Ultradian rhythms in accelerometric and autonomic data vary based on seizure occurrence in paediatric epilepsy patients

Abstract

Ultradian rhythms are physiological oscillations that resonate with period lengths shorter than 24 hours. This study examined the expression of ultradian rhythms in patients with epilepsy, a disease defined by an enduring seizure risk that may vary cyclically. Using a wearable device, we recorded heart rate, body temperature, electrodermal activity and limb accelerometry in patients admitted to the paediatric epilepsy monitoring unit. In our case-control design, we included recordings from 29 patients with tonic-clonic seizures and 29 non-seizing controls. We spectrally decomposed each signal to identify cycle lengths of interest and compared average spectral power- and period-related markers between groups. Additionally, we related seizure occurrence to the phase of ultradian rhythm in patients with recorded seizures. We observed prominent 2- and 4-hour-long ultradian rhythms of accelerometry, as well as 4-hour-long oscillations in heart rate. Patients with seizures displayed a higher peak power in the 2-hour accelerometry rhythm (U = 287, P = 0.038) and a period-lengthened 4-hour heart rate rhythm (U = 291.5, P = 0.037). Those that seized also displayed greater mean rhythmic electrodermal activity (U = 261; P = 0.013). Most seizures occurred during the falling-to-trough quarter phase of accelerometric rhythms (13 out of 27, χ² = 8.41, P = 0.038). Fluctuations in seizure risk or the occurrence of seizures may interrelate with ultradian rhythms of movement and autonomic function. Longitudinal assessments of ultradian patterns in larger patient samples may enable us to understand how such rhythms may improve the temporal precision of seizure forecasting models.

Keywords: accelerometry; autonomic activity; cyclic patterns; epilepsy; paediatric patients.

Graphical Abstract

Figure 1

Inclusion diagram. Summary of the selection of 58 out of 450 patients based on the study-specific inclusion and exclusion criteria.

Figure 2

Raw data and power spectral densities. Illustration of 14 hours of accelerometry (1st row), heart rate (2nd row), electrodermal activity (3rd row) and peripheral body temperature (4th row) recordings, smoothed over 40 data points (average filter). Means and standard error of raw data (A, averaged per minute) and power spectral density (B) for 29 control patients (green) and 29 seizure patients (blue). (C) Twenty-nine individual seizure patients’ ultradian rhythms. (D) Twenty-nine individual control patients’ ultradian rhythms.

Figure 3

Statistics. A shows boxplots of markers of interest (accelerometry 2-hour, U = 287, P = 0.038, and 4-hour peak power, U = 473, P = 0.414, heart rate 4-hour peak power, U = 412, P = 0.895, and peak period length, U = 291.5, P = 0.037, electrodermal activity mean power, U = 261; P = 0.013, and peripheral body temperature 3-hour peak power, U = 383, P = 0.560) per group. Each group consisted of 29 patients and group differences were tested by Mann–Whitney U-test. The red line indicates the mean, the bottom and top edges of the box indicate the 25th and 75th percentiles and the whiskers show the range for the most extreme data points that are not considered outliers, as indicated by red plus signs. B depicts the distribution of the 27 tonic–clonic seizures that were recorded during the analysed segments split by each hour of the 14-hour recording period.

Figure 4

Seizures and cycles. A illustrates two patients’ sinewave of 4-hour range max period length fitted for heart rate (grey = raw data, purple = fitted data) and 2-hour range max period length fitted for accelerometry (grey = raw data, red = fitted data) data. For visualization only, data were averaged per minute. Blue vertical lines illustrate the electrographic seizure onset. B shows cyclic phases for each of the 27 seizures (left), counts added up for 12 bins (middle-left), counts added up for 4 bins (middle-right) and counts added up for 2 bins (right). C depicts the sinewaves’ phases.