Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1.
BACKGROUND
Cognitive impairment is the most common complication of neurofibromatosis type 1 (NF1) in childhood. Current research suggests a strong relationship between cognitive deficits and brain T2-hyperintensities. The majority of these lesions disappear as the child ages. Cross-sectional data suggest that there also are improvements in intellect.


OBJECTIVE
To determine the natural history of cognitive functioning and MRI T2-hyperintensities from childhood into adulthood, and whether changes in MRI T2-hyperintensities over time are predictive of changes in cognitive functioning.


METHODS
The authors conducted a prospective longitudinal study of a cohort of 32 patients with NF1 and 11 unaffected sibling controls. All patients underwent neuropsychological assessments and 27 children underwent MRI examinations. The patients were then reassessed after an 8-year period.


RESULTS
and


CONCLUSIONS
There was no improvement in cognitive ability as the children with NF1 developed into adulthood compared with controls. Despite significant decreases in the number, size, and intensity of the T2-hyperintensities over the 8-year period, these changes were not associated with changes in cognitive ability. T2-hyperintensities in the cortex or subcortical or deep white matter are more frequent with age and these lesions are likely to have a different pathology than basal ganglia lesions. The best predictor of cognitive dysfunction in adulthood was the presence of T2-hyperintensities in childhood, rather than current lesion status. There is a limited time window (<18 years) in which the presence of T2-hyperintensities can be used as biologic markers of cognitive dysfunction.
Hyman
S L
SL
Neurogenetics Research Unit, The Children's Hospital at Westmead (Royal Alexandra Hospital for Children), NSW, Sydney, Australia.
Gill
D S
DS
Shores
E A
EA
Steinberg
A
A
Joy
P
P
Gibikote
S V
SV
North
K N
KN
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D001315:Australia / Q000453:epidemiology; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D018450:Disease Progression; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D006801:Humans; D007361:Intelligence Tests / Q000706:statistics & numerical data; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009456:Neurofibromatosis 1 / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011446:Prospective Studies; D035781:Siblings; D013997:Time Factors
D019786:Gadolinium DTPA