VEP, AEP may objectively measure Rett syndrome severity
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Visual and auditory evoked potentials showed promise as an objective measurement of Rett syndrome severity, according to a study published in Annals of Neurology.
“Currently, no disease modifying treatments exist for [Rett syndrome (RTT)],” Joni N. Saby, PhD, of the division of radiology research at Children’s Hospital of Philadelphia, and colleagues wrote. “Fortunately, many new therapeutics are being developed and tested at the preclinical level, and a few have made it to clinical trials (eg, NCT04181723 and NCT03758924). With novel treatments on the horizon, the identification and validation of central nervous system biomarkers in RTT will be useful to assess objectively both early treatment responsiveness and, ultimately, therapeutic efficacy.”
Saby and colleagues evaluated baseline evoked potentials (EPs) in patients 2 to 37 years old with and without RTT across five hospitals and medical centers. At 1 year following enrollment, they had complete data for 17 visual EP (VEP) participants and 21 auditory EP (AEP) participants.
Investigators had to make comparisons between the RTT group and the typically developing control group at baseline because only three of 24 individuals in the control group had complete data at 1 year.
While assessing VEP at baseline, RTT participants showed significantly lower N1 (U = 229; P < .001), N1–P1 (U = 170; P < .001) and P1–N2 (U = 199; P < .001) amplitudes than control participants. Further, baseline N1-P1 and P1-N2 amplitudes decreased with age in RTT participants, but there was no such association in TD participants.
Greater RTT severity was associated with lower amplitudes of N1 (clinical severity score [CSS], P = .022; motor-behavioral assessment [MBA], P = .035) and N1–P1 (CSS, P = .01; MBA, P = .008), which was evident at baseline and 1 year.
Baseline observation of AEP showed the RTT cohort had significantly lower amplitudes of P1-N1 (U = 386; P = .03) and N1–P2 (U = 351; P = .01) than the TD cohort. But P1 and AEP latency did not differ between RTT and control participants.
At baseline, P1, N1 and P2 latency significantly decreased with age in both the RTT and control groups with age. Greater RTT severity was associated with lower AEP amplitude, which was consistent between baseline and 1 year.
“Although RTT is not a degenerative condition, the severity of RTT-related symptoms tends to increase with age,” Saby and colleagues wrote. “The finding that VEP and AEP amplitudes decline with age in RTT suggests that these measures may reflect a progressive aspect of the disease process in addition to correlating with interindividual differences in disease severity.”
Although this was the first study to determine a connection between EPs and RTT severity, the researchers identified limitations including eye tracking at only one location, effect of attentiveness and cross-site variability of EP latency and amplitude. Saby and colleagues suggested future research should amend these faults and further examine the role of EPs in RTT.
“In order for EPs to be useful in the context of clinical trials, future work needs to (1) determine if EPs in RTT are responsive to treatment, (2) establish the criteria for which EPs in RTT are most reproducible, (3) further characterize how EPs in RTT change overtime in a given participant and (4) determine which component/combination of components is most suitable as a biomarker,” they wrote.
Perspective
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We eye care providers seem to be afraid of embracing electrophysiology. Whether it’s the widespread use of spectral-domain OCT or the resource- and time-consuming nature of the tests or the relatively-rare clinical need for them, we have relegated them to the corner of the imaging room. If we have the machines at all, they tend to be used only at tertiary referral centers. However, this technology is becoming more accessible, and at the same time research (like this article) is coming out on how useful electrophysiology can be in certain cases.
This article gives me hope for two reasons. One, ocular electrophysiology is starting to have a more practical and clinically relevant reason for existence. Second – and much more importantly – new therapeutics are in clinical trials to help manage Rett syndrome, a rare but severely-impairing disorder (with an unfortunate eponym in my opinion).
If you practice in a medical center in an area that doesn’t have ocular electrophysiology, then perhaps this article can serve as an inspiration to you. Perhaps it might be you who facilitates the acquisition of this technology in your eye clinic. Perhaps it might be you who studies the research, you who becomes trained in it, you who introduces yourself to neurology specialists and genetic disorder specialists in your area.
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