Surgical Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review

Abstract

Background and objectives: Early life epilepsies (epilepsies in children 1-36 months old) are common and may be refractory to antiseizure medications. We summarize findings of a systematic review commissioned by the American Epilepsy Society to assess evidence and identify evidence gaps for surgical treatments for epilepsy in children aged 1-36 months without infantile spasms.

Methods: EMBASE, MEDLINE, PubMed, and the Cochrane Library were searched for studies published from 1/1/1999 to 8/19/21. We included studies reporting data on children aged 1 month to ≤36 months undergoing surgical interventions or neurostimulation for epilepsy and enrolling ≥10 patients per procedure. We excluded studies of infants with infantile spasms or status epilepticus. For effectiveness outcomes (seizure freedom, seizure frequency), studies were required to report follow-up at ≥ 12 weeks. For harm outcomes, no minimum follow-up was required. Outcomes for all epilepsy types, regardless of etiology, were reported together.

Results: Eighteen studies (in 19 articles) met the inclusion criteria. Sixteen prestudies/poststudies reported on efficacy, and 12 studies addressed harms. Surgeries were performed from 1979 to 2020. Seizure freedom for infants undergoing hemispherectomy/hemispherotomy ranged from 7% to 76% at 1 year after surgery. For nonhemispheric surgeries, seizure freedom ranged from 40% to 70%. For efficacy, we concluded low strength of evidence (SOE) suggests some infants achieve seizure freedom after epilepsy surgery. Over half of infants undergoing hemispherectomy/hemispherotomy achieved a favorable outcome (Engel I or II, International League Against Epilepsy I to IV, or >50% seizure reduction) at follow-up of >1 year, although studies had key limitations. Surgical mortality was rare for functional hemispherectomy/hemispherotomy and nonhemispheric resections. Low SOE suggests postoperative hydrocephalus is uncommon for infants undergoing nonhemispheric procedures for epilepsy.

Discussion: Although existing evidence remains sparse and low quality, some infants achieve seizure freedom after surgery and ≥50% achieve favorable outcomes. Future prospective studies in this age group are needed. In addition to seizure outcomes, studies should evaluate other important outcomes (developmental outcomes, quality of life [QOL], sleep, functional performance, and caregiver QOL).

Trial registration information: This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Figure 1. Years When Surgical Procedures Were Performed

Note: Studies not appearing in this figure either were not included for effectiveness data or did not report the years when surgery was performed.

Figure 2. Seizure Freedom Rates after Hemispherectomy or Hemispherotomy

The vertical bars display 95% confidence intervals. When multiple studies reported the same follow-up times, we used horizontal offsets to improve visibility. Only 1 study (Cook) reported data across multiple time points. For studies only reporting a minimum follow-up interval (e.g., follow-up >1 year after surgery), data were plotted at that minimum time point. Of note, Otsuki et al. was not included as the study did not report follow-up duration for this subgroup. 95% confidence intervals are shown for each data point. All studies were prestudies/poststudies, so the precise cause of seizure freedom cannot be easily determined.

Figure 3. Seizure Freedom Rates after Multilobar, Lobar, or Focal Resection

The vertical bars display 95% confidence intervals. When multiple studies reported the same follow-up times, we used horizontal offsets to improve visibility. For studies that only reported a minimum follow-up interval (e.g., follow-up >1 year after surgery), data were plotted at that minimum time point. 95% confidence intervals are shown for each data point.