Dysautonomia and functional impairment in rare developmental and epileptic encephalopathies: the other nervous system

Abstract

Aim To determine whether functional impairments and autonomic symptoms are correlated in young people with developmental and epileptic encephalopathies (DEEs). Method Cross‐sectional, online surveys (2018–2020) of parents recruited from family groups obtained information on several aspects of children’s conditions including functional abilities (mobility, hand use, eating, and communication), 18 autonomic symptoms in six groups (cardiac, respiratory, sweating, temperature, gastrointestinal, and other), and parental stress. Bivariate and multivariable logistic regression analyses examined associations of dysautonomias with functional impairment, adjusted for type of DEE and age. Results Of 313 participants with full information on function and dysautonomias, 156 (50%) were females. The median age was 8 years (interquartile range 4–12y); 255 (81%) participants had symptoms in at least one autonomic symptom group; 283 (90%) had impairment in at least one functional domain. The number of functional impairment domains and of autonomic symptom groups varied significantly across DEE groups (both p<0.001). The number of functional impairment domains and of autonomic symptom groups were correlated (Spearman’s r=0.35, p<0.001) on bivariate and multivariable analysis adjusted for DEE group and age. Parental stress was also independently correlated with dysautonomias (p<0.001). Interpretation Parent‐reported dysautonomias are common in children with DEEs. They correlate with extent of functional impairment and may contribute to caregiver stress. Dysautonomic symptoms are common in young people with developmental and epileptic encephalopathies (DEEs). Burden of dysautonomias is strongly correlated with burden of functional impairments. Aspects of dysautonomic function may provide biomarkers of DEE disease severity.

Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials

“…Anne Berg led the team in a recent publication examining FDA’s PFDD guidances. 41 The paper discusses the challenges of adopting available COAs in severely impaired patient groups and strategies to adapt or modify existing COAs to be FFP for this population. Berg explores a range of potential adaptations, including alternative scoring, use of assessments in out-of-intended age ranges, and modifications for individuals with sensory or motor impairments.…”

Autonomic dysfunction in developmental and epileptic encephalopathies: a daily‐life issue

“…The study reported by Berg et al. provides important new observations 4 . Considering the lack of informative study in the literature, initiating a first evaluation using an online survey of patients with the help of family groups was very pertinent.…”

“…The study reported by Berg et al provides important new observations. 4 Considering the lack of informative study in the literature, initiating a first evaluation using an online survey of patients with the help of family groups was very pertinent. This approach suffers from methodological limitations, which are acknowledged by the authors, but it represents a mandatory first step before undertaking prospective studies to investigate some specific aspects in detail.…”