Alzheimer’s Disease: Silent Seizures In Brain Could Indicate Brain Dysfunction

Silent seizure activity in the deeper regions of the brain could be the first sign of brain dysfunction in Alzheimer’s disease, and possibly other neurodegenerative diseases, according to the authors of this study. Dr. Alice Lam, fellow at Massachusetts General Hospital Epilepsy Service, was the first author of the study. The two senior co-authors included Dr. Andrew Cole, director of Massachusetts General Hospital Epilepsy Service and professor of neurology at Harvard Medical School, and his colleague, 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.

Reason for the Study

The authors wanted to determine if silent seizure activity was present in the hippocampus of patients with Alzheimer’s disease, a finding they observed in mouse models of AD. They hypothesized that such seizure activity in the main memory region of the brain, namely the hippocampus, could contribute to and even accelerate the degenerative process of the brain in Alzheimer’s.

Dr Noebels said, “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."

Methods and Findings of the Study

• The research team identified two persons recently diagnosed with Alzheimer’s disease who had no past history or family history of convulsive seizures.
• Using a minimally invasive method, they inserted fine electrodes through a small natural opening in the skull and monitored the electrical activity of the deeper regions of the brain over several days.
• Simultaneously, the researchers recorded scalp (conventional) EEG readings.
• In these two patients, with no prior seizure history, the hippocampal tracings revealed clear clinically silent seizures.
• At the same time, the scalp EEG recordings which were simultaneously taken were normal, confirming that routine EEG tests do not record 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.

These findings suggest that silent seizure activity in the hippocampal region could be an important factor in memory issues and other cognitive defects in AD.

Genetic Analysis of The Patients

The research team went on to perform a genetic analysis of the patients to determine if they had gene mutations associated with either epilepsy or the three genes linked with Alzheimer’s disease.

The results were normal, confirming that they suffered from the sporadic (non-familial) form of AD.

Alzheimer’s Disease In Brief

Alzheimer’s Disease is a neurodegenerative disease associated with loss of memory and deterioration in cognition, as well as a worsening ability for independent activity in daily life, as the disease advances. Although a lot of research has been going on, the disease continues to be an enigma to a large extent.

The two forms of AD are the familial or inherited form and the sporadic form. The 3 genes linked to the familial form of the disease include the APP, PSEN1, and PSEN2.

The familial form is rare and accounts for only 5% of cases; it is associated with early onset of the disease while the sporadic form is much more common, and is associated with late onset of the disease in people above 65 years. The sporadic form is also associated with genetic mutations such as ABCA7, APOE, and BIN1.

Studies have shown that convulsive seizures can occur in the familial form of the disease, while in the sporadic form they are not reported often.

Scope of Current Research and Future Plans

• The findings suggest that other relevant investigations than those currently performed may be necessary during the diagnostic process.
• It gives an insight into the functioning of the brain in AD and opens up the opportunity for trying out novel forms of therapy.
• Future research plans include determining whether similar electrical changes occur in other neurodegenerative diseases as well.

"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.

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References:

1. Alice D Lam, Gina Deck, Alica Goldman, Emad N Eskandar, Jeffrey Noebels, Andrew J Cole. Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease. Nature Medicine, 2017; DOI: 10.1038/nm.4330

Source-Medindia