Evoked Potentials and EEG Analysis in Rett Syndrome and Related Developmental Encephalopathies: Towards a Biomarker for Translational Research

Joni N Saby, Sarika U Peters, Timothy P L Roberts, Charles A Nelson, Eric D Marsh, Joni N Saby, Sarika U Peters, Timothy P L Roberts, Charles A Nelson, Eric D Marsh

Abstract

Rett syndrome is a debilitating neurodevelopmental disorder for which no disease-modifying treatment is available. Fortunately, advances in our understanding of the genetics and pathophysiology of Rett syndrome has led to the development of promising new therapeutics for the condition. Several of these therapeutics are currently being tested in clinical trials with others likely to progress to clinical trials in the coming years. The failure of recent clinical trials for Rett syndrome and other neurodevelopmental disorders has highlighted the need for electrophysiological or other objective biological markers of treatment response to support the success of clinical trials moving forward. The purpose of this review is to describe the existing studies of electroencephalography (EEG) and evoked potentials (EPs) in Rett syndrome and discuss the open questions that must be addressed before the field can adopt these measures as surrogate endpoints in clinical trials. In addition to summarizing the human work on Rett syndrome, we also describe relevant studies with animal models and the limited research that has been carried out on Rett-related disorders, particularly methyl-CpG binding protein 2 (MECP2) duplication syndrome, CDKL5 deficiency disorder, and FOXG1 disorder.

Keywords: EEG; Rett syndrome; biomarker; developmental encephalopathy; evoked potential.

Copyright © 2020 Saby, Peters, Roberts, Nelson and Marsh.

Figures

Figure 1
Figure 1
Example of visual and auditory evoked potential (AEP) waveforms and head locations. Sample (unpublished) auditory and visual evoked potentials (AEPs/VEPs) from a 16-year-old individual with Rett syndrome (dotted line) and an age-matched typically developing (TD) control (solid line) The primary positive (P) and negative (N) components are indicated. The schematic on the left shows the location of the electrodes used for the auditory (Cz) and visual (Oz) responses. The auditory response was elicited using a 500 Hz tone. The visual response was elicited using a reversing checkerboard. Negativity is plotted up.

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