Subclinical Epileptiform Activity in Dementia with Lewy Bodies

Abstract

BackgroundPatients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α‐synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB.ObjectivesTo investigate if IED as measured with ear‐EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC).MethodsIn this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear‐EEG recordings, each lasting up to 2 days, over a period of 6 months.ResultsAt baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42–4.61; P‐value = 0.001). Most IED occurred at night.ConclusionsLong‐term outpatient ear‐EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Latest advances in mechanisms of epileptic activity in Alzheimer’s disease and dementia with Lewy Bodies

“…Hyperexcitability may begin or be a result of neuropathology and may arise due to a number of different factors at varying time points in AD and DLB. Though hyperexcitability has been previously explored in the context of AD (1,24,31,60,64,65), the role and mechanisms of hyperexcitability in DLB (66)(67)(68)(69), as well as its similarities and differences with AD requires more research. In this review, we explore shared and distinct molecular mechanisms associated with hyperexcitability in AD and DLB, encompassing factors such as genetic risk factors, Ca 2 and glutamate contributions, cholinergic pathways, AMPA and NMDA receptors, mTOR, pathological Aβ, tau and α-synuclein, genetic risk factors, altered microglial and astrocytic activity, and impaired inhibitory interneuron function (Figure 1).…”

Evaluating the Electroencephalographic Signal Quality of an In-Ear Wearable Device

“…Currently, scalp EEG systems are the primary tool for studying brain activity in lab conditions. However, with advancements in bioelectronics, several monitoring systems designed for in-ear EEGs have been proposed for real-world deployment and have demonstrated noteworthy results [ 17 , 18 , 19 ]. Despite this, there is a notable absence of universally agreed-upon benchmarks to define the performance and usability of these new wearable devices.…”

“…Additionally, ear-EEG technology shows promise in epilepsy, where in-ear EEG systems can be integrated as routine clinical tools for continuously monitoring epileptic activities outside clinical facilities, thereby enhancing the ability to capture pathological signals for improved diagnosis and follow-up [ 16 , 17 ]. Moreover, recent studies have demonstrated the reliability of in-ear EEGs for the long-term monitoring of epileptic activities in patients with Alzheimer’s disease [ 18 ] and Lewy body dementia [ 19 ], who are at higher risk of developing epileptic discharges. Taken together, in-ear EEG technology holds the potential for developing new monitoring procedures for various clinical conditions.…”

Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction

“…Sleep disturbances and epilepsy are known to be interlinked in AD and may exacerbate one another, having implications for memory deficits [ 127 ]. Cortical hyperexcitability is evident in patients with DLB who also have an increased risk of seizures or myoclonus [ 124 ], and often seizures may be subclinical [ 128 ]. In addition, patients with DLB frequently exhibit visual hallucinations and cognitive fluctuations [ 120 ], symptoms that may reflect changes in cortical network excitability [ 129 ].…”