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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.
Keywords
QUALITY-OF-LIFE, ONSET EIF2B-RELATED DISORDERS, INITIATION-FACTOR EIF2B, INDEX MARK 3, HEALTH-STATUS, MULTIPLE-SCLEROSIS, LONG-TERM, CACH/VWM SYNDROME, CEREBRAL-PALSY, LEUKOENCEPHALOPATHY

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Citation

Please use this url to cite or link to this publication:

MLA
Hamilton, Eline MC et al. “Natural History of Vanishing White Matter.” ANNALS OF NEUROLOGY 84.2 (2018): 274–288. Print.
APA
Hamilton, E. M., van der Lei, H. D., Vermeulen, G., Gerver, J. A., Lourenço, C. M., Naidu, S., Mierzewska, H., et al. (2018). Natural history of vanishing white matter. ANNALS OF NEUROLOGY, 84(2), 274–288.
Chicago author-date
Hamilton, Eline MC, Hannemieke DW van der Lei, Gerre Vermeulen, Jan AM Gerver, Charles M Lourenço, Sakkubai Naidu, Hanna Mierzewska, et al. 2018. “Natural History of Vanishing White Matter.” Annals of Neurology 84 (2): 274–288.
Chicago author-date (all authors)
Hamilton, Eline MC, Hannemieke DW van der Lei, Gerre Vermeulen, Jan AM Gerver, Charles M Lourenço, Sakkubai Naidu, Hanna Mierzewska, Reinoud JBJ Gemke, Henrica CW de Vet, Bernard MJ Uitdehaag, Birgit I Lissenberg-Witte, Marjo S van der Knaap, the VWM Research Group, M Maes, and Rudy Van Coster. 2018. “Natural History of Vanishing White Matter.” Annals of Neurology 84 (2): 274–288.
Vancouver
1.
Hamilton EM, van der Lei HD, Vermeulen G, Gerver JA, Lourenço CM, Naidu S, et al. Natural history of vanishing white matter. ANNALS OF NEUROLOGY. 2018;84(2):274–88.
IEEE
[1]
E. M. Hamilton et al., “Natural history of vanishing white matter,” ANNALS OF NEUROLOGY, vol. 84, no. 2, pp. 274–288, 2018.
@article{8618021,
  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.},
  author       = {Hamilton, Eline MC and van der Lei, Hannemieke DW and Vermeulen, Gerre and Gerver, Jan AM and Lourenço, Charles M and Naidu, Sakkubai and Mierzewska, Hanna and Gemke, Reinoud JBJ and de Vet, Henrica CW and Uitdehaag, Bernard MJ and Lissenberg-Witte, Birgit I and van der Knaap, Marjo S and VWM Research Group, the and Maes, M and Van Coster, Rudy},
  issn         = {0364-5134},
  journal      = {ANNALS OF NEUROLOGY},
  keywords     = {QUALITY-OF-LIFE,ONSET EIF2B-RELATED DISORDERS,INITIATION-FACTOR EIF2B,INDEX MARK 3,HEALTH-STATUS,MULTIPLE-SCLEROSIS,LONG-TERM,CACH/VWM SYNDROME,CEREBRAL-PALSY,LEUKOENCEPHALOPATHY},
  language     = {eng},
  number       = {2},
  pages        = {274--288},
  title        = {Natural history of vanishing white matter},
  url          = {http://dx.doi.org/10.1002/ana.25287},
  volume       = {84},
  year         = {2018},
}

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