Natural History of Vanishing White Matter

Eline M.C. Hamilton, Hannemieke D.W. van der Lei, Gerre Vermeulen, Jan A.M. Gerver, Charles M. Lourenço, Sakkubai Naidu, Hanna Mierzewska, Reinoud J.B.J. Gemke, Henrica C.W. de Vet, Bernard M.J. Uitdehaag, Birgit I. Lissenberg-Witte, V. W.M. Research Group, Marjo S. van der Knaap*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)274-288
Number of pages15
JournalAnnals of Neurology
Volume84
Issue number2
Early online date26 Jul 2018
DOIs
Publication statusPublished - Aug 2018

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Hamilton, E. M. C., van der Lei, H. D. W., Vermeulen, G., Gerver, J. A. M., Lourenço, C. M., Naidu, S., ... van der Knaap, M. S. (2018). Natural History of Vanishing White Matter. Annals of Neurology, 84(2), 274-288. https://doi.org/10.1002/ana.25287