Intraventricular hemorrhage volume and younger age at surgery may be risk factors for postoperative hydrocephalus after hemispherotomy in children.

OBJECTIVE: Hemispherotomy is an effective treatment for intractable hemispheric epilepsy; however, hydrocephalus remains a common complication of the procedure. The causes of hydrocephalus following hemispherotomy have not been fully elucidated; therefore, the purpose of this study was to identify the risk factors associated with the condition. METHODS: The authors investigated the records of all patients aged < 18 years who underwent hemispherotomy at their institution between 2003 and 2020 and were monitored for hydrocephalus for at least 1 year after the procedure. To identify the risk factors for hydrocephalus, the following information about each patient was collected: sex, corrected age at surgery, body weight at surgery, previous intracranial surgery, etiology of epilepsy, results of PET for hypermetabolism, side of surgery, type of operation (vertical or horizontal approach), operation time, blood loss during surgery, use of intraventricular drainage, occurrence of intraventricular hemorrhage (IVH) on the 1st postoperative day, duration of postoperative fever of > 38°C, and maximum C-reactive protein level after the operation. Multivariate logistic regression analyses were performed. RESULTS: This study included 51 children who underwent hemispherotomies for drug-resistant epilepsy at our hospital. Seven patients (13.7%) experienced hydrocephalus and were treated with ventricular or subdural peritoneal shunts or fenestration. Multivariate logistic analysis using the Bayesian information criterion revealed that 3 factors were associated with the occurrence of hydrocephalus: age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C. CONCLUSIONS: This study showed that younger age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C might be risk factors for hydrocephalus after hemispherotomy. The risk of hydrocephalus should be considered in cases of early surgical indication in children. Intraoperative hemostasis and postoperative use of anti-inflammatory measures may reduce the risk of hydrocephalus.

Safety, Feasibility, and Efficacy of Additional Extraventricular Anterior Commissurotomy With Corpus Callosotomy.

BACKGROUND: Corpus callosotomy (CC) is a palliative neurosurgical procedure for patients with intractable epilepsy and without resectable focal epileptogenic lesions. Anterior commissurotomy (AC) has been historically performed with CC. However, the efficacy and safety of adding AC to CC remain unknown. OBJECTIVE: To describe the surgical technique of extraventricular AC and retrospectively investigate its clinical efficacy and safety by assessing patients who underwent CC with and without AC. METHODS: AC has been added to CC at our institution since 2018. Fifty-five consecutive patients who received total callosotomy from 2016 to 2020 were included and categorized into 2 groups: 26 patients with additional AC and 29 patients without additional AC. Seizure outcome 1 year after surgery were compared between groups for assessing the efficacy of adding AC. The perioperative factors were compared for assessing the safety and feasibility. RESULTS: Seizure reduction rate (50% and 60%; P = .60) and disappearance of drop attacks (42% and 58%; P = .25) were not significantly different between CC and CC + AC groups. No statistical group differences were found in intraoperative estimated blood loss, number of days to first oral intake, duration of postoperative intravenous hydration, and length of hospital stay. CONCLUSION: Disconnection of the anterior commissure is a feasible and relatively safe procedure. This study failed to show the significant efficacy of adding AC to CC. However, further investigation is needed to prove its efficacy in ameliorating epilepsy.

Is Hippocampal Resection Necessary for Low-Grade Epilepsy-Associated Tumors in the Temporal Lobe?

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

Low EEG Gamma Entropy and Glucose Hypometabolism After Corpus Callosotomy Predicts Seizure Outcome After Subsequent Surgery.

Background: Patients with generalized epilepsy who had lateralized EEG abnormalities after corpus callosotomy (CC) occasionally undergo subsequent surgeries to control intractable epilepsy. Objectives: This study evaluated retrospectively the combination of EEG multiscale entropy (MSE) and FDG-PET for identifying lateralization of the epileptogenic zone after CC. Methods: This study included 14 patients with pharmacoresistant epilepsy who underwent curative epilepsy surgery after CC. Interictal scalp EEG and FDG-PET obtained after CC were investigated to determine (1) whether the MSE calculated from the EEG and FDG-PET findings was lateralized to the surgical side, and (2) whether the lateralization was associated with seizure outcomes. Results: Seizure reduction rate was higher in patients with lateralized findings to the surgical side than those without (MSE: p < 0.05, FDG-PET: p < 0.05, both: p < 0.01). Seizure free rate was higher in patients with lateralized findings in both MSE and FDG-PET than in those without (p < 0.05). Conclusions: This study demonstrated that patients with lateralization of MSE and FDG-PET to the surgical side had better seizure outcomes. The combination of MSE and conventional FDG-PET may help to select surgical candidates for additional surgery after CC with good postoperative seizure outcomes.

Predictors of Seizure Outcome after Repeat Pediatric Epilepsy Surgery: Reasons for Failure, Sex, Electrophysiology, and Temporal Lobe Surgery.

Considering that seizure freedom is one of the most important goals in the treatment of epilepsy, repeat epilepsy surgery could be considered for patients who continue to experience drug-resistant seizures after epilepsy surgery. However, the chance of seizure freedom is reported to be below 50% after reoperation for failed epilepsy surgery. This study aimed to elucidate the predictive factors for seizure outcomes after repeat pediatric epilepsy surgery. In all, 39 pediatric patients who underwent repeat curative epilepsy surgery between 2008 and 2020 at our institution were retrospectively studied. The relationship between preoperative clinical factors and postoperative seizure freedom at the last follow-up was statistically evaluated. The mean age at the first surgery was 5.5 years (0-16). The etiology of epilepsy was malformation of cortical development in 33 patients. The average time to seizure recurrence after the first surgery was 6.4 months (range, 0-26 months). In all, 16 patients (41.0%) achieved seizure freedom after the second surgery. Seven patients underwent a third surgery, and three (42.9%) achieved seizure freedom. Overall, 19 patients achieved seizure freedom after repeat epilepsy surgery (48.7%). Female sex, surgical failure due to technical limitations, congruent electroencephalography (EEG) findings, lesional magnetic resonance imaging (MRI) and Rt-sided surgery were predictive of seizure freedom, and surgery limited to the temporal lobe was predictive of residual seizures, as determined in the multivariate analysis. The reoperation of failed epilepsy surgery is challenging. Consideration of the above predictive factors can be helpful in deciding whether to reoperate on pediatric patients whose initial surgical intervention failed.

Epilepsy surgery in children under 3 years of age: surgical and developmental outcomes.

OBJECTIVE: Pediatric epilepsy surgery is known to be effective, but early surgery in infancy is not well characterized. Extensive cortical dysplasia, such as hemimegalencephaly, can cause refractory epilepsy shortly after birth, and early surgical intervention is indicated. However, the complication rate of early pediatric surgery is significant. In this study, the authors assessed the risk-benefit balance of early pediatric epilepsy surgery as relates to developmental outcomes. METHODS: This is a retrospective descriptive study of 75 patients who underwent their first curative epilepsy surgery at an age under 3 years at the authors' institution between 2006 and 2019 and had a minimum 1-year follow-up of seizure and developmental outcomes. Clinical information including surgical complications, seizure outcomes, and developmental quotient (DQ) was collected from medical records. The effects of clinical factors on DQ at 1 year after surgery were evaluated. RESULTS: The median age at surgery was 6 months, peaking at between 3 and 4 months. Operative procedures included 27 cases of hemispherotomy, 19 cases of multilobar surgery, and 29 cases of unilobar surgery. Seizure freedom was achieved in 82.7% of patients at 1 year and in 71.0% of patients at a mean follow-up of 62.8 months. The number of antiseizure medications (ASMs) decreased significantly after surgery, and 19 patients (30.6%) had discontinued their ASMs by the last follow-up. Postoperative complications requiring cerebrospinal fluid (CSF) diversion surgery, such as hydrocephalus and cyst formation, were observed in 13 patients (17.3%). The mean DQ values were 74.2 ± 34.3 preoperatively, 60.3 ± 23.3 at 1 year after surgery, and 53.4 ± 25.1 at the last follow-up. Multiple regression analysis revealed that the 1-year postoperative DQ was significantly influenced by preoperative DQ and postoperative seizure freedom but not by the occurrence of any surgical complication requiring CSF diversion surgery. CONCLUSIONS: Early pediatric epilepsy surgery has an acceptable risk-benefit balance. Seizure control after surgery is important for postoperative development.

Single-Institutional Experience of Chronic Intracranial Electroencephalography Based on the Combined Usage of Subdural and Depth Electrodes.

Implantation of subdural electrodes on the brain surface is still widely performed as one of the "gold standard methods" for the presurgical evaluation of epilepsy. Stereotactic insertion of depth electrodes to the brain can be added to detect brain activities in deep-seated lesions to which surface electrodes are insensitive. This study tried to clarify the efficacy and limitations of combined implantation of subdural and depth electrodes in intractable epilepsy patients. Fifty-three patients with drug-resistant epilepsy underwent combined implantation of subdural and depth electrodes for long-term intracranial electroencephalography (iEEG) before epilepsy surgery. The detectability of early ictal iEEG change (EIIC) were compared between the subdural and depth electrodes. We also examined clinical factors including resection of MRI lesion and EIIC with seizure freedom. Detectability of EIIC showed no significant difference between subdural and depth electrodes. However, the additional depth electrode was useful for detecting EIIC from apparently deep locations, such as the insula and mesial temporal structures, but not in detecting EIIC in patients with ulegyria (glial scar). Total removal of MRI lesion was associated with seizure freedom. Depth electrodes should be carefully used after consideration of the suspected etiology to avoid injudicious usage.

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome.

The efficacy of deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is accepted, but whether the efficacy of DBS treatment in the Japanese population is equivalent to those reported internationally and whether adverse effects are comparable are not yet known. This study evaluated the clinical practice and outcome of DBS for TS in a Japanese institution. This study included 25 consecutive patients with refractory TS treated with thalamic centromedian-parafascicular nucleus DBS. The severity of tics was evaluated with the Yale Global Tic Severity Scale (YGTSS) before surgery, at 1 year after surgery, and at the last follow-up of 3 years or more after surgery. The occurrence of adverse events, active contact locations, and stimulation conditions were also evaluated. YGTSS tic severity score decreased by average 45.2% at 1 year, and by 56.6% at the last follow-up. The reduction was significant for all aspects of the scores including motor tics, phonic tics, and impairment. The mean coordinates of active contacts were 7.62 mm lateral to the midline, 3.28 mm posterior to the midcommissural point, and 3.41 mm above anterior commissure-posterior commissure plane. Efficacy and stimulation conditions were equivalent to international reports. The stimulation-induced side effects included dysarthria (32.0%) and paresthesia (12.0%). Device infection occurred in three patients (12.0%) as a surgical complication. The DBS device was removed because of infection in two patients. DBS is an effective treatment for refractory TS, although careful indication is necessary because of the surgical risks and unknown long-term outcome.

Cognitive and developmental outcomes after pediatric insular epilepsy surgery for focal cortical dysplasia.

OBJECTIVE: Cognitive risk associated with insular cortex resection is not well understood. The authors reviewed cognitive and developmental outcomes in pediatric patients who underwent resection of the epileptogenic zone involving the insula. METHODS: A review was conducted of 15 patients who underwent resective epilepsy surgery involving the insular cortex for focal cortical dysplasia, with a minimum follow-up of 12 months. The median age at surgery was 5.6 years (range 0.3-13.6 years). Developmental/intelligence quotient (DQ/IQ) scores were evaluated before surgery, within 4 months after surgery, and at 12 months or more after surgery. Repeated measures multivariate ANOVA was used to evaluate the effects on outcomes of the within-subject factor (time) and between-subject factors (resection side, anterior insular resection, seizure control, and antiepileptic drug [AED] reduction). RESULTS: The mean preoperative DQ/IQ score was 60.7 ± 22.8. Left-side resection and anterior insular resection were performed in 9 patients each. Favorable seizure control (International League Against Epilepsy class 1-3) was achieved in 8 patients. Postoperative motor deficits were observed in 9 patients (permanent in 6, transient in 3). Within-subject changes in DQ/IQ were not significantly affected by insular resection (p = 0.13). Postoperative changes in DQ/IQ were not significantly affected by surgical side, anterior insular resection, AED reduction, or seizure outcome. Only verbal function showed no significant changes before and after surgery and no significant effects of within-subject factors. CONCLUSIONS: Resection involving the insula in children with impaired development or intelligence can be performed without significant reduction in DQ/IQ, but carries the risk of postoperative motor deficits.

Is intracranial electroencephalography useful for planning resective surgery in intractable epilepsy with ulegyria?

OBJECTIVE: Intractable epilepsy patients with ulegyria could be candidates for resective surgery. Complete resection of ulegyria in the epileptogenic hemisphere is associated with favorable seizure outcome, although the risk of postoperative functional deficits is higher. The authors evaluated the extent of resection and postsurgical outcomes in epilepsy patients with ulegyria who underwent intracranial electroencephalography (iEEG) monitoring prior to resection to clarify the efficacy of iEEG-guided partial resection of ulegyria. METHODS: Ten consecutive epilepsy patients with ulegyria (7 males and 3 females, age range at surgery 7-34 years) underwent iEEG prior to resective surgery between 2011 and 2017 with a minimum follow-up of 12 months (range 12-72 months). The diagnosis of ulegyria was based on the typical pattern of cortical atrophy especially at the bottom of the sulcus on MRI. An iEEG study was indicated after comprehensive preoperative evaluations, including high-field MRI, long-term video-EEG, magnetoencephalography, and FDG-PET. The resection planning was based on iEEG analysis. Total lesionectomy was not always performed, as preservation of cortical function was prioritized. RESULTS: Ulegyria was seen in the occipital and/or parietal lobe in 9 patients and bilaterally in 5 patients. Ictal EEG onset involved the temporal neocortex in 6 patients. Intracranial electrodes were implanted unilaterally in all except 1 patient with bilateral lesions. The extent of MRI lesion was covered by the electrodes. Seizure onset zones (SOZs) and irritative zones (IZs) were identified in all patients. SOZs and IZs were completely resected in 8 patients but were only partially removed in the remaining 2 patients because the eloquent cortices and the epileptogenic zones overlapped. Ulegyria of the epileptogenic side was totally resected in 1 patient. Seizure freedom was achieved in 4 patients, including 3 after partial lesionectomy. Extended resection of the temporal neocortex was performed in 4 patients, although postoperative seizure freedom was achieved only in 1 of these patients. Visual field deficit was seen in 4 patients. Three of 5 patients with bilateral lesions achieved seizure freedom after unilateral resective surgery. CONCLUSIONS: Intracranial EEG-guided partial lesionectomy provides a reasonable chance of postoperative seizure freedom with a lower risk of functional deficits. Patients with bilateral ulegyria should not be excluded from consideration as surgical candidates.

Ictal deafness in drug-resistant MRI-negative epilepsy.

Ictal clinical semiology indicates where the patient's seizure arises from and how it progresses. A patient's description of a focal sensory seizure may support a surgical decision even when MRI and PET abnormalities are absent. Ictal deafness is a focal auditory seizure characterized by suppression of hearing, presumably originating from the auditory cortex in the temporal lobe. However, the precise localization has not been confirmed with surgical cases. We present a case in which the region from where ictal deafness arose was confirmed by intracranial electroencephalography, with successful epilepsy surgery and review other published cases.

Surgical strategy to avoid ischemic complications of the pyramidal tract in resective epilepsy surgery of the insula: technical case report.

Surgical treatment of the insula is notorious for its high probability of motor complications, particularly when resecting the superoposterior part. Ischemic damage to the pyramidal tract in the corona radiata has been regarded as the cause of these complications, resulting from occlusion of the perforating arteries to the pyramidal tract through the insular cortex. The authors describe a strategy in which a small piece of gray matter is spared at the bottom of the periinsular sulcus, where the perforating arteries pass en route to the pyramidal tract, in order to avoid these complications. This method was successfully applied in 3 patients harboring focal cortical dysplasia in the posterior insula and frontoparietal operculum surrounding the periinsular sulcus. None of the patients developed permanent postoperative motor deficits, and seizure control was achieved in all 3 cases. The method described in this paper can be adopted for functional preservation of the pyramidal tract in the corona radiata when resecting epileptogenic pathologies involving insular and opercular regions.

Expression of astrocyte-related receptors in cortical dysplasia with intractable epilepsy.

Epilepsy is one of the major neurologic diseases, and astrocytes play important roles in epileptogenesis. To investigate possible roles of astrocyte-related receptors in patients with intractable epilepsy associated with focal cortical dysplasia (FCD) and other conditions, we examined resected epileptic foci from 31 patients, including 23 with FCD type I, IIa, or IIb, 5 with tuberous sclerosis complex, and 3 with low-grade astrocytoma. Control samples were from 21 autopsied brains of patients without epilepsy or neurologic deficits and 5 patients with pathologic gliosis without epilepsy. Immunohistochemical and immunoblot analyses with antibodies against purinergic receptor subtypes P2RY1, P2RY2, P2RY4, potassium channels Kv4.2 and Kir4.1, and metabotropic receptor subtypes mGluR1 and mGluR5 were performed. Anti-glial fibrillary acidic protein, anti-NeuN, and anti-CD68 immunostaining was used to identify astrocytes, neurons, and microglia, respectively. Most glial fibrillary acidic protein-immunopositive astrocyte cells in the brain samples from patients with epilepsy were P2RY1-, P2RY2-, P2RY4-, Kv4.2-, Kir4.1-, mGluR1-, and mGluR5-positive, whereas samples from controls and pathologic gliosis showed lower expression levels of these astrocyte-related receptors. Our findings suggest that, although these receptors are necessary for astrocyte transmission, formation of the neuron-glia network, and other physiologic functions, overexpression in the brains of patients with intractable epilepsy may be associated with activation of intracellular and glio-neuronal signaling pathways that contribute to epileptogenesis.

Persistent verbal and behavioral deficits after resection of the left supplementary motor area in epilepsy surgery.

An 8-year-old boy underwent a resection for focal cortical dysplasia at the left supplementary motor area (SMA) for the treatment of intractable epilepsy. The manifestations of SMA syndrome, such as transient mutism and right hemiparesis, resolved within a few weeks. Verbal disfluency and impaired executive function, accompanied by impulsivity and distractibility, persisted for more than 12months. The verbal and behavioral problems caused serious difficulties in the school life of the patient, until they became less evident at 18months after surgery. Tractography performed 18months after surgery revealed a defect in the subportion of fronto-parietal association fibers within the left superior longitudinal fascicles. Verbal influency can persist with unusually long duration after resection of SMA during childhood. Although not discernible on the routine neuroimaging, white matter damage beneath the SMA region could result in serious disabilities in executive function. These complications should be recognized for the prediction and assessment of deficits in children after surgical intervention involving this region.

Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy.

This study aimed to identify the effect of early hemispherotomy on development in a consecutive series of 12 infants with hemimegalencephaly (HME) demonstrating epileptic encephalopathy. Mean age at onset was 20.4 days (range, 1-140), mean age at surgery was 4.3 months (range, 2-9), and mean follow-up time was 78.8 months (range, 36-121). Eleven patients had a history of early infantile epileptic encephalopathy. Vertical parasagittal hemispherotomy was performed without mortality or severe morbidities. At follow-up, seizure freedom was obtained in 8 patients (66.7%), who showed significantly higher postoperative developmental quotient (DQ) (mean, 31.3; range, 7-61) than those with seizures (mean, 5.5; range, 3-8) (p=0.02). Within the seizure-free group, postoperative DQ correlated with preoperative seizure duration (r=-0.811, p=0.01). Our results showed that shorter seizure duration during early infancy could provide better postoperative DQ in infants with HME and epileptic encephalopathy.

Posterior disconnection in early infancy to treat intractable epilepsy with multilobar cortical dysplasia: three case report.

Extensive multilobar cortical dysplasias occasionally occur in children and can induce seizure onset in early infancy, causing severe epileptic encephalopathy. Surgical interventions in early infancy, such as disconnection of large parts of the brain, are challenging because of the degree of invasiveness and carry greater risks in infants compared with older children. Here we report the successful treatment of intractable epilepsy with multilobar cortical dysplasias in the posterior cortex by posterior disconnection in three infants (age 3 months). The patients showed good postoperative recovery and exhibited excellent seizure control at follow-up evaluation within a year after surgery. Developmental catch-up was also achieved and no early complications have been detected to date. Use of the posterior disconnection technique for early-stage extensive multilobar cortical dysplasias can result in good seizure control and developmental progress with little perioperative morbidity. However, the efficacy of this surgical technique needs to be verified with long-term follow up after surgery.

Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation: unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly.

Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are major causes of intractable epilepsy in children. The probable pathogenesis of FCD and HMG is the abnormal migration and differentiation of neurons. The aim of the present study was to clarify the abnormal cytoarchitecture, based on neuronal immaturation. Tissue samples were obtained from 16 FCD and seven HME patients, aged between 2 months and 12 years, who had been diagnosed as typical FCD and HME, following surgical treatment for intractable epilepsy. Paraffin-embedded sections were stained with the antibodies of three layer-markers that are usually present only during the fetal period, namely SATB2 (expressed in the upper layer of the normal fetal neocortex), FOXP1 (expressed in the 5th layer), and TBR1 (expressed in the 6th layer). In FCD, SATB2-positive (+) cells located in the middle and deep regions of FCD Ia and Ib, but only in the superficial region of FCD IIa and IIb. FOXP1+ cells diffusely located in the neocortex, especially the upper layer of FCD IIa and IIb. TBR1+ cells mainly located in the middle and deep regions, and also white matter. In FCD IIb, TBR1+ cells were in the superficial region. In HME, SATB2+ and FOXP1+ cells were found diffusely. TBR1+ cells were in the middle and deep regions. On the basis of continued expression of fetal cortical layer-specific markers in FCD and HME brains, the abnormal neocortical formation in both is likely to be the result of disrupted neuronal migration and dysmaturation. The expression pattern is different between FCD and HME.

Novel pathological abnormalities of deep brain structures including dysplastic neurons in anterior striatum associated with focal cortical dysplasia in epilepsy.

OBJECT: Some patients are not seizure free even after epileptogenic cortical resection. The authors recently described a case of frontal lobe epilepsy cured after the resection of periventricular white matter and striatum, in which dysplastic neurons were revealed. The authors attempted to confirm similar cases. METHODS: They reviewed the records of 8 children with frontal lobe epilepsy who had daily (7) or monthly (1) seizures and underwent resections including deep brain structures. RESULTS: Five patients underwent multiple resections. Neuroimaging of the deep structures showed the transmantle sign in 3 patients, ictal hyperperfusion in 6, reduced iomazenil uptake in 2, and spike dipole clustering in 6. All patients became seizure free postoperatively. Focal cortical dysplasia of various types was diagnosed in all patients. Dysmorphic neurons were found in the cortex and subcortical white matter of 5 patients. The striatum was verified in 3 patients in whom dysmorphic neurons were scattered. In the periventricular white matter, prominent astrocytosis was evident in all cases. CONCLUSIONS: Pathological abnormalities such as dysmorphic neurons and astrocytosis in deep brain structures would play a key role in epileptogenesis.