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Purpose: Lack of a potentially epileptogenic lesion on brain magnetic resonance imaging (MRI) is a poor prognostic marker for epilepsy surgery. We present a single-center series of childhood-onset MRI-negative drug-resistant epilepsy (DRE) and analyze surgical outcomes and predictors.Methods: Children with MRI-negative DRE who had resective surgery from January 2007 to December 2013 were identified using an institutional database. Relevant clinical, neurophysiological, imaging, and surgical data was extracted. The primary outcome measure was seizure freedom. Predictors of seizure freedom were obtained using multivariate logistic regression.Results: Out of 47 children with MRI-negative DRE, 12 (25.5%) were seizure free (International League Against Epilepsy [ILAE] outcome class I), after mean follow-up of 2.75 (±1.72) years. Seizure-free proportion was significantly higher in patients with single seizure semiology and concordant ictal EEG (50.0% vs. 15.2%, p=0.025). Multivariate analysis using only non-invasive pre-surgical data showed that children with daily seizures (OR 0.02, 95% CI<0.001-0.55), and earlier onset of seizures (OR 0.72, 95% CI 0.52-0.99) were less likely to be seizure-free. Also, each additional anti-epileptic drug (AED) tried before surgery decreased the probability of seizure-free outcome (OR 0.16, 95% CI 0.04-0.63). Repeat multivariate analysis after including surgical variables found no additional significant predictors of seizure-freedom. Cortical dysplasia (ILAE type IB) was the commonest histopathology.Conclusion: Surgical outcomes in children with MRI-negative DRE are determined by clinical factors including seizure frequency, age of onset of seizures, and number of failed AEDs. [ABSTRACT FROM AUTHOR]

Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean ± SD 13.4 ± 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in “match” and “mismatch” conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the “match” condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy. [ABSTRACT FROM AUTHOR]

Objectives Magnetoencephalography ( MEG) is used to guide intracranial electroencephalography ( ICEEG) monitoring and determine areas for resection. The purpose of this retrospective cross-sectional study was to report our experience using dipole modeling/dipole scanning, current density reconstructions, and beam-forming methods in a large cohort of pediatric patients with intractable epilepsy. Methods Source localization results for each algorithm and seizure-onset zone, defined by ICEEG, were described by three blinded reviewers according to five location criteria. The accuracy of each algorithm was then compared to ICEEG. The relationships between the accuracy of these algorithms (discordant, lobar concordant, sublobar concordant) and long-term seizure outcome was calculated using positive and negative predictive values. Results Thirty-two patients (mean age ± SD, 10.8 ± 5 years) were included in this retrospective review. No algorithms had sublobar concordance with ICEEG in all patients, including when algorithms were grouped by type (dipole modeling/dipole scanning, current density reconstruction, beam forming). Synthetic aperture magnetometry ( SAM) with excess kurtosis tended to be the most accurate, but there were no significant differences between algorithms. When comparing the source modeling with ICEEG findings, significantly more patients with a seizure-free outcome were found to have lobar or sublobar concordance of multiple signal classification ( MUSIC) (61.1%) and standardized low resolution brain electromagnetic tomography (s LORETA) (52.9%). Positive predictive values were highest for MUSIC (61.9%) and equivalent current dipole ( ECD) (57.1%). Negative predictive values were highest for SAM( g2)- VS (83%), minimum norm estimate ( MNE) (75%), MUSIC (73.7%), and ECD (73.5%). Significance This study describes the use of multiple MEG source estimation techniques and demonstrates that all algorithms have similar rates of concordance with ICEEG. Also, the concordance or discordance of MUSIC with ICEEG was the best predictor of long-term seizure outcome. [ABSTRACT FROM AUTHOR]

Purpose: Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure-onset zone is near eloquent cortex. Determining the seizure-onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High-frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown. Methods: We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG. Key Findings: Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%). Significance: Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome. [ABSTRACT FROM AUTHOR]

Highlights • Resection of HGM language sites is associated with worse neuropsychological outcomes. • Working memory was significantly worse in patients with resection of HGM naming sites. • Neuropsychological evaluation of children with epilepsy should include multiple cognitive and language domains. Abstract Background Language mapping with high-gamma modulation (HGM) has compared well with electrical cortical stimulation mapping (ESM). However, there is limited prospective data about its functional validity. We compared changes in neuropsychological evaluation (NPE) performed before and 1-year after epilepsy surgery, between patients with/without resection of cortical sites showing HGM during a visual naming task. Methods Pediatric drug-resistant epilepsy (DRE) patients underwent pre-surgical language localization with ESM and HGM using a visual naming task. Surgical decisions were based solely on ESM results. NPE difference scores were compared between patients with/without resection of HGM naming sites using principal component (PC) analysis. Follow-up NPE scores were modeled with resection group as main effect and respective pre-surgical score as a covariate, using analysis of covariance. Results Seventeen native English speakers (12 females), aged 6.5–20.2 years, were included. One year after epilepsy surgery, first PC score increased by (mean ± standard deviation) 14.4 ± 16.5 points in patients without resection, whereas it decreased by 7.6 ± 24.6 points in those with resection of HGM naming sites (p = 0.040). This PC score represented verbal comprehension, working memory, perceptual reasoning (Wechsler subscales); Woodcock-Johnson Tests of Achievement; and Peabody Picture Vocabulary Test. Subsequent analysis showed significant difference in working memory score between patients with/without resection of HGM naming sites (−15.2 points, 95% confidence limits −29.7 to −0.7, p = 0.041). Conclusion We highlight the functional consequences of resecting HGM language sites, and suggest that NPE of DRE patients should include comprehensive assessment of multiple linguistic and cognitive domains besides naming ability. [ABSTRACT FROM AUTHOR]

Resective epilepsy surgery can improve seizures when the epileptogenic zone (EZ) is limited to a well-defined region. High frequency oscillations (HFO) have been recognized as having a high association with the seizure onset zone. Therefore, we retrospectively identified ictal HFOs and determined their relationship to specific intracranial features of cortical tubers in children with TSC who underwent resective surgery. We identified 14 patients with drug resistant epilepsy secondary to TSC who underwent subdural grid and strip implantation for presurgical evaluation and subsequent resection with adequate post-surgical follow-up. We aimed to determine the relationship between ictal HFOs, post-resection outcome and neuroimaging features in this population. The largest tuber was identified in all 14 patients (100%). Four patients (29%) had unusual tubers. HFOs were observed at ictal onset in all 14 patients. Seven of 10 patients with complete resection of HFOs were seizure free. The better seizure outcome (ILAE = 1–3) was achieved with complete HFO resection regardless of the unique TSC structural features (p = 0.0140). Our study demonstrates the presence of ripple and fast ripple range HFOs at ictal onset in children with TSC. Our study showed that complete HFO resection led to the better surgical outcome, independent of MR imaging findings. [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]

Summary: Purpose: Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Methods: We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600Hz and 4000Hz for 10 and 2min respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Key findings: Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. Significance: Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy. [Copyright &y& Elsevier]

Abstract: Background and Purpose: The widespread propagation of synchronized neuronal firing in seizure disorders may affect cortical and subcortical brain regions. Diffusion tensor imaging (DTI) can noninvasively quantify white matter integrity. The purpose of this study was to investigate the abnormal changes of white matter in children and adolescents with focal temporal lobe epilepsy (TLE) using DTI. Materials and Methods: Eight patients with clinically diagnosed TLE and eight age- and sex-matched healthy controls were studied. DTI images were obtained with a 3-T magnetic resonance imaging scanner. The epileptic foci were localized with magnetoencephalography. Fractional anisotropy (FA), mean diffusivity (MD), parallel (λ||) and perpendicular (λ⊥) diffusivities in the genu of the corpus callosum, splenium of the corpus callosum (SCC), external capsule (EC), anterior limbs of the internal capsule (AIC), and the posterior limbs of the internal capsule (PIC) were calculated. The DTI parameters between patients and controls were statistically compared. Correlations of these DTI parameters of each selected structure with age of seizure onset and duration of epilepsy were analysed. Results: In comparison to controls, both patients'' seizure ipsilateral and contralateral had significantly lower FA in the AIC; PIC and SCC and higher MD, λ|| and λ⊥ in the EC, AIC, PIC and SCC. The MD, λ|| and λ⊥ were significantly correlated with age of seizure onset in the EC and PIC. λ|| was significantly correlated with the duration of epilepsy in the EC and PIC. Conclusion: The results of the present study indicate that children and adolescents with TLE had significant abnormalities in the white matter in the hemisphere with seizure foci. Furthermore, these abnormalities may extend to the other brain hemisphere. The age of seizure onset and duration of epilepsy may be important factors in determining the extent of influence of children and adolescents TLE on white matter. [Copyright &y& Elsevier]

Summary: Purpose: We aimed to determine the changes in neural correlates of auditory information processing such as auditory detection, encoding, and sensory discrimination in pediatric patients with intractable epilepsy. Methods: In this magnetoencephalography (MEG) study, 10 patients and 10 age- and gender-matched healthy controls were investigated with the multi-feature mismatch negativity (MMN) paradigm. Latencies and amplitudes of M100, M150, M200, and MMN event-related fields were evaluated. Results: All event-related fields in response to standard stimuli (M100, M150 and M200) and responses to occasional five deviant sounds, deviating from the standard stimuli either in duration, frequency, intensity, location, or by including a silent gap were reduced in amplitude in epilepsy patients compared with healthy controls. Conclusions: Our study suggests that auditory information processing is impaired in patients with drug-resistant epilepsy, being evident both in stimulus feature encoding (as reflected by changes of early event-related components, e.g., M100) and in cortical sound discrimination (as reflected by MMNm). The neural changes involving diminished M100 as well as MMNms for all five deviant sound types suggest wide-spread auditory information processing impairments in these patients. [ABSTRACT FROM AUTHOR]