Scientists discover ‘silent seizures’ in Alzheimer’s disease patients

Written by Amy Bamford

Scientists from Bayor College of Medicine (TX, USA) and Massachusetts General Hospital and Harvard Medical School (MA, USA) have observed clinically silent hippocampal seizures in two Alzheimer’s patients with no previous history of seizures. The results, published in Nature Medicine, show that episodic seizure-like electrical activity is detected during sleep, a period when memories are consolidated. These novel findings could open up new research avenues for further understanding and potential treatment of Alzheimer’s disease (AD).
Jeffrey Noebels, Bayor College of Medicine, explained:  “About 10 years ago, we were surprised to find ‘silent seizures’ in mouse models of AD,

“When we measured the animal’s brain electrical activity, we detected abnormal electrical discharges in the brain with a seizure-like pattern. The mice, however, did not present with convulsions. These ‘clinically silent seizures’ in the deep regions of the brain, we speculated, could lead to problems of memory.”

Mesial temporal activity was assessed in two patients with AD with no known history of seizures or EEG evidence. To measure activity in the hippocampal region, intracranial foramen oval electrodes were used.  Each patient’s brain was monitored over a period of several days and scalp EEG readings were also taken.

The hippocampal recordings presented clear clinically silent seizures and epileptiform spikes during sleep. However, EEG recordings did not detect abnormal brain activity, confirming that scalp EEG readings cannot record changes in deep brain activity.

“What was fascinating was that this activity was present at night when the patients were sleeping, a time thought to be critical for the consolidation of recent memories, a trait that is most impaired in early AD,” Noebels said.

Andrew Cole, Massachusetts General Hospital and Harvard Medical School, commented: “Based on our observations, we are particularly intrigued by the possibility that ‘silent seizure’ activity per se could contribute to or accelerate the degenerative process underlying AD.”

Additionally, Noebels and Alica Goldman, Bayor College of Medicine, performed genetic analysis on the patients’ samples to identify three genes with a known link to AD.

Noebels commented:  “It turned out that the patients didn’t have those either; they present with the sporadic form of the disease.”

Alicia Goldman, Bayor College of Medicine, said: “From a physician’s perspective, I think this work opened my eyes toward the need to look deeper into our patients’ condition in order to improve the quality of their lives as well as that of their caregivers,” Goldman said. “I think this work offers an opportunity for new investigations that could be relevant for moving forward the clinical practice of AD.”

These novel findings highlight the need for future research.

“Next, we need to determine whether this finding is common in AD, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs,” Cole concluded.

Sources: Lam DA, Deck G, Goldman A et al. Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer’s disease. Nat.Med. doi:10.1038/nm.4330 (2017) (Epub ahead of print);