Association between brain morphology and electrophysiological features in Congenital Zika Virus Syndrome: A cross-sectional, observational study

We detected sleep spindles in 25% of the subjects (N = 11/44 recordings with at least one sleep episode). Importantly, the age at the time of the EEG recording did not differ between subjects with and without spindles (177 ± 20 and 195 ± 20 days-old, respectively; Welch-corrected t = 0·6277, p = 0·5345, df=33). Also, sleep spindles were less prevalent in those with epilepsy. While sleep spindles were detected in 7 out of 17 non-epilepsy subjects (41%), only 4 out of 27 epilepsy subjects (15%) showed this type of sleep oscillation (Fisher’s exact test: p = 0.0754). Synchronous spindles were observed in two subjects, one who did not show IEDs (Fig. 7A,B) and another with it (Fig. 7C,D). Averaged spectrograms, centered at the max spindle power, revealed a consistent 2-s, 12 Hz oscillations (Fig. 7B) with max energy in central electrodes (in this example, F3-C3 and F4-C4; asterisks in Fig. 7A). Fewer synchronous spindles, with reduced (relative) power, were detected in the epilepsy subject (Fig. 7D). Our algorithm automatically detected 1372 events from 13 subjects. Almost half of the detected events showed the highest power in frequencies around 6 Hz (Fig. 7E). Visual inspection of these events revealed a slower and irregular oscillation, in the theta-band, with a harmonic in the power spectrum within the spindle frequency (supplementary Fig. 8A). In one subject, these electrographic events could last longer (supplementary Fig. 8B), although most of them have ~2 s duration (supplementary Fig. 8C). The power of these detected events was higher at 7 and 11 Hz (Fig. 7G), with no difference between subjects with and without epilepsy (data not shown). The inter-spindle interval (a measure of spindle rate) was not different between epilepsy and non-epilepsy subjects (Fig. 7H), although spindles were shorter in the former (Fig. 7I). Theta oscillation (detected as a spectral harmonic of the true spindle) showed a similar duration (supplementary Fig. 8D) and power (supplementary Fig. 8E) between epilepsy and non-epilepsy subjects. Interestingly, one subject in the epilepsy group showed clear unilateral spindle frequency decay (supplementary Fig. 9). While the left hemisphere (C3-P3) showed well-defined spindles, the right hemisphere regular spindles were usually followed by a theta oscillation (supplementary Fig. 9A). Individual analysis of these events showed that the intensity of this frequency decay varies significantly (supplementary Fig. 9B). Averaged spectrograms centered at the sleep spindle revealed the unilateral frequency decay (supplementary Fig. 9C). Finally, we found no association between the occurrence of sleep spindles and the growth of HC in the first year of life (supplementary Fig. 10). These observations suggest that the theta oscillation (with the frequency decay in one patient) might result from a corrupted sleep spindle generator network in subjects with epilepsy in CZVS.