Inflammatory neuropathology of infantile Alexander disease: A case report.
Alexander disease
Astrocyte
Macrophage chemotactic protein 1
Neuroinflammation
Steroid pulse therapy
Journal
Brain & development
ISSN: 1872-7131
Titre abrégé: Brain Dev
Pays: Netherlands
ID NLM: 7909235
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
19
05
2019
revised:
10
07
2019
accepted:
29
07
2019
pubmed:
29
8
2019
medline:
2
6
2020
entrez:
29
8
2019
Statut:
ppublish
Résumé
Alexander disease (AxD) is a rare fatal leukodystrophy caused by a dominant missense mutation in the glial fibrillary acidic protein. In a mouse model of AxD, the pathological astrocyte causes a pronounced immune response. The inflammatory environment in the brain might play an important role in the neuronal dysfunction of AxD. A 3-month-old girl diagnosed with infantile AxD presented with severe intractable seizures and a deteriorated neurological state. Steroid pulse therapy was effective at preventing the epileptic activity and progressive white matter abnormalities on magnetic resonance images, but the effect was temporary. Levels of interleukin (IL)-6, IL-8, and macrophage chemotactic protein 1 (MCP-1) in the cerebrospinal fluid were high at onset and reduced transiently after steroid pulse therapy. These results suggest that inflammatory responses of astrocyte and microglia can contribute to the neuropathology of AxD. Robust immunomodulation that targets activated astrocytes and microglia may be a novel therapeutic strategy to improve neurological prognosis in AxD.
Sections du résumé
BACKGROUND
BACKGROUND
Alexander disease (AxD) is a rare fatal leukodystrophy caused by a dominant missense mutation in the glial fibrillary acidic protein. In a mouse model of AxD, the pathological astrocyte causes a pronounced immune response. The inflammatory environment in the brain might play an important role in the neuronal dysfunction of AxD.
CASE
METHODS
A 3-month-old girl diagnosed with infantile AxD presented with severe intractable seizures and a deteriorated neurological state. Steroid pulse therapy was effective at preventing the epileptic activity and progressive white matter abnormalities on magnetic resonance images, but the effect was temporary. Levels of interleukin (IL)-6, IL-8, and macrophage chemotactic protein 1 (MCP-1) in the cerebrospinal fluid were high at onset and reduced transiently after steroid pulse therapy.
DISCUSSION
CONCLUSIONS
These results suggest that inflammatory responses of astrocyte and microglia can contribute to the neuropathology of AxD. Robust immunomodulation that targets activated astrocytes and microglia may be a novel therapeutic strategy to improve neurological prognosis in AxD.
Identifiants
pubmed: 31455510
pii: S0387-7604(19)30299-2
doi: 10.1016/j.braindev.2019.07.010
pii:
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Anti-Inflammatory Agents
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-68Informations de copyright
Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.