Functional hemispherotomy for epilepsy in the very young

Joshua Pepper Department of Neurosurgery,

Search for other papers by Joshua Pepper in
jns
Google Scholar
PubMed
Close
 MBBS
,
William B. Lo Department of Neurosurgery,

Search for other papers by William B. Lo in
jns
Google Scholar
PubMed
Close
 FRCS(NeuroSurg)
,
Shakti Agrawal Department of Neurology,

Search for other papers by Shakti Agrawal in
jns
Google Scholar
PubMed
Close
 MRCPCH
,
Rana Mohamed Department of Neurology,

Search for other papers by Rana Mohamed in
jns
Google Scholar
PubMed
Close
 MRCPCH
,
Jo Horton Department of Neuropsychology, and

Search for other papers by Jo Horton in
jns
Google Scholar
PubMed
Close
 QiCN
,
Selina Balloo Department of Neuropsychology, and

Search for other papers by Selina Balloo in
jns
Google Scholar
PubMed
Close
 PhD
,
Sunny Philip Department of Neurology,

Search for other papers by Sunny Philip in
jns
Google Scholar
PubMed
Close
 FRCPCH
,
Ashish Basnet Department of Neurosurgery,

Search for other papers by Ashish Basnet in
jns
Google Scholar
PubMed
Close
 MD
,
Welege Samantha Buddhika Wimalachandra Department of Neurosurgery,

Search for other papers by Welege Samantha Buddhika Wimalachandra in
jns
Google Scholar
PubMed
Close
 FRCS
,
Andrew Lawley Department of Neurology,

Search for other papers by Andrew Lawley in
jns
Google Scholar
PubMed
Close
 MD
,
Stefano Seri Department of Neurophysiology, Birmingham Children’s Hospital, Birmingham, United Kingdom

Search for other papers by Stefano Seri in
jns
Google Scholar
PubMed
Close
 MD
, and
A. Richard Walsh Department of Neurosurgery,

Search for other papers by A. Richard Walsh in
jns
Google Scholar
PubMed
Close
 FRCS
Free access

OBJECTIVE

Epilepsy is one of the most common neurological disorders in children. Among very young children, one-third are resistant to medical treatment, and lack of effective treatment may result in adverse outcomes. Although functional hemispherotomy is an established treatment for epilepsy, its outcome in the very young child has not been widely reported. In this study the authors investigated seizure and developmental results after hemispherotomy in children younger than 3 years.

METHODS

The authors reviewed a prospective database of all children younger than 3 years with medically intractable epilepsy who underwent functional hemispherotomy at the authors’ institution during the period between 2012 and 2020. Demographic data, epilepsy history, underlying etiology, operative and transfusion details, and seizure and developmental outcomes were analyzed.

RESULTS

Twelve patients were included in this study. The mean age (± SD) at seizure onset was 3 ± 2.6 months and at surgery was 1.3 ± 0.77 years, with a mean follow-up of 4 years. Diagnoses included hemimegalencephaly (n = 5), hemidysplasia (n = 2), hypoxic/hemorrhagic (n = 2), traumatic (n = 1), Sturge-Weber syndrome (n = 1), and mild hemispheric structural abnormality with EEG/PET correlates (n = 1). Eleven patients achieved an Engel class I outcome, and 1 patient achieved Engel class IV at last follow-up. No deaths, infections, cerebrovascular events, or unexpected long-term neurological deficits were recorded. All children progressed neurodevelopmentally following surgery, but their developmental levels remained behind their chronological age, with an overall mean composite Vineland Adaptive Behavior Scale score of 58 (normal: 86–114, low: < 70). One patient required insertion of a subdural peritoneal shunt, 1 patient required dural repair for a CSF fluid leak, and 1 patient required aspiration of a pseudomeningocele. In 2 patients, both of whom weighed less than 5.7 kg, the first operation was incomplete due to blood loss.

CONCLUSIONS

Hemispherotomy in children younger than 3 years offers excellent seizure control and an acceptable risk-to-benefit ratio in well-selected patients. Families of children weighing less than 6 kg should be counseled regarding the possibility of staged surgery. Postoperatively, children continue to make appropriate, despite delayed, developmental progress.

ABBREVIATIONS

ABC = Adaptive Behavior Composite; AED = antiepileptic drug; COM = communication domain of VABS; DLS = daily living skills domain of VABS; HOPS = Hemispherectomy Outcome Prediction Scale; MCA = middle cerebral artery; MOT = motor skills (fine and gross) domain of VABS; RCT = randomized controlled trial; SOC = socialization domain of VABS; VABS = Vineland Adaptive Behavior Scale.

OBJECTIVE

Epilepsy is one of the most common neurological disorders in children. Among very young children, one-third are resistant to medical treatment, and lack of effective treatment may result in adverse outcomes. Although functional hemispherotomy is an established treatment for epilepsy, its outcome in the very young child has not been widely reported. In this study the authors investigated seizure and developmental results after hemispherotomy in children younger than 3 years.

METHODS

The authors reviewed a prospective database of all children younger than 3 years with medically intractable epilepsy who underwent functional hemispherotomy at the authors’ institution during the period between 2012 and 2020. Demographic data, epilepsy history, underlying etiology, operative and transfusion details, and seizure and developmental outcomes were analyzed.

RESULTS

Twelve patients were included in this study. The mean age (± SD) at seizure onset was 3 ± 2.6 months and at surgery was 1.3 ± 0.77 years, with a mean follow-up of 4 years. Diagnoses included hemimegalencephaly (n = 5), hemidysplasia (n = 2), hypoxic/hemorrhagic (n = 2), traumatic (n = 1), Sturge-Weber syndrome (n = 1), and mild hemispheric structural abnormality with EEG/PET correlates (n = 1). Eleven patients achieved an Engel class I outcome, and 1 patient achieved Engel class IV at last follow-up. No deaths, infections, cerebrovascular events, or unexpected long-term neurological deficits were recorded. All children progressed neurodevelopmentally following surgery, but their developmental levels remained behind their chronological age, with an overall mean composite Vineland Adaptive Behavior Scale score of 58 (normal: 86–114, low: < 70). One patient required insertion of a subdural peritoneal shunt, 1 patient required dural repair for a CSF fluid leak, and 1 patient required aspiration of a pseudomeningocele. In 2 patients, both of whom weighed less than 5.7 kg, the first operation was incomplete due to blood loss.

CONCLUSIONS

Hemispherotomy in children younger than 3 years offers excellent seizure control and an acceptable risk-to-benefit ratio in well-selected patients. Families of children weighing less than 6 kg should be counseled regarding the possibility of staged surgery. Postoperatively, children continue to make appropriate, despite delayed, developmental progress.

In Brief

The authors studied seizure and developmental outcomes of very young children who have undergone hemispherotomy, a topic that has hitherto been sparsely reported. The study results show that young children have excellent seizure control, in the region of 90% (Engel class I), and continue to develop along their preexisting trajectory (i.e., they do not continue to exponentially fall behind their peers). The findings highlight the safety and seizure control effectiveness of hemispherotomies in very young children.

Epilepsy is one of the most common neurological disorders in childhood, with an incidence of approximately 40/100,000 persons per year.1 In general, outcomes for children with epilepsy are favorable, with two-thirds achieving seizure freedom.2 However, one-third of very young children with epilepsy, i.e., those younger than 3 years, develop medically intractable epilepsy, which if left untreated can result in developmental delay, intellectual disability, and premature death.3

Despite advancements in epilepsy surgery over the last 2 decades, the first randomized controlled trial (RCT) in children who had undergone pediatric epilepsy surgery was not published until 2017.4 This RCT and previous studies showed that in children younger than 3 years undergoing epilepsy surgery, two-thirds were seizure free without major complications.47 However, surgery in very young pediatric patients presents unique challenges in terms of surgical timing and approaches and anesthetic and surgical risks.

Functional hemispherotomy is indicated for medically intractable epilepsy, which may be caused by a spectrum of underlying pathological conditions.6,8,9 The rationale for operating on very young children is not only to prevent future seizures, but also to take advantage of the greater neuronal plasticity in these patients, which may facilitate postsurgical physical and cognitive development, although this aspect has been less studied.6 At the same time, the benefits of such surgery must be weighed against the surgical and anesthetic risks, especially in infants.10,11

Hemispheric operations with good outcomes in children with epilepsy were first described 7 decades ago.12 The surgical techniques of hemispheric resection and disconnection have evolved and in the modern era mostly involve functional hemispherotomy. This surgical procedure entails white matter disconnection of an entire hemisphere, including the peri-insular region, leaving the cortical mantle intact and vascularized.13

Studies examining the developmental outcomes of children undergoing epilepsy surgery at a younger age have found ongoing developmental progress postoperatively for the majority of infants.14 More favorable cognitive outcomes have been reported in infants with shorter seizure durations and younger age when surgery is performed.7

Here, we report the results of our investigation of functional hemispherotomy in patients younger than 3 years, with a focus on seizure outcome, complications, and development.

Methods

All patients who underwent functional hemispherotomy at our institution from 2012 to 2020 were identified in a prospectively kept database. Data were collected regarding the following variables: age, sex, primary diagnosis, radiological findings, medical comorbidities, developmental history, electroencephalography results, operative details, postoperative complications, seizure outcomes, and developmental stage. Seizure outcomes were categorized according to the Engel classification.6 For each patient, a Hemispherectomy Outcome Prediction Scale (HOPS) score was retrospectively calculated, for which scores indicate possible outcomes at 12 months postoperatively as follows: 0–2, 92.0%–96.3% likelihood of seizure freedom; 3–4, 70.0%–83.4% likelihood of seizure freedom; and 5–6, 51.4%–65.2% likelihood of seizure freedom.9

All children were administered the Vineland Adaptive Behavior Scale (VABS)16 questionnaire both prior to surgery and at long-term follow-up. The VABS is a semistructured interview that is administered to parents to assess their child’s adaptive functioning and development. The VABS consists of 3 main domains: communication (COM; receptive, expressive, and written language), daily living skills (DLS; personal, domestic, and community), and socialization (SOC: interpersonal relationships, play, and leisure). These domain scores are summed to form the Adaptive Behavior Composite (ABC) score. A fourth domain of motor skills (fine and gross) (MOT) is generated for younger age groups. Higher scores are indicative of higher levels of adaptive behavior.

Surgical Techniques for Functional Hemispherotomy

We performed the perisylvian (or periinsular) hemispherotomy using a modified version of the technique described by Schramm et al.17 To perform the first part of the suprasylvian disconnection, three tracts are made in the frontoparietal operculum, passing by and identifying the circular sulcus, to reach the lateral ventricle. The corona radiata is disconnected using suction and an ultrasonic aspirator. From within the lateral ventricle, a complete corpus callosotomy is performed. The frontobasal disconnection is performed followed by either a temporal lobectomy and amygdalohippocampectomy or a disconnection at the hippocampal tail and fimbria from the fornix. The infrasylvian disconnection of the temporal stem, via a tract through the temporal operculum, is carried out using a process similar to that used for the corona radiata disconnection. The insula is disconnected by undercutting along the junction between the insular cortex and extreme capsule, approaching from the circular sulcus. The dura is closed in a watertight fashion. An external ventricular drain is not routinely inserted.

Statistical Analysis

All averages presented are means ± SD unless otherwise stated. A Fisher’s exact test with a 2 × 2 contingency table was used to compare categorical data. For the VABS, an F-test was initially performed to test the null hypothesis that the variances of the two populations were equal. This was done for each scale of the VABS. A two-sample t-test was then performed on the subscales of the VABS, either using the assumption that variances are equal or unequal, comparing preoperative and postoperative scores. A p value < 0.05 was considered significant.

Results

Twelve patients were included in the study, with an average age at surgery of 15 ± 9 months (range 1.8–28.8 months); 8 of 12 patients were male (Table 1). The average age of seizure onset was 3.1 ± 2.8 months with follow-up of 4.0 ± 1.9 years. The median duration of admission was 11 days (range 7–69 days).

TABLE 1.

Summary of patient characteristics and clinical details

Pt No.SexAge at Op, mosAge at Sz OnsetPresenting Sz TypeDxGenetics
1M1.81 dayInfantile spasmsHemidysplasia, polymicrogyriaNo
2M2.22 daysEyelid flickering w/ desaturationHemimegalencephaly (histology polymicrogyria)PIK3CA mutation
3F64 mosEye fluttering, rt arm & leg jerking evolving into bilat convulsive SzsHemimegalencephalyPIK3CA mutation
4M10.04 mosMultifocal motor SzsPrenatal rt MCA infarctNo
5M13.99 daysCyanosis episodesHemimegalencephaly, polymicrogyriaNo
6M14.06 mosInfantile spasmsPrenatal intracerebral hemorrhage w/ hypoxic ischemic encephalopathy, West syndromeNo
7M16.33 mosInfantile spasmsHemidysplasia, polymicrogyriaNo
8M16.4NRInfantile spasmsHemimegalencephaly, tuberous sclerosisTSC2
9F16.63 mosConvulsive bilat w/ more rt-sided involvementHemimegalencephalyNo
10M25.84 mosInfantile spasmsHemispheric structural focal epileptic encephalopathy, West syndromeNo
11F28.76 wksRt focal hemispheric status*Nonaccidental injury, traumatic brain injury, extensive rt encephaloclastic changesNo
12F28.79 mosFocal twitching of rt arm & legSturge-Weber syndromeNot tested

CTG = cardiotocogram; Dx = diagnosis; NR = not recorded; Pt = patient; Sz = seizure.

Occurred after an episode of nonaccidental injury.

Seizure Characteristics

See Table 2 for more details of seizure characteristics and Table 3 for electroencephalography details. The average number of antiepileptic drugs (AEDs) tried before surgery was 4.4, including steroids. No patients were started on a ketogenic diet before surgery.

TABLE 2.

Preoperative seizure types

Pt No.No. of Sz TypesSz Description (frequency)No. of Preop AED TrialsNo. of Preop AEDs
121) Infantile spasms (7 hrs/day)

2) Asymmetric tonic Szs
43*
221) Eye/mouth deviation, eye flickering (50/day, lasting 5 sec each)

2) 1 generalized tonic-clonic Sz
22
311) Eye fluttering, rt arm & rt leg jerking evolving to bilat convulsive Szs (500/wk, clusters lasting >1 hr)53
421) Eye rolling/rhythmical jerking of rt leg (5/day)

2) Whole-body tonic spasms (30/day lasting up to 5 mins each)
53
541) Episodes of cyanosis

2) Rt-sided clonic jerking generalizing to both arms & legs & face (10/day)

3) Clusters of infantile spasms (10/day)

4) Vacant spells w/ nystagmus (clusters of 10–15/day)
53
611) Infantile spasms (6/day); stopped at 11 mos but EEG showed ongoing hemihypsarrhythmia52
711) Infantile spasms (40/day)42
821) Infantile spasms (30 spasms in a cluster, 35 clusters/wk)

2) Lt-eye movement w/ behavioral arrest
33*
931) Bilat convulsive Szs from rt-sided focus (2/day) culminating in extended status epilepticus

2) Rt hand clonic jerking (continuous during day)

3) Vacant episodes (1/wk)
63
1011) Infantile spasms (500/day)43
1121) Epileptic spasms (20/day)

2) Focal tonic lt arm spasms (continuous throughout day)
72
1231) Focal twitching rt arm & leg (10/day)

2) Vacant episodes w/ some body jerking (continuous throughout day)

3) Atonic episodes
33

Preoperative to redo hemispherotomy.

TABLE 3.

EEG characteristics

Pt No.EEG Characteristics
1Asymmetrical & asynchronous lt hemisphere activity represented by bursts of spike & polyspike activity lasting 2–4 sec followed by periods of suppression
2Asymmetrical w/ near continuous epileptiform activity over lt hemisphere
3Lt middle & posterior temporal w/ abrupt desynchronization & fast recurring spiking activity. Continuous interictal activity over lt posterior quadrant
4Modified hypsarrhythmia, bilat multifocal abnormalities, fast rhythm in rt frontal region. Continuous interictal discharges over rt temporal area
5Semicontinuous focal epileptiform discharges in lt occipital & occasionally lt frontal region
6Rt continuous hemihypsarrhythmia
7Tonic spasms w/ asymmetric EEG change. Asymmetric epileptic encephalopathy w/ predominately rt side involvement
8Suggestive of rt temporal occipital lead
9Sharpened theta lt frontal at start evolving into faster frequency & at end focal slow lt frontocentral region
10Slow delta waves w/ associated spikes; in sleep large amounts of diffuse slow wave delta w/ associated spike & sharp waves; bursts of spindling fast activity in rt frontocentral area followed by burst of slow wave & spike activity
11Continuous epileptiform discharges in rt posterior region while asleep & awake
12Generalized spike & wave w/ lt temporal predominance

Underlying Diagnosis

Of the 8 patients with hemispheric developmental abnormalities, 7 had an Engel class I outcome (patient numbers 1, 3, 5, 7, 8, 9, and 10) and 1 had an Engel class IV outcome (patient number 2). Of those with stable acquired pathology (hypoxic ischemic encephalopathy, hemorrhagic, traumatic), 3 of 3 patients (patient numbers 4, 6, and 11) had Engel class I outcomes, and the patient with progressive pathology (Sturge-Weber syndrome, patient number 12) had an Engel class I outcome at a mean follow-up of 3.8 years.

Five children presented with epileptic spasms (patient numbers 1, 6, 7, 8, and 10) and all achieved Engel class I outcomes at long-term follow-up.

Surgical Characteristics

Fourteen hemispherotomies were performed in 12 patients, two operations of which were to disconnect residual white matter in children who had undergone previous hemispherotomies (numbers 1 and 8) (Tables 4 and 5). Another child (number 7) had undergone a previous frontal lobectomy and underwent complete hemispherotomy due to ongoing high seizure burden. The mean operative time was 5.8 ± 0.86 hours. On average, 0.68 circulating volume of blood was transfused in all children, which equates to 54 ml/kg blood transfused. For the 2 children who had incomplete hemispherotomy due to excessive bleeding, the blood transfusion was 599 ml in patient 1 (1.5 circulating volume) and 1037 ml in patient 2 (2.3 circulating volume).

TABLE 4.

Engel class outcomes and VABS at last follow-up

Pt No.SideAge at Op, mosAge at Last FU, mosEngel ClassVABS Scores
12 mos PostopLast FUHOPSABCCOMDLSSOCMOT
1*Lt1.841.4IBIB36864687378
2Lt2.220.1IVBIVB36049547220
3Lt6.032.0IAIA2
4Rt10.037.1IAID37376727349
5Lt13.9103.4IAIA356365870
6Rt14.082.0IAIA26360597020
7Rt16.328.3IAIA26561409243
8*Rt16.488.4IVAIC24128593220
9Lt16.657.8IAIA26270627352
10Rt25.856.8IAIA26152596820
11Rt28.760.0IDIC24022415462
12Lt28.798.2IAIA24628624420

FU = follow-up.

After second surgery following first incomplete surgery.

Scores below 70 are suggestive of learning disability.

TABLE 5.

Summary of operative details

Pt No.Side of OpWt, kgOp Time, minsBlood Transfusion, mlWt-Adjusted Blood Transfusion, ml/kgLength of Inpatient Stay Postop, daysOp Completed as PlannedPrevious Epilepsy Op
1Lt5.0237559911969No, due to excessive blood lossNo
1Lt8.974155506111YesPrevious incomplete hemispherotomy
2Lt5.70325103718211No, due to excessive blood lossNo
3Lt8.00300117714715NoNo
4Rt11.052901101011YesNo
5Lt12.60600*3002410YesNo
6Rt9.003001201310YesNo
7Rt8.173954065014YesPrevious rt frontal disconnection
8Rt12.00360655557NoNo
8Rt13.32330*2902214YesPrevious incomplete hemispherotomy
9Lt11.704357106111YesNo
10Rt15.80320150910YesNo
11Rt14.303100010YesNo
12Lt10.603001501410YesNo

Wt = weight.

Total time in theater complex as surgical time not recorded.

Seizure Outcomes

At last follow-up, with optimized medical management of postoperative seizures, 11 children had Engel class I outcomes and 1 child had an Engel class IV outcome (Tables 3 and 4). Of the 11 children with Engel class I outcomes, 7 children maintained seizure-free status, i.e., Engel class IA (Fig. 1, Tables 3 and 4). Eight children had HOPS scores of 2 (6 with Engel class IA and 2 with Engel class IC outcomes). Four children had HOPS scores of 3, with these children having Engel outcomes of class IA, IB, ID, and 4B, respectively, at last follow-up.

FIG. 1.
FIG. 1.

Kaplan-Meier survival curve for seizure freedom. Note that 11 children achieved eventual seizure freedom despite continuing to have postoperative seizures initially.

Children With Postoperative Seizures

For the analysis of postoperative seizure outcome, children who had seizures between the first incomplete and second complete hemispherotomies were not included, as the surgical intent was not achieved. Patients who continued to have seizures after complete hemispherotomy were included. Patient number 2 underwent a hemispherotomy at 2 months of age, which was incomplete due to a large volume of blood loss during surgery. This patient’s seizures did not improve postoperatively and his seizure status was classified as Engel class IVA at last follow-up at 18 months of age. Patient number 4 had an excellent outcome after surgery at 10 months of age and was seizure free. Two years postoperatively, after an attempt to wean this patient from one of his AEDs, he had episodes of absence seizures, although at lower frequency than preoperatively. After recommencing the original dose of this AED he was completely seizure free (Engel class ID). Patient number 8, with tuberous sclerosis, was seizure free in the immediate postoperative period at 16 months old, but after a month his seizures worsened. Further investigation revealed that the hemispherotomy was incomplete, with a residual small insular connection. This patient then underwent completion of the hemispherotomy 4 months after the first surgery. Despite this procedure, he continued to have disabling seizures for 12 months. After a number of adjustments to his medications he was eventually rendered free of disabling seizures, and at last follow-up of 6 years he had not had a disabling seizure for more than 4 years and had only had 1 short-lasting focal seizure during an episode of illness 26 months previously (classified as Engel class IC). Patient 11 at 5 months postoperatively had a generalized seizure thought to be secondary to a febrile illness and was treated for underlying pneumonia. After this treatment the patient remained completely seizure free (Engel class IC) at last follow-up.

Antiepileptic Medications

At last follow-up, 6 patients were weaned off AEDs, 3 patients were on monotherapy, and the remaining 3 were taking two or more AEDs.

Neurological Outcomes and Development

Data for the VABS were available for 11 of 12 children (Tables 6 and 7). Ten of 11 children had VABS ABC scores below 70, which would classify them as being developmentally below the level expected for their chronological age. In comparing pre- and postoperative VABS scores, only the COM and MOT domains were found to be statistically significantly lower (Table 6). There was no statistically significant difference associated with the side of hemispherotomy on any of the developmental outcomes on the VABS (ABC, p = 0.86; COM, p = 0.96; DLS, p = 0.35; SOC, p = 0.88).

TABLE 6.

Grouped outcomes for VABS

COMDLSSOCABCMOT
Mean preop70.1468.7174.7171.6764.14
Mean postop49.0357.6365.5557.7238.4
t value2.251.341.161.872.82
p value0.040.210.260.080.01
TABLE 7.

Developmental characteristics

Pt No.Age, yrsDevelopmental AgeGross MotorFine Motor & VisionHearing & SpeechSocial
142–3 yrs in speech, 4 yrs in gross motorWalks, runs, & jumps, rt hemiplegiaScribbles, no rt-hand function2–3 words w/ meaning, can repeat words, understands wellCan feed himself w/ spoon, needs help undressing
216–8 mosHead control, sits w/ support, turns from prone to supine & vice versaLt hand stronger, holds & mouths objectsBabblesLaughs & interacts
343.5–4 yrsWalking, trying to run, rt hemiplegiaTraces letters, draws circles & squaresNormal speech (stories)Dry daytime, plays w/ peers
43.59–12 mosBottom shuffling, not bearing wt, lt hemiplegiaPicks up & mouths objects, holds bottle5 words w/ meaningAntisocial behavior
58.52–3 yrs in fine motor, speech is age appropriateRt hemiplegia, walks, runs, & jumps; just started to ride a bikeScribbles, draws circles, traces lettersAge appropriateNot toilet trained, interacts well
71.759 mosSitting, crawlingPincer grasp, lt-handedBabbles, "mama" nonspecificallyWaves bye, understands "no"
87.755–6 yrs in speech & social, 18–24 mos in motor developmentImmobile, crawls, stands w/ supportScribbles, colors2- to 3-word sentences, counts to 20Not toilet trained, interacts well
955 yrsWalks w/ walker, rt-sided hemiplegiaScribbles, needs help undressing, rt-sided hemiplegia2- to 3-word sentences, counts to 15Not toilet trained, interacts well
1052 yrs2 yrs developmentally18 mos developmentally18 mos developmentally18 mos developmentally
1153 yrs in speech & social, 12–18 mos in motor development12–18 mos developmentally12–18 mos developmentally2- to 3-word sentences, counts to 10, names 3 colorsNot toilet trained, interacts well
1285 yrsRt side hemiplegia, walks alone, cannot runWrites nameNormal speechToilet trained, needs help undressing

Incomplete First Operations

Four children had incomplete first operations (see Tables 4 and 5). Patient 1, who at 1.8 months weighed 5.1 kg, had an incomplete operation due to blood loss of 800 ml. He had completion hemispherotomy at just under 6 months of age, when he weighed 9.0 kg, and achieved Engel class IB at last follow-up. Patient 2, who at 2.1 months of age weighed 5.7 kg, had incomplete corpus callosotomy and insular undercutting due to blood loss of 1037 ml. He had an Engel class IVB outcome at last follow-up, with plans to complete the hemispherotomy. Patient 3 at 6 months of age was inadvertently extubated before the insular undercutting was completed. However, she had Engel class IA outcome at last follow-up of 3.8 years and was taking one AED. Patient number 8, with tuberous sclerosis, underwent hemispherotomy at 16 months of age. Although he had an initially good response 2 months postoperatively, his seizures were back at his baseline level and residual frontal and insular connections were identified. He underwent completion hemispherotomy 4 months after the first surgery and had an Engel class IC outcome at last follow-up of almost 8 years.

Complications

Three complications were noted. Two children developed pseudomeningocele, one of which was aspirated, the other required surgical exploration, dural repair, and insertion of an external ventricular drain. One child with previous severe head trauma and significant encephalomalacia developed a postoperative subdural effusion requiring eventual insertion of a subdural peritoneal shunt. There were no cases of aseptic meningitis and no deaths or significant long-term postsurgical complications in any child.

Discussion

In our experience functional hemispherotomies on very young children with medically intractable epilepsy secondary to hemispheric pathology and epileptic foci resulted in seizure freedom in nine-tenths of the cases. Our outcomes compare favorably to those of the few studies, both larger and smaller than the present study, in the published literature.7,9,18,19

Diagnosis

The underlying diagnosis in two-thirds of our patients was malformation of cortical development including hemimegalencephaly and hemidysplasia. The remaining underlying diagnoses were stable acquired pathology (ischemic, hemorrhagic, traumatic brain injury) or Sturge-Weber syndrome. A similar pattern of heterogeneity has been reported by other investigators.7,9,18,19

Seizure Outcomes

The overall Engel class I rate in this study at last follow-up was 92% (11 of 12 children). However, a number of children had postoperative seizures at time points ranging from 1 month to 14 months after surgery, which triggered the Kaplan-Meier graph giving an overall postoperative nonevent or "seizure freedom" rate of 64%. In all but one child these seizures were controlled completely with medication at last follow-up.

In a large international study to develop the Hemispherectomy Outcome Prediction Scale (HOPS), which involved 1257 children9 with a median age at surgery of 5.5 years, 83% of children had seizure freedom at 12 months, and this figure slowly decreased over time, with a 5-year rate of seizure freedom of 66%. Importantly, the investigators noted that the median time to seizure recurrence was 10 years. This delay phenomenon may explain the high rate of seizure freedom in our cohort with shorter follow-up. However, most of our children had HOPS scores of 2, which is associated with a > 90% seizure freedom rate.

Duchowny et al. reported their experience with 14 children younger than 3 years undergoing hemispherotomies.20 Nine (64%) of 14 children were seizure free with minimum follow-up of 1 year. This is lower than the Engel class I rate seen in our cohort. In many respects the two groups of study patients are the same, with a similar range of diagnoses and age at surgery. However, it is interesting to note that 11 (79%) of the 14 children in the study by Duchowny et al. had seizure onset when younger than 3 months. This contrasts with our group of patients, of whom only half had seizure onset at age 3 months or younger. Earlier age of seizure onset is known to be a poor predictor of seizure freedom.9

In a detailed study by Kadish et al., 22 children under 3 years of age underwent hemispherotomy.6 Of these, 54% (12 of 22) were seizure free. A further 3 patients who had previous intralobar and multilobar resections underwent hemispherotomy as a second procedure. One was seizure free at the 4.3-year long-term follow-up. In our cohort, there was also 1 patient (number 7) who had a previous right frontal disconnection who eventually proceeded to hemispherotomy, who was seizure free at long-term follow-up. The ages of seizure onset and surgery in the Kadish et al. study were broadly similar to those in the present study, and the patients had been treated with a similar number of AED trials prior to surgery, although more of the children in our study were weaned off AEDs postoperatively. None of our children underwent trials on a ketogenic diet prior to surgery, unlike 8% of the Kadish et al. cohort, but this is unlikely to explain the difference. While the hemispherotomy surgical technique is not made explicit, Kadish et al.’s report provides detailed clinical information. However, it is difficult to establish any other causative reasons for the large difference in seizure outcome between those reported by Kadish et al. and those reported in our study.

A large retrospective Canadian study by Steinbok et al. including 116 children younger than 3 years who underwent hemispheric surgery between 1987 and 2005 reported 58% seizure freedom at long-term follow-up for the 48 children who underwent hemispherotomy.7 The marked difference in the results for our study compared with those reported by Steinbok et al. may be attributable to the time frame for operations in this large Canadian study occurring from 1987 to 2005, whereas all of our operations occurred after 2012. The improvements in imaging, use of a more established multidisciplinary approach, and developments in microneurosurgery and subspecialization of neuroanesthesia during this 20- to 30-year time lag may explain a large part of this difference. Other factors such as age at seizure onset or surgery are similar for the two studies. Given that the report of this retrospective study does not break down details by operation, it is difficult to determine if there is a difference in underlying diagnosis or other causative factors that may be responsible for the outcome differences. Furthermore, in a large Chinese study of 83 children under 10 years of age, more than 80% were seizure free at the long-term follow-up after hemispherotomy.21 Although this cohort of children is older than ours, the similarities in range of underlying diagnoses, surgical techniques, and years in which surgery was performed may explain our more similar results.

Steinbok et al. noted that patients with cerebral infarct had the best outcomes (Engel class I or II) in all 7 patients, followed by patients with Sturge-Weber syndrome (10 of 11 patients), hemimegalencephaly (8 of 10 patients), and then cortical dysplasia (8 of 15 patients). The reverse situation was reported for a cohort of Chinese children undergoing hemispherotomy.7,21 We did not note either of these findings in our patients, likely because our study is underpowered to determine this etiological relationship to seizure outcome.

Blood Loss

In our group of patients most required a blood transfusion intraoperatively. For the most part, judicious replacement of any blood volume lost by group- and type-specific blood is a routine intraoperative practice in our surgical unit. Our practice is to achieve hemostasis and stop further disconnection if there is a significant remaining part to be performed and the blood loss has reached two circulating volumes. In 2 babies in our study, blood volume loss was extensive and resulted in the surgery being discontinued. Both babies were around 2 months old and weighed less than 5.7 kg. Interestingly, the largest weight-adjusted blood volume losses were in 2 children who were aged 6 months or younger and had PIK3CA overgrowth syndrome. This syndrome, for which we are not aware of previous reports in the context of the present study, is known to be associated with vascular malformations such as telangiectasia and low fibrinogen states, which may have increased the risk of higher volume blood loss.22 Apart from these 2 patients, blood loss was not a major operative concern for the remainder of our patients.

Blood loss and/or transfusion requirements in hemispherotomy are often not reported. Kumar et al. reported on a neonate with hemimegalencephaly for whom the operation was abandoned due to significant blood volume loss.23 These investigators also reported that most of their patients, with an age range between 11 days and 11.5 months, required half–blood volume transfusion with a mean weight-adjusted transfusion volume of 66 ml/kg. In a recent paper of 38 infants under 12 months of age who underwent a variety of epilepsy operations, none required a blood transfusion intraoperatively.19 This result contrasts to those in a study in which almost 90% of patients had intraoperative blood transfusion.24

To minimize blood loss, the University California, Los Angeles (UCLA) developed a modified lateral hemispherotomy in 1998 that included the ligation of the middle cerebral artery (MCA) and the removal of the central structures which were the indication for reoperations in Rasmussen’s encephalitis.25 So far, we have not adopted these two surgical steps, primarily because we are more familiar with our current functional hemispherotomy technique, which offers high seizure freedom and low reoperation rates. Furthermore, it is difficult to balance the benefit of reduced blood loss from MCA ligation from the risk of superficial hemosiderosis from larger resection.

Developmental Outcomes

In our study all children who underwent hemispherotomy continued to develop and maintained their preoperative development trajectories, but they did not catch up with their peers. As all of these children were younger than 3 years, and the average age at surgery was just over 12 months, we acknowledge the limitations and challenges in administering formal neuropsychological/developmental assessments in these patients. Even when children undergo neuropsychological tests prior to the age of 12 months, they may score within the "average" range, but the skills required to meet this are very limited and even very young children with significant pathology can be categorized as "average" by smiling or looking toward a sound.17 We also acknowledge that infant development, especially in the very young, may fluctuate widely in a short period. Therefore, comparisons between pre- and postoperative adaptive behavior assessments may not necessarily reflect the entire neurodevelopmental journey of these children and their development as shown in Tables 6 and 7. We acknowledge that at an average of 4 years of follow-up is short in the context of an entire life. Furthermore, all families offered surgery accepted it. Therefore, there is not a control group of untreated patients which would inform us of their neurodevelopment natural history.

The findings of the current study are consistent with those found in other studies examining developmental outcomes in children who had epilepsy surgery in early life, in that children with poorer preoperative development remained in the same category postsurgery.14,26 Moosa et al.27 reported poorer verbal language in children with an epilepsy onset at a younger age and children underwent a left hemispherotomy. These investigators concluded that children younger than 18 months with indeterminant language skills have poorer postoperative language skills. Kadish et al.6 noted a finding similar to one we observed in the present study in that children still continue to develop after surgery along the same trajectory they were on preoperatively, with only 14% improving their developmental category. Importantly, a number of authors have noted the developmental importance of early surgery in cases of medically refractory epilepsy. Even though these children do not vastly improve their development quotient, it is well recognized that later onset surgery or longer duration of catastrophic epilepsy results in children being even further behind their peers developmentally at long-term follow-up.28,29

Significance of Epileptic Spasms

The natural history of epileptic spasms needs special mention. It should be noted that 5 of our patients (patients 1, 6, 7, 8, and 10) presented with epileptic spasms in association with EEG findings of either hypsarrhythmia or modified hypsarrhythmia prior to their surgical intervention. It is widely known that the prognosis in such children, in terms of normal development, is poor despite treatment. Moderate or severe learning difficulties may be present in 70% to 90% of these patients at follow-up.3033 The prognosis is better in patients with no known associated etiologic factors, no abnormality on neurological examination, normal development before the onset of the spasm, and normal neuroimaging prior to therapy.30

Our patients had abnormal imaging and neurological examination, which placed them in an adverse prognostic category from the outset. In a small population-based study in Iceland, approximately one-third of children were diagnosed with autism spectrum disorders.34 A report from the United Kingdom Infantile Spasms Study (UKISS) shows evidence that age at onset of spasms is important in that earlier onset of spasms is followed by poorer developmental outcome at 4 years of age, independent of the effect of lead time to treatment, treatment allocation, or etiologic group.35 These data are also supported by another study from the US consensus report.36 Patients with infantile spasms carry an increased risk of mortality due to the underlying etiologic disease and comorbid conditions.31,37,38 From Tables 4 and 5, it is evident that 3 of 4 patients with infantile spasms for whom the developmental outcome data were available (patients 1, 7, 8, and 10) have had reasonably good outcomes in terms of their speech and social development, which is particularly known to be affected in children presenting with infantile spasms. All of these children ultimately had successful surgery and achieved Engel class I at last follow-up, suggesting a possible causative link between seizure and developmental outcome. Of course, these are small numbers and it is difficult to generalize these conclusions without further studies.

Ventriculoperitoneal Shunt Rate, Redo Surgery Rate, and Other Complications

In our cohort of 12 children there were no perioperative deaths, and all children were alive at a medium-term follow-up of almost 4 years. Hydrocephalus is one of the most common complications reported in patients after hemispherotomy, with a shunt insertion rate between 0% and 23.5%.7,19,23,24,39 In our series 1 patient (1 of 12) with significant encephalomalacic changes required the insertion of a long-term subdural peritoneal shunt. However, none of the patients required a ventriculoperitoneal shunt for hydrocephalus. This finding may be explained by two aspects of our technique. First, rather than performing a perisylvian C-shaped corticotomy exposure of the lateral ventricle, we access the ventricle via 3–5 tracts instead, allowing greater preservation of the cortical architecture and ventricular anatomy, and reducing the resection volume, which may in turn reduce the change in CSF dynamics. Second, following meticulous hemostasis, we routinely do not leave an external ventricular drain in situ, in contrast to the practice described by most centers. The rationale of postoperative external drainage is that it reduces blood product and surgical debris, thereby reducing the risk of hydrocephalus. However, by not overdraining/draining CSF, the ventricles may be better preserved and less collapsed, preventing microscopic adhesions or gliosis between resection surfaces which cause CSF obstruction.

Two patients in our cohort required redo surgery for incomplete disconnection, and 1 patient with incomplete disconnection is awaiting surgery. This redo rate is slightly higher in our patients at 25% than the range of 0%–20% for the very young in the literature.7,18,19,23 There were no deep or superficial wound infections, cerebral infarctions, or unexpected neurological deficits (besides hemiparesis and hemianopia, which are expected consequences of the surgery). These outcomes compare favorably with outcomes reported by others.7,19

Challenges of the Low-Weight Infant

In our experience there are marked physiological and surgical planning differences required for infants, particularly those weighing less than 6 kg. Infants have higher perioperative circulatory and respiratory complication rates than older children.40 In our group of children, the 2 patients with weights under 6 kg had incomplete hemispherotomies due to significant blood volume loss. Piastra and colleagues showed that infants younger than 1 year undergoing hemispherotomy had significantly greater risk of perioperative massive blood loss and hematological derangements, a finding we noted as well.11 Dorfer et al. in 2015 reported 4 cases of infants undergoing hemispherotomy, with weights from 4.3 to 7.5 kg and blood transfusion volumes of 43 to 107 ml/kg.10 The authors noted similar particular surgical and anesthetic challenges, including fragility of the brain, vulnerability to bleeding, incomplete disconnection, watertight dural closure, postoperative hemorrhage, temperature shift, volume derangement, electrolyte imbalance, under- or overtransfusion, and coagulopathy. Ultimately, all of their children had excellent seizure control outcomes at long-term follow-up. Interestingly, Honda et al. reported minimal complications and average blood transfusion volume of 34 ml/kg in a group of 12 infants with a mean age of 4 months with hemimegalencephaly who underwent hemispherotomy.15 However, the aim of the study by Honda et al. was investigation of the developmental and seizure outcomes of these children without making much note of the surgical and anesthetic considerations. Despite these challenges, low-weight infants with catastrophic epilepsy should be offered surgery and have excellent outcomes, but this requires multidisciplinary team input from an experienced team of pediatric epileptologists, pediatric neurosurgeons, neuroanesthesiologists, and intensive care doctors.

Study Limitations

This is a study of a small number of children but still represents a large series of hemispherotomies performed in children younger than 3 years with investigation of seizure outcome and developmental data. There is no blinding to outcome or control group, which may add a degree of bias.

Conclusions

Hemispherotomy in very young children results in excellent seizure outcome and can be considered a safe procedure. The decision to perform surgery in very young children with a weight under 6 kg should be carefully considered due to the risk of requiring an excessive number of blood transfusions. However, even incomplete disconnection offers some seizure control until it is safe to proceed with a second definitive surgery when the children gain more weight.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Lo, Pepper, Agrawal, Walsh. Acquisition of data: Pepper, Agrawal, Mohamed, Horton, Basnet, Wimalachandra. Analysis and interpretation of data: Lo, Pepper, Agrawal, Horton, Balloo, Philip. Drafting the article: Pepper, Horton, Wimalachandra. Critically revising the article: Lo, Pepper, Agrawal, Mohamed, Walsh. Reviewed submitted version of manuscript: Lo, Pepper, Agrawal, Mohamed, Philip, Lawley, Seri, Walsh. Statistical analysis: Pepper.

References

  • 1

    Wirrell EC, Grossardt BR, Wong-Kisiel LCL, Nickels KC. Incidence and classification of new-onset epilepsy and epilepsy syndromes in children in Olmsted County, Minnesota from 1980 to 2004: a population-based study. Epilepsy Res. 2011;95(1-2):110118.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Sillanpää M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain. 2006;129(Pt 3):617624.

  • 3

    Wirrell E, Wong-Kisiel L, Mandrekar J, Nickels K. Predictors and course of medically intractable epilepsy in young children presenting before 36 months of age: a retrospective, population-based study. Epilepsia. 2012;53(9):15631569.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Dwivedi R, Ramanujam B, Chandra PS, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med. 2017;377(17):16391647.

  • 5

    Delalande O, Bulteau C, Dellatolas G, et al. Vertical parasagittal hemispherotomy: surgical procedures and clinical long-term outcomes in a population of 83 children. Neurosurgery. 2007;60(2 Suppl 1):ONS19ONS32.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Kadish NE, Bast T, Reuner G, et al. Epilepsy surgery in the first 3 years of life: predictors of seizure freedom and cognitive development. Neurosurgery. 2019;84(6):E368E377.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Steinbok P, Gan PYC, Connolly MB, et al. Epilepsy surgery in the first 3 years of life: a Canadian survey. Epilepsia. 2009;50(6):14421449.

  • 8

    Basheer SN, Connolly MB, Lautzenhiser A, Sherman EMS, Hendson G, Steinbok P. Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function. Epilepsia. 2007;48(1):133140.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Weil AG, Lewis EC, Ibrahim GM, et al. Hemispherectomy Outcome Prediction Scale: development and validation of a seizure freedom prediction tool. Epilepsia. 2021;62(5):10641073.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Dorfer C, Ochi A, Snead OC III, et al. Functional hemispherectomy for catastrophic epilepsy in very young infants: technical considerations and complication avoidance. Childs Nerv Syst. 2015;31(11):21032109.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Piastra M, Pietrini D, Caresta E, et al. Hemispherectomy procedures in children: haematological issues. Childs Nerv Syst. 2004;20(7):453458.

  • 12

    Krynauw RA. Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry. 1950;13(4):243267.

  • 13

    Villemure JG, Mascott CR. Peri-insular hemispherotomy: surgical principles and anatomy. Neurosurgery. 1995;37(5):975981.

  • 14

    Loddenkemper T, Holland KD, Stanford LD, Kotagal P, Bingaman W, Wyllie E. Developmental outcome after epilepsy surgery in infancy. Pediatrics. 2007;119(5):930935.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Honda R, Kaido T, Sugai K, et al. Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy. Epilepsy Behav. 2013;29(1):3035.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Sparrow SS, Balla DA, Cicchetti DV. Vineland Adaptive Behavior Scales VABS: Expanded Form Manual. American Guidance Service; 1984.

  • 17

    Schramm J, Kral T, Clusmann H. Transsylvian keyhole functional hemispherectomy. Neurosurgery. 2001;49(4):891901.

  • 18

    González-Martínez JA, Gupta A, Kotagal P, et al. Hemispherectomy for catastrophic epilepsy in infants. Epilepsia. 2005;46(9):15181525.

  • 19

    Ye VC, Shah AH, Sur S, et al. Long-term outcomes after surgery for catastrophic epilepsy in infants: institutional experience and review of the literature. J Neurosurg Pediatr. 2020;26(2):157164.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Duchowny M, Jayakar P, Resnick T, et al. Epilepsy surgery in the first three years of life. Epilepsia. 1998;39(7):737743.

  • 21

    Ji T, Liu M, Wang S, et al. Seizure outcome and its prognostic predictors after hemispherotomy in children with refractory epilepsy in a Chinese pediatric epileptic center. Front Neurol. 2019;10:880.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Canaud G, Hammill AM, Adams D, Vikkula M, Keppler-Noreuil KM. A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations. Orphanet J Rare Dis. 2021;16(1):306.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Kumar RM, Koh S, Knupp K, Handler MH, O’Neill BR. Surgery for infants with catastrophic epilepsy: an analysis of complications and efficacy. Childs Nerv Syst. 2015;31(9):14791491.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Ramantani G, Kadish NE, Strobl K, et al. Seizure and cognitive outcomes of epilepsy surgery in infancy and early childhood. Eur J Paediatr Neurol. 2013;17(5):498506.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Cook SW, Nguyen ST, Hu B, et al. Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients. J Neurosurg. 2004;100(2 Suppl Pediatrics):125141.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Althausen A, Gleissner U, Hoppe C, et al. Long-term outcome of hemispheric surgery at different ages in 61 epilepsy patients. J Neurol Neurosurg Psychiatry. 2013;84(5):529536.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Moosa ANV, Jehi L, Marashly A, et al. Long-term functional outcomes and their predictors after hemispherectomy in 115 children. Epilepsia. 2013;54(10):17711779.

  • 28

    Asarnow RF, LoPresti C, Guthrie D, et al. Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms. Dev Med Child Neurol. 1997;39(7):430440.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Jonas R, Asarnow RF, LoPresti C, et al. Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms. Neurology. 2005;64(4):746750.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Riikonen R. Recent advances in the pharmacotherapy of infantile spasms. CNS Drugs. 2014;28(4):279290.

  • 31

    Riikonen R. Long-term otucome of West syndrome: a study of adults with a history of infantile spasms. Epilepsia. 1996;37(4):367372.

  • 32

    Riikonen R. A long-term follow-up study of 214 children with the syndrome of infantile spasms. Neuropediatrics. 1982;13(1):1423.

  • 33

    Trevathan E, Murphy CC, Yeargin-Allsopp M. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 1999;40(6):748751.

  • 34

    Saemundsen E, Ludvigsson P, Rafnsson V. Autism spectrum disorders in children with a history of infantile spasms: a population-based study. J Child Neurol. 2007;22(9):11021107.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    O’Callaghan FJK, Lux AL, Darke K, et al. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia. 2011;52(7):13591364.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51(10):21752189.

  • 37

    Harini C, Nagarajan E, Bergin AM, et al. Mortality in infantile spasms: a hospital-based study. Epilepsia. 2020;61(4):702713.

  • 38

    Riikonen R. Epidemiological data of West syndrome in Finland. Brain Dev. 2001;23(7):539541.

  • 39

    Dunkley C, Kung J, Scott RC, et al. Epilepsy surgery in children under 3 years. Epilepsy Res. 2011;93(2-3):96106.

  • 40

    Tiret L, Nivoche Y, Hatton F, Desmonts JM, Vourc’h G. Complications related to anaesthesia in infants and children. A prospective survey of 40240 anaesthetics. Br J Anaesth. 1988;61(3):263269.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand

Image from Tran et al. (pp 394–399).

  • FIG. 1.

    Kaplan-Meier survival curve for seizure freedom. Note that 11 children achieved eventual seizure freedom despite continuing to have postoperative seizures initially.

  • 1

    Wirrell EC, Grossardt BR, Wong-Kisiel LCL, Nickels KC. Incidence and classification of new-onset epilepsy and epilepsy syndromes in children in Olmsted County, Minnesota from 1980 to 2004: a population-based study. Epilepsy Res. 2011;95(1-2):110118.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Sillanpää M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain. 2006;129(Pt 3):617624.

  • 3

    Wirrell E, Wong-Kisiel L, Mandrekar J, Nickels K. Predictors and course of medically intractable epilepsy in young children presenting before 36 months of age: a retrospective, population-based study. Epilepsia. 2012;53(9):15631569.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Dwivedi R, Ramanujam B, Chandra PS, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med. 2017;377(17):16391647.

  • 5

    Delalande O, Bulteau C, Dellatolas G, et al. Vertical parasagittal hemispherotomy: surgical procedures and clinical long-term outcomes in a population of 83 children. Neurosurgery. 2007;60(2 Suppl 1):ONS19ONS32.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Kadish NE, Bast T, Reuner G, et al. Epilepsy surgery in the first 3 years of life: predictors of seizure freedom and cognitive development. Neurosurgery. 2019;84(6):E368E377.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Steinbok P, Gan PYC, Connolly MB, et al. Epilepsy surgery in the first 3 years of life: a Canadian survey. Epilepsia. 2009;50(6):14421449.

  • 8

    Basheer SN, Connolly MB, Lautzenhiser A, Sherman EMS, Hendson G, Steinbok P. Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function. Epilepsia. 2007;48(1):133140.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Weil AG, Lewis EC, Ibrahim GM, et al. Hemispherectomy Outcome Prediction Scale: development and validation of a seizure freedom prediction tool. Epilepsia. 2021;62(5):10641073.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Dorfer C, Ochi A, Snead OC III, et al. Functional hemispherectomy for catastrophic epilepsy in very young infants: technical considerations and complication avoidance. Childs Nerv Syst. 2015;31(11):21032109.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Piastra M, Pietrini D, Caresta E, et al. Hemispherectomy procedures in children: haematological issues. Childs Nerv Syst. 2004;20(7):453458.

  • 12

    Krynauw RA. Infantile hemiplegia treated by removing one cerebral hemisphere. J Neurol Neurosurg Psychiatry. 1950;13(4):243267.

  • 13

    Villemure JG, Mascott CR. Peri-insular hemispherotomy: surgical principles and anatomy. Neurosurgery. 1995;37(5):975981.

  • 14

    Loddenkemper T, Holland KD, Stanford LD, Kotagal P, Bingaman W, Wyllie E. Developmental outcome after epilepsy surgery in infancy. Pediatrics. 2007;119(5):930935.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Honda R, Kaido T, Sugai K, et al. Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy. Epilepsy Behav. 2013;29(1):3035.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Sparrow SS, Balla DA, Cicchetti DV. Vineland Adaptive Behavior Scales VABS: Expanded Form Manual. American Guidance Service; 1984.

  • 17

    Schramm J, Kral T, Clusmann H. Transsylvian keyhole functional hemispherectomy. Neurosurgery. 2001;49(4):891901.

  • 18

    González-Martínez JA, Gupta A, Kotagal P, et al. Hemispherectomy for catastrophic epilepsy in infants. Epilepsia. 2005;46(9):15181525.

  • 19

    Ye VC, Shah AH, Sur S, et al. Long-term outcomes after surgery for catastrophic epilepsy in infants: institutional experience and review of the literature. J Neurosurg Pediatr. 2020;26(2):157164.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Duchowny M, Jayakar P, Resnick T, et al. Epilepsy surgery in the first three years of life. Epilepsia. 1998;39(7):737743.

  • 21

    Ji T, Liu M, Wang S, et al. Seizure outcome and its prognostic predictors after hemispherotomy in children with refractory epilepsy in a Chinese pediatric epileptic center. Front Neurol. 2019;10:880.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Canaud G, Hammill AM, Adams D, Vikkula M, Keppler-Noreuil KM. A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations. Orphanet J Rare Dis. 2021;16(1):306.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Kumar RM, Koh S, Knupp K, Handler MH, O’Neill BR. Surgery for infants with catastrophic epilepsy: an analysis of complications and efficacy. Childs Nerv Syst. 2015;31(9):14791491.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Ramantani G, Kadish NE, Strobl K, et al. Seizure and cognitive outcomes of epilepsy surgery in infancy and early childhood. Eur J Paediatr Neurol. 2013;17(5):498506.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Cook SW, Nguyen ST, Hu B, et al. Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients. J Neurosurg. 2004;100(2 Suppl Pediatrics):125141.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Althausen A, Gleissner U, Hoppe C, et al. Long-term outcome of hemispheric surgery at different ages in 61 epilepsy patients. J Neurol Neurosurg Psychiatry. 2013;84(5):529536.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Moosa ANV, Jehi L, Marashly A, et al. Long-term functional outcomes and their predictors after hemispherectomy in 115 children. Epilepsia. 2013;54(10):17711779.

  • 28

    Asarnow RF, LoPresti C, Guthrie D, et al. Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms. Dev Med Child Neurol. 1997;39(7):430440.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Jonas R, Asarnow RF, LoPresti C, et al. Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms. Neurology. 2005;64(4):746750.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Riikonen R. Recent advances in the pharmacotherapy of infantile spasms. CNS Drugs. 2014;28(4):279290.

  • 31

    Riikonen R. Long-term otucome of West syndrome: a study of adults with a history of infantile spasms. Epilepsia. 1996;37(4):367372.

  • 32

    Riikonen R. A long-term follow-up study of 214 children with the syndrome of infantile spasms. Neuropediatrics. 1982;13(1):1423.

  • 33

    Trevathan E, Murphy CC, Yeargin-Allsopp M. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 1999;40(6):748751.

  • 34

    Saemundsen E, Ludvigsson P, Rafnsson V. Autism spectrum disorders in children with a history of infantile spasms: a population-based study. J Child Neurol. 2007;22(9):11021107.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    O’Callaghan FJK, Lux AL, Darke K, et al. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia. 2011;52(7):13591364.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51(10):21752189.

  • 37

    Harini C, Nagarajan E, Bergin AM, et al. Mortality in infantile spasms: a hospital-based study. Epilepsia. 2020;61(4):702713.

  • 38

    Riikonen R. Epidemiological data of West syndrome in Finland. Brain Dev. 2001;23(7):539541.

  • 39

    Dunkley C, Kung J, Scott RC, et al. Epilepsy surgery in children under 3 years. Epilepsy Res. 2011;93(2-3):96106.

  • 40

    Tiret L, Nivoche Y, Hatton F, Desmonts JM, Vourc’h G. Complications related to anaesthesia in infants and children. A prospective survey of 40240 anaesthetics. Br J Anaesth. 1988;61(3):263269.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 2968 157 0
Full Text Views 464 296 51
PDF Downloads 516 290 46
EPUB Downloads 0 0 0