Nav: Home

'Silent seizures' discovered in patients with Alzheimer's disease

May 01, 2017

Deep in the brains of two patients with Alzheimer's disease, the main memory structure, the hippocampus, displays episodic seizure-like electrical activity. These non-convulsive hippocampal seizures are the first signs of 'silent' brain electrical network dysfunction described in patients with Alzheimer's disease. The discovery, published in the journal Nature Medicine, provides a better understanding of the condition and can potentially lead to new treatments for this devastating disease affecting more than 5 million people in the U.S.

"About 10 years ago, we were surprised to find 'silent seizures' in mouse models of Alzheimer's disease," said co-senior author Dr. Jeffrey L. Noebels, professor of neurology, neuroscience, and molecular & human genetics, and director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor College of Medicine. "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."

It's been reported that in a group of patients with Alzheimer's disease, those that have a history of the disease in their families, convulsive seizures are common, especially in advanced cases. However, for most patients with Alzheimer's the condition does not run in the family. In this group of patients, which are said to present with the sporadic form of the disease, convulsive seizures are typically absent. "For this reason, measuring the brain's electrical activity with an electroencephalogram or EEG test is not required for diagnosis and rarely performed," Noebels said.

Even if the test was performed, previous studies in the epilepsy field had shown that seizures deep in the brain, such as the hippocampal region, cannot be detected with routine scalp EEG recordings. Detecting such brain activity requires placing electrodes deep in the brain.

From mouse model to patients


"My colleagues and I have been interested for years in determining whether 'silent seizures' are present in the hippocampus of patients with Alzheimer's disease," Noebels said. "We were able to answer this question when my colleague and senior co-author Dr. Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, told me that he had two candidates for the procedure."

Cole and Dr. Alice Lam, first-author of the study and a fellow at Massachusetts General Hospital Epilepsy Service, led the team that performed the test in the patients. They used a minimally invasive recording technique involving fine wires inserted through a small natural opening in the skull. This allowed the researchers to monitor this deep region continuously for several days. Simultaneously, the researchers recorded scalp EEG readings.

In the two patients, who had been diagnosed with Alzheimer's disease and had no previous history of epilepsy or behaviorally obvious seizures, the hippocampal recordings showed clear clinically silent seizures. At the same time, the EEG recordings that had been taken simultaneously showed no abnormal brain activity, confirming that EEG tests do not register 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 Alzheimer's disease," Noebels said.

"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 Alzheimer's disease," Cole said.

In addition, Noebels and his Baylor colleague, Dr. Alica Goldman, co-author and associate professor of neurology and neurophysiology, performed genetic analysis on the patients' samples.

"We determined that these two patients did not have a gene known to cause epilepsy. So Alica and I, who have been studying epilepsy genes for a long time, sequenced the patients' samples for the three genes known to be linked to Alzheimer's disease," Noebels said. "It turned out that the patients didn't have those either; they present with the sporadic form of the disease."

"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," said Cole. "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."

"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 Alzheimer's disease."

The need for future studies


"This work with two patients proves the concept that 'silent seizures' can occur in patients with Alzheimer's disease," Noebels said.

"Next, we need to determine whether this finding is common in Alzheimer's disease, present in other types of progressive degenerative neurocognitive diseases, and when in the course of the disease it occurs," Cole said.
-end-
Other authors that contributed to this work include Gina Deck at Massachusetts General Hospital and Harvard Medical School and Emad Eskandar at Baylor College of Medicine.

Financial support for this study was provided by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Massachusetts General Hospital, Citizens United for Research in Epilepsy (CURE) and The Blue Bird Circle Foundation.

Baylor College of Medicine

Related Epilepsy Articles:

Breaching the brain's defense causes epilepsy
Epileptic seizures can happen to anyone. But how do they occur and what initiates such a rapid response?
Using connectomics to understand epilepsy
Abnormalities in structural brain networks and how brain regions communicate may underlie a variety of disorders, including epilepsy, which is one focus of a two-part Special Issue on the Brain Connectome in Brain Connectivity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.
Epilepsy: Triangular relationship in the brain
When an epileptic seizure occurs in the brain, the nerve cells lose their usual pattern and fire in a very fast rhythm.
How concussions may lead to epilepsy
Researchers have identified a cellular response to repeated concussions that may contribute to seizures in mice like those observed following traumatic brain injury in humans.
Understanding epilepsy in pediatric tumors
A KAIST research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors.
Can medical marijuana help treat intractable epilepsy?
A new British Journal of Clinical Pharmacology review examines the potential of medicinal cannabis -- or medical marijuana -- for helping patients with intractable epilepsy, in which seizures fail to come under control with standard anticonvulsant treatment.
Fertility rates no different for women with epilepsy
'Myth-busting' study among women with no history of infertility finds that those with epilepsy are just as likely to become pregnant as those without.
Do women with epilepsy have similar likelihood of pregnancy?
Women with epilepsy without a history of infertility or related disorders who wanted to become pregnant were about as likely as their peers without epilepsy to become pregnant.
Hope for new treatment of severe epilepsy
Researchers at Lund University in Sweden believe they have found a method that in the future could help people suffering from epilepsy so severe that all current treatment is ineffective.
Many epilepsy patients take drug combinations that interact
In an Epilepsia analysis of 2008-2010 Medicare claims data, one in four older Americans with new-onset epilepsy and more than one-third with prevalent epilepsy received a combination of antiepileptic drugs and non-epilepsy drugs that could interact to alter the effectiveness of the non-epilepsy drugs.
More Epilepsy News and Epilepsy Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.