Generalized Epilepsy with Spike‐and‐Wave Discharge: A Reinterpretation of Its Electrographic and Clinical Manifestations1

Summary: Electrophysiological data obtained in generalized penicillin epilepsy of the cat indicate that bilaterally synchronous spike‐and‐wave discharge represents an abnormal response pattern of cortical neurons to afferent thalamocortical volleys normally involved in the elicitation of spindles. Such a response occurs under conditions of diffuse mild cortical hyperexcitability that causes cortical neurons to generate an increased number of action potentials per afferent volley. This secondarily leads to powerful activation of the in‐tracortical recurrent inhibitory pathway. The result is an alternation of short periods of increased cortical excitation corresponding to the EEG spike with longer‐lasting periods of intense cortical inhibition corresponding to the wave component of the spike‐and‐wave complex. This pattern of widespread synchronous oscillation between increased excitation and increased inhibition profoundly disrupts the normal pattern of cortical neuronal activity necessary for sustaining higher nervous functions, i.e., such components of mental activity as perception, cognition, memory, and voluntary motor activity. It is the disruption of these components of mental activity that occurs to a variable degree during generalized spike‐and‐wave discharge, rather than disruption of a more fundamental mechanism of maintenance of consciousness related to the sleep‐wakefulness cycle, which depends on upper brainstem functions, that characterizes the disturbances of higher nervous functions typical for the absence attack. According to the severity and pervasiveness of the disruption of normal cortical activity by the spike‐and‐wave pattern, impairment of mental function may range from an almost imperceptible degree of transient interference with mental processes to complete arrest of mental activity that can be considered as being equivalent to temporary loss of consciousness. Even though the regular alternation between periods of excitation and inhibition appearing synchronously in widespread cortical areas certainly is a highly abnormal pattern in terms of its temporal and spatial organization, the cycles of activities through which individual cortical neurons go during spike‐and‐wave discharge do not exceed the normal range of neuronal excitatory and inhibitory states. More particularly, the more excessive and definitely abnormal state of individual neuronal hyperexcitability, as represented by paroxysmal depolarization shifts that occur in focal epileptogenic lesions, does not seem to be a characteristic of this form of epilepsy. It is therefore proposed that the spike‐and‐wave pattern represents a milder form of epileptic neuronal behavior that can be considered as a first degree of epileptogenesis, whereas activity characterized at the neuronal level by paroxysmal depolarization shifts represents a more intense second degree of epileptogenesis. The two states may coexist in one brain, the first degree of epileptogenesis being, for instance, present diffusely either on a genetic or acquired basis, whereas in a circumscribed area the second degree of epileptogenesis may prevail and give a focal accentuation to both the electro‐graphic and clinical manifestations of an epileptogenic disorder that also exhibits some generalized features. Such a concept facilitates an understanding of the neurobiology of epileptogenic states, for which a multifactorial origin is becoming increasingly more apparent. On a more practical level, this concept makes it easier to understand the frequently encountered but often baffling coexistence of generalized and focal features in the EEGs of individual epileptic patients. The EEG under these conditions may reflect a topographical gradation of a diffuse epileptogenic process.