Visual evoked potentials detect cortical processing deficits in Rett syndrome.
OBJECTIVE
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation of the X-linked MECP2 gene and characterized by developmental regression during the first few years of life. The objective of this study was to investigate if the visual evoked potential (VEP) could be used as an unbiased, quantitative biomarker to monitor brain function in RTT.


METHODS
We recorded pattern-reversal VEPs in Mecp2 heterozygous female mice and 34 girls with RTT. The amplitudes and latencies of VEP waveform components were quantified, and were related to disease stage, clinical severity, and MECP2 mutation type in patients. Visual acuity was also assessed in both mice and patients by modulating the spatial frequency of the stimuli.


RESULTS
Mecp2 heterozygous female mice and RTT patients exhibited a similar decrease in VEP amplitude that was most striking in the later stages of the disorder. RTT patients also displayed a slower recovery from the principal peak of the VEP response that was impacted by MECP2 mutation type. When the spatial frequency of the stimulus was increased, both patients and mice displayed a deficit in discriminating smaller patterns, indicating lower visual spatial acuity in RTT.


CONCLUSIONS
VEP is a method that can be used to assess brain function across species and in children with severe disabilities like RTT. Our findings support the introduction of standardized VEP analysis in clinical and research settings to probe the neurobiological mechanism underlying functional impairment and to longitudinally monitor progression of the disorder and response to treatment.
Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Boston.|F. M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Boston.|Harvard Medical School, Boston.
Jocelyn J
JJ
LeBlanc
Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Boston.
Geneva
G
DeGregorio
F. M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Boston.
Eleonora
E
Centofante
Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Boston.
Vanessa K
VK
Vogel-Farley
Rett Syndrome Program, Department of Neurology, Boston Children's Hospital, Boston.
Katherine
K
Barnes
Harvard Medical School, Boston.|Rett Syndrome Program, Department of Neurology, Boston Children's Hospital, Boston.
Walter E
WE
Kaufmann
F. M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Boston.|Harvard Medical School, Boston.
Michela
M
Fagiolini
Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Boston.|Harvard Medical School, Boston.|Harvard Graduate School of Education, Cambridge, MA.
Charles A
CA
Nelson
D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D010775:Photic Stimulation; D015518:Rett Syndrome / Q000503:physiopathology*; D014792:Visual Acuity; D014793:Visual Cortex / Q000503:physiopathology*
D015415:Biomarkers; C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2