Counterintuitively, scalp EEG is often nonlateralizing or even paradoxically contralateralizing to the known structural lesion in hemispherectomy candidates. A published series of 68 children undergoing hemispherectomy found that six (9%) had paradoxical ictal onset of seizures.10
Five of these six patients were seizure free after greater than one year of follow-up. In our report two out of three patients with paradoxical ictal onset were seizure free. In a series of 28 children with unilateral hemispheric lesions, 75% had bilateral ictal or interictal findings on scalp EEG.8
Another published series identified 50 patients with generalized or bilateral EEG abnormalities; the majority of these patients had hemispherectomy and were seizure free.11
Our series was consistent with these reports, showing that contralateral or unlocalizing ictal onset is common and does not portend poor seizure outcome.
Conversely, a series of 12 patients found that there is an additive group of risks identifiable on EEG which may predict outcome: in this report, the three patients with contralateral hemispheric slowing, absence of ipsilateral slowing, bilateral independent spikes, and generalized discharges all had poor seizure outcome.7
Smith et al. found that five of 25 children had bilateral independent epileptogenic foci, and three of these five (60%) were seizure free postoperatively, considered a poor outcome in the overall sample.12
We report on a larger sample size of 24 patients with nonlateralizing discharges, and find no statistical difference in seizure outcome. It should be noted that we did not consider background frequency slowing in our analysis, which was factored in one of the studies cited.7
In our experience, background slowing was quite variable depending on frequency of seizures, patient’s age, AEDs, and the location of lesions. In our sample, when EEGs were re-classified considering both interictal and ictal EEG, 41/54 (76%) could be categorized as lateralizing. In this group of 41, nine were categorized on the basis of interictal lateralization in combination with ictal nonlateralization. Interestingly, the lateralizing group as a whole and the nonlateralizing/contralateral group had similar seizure outcomes. However, within the lateralizing group only 5/9 (56%) categorized on the basis of interictal abnormalities were seizure free, showing a trend toward poor seizure outcome. This finding serves to caution against using interictal scalp EEG for lateralization and surgical planning.
Our seizure outcome data (78% seizure free) and distribution of etiologies are similar to other published series.6,13–15
In previous reports, unihemispheric pathology such as RS and CVA had better outcomes after hemispherectomy compared to MCD.16
Cortical abnormalities in MCD are often bilateral or diffuse, resulting in the potential for multifocal sites of epileptogenesis. In a series reporting on 105 patients, 38% of patients with MCD had findings of bilateral abnormality on MRI, EEG, or both.6
Since unihemispheric pathologies have better outcomes after hemispherectomy, and MCDs have been reported to have a higher prevalence of bilateral EEG abnormalities, this might suggest that EEG non-lateralization in a patient with a likely MCD implies a less favorable pre-operative prognosis. In our series, the MCD subgroup of 21 patients had a similar seizure outcome and prevalence of nonlateralization compared to other etiologies. No difference in seizure outcome was seen between unihemispheric (RS, CVA and SWS) and MCD etiologies. Nine of 21 (43%) MCD patients had bilateral abnormalities on EEG, which was consistent with 24/54 (44%) for the entire population. Surprisingly, in the CVA subgroup, 13/20 (65%) had EEG nonlateralization.
Malformations of cortical development include a large spectrum, ranging from pathologies with typically bilateral imaging and pathological findings such as polymicrogyria17
to focal cortical dysplasia (FCD). Even in FCD, there is evidence of multifocal and bilateral sites of epileptogenesis in many cases.18
This fact is reflected by the care taken prior to offering respective surgery in MCD: there may be a higher burden of proof associated with the decision to proceed with hemispherectomy in MCD compared to unihemispheric pathologies. The prevalence of nonlateralization in MCD is consistent with published series, but the CVA group in our series demonstrated a high incidence of nonlateralization. We could speculate that the large number of nonlateralizing patients in the CVA group compared to the MCD group reflects either longer duration of epilepsy in the CVA group before surgery or perhaps a selection bias. For example, cases presenting with MCD as a likely preoperative etiology and nonlateralizing EEG findings may be less likely to proceed to hemispherectomy, and hence not included in this postsurgical analysis. The finding of MRI abnormalities consistent with prior CVA increases confidence in the potential benefit of hemispherectomy, and therefore nonlateralizing EEG may not be weighted very heavily in determining surgical candidacy in these cases. Further, there appears to be a relationship between duration of epilepsy and prevalence of nonlateralization. In our series, this relationship was statistically significant. The CVA group had a longer duration of epilepsy than the other etiology groups, making these patients more likely to have nonlateralizing findings on EEG. We emphasize that this finding is merely associated with duration of epilepsy and not predictive of prognosis.
Progressive disorders such as RS may worsen to involve both hemispheres, but whether scalp EEG nonlateralization is a sensitive indicator of this worsening is unknown. Nine of 10 (90%) of the RS patients in our analysis were seizure free and had lateralizing EEGs. Only one patient with RS had a nonlateralizing EEG, and this patient also had a poor surgical outcome. This child suffered from epilepsy for a much longer duration (11 years) than the typical RS patient, and consequently developed seizures from the other hemisphere. Due to small sample size, it is not clear whether the nonlateralizing EEG in our RS group is truly a prognostic indicator.
It is not clear whether contralateral EEG findings alone represent true epileptogenesis in individual patients. In studying six children with encephaloclastic lesions and paradoxical ictal onset, Garzon et al. presented three hypotheses to explain this phenomenon. The most plausible and often cited is that ictal low voltage fast rhythms originate in the diseased hemisphere,10
but the seizure may not be detectable by scalp EEG until propagated to the “healthy” hemisphere, at which time the more robust volume and organization of neurons in the contralateral hemisphere allow for rhythmic discharges detected on scalp EEG. In children with encephaloclastic lesions, this explanation seems sufficient; but when considering MCDs with no detectable hemispheric differences in brain volume and only subtle structural differences based on MRI, it would seem that the leading edge of the seizure should lateralize to the diseased hemisphere on scalp EEG. This hypothesis also may not explain cases where there is persistent contralateral EEG abnormalities following hemispherectomy. In our study, three patients had contralateral epileptiform discharges on postoperative EEG, but were seizure-free on the last follow-up. On the other hand, we have seen patients whose EEG abnormalities showed progression over several years from clear unilateral discharges to bilateral independent abnormalities along with worsening of cognitive development and seizure as well as MRI findings. Presumably frequent seizures starting in the diseased hemisphere but spreading to the contralateral side produce irritability in the “healthy” hemisphere. Our finding correlating long duration of seizure disorder preoperatively with nonlateralization on EEG supports this hypothesis. We believe that these cases illustrate true secondary epileptogenesis, but we are not certain when this process becomes irreversible and hemispherectomy can no longer be offered due to these concerns.
There were several limiting factors in this retrospective series. Multiple surgical techniques were used, based on institution and neurosurgeon preference. In four cases a second surgery was necessary to complete disconnection. Despite these potential confounders, previously published reports demonstrating similar efficacy between different surgical techniques make this a comparable dataset.19
With respect to EEG analysis, the patients’ records were oversimplified for ease of statistical analysis. Scalp EEGs were considered ‘nonlateralizing’ or ‘lateralizing’. In clinical practice, an epileptologist will consider the burden of abnormalities present in each hemisphere, as well as various qualitative features of the evaluation not included here, before making a recommendation for hemispherectomy. With respect to outcome analysis, this is a medium-sized sample with associated limitations. This was apparent when attempting to draw conclusions from the RS subgroup.
Seizure outcome is only one component of the patient outcome following hemispherectomy. The importance of effects on development cannot be overestimated, and a patient with occasional seizures but excellent developmental outcome would generally be considered a success. However, in the hemispherectomy literature development appears to follow seizure outcome. In a series following developmental assessments postoperatively after hemispherectomy, a reduction in seizures was associated with a constant improvement in intellectual function.20
Estimating the effect of an abnormal contralateral hemisphere on developmental outcome is difficult. Recently published data indicates that MRI—but not EEG—abnormalities in the hemisphere contralateral to the hemispherectomy have an important negative developmental prognosis. In a retrospective analysis of the developmental outcomes of 43 patients, those with contralateral MRI abnormalities had poor postoperative development and a lower incidence of seizure freedom. In this same study, 24 patients had contralateral interictal discharges prior to hemispherectomy. There was no difference in the cognitive outcomes of these patients.21
In our series methodological issues limited the acquisition of neuropsychological and developmental outcome data in the majority of cases.
In summary, hemispherectomy is effective in achieving seizure freedom in selected candidates. Our series demonstrates that patients with bilateral or contralateral EEG abnormalities have an excellent seizure outcome postoperatively. Nonlateralization on EEG was seen in a large minority of patients, in all etiologies, including CVA and MCD. It is important not to exclude hemispherectomy based on scalp EEG; candidacy should be determined based on other clinical factors and evaluations.