A Psychometric Evaluation of the Motor-Behavioral Assessment Scale for Use as an Outcome Measure in Rett Syndrome Clinical Trials

Raspa, Melissa; Bann, Carla; Gwaltney, Angela; Benke, Timothy A.; Fu, Changlin; Glaze, Daniel G.; Haas, Richard; Heydemann, Peter; Jones, Mary; Kaufmann, Walter E.; Lieberman, David N.; Marsh, Eric D.; Peters, Sarika U.; Ryther, Robin; Standridge, Shannon; Skinner, Steven A.; Percy, Alan K.; Neul, Jeffrey L.

doi:10.1352/1944-7558-125.6.493

Cited by 33 publications

(23 citation statements)

References 35 publications

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“…Two clinician-completed assessments were used to estimate overall severity: the Clinical Severity Score (CSS) 27 , 28 and the Motor-Behavioral Assessment (MBA). 28 , 29 These assessments were created for Rett syndrome, but account for many symptoms of CDD including epilepsy and motor, cognitive and autonomic disturbances. The CSS has 13 items with a maximum score of 58.…”

Section: Methodsmentioning

confidence: 99%

Electrophysiological biomarkers of brain function in CDKL5 deficiency disorder

Saby

Mulcahey

Zavez

et al. 2022

Brain Communications

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CDKL5 deficiency disorder is a debilitating developmental and epileptic encephalopathy for which no targeted treatment exists. A number of promising therapeutics are under development for CDKL5 deficiency disorder but a lack of validated biomarkers of brain function and clinical severity may limit the ability to objectively assess the efficacy of new treatments as they become available. To address this need, the current study quantified electrophysiological measures in individuals with CDKL5 deficiency disorder and the association between these parameters and clinical severity. Visual and auditory evoked potentials, as well as resting EEG, were acquired across five clinical sites from 26 individuals with CDKL5 deficiency disorder. Evoked potential and quantitative EEG features were calculated and compared to typically developing individuals in an age- and sex-matched cohort. Baseline and Year 1 data, when available, were analyzed and the repeatability of the results was tested. Two clinician-completed severity scales were used for evaluating the clinical relevance of the electrophysiological parameters. Group-level comparisons revealed reduced visual evoked potential amplitude in CDKL5 deficiency disorder individuals versus typically-developing individuals. There were no group differences in the latency of the visual evoked potentials or in the latency or amplitude of the auditory evoked potentials. Within the CDKL5 deficiency disorder group, auditory evoked potential amplitude correlated with disease severity at Baseline as well as Year 1. Multiple quantitative EEG features differed between CDKL5 deficiency disorder and typically-developing participants, including amplitude standard deviation, 1/f slope, and global delta, theta, alpha, and beta power. Multiple quantitative EEG features correlated with clinical severity, including amplitude skewness, theta/delta ratio, and alpha/delta ratio. Theta/delta ratio was the overall strongest predictor of severity and also among the most repeatable qEEG measures from Baseline to Year 1. Together, the present findings point to the utility of evoked potentials and quantitative EEG parameters as objective measures of brain function and disease severity in future clinical trials for CDKL5 deficiency disorder. The results also underscore the utility of the current methods, which could be similarly applied to the identification and validation of electrophysiological biomarkers of brain function for other developmental encephalopathies.

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Section: Methodsmentioning

confidence: 99%

Electrophysiological biomarkers of brain function in CDKL5 deficiency disorder

Saby

Mulcahey

Zavez

et al. 2022

Brain Communications

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“…Both the CGI-I and the RSBQ are currently being utilized in several human trials. The CGI scales were developed initially in RTT for the first Trofinetide trials [32]. This is a clinician's assessment of global function which is divided into two forms, Clinical Global Impression -Severity (CGI-S) and Clinical Global Impression -Improvement (CGI-I), both as 7-point Likert scales.…”

Section: Current Challenges For Clinical Trials In Rttmentioning

confidence: 99%

Current Status of Developmental Encephalopathies: Rett Syndrome, MECP2 Duplication Disorder, CDKL5 Deficiency Disorder and FOXG1 Disorder

Percy

Neul

Peters

et al. 2023

TRD

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This review describes the similarities and differences between the developmental encephalopathies including Rett syndrome (RTT), MECP2 Duplication Disorder (MDD), CDKL5 Deficiency Disorder (CDD), and FOXG1 Disorder (FD). RTT and MDD represent opposite ends of deficiency and duplication of MECP2 whereas CDD and FD were initially described as variants of RTT before their specific genetic variants were identified and they were recognized as distinct disorders. The subsequent discussions outline the clinical features, phenotype-genotype relationships, and potential for therapeutic intervention including gene replacement. Natural history studies involving each disorder are providing the essential underpinnings for developing outcome measures and biomarkers to enhance the advancement of such treatment efforts.

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“…For example, several new disease-specific scales have been developed, adapted, and validated for Rett syndrome that highlight the core symptomatic profile of the disorder expected to be modified through therapeutic interventions. 83 , 84 , 85 …”

Section: Clinical Considerationsmentioning

confidence: 99%