Each of the chapters in this section uses a different approach to address one of two challenges in epileptology: (a) the relationship connecting seizure semiology, the structures involved in epileptogenesis, and related lesions and (b) the interplay between predisposing and precipitating factors in igniting seizures. In addition, chapters on familial epilepsies involving the temporal lobe (Chapter 248), frontal lobe (Chapter 249), and variable foci (Chapter 255) reflect the increasingly recognized role of genetics in the etiology of seizure disorders, including those without an apparent familial seizure history.

The precise definition of the structures or systems responsible for ictal phenomena has long posed a challenge to the best efforts of distinguished investigators. For Hughlings Jackson, “the study of partial seizures became the starting point for the study of localization of function within the central nervous system.”³¹ As described by Jasper,³¹ Sherrington electrically stimulated the cortex of anthropoid apes to examine functional–structural relationships. The early stimulation studies in humans performed by Foerster¹⁷ preceded the exhaustive studies carried out by Penfield and Jasper in the course of evaluating patients for epilepsy surgery; these culminated in their classic work, Epilepsy and the Functional Anatomy of the Human Brain.³¹ Interictal electroencephalography (EEG) has provided helpful correlative data to clarify the localizing significance of ictal symptomatology,^11,31 as has intracranial recording.³ However, Williamson and Engel (see Chapter 246) caution that sophisticated techniques for correlating ictal electrical activity with clinical phenomena have only revealed the complexities of anatomic–symptomatologic relationships.

A second method of identifying structures or systems responsible for ictal phenomena has been to correlate the latter with structural lesions. In Chapter 246, the authors indicate that Hughlings Jackson first recognized the correlation between ictal behavior and the location of structural abnormalities in the brain. Defining “specific lesions” as “discrete focal (or regional) structural pathologies that are associated with chronic partial epilepsy,” Chapter 251 examines such relationships. These authors review changes in neurotransmitters in the vicinity of tumors, favoring excitation over inhibition. They cite the finding of Awad et al.⁵ that lesionectomy alone more often renders patients seizure free than resection of epileptogenic cortex without regard to lesion, supporting a direct relationship between structure and ictogenesis. Fortunately, improved neuroimaging now more accurately identifies focal or regional epileptogenic lesions (Chapters 247 and 251).

However, several factors complicate such relationships. Penfield³¹ demonstrated that the form of the attack is considered to be due to the functional characteristics of the local area of onset within the brain, the strength of initial discharge, and the path of its spread to other brain areas. Rasmussen³² acknowledged this factor of propagation in elaborating a concept of secondary localizational aspects of epileptic phenomena. His review of seizure-free patients after frontal lobe resection found no correlation between surgery site and seizure characteristics. Variability of propagation patterns is a principal factor in confounding any anatomic classification of seizures.

Williamson⁴¹ indicated that rapid spread of frontal seizures clouds the localizing value of many ictal phenomena. Varying and bilateral motor ictal phenomena may be consequent to multiply targeted intracortical and corticofugal projections within the motor system, including ipsilateral projections to proximal limbs.^8,14,41 Abundant projections from the occipital cortex to anterior temporal areas^24,35 effect the dyscognitive seizures from occipital epileptogenesis. More recently demonstrated temporal-to-occipital projections^4,16,25 are likely among factors producing visual auras from extraoccipital seizure origins.⁷ In addition, a seizure disorder beginning while the brain is developing may lead to abnormal patterns of innervation.^19,38 For example, a seizure-related failure of “pruning” through apoptosis may produce a permanently abnormal connectivity.²²

Moreover, epileptogenic regions may be remote from a lesion that is also epileptogenic (Chapter 251). Temporal epileptogenic regions may coexist with epileptogenic occipital lesions^10,29 or with parietal arteriovenous malformations.⁴³ For undetermined reasons, lesions may be unevenly epileptogenic around their peripheries. Thus, O’Brien et al. (Chapter 252) cite works indicating that resection of a lesion as well as epileptogenic cortex is necessary for optimal seizure reduction.^6,39,44 A further confounding factor impeding the establishment of structural–semiologic relationships is the possibility that lesions may extend beyond their manifestations on neuroimaging studies. This factor may underlie the relative ineffectiveness of surgery as treatment for epileptogenic neuronal migration disorders (Chapter 251).