Hamilton EMC, van der Lei HDW, Vermeulen G, Gerver JAM,
Lourenço CM, Naidu S, Mierzewska H, Gemke RJBJ, de Vet HCW, Uitdehaag BMJ,
Lissenberg-Witte BI, Research Group V, van der Knaap MS. Natural History of Vanishing
White Matter. Ann Neurol. 2018 Aug;84(2):274-288.
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.
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