Altered Sleep Microarchitecture and Cognitive Impairment in Patients With Temporal Lobe Epilepsy

Abstract

Objectives:To investigate the spatiotemporal characteristics of sleep waveforms in temporal lobe epilepsy (TLE) and examine their association with cognition.Methods:In this retrospective, cross-sectional study, we examined overnight EEG data from adult patients with temporal lobe epilepsy (TLE) and non-epilepsy comparisons (NEC) admitted to the epilepsy monitoring unit (EMU) at Mass General Brigham hospitals. Automated algorithms were used to characterize sleep macro-architecture (sleep stages), and micro-architecture (spindles, slow oscillations) on scalp EEG, and to detect hippocampal interictal epileptiform discharges (hIEDs) from foramen ovale (FO) electrodes simultaneously recorded in a subset of TLE patients. We examined the association of sleep features and hIEDs with memory and executive function from clinical neuropsychological evaluations.Results:A total of 81 TLE and 28 NEC adult patients were included with similar mean ages. There were no significant differences in sleep macro-architecture between groups, including relative time spent in each sleep stage, sleep efficiency, and sleep fragmentation. In contrast, the spatiotemporal characteristics of sleep micro-architecture were altered in TLE compared to NEC and were associated with cognitive impairments. Specifically, we observed a ∼30% reduction in spindle density in TLE compared to NEC patients, which was significantly associated with worse memory performance. Spindle-slow oscillation (SO) coupling strength was also reduced in TLE and, in contrast to spindles, was associated with diminished executive function. We found no significant association between sleep macro- and micro-architectural parameters and hIEDs.Conclusion:There is a fundamental alteration of sleep micro-architecture in TLE, characterized by a reduction in spindle density and spindle-SO coupling, and these changes may contribute to neurocognitive comorbidity in this disorder.

Impaired sleep-dependent memory consolidation predicted by reduced sleep spindles in Rolandic epilepsy

“…In contrast to measures of spike rate, sleep spindle rate predicts IQ, processing speed, and sensorimotor coordination in RE 8 , and changes in spindle rate predict cognitive response to high-dose benzodiazepine treatment in severe epileptic encephalopathies 9 . Similar findings have subsequently been reported in other epilepsy populations 11,12 , suggesting that sleep spindle deficits may provide a robust, generalizable biomarker for several cognitive symptoms observed in epilepsy.…”

Unlocking the Mysteries of Slumber: Unveiling the Intricate Ties Between Sleep, Epilepsy, and Cognition

“…Bender et al found no significant differences in sleep macroarchitecture, such as sleep efficiency, fragmentation, and time spent in different stages of sleep, between TLE and controls. 6 However, they did observe a notable reduction in sleep microarchitecture, specifically spindle density, in TLE patients, particularly ipsilateral to the side of the ictal onset. 6 This finding suggests a possible link between alteration in sleep microarchitecture and abnormal epileptic network.…”

“… 5 Concurrently, Bender et al examined this relationship in adults with temporal lobe epilepsy (TLE), utilizing scalp EEG and/or foramen ovale electrodes. 6 While these studies provided answers to several critical questions, they also opened up many more new avenues of inquiry along the way.…”

Overlapping and distinct phenotypic profiles in Alzheimer’s disease and late onset epilepsy: a biologically-based approach

“…These could be secondary to early involvement of dentate gyrus/CA3 and CA1, subfields responsible for pattern separation and integration ( Figures 3 , 4 ; Table 1 ) ( 29 , 35 ). Furthermore, difficulty with long term consolidation could be secondary to increased frequency of interictal discharges during NREM sleep ( 59 , 60 ) or decreased spindle activity seen during NREM sleep ( 61 ). Additionally, TLE patients with unilateral onset of left or right hemisphere seizures may exhibit a material-specific impairment in memory for verbal or nonverbal material ( 62 ).…”

“…Bilateral frontotemporal slowing and mild slowing and desynchronization in the posterior dominant rhythm have been linked to the degree of amyloid and tau deposition, respectively ( 19 ). Sleep EEG in patients with temporal lobe epilepsy shows decreased spindle density ( 61 ). While mesial temporal IEDs can be difficult to detect with conventional scalp EEG, our center has had improved sensitivity with adding subtemporal (T1/T2) leads.…”