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Natural History of Vanishing White Matter
Author(s) -
Hamilton Eline M. C.,
van der Lei Hannemieke D. W.,
Vermeulen Gerre,
Gerver Jan A. M.,
Lourenço Charles M.,
Naidu Sakkubai,
Mierzewska Hanna,
Gemke Reinoud J. B. J.,
de Vet Henrica C. W.,
Uitdehaag Bernard M. J.,
LissenbergWitte Birgit I.,
van der Knaap Marjo S.
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25287
Subject(s) - natural history , age of onset , medicine , disease , pediatrics , natural history study , proportional hazards model , white matter , family history , magnetic resonance imaging , radiology
Objective To comprehensively describe the natural history of vanishing white matter (VWM), aiming at improving counseling of patients/families and providing natural history data for future therapeutic trials. Methods We performed a longitudinal multicenter study among 296 genetically confirmed VWM patients. Clinical information was obtained via disease‐specific clinical questionnaire, Health Utilities Index and Guy's Neurological Disability Scale assessments, and chart review. Results First disease signs occurred at a median age of 3 years (mode = 2 years, range = before birth to 54 years); 60% of patients were symptomatic before the age of 4 years. The nature of the first signs varied for different ages of onset. Overall, motor problems were the most common presenting sign, especially in children. Adolescent and adult onset patients were more likely to exhibit cognitive problems early after disease onset. One hundred two patients were deceased. Multivariate Cox regression analysis revealed a positive relation between age at onset and both preservation of ambulation and survival. Absence of stress‐provoked episodes and absence of seizures predicted more favorable outcome. In patients with onset before 4 years, earlier onset was associated with more severe disability and higher mortality. For onset from 4 years on, disease course was generally milder, with a wide variation in severity. There were no significant differences for sex or for the 5 eIF2B gene groups. The results confirm the presence of a genotype–phenotype correlation. Interpretation The VWM disease spectrum consists of a continuum with extremely wide variability. Age at onset is a strong predictor for disease course. Ann Neurol 2018;84:274–288