Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

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Plantation ecosystems are more vulnerable than natural ones to global climate change. Using the dendrochronology method, we established tree-ring width chronologies of Pinus tabuliformis distributed in the semi-arid region of Northeast China. We examined its growth dynamics, analyzed the relationship between radical growth and climate factors, and explored the effects of global warming on the growth and distribution of P. tabuliformis. The results showed that tree-ring width chronologies of P. tabuliformis were negatively correlated with mean temperature of growing season (May-July), and positively correlated with precipitation and Palmer drought severity index (PDSI) in the early growing season (April) and in the growing season (May-July). Water availability was the main limiting factor for the radial growth of P. tabuliformis. Along the increasing precipitation gradient from southwest to northeast, tree growth became more sensitive to annual mean temperature, and the correlation with annual precipitation shifted from positive to negative, indicating that tree growth in the relative arid area (southwest of the study area) was more severely restricted by water availability. Drought stress caused by climate warming resulted in growth declines at some sites in the southwest area. With the continuous warming-drying climate, the distribution boundary of P. tabuliformis in the study area would shrink locally, with the suitable growth boundary moving northward.

Comparison of the real-world effectiveness of vertical versus lateral functional hemispherotomy techniques for pediatric drug-resistant epilepsy: A post hoc analysis of the HOPS study.

OBJECTIVE: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom. METHODS: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method. RESULTS: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique. SIGNIFICANCE: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

OBJECTIVE: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. METHODS: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. RESULTS: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom. SIGNIFICANCE: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.

Clinical features and surgical outcomes in young children with focal cortical dysplasia type II.

AIMS: To investigate clinical characteristics and surgery outcomes of young children with focal cortical dysplasia (FCD) type II. METHODS: Young children (onset age ≤6 years) with FCDII who underwent epileptic surgery in Children Epilepsy Center of Peking University First Hospital in 2014-2018 were followed up for at least 6 months after surgery. RESULTS: One hundred and twelve children with FCDII were included, with median age of onset 0.9 years (0.01-5.9), who underwent surgery at 4.1 years old (0.8-16.2). Focal seizures were most frequent (90.2%) and epileptic spasms presented in 23 (20.5%) cases. Epileptic encephalopathy was not uncommon (12.5%), associated with earlier epilepsy onset and higher rate of bilateral onset on ictal EEG (OR = 0.213, 9.059; P = .041, .004). At the last follow-up, 88.4% achieved seizure-free. Before surgery, 49.1% showed moderate/severe developmental delay, associated with earlier seizure onset and higher rate of history of epileptic encephalopathy (OR = 0.740, 5.160, P = .023, .042). For 48 children with preoperatively moderate/severe developmental delay, DQ rank at 6 months postsurgery was improved in only four cases. CONCLUSION: For young children with FCDII, they tend to present with epileptic encephalopathies and show moderate/severe developmental delay before surgery. The seizure outcome was favorable after surgery. For children with preoperatively moderate/severe developmental delay, developmental outcome at 6 months after surgery was not satisfactory.

[Surgery for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia].

OBJECTIVE: To investigate the clinical features and surgical strategy for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia and to assess the surgical outcomes. METHODS: The clinical features and preoperative evaluation results of 14 children with intractable epilepsy due to posterior quadrantic cortical dysplasia were retrospectively analyzed. The localization values of video-electroencephalography and intraoperative monitoring and the indications, advantages and disadvantages of temporoparietooccipital disconnection were evaluated. RESULTS: The 14 children had different seizure types, of which spasm was the most common one. The lesions of cortical dysplasia involved the central cerebral region in 2 cases. After temporoparietooccipital disconnection in 14 patients, 13 cases were seizure-free; only one case still had seizures, but the frequency dropped by more than 50%. CONCLUSIONS: Temporoparietooccipital disconnection is a safe and effective surgical procedure for children with intractable epilepsy due to posterior quadrantic cortical dysplasia.

Saliva and Plasma Monohydroxycarbamazepine Concentrations in Pediatric Patients With Epilepsy.

BACKGROUND: Monohydroxycarbamazepine (MHD, 10-hydroxy-carbamazepine) is the main active metabolite of oxcarbazepine (OXC). The present study aims to investigate the relationship between plasma and saliva concentrations of MHD in Chinese children with epilepsy. METHODS: Plasma and saliva samples were collected and MHD levels were measured by high-performance liquid chromatography system. Linear regression analysis was conducted between the dose of OXC and saliva concentrations, between the dose of OXC and plasma concentrations, and between the saliva concentrations and plasma concentrations. Student's t-test was used for unpaired data. A one-way analysis of variance was used for analyzing co-medication in subgroups of patients. RESULTS: A total of 58 blood samples and 58 saliva samples were obtained from 52 pediatric epileptic patients, with a median age of 5.67 years (0.58-15 years, 23 males and 29 females). There was an apparent positive correlation between the plasma and saliva MHD concentrations [Y = 0.77x - 0.85 (n = 58), R = 0.908, P < 0.01]. MHD plasma and saliva concentrations were positively correlated to daily drug dose (r = 0.461 and 0.417; P < 0.01 respectively). The saliva/plasma MHD ratio was around 0.71 and had no significant difference with age, gender, and combined medications. When data were analyzed for subgroups (one group taking OXC as monotherapy, the second group taking OXC in add-on with non-enzyme-inducing antiepileptic drugs, and the third group taking OXC in add-on with hepatic-enzyme-inducing antiepileptic drugs or moderate inducers), no significant difference was found between plasma and saliva MHD concentrations in all the above 3 groups. CONCLUSIONS: High correlation between plasma and saliva MHD levels supported the use of saliva as an alternative to plasma for OXC monitoring in children with epilepsy.

[Correlation between characteristics of interictal epileptiform discharge and histopathological change in epilepsy patients with focal cortical dysplasia].

OBJECTIVE: To discuss the correlation between characteristics of interictal epileptiform discharge (IED) and histopathological changes in epilepsy patients with focal cortical dysplasia (FCD) in order to explore the epileptogenicity of various IED. METHODS: Twenty-two consecutive patients suspected as with FCD who were to undergo epilepsy surgery received intracranial electrode implantation and long-term video-EEG monitoring before the resective surgery and the postoperative pathology proved the diagnosis of FCD. According the long-term EEG monitoring results, the IEDs were divided into four catalogs: isolated spike, slow repetitive spike, repetitive spike, and paroxysmal fast. The possible epileptogenic cortex with intense IED was resected in the operation to undergo histopathologic study and hemi-quantificational scoring of parvalbumin (PV) by immunocytochemistry. RESULTS: The resected specimens of 20 cases were studied. There were not significant differences in the PV quantificational score between any 2 IED subtypes (F = 1.198, P = 0.342). However, the spike type had the highest PV score: 8.00, while the repetitive spike type had the lowest PV score: 5.60. On the other hand, FCD of different severity in terms of pathological changes tended to have different kind of IED. CONCLUSION: Despite the insignificant differences between various kinds of IED, isolated spike has the highest PV scores meaning lower epileptogenicity. Slow repetitive spike, repetitive spike, and paroxysmal fast tend to occur in more severe FCD patients which mean a great possibility of epileptogenicity.

[Surgical treatment of lesional temporal lobe epilepsy].

OBJECTIVE: To discuss the presurgical evaluation and surgical treatment of lesional temporal lobe epilepsy (LTLE). METHODS: We retrospectively studied the patients whose MRI or CT showed lesions on one of the temporal lobes among patients who underwent epilepsy surgeries in our institute. All patients were divided into satisfactory and unsatisfactory group according to outcomes after operation. The characteristics of the lesions, neurophysiological features and results of pathologies were analyzed statistically. RESULT: Favorable surgical outcome was obtained in 24 patients, the satisfactory rate was 75%. The lesions of 17 patients were cortical malformations and the satisfactory rate of this group was 65%, which was less favorable than that of tumor group, (87%). 21 patients with their lesions located within the border of standard temporal lobectomy, had better surgical outcome than the others whose lesions were beyond the border (P<0.05). The satisfactory rate of 8 patients with lesions located within mesial structure of temporal lobe was no different compared with that of the others who had lesions outside the mesial structure (P>0.05). There were 19 patients who had consistency of the location of the lesion on MRI with the focal interictal epileptiform discharges on scalp EEG in satisfactory group, while there were only 3 patients in unsatisfactory group (P<0.05). CONCLUSION: For a LTLE patient, epilepsy surgery should be the first choice to be considered. Careful presurgical studies of the lesion, including its location, pathological property and neurophysiological characteristics, were very helpful for improving the surgical outcome.

[A comparative study on intraoperative electrocorticography with long-term intracranial EEG for localizing epileptogenic zone].

OBJECTIVE: To discuss the localizing methods for epileptogenic zone with intraoperative electrocorticography (ECoG) by comparing it with long-term intracranial EEG. METHODS: Twenty-two patients was enrolled, who received epilepsy surgeries consecutively in our institute since April 2005 to August 2006. All patients underwent intracranial electrode implantations with long-term video-EEG monitoring before the resective surgeries and the postoperative pathologies were all proved to be focal cortical dysplasia. The extra-operative and ECoG digital EEGs were statistically analyzed and compared with each other, including interictal epileptic discharge (IED) frequency, amplitude and their correlations with ictal discharge (ID). RESULTS: In the long-term intracranial EEG, significant difference was found between IED frequency derived from ID onset verus none-onset electrodes (Z = 12.213, P < 0.001), ROC analysis showed that IED frequency is a moderately good indicator for ID, the area under the ROC curve was 0. 758 (95% CI, 0.707-0.810). There was significant difference in IED amplitude between ID and none-ID electrodes (Z = 11.765, P < 0.001). The IED frequency was significantly lower during ECoG than during long-term extra-operative monitoring (rho = 0.518, P = 0. 014). A significant positive correlation in the IED frequency pattern was found between intra-operative ECoG and extra-operative recording when the average IED frequency was over 3 spikes /min. In ECoG, the correlation of IED with ID was similar in the 'frequent' (> or = 10 spikes/min) and 'occasional' (3-10 spikes/min) groups and very different in the 'rare' (< or = C3 spikes/min) group (rho = 0.408, P = 0.147). CONCLUSIONS: The IED from long-term EEG recording had moderate correlation in frequency and amplitude with ID position. IED frequency was usually decreased on ECoG when compared with long-term monitoring. However, ECoG could reliably reflect the IED pattern and the correlations between IED with ID in term of frequency and amplitude in the long-term EEG monitoring, when IED frequency exceeded 3 spikes/min. Under this circumstance, IED could be used for localizing the epileptogenic zone.