Thanks for your response, I did not want to be too specific to encourage ideas but I ended up too vague. To rephrase, in temporal lobe epilepsy for example, do you feel (either from practice, research, readings...) that seizures, IQ, clinical features...) worsen in refractory or poorly controlled patients? Do you observe an evolution or are patients stable in their presentation?

I hope this helps! I am really interested to know what the feeling is across the board.

Hi Celia,

As pointed out, it's a difficult question to answer, and would really depend on from which perspective you are looking. Plus, 'Epilepsy' is not one condition; there are many forms, all of which are symptomatic of something problematic going on in the brain (notice the intentional vagueness!).

In the human imaging literature, there is a vast amount of research, primarily quantitative MRI, indicating that, yes, chronic uncontrolled epilepsy is harmful to the brain, and results in progressive further deterioration. This is shown in cross-sectional (a little problematic) and longitudinal studies. This is supported by some animal research. Furthermore, there is a big neuropsychological literature showing that uncontrolled chronic epilepsy causes progressive neurocognitive decline, far beyond what would be expected in neurological healthy people.

The vast majority of this evidence - in humans at least - comes from uncontrolled seizures in chronic focal epilepsy. I don't think that the literature is as clear in generalised / idiopathic epilepsies.

The general thinking in the most common intractable focal epilepsy - temporal lobe epilepsy due to hippocampal sclerosis - is that an early aberrant neurological event causes some alteration in brain physiology / anatomy (e.g. hippocampal pathology), there is then a latent period (can be decades) which supports unnoticed (because it's asymptomatic) epileptogenic processes (e.g. pathological development of anatomy & physiology that would later support the generation of epileptic seizures), habitual epilepsy kicks in, and if uncontrolled will lead to further brain degeneration (both hippocampal and extrahippocampal). I've got to admit, it's probably not as simple as this, and this hasn't been conclusively demonstrated in humans. And it's hard to disentangle the potentially degenerative effects of seizures from the effects of anti epileptic drugs and other factors.

Happy to point you to some relevant studies if you like, but this literature is huge!

Cheers,

Simon.

Thank you for your responses!

Daniel, this paper is useful indeed, and Simon thank you for the insight - I'd be very grateful if you could offer some pointers!

The attached review has been useful, but key referenced papers are over 40 years old so anything more recent would be welcomed. I also found the Helmstaedter (2003) longitudinal study.

However I was surprised by your response since one of the few papers I found, "Is Partial Epilepsy Progressive? Ten-Year Follow-Up of EEG

and Neuropsychological Changes in Adults with Partial Seizures" by Holmes (1998) concludes that "for most adults with medically intractable

complex partial epilepsy, the EEG and neuropsychological test

scores remain reasonably stable over a decade." This sparked my interest since it seems counterintuitive...

EEG signatures of ictal and interictal activity have been shown to be stable over time. This illustrates my point that it depends from what position you're looking. A lot of the human MRI, animal and neuropsychological (including Christoph Helmstaedter's work) literature do indicate that some epilepsy conditions results in progressive deterioration that is over and above what would be expected in healthy people.

From my standpoint, which is a neuroimaging one (structural and functional MRI), chronic uncontrolled focal epilepsy that causes frequent loss of consciousness (i.e. previously called complex partial seizures) despite the unsuccessful use of multiple AEDs does cause progressive neurological deterioration when patients are followed up over a sufficient time period. But note the caveats - seizure type, sufficient time, imaging, uncontrolled seizures....

Dear Celia:

Epilepsy is a chronic neurological condition characterized by uncontrolled excessive activity by either a part or all of the CNS. When the basal level of excitability of all or part of the CNS rise above a certain critical threshold, an individual may become vulnerable to epileptic attacks.

Some, important terms to recognize in Epilepsy and location of the focus are the two major types of seizure:

1-Partial seizures: Almost always result from some organic lesion of the brain.

2-Generalized seizures

Other important terminology and description:

-Focal seizures

-Psychomotor Epilepsy is a complex partial seizure

-Petit mal seizures: Generalized epilepsy where EEG has spike and wave components - It occurs in two forms: myoclonic and absence. IN THE MYOCLONIC FORM, THE INDIVIDUAL EXHIBITS A SINGLE VIOLENT JERK OF THE MUSCLE IN ARMS OR HEAD AND THEN STOPS IMMEDIATELY. THIS TYPE OF ATTACK FREQUENTLY BECOMES PROGRESSIVE AND MORE SEVERE UNTIL THE PERSON EXPERIENCES A GRAND MAL.

THE ABSENSE TYPE IN RARE INSTANCES CAN INITIATE GRAND MAL ATTACK.

-Grand mal seizures: Generalized epilepsy where EEG has tonic and clonic phases

-Interictal spikes in EEG occurring between full-blown seizures arising from depolarization shifts

-Temporal lobe epilepsy

-Jacksonian epilepsy

So, in order to answer your question and aside from the points discussed above, there is no definite indication that epilepsy is progressive. To be progressive there should be proliferation of the major causes that started epilepsy, e.g., diseased brain tissue, infection, or tumors.

I hope that this helps!

This is the crux of the issue - do seizures, as individual neurological events, worsen/damage a patient's clinical features beyond their underlying cause(s)?

Interestingly this is the first "no" it seems.

I realize this is very difficult to distinguish, which is why I was wondering what the 'feel' was in practice, etc. I guess temporal epilepsies are better suited for this sort of investigation. (my main interests are in partial/focal with or without secondary generalization)

From a cognitive perspective, I believe Helmstaedter's "Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease" (which many of you already referenced) may be particularly interesting to you. Brain (2009) 132, 2822-2830. His conclusion is that there is a decline in developmental trajectory that impedes neuropsychological development. This later interacts with age to lead to an earlier cognitive decline than would be expected in a healthy individual. There is other evidence, however, that epilepsy does indeed induce a "dementing condition" if you will. For instance, hippocampal sclerosis has been shown to evolve over time, and the degree of hippocampal sclerosis correlates highly with memory impairment. Also, events such as episodes of status lead to progressive decline. My hunch is that both processes are occurring.

Thank you very much for the insight.