Multisite Study of Evoked Potentials in Rett Syndrome.


Saby JN(1), Benke TA(2), Peters SU(3), Standridge SM(4), Matsuzaki J(1), Cutri-French C(5), Swanson LC(6), Lieberman DN(6), Key AP(7), Percy AK(8), Neul JL(3), Nelson CA(9)(10), Roberts TPL(1), Marsh ED(5).
Author information:
(1)Division of Radiology Research, Children's Hospital of Philadelphia, Philadelphia, PA.
(2)Department of Pediatrics, Neurology, Pharmacology and Otolaryngology, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
(3)Department of Pediatrics, Vanderbilt University Medical Center, Vanderbilt Kennedy Center, Nashville, TN.
(4)Cincinnati Children's Hospital Medical Center, Division of Neurology and University of Cincinnati College of Medicine, Cincinnati, OH.
(5)Division of Child Neurology, Children's Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
(6)Department of Neurology, Boston Children's Hospital, Boston, MA.
(7)Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, Vanderbilt Kennedy Center, Nashville, TN.
(8)Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
(9)Laboratories of Cognitive Neuroscience, Boston Children's Hospital, Boston, MA.
(10)Department of Pediatrics, Harvard Medical School, Boston, MA.


OBJECTIVE: The aim of the current study was to evaluate the utility of evoked potentials as a biomarker of cortical function in Rett syndrome (RTT). As a number of disease-modifying therapeutics are currently under development, there is a pressing need for biomarkers to objectively and precisely assess the effectiveness of these treatments. METHOD: Yearly visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were acquired from individuals with RTT, aged 2 to 37 years, and control participants across 5 sites as part of the Rett Syndrome and Related Disorders Natural History Study. Baseline and year 1 data, when available, were analyzed and the repeatability of the results was tested. Two syndrome-specific measures from the Natural History Study were used for evaluating the clinical relevance of the VEP and AEP parameters. RESULTS: At the baseline study, group level comparisons revealed reduced VEP and AEP amplitude in RTT compared to control participants. Further analyses within the RTT group indicated that this reduction was associated with RTT-related symptoms, with greater severity associated with lower VEP and AEP amplitude. In participants with RTT, VEP and AEP amplitude was also negatively associated with age. Year 1 follow-up data analyses yielded similar findings and evidence of repeatability of EPs at the individual level. INTERPRETATION: The present findings indicate the promise of evoked potentials (EPs) as an objective measure of disease severity in individuals with RTT. Our multisite approach demonstrates potential research and clinical applications to provide unbiased assessment of disease staging, prognosis, and response to therapy. ANN NEUROL 2021;89:790-802.