Some excitatory and inhibitory factors involved in the epileptic state.

Many factors are involved in the determination of the epileptic threshold and the precipitation of epileptic seizures. The balance between the underlying excitatory and inhibitory mechanisms are often imperfectly understood. However, some of these factors must be fully considered if the management of those with epilepsy is to be effective. This applies especially to children. Certain types of epilepsy are genetically determined, and others are age-related. Development of the brain plays a crucial role in the changing liability to epilepsy. If these processes are disturbed by various lesions and diseases, such as metabolic and toxic disorders, protective mechanisms may suffer. Kindling and mirror foci, the role of the cerebellum, and reflex epilepsy will be discussed. There are some seizure-inducing factors which are susceptible to change, and can be as important as anti-epileptic drugs in controlling seizures. The use and limitations of these measures, and of drugs, will be considered.

Hypothesis: the classification of epileptic seizures according to systems of the CNS.

Several comprehensive classifications of the epilepsies and epileptic syndromes have been proposed and the purpose of the last one (1985) was to supplement the International Classification of Epileptic Seizures as accepted by the General Assembly of the International League Against Epilepsy in 1981. These efforts represent a major contribution to a difficult problem, which must be continued as further scientific advances permit. Categorization according to clinical seizure type is a logical approach, inasmuch as response to antiepileptic medication depends more on seizure type than on etiological or other factors. A limitation of this approach, however, has arisen as a result of the Commission's failure to relate clinical seizure types to the underlying neurophysiology that mediates them. This has resulted in the categorization of absence as a generalized form of seizure along with generalized tonic-clonic seizures (GTCS). On the other hand, temporal lobe seizures (including automatisms) have been categorized as a complex form of partial seizures, which emphasizes their focal origin. It is the belief of the authors that a further clarification might be achieved, if a differentiation of seizure types is made with respect to the underlying CNS circuitry which mediates the sustained discharge that determines the clinical manifestations of each type. Focal origins, while significant, assume a secondary importance, since they do not explain the sustained discharge that mediates clinical seizure types, except in the case of elementary partial seizures (EPS) that remain discretely localized. In contradistinction to GTCS that essentially involve the entire CNS, absence and complex partial seizures (CPS) should be categorized as limited forms of seizures, mediated by bilateral, regional systems.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of seizure-inducing factors in youth.

Of over forty known epileptogenic mechanisms, some eight involve transient conditions, the regulation of which necessarily involves the understanding cooperation of the patient/parents. Tension states, alterations of the wake-sleep cycle, fatigue and sleep deprivation, CNS stimulation by sensory or drug means, and shifts of the water and acid-base balances constitute the bulk of such seizure-inducing factors. The relative lack of CNS homeostatic control, due to immature development of the blood-brain barrier and cerebral maturation, serve to exaggerate these problems in childhood. In a referred group of 150 refractory epileptic children, the seizure-inducing mechanisms were found to be important (50% reduction of seizure incidence) in 20% and to be of "crucial" importance (complete control) in an additional 14%. These results indicate the importance of such mechanisms in selected children with epilepsy, who were only marginally or inadequately controlled by drug therapy. Reviews of the literature have suggested that this more comprehensive approach to the therapeutic management of epilepsy has not been adequately exploited.

A study of intrathecal, cerebrospinal fluid-to-brain exchange.

A cerebrospinal fluid (CSF) to brain exchange has been postulated for lipid-soluble and small molecular substances and has led to nearly 100 attempts per year to produce central effects via intrathecal injections. With few exceptions, however, modern neurological practice has avoided this approach because of its demonstrated ineffectiveness and dangers. The practicability of an intrathecal CSF to brain exchange was tested by cisternal infusions of mock CSF at different infusion pressures that might counteract central nervous system intoxications of systemic origin. Those efforts failed in different test situations with each of three barbiturates. Steady state doses at a selected level of barbiturate anesthesia were the same, whether induced by cisternal infusion or intravenously, and this was true for barbiturates of widely different lipid solubility. The cerebral response to pentylenetetrazol was delayed well beyond its rate of response when introduced intravenously. These results suggested that the bulk clearance rate and venous resorption of CSF were sufficient to prevent significant diffusion of the barbiturate or even mock CSF into the brain following intrathecal injection. Because central effects that follow venous resorption may be confused with direct central effects, many previous clinical reports are questioned. Apparent exceptions to the ineffectiveness of intrathecal therapy, such as spinal anesthesia, were discussed in terms of their special local effects. The relative effectiveness of intrathecal agents should be evaluated by comparing maintenance doses for a given central effect, when produced by both intrathecal and i.v. routes. Previous reports on rates of intrathecal infusion, intracranial pressure relationships, and the relative safety of such infusions were confirmed and extended.

The importance of seizure-inducing factors in the control of refractory forms of epilepsy.

Of over 40 known epileptogenic mechanisms, some 10 vary from hour to hour, depending upon habit factors and the daily activities of the patients. Tension states, alterations of level of consciousness, sleep deprivation, disturbances of water and acid-base balances, sensory and drug stimulation, and drug withdrawal are the principal factors involved. Their importance varies widely in patients, as well as with time. This fact and the concentration of physicians upon drug therapy have served to deemphasize this aspect of antiepileptic therapy. This point was clearly verified by reviews of the literature. In a prospective study of 500 drug-resistant patients, such seizure-inducing mechanisms were studied. Methods of identification, evaluation, and regulation were developed. The results indicate that in selected patients the regulation of such factors may play a significant role in the stabilization and improvement of the underlying epileptic condition. In 17% of a refractory group, such factors were found to be of crucial importance. In spite of intensive efforts with drug therapy over the past 4 decades, the incidence of drug-resistant cases remains high. The more comprehensive approach suggested offers an attractive, partial solution to this difficult problem.