Silent seizure activity in the deeper regions of the
brain could be the first sign of brain dysfunction in
- Alzheimer's disease (AD) is a progressive neurodegenerative disease
characterized by memory problems and cognition.
- Current study identifies silent seizure activity in the
hippocampus, the chief memory structure, in patients with the sporadic
form of the disease.
- Alzheimer's disease patients might thus need further relevant
investigations, and newer treatment options may be necessary to improve
the quality of their lives.
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
for the Study
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
‘Identification of silent seizures in Alzheimer’s disease helps open up possibilities of new forms of investigations and treatment.’
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."
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
- 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
- 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.
findings suggest that silent seizure
activity in the hippocampal region could be an important factor in memory
and other cognitive defects in AD.
Analysis of The Patients
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
results were normal, confirming that
they suffered from the sporadic (non-familial) form of AD
Disease In Brief
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.
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,
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.
have shown that convulsive seizures can occur in the familial form of the
disease, while in the sporadic form they are not reported often.
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.
- 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