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@ARTICLE{vanVoorst:282299,
author = {van Voorst, Romy J and Schoenmakers, Daphne H and
Bonkowsky, Joshua L and Vanderver, Adeline and
Krägeloh-Mann, Ingeborg and Bernard, Geneviève and
Bertini, Enrico and Fatemi, Ali and Sgobbi, Paulo V and
Wolf, Nicole I and Groeschel, Samuel and Tonduti, Davide and
Sevin, Caroline and Orthmann-Murphy, Jennifer L and Schöls,
Ludger and Salsano, Ettore and Brais, Bernard and Jaffe,
Nicole and Ter Horst, Kasper W and Hannema, Sabine E and
Hayes, Katherine G and Meyburg, Jochen and van Heerde, Marc
and Sbrocchi, Anne Marie and van Spaendonk, Rosalina and
Thiffault, Isabelle and Hofsteenge, Geesje H and
Sudmeier-Broek, Carolina and Timmer, Corrie and Skwirut,
Donna and Buck, Allyson and Hollberg, Bret and Chapleau, Ron
and Dekker, Hanka and Campbell, Susan G and Abbink, Truus E
M and Leferink, Prisca S and van der Knaap, Marjo S},
title = {{C}onsensus-{B}ased {E}xpert {R}ecommendations for
{D}iagnosis and {C}linical {M}anagement of {V}anishing
{W}hite {M}atter.},
journal = {Neurology},
volume = {105},
number = {11},
issn = {0028-3878},
address = {Philadelphia, Pa.},
publisher = {Wolters Kluwer},
reportid = {DZNE-2025-01269},
pages = {e214320},
year = {2025},
abstract = {Vanishing white matter (VWM) is a rare disorder,
characterized by degeneration of CNS white matter,
clinically often exacerbated by stressors such as fever and
minor head trauma. VWM is caused by biallelic pathogenic
variants in the EIF2B1-5 genes, causing reduced activity of
eukaryotic initiation of translation factor 2B, resulting in
dysregulation of the integrated stress response (ISR). New
scientific insights and increased clinical trials in
experimental therapies highlight the need for clinical
guidelines to improve and standardize care for patients with
VWM worldwide. Standardized care is important for therapy
development, as it lessens clinical variability of trial
participants at study entry, enabling more sensitive
evaluation of treatment outcomes. The aim of this study was
to develop expert consensus-based recommendations for
diagnosis and management of VWM. A real-time Delphi process
with a multidisciplinary expert panel was conducted to
formulate consensus-based recommendations. A literature
review was performed to determine the strength of available
evidence supporting each recommendation. The consensus
yielded 43 recommendations on diagnosis, including genetic
and MRI criteria, and on clinical management concerning
disease progression, acute and long-term care, and
preventive strategies. All known pathogenic and likely
pathogenic EIF2B1-5 variants were identified from the
literature and Amsterdam Leukodystrophy Center laboratory.
An overview of these EIF2B1-5 variants was composed to
facilitate diagnosis. Clinically used drugs may activate the
ISR, posing a risk in VWM, or have no effect on or suppress
the ISR, being probably safe in VWM. A second literature
search explored the effects of clinically frequently used
drugs on the ISR. Drugs were categorized into those likely
to activate the ISR, suppress it, and have no likely effects
on the ISR. Final judgment was achieved in a consensus
meeting of experts. A patient management card was developed
with input from clinical experts and patient advocates to
provide information on these consensus-based recommendations
in lay language and bridge the gap between scientific
evidence and expert opinion on one side and the practical
needs of clinicians and families on the other side. This
study contributes to improving and standardizing VWM care
based on scientific and expert insights, while highlighting
key areas for future research.},
subtyp = {Review Article},
keywords = {Humans / Leukoencephalopathies: therapy /
Leukoencephalopathies: diagnosis / Leukoencephalopathies:
genetics / Consensus / Disease Management / Delphi Technique
/ Eukaryotic Initiation Factor-2B: genetics / Magnetic
Resonance Imaging / White Matter: diagnostic imaging /
Eukaryotic Initiation Factor-2B (NLM Chemicals)},
cin = {AG Schöls},
ddc = {610},
cid = {I:(DE-2719)5000005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41232062},
pmc = {pmc:PMC12615013},
doi = {10.1212/WNL.0000000000214320},
url = {https://pub.dzne.de/record/282299},
}