The history and clinical findings in candidates for hemispherectomy (1,7,8,25, 26, 27, 28, 29) usually reveal a severe hemispheric encephalopathy. Common etiologies include malformations of cortical development involving multiple lobes or the entire hemisphere with hemimegalencephaly or without hemispheric enlargement, ischemic stroke, and predominantly unilateral perinatal ischemic injury mimicking periventricular leukomalacia. Less common are Sturge-Weber and Rasmussen syndromes. Patients may have a facial port-wine stain as in Sturge-Weber syndrome. Patients with hemimegalencephaly may show ipsilateral somatic overgrowth or the cutaneous findings of epidermal nevus syndrome or hypomelanosis of Ito. They usually have hemiparesis associated with a hemisensory deficit that is often difficult to assess in small children. Most patients have a homonymous hemianopsia or, in the case of progressive syndromes, will acquire one. In many patients with congenital hemiplegia, body asymmetry will be obvious, at times complicated by sympathetic dysfunction on the affected side.

The type and frequency of seizures in these patients are variable, but the onset usually dates from early infancy, often from the first few days of life. Most of these patients have different types of seizures, such as partial motor, absences, or complex partial attacks. A number of patients, particularly infants, have seizures that by definition are nonlocalizing, such as generalized tonic and atonic seizures, myoclonic seizures, or infantile spasms. The clinical detection of the focal origin and onset of seizures continues to be a challenge in infants. Clinical semiology generally does not help localize or lateralize seizure onset in children younger than 2 years (28).

As in all surgical candidates, a careful evaluation to establish seizure intractability should be undertaken. This is usually not a problem, given the often catastrophic presentation in most of these children (28,30). A careful review of pharmacologic management with optimal doses of anticonvulsant medication (1), both as monotherapy and in combination therapy, should be carried out. If previous pharmacologic management has been less than ideal, additional drug trials should be undertaken. However, surgery should not be delayed in a child with daily or frequent prolonged seizures with a low likelihood of response, as in hemimegalencephaly or other malformations of cortical development.

No surgical procedure arouses as much initial disbelief as hemispherectomy. Repeated discussions with the family are essential and should include interpretations of the operative procedure. The possibility of surgical treatment should be broached early, with emphasis on the extent of the procedure and its potential results. The risks of operative complications, as well as the possibility of aggravating incomplete deficits, such as a mild hemiparesis or an incomplete hemianopsia, should be mentioned. On the other hand, the high chance of seizure freedom after surgery compared with nonsurgical options, as well as potential postsurgical benefits in behavior and development should be explored.

Optimal visualization of both hemispheres is mandatory with high-resolution magnetic resonance imaging (MRI), which has helped define many associated structural anomalies, such as gliotic changes with encephaloclastic porencephalies or Rasmussen encephalitis (31), progressive atrophic changes with Sturge-Weber syndrome or Rasmussen encephalitis, and changes seen in migrational hemispheric syndromes, such as increased gray-matter thickness, poor gray-white differentiation, abnormal gyral and sulcal patterns, and the abnormal clefts characteristic of widespread cortical dysplasia and hemimegalencephaly (32). MRI with gadolinium enhancement can define pial angiomatosis. Venous magnetic resonance angiography can identify the vascular changes associated with venous drainage in patients with Sturge-Weber syndrome, cortical dysplasia, or hemimegalencephaly, precluding the need for an arteriogram. Computed tomography (CT) scans often show large porencephalic lesions, particularly if calcifications are present, and atrophic changes.

Indirect measurement of cerebral blood flow by single-photon-emission computed tomography (SPECT) has become an important tool in the evaluation of children with epilepsy (33). In patients with active epileptogenic abnormalities, such as those with epilepsia partialis continua, the
areas of highest perfusion may help define the most epileptogenic tissue. In one study (34), interictal hypoperfusion was superior to MRI with gadolinium in establishing the extent of brain damage from pial angiomatosis in Sturge-Weber syndrome. Hypoperfusion of the contralateral cerebellar hemisphere, reflecting corticopontocerebellar pathways, may be another helpful lateralizing sign. Unilateral hypoperfusion in brain SPECT correlated with good results in patients whose electroencephalographic (EEG) findings point to involvement of the contralateral hemisphere (34). Return of regional cerebral blood flow to normal in the nonaffected hemisphere may indicate more normal functioning and maturation after seizures are controlled (35).

Positron emission tomography (PET) provides an indication of the metabolic state of the hemisphere (36). Hypometabolism in the abnormal hemisphere is a helpful lateralizing sign. In children with Sturge-Weber syndrome (37), PET frequently shows a markedly depressed metabolic rate in the affected hemisphere, extending beyond the abnormalities seen on brain MRI or CT. Cortical hypometabolism in the opposite hemisphere in patients with hemimegalencephaly has indicated bilateral abnormalities with a higher chance of partial or no seizure control after surgery. Ipsilateral hypometabolic changes or ipsilateral areas of hypermetabolism surrounded by hypometabolic changes, usually related to intense epileptic activity, have been found in children with lateralized scalp EEG but normal MRI results (38,39); this may aid in deciding whether to perform hemispherectomy, hemispherotomy, or multiple lobar resections and in predicting whether good postoperative results will be achieved. Metabolic recovery of the ipsilateral caudate nucleus (40) and other brain regions, such as the lateral premotor, caudal sensory motor, and inferior parietal cortices (41), often years after hemispherectomy, may be an indication of functional reorganization (40) and may parallel functional improvement (42).

Proton magnetic resonance spectroscopy (43,44) reveals decreased N-acetylaspartate (NAA) levels in patients with Rasmussen encephalitis; this involves the entire hemisphere and correlates with brain atrophy. Elevated levels of glutamine and glutamate may be significant, high-lighting the potential role of abnormal excitatory neurotransmitters in the generation of seizures (43). A marked decrease in the size of spectral peaks, centered at 0.98 and 1.3 parts per million (ppm) coupled with an increased choline level, may indicate concurrent active demyelination and cell death (43).

Functional MRI has been used to study reorganization of sensorimotor function. In some patients, activation of premotor, supplementary motor, and inferior parietal cortices with passive movement of the hemiplegic hand have been found in the ipsilateral hemisphere (45,46). Sensory evoked responses of lower amplitude and increased latency compared with those on the normal side (47) have been recorded. Transcranial magnetic stimulation and motorevoked potentials have shown that the reorganization of motor function follows a diverse pattern and does not correlate with the degree of neurologic impairment (48,49).

Scalp video-EEG monitoring is essential in the evaluation of hemispheric syndromes (1,50,51), from both diagnostic and prognostic standpoints. Well-localized or -lateralized interictal and ictal EEG abnormalities correlating with the clinical and imaging findings usually predict excellent postsurgical results, although bilateral epileptogenic abnormalities, including hypsarrhythmia, may be seen. In these instances, subtle clues such as continuous regional slowing; predominance of epileptiform abnormalities in one region; absence of background or physiologic rhythms such as spindles; vertex waves over one hemisphere; or focal ictal EEG onset may help localize or lateralize the epileptogenic zone(s).

Sometimes the scalp electroencephalogram shows bilateral independent discharges, suggesting epileptogenicity in both hemispheres, particularly in postmeningitic, posttraumatic, or posthemorrhagic encephalopathies. This finding may also represent the development of secondary epileptogenesis in the contralateral hemisphere. When good clinical, functional, and MRI lateralization is associated with large encephaloclastic porencephaly, a review of previous electroencephalogram recordings may help to clarify the significance of the contralateral findings (28).

Ipsilateral burst suppression, particularly during sleep, has been reported in patients with hemimegalencephaly (52,53) and represents a good lateralizing finding.

The following findings on scalp electroencephalography (considered independently) are indicative of a good outcome: the presence of (a) ipsilateral suppression of physiologic rhythms in the abnormal hemisphere; (b) multifocal epileptic activity confined to the damaged hemisphere; or (c) bilateral but synchronous discharges maximum in the abnormal hemisphere (54); and the absence of (d) contralateral slowing; (e) generalized or bilateral independent spiking (55); and (f) abnormalities in background activity over the “good hemisphere.” Increasingly, however, evidence shows that the prognosis depends on multiple factors like the etiology, unilateral or bilateral MRI findings, and the completeness of the resection rather than on the presence of specific EEG patterns (56,57).

Early psychological evaluation is important to establish the level of cognitive function. Serial testing can ascertain whether improvement or deterioration has taken place. In children younger than age 5 years, periodic application of Griffith’s developmental scales is usually sufficient for
assessment. Older children, adolescents, and adults require formal psychological testing to assess all aspects of neuropsychological function. Intellectual function in patients with diffuse hemispheric syndromes varies (58, 59, 60, 61). Children with early static injury to one hemisphere and timely control of seizures may have intelligence approaching the low-normal range. Severe intellectual impairment may indicate bilateral diffuse hemispheric involvement or chronic interference caused by frequent seizures or by frequent or continuous EEG epileptic activity (62).

The best development is often seen in children who began with a better neuropsychological profile, even if they deteriorated after the onset of seizures. Children with profound mental retardation tend to do less well as far as global development is concerned, even if hemispherectomy completely eliminates the seizures. Another important factor is the presence of migration disorders, particularly hemimegalencephaly. As a group, these children seem to respond less well to hemispherectomy, both in seizure control and in developmental gains. With early severe hemispheric lesions, usually associated with a profound hemiparesis, shift of language to the other hemisphere is to be expected. Results of dichotic listening testing (63) point to complete lateralization of speech by age 5 years. When this technique is used in children able to understand it, contralateral paradoxical ear extinction is usually noted. Some preservation of auditory spatial localization has been noted in hemispherectomized patients, some of whom perform at normal or near-normal levels, particularly if early damage occurred (64). Some children, especially those with Rasmussen encephalitis or other progressive hemispheric syndromes affecting the dominant hemisphere, may need speech assessment with the intracarotid amobarbital test to determine lateralization or shift of speech. Functional MRI and PET language activation show promise in the assessment of speech localization.

Integrity of both hemispheres appears to greatly facilitate the acquisition of new knowledge and functions in the developing brain. However, the importance of language development, or language shift in children with progressive encephalopathy of the dominant hemisphere, cannot be overemphasized. According to Taylor (61) and other researchers, the left hemisphere appears to be phylogenetically superior to the right in language acquisition. Some shift of language seems to occur even in patients with disease onset in later childhood. Most investigators agree that right hemispherectomy patients perform syntactic comprehension tests consistent with their estimated mental age (60), whereas only a few patients with left hemispherectomy achieve this level. The same can be said for speech perception, although studies have failed to show a difference in overall speech production between the two groups. It seems that once speech is acquired (60), it can be maintained by an intact cerebral hemisphere on the right or the left side. Two other important considerations in language development or shifting are the common association of nonverbal cognitive deficits in these children and the different capacity of the two hemispheres in relation to language acquisition across individuals.

Clearly, however, transferred speech, irrespective of how early the insult, is never as well developed as naturally acquired speech. Language after dominant-hemisphere disconnection, especially in older children with Rasmussen syndrome, remains abnormal.

Neuropsychological assessments (65) of posthemispherectomy patients suggest that in infancy the two hemispheres are equally capable of supporting the development of reading skills, both an orthographic input lexicon and phonologic output lexicon, and can access a semantic system based on these. However, the left hemisphere seems to be superior for the development of spelling. Generally, the left hemisphere after right hemispherectomy is better able to perform grapheme-to-phoneme transformations under simple conditions but still shows some degree of phonologic dyslexia. Neither hemisphere seems to support the development of phoneme-to-grapheme transformation (phonologic dysgraphia) to assist in spelling.