Specific Epileptiform Abnormalities are Linked to Seizures in Alzheimer Disease

While epileptiform abnormalities are common in patients with Alzheimer disease (AD), not all forms are the same; there are specific characteristics associated with clinical seizures in this group, including occurrence during wakefulness and REM, right temporal hyperexcitability, and robust morphology, according to study results published in Neurology.

Previous studies have suggested that neuronal hyperexcitability may be an important electrical abnormality that can play a significant role in memory failure and disease progression in early stages of AD. Seizures, a potential presenting symptom of AD, are reported in 10-22% of patients with this disease. The aim of the current study was to investigate the association between scalp EEG biomarkers of hyperexcitability with clinical seizures in patients with AD.

This cross-sectional study included participants, aged 50-90 years, who completed 24-hour ambulatory scale EEGs, including 43 cognitively normal elderly healthy controls, 41 patients with probable AD and no history or risk factors for epilepsy (AD-NoEp), and 15 patients with probable AD and epilepsy related to the disease (AD-Ep).

The EEGs were reviewed by 2 board-certified epileptologists who marked all seizures, sharp waves, temporal intermittent rhythmic delta activity, sharp transients of uncertain significance, and small sharp spikes. Study researchers polled a panel of 9 epileptologists to gather a robust consensus.

Epileptiform abnormalities were common in patients with AD, as the frequency of overall epileptiform EEGS increased from 4.7% of healthy controls, to 22% of the AD-NoEp group, and up to 53.3% of the AD-Ep group.

Compared with healthy controls, the proportion of epileptiform abnormalities was significantly greater in those in the AD-NoEp cohort (odds ratio [OR], 5.77; 95% CI, 1.16-28.57; P = .024). Furthermore, this proportion was also significantly greater in patients in the AD-Ep cohort compared with those in the AD-NoEp cohort (OR, 4.06; 95% CI, 1.16-14.26; P =.046).

Several specific features of epileptiform discharges were associated with clinical seizures, as they were more common in the AD-Ep group patients compared with the AD-NoEP and healthy controls groups. These included robust morphology, higher median frequency of epileptiform discharges in each EEG recording (23 vs 3 vs 1.5 per 24 hours, respectively), occurrence during wakefulness and REM (28.7% vs 2.4% vs 0%, respectively), and right temporal location (42.9% vs 0% vs 0%, respectively).

EEG waveforms known as temporal intermittent rhythmic delta activity were exclusively left temporal in patients of the healthy control and AD-NoEp groups. These waveforms, however, were largely bi-temporal patients in the AD-Ep group.

Frequent small sharp spikes, also known as benign epileptiform transients of sleep, may serve as a biomarker of hyperexcitability in patients with AD, as these were specifically associated with epileptiform EEGs.

The study had several limitations, including the relatively small sample size, the retrospective obtainment of some of data, and the predominantly white and highly educated demographic of participants. Additionally, many participants lacked biomarker data required to confirm the diagnosis of AD.

“[T]his study demonstrates the frequency and asymmetry of epileptiform abnormalities in early stages of AD and details an important relationship between electrical and clinical manifestations of hyperexcitability in AD,” concluded the researchers.

Reference

Lam AD, Sarkis RA, Pellerin KR, et al. Association of epileptiform abnormalities and seizures in Alzheimer disease. Neurology. Published online August 6, 2020. doi:10.1212/WNL.0000000000010612