LASSE: abstract

Topic: The concept of thresholds in epilepsy

Peter Wolf

 

Danish Epilepsy Centre Dianalund and National Hospital Copenhagen, Denmark

 

This lecture and practical discussions will address the concept of thresholds in epilepsy. It is well known that with adequate stimulation every brain can be induced to produce epileptic seizures. The seizure threshold is a theoretical construct expressing the brain’s intrinsic resistance to generate seizures. Epilepsy can be defined as a condition where the seizure threshold is abnormally low. The seizure threshold is probably not constant but subject to e.g. circadian and other periodic changes as well as to influences of external factors.

 

The therapeutic and toxic thresholds are operational concepts to support rational antiepileptic drug (AED) treatment by defining the individual therapeutic range of a given AED in a given patient. The therapeutic threshold can be determined by measuring the AED levels with the highest subtherapeutic, and the lowest therapeutic treatment. To be effective, the AED levels must be kept above the therapeutic threshold. Apart from this practical aspect, the therapeutic threshold can also be understood as an indirect expression of the patient’s seizure propensity. Thus, recent data indicate that the therapeutic threshold is not necessarily a constant function in time but that it has a tendency to decrease during a period of full seizure control where the seizure propensity may decline.

 

The toxic threshold can be determined by measuring the AED levels with the highest subtoxic and the lowest toxic dose. This threshold probably is a stable individual expression of tolerance.

 

At the end the students should be able 1) to apply AED monitoring rationally by  working with the concept of individual thresholds for therapeutic effect and toxicity; and 2) to understand epilepsy as a dynamic condition where seizures occur as the result of antagonistic, both ictogenic and antiepileptic mechanisms which may change over time.