Dear Roman,

This is fascinating indeed!

There is a known mechanism for seizure activity to upregulate neurotrophic signaling, but longer seizures (and of course SE even more) can damage as well, so I'm surprised that the SE resulted in the most improvement. I'm certain that the age of the patient is key in this as well!

I'm looking forward to hearing more about this from others, or hearing further details from you! (for example, did resting state EEG look different before and after SE?)

Dear Alberto, thank you. I'm sorry, but there are only few objective data about this child, since his parents don't like to carry out any experiments on him. So there are no EEG data, nor MRI. All I know that MRI was done in 2 years, and everything is ok. And EEG has only spike-slow wave complexes, which correspond to phantom absences. Could you please give me any links at evidences about upregulation of neurotrophic signaling.

Dear Nicolas, thank you too! Could you please explain what do you mean on «young» and «old» neurons? Is this the age of the cells, or of the organism as a whole?

For the basic science side of the BDNF/neurotrophic signaling in epilepsy/epileptogenesis question, I can recommend any of a series of articles from Helen Scharfman's lab at NYU/NKI. If I recall correctly, Binder is the author on a lot of them.

Also from the animal literature, I can point to work by the late, great Karen Gale, who described neurotrophic responses after electroshock seizures:

https://www.ncbi.nlm.nih.gov/m/pubmed/20170723/

https://doi.org/10.1016/S0306-4522(98)00636-8

https://doi.org/10.1016/S0306-4522(02)00265-8

As far as I know, there's no hard literature reports of what you are seeing. Maybe you'll be the first to describe this phenomenon in detail!!

Thank you very much. It's all very interesting.

Thank you for great answer. Could you please give me any clues to the age of threshold when the excitatory neurotransmission starts to damage brain more? Of course not exact number, but a fuzzy intermal, perhaps...

As as epileptologist, I have to say that this phenomenon is kind of common in children with epilepsy.

We have to understand epilepsy as a network dysfunction. Epileptic discharges seen in EEG can cause an interference in distant eloquent areas of the brain (what we call "functional deficit zone").

In children this can translate into learning difficulties.

If we consider patients like yours, with repetitive status epilepticus, these patients often have an improvement in cognitive function after the resolution of the seizure.

It's possible that your patient is living with non-convulsive status epilepticus most of the time....

That's why serial EEG is important in cases like that.

Thanks for a very interesting perspective, Andre!

I am especially fascinated by the possibility you raised of constant, subclinical seizures being the culprit for the learning disability. Could it be that the severe convulsive SE episodes lead to post ictal depression of the networks, which gives the child some time with normal function?

That raises another interesting question: are severe seizures like that overall potentially desirable in a child like this? If so, could a functional therapy consist of controlled periodical withdrawal of AEDs or something like that?

Thanks again for the answer.

Seizures are one possibility, but even interictal discharges could have a similar effect in cognition.

Neurons in wake state tend to fire in a de-synchronized manner. In sleep, they become "more synchronized" because of the normal oscillations of NREM sleep (spindles, slow waves, etc.). Epileptic discharges tend to appear more in these synchronized states.

With that in mind, think of a seizure as the "ultimate synchronization" of the whole brain. When a seizure ends, the brain gets back it's normal function (de-synchronized).

Now think of electroconvulsive therapy normally used in psychiatry. It has the same principle. Generating a seizure to change the brain function.

As your question about opening some space in treatment for programmed seizures, I don't think it's a good idea because frequent seizures ( especially generalized tonic-clonic seizures are a risk factor for SUDEP (sudden unexpected death in epilepsy).

Regarding treatment, what we have right now, is medication, Neuromodulation, and surgery.

We have to understand more of these neural networks and how epilepsy interacts with the brain.

Hello, Dr. Giorelli.

You give us several important clues. But what could you say, if the child, about whom we are talking, is normally developed? He looks very usual as 6 years old prescholar. He started to study writing and reading, he has several abilities that few of his age have (for example, he can do puzzle of 1500 items, I can't).

The cognitive development after the seizures, about which I talk, looks like very strong improvements in all skills and abilities.

Hi Dr. Dushkin,

It is fairly well described that epileptic encephalopaties can cause a cognitive decline in otherwise normally developed children (like in Landau-Kleffner Syndrome, etc...), but gaining "extra" cognitive abillities after seizures...I'm not aware of that.

The pooled evidence so far, points towards a clear decline in cognition in children with refractory epilepsy and it's not only seizure-related. Interictal EEG activity could impair cognition as well.

On the other hand, we know of cases of children with refractory seizures with a fairly good cognitive performance (until now....).

I have a case of a 6 yo. boy with seizures since 3 yo., diagnosed with tuberous sclerosis complex - TSC2. He had until 4 months ago a seizure frequency of 15-20 tonic seizures/day. He has "tons" of epileptic discharges in serials EEGs and a normal MRI. This boy never had any cognitive decline and had a normal development ( so far...) despite the heavy burden of epileptic ativity/seizures and all the anti-seizure medication (including Cannabidiol) that we tried.

I suggest you perform a formal neurological (MRI and EEG) and neuropsychological evaluation in your patient in order to check where he is at, on a cognitive level, and then register these "seizure-related" improvements.

Maybe you have something here...

I add here an interesting review about preventing cognitive impairment in children with epilepsy.

I hope I was of some help.

Thank you very much, Dr. Giorelli. You helped a lot.

Hello. Dr. Dushkin. I do not have my doctorate yet. What you are describing sounds very plausible with my experience with neurofeedback.

This technology uses the EEG capability to train the brain to build connectivity and train the various portions of the brain to build better connections. I have seen it remediate various mental disorders and seizure disorders.

Dear Jean, could you please describe more the technology of neurofeedback please?

9.

Developments in Neurofeedback: Should Health Educators Be Paying Attention?

Full Text Available

Academic Journal

By: Cleary, Michael J. Health Educator. Fall2011, Vol. 43 Issue 2, p21-26. 6p. 2 Charts. , Database: Education Research CompleteAdd to folderPDF Full Text (356KB)

Hi Dr. Dushkin,

This article can explain it better than I can. I hope this will help you.

Jean

In case you have any difficulty in obtaining the article, , Dr. Cleary's email is:

[email protected]

Great! Thank you very much.

Glad to be helpful.