Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease

Abstract

We directly assessed mesial temporal activity using intracranial foramen ovale electrodes in two patients with Alzheimer's disease (AD) without a history or EEG evidence of seizures. We detected clinically silent hippocampal seizures and epileptiform spikes during sleep, a period when these abnormalities were most likely to interfere with memory consolidation. The findings in these index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.

Figure 1

Subclinical mTL seizures and spikes captured with FO electrodes in two AD patients. (A–C): Patient #1. A. Skull x-rays demonstrating radiopaque FO electrodes, with lateral (left) and anterior-posterior (right) views. B. Left mTL spikes (arrowheads), without scalp EEG correlate. Calibration scale: 200uV, 1 sec. C. Electrographic seizure from the left mTL (arrow), without scalp EEG ictal correlate. Panels show continuous EEG spanning 60 seconds. Calibration scale: 150uV, 1 sec. (D–E): Patient #2. D. Right mTL spikes (arrowheads), without scalp EEG correlate. Calibration scale: 200uV, 1 sec. E. Three types of epileptiform discharges. Left: Right mTL spike (arrowhead) with scalp EEG correlate resembling benign epileptiform transient of sleep (box). Middle: Bifrontal spike-wave on scalp EEG (box) without FO correlate. Right: Left temporal sharp wave on scalp EEG (box) without FO correlate. Calibration scale: 200uV, 1 sec. (B–D): Anterior-posterior bipolar montage. L Temp = left temporal (Fp1-F7, F7-T3, T3-T5, T5-O1), R Temp = right temporal (Fp2-F8, F8-T4, T4-T6, T6-O2), L ParaS = left parasagittal (Fp1-F3, F3-C3, C3-P3, P3-O1), R ParaS = right parasagittal (Fp2-F4, F4-C4, C4-P4, P4-O2), Vertex (Fz-Cz, Cz-Pz), Coronal = coronal ring (T1-T3, T3-C3, C3-Cz, Cz-C4, C4-T4, T4-T2, T2-T1), LFO = left FO (LFO1–2, LFO2–3, LFO3–4), RFO = right FO (RFO1–2, RFO2–3, RFO3–4). (E): Referential montage (C2 reference). L Hemi = left hemisphere (Fp1, F7, T1, T3, T5, F3, C3, P3, O1), Vertex (Fz, Cz, Pz), R Hemi = right hemisphere (Fp2, F8, T2, T4, T6, F4, C4, P4, O2), LFO = left FO (LFO1, LFO2, LFO3, LFO4), RFO = right FO (RFO1, RFO2, RFO3, RFO4). Contact 1 is deepest on FOs.

Figure 2

mTL spikes detected on FO electrodes are absent from scalp EEG recordings. Quantification and comparison of spike frequencies simultaneously observed on scalp EEG (SE) and FO electrodes, during wakefulness and sleep, for Patient #1 and #2.