The question as to the validity of the concept has been explored in the book by Trimble and Schmitz (14), where translations of the original papers from Landolt and Tellenbach are given, with contemporary observations from several investigators. The observations of Landolt were largely ignored by several generations of neurologists, for two main reasons. First, he published mainly in German, and second it brought neurology uncomfortably close to psychiatry. The idea that suppression of seizures could be harmful to patients was a complete anathema to many who were of the view (correctly) that the first and main aim of the treatment of epilepsy must be to control seizures, and that (incorrectly) the brain was some kind of static machinery that yielded its secrets to the pathologist’s knife. The observations were made at an historical time of perhaps the greatest division of the two specialties (neurology and psychiatry) and before a distinct breed of specialists emerged with a special interest in epilepsy—epileptologists. Further, the number of drugs available for the treatment of the condition were distinctly limited.

Landolt’s contribution raised many important issues that are still germane today. Seizures are not the same as epilepsy, and the two are frequently confused. Seizures are but one manifestation of an underlying disease process, the latter being present well before and after the seizure has been expressed clinically. The underlying dysfunction, continuing in time, has other effects, many more subtle than the seizures, but nonetheless important clinically. Cognitive dysfunction is but one possibility, with psychosis being another possibility. Landolt and Tellenbach pointed out how the underlying epilepsy in many of their cases was “psychomotor,” implying a temporal lobe pathology underlying the seizures. At this time the concept of the limbic system and its anatomical connections and relationship to the control of emotional behavior was barely on the horizon, and the ideas of neurotransmission were in their infancy. However, the observation that suppression of seizures of a temporal lobe origin could lead to an alternative clinical expression has been but one of the pieces of the jigsaw of unraveling the role of the limbic lobe of the brain in the regulation of behavior. The concept did indeed bring psychiatry close to epileptology. Electroconvulsive therapy emerged as an effective treatment for severe psychiatric disorders, some behavior disorders associated with epilepsy had a sounder neuroanatomical/neurophysiological basis and could be acknowledged clinically, and some of the earlier paradoxes were resolved. As Wolf and Trimble (10) noted, the antagonism was not between epilepsy and schizophrenia, but between seizures and the symptoms and signs of psychotic states. In other words, within the increased association between epilepsy and psychoses was an antagonism between seizures and hallucinations and delusions. In chronic cases this emerged when the pattern of the seizures changed in the longitudinal course of epilepsy, with
seizure diminishing and the psychotic symptoms emerging. However, acutely this could be revealed through states of forced normalization.

The original observations of Landolt were made when patients were given ethosuximide, then a new antiepileptic drug (AED). Patients became seizure-free, and in some the psychosis erupted. This potential, for the sudden transformation of an aberrant cerebral process from one state to another, helps explain a mutability of the clinical picture. The latter then is understood as being based on changing the underlying neurophysiological/neurochemical status of the brain, brought about by artificially altering the neuromodulators within the brain, more specifically by the enhancement of inhibitory factors. This makes heuristic sense, if the brain is viewed as a dynamic but self-contained energy system; sudden change does not allow for the resetting of a previously established homeostasis. Landolt referred to his phenomenon as based upon a “supranormal” inhibitory process, but he could not, in the absence of the neurochemical understanding that we now have, take this any further.

Stevens (15) has put forward the view that “all that spikes are not fits,” and that inhibition by dopamine, γ-aminobutyric acid (GABA), and other transmitters is essential to prevent the normal brain from being in a continual state of status. In her model, however, excess inhibition predisposes to psychosis (e.g., dopamine agonism being psychotogenic), the alternative to this being the stunning effect of clozapine, the antipsychotic drug most likely to provoke seizures, in intractable cases of psychosis. These observations and theories, derived from psychiatry and neurology, have not only enhanced our understanding of the basic mechanisms of the psychosis, but have also allowed us to understand some of the behavior consequences of prescription of AEDs better. Psychosis and depression are the most frequently noted behavioral effects, and are commonly the reason to stop such drugs. In many cases this occurs in the setting of seizure resolution, and if EEG is performed, in the presence of normalization (16). Although examples of the latter may be seen with most of the AEDs, those which are GABAergic seem the most relevant, again enhancing our understanding of the neurochemical basis of behavior, and leading to caution in the clinical use of such drugs in certain populations (17).