My wife died in November at Pleasant Manor after almost 20 years from the onset of the earliest symptoms of dementia.
The evidence based on her history and MRI findings of hippocampal atrophy strongly suggested she had Alzheimer’s disease, but as often happens, it was more complicated than that.
MRI studies also revealed evidence of two small, old infarcts, one in her brainstem and the other in her cerebellum, which suggested that vascular disease and Alzheimer’s disease coexisted, and both contributed to her dementia.
Beginning a few years before COVID-19, Jan sometimes slumped unresponsive over to one side if seated or slipped to the ground if standing, only to recover within a few several minutes, throughout which her pulse and colour barely changed.
These incidents were investigated with no cause found. Then, beginning in the last year and a half of her life when she was in Pleasant Manor, she developed periods when she was unresponsive or barely so, from which she would recover after several hours, none the worse for the experience — sometimes more attentive and engageable than in the several week runup to the unresponsive events.
To me, these events looked like non-convulsive seizures whose onset was often heralded by increasingly common small random muscle twitches in her limbs for the two or three weeks before she became unresponsive.
The progression suggested a buildup in epileptic activity over weeks culminating in a period of relative unresponsiveness lasting several hours, in turn followed by a period of becoming the “best” in weeks in which Jan was more engageable and brighter — perhaps a period when her brain was “defragged,” to borrow an old term from computer science, which created the several day period when in common parlance she was “more with it.”
Those were my thoughts, but where was the evidence? I talked to epilepsy colleagues who agreed but admitted that they knew little about the frequency or nature of epilepsy in Alzheimer’s disease or other dementias. A literature search revealed similar ignorance except for the suggestion that epileptic phenomena were common in Alzheimer’s disease late in the disease.
Then, in late April, a review article titled, “Tiny probes make sense of abnormal bursts in the epileptic brain” written by Jennie Erin Smith for one of the best general science journals, Science, caught my notice.
The original study she reviewed was published in Nature Neuroscience and shed new light on how subclinical epileptiform electrical discharges in the brain might not only trigger clinically overt seizures but interfere with memory and other cognitive functions.
That was an eye-opener for me.
Quoting from Smith’s review: “Seizures are the most dramatic symptom of epilepsy, but they’re not the only type of abnormal activity … brief electrical bursts, called interictal epileptiform discharges … can occur hundreds or thousands of times a day, usually without a person noticing … although not as dangerous as seizures, they can cause temporary confusion and contribute to long-term cognitive problems, even in those whose obvious clinical seizures are controlled.”
In the original study that prompted the review, scientists at the University of California San Francisco inserted fine multi-electrodes into epileptogenic regions of brains of patients undergoing resection of that region for the treatment of temporal lobe epilepsy. The high resolution of these recordings allowed them to record abnormal spontaneous electrical discharges from as many as hundred single cortical neurons at a time.
What really caught my attention in the study was the surprising finding that “some of those discharges recruited some of the same neurons involved in speech perception, pulling them briefly off their jobs.” That observation suggests that ongoing, abnormal electrical bursts occurring between overt clinical seizures might well impair cognitive and memory functions.
Returning to Jan, the question was whether some part of her ongoing impaired cognition and awareness was in some way related to similar epileptiform discharges.
The only sure way to resolve that question would have been to transfer Jan to an epilepsy unit equipped to carry out several days of continuous electroencephalographic recording with surface electrodes, but for practical reasons that wouldn’t have worked.
However the question remains: do some patients with mid-to-late-stage dementia have abnormal electrical activity in their brains that contributes to their cognitive decline? The observation that she was noticeably brighter and more attentive in the immediate aftermath of several-hour periods of lost consciousness is consistent with such a hypothesis.
One way to test the hypothesis would be to carry out a small clinical trial designed to see whether selective anti-seizure drugs over a several-week period improve cognition, especially in those patients who like Jan, have clinical evidence of myoclonic jerks suggestive of abnormal electrical discharges in their brains.
I’m not sure whether such a study is practical given the high workload in long-term care facilities these days, but it’s worth considering.
Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.
