Epilepsy Essentials: Hemispherectomy for Early-Onset Pediatric Epilepsy: A Big Surgery for Small People

Epilepsy occurs in approximately 1 in 200 children, about one-third of whom have seizures refractory to medications.¹ Morbidity among these individuals is high, with increased risks for injury related to seizures, hospitalizations for status epilepticus, developmental delays, and comorbid psychiatric conditions. Children and adolescents with medication-refractory epilepsy use 2 to 4 times more medical care than do those with well-controlled epilepsy.² In addition, mortality of all causes, including sudden unexpected death in epilepsy, is highest among this population. As a result, many parents of children with uncontrolled epilepsy and pediatric epileptologists seek epilepsy surgery as a possible curative option, along with the potential to wean antiseizure medications and avoid drug-associated side effects. An estimated 20% to 40% of pediatric epilepsy surgeries are anatomic or functional hemispherectomies.³

Hemispherectomy: A Brief History and Indications

The first reported hemispherectomies were performed in the late 1920s and early 1930s for gliomas; the majority of these individuals had poor mortality outcomes in the immediate postoperative period, but there was 1 report of an individual who was seizure-free and remained ambulatory, although hemiparetic, 2 years postsurgery at the time of publication.⁴ The first reported hemispherectomy for epilepsy was performed in 1938 by Dr. K.G. McKenzie on a 16-year-old patient with a history of traumatic brain injury at 3 weeks of age that led to left hemiplegia and epilepsy; the right hemispherectomy was successful in abating the seizures.⁴ Since then, children and adolescents have been the main population undergoing hemispherectomies for epilepsy, as most conditions amenable to the procedure tend to present among young people, who also benefit from increased neuroplasticity.

Candidates for hemispherectomy ideally should have seizure onset from only 1 hemisphere, with the affected area too large for a focal resection to address the disorder. The most common indications for hemispherectomy include malformations of cortical development (eg, hemimegalencephaly, hemispheric focal cortical dysplasia, polymicrogyria), history of ischemia (eg, perinatal stroke), and Rasmussen encephalitis, a poorly understood inflammatory condition leading to progressive atrophy of a unilateral hemisphere with progressive contralateral hemiplegia and development of epilepsia partialis continua. Individuals with Sturge-Weber syndrome,⁵ hemiconvulsion-hemiplegia-epilepsy syndrome,⁴ or intracranial infections leading to hemiparesis and refractory seizures⁶ also may be candidates for hemispherectomy (Table).

Hemispherectomy Types and Complications

The first surgical technique developed was the anatomic hemispherectomy (AH), which involved removal of the entire cerebral hemisphere, at times also including the basal ganglia and thalamus. Modern surgeries typically attempt to achieve disconnection of the corona radiata, disconnection of the mesial temporal structures, total corpus callosotomy, and disconnection of the frontal horizontal fibers (Figure 1, Row A).⁷

Hemidecortication is the surgical removal of the cortex of one hemisphere while keeping the white matter intact and, therefore, the underlying ventricles unexposed; this was developed to avoid superficial hemosiderosis. Dr. Rasmussen further adapted this technique to what is called a functional hemispherectomy (FH); in this procedure, disconnection of the corpus callosum and upper brainstem is performed, as well as removal of the temporal lobe and central portion of frontoparietal lobe (Figure 1, Row B). This was adapted further in the 1990s to hemispherotomy, which is similar to a hemispherectomy but with less brain removed in order to reduce risk of complication, while still achieving disconnection of the affected hemisphere. Revision hemispherectomies may be chosen if the initial hemispherectomy does not lead to seizure freedom, presumably because of incomplete disconnection (although the possibility of contralateral hemispheric seizures must be ruled out). This may involve converting an FH to an AH, or performing further resection or disconnection of tissue that is suspected to remain connected.^4,7

Short-term complications include infection, aseptic meningitis, and transient neurologic deficits, which are not unique to AH, but a risk for any intracranial operation; rarely, contralateral strokes or death can occur, with mortality reported at under 1% for both AH and FH.^4,8,9 Late complications of AH (and, to a lesser degree, FH) include obstructive hydrocephalus, superficial cortical hemosiderosis, and chronic subdural fluid collection. The late complications of AH can be alleviated by placing resection cavity drains for the immediate postoperative period^4,10 or cauterizing the choroid plexus,¹¹ with placement of ventricular shunts as necessary.

Outcomes and Neurologic Consequences

Seizure freedom (Engel I) after hemispherectomy is estimated to occur in 54% to 90% of cases;^4,7,8 however, an overwhelming majority of individuals show at least some level of improvement in seizure frequency. A published seizure freedom prediction tool¹² can be used preoperatively during surgical planning to identify individuals appropriate for this procedure and to discuss likely outcomes with the individual’s caregivers. In terms of seizure freedom, AH is considered superior to FH because of the greater likelihood of incomplete disconnection in FH; however, given the higher complication rate with AH, it can be reasonable to attempt FH first.⁴

For epilepsy surgeries in general (including hemispherectomy), Harris et al¹³ recently reported a steep decline in seizure freedom within the first 2 years after epilepsy surgery, but rates remain stable following this time period. The same research team discovered that approximately 50% to 66% of individuals who underwent epilepsy surgery remained free of seizures in the long term (more than 10 years after surgery). They also found that individuals who underwent hemispheric surgeries experienced a higher rate of seizure freedom compared with those who had lobectomies. Much of these data are from small, single-center case reports, and most centers tend to perform a specific surgical technique, making it difficult to compare different techniques and outcomes.

After hemispherectomy, individuals often develop varying degrees of hemiparesis and contralateral homonymous hemianopsia; however, a large percentage of hemispherectomy candidates had a neurologic deficit (hemiparesis or hemianopia) before surgery because of their disease.⁴ Hemiparesis can be exacerbated immediately postoperatively, and most commonly, there is a loss of distal motor function in the leg and arm contralateral to the removed or disconnected hemisphere, with relative preservation of proximal motor function.^4,7 Most individuals remain ambulatory, although they may require an ankle-foot orthosis because of limited ankle dorsiflexion. There is often decreased fine motor control in the hand on the contralateral side, which becomes more of a “helper hand.” The degree of hemiparesis typically is less among individuals undergoing hemispherectomy because of a perinatal stroke, presumably because motor function has transitioned to the contralateral, unaffected hemisphere.⁴

A spectrum of cognitive outcomes after surgery exists. The majority of children and adolescents (estimated 74% to 88%) who are good epilepsy surgical candidates also present with severe developmental delay and behavioral problems before surgery.³ After epilepsy surgery, a decline or improvement in cognitive skills may occur; cognitive function typically remains stable.^3,4,14 The etiology appears to have an effect on cognitive function before and after surgery; hemispheric cortical malformations, such as hemimegalencephaly, tend to be associated with greater cognitive deficits before surgery than occurs with acquired etiologies, such as perinatal strokes or progressive hemispheric disease.^3,8 An improvement in cognitive function postoperatively is associated with the following factors: lower preoperative IQ, malformations of cortical development excluding hemimegalencephaly (thought to be attributable to contralateral hemispheric disease), normal MRI of the remaining hemisphere, seizure onset at a later age, shorter seizure duration, achieving seizure freedom after hemispherectomy, the ability to taper off from antiseizure medications after surgery, and younger age at the time of surgery.^3,4 In one center’s experiences with functional hemispherectomies, verbal memory improved in the postoperative period.¹⁴

Early vs Later Surgery

The majority of refractory epilepsy cases occur in childhood, and among this population, earlier onset of seizures is associated with more severe course and epileptic encephalopathy. Refractory seizures hinder development, causing developmental stagnation or regression; prompt treatment is necessary because frequent epileptic discharges and seizures arising from the affected hemisphere can be detrimental to the healthy contralateral hemisphere.¹³ Control of seizures and epileptic discharges can possibly alter the developmental trajectory. Furthermore, there is the possibility of improving quality of life with down-titration or discontinuation of antiseizure medications. Early epilepsy surgery also may lead to prompter histopathologic diagnosis, allowing earlier access to appropriate targeted therapies.¹³

Among children and adolescents with severe early-onset seizures, epilepsy surgery can result in clear improvement in cognition, although these individuals’ intelligence quotients often remain in the lower range.³ Whereas the case for early surgery is strong, establishing that an individual has drug-resistant epilepsy can take time. An individual is considered a suitable candidate for surgery if specific criteria are met, including a clearly identifiable epileptogenic region to target and inadequate seizure control despite trials of 2 antiseizure medications. Hale et al¹⁵ recently reported that identification of a lesion in itself is the largest factor in development of drug-resistant epilepsy, and awaiting trials of multiple antiseizure medications before referral for presurgical evaluation may be unnecessary. Hesitancy among physicians and caregivers to proceed with surgery in very young patients may exist because of misconceptions that epilepsy surgery is more dangerous in infants or small children; however, ample data show that hemispherectomies using modern techniques even in infants younger than 1 year are efficacious and safe.^16,17 In addition, despite initial costs, epilepsy surgery tends to be more cost-effective than medication in the long term, with 1 study in Canada estimating that after 8 years from surgery, costs were lower in the surgical group compared with the medication-only group.¹⁸ Ongoing research is examining the optimal timing of surgery for early-onset pediatric epilepsy.

Conclusion

Hemispherectomy is a highly effective, safe treatment option for children and adolescents with refractory seizures arising from a single hemisphere; can be curative of seizures in certain causes of epilepsy; and can lead to improvement in cognition and overall developmental trajectories. Conducting surgery early in the course of severe epilepsy is likely to result in better outcomes. More research into hemispherectomies in children is needed because most of the published studies have included small numbers of participants, used a variety of techniques, and had short follow-up duration, impeding determination of the optimal technique and timing of surgery. Large-scale observational studies or a well-controlled clinical trial will be essential to establish the effectiveness of this treatment.