Taking another look at “kindling”

Research ethics prohibit human studies that could show whether the kindling model in rodents applies to human epilepsy.

Research ethics prohibit human studies that could show whether the kindling model in rodents applies to human epilepsy.

In my 5/23/11 post “Can video game seizures lead to epilepsy?” I briefly discussed the theory of kindling and suggested that even though it’s controversial, it could be relevant for conceptualizing the potential effects of repeated visually induced seizures. I then made something of a leap from acknowledging that it could be a shaky basis for a model of human seizure development to suggesting it might allow researchers hypothesize that having many provoked seizures might bring about spontaneous seizures.

I heard from Robert Fisher, MD, PhD, Professor of Neurology at Stanford and Director of Stanford’s Comprehensive Epilepsy Center, and an authority on both visually induced seizures and deep electrical brain stimulation, pointing out that electrical stimulation administered under certain conditions actually inhibits seizures. Dr. Fisher, who was the lead author of a 2005 paper reviewing what is known from studies on photosensitivity and visually induced seizures, advised caution in entertaining the idea that reflex seizures may eventually lead to epilepsy.

In response to my post he offered this: “The kindling story is controversial.  My own view is that kindling is a laboratory model, but that seizures themselves don’t have the right characteristics to kindle other seizures in people.  It isn’t just any electrical excitation that produces kindling, only excitation with certain characteristics, and other stimuli may be inactive or anti-kindling.  This is not to say that kindling never happens; it may, though I can’t prove it. But clinical kindling must not happen very often or epilepsy surgery wouldn’t work as well as it does.”  

In other words, even if seizures caused by directly applying electricity to the brain can under certain circumstances lead to spontaneous seizures in some lab animals, the kindling model doesn’t show that seizures triggered in humans in response to a visual stimulus might have that effect. Perhaps in examining the long-term consequences of many, many visually triggered seizures, a more appropriate question to investigate would be whether the effects on the brain of, say, 500 partial video game seizures differ from the effects of 500 spontaneous partial ones. My thanks to Dr. Fisher for keeping me on track.

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