‘Silent’ seizures detected in Alzheimer’s patients

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An MRI scan of an Alzheimer’s-affected brain highlighting the hipppocampus.
Credit: Zephyr / Science Photo Library

Symptomless “silent” seizures discovered a decade ago in mice with Alzheimer’s disease have been detected for the first time in humans.

The discovery potentially opens up new avenues for treatment of the debilitating disease, which affects about one in 10 people over the age of 65 and three in 10 over the age of 85.

A team of neuroscientists led by Jeffrey Noebels, of Baylor College of Medicine in Texas, report in Nature Medicine that the seizures, deep in the hippocampus, were recorded in two Alzheimer’s patients who volunteered to have probes inserted into their brains.

Ever since Noebels and his colleagues detected the silent seizures in mice, it has been thought that similar electrical discharges happen in human brains hit by Alzheimer’s.

Collecting the evidence, however, has been a challenge. The silent seizures, by definition, do not induce convulsions and thus go unnoticed by patients or doctors.

While epilepsy is often present in people with a family history of Alzheimer’s, it is typically absent in the majority of patients, who have the “sporadic” or non-family-related variant of the disease.

An electroencephalogram (or EEG) test to measure the brain’s electrical activity is therefore rarely, if ever, conducted during diagnosis. Scalp-based EEGs, in any event, are not sufficiently sensitive to pick up electrical disturbances in the hippocampus.

The key to knowing if silent seizures are, in fact, a symptom of Alzheimer’s came when Noebels’ colleague and paper co-author, Andrew Cole, director of the Massachusetts General Hospital Epilepsy Service, found two patients willing to undergo deep-brain monitoring procedures.

The two patients had fine wires inserted into their hippocampi that remained in place for several days, allowing the scientists to monitor brain activity continually. The pair also consented to scalp EEGs.

In both cases, the inserted probes recorded clear evidence of asymptomatic seizures, while the scalp EEGs missed the whole show.

“What was fascinating,” Noebels says, “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 Alzheimer’s disease.”

Coles adds: “It is very exciting that we were able to move from an observation in genetically engineered mouse models of Alzheimer’s to a demonstration of the same phenomenon in patients with verified Alzheimer’s disease.”

“This is a critical step toward a better understanding of network dysfunction in the disease and opens the window to novel therapeutic approaches for this common condition.”

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