Zonisamide: A Comprehensive, Updated Review for the Clinician.

Purpose of Review: Zonisamide (ZNS) was first approved in the United States in 2000 for the adjunctive treatment of patients aged 16 years or older with partial (focal) seizures. Although ZNS has been proven to treat multiple seizure types, it has been largely underutilized in US clinical practice. Recent Findings: Published literature demonstrated that antiseizure medications (ASMs) acting on Na+ and Ca2+ channels may add beneficial effects in many seizure types by reducing seizure frequency and leading to overall improvements. In addition, effects of ZNS may lead to clinical improvements in Parkinson disease, alcohol and sleep disorders, pain, and migraine. ZNS is available in multiple formulations and is a safe and effective, broad spectrum ASM. Summary: The purpose of this review was to provide an update to what is known about the efficacy of ZNS and where it shows benefits in the treatment of patients with epilepsy and other CNS disorders through its many unique mechanisms of action.

Proposed anti-seizure medication combinations with rufinamide in the treatment of Lennox-Gastaut syndrome: Narrative review and expert opinion.

Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5 Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such "rational polytherapy" involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors' clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS.

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown. METHODS: The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children's Hospital in Miami, Florida, are presented. Patients 15-22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA). RESULTS: In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort. CONCLUSIONS: This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms.

Sustained seizure freedom with adjunctive perampanel in patients with convulsive seizures: Post hoc analysis of open-label extension studies 307 and 332.

OBJECTIVE: Since increased mortality rates have been associated with convulsive seizures, it is important to achieve seizure control in these patients. Here, we report post hoc analyses to assess long-term seizure-freedom rates with adjunctive perampanel in patients (aged ≥ 12 years) with refractory focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who participated in open-label extension (OLEx) studies. METHODS: Patients with focal-onset seizures, with/without FBTCS, who completed double-blind, Phase III Studies 304, 305, or 306 could enter OLEx Study 307 (16-week blinded Conversion; 256-week Maintenance). Patients with GTCS who completed the double-blind phase of Study 332 could enter the OLEx Phase (6-week blinded Conversion; 136-week Maintenance). Maximum perampanel dose: 12 mg/day. Seizure-freedom rates for up to 24 months were assessed in perampanel-treated patients who achieved seizure freedom during the double-blind studies to determine if their seizure-free status was maintained during the OLEx. In addition, to ensure any patients who only achieved seizure freedom during the OLEx were captured, seizure-freedom rates were also assessed in all patients who achieved and maintained a seizure-free status for a period of at least six consecutive months at any time during the double-blind and/or OLEx studies; some of these patients may have received placebo during the double-blind study but only their time on perampanel is included in the seizure-free analysis. Univariate and multivariate analyses were used to identify predictive factors for achieving seizure freedom for at least 6 months. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 53.8% (n = 42/78) of patients who received perampanel and were FBTCS free during the double-blind studies remained seizure free for up to 24 months during Study 307, and 31.6% (n = 6/19) of patients who were GTCS free during the double-blind phase of Study 332 remained seizure free for up to 24 months during the OLEx Phase. Over 40% (FBTCS, 41.5% [n = 197/475]; GTCS, 52.9% [n = 73/138]) of patients were seizure free for a period of at least six consecutive months. Multivariate analysis showed that the best predictors of achieving seizure freedom from FBTCS for at least 6 months were lower baseline seizure frequency (p = 0.0014) and absence of enzyme-inducing anti-seizure medications at baseline (p = 0.0056); multivariate analysis was not conducted for GTCS since only one variable was identified as a significant predictor of seizure freedom in the univariate analysis (lower baseline seizure frequency). Perampanel was generally well tolerated with no new safety signals identified. The most common TEAE was dizziness. For both seizure types, 10% or fewer seizure-free patients discontinued perampanel due to TEAEs. CONCLUSIONS: These results suggest that adjunctive perampanel may be a suitable long-term treatment option for patients (aged ≥ 12 years) with convulsive seizures to achieve and maintain seizure freedom.

Influence of titration of antiseizure medications on treatment selection: Results of an online survey with clinicians in the United States.

INTRODUCTION: Most antiseizure medications (ASM) need to be titrated before the optimal dose is achieved. Titration can last several weeks to months. We assessed the impact titration schedules have on ASM treatment-related decisions in the United States (US). METHODS: An online survey was conducted with different healthcare providers (HCPs) in the US involved in the treatment and management of patients with epilepsy. The survey contained three sections: the first section with screening questions; the second on key factors that influence a HCP's decision-making when selecting treatments for different types of seizures and different treatment lines; and the third on the HCP's knowledge and perceptions regarding ASM titration for the treatment of patients with epilepsy. RESULTS: One-hundred and fifty HCPs (63% neurologists) completed the survey. Most HCPs considered titration schedule to be important, with only 1-3% of HCPs, depending on type of seizure, considering the titration schedule to be "not important at all" when prescribing therapy. Healthcare providers' acceptance of titration increased with shorter durations (≥50% accepted titration periods of ≤2 weeks), and lower number of tablets/capsules per dose (≥50% accepted ≤3 tablets/capsules per dose), doses (≥50% accepted ≤2 doses/day), and steps (≥50% accepted ≤3 steps/dose change). Most HCPs (68-91% depending on type of seizure) considered a titration duration of 6 or more weeks only somewhat acceptable or somewhat or highly unacceptable. Almost all HCPs selected "somewhat familiar", "familiar", or "very familiar" as the attribute that best defines their knowledge level of titration, with only 4% selecting "a little familiar". While 87% of HCPs agreed or strongly agreed that they could easily understand titration schedules, only 27% of them agreed or strongly agreed that patients could easily understand titration schedules and 58% of HCPs considered that adhering to the titration schedule was difficult for patients. Most HCPs agreed or strongly agreed that a complex or long titration schedule renders it difficult to achieve their treatment objectives. CONCLUSIONS: Healthcare providers take into account the duration and complexity of the titration period in their ASM prescribing decision-making and prefer shorter and simpler titration schedules, particularly for patients who are experiencing convulsive seizures and starting monotherapy. There was a clear difference between the HCP's belief in their own ability to understand a titration schedule, and their belief that the patient would be able to follow the titration schedule appropriately.

Uridine-responsive epileptic encephalopathy due to inherited variants in CAD: A Tale of Two Siblings.

We report two siblings with intractable epilepsy, developmental regression, and progressive cerebellar atrophy due to biallelic variants in the gene CAD. For the affected girl, uridine started at age 5 resulted in dramatic improvements in seizure control and development, cessation of cerebellar atrophy, and resolution of hematological abnormalities. Her older brother had a more severe course and only modest response to uridine started at 14 years old. Treatment of this progressive condition via uridine supplementation provides an example of precision diagnosis and treatment using clear outcome measures and biomarkers to monitor efficacy.

Early Implantation as a Main Predictor of Response to Vagus Nerve Stimulation in Childhood-Onset Refractory Epilepsy.

OBJECTIVE: We describe a multicenter experience with vagus nerve stimulator implantation in pediatric patients with drug-resistant epilepsy. Our goal was to assess vagus nerve stimulation efficacy and identify potential predictors of favorable outcome. METHODS: This is a retrospective study. Inclusion criteria: ≤18 years at time of vagus nerve stimulator implantation, at least 1 year of follow-up. All patients were previously found to be unsuitable for an excisional procedure. Favorable clinical outcome and effective vagus nerve stimulation therapy were defined as seizure reduction >50%. Outcome data were reviewed at 1, 2, 3, and 5 years after vagus nerve stimulator implantation. Fisher exact test and multiple logistic regression analysis were employed. RESULTS: Eighty-nine patients met inclusion criteria. Responder rate (seizure frequency reduction >50%) at 1-year follow-up was 25.8% (4.5% seizure-free). At last follow-up, 31.5% had a favorable outcome and 5.2% were seizure free. The only factor significantly predicting favorable outcome was time to vagus nerve stimulator implantation, with the best outcome achieved when vagus nerve stimulator implantation was performed within 3 years of seizure onset. Implantation between 3 and 5 years after epilepsy onset correlated with better long-term seizure freedom (13.3% at T5). Overall, 65.2% of patients evidenced improved quality of life at last follow-up. However, 12.4% had adverse events, but most were mild and disappeared after 3-4 months. CONCLUSIONS: Early vagus nerve stimulator implantation within 5 years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients. Improved quality of life and a low incidence of significant adverse events were observed.

Analysis of cutaneous allergic reactions in clinical trials of eslicarbazepine acetate.

OBJECTIVES: To evaluate cutaneous allergic reactions in clinical trials of adjunctive eslicarbazepine acetate (ESL) for focal seizures. MATERIALS AND METHODS: Data were analyzed from three phase III randomized, double-blind, placebo-controlled studies of adjunctive ESL in adults (placebo, n = 426; ESL, n = 1021) and two randomized, double-blind, placebo-controlled studies (and open-label extensions [OLEs]) of adjunctive ESL in children aged 4-17 years (placebo, n = 160; ESL, n = 202; OLE, n = 337). RESULTS: Adult studies: Rash (ESL 1.9%, placebo 0.9%) and pruritus (ESL 1.2%, placebo 0.9%) were the most frequent rash-related treatment-emergent adverse events (TEAEs). Most rash-related TEAEs were mild or moderate in severity. Incidence of rash increased with increasing ESL dose, but was not higher for patients who initiated treatment with higher ESL doses. Pediatric studies: Allergic dermatitis (ESL 3.0%, placebo 0) and rash (controlled studies: ESL 1.0%, placebo 1.3%; OLE periods: ESL ≤1.2%) were the most frequent rash-related TEAEs. There was one case of DRESS in the ESL group. Most rash-related TEAEs were mild or moderate in severity and judged as not related to treatment with ESL. CONCLUSIONS: Serious skin rashes were rare during adult and pediatric clinical trials of ESL. Although the incidence of rash with ESL was low, it is important for patients/caregivers to be made aware of the potential signs and symptoms associated with serious skin rashes.

Early Diagnosis and Treatment of Lennox-Gastaut Syndrome.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood-onset epilepsy associated with high morbidity and mortality. The peak period for manifestations of Lennox-Gastaut syndrome is between ages 3 and 5 years, a time of critical brain development and corresponding vulnerability to the electroclinical dysfunction arising from Lennox-Gastaut syndrome. Diagnosis is based on a triad of symptoms: multiple seizure types, cognitive impairment, and slow spike-and-wave pattern on electroencephalography. In practice, Lennox-Gastaut syndrome presentation is diverse, and there may be a delay between initial symptoms and emergence of the full triad of clinical features. Additionally, differential diagnosis is complicated by the resemblance of Lennox-Gastaut syndrome to other forms of epilepsy and by the need for varied diagnostic techniques requiring specific clinical skills. Because diagnosis is complex and early intervention may lead to improved outcomes, clinicians should consider treatment when Lennox-Gastaut syndrome symptoms are present, even in the absence of a formal diagnosis.

Medically resistant pediatric insular-opercular/perisylvian epilepsy. Part 2: outcome following resective surgery.

OBJECTIVE Seizure onset in the insular cortex as a cause of refractory epilepsy is underrepresented in the pediatric population, possibly due to difficulties localizing seizure onset in deep anatomical structures and limited surgical access to the insula, a complex anatomical structure with a rich overlying vascular network. Insular seizure semiology may mimic frontal, temporal, or parietal lobe semiology, resulting in false localization, incomplete resection, and poor outcome. METHODS The authors retrospectively reviewed the records of all pediatric patients who underwent insular cortical resections for intractable epilepsy at Miami Children's Hospital from 2009 to 2015. Presurgical evaluation included video electroencephalography monitoring and anatomical/functional neuroimaging. All patients underwent excisional procedures utilizing intraoperative electrocorticography or extraoperative subdural/depth electrode recording. RESULTS Thirteen children (age range 6 months-16 years) with intractable focal epilepsy underwent insular-opercular resection. Seven children described symptoms that were suggestive of insular seizure origin. Discharges on scalp EEG revealed wide fields. Four patients were MRI negative (i.e., there were no insular or brain abnormalities on MRI), 4 demonstrated insular signal abnormalities, and 5 had extrainsular abnormalities. Ten patients had insular involvement on PET/SPECT. All patients underwent invasive investigation with insular sampling; in 2 patients resection was based on intraoperative electrocorticography, whereas 11 underwent surgery after invasive EEG monitoring with extraoperative monitoring. Four patients required an extended insular resection after a failed initial surgery. Postoperatively, 2 patients had transient hemiplegia. No patients had new permanent neurological deficits. At the most recent follow-up (mean 43.8 months), 9 (69%) children were seizure free and 1 had greater than 90% seizure reduction. CONCLUSIONS Primary insular seizure origin should be considered in children with treatment-resistant focal seizures that are believed to arise within the perisylvian region based on semiology, widespread electrical field on scalp EEG, or insular abnormality on anatomical/functional neuroimaging. There is a reasonable chance of seizure freedom in this group of patients, and the surgical risks are low.

The diagnostic utility of 3D-ESI rotating and moving dipole methodology in the pre-surgical evaluation of MRI-negative childhood epilepsy due to focal cortical dysplasia.

OBJECTIVE: This study investigates whether a combined rotating dipole (RD) and moving dipole (MD) solution enhances three-dimensional electroencephalography (EEG) source imaging (3D-ESI) localization in magnetic resonance imaging (MRI)-negative pediatric patients with focal cortical dysplasia (FCD). METHODS: We retrospectively selected 14 MRI-negative patients with FCD from a cohort of 60 pediatric patients previously used to evaluate the diagnostic utility of 3D-ESI in epilepsy surgery. Patients were younger than 18 years at time of surgery and had at least 1 year of outcome data. RD and MD models were constructed for each interictal spike or sharp wave, and it was determined whether each inverse algorithm localized within the surgical resection cavity (SRC). We also compared the 3D-ESI findings and surgical outcome with positron emission tomography (PET) and ictal single photon emission computed tomography (iSPECT). RESULTS: RD analyses revealed a high concordance with the SRC (78.6%), particularly for temporal lobe resection (100.0%), and showed superior localization compared to PET and iSPECT, with the highest correlation in FCD type I and temporal lobe resection. Furthermore, the RD method was superior to iSPECT in FCD type II cases and to PET in extratemporal resections. RD and MD results were comparable, but in 18.2% of patients with FCD type I with localizing RDs, the MD solution was only partially within the SRC; in all of these patients 3D-ESI also correlated with superior surgical outcome compared to PET and iSPECT, especially when RD and MD solutions were analyzed together. SIGNIFICANCE: 3D-ESI in MRI-negative cases showed superior localization compared to iSPECT or PET, especially in FCD type I and temporal lobe epilepsy, and correlated with superior surgical outcome compared to iSPECT and PET at 1 year and 2 years postoperatively, especially when RD and MD solutions were analyzed together. These findings suggest that 3D-ESI based on a combined RD-MD solution improves surgical accuracy in MRI-negative patients with FCD.

Challenges in identifying Lennox-Gastaut syndrome in adults: A case series illustrating its changing nature.

The variable presentation and progression of Lennox-Gastaut syndrome (LGS) can make it difficult to recognize, particularly in adults. To improve diagnosis, a retrospective chart review was conducted on patients who were diagnosed as adults and/or were followed for several years after diagnosis. We present 5 cases that illustrate changes in LGS features over time. Cases 1 and 2 were diagnosed by age 8 with intractable seizures, developmental delay, and abnormal EEGs with 1.5-2 Hz SSW discharges. However, seizure type and frequency changed over time for both patients, and the incidence of SSW discharges decreased. Cases 3, 4, and 5 were diagnosed with LGS as adults based on current and past features and symptoms, including treatment-resistant seizures, cognitive and motor impairment, and abnormal EEG findings. While incomplete, their records indicate that an earlier LGS diagnosis may have been missed or lost to history. These cases demonstrate the need to thoroughly and continuously evaluate all aspects of a patient's encephalopathy, bearing in mind the potential for LGS features to change over time.

The diagnostic utility of 3D electroencephalography source imaging in pediatric epilepsy surgery.

OBJECTIVE: The aim of this study was to investigate the utility of three-dimensional electroencephalography source imaging (3D-ESI) with low-resolution electroencephalographic data in the pediatric noninvasive presurgical evaluation, and to compare the findings with positron emission tomography (PET) and ictal single-photon emission computed tomography (iSPECT). METHODS: We retrospectively selected 60 patients from a database of 594 patients who underwent excisional surgery for drug-resistant epilepsy. Patients were <18 years at time of surgery, had at least one presurgical volumetric brain magnetic resonance imaging (MRI), and at least 1 year of outcome data. 3D-ESI was performed with NeuroScan software CURRY V.7.0. For each patient the surgical resection was planned utilizing 3D-ESI as an adjunctive tool to supplement MRI and electrocorticographic data. Our analyses addressed three critical variables: pathology (focal cortical dysplasia vs. other pathologies), imaging (MRI negative vs. positive cases), and surgery (temporal resection vs. extratemporal and multilobar resections). We also compared the localizing utility and surgical outcome of 3D-ESI findings with PET, iSPECT, and the colocalized surgical resection. Statistical analyses were performed using the Statistical Package for the Social Sciences, Version 20. RESULTS: Mean age at surgery was 11.18 years (range 1-18 years). 3D-ESI showed a strong correlation with the surgical resection cavity (65.0%), particularly within the temporal lobe. 3D-ESI demonstrated better localization in MRI-negative cases (78.6%), which was not statistically significant. 3D-ESI also correlated with a superior surgical outcome profile compared to PET and iSPECT. SIGNIFICANCE: Our findings demonstrate that 3D-ESI data obtained with low-resolution electroencephalography achieves reasonably accurate noninvasive localization of epileptic spikes in pediatric focal epilepsy, especially in temporal lobe and MRI-negative cases, and is comparable to iSPECT and PET. Given its lesser expense and lack of radiation exposure, 3D-ESI is a useful and efficient tool for evaluating surgical candidacy in pediatric epilepsy surgery centers, particularly if PET and iSPECT are unavailable.

Minimally resective epilepsy surgery in MRI-negative children.

AIM: Performing epilepsy surgery on children with non-lesional brain MRI often results in large lobar or multilobar resections. The aim of this study was to determine if smaller resections result in a comparable rate of seizure freedom. METHODS: We reviewed 25 children who had undergone focal corticectomies restricted to one aspect of a single lobe or the insula at our institution within a 5.5-year period. Data collected in the comprehensive non-invasive pre-surgical evaluation (including scalp video-EEG, volumetric MRI, functional MRI, EEG source localization, and SPECT and PET), as well as from invasive recordings performed in each patient, was reviewed. Data from each functional modality was identified as convergent or divergent with the epileptogenic zone using image coregistration. Specific biomarkers (from extra-operative and invasive testing) previously indicated to be indicative of focal epileptogenicity were used to further tailor each resection to an epileptogenic epicentre. Tissue pathology and postoperative outcomes were obtained from all 25 patients. RESULTS: Two years postoperatively, 15/25 (60%) children were seizure-free, three (12%) experienced >90% reduction in seizure frequency, two (8%) had a 50-90% reduction in seizure frequency, and the remaining five (20%) had no change in seizure burden. There was no significant difference in outcome based on numerous pre- and postoperative factors including location of resection, the number of preoperative functional tests providing convergent data, and tissue pathology. CONCLUSION: In MRI-negative children with focal epilepsy, an epileptogenic epicentre within a larger epileptogenic zone can be identified when specific biomarkers are recognized on non-invasive and invasive testing. When such children undergo resection of a small, well-defined epileptogenic epicentre, favourable outcomes can be achieved.

The diagnostic utility of intracranial EEG monitoring for epilepsy surgery in children.

OBJECTIVE: There are limited data on the indications for the use of chronic invasive electroencephalography (EEG) monitoring (IEM) for pediatric epilepsy surgery. METHODS: We retrospectively studied 102 children who underwent intracranial monitoring to map critical cortex, localize the epileptogenic region, or resolve divergent findings. We assessed IEM utility based on changes to the resection plan following analysis of noninvasive data. RESULTS: IEM was judged useful in 87% of cases and had greatest utility for resolving discordant data and localizing extratemporal and multilobar epileptogenic zones. IEM data were least useful for seizure onset in the temporal lobe and had little utility for direct cortical stimulation mapping unless functional magnetic resonance imaging (fMRI) revealed atypical language representation or the epileptogenic zone was in proximity to critical cortex. SIGNIFICANCE: IEM utility was demonstrated for a majority of cases with well-defined indications. The method of assessing utility will facilitate multicentric studies toward developing future consensus and practice guidelines.

The consequences of refractory epilepsy and its treatment.

Seizures in some 30% to 40% of patients with epilepsy fail to respond to antiepileptic drugs or other treatments. While much has been made of the risks of new drug therapies, not enough attention has been given to the risks of uncontrolled and progressive epilepsy. This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research. Eight international epilepsy experts from Europe, the United States, and South America met on May 4, 2013, to present, review, and discuss relevant concepts, data, and literature on the consequences of refractory epilepsy. While patients with refractory epilepsy represent the minority of the population with epilepsy, they require the overwhelming majority of time, effort, and focus from treating physicians. They also represent the greatest economic and psychosocial burdens. Diagnostic procedures and medical/surgical treatments are not without risks. Overlooked, however, is that these risks are usually smaller than the risks of long-term, uncontrolled seizures. Refractory epilepsy may be progressive, carrying risks of structural damage to the brain and nervous system, comorbidities (osteoporosis, fractures), and increased mortality (from suicide, accidents, sudden unexpected death in epilepsy, pneumonia, vascular disease), as well as psychological (depression, anxiety), educational, social (stigma, driving), and vocational consequences. Adding to this burden is neuropsychiatric impairment caused by underlying epileptogenic processes ("essential comorbidities"), which appears to be independent of the effects of ongoing seizures themselves. Tolerating persistent seizures or chronic medicinal adverse effects has risks and consequences that often outweigh risks of seemingly "more aggressive" treatments. Future research should focus not only on controlling seizures but also on preventing these consequences.

Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia.

AIMS: To identify variables that influence the extent of ictal single-photon emission computed tomography (SPECT) findings in paediatric patients with focal cortical dysplasia (FCD). METHODS: We visually evaluated 98 ictal SPECT studies from 67 children treated surgically for intractable epilepsy caused by FCD. SPECT findings were classified as "non-localised", "well-localised", and "extensive" and compared with parameters of injected seizures (seizure type and duration, injection time, and scalp EEG ictal pattern), presence of structural pathology on MRI, type of surgery performed after SPECT study, and histological findings. RESULTS: A shorter injection time and duration of injected seizure was associated with more localised SPECT hyperperfusion. SPECT findings were not significantly influenced by type of injected seizure. Widespread ictal scalp EEG patterns were associated with extensive SPECT findings. Larger zones of hyperperfusion were more common in patients with lesional MRI and patients undergoing multilobar resections. SPECT studies demonstrating good localisation were more common in patients with mild malformations of cortical development. CONCLUSION: Early ictal SPECT radiotracer injection is crucial for successful localisation of the epileptogenic zone. Seizure duration, type of scalp EEG findings, and presence of structural pathology on MRI may influence the extent of ictal SPECT hyperperfusion, which was associated with certain types of epilepsy surgery as well as histopathological findings.

Predictors of seizure-free outcome after epilepsy surgery for pediatric tuberous sclerosis complex.

PURPOSE: Variable predictors of postsurgical seizure outcome have been reported in children with tuberous sclerosis complex (TSC). We analyzed a large surgical series of pediatric TSC patients in order to identify prognostic factors crucial for selection of subjects for epilepsy surgery. METHODS: Thirty-three children with TSC who underwent excisional epilepsy surgery at Miami Children's Hospital were retrospectively reviewed. A total of 29 clinical, neuropsychological, electroencephalography (EEG), magnetic resonance imaging (MRI), and surgical variables were analyzed and related to seizure outcomes. Univariate Barnard's exact test, Wilcoxon's rank-sum test, and multivariate statistical Cox's model were used to examine the significance of associations between the variables and seizure outcome. KEY FINDINGS: Eighteen patients (55%) have been seizure-free 2 years after (final) surgery; postoperative complications occurred in five subjects (15%). Complete removal of epileptogenic tissue detected by both MRI and intracranial EEG, regional scalp interictal EEG patterns, and agreement of interictal and ictal EEG localization were the most powerful predictors of seizure-free outcome. Other significant predictors included occurrence of regional scalp ictal EEG patterns, fewer brain regions affected by tubers, presence of preoperative hemiparesis, and one-stage surgery. Remaining factors such as age at seizure onset, incidence of infantile spasms or other seizure types, duration of epilepsy, seizure frequency, mental retardation, as well as types and extent of resections did not influence outcome. SIGNIFICANCE: Perioperative features rather than preoperative variables are the most important determinants of postsurgical seizure outcome in patients with TSC. Our findings may assist in the surgical management of these patients.

Localizing value of ictal SPECT is comparable to MRI and EEG in children with focal cortical dysplasia.

PURPOSE: To assess the predictive value of ictal single-photon emission computed tomography (SPECT) for outcome after excisional epilepsy surgery in a large population of children with focal cortical dysplasia (FCD). METHODS: One hundred seventy-three ictal SPECT studies in 106 children with histologically proven FCD were retrospectively analyzed. The extent and location of ictal hyperperfusion and completeness of surgical removal were assessed. Completeness of resection of epileptogenic regions defined by ictal SPECT, electroencephalography (EEG), and magnetic resonance imaging (MRI) were compared and correlated with postoperative seizure outcome. In addition, subcortical activation of the cerebellum, basal ganglia, and thalamus were analyzed. KEY FINDINGS: The extent of hyperperfusion was focal or lobar in 58%, whereas multilobar activations occurred in only 32%; hemispheric or bilateral findings were rare. Favorable postsurgical seizure outcome was achieved in 67% patients with nonlocalized SPECT findings, 45% with nonresected ictal hyperperfusion, 36% with partially resected ictal hyperperfusion, and 86% when the zone of ictal hyperperfusion was completely resected (p = 0.000198). The favorable postsurgical outcome after complete removal of the SPECT hyperperfusion zone surpassed the 75% rate of seizure freedom in patients with removal of MRI/EEG-defined epileptogenic region. A similar predictive value of ictal SPECT for seizure outcome was found in nonoperated patients and subjects who were undergoing reoperation. Subcortical activation conferred no predictive value. SIGNIFICANCE: Ictal SPECT helps to define the epileptogenic zone in a high proportion of children with FCD undergoing surgical evaluation. Complete removal of both SPECT and MRI/EEG-defined regions is a strong predictor of surgical success and has important implications for surgical planning.