Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.     

Individualized prediction of seizure relapse and outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery

The objective of this study was to create a clinically useful tool for individualized prediction of seizure outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery. We used data from the European retrospective TimeToStop study, which included 766 children from 15 centers, to perform a proportional hazard regression analysis. The 2 outcome measures were seizure recurrence and seizure freedom in the last year of follow‐up. Prognostic factors were identified through systematic review of the literature. The strongest predictors for each outcome were selected through backward selection, after which nomograms were created. The final models included 3 to 5 factors per model. Discrimination in terms of adjusted concordance statistic was 0.68 (95% confidence interval [CI] 0.67‐0.69) for predicting seizure recurrence and 0.73 (95% CI 0.72‐0.75) for predicting eventual seizure freedom. An online prediction tool is provided on www.epilepsypredictiontools.info/ttswithdrawal . The presented models can improve counseling of patients and parents regarding postoperative antiepileptic drug policies, by estimating individualized risks of seizure recurrence and eventual outcome.     

Magnetoencephalography using total intravenous anesthesia in pediatric patients with intractable epilepsy: lesional vs nonlesional epilepsy

Purpose: Magnetoencephalography (MEG) provides source localization of interictal spikes. We use total intravenous anesthesia (TIVA) with propofol to immobilize uncooperative children. We evaluate the effect of TIVA on interictal spikes in children who have intractable epilepsy with or without MRI lesions. Methods: We studied 28 children (3–14 years; mean, 6.6). We intravenously administered propofol (30–60 μg/kg/min) to record MEG with simultaneous EEG. We evaluated MEG spike sources (MEGSSs). We compared spikes on simultaneous EEG under TIVA with those on scalp video-EEG without TIVA. Results: There was a significant decrease in frequent spikes (10 patients, 36%) on simultaneous EEG under TIVA compared to those (22 patients, 79%) on scalp video-EEG without TIVA (P < 0.01). MEGSSs were present in 21 (75%) of 28 patients. Clustered MEGSSs occurred in 15 (83%) of 18 lesional patients but in 3 (30%) of 10 nonlesional patients (P < 0.05). MEGSSs were more frequently absent in nonlesional (6 patients, 60%) than lesional (one patient, 5%) patients (P < 0.01). Thirteen patients with MRI and/or histopathologically confirmed neuronal migration disorder most frequently showed clustered MEGSSs (11 patients, 85%) compared to those of other lesional and nonlesional patients. Conclusion: Propofol-based TIVA reduced interictal spikes on simultaneous EEG. TIVA for MEG still had utility in identifying spike sources in a subset of pediatric patients with intractable epilepsy who were uncooperative and surgical candidates. In lesional patients, MEG under TIVA frequently localized the clustered MEGSSs. Neuronal migration disorders were intrinsically epileptogenic and produced clustered MEGSSs under TIVA. Nonlesional patients often had no MEGSS under TIVA.     

Predictors of seizure outcome following cortical resection in pediatric and adolescent patients with medically refractory epilepsy

Several preoperative clinical variables have been reported to have value as predictors of seizure outcome following the surgical resection of epileptogenic focus in adults who have had medically refractory epilepsy. The present paper reports the results of a retrospective review of the ability of these variables to predict seizure outcome in a group of pediatric patients who had medically refractory epilepsy and underwent surgical resection of an epileptogenic focus at the Children's Hospital of Eastern Ontario. Variables in this review included age at first seizure, age at time of surgery, duration of seizures, seizure type, sex, family history, etiology, level of intelligence, EEG data, results of imaging studies, findings on examination of the central nervous system, and location and site of surgical resection. We found 64 patients who met the entry criteria for this review. Normal intelligence and tumor as etiology were associated with a good postoperative seizure outcome in patients who had a temporal resection; no variables had positive correlation with outcome in the extratemporal group. Caution must be used in the extrapolation of data and inclusion of studies of predictors of seizure outcome for adults to pediatric age groups. Received: 8 June 1998     

Prognosis of seizure recurrence after stopping antiepileptic drugs in seizure-free patients: A long-term population-based study of childhood-onset epilepsy

The long-term outcome with respect to seizure relapse after planned discontinuation of antiepileptic drugs (AEDs) in seizure-free patients is not well known. Relapse and its treatment outcome were evaluated in a longitudinal population-based study of 148 patients from the onset of their epilepsy to an average follow-up of 37 years. During the study, AEDs were completely discontinued by 90 patients; 58 patients remained on medication. Seizure relapse after AED discontinuation was observed in 33 (37%) of 90 patients at an average follow-up of 32 years. Among 8 of the 33 patients who elected to restart AEDs, 2 achieved 5-year terminal remission (5YTR), but only 10–19 years after restarting treatment. The other 6 patients never achieved 5YTR, and 2 of the 6 never entered a 5-year remission period during follow-up. Factors associated with failure to reach 5YTR after treatment of relapse were symptomatic etiology and localization-related epilepsy. In conclusion, drug discontinuation after seizure freedom results in relapse in one-third of patients. Reinstitution of a medication that worked for years fails to achieve control in one of four patients. These risks need to be considered, although there is no evidence that discontinuation is responsible for the poor prognosis for treatment of seizure recurrence.     

Long-term follow-up of the ketogenic diet for refractory epilepsy: Multicenter Argentinean experience in 216 pediatric patients

Purpose

In this Argentinean retrospective, collaborative, multicenter study, we examine the efficacy and tolerability of the ketogenic diet (KD) for different epilepsy syndromes.

Materials and methods

we evaluated the clinical records of 216 patients started on the KD between March 1, 1990 and December 31, 2010.

Results

One hundred forty of the initial patients (65%) remained on the diet at the end of the study period. Twenty-nine patients (20.5%) became seizure free and 50 children (36%) had a 75–99% decrease in seizures. Thus, 56.5% of the patients had a seizure control of more than 75%. The best results were found in patients with epilepsy with myoclonic-astatic seizures, Lennox–Gastaut syndrome, and West syndrome. Good results were also found in patients with Dravet syndrome, in those with symptomatic focal epilepsy secondary to malformations of cortical development, and in patients with tuberous sclerosis. Seizures were significantly reduced in four patients with fever-induced refractory epileptic encephalopathy in school-age children and in two patients with epileptic encephalopathy with continuous spikes and waves during slow sleep. The median period of follow-up after discontinuation of the diet was 6 years. Twenty patients who had become seizure free discontinued the diet, but seizures recurred in five (25%). Of 40 patients with a seizure reduction of more than 50% who discontinued the diet, 10 presented with recurrent seizures.

Conclusion

The ketogenic diet is a good option in the treatment of refractory epilepsy. After discontinuing the diet, seizures recurrence occurred in few patients.     

Long-term seizure outcome and its predictors in patients with recurrent seizures during the first year aftertemporal lobe resective epilepsy surgery

Purpose: The existing data on the implications of the characteristics of seizures that recur during the first year following epilepsy surgery on subsequent seizure outcome are conflicting. We investigated the impact of recurrent seizures in the first postoperative year and their attributes on long‐term seizure outcome. Methods: We studied the postoperative courses of 492 patients who had completed two or more years of follow‐up after temporal lobe resective epilepsy surgery. We used Kaplan‐Meier survival curves to define long‐term seizure outcome and assessed the predictive value of recurrent seizure characteristics on the outcome by univariate and multivariate proportional hazards regression models. Key Findings: In our patients, seizure recurrences during the first postoperative year, irrespective of the attributes of recurrent seizures (such as provoked vs. unprovoked, and timing and number of recurrences), imparted fourfold to sevenfold increased hazards for continued seizures beyond the first postoperative year. Although patients with complex partial seizures with or without secondary generalized tonic–clonic seizures (CPS/GTCS) had a sixfold increased risk, those with auras alone had only a borderline risk for seizures beyond the first postoperative year. In the multivariate model, CPS/GTCS as the predominant seizure type and three or more seizure recurrences during the first postoperative year independently predicted unfavorable long‐term seizure outcome. Significance: Our study provides valuable information that is helpful in prognosticating and counseling patients, and in making rational decisions on the withdrawal of antiepileptic drugs following surgery. Our findings enhance the general understanding of the etiopathogenesis of surgical failure.     

Mental retardation in pediatric candidates for epilepsy surgery: the role of early seizure onset

PURPOSE: We sought to determine whether early age at seizure onset is a risk factor for mental retardation, independent of etiology. Assessment of risk for mental retardation with continued uncontrolled seizures plays a role in considerations of timing for epilepsy surgery. Previous studies have indicated that onset of seizures in the first years of life may be a risk factor for mental retardation, but the etiologies of the epilepsies were not included in the analyses. METHODS: Intellectual function was assessed at ages 2-20 years during presurgical evaluation in 100 patients with intractable epilepsy due to focal lesions limited to part of one lobe of the brain. Mental retardation (MR) was defined as Full-Scale Intelligence Quotient (FSIQ) < or =70. The age at seizure onset and the seizure frequency were obtained retrospectively. RESULTS: Younger ages at seizure onset were associated with lower FSIQ scores, and mean FSIQ was also significantly lower for patients with onset of epilepsy at < or =24 months of age (74.0 +/- 21.5) versus that in patients with onset of epilepsy later in life (87.8 +/- 18.8; p = 0.005). The frequency of patients with MR was significantly higher for patients with seizure onset at < or =24 months of age (15 of 33, 46%) than for patients with seizure onset later in life (eight of 67, 12%; p < 0.001). This difference persisted within etiologic subgroups. For patients with focal malformation of cortical development, MR was seen in eight (50%) of 16 patients with seizure onset at < or =24 months versus two (10%) of 20 patients with seizure onset at >24 months (p < 0.001); for patients with tumor, MR was seen in four (50%) of eight patients with seizure onset at < or =24 months versus four (13%) of 30 patients with seizure onset at >24 months (p = 0.003); and for patients with hippocampal sclerosis, MR was seen in two (28%) of seven patients with seizure onset at < or =24 months versus none of 30 patients with seizure onset at >24 months (NS). Within the subgroup with daily seizures, MR was present in 13 (65%) of 20 patients with seizure onset at < or =24 months versus five (17%) of 29 patients with seizure onset later in life (p = 0.001). CONCLUSIONS: These results indicate that onset of intractable epilepsy within the first 24 months of life is a significant risk factor for MR, especially if seizures occur daily. The risk based on early age at seizure onset appeared independent of etiology and persisted within subgroups of patients with focal malformation of cortical development, tumor, or hippocampal sclerosis. Prospective studies will be important to clarify whether early surgical intervention may reduce the risk for subsequent MR in carefully selected infants.     

Temporal lobe epilepsy surgery: outcome, complications, and late mortality rate in 215 patients

PURPOSE: We studied the surgical outcome, complications, and the late mortality rate in a large group of patients with medically refractory temporal lobe epilepsy (TLE). METHODS: Two-hundred fifteen patients with TLE were treated surgically between 1984 and 1999 after a comprehensive presurgical evaluation. Patients were followed up at 6 weeks, 3-6 months, and yearly thereafter. In addition, questionnaires were sent on the anniversary of their surgery. Surgical outcome (Engel's classification), complication rate, and factors contributing to late mortality were analyzed. Standardized mortality ratios (SMRs) were calculated. RESULTS: There was no surgical mortality. Two (0.9%) had mild hemiparesis, one (0.4%) had a hemianopia, seven (3.2%) had transient cranial nerve palsies, and eight (3.7%) had transient postoperative language difficulties. One hundred forty-eight (69%) became seizure free, 43 (20%) had rare seizures, 14 (6.5%) had worthwhile seizure reduction, and 10 (4.6%) had no improvement (follow-up, 1-15 years). Three (2%) of 148 seizure-free patients died during follow-up, compared with eight (11.9%) of 67 not seizure-free patients. The mean duration of epilepsy before surgery for the surviving patients was 17.8 years, and for those patients who died, 25.9 years (p < 0.05). Six (5.7%) of 104 patients with right-sided resections died during follow-up, compared with five (4.5%) of 111 with left-sided resections. CONCLUSIONS: Eighty-nine percent of patients became seizure free or had rare seizures, with low morbidity, and no surgical mortality. The late mortality occurred predominantly in patients with persistent seizures (SMR, 7.4). Those patients who died had a longer duration of epilepsy before surgery. In contrast, among those patients who became seizure free, the mortality rate was much lower, and similar to the general population of Indiana (SMR, 1.7).     

Talampanel,a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy

PURPOSE: Talampanel (LY300164), a potent and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor antagonist, is a potential new antiepileptic drug (AED). This study examines the single- and multiple-dose pharmacokinetics, safety, and tolerability of talampanel in patients with intractable epilepsy and assesses the potential for pharmacokinetic interaction. METHODS: Eleven of 14 patients entered into the study completed. Fourteen patients were evaluated for safety, 13 patients were used in the single-dose, and 11 patients in the multiple-dose pharmacokinetic analysis. Each patient initially received a single 35-mg dose of talampanel followed by the measurement of pharmacokinetic profiles. A 21-day t.i.d. dosing regimen was then determined for each patient based on his or her initial pharmacokinetic profile. Adverse events were recorded by patients or their carers. RESULTS: After oral ingestion, talampanel was rapidly absorbed, with maximal plasma concentrations achieved within 1-3 h. Talampanel concentrations in patients taking enzyme-inducing AEDs were 50% lower than those seen in healthy volunteers. Mean talampanel t1/2 values were 3.0 h compared with 4.2 h in healthy volunteers. After multiple-dose and steady-state, talampanel t1/2 values were increased to 5.6 h Talampanel and valproic acid (VPA) appear to inhibit each other's metabolism mutually. Talampanel had no effect on plasma concentrations of other AEDs. Multiple-dose talampanel administration was associated with nonlinear pharmacokinetics. No serious adverse events were reported; the most frequently reported being dizziness, ataxia, drowsiness, and headaches CONCLUSIONS: Talampanel dosing strategies may be reliant on concomitant AED medication, as enzyme-inducing AEDs enhance, whereas VPA inhibits its metabolism. Talampanel was well tolerated, although adverse events occurred at lower doses compared with those in healthy subjects, probably because of the additive effect of concomitant AEDs.     

Postsurgical outcome in pediatric patients with epilepsy: a comparison of patients with intellectual disabilities, subaverage intelligence, and average-range intelligence

PURPOSE: Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patient's ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents. METHODS: Pediatric patients with intellectual disabilities (IQ < or = 70), subaverage intelligence (IQ between 71 and 85), or average-range intelligence (IQ > 85) were matched according to several clinical and etiologic criteria to determine the influence of IQ (N = 66). RESULTS: No dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level was found. All groups slightly improved in attention while memory functions tended to decrease and executive functions were stable. School placement remained unchanged for the majority of patients. Between 67 and 78% were seizure free 1 year after surgery (Engel outcome class I). CONCLUSIONS: IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average-range intelligence, the decision to operate on patients with a low level of intelligence should depend on the results of the presurgical diagnostics. If the results of the neuropsychological examination indicate diffuse functional impairment, this should not hinder further steps, if all other findings are consistent.     

VNS in patients with previous unsuccessful resective epilepsy surgery: antiepileptic and psychotropic effects

OBJECTIVES: To assess the efficacy of vagus nerve stimulation (VNS) in patients with medically and surgically intractable complex partial seizures (CPS). PATIENTS AND METHODS: Sixteen patients with previous temporal [15] and frontal [one] resections were treated with VNS between 1994 and 1999 at King's College Hospital, London, UK. Post-operative video-electroencephalogram telemetry had shown that CPS started from the operated side in 12 patients, contralaterally in three and bilaterally independently in one. RESULTS: Three patients (18.75%) had 50% or more reduction in seizure frequency, but one showed severe worsening of epilepsy, which remitted upon VNS discontinuation. The antiepileptic effect of VNS was not different with respect to the type of operation (anterior temporal lobectomy vs amygdalohippocampectomy), the side of operation, or the side of seizure onset. We observed psychotropic effects in two patients with post-ictal psychosis, in two others with depression, and in a child with severe behavioral disorder. CONCLUSIONS: VNS may have a rather limited antiepileptic role to play in patients with persistent seizures following epilepsy surgery, but may independently possess useful antipsychotic and mood-stabilizing properties.     

Caregiver measures for seizure control, efficacy, and tolerability of antiepileptic drugs for childhood epilepsy: results of a preference survey

We sought to identify and quantify caregiver-defined characteristics of efficacy related to the perceived success of antiepileptic drug (AED) use. A 22-question survey was designed using physician input, focus groups, and clinical trial endpoints. Responses were pooled and analyzed with regard to seizure type and treatment, categorized as controlled (exposure to 1 AED), adjunctive (exposure to 2 AEDs), or refractory (exposure to ≥ 3 AEDs). Two hundred ninety-five surveys were completed: 109 (37%) controlled, 84 (28%) adjunctive, and 102 (35%) refractory. Seizure freedom and median seizure reduction > 90% maintained for > 1 year were reported as the most important indicators of medication efficacy by the majority of respondents. These measures were the same regardless of seizure type or treatment category. Our results demonstrate that current trial design may be inadequate to address the expectations of patients. Incorporating patient-defined AED efficacy measures may improve satisfaction and informed decision making regarding epilepsy treatment.     

Defining early seizure outcomes in pediatric epilepsy: the good, the bad and the in-between

PURPOSE: To examine different approaches to classifying seizure outcomes. METHODS: In a prospective cohort study of children (N=613) with newly diagnosed epilepsy, seizure outcomes at 2 years were classified as 'good' (> or =1 year remission), 'bad' or 'intractable' (> or = AED failures, > or =1 seizure/month over > or =18 months), and 'indeterminate' (neither 'good' nor 'bad'). Outcomes at 2 years were compared to outcomes in those followed 4 or more years. The associations of three commonly studied prognostic factors, etiology, age at onset, and syndromic grouping with the three-level outcome were assessed. RESULTS: 595 (97.1%) children were followed > or =2 years. A 'good', indeterminate, and 'bad' outcome was present in 314 (52.8%), 235 (38.3%), and 46 (7.7%) children. Problems with treatment were recorded in 64.7% of the indeterminate group. In 390 children followed > or =4 years, early 'good' and 'bad' outcomes persisted in approximately 80%. About half of those with indeterminate 2-year outcomes later achieved remission, 8% met criteria for intractability, and 37% remained indeterminate. Most of the associations with etiology, age, and syndrome were due to variation in the proportion that met criteria for intractability and not remission. CONCLUSIONS: Many children have indeterminate outcomes, often in association with treatment issues. Clearly 'good' and 'bad' early outcomes can be identified and persist > or =2 years later. In the absence of pharmaco-resistance, lack of early remission (indeterminate outcome) is usually not associated with a bad outcome, at least over the next few years.     

Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience

PURPOSE: Although epilepsy surgery, especially temporal lobe epilepsy surgery, is well established to control seizures in patients remaining on antiepileptic drug (AED) treatment, less information is available about how many seizure-free surgical patients will relapse after discontinuation of AEDs under medical supervision. METHODS: A literature review yielded six retrospective clinical observations. RESULTS: After planned discontinuation of AEDs in patients rendered seizure free after epilepsy surgery, most often various forms of temporal lobe surgery, the mean percentage recurrence rate in adults in four studies was 33.8%[95% confidence interval (CI), 32.4-35.2%], with maximum follow-up ranging from 1 to 5 years. Seizure recurrence increased during the follow-up of 1 to 3 years and occurred within 3 years of AED discontinuation. In one study of children with temporal lobe epilepsy, the recurrence rate was 20%. More than 90% of adult patients with seizure recurrence regained seizure control with reinstitution of previous AED therapy. Seizure recurrence was unaffected by the duration of postoperative AED treatment; as a consequence, delaying discontinuation beyond 1 to 2 years of complete postoperative seizure control seems to have no added benefit. The occurrence of rare seizures or auras after surgery did not eliminate the possibility of eventual successful AED discontinuation. CONCLUSIONS: AED discontinuation is associated with a seizure recurrence in one in three patients rendered seizure free by epilepsy surgery. These results will be useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.     

Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse,a point mutation at the Pax-6-locus

Summary The mouse Small eye (Sey) locus is situated on chromosome 2. Molecular analyses have shown that Sey^Neu represents a point mutation leading to a splice site error and loss of the functional gene product. The Sey locus has been shown to be identical with the paired box (Pax)-6 gene, which contains paired-like and homcobox domains and is a developmental control gene. Pax-6 expression occurs in many parts of the central nervous system during embryogenesis. Therefore, we may expect the Sey mutation to result in abnormal development of the central nervous system. The present study shows that Pax-6 mutation has a bimodal effect upon neurogenesis in mouse: it causes a delay of premigratory neurons in a stage-, region-, and genedose-dependent manner. Additionally, Sey mutation impairs axonal growth and differentiation. Neurons of the cortical plate cease differentiation on approximately day 16 of gestation and appear to have increased cohesion: their cytoplasm is swollen and vacuolated. These changes coincide both with reduced formation of axons and with the onset of vacuolar degeneration in existing axons, glial cells and radial glial fibers. Consequently, there is an impairment of the peripheral migration of putative neurons so that the neonatal lesion pattern of the neocortical roof becomes dominated by a broad spectrum of neuronal migration disorders.Supported in part by a DAAD grant ARC for scientific cooperation between Germany and Great Britain     

The effect of antiepileptic drugs on coagulation and bleeding in the perioperative period of epilepsy surgery: The Cleveland Clinic experience

Antiepileptic drugs (AED) are known to cause coagulation disturbances. We retrospectively analyzed the effect of AED on coagulation parameters in children who underwent craniotomy for epilepsy surgery. A total of 84 children were included. Perioperative coagulation parameters, the number and type of AED, estimated blood loss and the amount of blood products transfused were recorded. The most commonly used AED was lamotrigine. Of all patients, 7.1% were taking valproate. None of the patients showed significantly abnormal prothrombin time, activated partial thromboplastin time, or platelet count preoperatively. Thirty-eight percent of patients were transfused with allogeneic red blood cells and 4.7% of all patients showed significant coagulopathy intraoperatively and postoperatively. We concluded that the number of AED does not appear to be associated with preoperative coagulation disorders or blood transfusion requirements. However, caution should be taken in patients taking AED who undergo complex brain epilepsy surgery due to the potential for significant blood loss.     

Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function

PURPOSE: To describe seizure control, complications, adaptive function and language skills following hemispheric surgery for epilepsy. METHODS: Retrospective chart review of patients who underwent hemispheric surgery from July 1993 to June 2004 with a minimum follow-up of 12 months. RESULTS: The study population comprised 24 children, median age at seizure onset six months and median age at surgery 41 months. Etiology included malformations of cortical development (7), infarction (7), Sturge-Weber Syndrome (6), and Rasmussen's encephalitis (4). The most frequent complication was intraoperative bleeding (17 transfused). Age <2 yr, weight <11 kg, and hemidecortication were risk factors for transfusion. Postoperative complications included aseptic meningitis (6), and hydrocephalus (3). At median follow-up of 7 yr, 79% of patients are seizure free. Children with malformations of cortical development and Rasmussen's encephalitis were more likely to have ongoing seizures. Overall adaptive function scores were low, but relative strengths in verbal abilities were observed. Shorter duration of epilepsy prior to surgery was related significantly to better adaptive functioning. CONCLUSIONS: Hemispheric surgery is an effective therapy for refractory epilepsy in children. The most common complication was bleeding. Duration of epilepsy prior to surgery is an important factor in determining adaptive outcome.     

Interictal EEG spikes identify the region of electrographic seizure onset in some,but not all,pediatric epilepsy patients

Purpose : The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial electroencephalography (IEEG). Although ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure‐onset location, although these studies were based upon relatively short EEG epochs. Methods : We employ a previously validated, computerized spike detector to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extratemporal lobe epilepsy. Approximately 8 h of IEEG, randomly selected 30‐min segments of continuous interictal IEEG per patient, were analyzed over all intracranial electrode contacts. Results : When spike frequency was averaged over the 16‐time segments, electrodes with the highest mean spike frequency were found to be within the seizure‐onset region in 11 of 19 patients. There was significant variability between individual 30‐min segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low‐voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure‐onset region. Conclusions : Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori.