Epilepsy surgery in children
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_1033_16
Source of Support: None, Conflict of Interest: None
Approximately 60% of all patients with epilepsy suffer from focal epilepsy syndromes. In approximately 15% of these patients, the seizures are not adequately controlled with anticonvulsive drugs, and such patients are potential candidates for surgical treatment and majority are children. Epilepsy surgery in children, who have been carefully chosen, can result in either seizure freedom or a marked (>90%) reduction in seizures in approximately two-third of children with intractable seizures. In the multimodality presurgical evaluation approach, sufficient concordance should be established among various independent investigations, thus identifying the location and extent of the epileptogenic zone with a high degree of confidence. Early surgery improves the quality of life and cognitive and developmental outcome of the child. Surgically remediable epilepsies in children should be identified early and include temporal lobe epilepsy with focal lesions, lesional extratemporal epilepsies, hemispherical epilepsies, and gelastic epilepsy with hypothalamic hamartoma, and can be treated by resective or disconnection surgery. Palliative procedures include corpus callosotomy and vagal nerve stimulation for children with diffuse and multifocal epilepsies, who are not candidates for resective surgery. Deep brain stimulation in patients with epilepsy is still under evaluation. For children with “surgically remedial epilepsy,” surgery should be offered as a procedure of choice rather than as a treatment of last resort.
Keywords: Epilepsy, children, pediatric seizures, surgery, temporal lobe epilepsy
Approximately 60% of all patients with epilepsy suffer from focal epilepsy syndromes. In approximately 15% of these patients, the seizures are not adequately controlled with antiepileptic drugs (AEDs), making them potential candidates for surgical treatment. Nearly one-third of all patients with new onset epilepsy will have incompletely controlled epilepsy. Importantly, majority of individuals with epilepsy are below 18 years of age, with medically intractable epilepsy being present in nearly one-fourth of them.
Recent advances in both neuroimaging and neurosurgery have helped to improve the evaluation of children with medically refractory epilepsies. Consequently, a surge in referral of children with epilepsy for surgical consideration has been reported across the globe. Importantly, epilepsy surgery in children who have been meticulously screened can result in either seizure freedom or a marked (>90%) reduction in seizures in approximately two-third of children with intractable seizures., Infants and children benefit from epilepsy surgery, with encouraging results published in recent series.,
Consequences of ongoing seizures in childhood
The onset of epilepsy at a younger age is associated with a poor developmental outcome in children. Ongoing/recurrent seizures in severe epilepsy have been associated with developmental delay, cognitive decline, poor quality of life, increased risk of injury, and sudden death. An early seizure control curtails developmental delays.
Children are different from adults
The approach to epilepsy surgery in children is unique from that in adults.,
Selection of the ideal candidate
Distinctive features of pediatric epilepsy surgery
Children are not miniature adults. Resection of the epileptogenic foci can be either temporal or extratemporal. Earlier, temporal lobectomy was the most commonly reported procedure. Improved neuroimaging and neurosurgery facilities have accounted for increased extratemporal resections in recent times. Extratemporal resection is difficult to plan in the absence of a distinctive structural lesion on MRI; advances in neuroimaging technology have increased the sensitivity of identifying children who can be considered for surgery. Invasive electroencephalogram (EEG) evaluation may still be required to determine the extent of resection and the relationship of the epileptogenic focus with the eloquent cortex. Functional hemispherotomy, disconnection of one cerebral hemisphere, is considered in a significantly higher proportion of children than in adults and accounts for one-third of the surgeries in major pediatric epilepsy surgery centres., It is sometimes difficult in children to determine whether a given epilepsy syndrome is focal and amenable to be controlled by epilepsy surgery. Chugani et al., have shown that the use of positron emission computed tomography (PET) in infantile spasms increased the number of children who could be considered for resective surgery.
Multiple epileptogenic foci are common in certain pediatric epilepsy syndromes. Children with neurocutaneous syndromes present with catastrophic epilepsy early in life and may benefit from early surgery. Children with tuberous sclerosis (TS) presenting with stereotypic seizures are likely to benefit from surgery if it can be demonstrated that most or all seizures are arising from a single tuber., Sturge– Weber syndrome More Details is characterized by a facial capillary hemangioma involving the periorbital area, forehead, or scalp, a venous angioma of the leptomeninges (usually unilateral), and in a proportion of cases, a choroidal angioma. Studies suggest that early-onset seizures with this diagnosis are associated with a poor cognitive outcome, and an early resective surgery, either lobar, multilobar, or a hemispherectomy, may be associated with an improved outcome.,
Types of epilepsy surgery in children
At present, four types of surgical procedures are performed in the clinical practice
The goals of the pre-surgical evaluation are to
Different diagnostic tools area being used by epileptologists to identify different cortical zones– the symptomatogenic zone, the irritative and ictal onset zone, the epileptogenic lesion and the functional deficit zone – each one of which is more or less a precise index of the epileptogenic zone. The current diagnostic techniques used in the definition of these cortical zones are video EEG monitoring, magnetic resonance imaging (MRI), ictal single photon emission computed tomography (SPECT), and PET. A detailed developmental and neuropsychological assessment as well as evaluation for behavioural problems should be performed. Intracarotid amobarbital (WADA) test and functional magnetic resonance imaging (fMRI) are indicated in selected cases; however, they can mainly be performed in older, cooperative children and adolescents. Ictal SPECT and interictal PET may be used as adjunctive tests to add further information. Magnetoencephalography (MEG) can complement the scalp EEG data in defining the extent and location of the epileptogenic zone.
In children, a non-invasive approach is preferred, more recently, made possible by the developments in neuroimaging. Expertise should be available within a pediatric epilepsy surgery centre in the areas of pediatric neurophysiology, neuroimaging, and neuropsychology. Successful epilepsy surgery requires a multidisciplinary team approach with discussion of the individual patient's presurgical evaluation data in detail in a patient management conference. It will improve patient care and communication among members of the team. None of the currently available preoperative workup techniques can exactly delineate the epileptogenic zone. However, with the multimodality presurgical evaluation approach, sufficient concordance should be established among various independent investigations, thus identifying the location and extent of the epileptogenic zone with a high degree of confidence. This will result in a good surgical outcome.
Surgically remediable epilepsy syndromes of childhood
Surgery can be considered at any age in the pediatric population from infancy through early childhood and adolescence. The surgically remediable epilepsies in children are temporal lobe epilepsy with hippocampal sclerosis (HS), lesional temporal and extratemporal epilepsies, the hemispherical epilepsy syndromes, and hypothalamic hamartoma.
Temporal lobe epilepsy
Carpay et al., found that 51% of the children who failed the first AED therapy had a good response to a second AED. However, the likelihood of achieving a remission of longer than 1 year with subsequent drug regimens was only 29% after the failure of two AEDs and 10% after three AEDs had failed. Hippocampal sclerosis and a dual pathology (hippocampal sclerosis and another lesion) were associated with only 11% and 3% seizure freedom at the last follow-up in medically treated cases, respectively., Early surgical intervention avoids the long-term risks associated with AED therapy. Children undergoing temporal lobectomy for refractory epilepsy show an improvement in the quality of life and visual memory after surgery. The complication rates are less than 5%.,
Presurgical evaluation in temporal lobe epilepsy
Successful surgery for epilepsy depends on correctly identifying the ictal-onset zone. Ictal scalp EEG monitoring is essential for determining the region of seizure onset, especially in differentiating mesial versus neocortical onset. Patients with mesial TLE may have a higher seizure-free outcome with surgery compared to patients with neocortical temporal and extratemporal lobe epilepsies, particularly if a single MRI lesion is present. MRI positive TLE is associated with a favorable outcome. Patients with lesional TLE, such as hippocampal sclerosis or a foreign tissue lesion (tumor or vascular anomaly), have a higher probability of seizure freedom after resection than those with a normal MRI [Figure 1]. Postsurgical seizure-free outcome is seen in 70–90% of the patients with mesial TLE with hippocampal sclerosis compared to a lowered seizure-free outcome of 60% in patients with nonlesional TLE. Multimodality noninvasive imaging modalities are increasingly used to determine the presumed epileptogenic focus when the scalp EEG and/or MRI is non-localizing or subtle or normal [Figure 2]. These include ictal single photon emission computed tomography (SPECT), subtraction ictal SPECT co-registered to MRI (SISCOM), PET, MEG, and MRS. The ability of SISCOM to detect epileptogenic lesions is in the range of 88% compared to 39% by ictal SPECT alone. Bell et al., demonstrated that SISCOM abnormality localized to the resection site is predictive of seizure-free outcome among patients with MRI negative TLE. In patients with TLE and a normal MRI, unilateral PET hypometabolism has a positive predictive value between 70 and 80%.
Neuropsychological assessment prior to surgery identifies areas of existing dysfunction, assists in determining language lateralization, and provides guidance in weighing the risks and benefits of surgery. TLE in children was found to have a long-lasting impact on verbal learning and memory. Language transfer to the normal hemisphere and atypical language lateralization were noted among 12% of epilepsy patients, particularly among those with congenital lesions or those who had sustained a left hemispheric insult before the age of 6 years.
Intracarotid sodium amobarbital testing (Wada test) is used to determine language lateralization and to screen for verbal memory dominance. Among children who underwent a temporal lobectomy, better verbal memory performance after an injection ipsilateral to the side of surgery than after a contralateral injection (Wada memory asymmetries) predicted preserved postoperative verbal memory capacity. fMRI is a noninvasive option to determine language lateralization as well as to identify patients at a higher risk of verbal memory decline following surgery. If both the Wada test as well as the fMRI are not feasible, language lateralization and verbal memory capacity may be determined by neuropsychological testing.
Intraoperative electrocorticography (ECoG) has been used to localize the irritative zone and guide the extent of surgical resection. ECoG is unlikely to influence surgical resection while performing a standard anterior temporal lobectomy in patients with mesial TLE with HS; however, it helps in planning resections in the presence of dual pathologies, tumoral lesions, and dysplasia.
Complications of dominant temporal lobectomy include language and memory impairments, with naming and fluency deficits seen in 50% of the patients. Verbal memory impairment depends on whether or not resection was done in the dominant hemisphere as well as the preoperative level of function; those with a higher preoperative function are more likely to show decline. Significant visual field deficits have been described in approximately 35% of the patients undergoing a temporal lobectomy; however, approximately 38% of these patients experience improvement within the first year after surgery. Other rare complications are hemiparesis, dysphasia, and hemianopia.
Hippocampal sclerosis is the most common etiology causing epilepsy among adult candidates who are candidates for epilepsy surgery, but it is not the main cause in pediatric patients. In the Cleveland Clinic pediatric epilepsy surgery series, hippocampal sclerosis was the etiology for only 15% of 74 adolescents and 12% of 62 preadolescent children. The most common causes among pediatric surgical candidates were low grade tumors and focal malformations of cortical development, which together accounted for the etiology in 57% of the adolescents, 70% of the preadolescent children, and 90% of the infants., Duchowny et al., reported low grade tumors or malformations of cortical development in 90% of the infants in the series from Miami Children's Hospital. In children, if hippocampal sclerosis is present, it is frequently associated with an extrahippocampal pathology such as cortical dysplasia or a low-grade tumor. Such dual pathologies has been reported in 31–79% of all cases of mesial temporal sclerosis in children.,
Surgery for extratemporal epilepsy in children results in a lower frequency of seizure freedom (45%) compared with that of temporal lobectomy (68%); however, patients who undergo extratemporal resections experience substantial improvement in the seizure control (35%) when compared with temporal lobectomies (24%). In a study by Adler et al., among 35 patients whose seizures initially occurred before the age of 16 years, 40% were seizure free, and another 23% had a 75% or higher reduction in seizure frequency. In another long-term follow-up study of 45 children (<16 years of age) who underwent a frontal lobe surgery, after a median follow up of 15 years, it was noted that 20% patients had a seizure free response (with or without auras), and another 9% had fewer than 3 seizures per year. Gilliam et al., described 15 children who underwent an extratemporal surgery (10 frontal, 1 parietal, 1 occipital, and 3 hemispheric resectiions); the seizure freedom was 60% with frontal lobe epilepsy, and another 20% had more than 95% seizure reduction. Pathology in the form of cortical dysplasia, gliosis, or tumor was found in all extratemporal specimens and did not appear to predict outcome. Wyllie et al., reported 48 extratemporal and multilobar resections in children and adolescents monitored for more than a year. Of these individuals, 54% were seizure free, and another 20% had only rare seizures. Focal abnormalities were present on MRI in 85% of the patients. Multimodality evaluation helps to delineate the epileptogenic zone, especially in focal cortical dysplasia [Figure 3]. The use of modern techniques has effected a considerable improvement in seizure relief in children (and adults) with seizures of extratemporal onset. However, management of patients who have no lesions on neuroimaging studies remain a challenge. If no structural abnormality is identified, additional noninvasive testing (SPECT, PET, MEG) should be considered to facilitate intracranial electrode implantation.
Developmental brain abnormalities (e.g., cortical dysplasia, tuberous sclerosis complex, Sturge–Weber syndrome) and low grade cortical tumors (gangliogliomas, desmoplastic infantile gangliogliomas, oligodendrogliomas, and astrocytomas) are the most common pathologies in children with epilepsies of extratemporal origin.,
White et al., reported a review of 150 patients from the literature, the vast majority of whom were younger than 16 years and had a 67% seizure freedom after a hemispherectomy. This dramatic improvement in children with intractable epilepsy, in addition to improvement in alertness and behavior, resulted in further use of this procedure in epilepsy centers. However, during the long-term follow-up, these patients within 5 to 20 years had complications such as superficial cerebral hemosiderosis. Hence, the standard anatomical hemispherectomy was modified by leaving the frontal and occipital poles intact with a vascular stalk but disconnecting the underlying white matter, i.e., a functional hemispherotomy. This modification preserved the high rates of seizure freedom and effectively eliminated superficial cerebral hemosiderosis. Subsequently, several modifications have been developed and the techniques were applied to various cerebral pathologies including encephalomalacia from infections and infarction, malformation of cortical development (e.g., hemimegalencephaly), Sturge–Weber syndrome, and Rasmussen syndrome) [Figure 4].,,, Approximately 80% of the patients in these reports had more than 90% seizure reduction or seizure-free result from the surgery. Seizure control was preserved in patients monitored for more than 30 years. The outcome was related to the underlying pathology, with a better result in Rasmussen syndrome than in vascular or dysplastic etiologies. The perioperative mortality associated with hemispherotomy ranged from 0–6% in larger series. The most common morbidities included shunt infections, hydrocephalus, and intraoperative bleeding, which appeared to vary in frequency depending upon the type of procedure used. Motor function was unchanged after surgery, and some children had improved cognition and behavior.
Candidates for hemispherotomy
Hemispherotomy has proven to be an extremely effective operation for intractable seizures associated with multilobar hemispherical pathology., Children with intractable partial seizures of all types, who have a structural abnormality that involves most of one hemisphere, and who are already hemiparetic with a homonymous hemianopia, should be considered for hemispherotomy. An early surgery should be contemplated for several underlying pathologies that have a favorable outcome (e.g., Rasmussen syndrome, Sturge–Weber syndrome, and hemimegalencephaly, owing to malformations of cortical development). Hemispherotomy should not be delayed in patients with Rasmussen syndrome and cortical dysplasia, even when full hemiparesis and hemianopia have not developed. Language function also improved in most patients in this series, independent of the resected side, suggesting that the constant storm of epileptiform activity was inhibiting the normally functioning hemisphere.
The association of gelastic and/or dacrystic seizures with hypothalamic hamartomas (HHs) is now well recognized. The associated symptoms include other seizure types, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. In a majority of cases, epilepsy begins during the neonatal or early childhood period, usually in the form of gelastic seizures. In the majority of patients, epilepsy will prove to be drug resistant, manifesting with multiple seizure types and progressive cognitive and developmental deterioration. Surgical treatment can result in seizure freedom in up to 50% of the patients and can be accompanied by significant improvements in behavior, cognition, and quality of life. Partial treatment of HHs is sufficient to reduce seizure frequency and improve behavior and quality of life with lesser risk.
High-resolution MRI remains the procedure of choice for identifying HHs, which may be as small as a few millimeters to a few centimeters in size [Figure 5]. Hamartomas are usually isointense to gray matter on T1-weighted imaging and hyperintense or isointense on T2-weighted imaging and do not enhance after gadolinium administration. Demonstration of the lesion is not always easy and may require a careful MRI examination with thin slice volume sequences to demonstrate small lesions. Thee lesion also varies considerably in size and location and these factors influence the surgical approach. In particular, the relationship of the lesion to the hypothalamus, the interpeduncular cistern, and the wall of the third ventricle are important and need to be demonstrated by the imaging. The hamartomas may be pedunculated or sessile.
Corpus callosotomy is a palliative surgical procedure performed in children with intractable seizures who are not candidates for focal resective surgery. It is a particularly useful technique for atonic, tonic–clonic, and tonic seizures. Surgeries include complete section of the corpus callosum, anterior two-thirds section with or without the hippocampal commissure, and a two-staged procedure. There was no difference in outcome based upon the age of the patient and the outcome was considerably better if the degree of mental retardation was not severe and if the cerebral abnormality was focal rather than diffuse. Generalized tonic–clonic and atonic seizures were reduced by 80–100%. In another study, 83% of children had more than an 80% reduction in tonic, tonic–clonic, or atonic seizures after a partial or two-stage callosotomy, with 2 or more years of follow-up. The second procedure completing the callosotomy was performed months after the anterior section if adequate seizure relief was not achieved. No mortality and only transient hemiparesis were reported in this series. Other complications reported include transient dysphasia, more intense focal seizures, memory problems, and split brain syndromes (e.g., the inability to name an object placed in the right hand due to disconnection of the involved sensory cortex from the left hemispheric language centres). However, individuals with severe developmental deficits and little or no language skills may undergo a single-stage complete callosotomy without apparent harm.
Vagus nerve stimulation therapy
Vagus nerve stimulation (VNS) was approved by the Food and Drug Administration in 1997 as an adjunctive therapy for refractory partial-onset seizures in patients aged 12 years and older. The VNS, in addition to providing programmable stimulation, can be turned on intermittently by the caregiver using an external magnet swiped over the generator during a seizure in an effort to abort it. The precise mechanism of action of the VNS is not clear. It is believed to work through both immediate and long-term changes. Immediate mechanisms include changes in the nucleus of tractus solitarius and its connections. This probably causes synchronization and desynchronization of brain electrical activity. Long-term mechanisms are thought to include changes in neurotransmitter concentrations and regional cerebral blood flow. Some researchers hypothesize that the VNS works through increased activity of noradrenergic and serotoninergic pathways, thus increasing the seizure threshold.
Efficacy with vagus nerve stimulation therapy
There are no randomized double-blind controlled trials performed exclusively with children. In a study involving 60 children with partial seizures or generalized seizures, 29% had more than a 50% reduction in seizure frequency. The median reductions in seizure frequency were 23%, 31%, 34%, and 42% at 13, 6, 12, and 18 months, respectively. The response rate was not different among the various seizure types. A study of 13 patients with Lennox–Gastaut syndrome treated with the VNS reported a median reduction in seizure frequency of 52% in the first 6 months. The VNS was found to improve independence, learning, and mood, at times independent of its antiepileptic effect.
Deep brain stimulation
Success of deep brain stimulation (DBS) in relieving a significant number of symptoms in various movement disorders paved the way for studies investigating the effectiveness of this modality in controlling epilepsy. Open-label and small blinded trials have provided promising evidence for the use of DBS in refractory seizures. The targets used were amygdalo-hippocampus, anterior nucleus of the thalamus, head of the caudate nucleus, cerebellum, subthalamic nuclei, and centromedian nucleus of the thalamus. Recently, a randomized, double-blind, multicenter SANTE (Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy) trial had been completed. The trial enrolled 110 people with partial-onset seizures. After 25 months, 56% of 110 patients showed a reduction in seizures. The parameters chosen in this study were a stimulation of 1 minute “on” with 5 minutes of no stimulation, or the “off” mode.
Multiple subpial transection
This technique was developed by Morrell et al. The results of an international meta-analysis have suggested that multiple subpial transection (MST) alone has efficacy and causes only minimal neurologic compromise in patients with intractable seizures who cannot be treated with resective surgery. It is a novel technique for the treatment of intractable epilepsy originating from the eloquent cortex such as the language cortex or the sensorimotor cortex. The aim of MST is to impair the capacity of cortical tissue to generate sufficient neuronal synchrony to produce epileptiform discharges, without interfering with its capacity to mediate physiologic functions. MST induces minimal or no functional deficits after surgery due to preservation of cortical vertical columns.
Role of invasive EEG in pediatric epilepsy surgery
While planning a safe resection, an intracranial EEG recording helps to precisely localize the epileptogenic zone, especially when the latter is located in close proximity to the functional cortex. The area defined by stereotactically inserted depth electrodes is representative of the output obtained from the EEG recording from buried gray matter, which is not accessible with other surface electrodes. According to the Mayo clinic experience,, invasive recordings are necessary when there is:
Complications of depth electrodes such as an intracerebral hemorrhage, are reported in 1–4% cases with rare fatalities. Reports on the use of subdural electrode grids have shown them to be well tolerated in young children, allowing localization of both the seizure onset and function., This is particularly necessary in children with an extratemporal epilepsy.
Outcome of epilepsy surgery in children
Based on the results from several recent pediatric surgical series, the chance of a favorable seizure outcome after surgery is not adversely affected by a younger age, with seizure-free postoperative outcome reported for 60–65% of infants, 59–67% of children, and 69% of adolescents, compared to 64% reported in a large, predominantly adult series. Some subgroups of patients may be more likely than others to have a seizure-free outcome after epilepsy surgery. Results are better and more patients attain seizure freedom after temporal resection (78%) than after extratemporal or multilobar resection (54%), with intermediate results after hemispherotomy (69%). Seizure-free outcome is higher when the etiology is a tumor (82%) than when it is cortical dysplasia (52%), and this difference persists whether the resection was temporal or extratemporal/multilobar. In children with intractable temporal lobe epilepsy caused by hippocampal sclerosis, 78% seizure-freedom was attained, and these results were similar to those in adults. The presence of a focal lesion on MRI is the single most predictor for a favorable outcome across all the series.
Potential risks of epilepsy surgery
The most serious risk of epilepsy surgery is perioperative mortality. Isolated deaths have been reported in several pediatric series, with a frequency of 1.3%. The risk may be higher in infants because of the extensive surgery required in the face of a small blood volume. The mortality of epilepsy surgery must be balanced against the mortality of medically treated uncontrolled seizures. Other risks of epilepsy surgery include the development of new postoperative neurologic deficits. However, a young age confers some advantages because of developmental plasticity.
Advances in structural and functional neuroimaging, neurosurgery, and neuroanesthesia have improved the outcomes of surgery for children with intractable epilepsy. Children with intractable epilepsies should be evaluated early at specialized epilepsy surgery centres to avoid the long-term consequences and morbidity associated with epilepsy. Surgically remediable epilepsies should be identified early and include TLE with hippocampal sclerosis, lesional temporal, extratemporal epilepsies, hemispherical epilepsies, and gelastic epilepsy with a hypothalamic hamartoma. Palliative procedures include corpus callosotomy and VNS, while DBS in epilepsy is still under evaluation.
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Conflicts of interest
There are no conflicts of interest.
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