Epilepsy surgery in developmental and epileptic encephalopathies.

Developmental and epileptic encephalopathies (DEEs) present significant treatment challenges due to frequent, drug-resistant seizures and comorbidities that impact quality of life. DEEs include both developmental encephalopathy from underlying pathology and epileptic encephalopathy where seizures exacerbate cognitive and behavioral impairments. Classification by syndrome and etiology is essential for therapy and prognosis, with common syndromes like infantile epileptic spasms syndrome and Dravet syndrome having specific first-line treatments. Etiologies are predominantly genetic, structural, or combined, with targeted therapies increasingly available. Surgery aims to improve seizure control but also may improve development, if the epileptic encephalopathy can be ameliorated. Timely intervention can reduce seizures and epileptiform discharges, maximizing developmental potential and allowing reduction in antiseizure medication. In cases requiring extensive resections, new deficits may be offset by developmental gains. Studies indicate that parents are generally willing to accept some deficits for significant seizure reduction.

Endoscopic callosotomy as a minimally invasive approach to treat paediatric refractory epilepsy: case series.

BACKGROUND: Endoscopic callosotomy has emerged as a promising and minimally invasive technique for the treatment of refractory epilepsy. This paper aims to review the clinical outcomes and advancements associated with endoscopic callosotomy as a therapeutic option. MATERIALS AND METHODS: This study includes 14 Paediatric patients diagnosed and managed at Al-azhar university hospitals. Those 14 patients were studied over 2 years. All patients underwent a corpus callosotomy using the bimanual endoscopic technique. RESULTS: Endoscopic anterior corpus callosotomy was done in 13 patients while one case underwent endoscopic complete callosotomy. The most frequent complication was transient disconnection syndrome followed by transient Urinary incontinence and one case had minor CSF leak. As regard seizure freedom outcome (Engel's Outcome Scale): 4 cases (28.6%) became seizure free (Engle class I), 5 cases (35.7%) with Engle class II, 1 case (7.1%) with Engle class III and 4 cases (28.6%) classify as Engle class IV. CONCLUSION: As a minimally invasive technique with a favorable impact on cognitive function, less complications and a significant reduction in seizure frequency and severity in the majority of paediatric patients, endoscopic corpus callosotomy offeres substantial benefits in managing refractory epilepsy in paediatric.

Changes in interhemispheric coherence after total corpus callosotomy: a scalp EEG study in children with non-lesional generalized epilepsy.

PURPOSE: Coherence analysis in electroencephalography (EEG) allows measurement of the degree of consistency of amplitude between pairs of electrodes. Theoretically, disconnective epilepsy surgery should decrease coherence between corresponding areas. The study aimed to evaluate postoperative changes in interhemispheric coherence values after corpus callosotomy (CC). METHODS: Non-lesional, drug-resistant, generalized epilepsy patients who underwent total CC were retrospectively collected. To evaluate coherence, we divided the scalp interictal EEG into "baseline" and "discharge" states after excluding periods with artifacts. Interhemispheric coherence values were obtained between eight pairs of symmetrically opposite scalp electrodes in six different frequency bands. We analyzed both pre- and postoperative EEG sessions and calculated the percentage of difference (POD) in coherence values. RESULTS: We collected 13 patients and analyzed 2496 interhemispheric coherence values. Preoperative coherence values differed significantly between baseline and discharge states (p = 0.0003), but postoperative values did not (p = 0.11). For baseline state, coherence values were decreased after CC and median POD was - 22.3% (p < 0.0001). Delta frequency showed the most decreased POD (-44.3%, p = 0.0009). Median POD was lowest in the Fp1-Fp2 pair of electrodes. For discharge state, coherence values were decreased after CC and median POD was - 24.7% (p < 0.0001). Delta frequency again showed the most decreased POD (-55.9%, p = 0.0016). Median POD was lowest in the F7-F8 pair. CONCLUSION: After total CC, interhemispheric coherence decreased significantly in both baseline and discharge states. The most decreased frequency band was the delta band, which may be used as a representative frequency band in future studies.

Surgical outcomes of open and laser interstitial thermal therapy approaches for corpus callosotomy in pediatric epilepsy.

OBJECTIVE: Corpus callosotomy (CC) is a palliative surgical intervention for patients with medically refractory epilepsy that has evolved in recent years to include a less-invasive alternative with the use of laser interstitial thermal therapy (LITT). LITT works by heating a stereotactically placed laser fiber to ablative temperatures under real-time magnetic resonance imaging (MRI) thermometry. This study aims to (1) describe the surgical outcomes of CC in a large cohort of children with medically refractory epilepsy, (2) compare anterior and complete CC, and (3) review LITT as a surgical alternative to open craniotomy for CC. METHODS: This retrospective cohort study included 103 patients <21 years of age with at least 1 year follow-up at a single institution between 2003 and 2021. Surgical outcomes and the comparative effectiveness of anterior vs complete and open versus LITT surgical approaches were assessed. RESULTS: CC was the most common surgical disconnection (65%, n = 67) followed by anterior two-thirds (35%, n = 36), with a portion proceeding to posterior completion (28%, n = 10). The overall surgical complication rate was 6% (n = 6/103). Open craniotomy was the most common approach (87%, n = 90), with LITT used increasingly in recent years (13%, n = 13). Compared to open, LITT had shorter hospital stay (3 days [interquartile range (IQR) 2-5] vs 5 days [IQR 3-7]; p < .05). Modified Engel class I, II, III, and IV outcomes at last follow-up were 19.8% (n = 17/86), 19.8% (n = 17/86), 40.2% (n = 35/86), and 19.8% (n = 17/86). Of the 70 patients with preoperative drop seizures, 75% resolved postoperatively (n = 52/69). SIGNIFICANCE: No significant differences in seizure outcome between patients who underwent only anterior CC and complete CC were observed. LITT is a less-invasive surgical alternative to open craniotomy for CC, associated with similar seizure outcomes, lower blood loss, shorter hospital stays, and lower complication rates, but with longer operative times, when compared with the open craniotomy approach.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

The clinical features of patients with seizure freedom and failure after total corpus callosotomy for childhood-onset refractory epilepsy.

BACKGROUND: Corpus callosotomy is a palliative surgery for medically refractory epilepsy. We aim to analyze the clinical features of patients with seizure freedom and failure after total corpus callosotomy for childhood-onset refractory epilepsy. METHODS: We retrospectively reviewed the clinical courses of patients with childhood-onset refractory epilepsy undergoing total corpus callosotomy between May 2009 and March 2019. Seizure outcome at the last follow-up was the primary outcome. The clinical features of patients with seizure freedom and failure after callosotomy were compared. RESULTS: Eighty patients with childhood-onset refractory epilepsy underwent total corpus callosotomy; 15 (18.8%) obtained freedom from all seizures and 19 (23.8%) had unworthwhile improvement and failure. The mean ages at seizure onset in patients with seizure freedom and failure after callosotomy were 5.7 and 5.9 years; and mean seizure durations were 9.4 and 11.5 years, respectively. Univariate analysis found epilepsy syndrome (p = 0.047), mental retardation (p = 0.007), previous medical history (p = 0.004), ≥10 seizures per day (p = 0.024), theta waves in the background electroencephalogram (p = 0.024), and acute postoperative seizure (p = 0.000) were associated with failure after callosotomy. Seizure freedom after callosotomy was more common among patients with less than 10 seizures per day. CONCLUSIONS: Total corpus callosotomy is an effective palliative procedure for childhood-onset refractory epilepsy, particularly for patients with specific clinical characteristics. Callosotomy has a high seizure-free rate in well-selected patients.

Callosotomy vs Vagus Nerve Stimulation in the Treatment of Lennox-Gastaut Syndrome: A Systematic Review With Meta-Analysis.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe drug-resistant epileptic syndrome. Palliative treatments such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) have emerged as treatments to reduce the number of seizures in patients. The aim of this study is to compare the effectiveness of CC and VNS in patients with LGS studied in the last 30 years. MATERIALS AND METHODS: We conducted a systematic review with meta-analysis and collected papers from PubMed (MEDLINE), Ovidsp, Web of Science, and Cochrane Library data bases. The articles analyzed were published between January 1990 and December 2020. Keywords were chosen based on internal and external validation in the PubMed data base (the analysis is available in the Supplementary Data Supplementary Appendix). Prospective or retrospective case reports (n ≥ 2), case series, cohort studies, or case-control studies involving patients with LGS were included in the analysis. We selected studies that had no age or sex restriction and that provided data on seizures before and after treatments. Studies not written in English, published without peer review, or not indexed in the data bases were excluded. Other exclusion criteria were the absence of seizure data and the impossibility of extracting this information from the studies. To analyze the results, we used the random-effects model based on the assessment of heterogeneity (I2 statistics) in two scenarios. In scenario 1, we assessed the incidence of patients with a seizure reduction ≥ 50%; in scenario 2, we assessed the incidence of patients with a seizure reduction > 0%. RESULTS: Of the 7418 articles found using the keywords, 32 were considered eligible. Of these, 18 articles were on VNS (175 patients) and 14 on CC (107 patients). For scenario 1 (seizure reduction ≥ 50%), CC had an incidence of 65% (95% CI, 37%-94%), with an I2 value of 82.7%; VNS had an incidence of 34% (95% CI, 11%-57%), with an I2 value of 80.7%. For scenario 2 (seizure reduction > 0%), CC had an incidence of 80% (95% CI, 58%-100%), with an I2 value of 84.7%; VNS had an incidence of 64% (95% CI, 38%-89%), with an I2 value of 90.8%. There was an overlap of confidence intervals, with no statistical difference between the treatments in both scenarios. DISCUSSION: Our analysis of LGS showed that the CC and VNS treatments are significantly beneficial to reducing seizures, without superiority between them.

Corpus callosum area and sectioning: a radioanatomical study correlated with MRI and cadaver morphometry.

PURPOSE: The corpus callosum (CC) is the primary interhemispheric connection between the two cerebral hemispheres. Besides their similar morphological characters, there are differences in their measurements. This study aimed to divide the CC into groups using planes based on the anterior commissure (AC) and posterior commissure (PC) and to detect differences in CC magnetic resonance imaging (MRI) and cadaver samples between these groups. METHODS: The study included 80 patients (40 male and 40 female patients) who underwent normal MRI in the midsagittal plane, and 38 cerebral hemispheres from 40 adult cadaver brains, with each hemisected in the midsagittal plane. The medial surface of the CC was divided vertically into three parts (the anterior, middle, and posterior zones) according to the AC and PC. Areas and parameters were measured in both the cadaveric hemispheres and patient MRI images. RESULTS: The total CC area and CC areas between, anterior, and posterior to the AC-PC vertical lines were the same in both the MRI and cadaver samples. In addition, morphometric measurements like the CC length, AC-PC length, and CC height at the AC and PC vertical lines, and their correlations were also found to be similar between the MRI and cadaver samples. CONCLUSION: This study proposes three areas according to AC and PC classification (anterior, middle, and posterior). This new proposed classification is suitable for stereotactic interventions and is useful for obtaining data from MRI images. However, it should be kept in mind that there may be changes and variations.

Microsurgical anatomy of the anterior cerebral artery and the arterial supply of the cingulate gyrus.

PURPOSE: The cingulate gyrus is a potential surgical area to treat tumours, psychiatric diseases, intractable pain and vascular malformations. The aim of the study was to define the topographic anatomy and arterial supply of the cingulate gyrus located on the medial surface of the cerebral hemisphere. METHODS: We studied thirty-six hemispheres, each hemisected in the midsagittal plane. The vertical thickness of the cingulate gyrus was measured at the anterior commissure (AC), posterior commissure (PC), and genu levels of the corpus callosum. The branches of the anterior and posterior cerebral arteries supplying each zone were noted separately. The arterial pathways were transformed to digital data in AutoCAD to identify the condensation and reduction areas. RESULTS: The mean AC-PC distance was 27.17 ± 1.63 mm. The thinnest region was the genu level of the corpus callosum (10.29 mm). The superior internal parietal artery (SIPA), inferior internal parietal artery (IIPA) and pericallosal artery (PrCA) supplied all zones of the cingulate gyrus. The anterior zone received the greatest supply. The arterial condensation and reduction areas on both sides of cingulate gyrus and its x, y, and z coordinates specified. CONCLUSIONS: The target cingulotomy (TC) area was determined for anterior cingulotomy. The properties of the TC area are that the thinnest region of the cingulate gyrus is supplied relatively less than other areas and is close to the anterior cingulotomy areas in the literature. The arterial reduction area (ARA) was found to be suitable for corpus callosotomy in terms of avoiding haemorrhage.

Interhemispheric Integration after Callosotomy: A Meta-Analysis of Poffenberger and Redundant-Target Paradigms.

The central role of the corpus callosum in integrating perception and cognition across the cerebral hemispheres makes it highly desirable for clinical and basic research to have a repertoire of experimental paradigms assessing callosal functioning. Here, the objective was to assess the validity of two such paradigms (Poffenberger, redundant-target paradigms) by conducting single-step meta-analyses on individual case data of callosotomy patients. Studies were identified by systematic literature search (source: Pubmed and WebOfKnowledge, date: 07.03.2022) and all studies were included that reported callosotomy case data for either paradigm. Twenty-two studies (38 unique cases) provided 116 observations of the crossed-uncrossed difference (CUD) for the Poffenberger paradigm, while ten studies (22 cases, 103 observations) provided bilateral redundancy gain (bRG) measures. Using linear-mixed models with "individual" and "experiment" as random-effects variable, the mean CUD was estimated at 60.6 ms (CI95%: 45.3; 75.9) for commissurotomy, 43.5 ms (26.7; 60.2) for complete callosotomy, and 8.8 ms (1.1; 16.6) for partial anterior-medial callosotomy patients. The estimates of commissurotomy/callosotomy patients differed significantly from patients with partial callosotomy and healthy controls. The mean bRGmin (minimum unilateral reference) was estimated at 42.8 ms (27.1;58.4) for patients with complete and 30.8 ms (16.8; 44.7) for patients with partial callosotomy, both differing significantly from controls. One limitation was that different formulas for bRG were used, making it necessary to split the sample and reducing test power of some analyses. Nevertheless, the present findings suggest that both paradigms assess interhemispheric callosal integration, confirming their construct validity, but likely test distinct callosal functions.

Surgical Treatment of Drug-Resistant Generalized Epilepsy.

PURPOSE OF REVIEW: To summarize current evidence and recent developments in the surgical treatment of drug-resistant generalized epilepsy. RECENT FINDINGS: Current surgical treatments of drug-resistant generalized epilepsy include vagus nerve stimulation (VNS), deep brain stimulation (DBS) and corpus callosotomy (CC). Neurostimulation with VNS and/or DBS has been shown to be effective in reducing seizure frequency in patients with generalized epilepsy. DBS for generalized epilepsy is primarily consisted of open-loop stimulation directed at the centromedian (CM) nucleus in the thalamus, though closed-loop stimulation and additional targets are being explored. CC can be effective in treating some seizure types and can be performed using traditional surgical techniques or with the less invasive methods of laser ablation and radiosurgery. This current literature supports the use of VNS, DBS and CC, alone or in combination, as palliative treatments of drug-resistant generalized epilepsy.

Using a Robotic-Assisted Approach for Stereotactic Laser Ablation Corpus Callosotomy: A Technical Report.

BACKGROUND: Corpus callosotomy for medically intractable epilepsy is an effective ablative procedure traditionally achieved using either standard open craniotomy or with less-invasive approaches. Advances in robotic-assisted stereotactic guidance for neurosurgery can be applied for LITT for corpus callosotomy. CLINICAL PRESENTATIONS: Two patients were included in this study. One was a 25-year-old female patient with extensive bi-hemispheric malformations of cortical development and medically refractory epilepsy, and the other was an 18-year-old male with medically refractory epilepsy and atonic seizures, who underwent a complete corpus callosotomy using robotic-assisted stereotactic guidance for LITT. RESULTS: Both patients underwent successful intended corpus callosotomy with volumetric analysis demonstrating a length disconnection of 74% and a volume disconnection of 55% for patient 1 and a length disconnection of 83% and a volume disconnection of 33% for patient 2. Postoperatively, both patients had clinical reductions in seizure. CONCLUSION: Our experience demonstrates that robotic guidance systems can safely and effectively be adapted for minimally invasive LITT corpus callosotomy.

A simulation study to investigate the use of concentric tube robots for epilepsy surgery.

PURPOSE: Patients with pharmacoresistant refractory epilepsy may require epilepsy surgery to prevent future seizure occurrences. Conventional surgery consists of a large craniotomy with straight rigid tools with associated outcomes of morbidity, large tissue resections, and long post-operative recovery times. Concentric tube robots have recently been developed as a promising application to neurosurgery due to their nonlinear form and small diameter. The authors present a concept study to explore the feasibility of performing minimally invasive hemispherotomy with concentric tube robots. METHODS: A model simulation was used to achieve the optimal design and surgical path planning parameters of the concentric tube robot for corpus callosotomy and temporal lobectomy. A single medial burr hole was chosen to access the lateral ventricles for both white matter disconnections. RESULTS: The concentric tube robot was able to accurately reach the designated surgical paths on the corpus callosum and the temporal lobe. CONCLUSION: In a model simulation, the authors demonstrated the feasibility of performing corpus callosotomy and temporal lobectomy using concentric tube robots. Further advancements in the technology may increase the applicability of this technique for epilepsy surgery to better patient outcomes.

Surgical aspects using an exoscope for corpus callosotomy: initial experience for epilepsy surgery.

The exoscope is a new form of optic device that has begun to be used in the last decade. The exoscope provides high-quality magnification and illumination at depth, allowing easy manipulation of surgical instruments even in narrow surgical fields. Exoscopic corpus callosotomy (CC) has not been reported. We report herein our initial experience with the utility of exoscopic CC. A 3-year-old boy diagnosed with West syndrome at 4 months old was referred to our hospital. As the seizure spasms were considered to carry a risk of severe traumatic injury, we performed exoscopic CC as palliative therapy. An EX VITOM 3D exoscope and 4K-3D surgical monitor were used during the procedure. No surgical complications that could be related to exoscope use were noted. Operative time for exoscopic CC was comparable to that for microscopic CC, despite a lack of previous experience with the equipment. Stereoscopic vision was easily obtained. The exoscope was perceived as providing higher quality magnification. We report our first clinical experience of exoscopic CC. The exoscope appears useful in the field of epilepsy surgery.

The role of surgery in the management of Lennox-Gastaut syndrome: A systematic review and meta-analysis of the clinical evidence.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood onset epilepsy in which patients require multiple medications and may be candidates for palliative surgical intervention. In this meta-analysis, we sought to evaluate the impact of palliative vagus nerve stimulation (VNS), corpus callosotomy (CC), and resective surgery (RS) by analyzing their impact on seizure control, antiepileptic drug (AED) usage, quality of life (QOL), behavior, cognition, prognostic factors, and complications. A systematic search of PubMed MEDLINE, Scopus, and Cochrane Database of Systematic Reviews was performed to find articles that met the following criteria: (1) prospective/retrospective study with original data, (2) at least one LGS surgery patient aged less than 18 years, and (3) information on seizure frequency reduction (measured as percentage, Engel class, or qualitative comment). Seizures were analyzed quantitatively in a meta-analysis of proportions and a random-effects model, whereas other outcomes were analyzed qualitatively. Forty studies with 892 LGS patients met the selection criteria, with 19 reporting on CC, 17 on VNS, four on RS, two on RS + CC, one on CC + VNS, and one on deep brain stimulation. CC seizure reduction rate was 74.1% (95% confidence interval [CI] = 64.5%-83.7%), and VNS was 54.6% (95% CI = 42.9%-66.3%), which was significantly different (p < .001). RS seizure reduction was 88.9% (95% CI = 66.1%-99.7%). Many VNS patients reported alertness improvements, and most had no major complications. VNS was most effective for atonic/tonic seizures; higher stimulation settings correlated with better outcomes. CC patients reported moderate cognitive and QOL improvements; disconnection syndrome, transient weakness, and respiratory complications were noted. Greater callosotomy extent correlated with better outcomes. AED usage most often did not change after surgery. RS showed considerable QOL improvements for patients with localized seizure foci. In the reported literature, CC appeared to be more effective than VNS for seizure reduction. VNS may provide a similar or higher level of QOL improvement with lower aggregate risk of complications. Patient selection, anatomy, and seizure type will inform decision-making.

An observational report of swallowing outcomes following corpus callosotomy.

AIM: Determine swallowing outcomes following corpus callosotomy (CC) surgery. METHODS: Retrospective chart review of patients undergoing CC between July 2016 and November 2018 at a large, urban children's hospital. RESULTS: Of the 18 patients without prior history of dysphagia who underwent CC, 15 received speech pathology consults for bedside swallowing evaluation (BSE). Four patients were referred for a videofluroscopic swallow study (VFSS), and 3 showed no signs of difficulty and were advanced to regular diets with thin liquids. One patient demonstrated swallowing difficulties during the VFSS and was placed on a regular diet with nectar thick liquids. Following a repeat swallow study 17 days post-surgery, the patient was advanced to thin liquids. INTERPRETATION: Postoperative dysphagia following CC is an uncommon and transient complication. Patients undergoing CC should have their swallowing evaluated prior to advancing their postoperative diet but are likely to return to normal diet and thin liquids by discharge.

Higher intelligence may be a risk factor for postoperative transient disturbance of consciousness after corpus callosotomy.

INTRODUCTION: Corpus callosotomy (CC) is an established surgical option for palliative treatment of medically intractable epilepsy, especially for seizures with drop attacks. We postulated that specific risk factors for post-CC transient disturbance of consciousness (pCTDC) are associated with CC. The purpose of this study was to review patients with intractable epilepsy who underwent CC and to statistically analyze risk factors for pCTDC. METHODS: Inclusion criteria for patients who underwent CC between January 2009 and November 2019 were: (1) ≥2 years old and (2) followed up for more than 8 months. The state of consciousness before and after CC was evaluated with the Glasgow coma scale. We statistically assessed predictors for pCTDC as the primary outcome. RESULTS: Fifty-six patients (19 females, 37 males) were enrolled, and the age range was 2-57 years old. Thirty-seven (66.1%) patients developed pCTDC. The mean period from the beginning of the state of pCTDC to recovery to their baseline conscious level was 4.9 days (range: 2-25 days). All three (100%) normal intelligence level patients, 13 (81%) of 16 patients with a moderately impaired level of intelligence, and 21 (57%) of 37 patients with a severely impaired level of intelligence exhibited pCTDC. Univariate (p = 0.044) and multivariate (p = 0.006) logistic regression analyses for predictors of pCTDC showed that intellectual function was statistically significant. CONCLUSION: Two-thirds of patients developed pCTDC. One risk factor for pCTDC may be higher intellectual function.

Bilateral epileptic networks in congenital and acquired corpus callosum defects: EEG-fMRI study.

OBJECTIVES: Electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC. METHODS: We included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways. RESULTS: 96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus. SIGNIFICANCE: Focal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries.

Developmental outcome after corpus callosotomy for infants and young children with drug-resistant epilepsy.

AIM: To examine the developmental and seizure outcomes after corpus callosotomy (CC) in early childhood. METHODS: We retrospectively identified 106 patients who underwent CC for drug-resistant epilepsy before the age of 6 years, at the Nagasaki Medical Center, between July 2002 and July 2016. Patients' developmental outcomes were evaluated one year after CC using the Kinder Infant Development Scale. RESULTS: The mean preoperative developmental quotient (DQ) was 25.0 (standard deviation [SD], 20.8), and the mean difference between preoperative DQ and one-year postoperative DQ was -1.6 points (SD, 11.6). However, 42.5% of patients had a mean DQ increase of 6.5 points (SD, 6.4), one year after CC from that before surgery. Factors related to the improvement in postoperative DQ were 'low preoperative DQ', 'developmental gain 1 month postoperatively', and 'postoperative seizure-free state'. Approximately 21.7% of patients were seizure-free 1 year after CC. INTERPRETATION: Performing CC, in infancy and early childhood for patients with drug-resistant epilepsy and severe developmental impairment, was associated with improved development in 42.5% of patients. Remission of seizures, even if only for a short period, contributed to developmental improvement. From a developmental perspective, CC for drug-resistant epilepsy in early childhood is an effective treatment.

Efficacy and safety of corpus callosotomy and ketogenic diet in children with Lennox Gastaut syndrome: a systematic review and meta-analysis.

BACKGROUND: Both corpus callosotomy (CC) and the ketogenic diet (KD) are commonly used in patients with Lennox Gastaut syndrome (LGS), as a significant proportion of these patients develop pharmacoresistant epilepsy. But no systematic review has yet compared the efficacy and safety of these two measures. METHODS: We conducted a systematic search on various databases to collating all available literature until 30th November 2020 with a primary objective to compare the efficacy of KD and CC in terms of the proportion of patients with complete seizure freedom, at least 75% and 50% reduction in seizure frequency at various time points after the institution of these modalities. We also attempted to compare the proportion and nature of adverse effects, impact on EEG, cognition, and behavior with these modalities. We only included original articles enrolling at least 10 patients with CC or KD for quantitative synthesis to determine a pooled estimate. We used a fixed or random effects model, depending on the degree of heterogeneity. RESULTS: We selected 23 and 7 articles describing the efficacy of CC and KD in 436 and 185 LGS patients out of 217 search items, but none of the studies compared directly these two entities. The indirect comparison between the pooled estimate of all patients with individual modalities revealed more patients with CC had seizure freedom, at least 75% and 50% reduction in seizure frequency (p=0.0001, 0.01, and 0.04 respectively). The proportion of patients with adverse effects was also higher for CC patients (p=0.01), although the proportion with serious adverse effects was not significantly different between the two modalities. Patients selected for CC were older, had higher seizure burden, more lag time after the onset of seizures, and received more number of antiseizure medications previously. Due to the availability of limited data, a firm conclusion could not be determined regarding the effect on EEG, cognition, and behavior with CC and KD. CONCLUSION: CC is more efficacious than KD in reducing seizure frequency in patients with LGS, although it has relatively more adverse effects during the immediate perioperative period.