Development of a neurologic severity scale for Aicardi Goutières Syndrome.
Genetic
Interferonopathy
Leukodystrophy
Neurodegenerative
Outcome measure
Journal
Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
18
02
2020
revised:
29
03
2020
accepted:
30
03
2020
pubmed:
14
4
2020
medline:
7
4
2021
entrez:
14
4
2020
Statut:
ppublish
Résumé
Aicardi Goutières Syndrome (AGS) is a severe, autoinflammatory leukodystrophy characterized by global neurologic dysfunction. Our goal was to create an easy-to-apply scale relevant to the unique developmental challenges associated with AGS. All individuals were recruited through our natural history study. Individuals were classified by AGS severity as mild, moderate, or severe, and clinical encounters were assigned a composite score for neurologic function calculated from the sum of three functional classification scales. Through expert consensus, we identified 11 key items to reflect the severity of AGS across gross motor, fine motor, and cognitive skills to create the AGS Scale. There was strong interrater reliability. The AGS scale was applied across available medical records to evaluate neurologic function over time. The AGS scale was compared to performance on a standard measure of gross motor function (Gross Motor Function Measure-88, GMFM-88) and a putative diagnostic biomarker of disease, the interferon signaling gene expression score (ISG). The AGS scale score correlated with severity classifications and the composite neurologic function scores. When retrospectively applied across our natural history study, the majority of individuals demonstrated an initial decline in function followed by stable scores. Within the first 6 months of disease, the AGS score was the most dynamic. The AGS scale correlated with performance by the GMFM-88, but did not correlate with ISG levels. This study demonstrates the utility of the AGS scale as a multimodal tool for the assessment of neurologic function in AGS. The AGS scale correlates with clinical severity and with a more labor-intensive tool, GMFM-88. This study underscores the limitations of the ISG score as a marker of disease severity. With the AGS scale, we found that AGS neurologic severity is the most dynamic early in disease. This novel AGS scale is a promising tool to longitudinally follow neurologic function in this unique population.
Sections du résumé
BACKGROUND AND PURPOSE
Aicardi Goutières Syndrome (AGS) is a severe, autoinflammatory leukodystrophy characterized by global neurologic dysfunction. Our goal was to create an easy-to-apply scale relevant to the unique developmental challenges associated with AGS.
METHODS
All individuals were recruited through our natural history study. Individuals were classified by AGS severity as mild, moderate, or severe, and clinical encounters were assigned a composite score for neurologic function calculated from the sum of three functional classification scales. Through expert consensus, we identified 11 key items to reflect the severity of AGS across gross motor, fine motor, and cognitive skills to create the AGS Scale. There was strong interrater reliability. The AGS scale was applied across available medical records to evaluate neurologic function over time. The AGS scale was compared to performance on a standard measure of gross motor function (Gross Motor Function Measure-88, GMFM-88) and a putative diagnostic biomarker of disease, the interferon signaling gene expression score (ISG).
RESULTS
The AGS scale score correlated with severity classifications and the composite neurologic function scores. When retrospectively applied across our natural history study, the majority of individuals demonstrated an initial decline in function followed by stable scores. Within the first 6 months of disease, the AGS score was the most dynamic. The AGS scale correlated with performance by the GMFM-88, but did not correlate with ISG levels.
CONCLUSIONS
This study demonstrates the utility of the AGS scale as a multimodal tool for the assessment of neurologic function in AGS. The AGS scale correlates with clinical severity and with a more labor-intensive tool, GMFM-88. This study underscores the limitations of the ISG score as a marker of disease severity. With the AGS scale, we found that AGS neurologic severity is the most dynamic early in disease. This novel AGS scale is a promising tool to longitudinally follow neurologic function in this unique population.
Identifiants
pubmed: 32279991
pii: S1096-7192(20)30082-2
doi: 10.1016/j.ymgme.2020.03.008
pmc: PMC7366613
mid: NIHMS1608143
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
153-160Subventions
Organisme : NCATS NIH HHS
ID : 1 U54TR002823-01
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001879
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS115052
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS114113
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS106845
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
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