Detection of neurophysiological features in female R255X MeCP2 mutation mice

Dong, Hong‐Wei; Erickson, Kirsty R; Lee, Jessica R.; Merritt, Jonathan K; Fu, Changlin; Neul, Jeffrey L.

doi:10.1016/j.nbd.2020.105083

Cited by 14 publications

(18 citation statements)

References 55 publications

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“…The finding that visual and auditory EPs are attenuated in RTT and that the extent of this change is related to clinical severity, points to the potential utility of EP amplitude as a biomarker of brain function in this group. Research at the preclinical level has reported similar abnormalities in the VEP and AEP in animal models of the condition 12,25–28 and has identified potential mechanisms underlying the attenuation of the responses for reviews, see refs. 29 and 30.…”

Section: Discussionmentioning

confidence: 94%

Multisite Study of Evoked Potentials in Rett Syndrome

Saby

Benke

Peters

et al. 2021

Annals of Neurology

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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

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Section: Discussionmentioning

confidence: 94%

Multisite Study of Evoked Potentials in Rett Syndrome

Saby

Benke

Peters

et al. 2021

Annals of Neurology

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“…No time limitations or study design restrictions were applied. Studies would be excluded if on animal research ( 32 – 46 ) or if participants were RTT individuals with other central nervous system complications (e.g., neurofibroma) ( 47 ) or sleep intervention [e.g., PSG data from RTT cases after adeno(tonsil)ectomy surgery (A&T) history].…”

Section: Methodsmentioning

confidence: 99%

A meta-review of standard polysomnography parameters in Rett Syndrome

Zhang

Spruyt²

2022

Front. Neurol.

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Rett Syndrome (RTT, OMIM 312750), a unique rare neurodevelopmental disorder, mostly affects females and causes severe multi-disabilities including poor sleep. This meta-analysis systematically reviewed the polysomnographic (PSG) data of individuals with RTT on both sleep macrostructure and sleep respiratory indexes and compared them to literature normative values. Studies were collected from PubMed, Web of Science, PsycINFO, Ebsco, Scopus, and Cochrane Library till 26 April 2022. Across 13 included studies, the 134 selected RTT cases were mostly females being MECP2 (n = 41) and CDKL5 (n = 4) positive. They were further stratified by gene, age, and clinical features. Findings of comparison with literature normative values suggested shorter total sleep time (TST) and sleep onset latency (SOL), twice as long wake after sleep onset (WASO) with lower sleep efficiency (SEI) in RTT, as well as increased non-rapid eye movement stage 3 (stage N3) and decreased rapid eye movement sleep. Based on limited data per stratifications, we found in RTT cases <5 years old lower stage N3, and in RTT cases >5 years old less WASO and more WASO in the epileptic strata. However, meta-results generated from studies designed with comparison groups only showed lower stage N1 in RTT than in healthy comparison, together with similar SEI and stage N3 to primary snoring subjects. For sleep respiratory indexes, severe disordered sleep breathing was confirmed across roughly all RTT strata. We are the first study to meta-analyze PSG data of subjects with RTT, illustrating shorter TST and aberrant sleep staging in RTT that may vary with age or the presence of epilepsy. Severe nocturnal hypoxemia with apneic events was also demonstrated. More studies are needed to explore and elucidate the pathophysiological mechanisms of these sleep findings in the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198099, identifier: CRD 42020198099.

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“…EMG activity and simultaneous video recordings were used to determine wake (continuous movement) or sleep (prolonged periods of no movement). All recorded EEG/EMG will be scored as 10 second epochs of awake (low EEG amplitudes with large EMG amplitudes), NREM sleep (high EEG amplitudes and dominant frequency <4 Hz), or REM sleep (uniform EEG waveforms and dominant theta frequency 6-10 Hz) (Andrillon et al, 2011;Campbell, 2009;Dong et al, 2020;Kent et al, 2018;Paul et al, 2006) by a blinded person. For transition epochs containing both wake and sleep states, we defined a state duration >5 seconds as dominant.…”

Section: Methodsmentioning

confidence: 99%

Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome

Catron

Howe

Besing

et al. 2022

Preprint

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Sleep is the brain state when cortical activity decreases and memory consolidates. However, in human epileptic patients, including genetic epileptic seizures such as Dravet syndrome, sleep is the preferential period when epileptic spike-wave discharges (SWDs) appear, with more severe epileptic symptoms in female patients than male patients, which influencing patient sleep quality and memory. Currently, seizure onset mechanisms during sleep period still remain unknown. Our previous work has shown that the sleep-like state-dependent synaptic potentiation mechanism can trigger epileptic SWDs (Zhang et al., 2021). In this study, using one heterozygous (het) knock-in (KI) transgenic mice (GABAA receptor γ2 subunit Gabrg2Q390X mutation) and an optogenetic method, we hypothesized that slow-wave oscillations (SWOs) themselves in vivo could trigger epileptic seizures. We found that epileptic SWDs in het Gabrg2+/Q390X KI mice exhibited preferential incidence during NREM sleep period, accompanied by motor immobility/ facial myoclonus/vibrissal twitching, with more frequent incidence in female het KI mice than male het KI mice. Optogenetic induced SWOs in vivo significantly increased epileptic seizure incidence in het Gabrg2+/Q390X KI mice with increased duration of NREM sleep or quiet-wakeful states. Furthermore, suppression of SWO-related homeostatic synaptic potentiation by 4-(diethylamino)-benzaldehyde (DEAB) injection (i.p.) greatly decreased seizure incidence in het KI mice, suggesting that SWOs did trigger seizure activity in het KI mice. In addition, EEG delta-frequency (0.1-4 Hz) power spectral density during NREM sleep was significantly larger in female het Gabrg2+/Q390X KI mice than male het Gabrg2+/Q390X KI mice, which likely contributes to the gender difference in seizure incidence during NREM sleep/quiet-wake as that in human patients.

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Detection of neurophysiological features in female R255X MeCP2 mutation mice

Cited by 14 publications

References 55 publications

Multisite Study of Evoked Potentials in Rett Syndrome

Multisite Study of Evoked Potentials in Rett Syndrome

A meta-review of standard polysomnography parameters in Rett Syndrome

Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome

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