Hemispheric Lesions

Epileptogenic lesions affecting the whole or most of a hemisphere are more common in pediatric than adult epilepsy surgery candidates. Malformations of cortical development (MCD), Sturge-Weber syndrome, encephalomalacia caused by a variety of insults, and Rasmussen’s encephalitis constitute the four major groups. These groups are typically associated with hemiparesis, with or without hemianopsia.

Focal Lesions

The single major group of early focal epileptogenic lesions requiring epilepsy surgery is focal cortical dysplasia.7,36 Other focal malformations would include heterotopia, polymicrogyria, schizencephaly, and hypothalamic hamarto-mas.37 Dysembryoplastic neuroepithelial tumors and the multifocal cortical tubers of tuberous sclerosis also fall in the spectrum of dysplasias on the border zone of neoplasms.37 Other early tumors include ganglioglioma, gangliocytoma, and pleomorphic xanthoastrocytoma.7,38 Focal areas of glio-sis caused by remote vascular insult, trauma, and infection constitute the rest of early focal lesions.9,39

Mesial temporal sclerosis (MTS) is an uncommon lesion in early life,9 although cases in patients as young as 4 months have been described.40 In pediatric epilepsy, surgery candidates, MTS is more likely to exist as dual pathology with ipsilateral anterior temporal cortical dysplasia.9,38,41

Nonlesional MRI

Despite advances in structural neuroimaging, a significant number of patients with drug-resistant focal epilepsy do not have an identifiable structural lesion on MRI. Successful surgical excision has been performed in some of these apparently nonlesional patients on the basis of convergence of clinical and electrophysiological data7 or supported by functional imaging studies such as positron emission tomography or ictal single photon emission computed tomography.11 Histopathology revealed evidence of cortical dysplasia, neuronal heterotopia, and focal gliosis as the substrates of epilepsy in majority of MRI-negative lesions.7,42

Early Lesions: Role of Adaptive Plasticity

Unlike in adults, plasticity of the young brain serves as a cushion against new postoperative neurological deficits after resection of eloquent regions, including language, motor, and primary visual cortex areas.43–45 Plasticity, in simple terms, refers to the recruitment of neurons to perform an eloquent function that is otherwise not destined to. Such gain of function through plasticity is referred to as adaptive plasticity.44 The classic example is transfer of language functions to the right hemisphere with early left hemispheric injuries.43,46–50 Dominant handedness can also transfer effectively with early injuries. Handedness is determined by the presence of praxis center in the inferior parietal lobule rather than language areas.51 However language and praxis centers often exist in the same hemisphere, and, hence, handedness is a surrogate marker for language dominance.51,52 Motor, sensory, and visual functions have limited plasticity, and the contribution of neuronal plasticity to recovery is limited. Plasticity of cognitive functions is difficult to evaluate separately but likely to be significantly more than sensorimotor functions.

Plasticity and the resultant transfer of functions are best studied in the language domain. The anatomical location of Broca’s area and Wernicke’s area are fairly consistent in the majority of normal subjects. Epileptogenic lesions in and around these locations displace the language functions to adjacent areas or in extreme instances to the homologous area in opposite hemisphere.49,50,53 Three major factors influence the transfer of the language functions: age at insult and the size and the nature of the lesion. Younger age at insult, large lesions, and destructive lesions are more likely to shift the language areas. Of these, the most important factor is age at insult; 6 years is generally the cut-off for effective language transfer to occur.50 However, these early lesions may not manifest with epilepsy until later, technically beyond the period of effective plasticity. In these instances, the age at the time of brain injury is more important than the ageat onset of epilepsy or age at surgery. Hence these plasticity rules may apply even in adults, provided the lesion is acquired within the period of plasticity window, typically before 6 years of age. Even though effective transfer of functions occurs when the brain injury occurs early in life, some degree of plasticity may be possible in late childhood and even in adults.47,54,55 Large hemispheric lesions, as in perinatal stroke or hemimegalencephaly, shift language areas to the opposite hemisphere.49,50 On the contrary, smaller lesions such as tumors tend to displace language areas to adjacent areas in the same hemisphere.53 This information is critical when operating such lesions, because peritumoral bed may have language function.

Transferred language function is never as good as naturally acquired language, and several studies suggest that the left hemisphere is phylogenetically superior in language acquisition in most patients.43,56 This applies more so to expressive compared with receptive language functions. Wada testing is difficult to perform in children with neurocognitive deficits but has been reported to be of help in selected cases in the past.57 Functional MRI and child-specific language testing paradigms may soon replace Wada testing for language lateralization.58,59

Early Lesions: EEG Manifestations

Interactions between an early epileptogenic brain lesion and normal developmental processes may result in EEG patterns that are different from, and more diffuse than, those seen in patients with lesions acquired after brain maturity. This was first recognized in young children who presented with the generalized pattern of hypsarrhythmia and infantile spasms and had seizure-free outcome after resection of a congenital or early acquired focal or hemispheric brain lesion.11,42 Subsequently, successful epilepsy surgery was also reported for older children and adolescents with early brain lesions and other generalized EEG patterns, including the generalized pattern of slow spike-wave complexes traditionally associated with Lennox-Gastaut syndrome ( Fig. 3.1 ) or the contra-lesional patterns (maximum epileptiform abnormalities over the hemisphere contralateral to the lesion) seen in the setting of extensive unilateral encephalomalacia ( Fig. 3.2 ).26,60

Neither West syndrome with hypsarrhythmia nor Lennox-Gastaut syndrome with generalized slow spike wave complexes were recognized as surgically amenable initially.61,62 These syndromes are not etiology specific and can occur in response to a wide variety of cerebral insults. The occurrence of identifiable focal and multifocal lesions in these disorders prompted several centers to attempt le-sionectomies in these patients who otherwise had multi-drug-resistant epilepsy with very high seizure burden with very few options left.8,11,26,60,63–65 Successful surgery in these patients has widened the spectrum of epilepsy phenotypes amenable to surgery.

The key factor for manifestation of the generalized patterns in these surgical candidates appeared to be the age at the time of lesion occurrence (78% pre- or perinatal; 90% within the first 2 years of life in one series)26 rather than the age at evaluation for epilepsy surgery (0.2 to 24 years, median 8 years). This phenomenon of “generalized patterns in focal lesions” follows the rules similar to the adaptive plasticity rules in language transfer described earlier. When we assess an individual for left hemispherectomy at any age, the important factor deciding the side of language dominance is age at lesion occurrence, not age at presurgical evaluation.50 Generalized EEG patterns seen in focal lesions appear to follow the same rules.26

Although not all children or adolescents with early lesions will present with generalized or contralesional epileptiform discharges, it is important to be aware of the phenomenon so that carefully selected children with focal or unilateral epileptogenic lesions are not excluded from surgical consideration. In one series,26 seizure-free outcome did not differ between children and adolescents with early brain lesions who had generalized EEG abnormalities (72% of patients were seizure free at last follow-up) compared with children with ipsilesional epileptiform discharges. The contralesional EEG abnormalities (24% of patients) appeared to represent an altered expression of diffuse EEG pattern, decreased on the ipsilesional side affected by large destructive lesion. Such false localizing and lateralizing EEG abnormalities are not limited to large destructive hemispheric lesions. Even in typical focal epileptic syndromes, such as temporal lobe epilepsy caused by neoplasms in childhood, may express multiregional and contralesional EEG abnormalities that disappeared after successful removal of the focal epileptogenic lesions.66,67 Most of the patients in the latter series had early onset brain lesions.

The mechanisms underlying the generalized epileptiform abnormalities in focal cerebral lesions are unknown. Some practitioners view this as a form of maladaptive plasticity of immature brain.44,60 The lesions in the environment of immature or maturing neural network of the young brain alter the neural circuits, leading to spontaneous hypersynchrony, resulting in generalized features.68 Some authors suggested involvement of the thalamocortical networks.69 Generalized epileptiform abnormalities have been described with hypo-thalamic hamartomas, as well.65 In a study on the evolution of epilepsy in hypothalamic hamartomas in children, gelas-tic seizures were noted in infancy, followed by generalized tonic seizures at approximately 6 years of age. Early EEGs were normal but later became progressively abnormal with the emergence of generalized epileptiform abnormalities. Intraoperative EEG showed persistence of generalized interictal spike-wave, even after removal of hamartoma; however, these discharges resolved in postoperative studies. This observation suggests that the generalized epileptiform discharges may be a result of secondary epileptogenesis similar to the kindling phenomenon seen in animals.70 These discharges may ultimately resolve if the kindling primary focus is removed before the secondary epileptogenic areas become completely independent.