Subclinical mesial temporal lobe activity in Alzheimer’s Disease

Abstract

AbstractBackgroundAnimal and human studies of Alzheimer’s disease (AD) demonstrated that aberrant network activity with neuronal hyperexcitability plays a role in disease pathogenesis and cognitive functioning. Suppressing network hyperexcitability with levetiracetam improved cognitive functioning in familial AD mice and executive functioning in patients with AD and epileptiform activity. Manifestations of network hyperexcitability are unsensitive biomarkers since they are mostly subclinical and not visible on scalp EEG. (Lam et al. 2019, Vossel et al. 2021, Sanchez et al. 2012). Our purpose was to identify subclinical epileptiform activity in two patients with mild cognitive impairment (MCI) and one patient with moderate AD, with a suspicion of network hyperexcitability based on either spikes on 24‐h scalp EEG or a history suspect for seizures without epileptiform discharges on scalp EEG.MethodThree patients were implanted with bilateral foramen ovale (FO) electrodes to obtain more direct measures of mesial temporal lobe epileptiform activity. Scalp EEG according to the 10‐20 system and polysomnography were simultaneously recorded in all subjects for three to five consecutive days. Polysomnography was scored according to the AASM scoring rules. Persyst 14 software was used for automatic spike detection.ResultInvasive recordings showed interictal epileptic activity in all three patients, which was occasional during wakefulness and abundant during sleep. In one patient two nocturnal unilateral mesiotemporal seizures, characterized by arousal, were recorded during N1 sleep, while at the same time no epileptiform activity was visible on scalp EEG.ConclusionIn patients with AD subclinical mesial temporal epileptiform activity can be present with a normal scalp EEG. Epileptic activity is predominantly found during sleep. Our findings suggest an important role for network hyperexcitability in AD disease pathogenesis.