John Rosendahl Østergaard

Natural History of Vanishing White Matter

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  • ana.25287

    Final published version, 1.08 MB, PDF document

DOI

  • Eline M C Hamilton, Department of Child Neurology and Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
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  • Hannemieke D W van der Lei, Department of Child Neurology and Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
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  • Gerre Vermeulen, Department of Child Neurology and Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
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  • Jan A M Gerver, Department of Child Neurology and Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
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  • Charles M Lourenço, Clinics Hospital of Ribeirão Preto, University of São Paulo, São Paulo, Brasil.
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  • Sakkubai Naidu, Department of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
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  • Hanna Mierzewska, Department of Child and Adolescent Neurology, Institute of Mother and Child, Warsaw, Poland.
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  • Reinoud J B J Gemke, Department of Pediatrics, VU University Medical Center Amsterdam, and Dutch Childhood Oncology Group, The Hague, The Netherlands.
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  • Henrica C W de Vet, Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
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  • Bernard M J Uitdehaag, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
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  • Birgit I Lissenberg-Witte, Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
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  • Marjo S van der Knaap, Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.
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  • VWM Research Group
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  • John Rosendahl Østergaard (Member of author collaboration)

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
JournalAnnals of Neurology
Volume84
Issue2
Pages (from-to)274-288
Number of pages15
ISSN0364-5134
DOIs
Publication statusPublished - Aug 2018

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