Disparate effects of hormones and vigabatrin on sleep slow waves in patients with West syndrome - An indication of their mode of action?

Abstract

Synaptic downscaling during sleep, a physiological process to restore synaptic homeostasis and maintain learning efficiency and healthy brain development, has been related to a reduction of the slope of sleep slow waves (SSW). However, such synaptic downscaling seems not to be reflected in high-amplitude SSW. Recently we have shown reduced SSW slopes during hormonal treatment (adrenocorticotrophic hormone, prednisolone) in patients with West syndrome (WS). Yet, whether this reduction was related to successful treatment or reflects a specific effect of hormone therapy is unknown. Thus, we retrospectively analysed nap electroencephalograms of 61 patients with WS successfully treated with hormones, vigabatrin (VGB), or both. The slope of SSW during treatment (T1) and 2-7months later (T2) when hormonal treatment was tapered off were compared between the treatment groups and healthy, age-matched controls. At T1 hormone treatment reduced the slope of low-amplitude SSW, whereas VGB increased the slope of high-amplitude SSW (linear mixed effect model: FGroup =7.04, p<0.001; FAmplitude =1,646.68, p<0.001; FGroup*Amplitude =3.38, p<0.001). At T2, untreated patients did not differ anymore from healthy controls, whereas those still under VGB showed the same alterations as those with VGB at T1. This result indicates a disparate effect of VGB and hormone on the SSW slope. In particular, hormones seem to reduce the slope of cortical generated low-amplitude SSW, similar to the physiological synaptic downscaling during sleep. Thus, a loss of functional neuronal connectivity might be an alternative explanation of the antiepileptic effect of hormonal treatment.