Cited By ~ 473

Author(s):

Lauren B Krupp ◽

Marc Tardieu ◽

Maria Pia Amato ◽

Brenda Banwell ◽

Tanuja Chitnis ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Acute Disseminated Encephalomyelitis ◽

Study Group ◽

Pediatric Multiple Sclerosis ◽

Immune Mediated ◽

International Pediatric ◽

Demyelinating Disorders ◽

Multiple Sclerosis Study Group

Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope. Objective: The purpose of this review is to revise the 2007 definitions in order to incorporate advances in delineating the clinical and neuroradiologic features of these disorders. Methods: Through a consensus process, in which input was sought from the 150 members of the Study Group, criteria were drafted, revised and finalized. Final approval was sought through a web survey. Results: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyelitis optica and pediatric MS. These criteria were approved by 93% or more of the 56 Study Group members who responded to the final survey. Conclusions: These definitions are proposed for clinical and research purposes. Their utility will depend on the outcomes of their application in prospective research.

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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 ◽

The Central Nervous System ◽

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.

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Pediatric immune-mediated central nervous system demyelinating disorders

Journal of the Neurological Sciences ◽

10.1016/j.jns.2015.09.167 ◽

2015 ◽

Vol 357 ◽

pp. e463

Author(s):

S. Tenembaum

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Immune Mediated ◽

Demyelinating Disorders

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Inflammatory Demyelinating Central Nervous System Diseases in Childhood: Clinical and Paraclinical Profiles in 133 Patients

Autoimmune Diseases ◽

10.1155/2012/957802 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6

Author(s):

Derya Kaya ◽

Egemen İdiman ◽

Serkan Özakbaş

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Disease Onset ◽

Progressive Multiple Sclerosis ◽

Western Turkey ◽

Mri Features ◽

Cranial Mri ◽

Multiple Sclerosis Patients ◽

Demyelinating Disorders

In a retrospective review of patients with acquired demyelinating disorders of the central nervous system, 133 patients (5.6%) whose diseases started in childhood, were selected from 2369 patients, who had medical records in the Neurology Department of Dokuz Eylul University. Out of 133, 98 had relapsing remitting multiple sclerosis, 21 had secondary progressive multiple sclerosis, 8 had clinically isolated syndrome, 3 had neuromyelitis optica, 2 had Marburg disease, and 1 had radiologically isolated syndrome. In 55 patients (41.3%), disease onset was before age 16. Polysymptomatic presentation (22.6%) was the most common initial feature. The EDSS scores ranged from 0 to 9 with a median of 2.0 () for 126 patients. MRI records of 111 patients were obtained. 97 patients had clinically definite multiple sclerosis. 11 MS patients (11.3%) did not initially present the diagnostic MRI features. All of the remaining multiple sclerosis patients fulfilled Barkhof-Tintore criteria (100%) and 88.7% fulfilled KIDMUS criteria. Cranial MRI of NMO patients was normal. Our findings demonstrate some important clinical and paraclinical features that can help the literature on acquired demyelinating disorders of childhood by utilizing data from Western Turkey.

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