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Objective: To evaluate the outcome, including drug-resistant epilepsy (DRE) in children with newly diagnosed partial onset epilepsy treated with carbamazepine (CBZ).Methods: A retrospective medical records review and telephone questionnaire were undertaken on a total of 100 subjects.Results: Long-term follow-up was obtained on 79 children with a mean duration of 7.1 years from CBZ initiation. A total of 66 (83.5%) subjects achieved 2-year seizure remission, 48 (72.7%) subjects did so with CBZ monotherapy. Seven (10.6%) had seizure recurrence after 2-year seizure remission. DRE was diagnosed in seven (8.9%) subjects and five subjects had epilepsy surgery. The mean duration from seizure onset to epilepsy surgery was 5.3 (±2.1) years. Contributing factors for the prolonged duration from seizure onset to epilepsy surgery were identified including: relapsing–remitting course of seizure, family reluctance for epilepsy surgery and uncontrolled psychological problems.Conclusions: Over 80% of children with newly diagnosed partial onset epilepsy who were initially treated with CBZ achieved 2-year seizure remission, and more than 70% of this group did so with CBZ monotherapy. The majority of these patients maintained seizure remission overtime. However, 8.9% of this population met the criteria for DRE and most of them had epilepsy surgery. The duration from seizure onset to epilepsy surgery is an important potential area for improvement in DRE patient care. [ABSTRACT FROM PUBLISHER]

Abstract: The role of neuronal voltage-gated sodium channel, α-1 subunit (SCN1A) gene mutations in Dravet syndrome is well-established. With a broader phenotype than initially described, some patients lack features of Dravet syndrome as defined by the International League Against Epilepsy. We evaluated the predictive value of International League Against Epilepsy criteria for a positive mutation in a cohort of consecutively tested children. Mutations of SCN1A were evident in 16 of 69 children. Exhibiting ≥4 International League Against Epilepsy criteria demonstrated 100% sensitivity. Seven criteria (resistance to multiple antiepileptic drugs, multiple seizure types, abnormal electroencephalogram features, exacerbation with hyperthermia, normal development before seizure onset, seizures beginning before age 1 year, and psychomotor retardation) were present in ≥85% of mutation-positive cases. The three criteria that best predicted a mutation in SCN1A included exacerbation with hyperthermia, normal development before seizure onset, and the appearance of ataxia, pyramidal signs, or interictal myoclonus. We have demonstrated a high-sensitivity testing strategy for detecting mutations of SCN1A in children with suspected Dravet syndrome. [Copyright &y& Elsevier]

Abstract: Few randomized, controlled trials evaluating antiepileptic drug (AED) efficacy and tolerability have focused solely on patients with juvenile myoclonic epilepsy (JME). We conducted a pilot, randomized controlled trial comparing topiramate (N =19) and valproate (N =9) in adolescents/adults with JME to evaluate clinical response when these broad-spectrum agents are titrated to optimal effect. Rating scales were used to systematically assess tolerability. Among patients completing 26 weeks of treatment, 8 of 12 (67%) in the topiramate group and 4 of 7 (57%) in the valproate group were seizure-free during the 12-week maintenance period. Median daily dose was 250mg topiramate or 750mg valproate. Two (11%) topiramate-treated patients and one (11%) valproate-treated patient discontinued due to adverse events. Systemic toxicity scores, but not neurotoxicity scores, differed substantially between the two groups; greater systemic toxicity was associated with valproate. Our preliminary findings that topiramate may be an effective, well-tolerated alternative to valproate warrant validation in a double-blind trial. [Copyright &y& Elsevier]

Background: Neurosurgical resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex. An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex. Methods: Patients 3 years of age or older with serial growth of subependymal giant-cell astrocytomas were eligible for this open-label study. The primary efficacy end point was the change in volume of subependymal giant-cell astrocytomas between baseline and 6 months. We gave everolimus orally, at a dose of 3.0 mg per square meter of body-surface area, to achieve a trough concentration of 5 to 15 ng per milliliter. Results: We enrolled 28 patients. Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). Marked reductions were seen within 3 months and were sustained. There were no new lesions, worsening hydrocephalus, evidence of increased intracranial pressure, or necessity for surgical resection or other therapy for subependymal giant-cell astrocytoma. Of the 16 patients for whom 24-hour video electroencephalography data were available, seizure frequency for the 6-month study period (vs. the previous 6-month period) decreased in 9, did not change in 6, and increased in 1 (median change, −1 seizure; P=0.02). The mean (±SD) score on the validated Quality-of-Life in Childhood Epilepsy questionnaire (on which scores can range from 0 to 100, with higher scores indicating a better quality of life) was improved at 3 months (63.4±12.4) and 6 months (62.1±14.2) over the baseline score (57.8±14.0). Single cases of grade 3 treatment-related sinusitis, pneumonia, viral bronchitis, tooth infection, stomatitis, and leukopenia were reported. Conclusions: Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed. (Funded by Novartis; ClinicalTrials.gov number, NCT00411619.) N Engl J Med 2010;363:1801-11. [ABSTRACT FROM AUTHOR]

Purpose We studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM). Methods As individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who received and did not receive FOS were compared for the incidence and thresholds of ADs, seizures, and functional responses. Results Before ESM, 40 and 82 patients respectively were pre-medicated/not pre-medicated with FOS. The incidence of ESM-induced seizures was significantly lower in FOS pre-medicated patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM-induced seizures in patients with symptomatogenic zone ipsilateral to the side of ESM. Although FOS dose had no significant effect on minimum language, minimum motor, or AD thresholds; seizure and temporal language thresholds showed trends approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM-induced seizures was significantly lower in those who received FOS at a dose of ≤12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p = 0.046), while the temporal language thresholds were not significantly different (6.3 vs. 6.5 mA, p = 0.897). Conclusions This study provides class III evidence that FOS pre-medication before ESM decreases the incidence of ESM-induced seizures, but increases temporal language threshold. FOS pre-medication may thus be considered before ESM. Future studies should prospectively verify these observations and characterize dose-response relationships. [ABSTRACT FROM AUTHOR]

Purpose There is wide variation in clinical practice regarding the role of electrocorticography immediately after resection (post-resection ECoG) for pediatric epilepsy surgery. Results can guide further resection of potentially epileptogenic tissue. We hypothesized that post-resection ECoG spiking represents a biomarker of the epileptogenic zone and predicts seizure outcome in children undergoing epilepsy surgery. Methods We retrospectively identified 124 children with post-resection ECoG performed on the margins of resection. ECoG records were scored in a blinded fashion based on presence of frequent spiking. For patients identified as having additional resection based on clinical post-resection ECoG interpretation, these “second-look” ECoG results were re-reviewed for ongoing discharges or completeness of resection. Frequent spike populations were grouped using a standard scoring system into three ranges: 0.1–0.5 Hz, 0.5–1 Hz, >1 Hz. Seizure outcomes were determined at minimum 12-month followup. Results Of 124 patients who met inclusion criteria, 60 (48%) had an identified spike population on post-resection ECoG. Thirty (50%) of these had further resection based on clinical interpretation. Overall, good outcome (ILAE 1) was seen in 56/124 (45%). Completeness of resection of spiking (absence of spiking on initial post-resection ECoG or resolution of spiking after further resection) showed a trend toward good outcome (OR 2.03, p = 0.099). Patients with completeness of resection had good outcome in 41/80 (51%) of cases; patients with continued spikes had good outcome in 15/44 (35%) of cases. Conclusions Post-resection ECoG identifies residual epileptogenic tissue in a significant number of children. Lower frequency or absence of discharges on initial recording showed a trend toward good outcome. Completeness of resection demonstrated on final ECoG recording did not show a significant difference in outcome. This suggests that post-resection discharges represent a prognostic marker rather than a remediable biomarker of the epileptogenic zone in all patients. Resecting residual spike-generating cortex may be beneficial in selected patients, including children with tumors. [ABSTRACT FROM AUTHOR]