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PurposeAtonic seizures are associated with a particularly poor response to medical treatment. We performed a systematic review and meta-analysis to compare the efficacy of corpus callosotomy (CC) and vagus nerve stimulation (VNS) in the management of atonic seizures in the pediatric population.MethodsA literature search was performed in compliance...
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Citations
... Vagus nerve stimulation (VNS) and corpus callosotomy (CC) are palliative therapies used to reduce seizure burden and improve quality of life in Lennox Gastaut Syndrome (LGS) (9,10). VNS has been approved in the US since 1997 and is effective in reducing seizures by more than 50% with longer device usage (11). ...
... A recent meta-analysis comparing CC ablation to VNS demonstrates that CC has a notable advantage over VNS in treating atonic seizures in pediatric patients. This benefit, however, should be carefully measured against the increased risks of re-operation and disconnection syndrome (10). It is important to note, however, that often both surgeries are utilized in patients with severe LGS and that their effects are not mutually exclusive. ...
Lennox Gastaut Syndrome (LGS) is characterized by drug-resistant epilepsy that typically leads to decreased quality of life and deleterious neurodevelopmental comorbidities from medically refractory seizures. In recent years there has been a dramatic increase in the development and availability of novel treatment strategies for Lennox Gastaut Syndrome patient to improve seizure. Recent advances in neuromodulation and minimally invasive magnetic resonance guided laser interstitial thermal therapy (MRgLITT) have paved the way for new treatments strategies including deep brain stimulation (DBS), responsive neurostimulation (RNS), and MRgLITT corpus callosum ablation. These new strategies offer hope for children with drug-resistant generalized epilepsies, but important questions remain about the safety and effectiveness of these new approaches. In this review, we describe the opportunities presented by these new strategies and how each treatment strategy is currently being employed. Next, we will critically assess available evidence for these new approaches compared to traditional palliative epilepsy surgery approaches, such as vagus nerve stimulation (VNS) and open microsurgical corpus callosotomy (CC). Finally, we will describe future directions that would help define which of the available strategies should be employed and when.
... p = 0.003) for CC. 39 In this meta-analysis, CC was associated with a higher prevalence of complications requiring reoperation (6.6% vs. 3.8% in VNS) and 14% developed symptomatic disconnection syndrome. 39 A decision analytic model showed CC to have 15% greater likelihood of a positive outcome for all seizures, but perpatient costs for CC were over $68 000 more than those of VNS. ...
... 39 In this meta-analysis, CC was associated with a higher prevalence of complications requiring reoperation (6.6% vs. 3.8% in VNS) and 14% developed symptomatic disconnection syndrome. 39 A decision analytic model showed CC to have 15% greater likelihood of a positive outcome for all seizures, but perpatient costs for CC were over $68 000 more than those of VNS. For atonic seizures, CC had 27% greater likelihood of positive outcome and the same incremental cost. ...
Objective
Evaluate the long‐term efficacy of vagus nerve stimulation (VNS) in patients with developmental and epileptic encephalopathies (DEE) compared with epilepsy patients without intellectual disability (ID).
Methods
Long‐term outcomes from a Norwegian VNS quality registry are reported in 105 patients with DEEs (Lennox–Gastaut syndrome [LGS] n = 62; Dravet n = 16; Rett n = 9; other syndromes n = 18) were compared with 212 epilepsy patients without ID, with median follow‐up of 88 and 72 months, respectively. Total seizure reduction was evaluated at 6, 12, 24, 36, and 60 months. Effect on different seizure types was evaluated at baseline and last observation carried forward (LOCF).
Results
Median monthly seizure frequency at LOCF was reduced by 42.2% (p < 0.001) in patients with DEE and by 55.8% (p < 0.001) in patients without ID. In DEE patients, ≥50% seizure reduction at 6 and 24 months were 17.1% and 37.1%, respectively, and 33.5% and 48.6% for patients without ID. Seizure reduction ≥75% at 60 months occurred in 14.3% of DEE patients and 23.1% of patients without ID. Highest median reduction was for atonic seizures, most notably 64.6% for LGS patients. A better effect was seen at 2 years among DEE patients with unchanged medication compared with those with changed medication (54.5% vs. 35.6% responders, p = 0.078). More DEE patients were reported to have greater improvement in ictal or postictal severity (43.8% vs. 28.3%, p = 0.006) and alertness (62.9% vs. 31.6%, p < 0.001) than patients without ID. For both groups, use of the magnet reduced seizure severity. Hoarseness was the most common adverse effect in both groups. In addition, DEE patients were frequently reported to have sleep disturbance, general discomfort, or abdominal problems.
Significance
Our data indicate that VNS is very effective for atonic seizures. Patients without ID had best overall seizure reduction, however, patients with DEE had higher retention rates probably due to other positive effects.
Plain Language Summary
DEE refers to a group of patients with severe epilepsy and intellectual disability. Many of these patients have restricted lifestyles with frequent seizures. VNS is a treatment option for patients who do not respond well to medicines, either because of insufficient effect or serious adverse effects. Our study shows that VNS is well tolerated in this patient group and leads to a reduction in all seizure types, most notably for seizures leading to fall. Many patients experience other positive effects like shorter and milder seizures, as well as improvement in alertness.
... Patients in this study failed a median of 5 ASMs prior to referral with many failing VNS, dietary therapy and other interventions prior to surgery. Knowing that the likelihood of significant seizure reduction is minimal after failing a second ASM and despite good evidence showing better seizure outcomes with callosotomy compared to VNS and diet, this delay is likely unwarranted (18,19,20,21,22). Furthermore, growing evidence supports that early surgical intervention for epilepsy has a favorable impact on outcomes, making duration of epilepsy a modifiable risk factor for poor outcome (14,15,16,1,26). ...
Objectives
Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug‐resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi‐institutional epilepsy surgery database to characterize the use of CC across participating centers.
Methods
Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0–18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically.
Results
Eighty‐three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0–9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1–20) and 10.46 (.2–20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini‐craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow‐up was 12.8 months (range 1–39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant.
Significance
CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less‐invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.
... There have been several systematic reviews and meta-analyses of surgeries for DRE, but only two articles have focused on CC (Chan et al., 2018;Graham et al., 2016), while others have compared CC to other treatments, such as vagus nerve stimulation (VNS) and ketogenic diet (Rolston et al., 2015;Sharawat et al., 2021;Ye et al., 2021). ...
... Meanwhile, the rate of complete SF from drop attacks after TCC was significantly higher than that after ACC (71.52% vs. 57.11%). Currently, the palliative surgical treatment for DRE mainly includes CC and VNS.Ye et al. (2021) pointed out that CC is superior to VNS for the management of atonic seizures in the pediatric population. A metaanalysis comparing the efficacy of different surgical treatments for controlling Lennox-Gastaut syndrome found that the rate of seizure reduction was significantly higher than VNS (74.1% vs. 54.6%, ...
Background:
Corpus callosotomy (CC) is appropriate for patients with seizures of a bilateral or diffuse origin, or those with seizures of a unilateral origin with rapid spread to the contralateral cerebral hemisphere. The efficiency of CC in patients with drug-resistant epilepsy is a long-term concern because most articles reporting the surgical results of CC arise from small case series, and the durations of follow-up vary.
Methods:
PubMed, Embase, Cochrane Library, and Web of Science were searched to identify papers published before November 8, 2021. The systematic review was completed following PRISMA guidelines. Outcomes were analyzed by meta-analysis of the proportions.
Results:
A total of 1644 patients with drug-resistant epilepsy (49 retrospective or prospective case series studies) underwent CC, and the follow-up time of all patients was at least 1 year. The rate of complete seizure freedom (SF) was 12.38% (95% confidence interval [CI], 8.17%-17.21%). Meanwhile, the rate of complete SF from drop attacks was 61.86% (95% CI, 51.87%-71.41%). The rates of complete SF after total corpus callosotomy (TCC) and anterior corpus callosotomy (ACC) were 11.41% (95% CI, 5.33%-18.91%) and 6.75% (95% CI, 2.76%-11.85%), respectively. Additionally, the rate of complete SF from drop attacks after TCC was significantly higher than that after ACC (71.52%, 95% CI, 54.22%-86.35% vs. 57.11%, 95% CI, 42.17%-71.49%). The quality of evidence for the three outcomes by GRADE assessment was low to moderate.
Conclusion:
There was no significant difference in the rate of complete SF between TCC and ACC. TCC had a significantly higher rate of complete SF from drop attacks than did ACC. Furthermore, CC for the treatment of drug-resistant epilepsy remains an important problem for further investigation because there are no universally accepted standardized guidelines for the extent of CC and its benefit to patients. In future research, we will focus on this issue.
... It was even recommended as the first-line therapy for treatment of myoclonic-atonic seizures (50). In addition to medical treatment, some surgical treatments significantly improve refractory atonic seizures, such as corpus callosotomy (CC) and vagus nerve stimulation (VNS), both CC and VNS being well tolerated for the treatment of refractory atonic seizures (50)(51)(52). ...
Alexander's disease (AxD) is a rare autosomal dominant hereditary disorder that is caused by the mutations in the GFAP gene, which encodes the glial fibrillary acidic protein (GFAP). This neurogenerative disease has many clinical manifestations, and the onset of disease spans a wide range of ages, from newborns to children, adults, and even the elderly. An overaccumulation of the expression of GFAP has a close causal relationship with the pathogenesis of Alexander's disease. Usually, the disease has severe morbidity and high mortality, and can be divided into three distinct subgroups that are based on the age of clinical presentation: infantile (0–2 years), juvenile (2–13 years), and adult (>13 years). Children often present with epilepsy, macrocephaly, and psychomotor retardation, while adolescents and adults mainly present with muscle weakness, spasticity, and bulbar symptoms. Atonic seizures are a type of epilepsy that often appears in the Lennox–Gastaut syndrome and myoclonic–astatic epilepsy in early childhood; however, the prognosis is often poor. Atonic episodes are characterized by a sudden or frequent reduction in muscle tone that can be local (such as head, neck, or limb) or generalized. Here, we report a 4-year-old girl whose main symptoms were intermittent head drop movements, which could break the frontal frame and even bleed in severe conditions. A video-encephalography (VEEG) showed that the nodding movements were atonic seizures. A head magnetic resonance imaging (MRI) revealed abnormal signals in the bilateral paraventricular and bilateral subfrontal cortex. The gene detection analyses indicated that the GFAP gene exon 1 c.262 C>T was caused by a heterozygous mutation, as both her parents were of the wild-type. The girl had no other abnormal manifestations except atonic seizures. She could communicate normally and go to kindergarten. After an oral administration of sodium valproate, there were no atonic attacks. Although epilepsy is a common symptom of Alexander's disease, atonic seizures have not been reported to date. Therefore, we report a case of Alexander's disease with atonic seizures as the main symptom and provide a review of the literature.
... Theoretically, CC disturbs the spreading of seizure activities to the other hemisphere, but is also considered to have an anti-threshold effect for generalized seizures. In human medicine, especially in children, CC is most effective in preventing drop attacks and following head trauma; approximately 60-80 % of pediatric patients that underwent CC showed ≥ 50 % seizure reduction (Graham et al., 2016;Ye et al., 2021). CC has also been shown to be effective for GTCS with 50-70 % of human patients having ≥ 50 % seizure reduction than those for drop attacks. ...
Epilepsy surgery is functional neurosurgery applied to drug-resistant epilepsy. Although epilepsy surgery has been established and achieves fair to good outcomes in human medicine, it is still an underdeveloped area in veterinary medicine. With the spread of advanced imaging and neurosurgical modalities, intracranial surgery has become commonplace in the veterinary field, and, therefore, it is natural that expectations for epilepsy surgery increase. This review summarizes current standards of intracranial epilepsy surgery in human medicine and describes its current status and expectation in veterinary medicine. Intracranial epilepsy surgery is classified generally into resection surgery, represented by cortical resection, lobectomy, and lesionectomy, and disconnection surgery, such as corpus callosotomy and multiple subpial transection. In dogs with drug-resistant epilepsy, corpus callosotomy is available as a disconnection surgery for generalized epilepsy. However, other types of disconnection and resection surgeries for focal epilepsy are limited to experimental studies in laboratory dogs and/or anecdotal case reports of lesionectomy, such as tumor or encephalocele removal, without epileptogenic evidence. Veterinary epilepsy surgery is a new and challenging neurosurgery field; with the development of presurgical evaluations such as advanced electroencephalography and neuroimaging, it may become more readily practiced.
... Clinical outcomes and complication probabilities were obtained from recent systematic reviews that synthesize and compare CC and VNS literature. 8,15 Given that LGS patients have multiple seizure types, seizure reduction probabilities were considered as an average of seizure reduction from all seizure types. 8 Seizure freedom and >50% seizure reduction were considered as discrete probabilities; thus, rates of seizure freedom were subtracted from rates of >50% seizure reduction to calculate the probabilities of seizure freedom and >50% seizure reduction. ...
Objective
Palliative epilepsy surgery via corpus callosotomy (CC) or vagus nerve stimulation (VNS) is commonly employed for drug‐resistant seizures in Lennox‐Gastaut Syndrome (LGS). VNS is less effective at reducing seizures but has fewer adverse events, CC is more effective for seizure control, particularly atonic seizures, but can be associated with serious adverse events, and yet their relative cost‐effectiveness remains unknown.
Methods
To determine which option is most cost‐effective, a decision analytic model was developed to evaluate the risks and benefits of CC and VNS at 1 year based on costs in the United States. Our primary outcome measure was positive seizure outcomes, defined as >50% seizure reduction without procedural complications.
Results
CC had a 15% greater likelihood of a positive seizure outcome, but per patient costs were $68 147 more than VNS, or $451 952 per positive seizure outcome gained. One‐way sensitivity analyses demonstrate that probabilities of seizure freedom or reduction by VNS or CC and CC cost were most influential on results. When considering atonic seizures, CC had a 27% greater positive outcome likelihood than VNS, the same incremental cost, and cost $250 556 per positive seizure outcome gained.
Significance
This exploratory model suggests that VNS is more cost‐effective relative to CC at 1 year.
... Satisfactory efficacy of both techniques for drug-resistant epilepsy has been demonstrated, with the proportion of a ≥50% reduction in seizure frequency reported as 40-70% for VNS [1][2][3][4][5][6] and 63-79% for CC [1][2][3]7]. On the one hand, VNS is less invasive and carries a low risk of severe complications such as epidural or subdural hematoma and disconnection syndrome, which are complications of CC [2,[8][9][10]. On the other hand, CC is more likely to improve seizure frequency or severity than VNS, particularly for drop attacks or epileptic spasms [9][10][11][12]. ...
... On the one hand, VNS is less invasive and carries a low risk of severe complications such as epidural or subdural hematoma and disconnection syndrome, which are complications of CC [2,[8][9][10]. On the other hand, CC is more likely to improve seizure frequency or severity than VNS, particularly for drop attacks or epileptic spasms [9][10][11][12]. The selection of these two techniques appears to depend on seizure type, surgical risk, and the wishes of the patient and caregivers, although no universally accepted indications have been determined. ...
Objective:
The effectiveness of vagus nerve stimulation (VNS) for residual seizures after corpus callosotomy (CC) has not yet been fully investigated. We hypothesized that seizure control would be improved by VNS after CC. The purpose of this study was to compare seizure frequency between patients with implantation of a VNS generator (post-VNS group) or without VNS (non-post-VNS group) following CC.
Methods:
We retrospectively reviewed patients who underwent CC between January 2009 and May 2019 in our institution. We evaluated proportions of ≥50% reduction in seizure frequency (responders) and seizure reduction rate 1 and 2 years after VNS. To investigate factors related to responders, uni- and multivariate logistic regression analyses were performed regarding age, number of anti-seizure medications (ASMs), addition of novel ASMs (levetiracetam, lacosamide or perampanel), and post-VNS or non-post-VNS status.
Results:
Thirteen post-VNS patients and 24 non-post-VNS patients were analyzed in this study. Responder rate at 1 year after VNS differed significantly between the post-VNS group (53.9%) and non-post-VNS group (12.5%, p = 0.017). Number of ASMs at the time of CC and post-VNS were significantly associated with responders in univariate analyses (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.13-0.88, p = 0.025 and OR 8.2, 95%CI 1.6-41.6, p = 0.011, respectively), whereas age, sex, seizure frequency, and addition of novel ASMs were not. In multivariate analysis, the presence of VNS procedures after CC was the only factor favorably associated with responder status (OR 82.2, 95%CI 1.55-4355.7, p = 0.03).
Conclusions:
VNS therapy after CC may increase the proportion of responders independent of the addition of novel ASMs.
Purpose
To assess preferences and outcome expectations for vagus nerve stimulation (VNS) and corpus callosotomy (CC) surgeries in the treatment of atonic seizure in Lennox-Gastaut syndrome (LGS).
Methods
A total of 260 surveys were collected from patients are caregivers of LGS patients via Research Electronic Data Capture (REDCap).
Results
Respondents reported an average acceptable atonic seizure reduction rate of 55.9% following VNS and 74.7% following CC. 21.3% (n = 50) were willing to be randomized. Respondents reported low willingness for randomization and a higher seizure reduction expectation with CC.
Conclusion
Our findings guide surgical approaches for clinicians to consider patient preference in order to design future studies comparing effectiveness between these two procedures.
