Rationale:
Parents of children with Dravet Syndrome report frequent nocturnal seizures and nocturnal awakening as well as a variety of dysautonomic symptoms. Sleep and autonomic nervous system are closely related However, the interface between these factors and nocturnal seizures in Dravet syndrome has not been previously examined.
Methods:
Members of the Dravet Syndrome Foundation (DSF) participated in an on-line study constructed in CLIRINX ©. Questions focused on recent seizures (within the past 6 months), occurrence and frequency of nocturnal seizures and of nocturnal awakenings and of 18 autonomic symptoms reflecting cardiac (tachycardia, bradycardia, arrhythmia), respiratory (fast-deep breathing, apnea, cyanosis, swallowing air), diaphoresis (excessive or lack of sweating, sweaty hands), temperature regulation (hands or feet cold or become red or blue, one side of body colder than other, excessively cold, face or chest flushed) and other (excessive drooling, abnormal pupillary response) autonomic symptoms. The autonomic symptoms were identified from a parent-generated list of concerns. Data were analyzed in R © with chi-square and non-parametric tests as appropriate for the data.
Results:
The 76 parent-respondents reported for their children-participants of whom 41 (54%) were female. Median age was 7.5 years (IQR 4.7 to 15.3, max 37.2) Recent seizures were reported in 73 (96%) of participants, and 37 (49%) reported nocturnal seizures. Nocturnal awakening without seizures occurred in 53 (70%). One or more dysautonomic symptoms was reported in 64/72 participants (84%) completing the dysautonomia section of the survey. The median number of dysautonomic symptoms was 1.5 (IQR 1 to 4, max 13). These were dichotomized for analytic purposes near the median (0 or 1 versus 2+). The most common dysautonomic symptom category was temperature dysregulation (41, 57%), followed by diaphoresis (39, 54%), other (30, 42%), respiratory (18, 25%), and cardiac (12, 17%). Participants with 2+ versus 0 or 1 dysautonomic symptoms were more likely to report nocturnal seizures (27/43 (63%) vs 11/29 (38%), p=0.04) and nocturnal awakenings (38/42 (90%) vs 13/26 (50%), p=0.0002). Nocturnal awakenings were about as common in children with as without nocturnal seizures (78% vs 73%, p=0.68). The associations between each dysautonomia category and nocturnal seizures versus awakenings were similar except for cardiac, which was strongly associated with nocturnal seizures but not non-seizure awakenings (Fig. 1). Participants' age at survey was not clearly associated with report of dysautonomias (Fig. 2). A diagnosis of a sleep disorder was reported in 25 (33%) participants (apnea, N=13, insomnia, N=4, night terrors, N=4, other N=3) but these were not associated with reported dysautonomias, nocturnal seizures, or nighttime awakenings.
Conclusions:
Parents of young people with Dravet syndrome report frequent sleep disruptions associated with nocturnal seizures as well as non-seizure-related awakenings. Both types of awakenings are correlated with reported dysautonomic symptoms. Our findings emphasize the growing evidence of sleep and autonomic function involvements in Dravet syndrome and other early life epilepsies. The involvement of sleep and autonomic function could reflect inherent mechanisms of the disease and might be potential clinical targets for precision therapeutic interventions in the future.
Funding: Supported by the Stanley Manne Children’s Research Institute and Ann & Robert H. Lurie Children’s Hospital of Chicago under the Precision Medicine Strategic Research Initiative and the Pediatric Epilepsy Research Foundation (PERF).