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.

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.

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.

Identification of Negative BOLD Responses in Epilepsy Using Windkessel Models.

Alongside positive blood oxygenation level-dependent (BOLD) responses associated with interictal epileptic discharges, a variety of negative BOLD responses (NBRs) are typically found in epileptic patients. Previous studies suggest that, in general, up to four mechanisms might underlie the genesis of NBRs in the brain: (i) neuronal disruption of network activity, (ii) altered balance of neurometabolic/vascular couplings, (iii) arterial blood stealing, and (iv) enhanced cortical inhibition. Detecting and classifying these mechanisms from BOLD signals are pivotal for the improvement of the specificity of the electroencephalography-functional magnetic resonance imaging (EEG-fMRI) image modality to identify the seizure-onset zones in refractory local epilepsy. This requires models with physiological interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a Windkessel model with viscoelastic compliance/inductance in combination with dynamic models of both neuronal population activity and tissue/blood O2 to classify the hemodynamic response functions (HRFs) linked to the above mechanisms in the irritative zones of epileptic patients. First, we evaluated the most relevant imprints on the BOLD response caused by variations of key model parameters. Second, we demonstrated that a general linear model is enough to accurately represent the four different types of NBRs. Third, we tested the ability of a machine learning classifier, built from a simulated ensemble of HRFs, to predict the mechanism underlying the BOLD signal from irritative zones. Cross-validation indicates that these four mechanisms can be classified from realistic fMRI BOLD signals. To demonstrate proof of concept, we applied our methodology to EEG-fMRI data from five epileptic patients undergoing neurosurgery, suggesting the presence of some of these mechanisms. We concluded that a proper identification and interpretation of NBR mechanisms in epilepsy can be performed by combining general linear models and biophysically inspired models.

Low-grade focal cortical dysplasia is associated with prenatal and perinatal brain injury.

PURPOSE: Prenatal and perinatal adverse events are reported to have a pathogenetic role in focal cortical dysplasia (FCD). However, no data are available regarding the prevalence and significance of this association. A cohort of children with significant prenatal and perinatal brain injury and histologically proven mild malformations of cortical development (mMCD) or FCD was analyzed. METHODS: We retrospectively evaluated a surgical series of 200 patients with histologically confirmed mMCD/FCD. Combined historical and radiologic inclusion criteria were used to identify patients with prenatal and perinatal risk factors. Electroclinical, imaging, neuropsychological, surgical, histopathologic, and seizure outcome data were reviewed. RESULTS: Prenatal and perinatal insults including severe prematurity, asphyxia, bleeding, hydrocephalus, and stroke occurred in 12.5% of children with mMCD/FCD (n = 25). Their epilepsy was characterized by early seizure onset, high seizure frequency, and absence of seizure control. Patients with significant prenatal and perinatal risk factors had more abnormal neurologic findings, lower intelligence quotient (IQ) scores, and slower background EEG activity than mMCD/FCD subjects without prenatal or perinatal brain injury. MRI evidence of cortical malformations was identified in 74% of patients. Most patients underwent large multilobar resections or hemispherectomies; 54% were seizure-free 2 years after surgery. Histologically "milder" forms of cortical malformations (mMCD and FCD type I) were observed most commonly in our series. CONCLUSIONS: Surgically remediable low-grade cortical malformations may occur in children with significant prenatally and perinatally acquired encephalopathies and play an important role in the pathogenesis of their epilepsy. Presurgical detection of dysplastic cortex has important practical consequences for surgical planning.

Different features of histopathological subtypes of pediatric focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most frequent pathological finding in pediatric epilepsy surgery patients. Several histopathological types of FCD are distinguished. The aim of the study was to define distinctive features of FCD subtypes. METHODS: We retrospectively reviewed clinical, electroencephalographic, magnetic resonance imaging, neuropsychological, and surgical variables, and seizure outcome data in 200 children. Cortical malformations were histopathologically confirmed in all patients, including mild malformation of cortical development type II (mMCD) in 36, FCD type Ia in 55, FCD type Ib in 39, FCD type IIa in 35, and FCD type IIb in 35 subjects. RESULTS: Perinatal risk factors were more frequent in mMCD/FCD type I than FCD type II. Children with FCD type IIb had more localized ictal electroencephalographic patterns and magnetic resonance imaging changes. Increased cortical thickness, abnormal gyral/sulcal patterns, gray/white matter junction blurring, and gray matter signal abnormality in fluid-attenuated inversion recovery and T2-weighted sequences occurred more often in FCD type II, were infrequent in FCD type I, and rare in mMCD. Lobar hypoplasia/atrophy was common in FCD type I. Hippocampal sclerosis was most frequent in FCD type I. Neuropsychological testing demonstrated no significant differences between the groups. There was a trend toward better surgical outcomes in FCD type II compared with FCD type I patients. INTERPRETATION: Different histopathological types of mMCD/FCD have distinct clinical and imaging characteristics. The ability to predict the subtype before surgery could influence surgical planning. Invasive electroencephalographic study should be considered when mMCD/FCD type I is expected based on noninvasive tests.

Near infrared spectroscopy in the management of status epilepticus in a young infant.

We report the medication management of electroencephalographic status epilepticus with subtle clinical manifestations in a young infant while simultaneously recording electroencephalographic activity and cerebral regional oxygen saturation (rSO(2)) index using near infrared spectroscopy (NIRS). We found that antiepileptic drugs equally influence the frequency of rSO(2) index fluctuations and electroencephalographic seizures. The purpose of this report is to illustrate the use of NIRS in the medication management of an infant with status epilepticus and subtle or no clinical manifestations; and to suggest that if future studies confirm our finding, NIRS may be reliably used to gauge the effects of antiepileptic medications in similar patients.

Near-infrared spectroscopy to define cognitive frontal lobe functions.

Near-infrared spectroscopy (NIRS) monitors changes in the regional cerebral oxygenation (rSO) and has been used to study cerebral physiologic functions in normal states and during epileptic seizures. Yet, the limitations and pitfalls of the technique are not fully understood. The authors evaluated NIRS changes over the frontal lobes during language tasks known to be associated with the integrity of the dominant frontal lobe in 17 normal adults (handedness: 14 right, 3 left). Recording protocol involved a baseline (3 minutes) with the subject relaxed and thinking of a blue sky and a second baseline during voluntary mouth movements mimicking speech. Two standardized neuropsychological word-generation tasks (controlled word-association tests: CFL and Animals) were then administered (4 minutes total) followed again by the two baseline procedures. Mouth movement without verbalization increased rSO values in excess of 2 SD of baseline fluctuations in 70% of the subjects. A t-test comparison of these baseline measurements was statistically significant (P < 0.0001). A general linear model repeated-measures procedure was then used to statistically examine NIRS increments during the cognitive tasks above and beyond the contribution produced by mouth movements during the second baseline. Compared to the second baseline, rSO further increased significantly during the word generation tasks (left frontal F value = 21.4, P < 0.0001; right frontal F value = 15.2, P < 0.001), confirming the utility of the technique. There was no apparent difference related to handedness. These findings corroborate the usefulness of NIRS to demonstrate focal cerebral activation during an "executive" language task. However, interpretation of changes can be confounded by extracerebral factors such as mouth movement, a finding of particular relevance in NIRS clinical applications.

Surgical outcomes and seizure control rates after resection of dysembryoplastic neuroepithelial tumors.

OBJECT: In this study the authors review the outcomes in pediatric patients who presented with seizures and underwent resection of dysembryoplastic neuroepithelial tumors (DNETs). The authors focus on the diagnostic evaluation and surgical techniques that facilitate gross-total tumor resection and subsequent freedom from seizures. METHODS: Eighteen patients between the ages of 1 month and 13 years who presented with seizures underwent resection of DNETs between January 1992 and December 2004. Preoperative evaluation included magnetic resonance (MR) imaging and interictal scalp electroencephalography (EEG) in all patients, functional MR imaging in eight patients, video monitoring with ictal scalp EEG in 12 patients, interictal single-photon emission computerized tomography (SPECT) scanning in one patient, and ictal SPECT scanning in two patients. Thirteen patients underwent one-stage procedures, whereas five underwent two-stage procedures (implantation of monitoring electrodes followed by tumor resection), either for functional language mapping (three patients) or due to inconclusive preoperative data (two patients). Intraoperative electrocorticography (ECoG) was performed in 17 patients and led to resection of the cerebral cortex beyond the tumor margins in 10 of them. According to operative reports, gross-total tumor resections were achieved in all patients, but one child had minimal residual tumor on postoperative MR images that has remained stable. The only surgical complication was a transient third cranial nerve palsy. Over a median follow-up duration of 1.6 years, all patients are seizure free and without radiographically detected tumor recurrence. CONCLUSIONS: Dysembryoplastic neuroepithelial tumors are a highly treatable cause of epilepsy in children. Excellent rates of complete tumor resection and seizure control with minimal morbidity can be attained using intraoperative ECoG and two-stage surgical procedures when appropriate.

Cerebral regional oxygen fluctuations and decline during clinically silent focal electroencephalographic seizures in a neonate.

We describe a neonate with tuberous sclerosis complex and right frontal cortical dysplasia who underwent simultaneous near-infrared spectroscopy and electroencephalography (EEG) during repetitive clinically silent right frontal EEG seizures. The seizures produced a progressive decline in regional oxygen saturation index and wider regional oxygen saturation index fluctuations in the right hemisphere than in the left hemisphere. We conclude that recurrent clinically silent focal EEG seizures in this neonate were associated with lateralizing near-infrared spectroscopy changes suggestive of relative cerebral hypoxia.

Agenesis of the arcuate fasciculi in congenital bilateral perisylvian syndrome: a diffusion tensor imaging and tractography study.

OBJECTIVE: To describe the absence of the arcuate fasciculi in 2 cases of congenital bilateral perisylvian syndrome (CBPS). DESIGN: Case series. SETTING: Pediatric referral hospital-based study. PATIENTS: Two patients with CBPS, referred to our institution as candidates for surgical treatment of epilepsy. Intervention Diffusion tensor imaging (1.5-T scanner; 15 encoding directions; b = 800 s/mm(2)) and deterministic tractography of the main projection and association tracts. MAIN OUTCOME MEASURES: Neuropsychology evaluation; fractional anisotropy, apparent diffusion coefficients, and anatomical aspect of the tracts. RESULTS: Absence of the arcuate fasciculus was observed in both subjects. Ancillary findings were complete absence of the superior longitudinal fasciculi in 1 case and underdevelopment in the other. Low fractional anisotropy of the left inferior occipitofrontal fasciculus was found in both cases. The same tract was maloriented in 1 of the cases. CONCLUSION: Agenesis of the arcuate fasciculus may accompany CBPS.

Epilepsy surgery in patients with normal or nonfocal MRI scans: integrative strategies offer long-term seizure relief.

PURPOSE: Excisional surgery achieves seizure freedom in a large proportion of children with intractable lesional epilepsy, but the outcome for children without a focal lesion on MRI is less clear. We report the outcome of a cohort predominantly of children with nonlesional intractable partial epilepsy undergoing resective surgery. METHODS: We studied 102 patients with nonlesional intractable partial epilepsy who underwent excisional surgery. The epileptogenic region was identified by integrating clinical exam and video-EEG data complemented by ictal SPECT (n = 40), PET (n = 10), extraoperative subdural monitoring (n = 80), and electrocorticography (n = 22). All patients had follow-up greater than 2 years, 76 patients had 5-year follow-up, and 43 patients had 10-year follow-up. RESULTS: A total of 66 resections were unilobar; 36 were multilobar. One patient died of causes unrelated to seizures or surgery. At 2-year follow-up, 44 of 101 patients were seizure-free, 15 experienced >90% reduction, 17 had >50% reduction, and 25 were unchanged. At 5-year follow-up, 35 of 76 patients were seizure-free, 12 experienced >90% reduction, 12 had >50% reduction, and 17 were unchanged. At 10-year follow-up, 16 of 43 patients were seizure-free, 13 experienced >90% reduction, 7 had >50% reduction, and 7 were unchanged. Outcomes correlated with the presence of convergent focal interictal spikes (p < 0.005) on the scalp EEG and completeness of resection (p < 0.0005). CONCLUSIONS: Our findings demonstrate that excisional surgery is successful in the majority of children with nonlesional partial epilepsy. A multimodal integrative approach can minimize the size of resection and alleviate the need for invasive EEG monitoring. Focal interictal spikes and completeness of resection predict good outcome. The benefits of surgery are long-lasting.

Surgery for epilepsy due to cortical malformations: ten-year follow-up.

Children with malformations of cortical development represent a significant proportion of pediatric epilepsy surgery candidates. From a cohort of 40 children operated on between 1980 and 1992 with malformation of cortical development, 38 were alive and had data 10 years after surgery. Age at surgery ranged from 6 months to 18 years (mean, 9.6 years). Thirty-six had partial seizures, and two had infantile spasms; 20 were nonlesional. Pathologic diagnoses were cortical dysplasia (n = 31) and developmental tumor (n = 7). At 10-year follow-up, 15 (40%) were seizure free, 10 (26%) had >90% seizure reduction, and 13 (34%) were improved or unchanged. Children seizure free at two-year follow-up were likely to remain seizure free. Ten-year seizure freedom was 72% in children with developmental tumors and 32% in the cortical dysplasia group. Complete resection was statistically significant for favorable outcome, and no patient with an incomplete resection was seizure free.

Seizure disorders: functional MR imaging for diagnostic evaluation and surgical treatment--prospective study.

PURPOSE: To prospectively evaluate effect of functional magnetic resonance (MR) imaging on diagnostic work-up and treatment planning in patients with seizure disorders who are candidates for surgical treatment. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was obtained either from the patient or the parent or guardian in all patients. This study was conducted with Health Insurance Portability and Accountability Act compliance. Sixty consecutively enrolled patients (33 males, 27 females; mean age, 15.8 years +/- 8.7 [standard deviation]; range, 6.8-44.2 years) were prospectively examined. Forty-five (75%) patients were right handed, nine (15%) were left handed, and six (10%) had indeterminate hand dominance. Prospective questionnaires were used to evaluate diagnostic work-up, counseling, and treatment plans of the seizure team before and after functional MR imaging. Confidence level scales were used to determine effect of functional MR imaging on diagnostic and therapeutic thinking. Paired t test and 95% confidence interval analyses were performed. RESULTS: In 53 patients, language mapping was performed; in 33, motor mapping; and in seven, visual mapping. The study revealed change in anatomic location or lateralization of language-receptive (Wernicke) (28% of patients) and language-expressive (Broca) (21% of patients) areas. Statistically significant increases were found in confidence levels after functional MR imaging in regard to motor and visual cortical function evaluation. In 35 (58%) of 60 patients, the seizure team thought that functional MR imaging results altered patient and family counseling. In 38 (63%) of 60 patients, functional MR imaging results helped to avoid further studies, including Wada test. In 31 (52%) and 25 (42%) of 60 patients, intraoperative mapping and surgical plans, respectively, were altered because of functional MR imaging results. In five (8%) patients, two-stage surgery with extra-operative direct electrical stimulation mapping was averted, and resection was accomplished in one stage. In four (7%) patients, extent of surgical resection was altered because eloquent areas were identified close to seizure focus. CONCLUSION: Functional MR imaging results influenced diagnostic and therapeutic decision making of the seizure team; results indicated language dominance changed, confidence level in identification of critical brain function areas increased, patient and family counseling were altered, and intraoperative mapping and surgical approach were altered.

The use of stereotactic radiosurgery to treat intractable childhood partial epilepsy.

PURPOSE: Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep-seated lesions are often associated with morbidity. Stereotactic radiosurgery is a noninvasive procedure that effectively treats patients with vascular malformations and brain tumors, but its efficacy for epileptogenic foci is limited, especially in children. METHODS: Between 1995 and 1999, four candidates who had medically uncontrolled seizures and localized seizure foci were selected for stereotactic radiosurgery, with a mean age of 9.75 years at the time of surgery (range, 4-17 years). Seizure foci were identified on the basis of ictal and interictal video-EEG. Magnetic resonance (MR) images were obtained before and after surgery. Ictal single-photon emission computed tomography (SPECT) was performed by using stabilized hexamethyl-propyleneamine oxime (HMPAO; 300 microcuries/kg) with early injection after electrographic ictal onset. The clinical features of the patients are given. All radiosurgical procedures were performed with the gamma knife unit with the Leksell stereotactic frame, stereotactic MRI imaging, and the Gamma Plan workstation. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients had hypothalamic hamartoma (HH), and two had neocortical epilepsy. At mean follow-up of 39.2 months (range, 26-69 months), two patients were seizure free, one with a HH and one with a suggestive developmental tumor in the insular cortex by MRI findings. The other patient with HH had 90% reduction of seizures. One patient with a widespread seizure focus that involved the motor strip was unimproved. The two patients with HH also exhibited markedly improved neurobehavioral status after surgery. There were no significant complications of radiosurgical therapy. CONCLUSIONS: Our findings suggest that gamma knife surgery is a potentially valuable treatment modality for children with medically intractable epilepsy due to a well-localized seizure focus that is difficult to excise by conventional techniques or for whom they are deemed unsuitable. More widespread application in childhood epilepsy should be investigated in larger series.

Características clíniacs de los trastornos de la migración neuronal

El presente artículo presenta la descripción de un grupo de 22 pacientes en edad pediátrica, con trastornos de la migración neuronal estudiados en el Departamento Neuro Pediátrico del hospital Militar Central. Se enfatizan los hallazgos clínicos y se demuestra el valioso aporte de las imágenes diagnósticas para la identificación y clasificación de estas anomalías