Distinctive MRI features of the epileptogenic zone in children with tuberous sclerosis.

OBJECTIVE: Localization of the epileptogenic zone (EZ) is challenging in children with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI could identify the EZ in TSC patients independent of the clinical and diagnostic data. METHODS: Presurgical MRI's of 34 children with TSC who underwent epilepsy surgery at Miami Children's Hospital were retrospectively reevaluated by experts blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic changes) and abnormalities of the perituberal cortex typical of focal cortical dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle change, gray/white matter junction blurring) were identified and their localization was compared with the resection site. Sensitivity, specificity and accuracy of individual MRI features to localize the EZ were determined and statistically compared between postoperatively seizure-free and non-seizure-free patients as well as clusters of features typical of FCD and TSC. RESULTS: MRI alone correctly localized the resection cavity in all 19 postoperatively seizure-free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%, respectively) were superior to those typical of TCS (79%, 75% and 75%, p<0.0001). Increased cortical thickness and abnormal gyral formation outside tubers occurred only in the resection site. Resection sites were better predicted by MRI in seizure-free than in non-seizure-free patients. CONCLUSION: Thorough MRI evaluation identifies the EZ in a significant proportion of TSC patients. Epileptogenic regions were mostly characterized by "FCD-like" changes outside cortical tubers. The findings may have important practical consequences for surgical planning in TSC.

Comparative reliability analysis of publicly available software packages for automatic intracranial volume estimation.

Intracranial volume is an important measure in brain research often used as a correction factor in inter subject studies. The current study investigates the resulting outcome in terms of the type of software used for automatically estimating ICV measure. Five groups of 70 subjects are considered, including adult controls (AC) (n=11), adult with dementia (AD) (n=11), pediatric controls (PC) (n=18) and two groups of pediatric epilepsy subjects (PE1.5 and PE3) (n=30) using 1.5 T and 3T scanners, respectively. Reference measurements were calculated for each subject by manually tracing intracranial cavity without sub-sampling. Four publicly available software packages (AFNI, Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the five groups. Linear regression analyses suggest that reference measurement discrepancy could be explained best by SPM [R(2)= 0.67;p <; 0.01] for the AC group, Freesurfer [R(2) = 0.46; p = 0.02] for the AD group, AFNI [R(2)=0.97;p<; 0.01] for the PC group and FSL [R(2) = 0.6; p = 0.1] for the PE1.5 and [R(2) = 0.6; p <; 0.01] for PE3 groups. The study demonstrates that the choice of the automated software for ICV estimation is dependent on the population under consideration and whether the software used is atlas-based or not.

Predictors of seizure freedom after incomplete resection in children.

OBJECTIVE: Incomplete resection of the epileptogenic zone (EZ) is the most important predictor of poor outcome after resective surgery for intractable epilepsy. We analyzed the contribution of preoperative and perioperative variables including MRI and EEG data as predictors of seizure-free (SF) outcome after incomplete resection. METHODS: We retrospectively reviewed patients <18 years of age with incomplete resection for epilepsy with 2 years of follow-up. Fourteen preoperative and perioperative variables were compared in SF and non-SF (NSF) patients. We compared lesional patients, categorized by reason for incompleteness, to lesional patients with complete resection. We analyzed for effect of complete EEG resection on SF outcome in patients with incompletely resected MRI lesions and vice versa. RESULTS: Eighty-three patients with incomplete resection were included with 41% becoming SF. Forty-eight lesional patients with complete resection were included. Thirty-eight percent (57/151) of patients with incomplete resection and 34% (47/138) with complete resection were excluded secondary to lack of follow-up or incomplete records. Contiguous MRI lesions were predictive of seizure freedom after incomplete resection. Fifty-seven percent of patients incomplete by MRI alone, 52% incomplete by EEG alone, and 24% incomplete by both became SF compared to 77% of patients with complete resection (p = 0.0005). CONCLUSIONS: Complete resection of the MRI- and EEG-defined EZ is the best predictor of seizure freedom, though patients incomplete by EEG or MRI alone have better outcome compared to patients incomplete by both. More than one-third of patients with incomplete resection become SF, with contiguous MRI lesions a predictor of SF outcome.

Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome.

BACKGROUND: Focal cortical dysplasia (FCD) is recognized as the major cause of focal intractable epilepsy in childhood. Various factors influencing postsurgical seizure outcome in pediatric patients with FCD have been reported. OBJECTIVE: To analyze different variables in relation to seizure outcome in order to identify prognostic factors for selection of pediatric patients with FCD for epilepsy surgery. METHODS: A cohort of 149 patients with histologically confirmed mild malformations of cortical development or FCD with at least 2 years of postoperative follow-up was retrospectively studied; 113 subjects had at least 5 years of postoperative follow-up. Twenty-eight clinical, EEG, MRI, neuropsychological, surgical, and histopathologic parameters were evaluated. RESULTS: The only significant predictor of surgical success was completeness of surgical resection, defined as complete removal of the structural MRI lesion (if present) and the cortical region exhibiting prominent ictal and interictal abnormalities on intracranial EEG. Unfavorable surgical outcomes are mostly caused by overlap of dysplastic and eloquent cortical regions. There were nonsignificant trends toward better outcomes in patients with normal intelligence, after hemispherectomy and with FCD type II. Other factors such as age at seizure onset, duration of epilepsy, seizure frequency, associated pathologies including hippocampal sclerosis, extent of EEG and MRI abnormalities, as well as extent and localization of resections did not influence outcome. Twenty-five percent of patients changed Engel's class of seizure outcome after the second postoperative year. CONCLUSIONS: The ability to define and fully excise the entire region of dysplastic cortex is the most powerful variable influencing outcome in pediatric patients with focal cortical dysplasia.

Distinct clinicopathologic subtypes of cortical dysplasia of Taylor.

BACKGROUND: Two pathologic subtypes based on the presence or absence of balloon cells have been described in cortical dysplasia of Taylor (CDT). OBJECTIVE: To determine whether the pathologic subtype has any distinct clinical or MRI features that are relevant to management. METHODS: The histopathologic, clinical, and MRI features of 34 children with CDT who underwent epilepsy surgery at Miami Children's Hospital from 1990 to 2001 were investigated. RESULTS: Bizarre neuronal cytomegaly was the primary pathologic feature of 15 patients with the dysplasia-only subtype, and 19 cases showed additional characteristics including balloon cells and marked white matter abnormalities. Both groups presented with severe intractable epilepsy of very-early-onset, multiple daily seizures, cognitive disability, and focal neurologic deficits. The dysplasia-only subtype had higher rates of neonatal onset, hemiparesis, and severe mental retardation (p < 0.05). The MRI features of focal cortical thickening with associated cortical T2 signal change showed excellent sensitivity (94%) and reasonable specificity (73%) for the diagnosis of the balloon cell subtype. The overall surgical outcome was 59% seizure freedom at 2 years. CONCLUSIONS: Children with cortical dysplasia of Taylor type have in common a very-early-onset, severe epilepsy with neurologic co-morbidity. Patients with the non-balloon cell pathologic subtype have a more severe phenotype. A trend toward a better outcome in the balloon cell group suggests that preoperative identification of these subtypes may impact surgical planning.

Absence of hippocampal sclerosis in children with multiple daily seizures since infancy.

We report a series of nine children with multiple daily seizures since infancy who underwent functional hemispherectomy that included en bloc resection of the hippocampus and the temporal neocortex. In all cases, the hippocampi were normal by conventional histology despite the fact that these patients had suffered from recurrent seizures over a long period of time. This observation suggests that extremely frequent seizures in childhood are not invariably associated with the development of hippocampal sclerosis.

Continuous-display four-channel electroencephalographic monitoring in the evaluation of neonates with paroxysmal motor events.

The objective of this study was to determine the value of continuous-display four-channel electroencephalographic (EEG) monitoring to distinguish epileptic front nonepileptic paroxysmal motor events. Five full-term neonates with paroxysmal motor events were included in the study. Nurses were instructed to print contiguous pages of the continuous-display four-channel EEG monitoring and to activate the event marker on the simultaneously conducted continuous video-EEG telemetry unit during each paroxysmal motor event. The printouts from the continuous-display four-channel EEG monitoring were interpreted and compared with the corresponding segments of continuous video-EEG telemetry. Thirty paroxysmal motor events were captured. Sixteen paroxysmal motor events were epileptic, and 14 were nonepileptic. The interpretation of the printouts of the continuous four-channel EEG monitoring concurred with an independent interpretation of the corresponding video-EEG telemetry segments in all of the events. Continuous-display four-channel EEG monitoring is a valuable tool in the evaluation of neonates with paroxysmal motor events since it reliably distinguishes epileptic and nonepileptic events.

Benign rolandic epilepsy: clinical and electroencephalographic correlates.

Benign rolandic epilepsy (BRE) is known for its dissociation from structural alterations. Nevertheless, the number of cases with reported organic lesions has been increasing. This led to the creation of two subgroups, "benign" and "non benign" BRE, and resulted in the need for additional parameters to define electrographic benignity. We assessed the possible associations between interictal electroencephalographic findings and clinical behavior in 60 BRE cases, testing four parameters of electrographic benignity (paroxysm morphology, horizontal dipole, base rhythms, laterality of rolandic spikes). We also assessed the relationship between neuroimaging findings and electrographic and clinical classifications, and found a statistically significant association (sensitivity=73.5%; specificity=81.8%; positive predictive value=94. 8%; negative predictive value=40.9%). Three of the electrographic parameters proposed were associated with clinical classification: paroxysm morphology, horizontal dipole, and base rhythms. Cases electrographically classified as benign have 21 times more chances to be equally classified as clinically benign according with the tested criteria.

Epilepsy surgery in children with tuberous sclerosis complex: presurgical evaluation and outcome.

PURPOSE: Children with tuberous sclerosis complex (TSC) benefit from excisional surgery if seizures can be localized to a single tuber. We evaluated the role of noninvasive studies to localize the epileptogenic tuber/region (ET/R) and the outcome of focal resection. METHODS: We identified 21 children with TSC, ages 3 months to 15 years (mean 4.8 years). All had video-(electroencephalogram) EEG and magnetic resonance imaging (MRI) scans, and 18 also had ictal single photon emission-computed tomography (SPECT) studies. An ET/R was localized in 17 patients. Thirteen patients underwent resection guided by intraoperative electrocorticography (n = 7) or subdural monitoring (n = 6). RESULTS: Interictal EEG revealed a principal spike focus (PSF) that corresponded to the ET/R in 14 children. In seven, PSFs occurred in rhythmic runs. PSFs were not observed remote from the ET/R. Focal polymorphic slowing and attenuation occurred in the region of the PSF in 11 patients. Sixteen patients demonstrated an ictal focus corresponding to the ET/R. Ictal SPECT revealed focal hyperperfusion correlating with the ET/R in 10 patients. Although the MRIs in all children revealed multiple tubers, the ET/R corresponded to a large discrete tuber in 8 patients and a calcified tuber in 13 patients. Patchy calcified tubers were also seen elsewhere in six patients. At a mean follow-up of 26 months, 9 of the 13 children who underwent surgery were seizure-free, one had greater than 75% reduction in seizures, two were unchanged, and one was lost to follow-up. New seizures developed in one child from a contralateral tuber. CONCLUSIONS: Surgical resection of an ET/R alleviates seizures in most children with TSC and intractable epilepsy. The scalp EEG and MRI help define the ET/R and improve case selection when ictal SPECT is nonlocalizing.

Aberrant neural circuits in malformations of cortical development and focal epilepsy.

Malformations of cortical development (MCD) account for a high proportion of medically resistant partial seizures in children and figure prominently in pediatric surgical series. In contrast to the results of epilepsy surgery for postnatally acquired lesions, seizure freedom in patients with MCD is less certain owing to difficulties in defining the epileptic zone, and fully excising the epileptogenic cortex. The authors present evidence that, compared with postnatally acquired lesions such as those due to tumors or trauma, focal epileptogenesis associated with MCD is best conceptualized as a disorder of widespread and patchy disturbance of cortical networks. This developmental perspective implies that the epileptogenic region in MCD is rarely discrete even in patients with focal anatomic lesions, and may include remote cortical or subcortical areas. Preoperative investigative protocols based on this model have improved surgical results, but outcome remains far from optimal and further progress in understanding the complex developmentally based features of MCD is required.

Neurophysiological evaluation of children with traumatic radiculopathy, plexopathy, and peripheral neuropathy.

Neurophysiological evaluation of children with traumatic peripheral nervous system injury is accomplished with electromyography, motor and sensory nerve conduction studies, and somatosensory and motor-evoked potentials. Preoperative neurophysiological tests are performed if motor deficits persist for more than 3 months. Evidence of reinnervation on these neurophysiological tests predates clinical recovery by weeks, hence they help determine the site of the lesion and provide objective measures for selecting candidates for surgical exploration. Intraoperative neurophysiological tests help to identify and confirm the integrity of nerves and to develop the optimal surgical strategy. Postoperative evaluations every 3 to 6 months may determine efficacy of treatment.

Predictors of outcome in pediatric epilepsy surgery.

OBJECTIVE: To determine the correlation between pre- and perioperative variables on the outcome of children undergoing focal resections for medically intractable partial epilepsy. METHODS: Retrospective analysis of pre- and perioperative variables in a cohort of 75 patients younger than 12 years of age who underwent excisional surgery and had at least 1 year of follow-up. Outcome, measured by postoperative seizure frequency, was analyzed as a function of age at seizure onset, duration of epilepsy, presence of cognitive impairment, lobe of seizure origin, presence of a lesion, histopathology, and completeness of resection. Completeness of resection was defined on the basis of excising both the entire structural lesion if present and the region revealing prominent interictal and ictal abnormalities on intracranial EEG. RESULTS: Seventy-seven percent of patients had good outcomes (class 1 or 2), and 59% were seizure-free. Lesional status, site of resection, and pathologic diagnoses were not significant predictors of outcome except for in multilobar resection, for which overall outcome was relatively poor (44% class 3 or 4; 22% seizure-free). Completeness of resection was the only significant predictor of good outcome (p < 0.001), with 92% of patients who underwent complete resection of the epileptogenic zone achieving good outcome compared with 50% of patients who had incomplete resections. CONCLUSION: In this series of pediatric patients, complete resection of the lesion and the electrographically abnormal region was the main determinant of outcome after focal resections. Except for multilobar resections, other factors examined in this study did not significantly influence postoperative seizure prognosis and should not influence candidate selection for the surgical process.

Selection criteria and preoperative investigation of patients with focal epilepsy who lack a localized structural lesion.

Children with medically resistant epilepsy are often referred for surgical evaluation. The absence of a specific focal lesion on MRI may render the work-up difficult. In response to the need to localize the primary area of epileptogenesis, surgery protocols are being developed which rely on clinical semiology, EEG and functional imaging data. In selected cases, intracranial EEG monitoring may be required. While testing more often depends on the convergence of modalities, it is possible to localize seizure origin in the majority of children, and fully excise the epileptogenic region. This review presents the etiology and preoperative modalities available for children with intractable, non-lesional epilepsy.

Invasive EEG monitoring in children: when, where, and what?

With rapid advances in noninvasive technology, the need for chronic intracranial monitoring to define the epileptogenic region has diminished significantly. Its role in presurgical evaluation has come under scrutiny particularly in adults with lesional epilepsy. With the shift in surgical candidacy toward the younger age groups, however, invasive monitoring has regained its utility especially in children with normal imaging studies and cortical dysplasia. This review critically evaluates its continuing role, attempting to assess cost-benefit under specific clinical scenarios and proposes how the findings can be incorporated into the challenging task of surgical planning in intractable childhood epilepsy.

The localizing value of ictal SPECT in children with tuberous sclerosis complex and refractory partial epilepsy.

Although multiple cortical tubers are a hallmark of tuberous sclerosis complex (TSC), seizures often originate from a single tuber, making excisional surgery a therapeutic option for intractable patients. To assess the role of ictal single photon emission computed tomography (SPECT) in defining the epileptogenic tuber, we reviewed videoelectroencephalography (V/EEG) data, magnetic resonance imaging (MRI) and SPECT scans of 15 patients (aged 3 months to 15 years, mean 5.1) with medically resistant partial seizures and TSC. SPECT scans were performed using Tc-99m-hexamethylpropyleneamine oxime (HMPAO) injected within 30 seconds of electrographic seizure onset and were graded on a scale from 1 to 5 (1 weakly perfused, 5 strongly perfused). The scalp EEG revealed localized seizure origin in ten patients; five had concordant hyperperfused SPECT regions consisting of comma-shaped areas surrounding hypoperfused areas in the candidate tuber. Strongly hyperperfused regions (grade 3-5) were noted in two patients whose ictal EEG patterns were characterized by sustained, rhythmic fast activity or spiking. The other five patients had nonlocalizing or poorly sustained ictal EEG patterns; one patient in this group had focal hyperperfusion. Invasive EEG recordings in two patients revealed propagated EEG patterns that correlated with the ictal SPECT findings. These findings indicate a strong correlation between ictal SPECT and ictal scalp EEG, especially when there are sustained rhythmic fast ictal EEG patterns.

[Epilepsy treatment by vagal stimulation]. / Tratamiento de la epilepsia por medio de la estimulación vagal.

INTRODUCTION: Vagal nerve stimulation is the latest therapeutic modality for the treatment of epilepsy. It consists of a lead implanted in the left vagal nerve which is connected to a subcutaneous stimulator implanted in the left axillary or pectorial region. DEVELOPMENT: The stimulator is programmed to intermittently stimulate the vagal nerve throughout the day and a magnet also allows the patient to control the stimulation from the outside. This treatment has been used in patients with intractable partial seizures who are not candidates for epilepsy surgery. The results reported have varied but in general the procedure appears promising with at least 50% of the implanted having over 50% improvement in their seizure frequency and many having complete control without significant side effects. CONCLUSION: Further review of the results are still needed to fully determine the true value of this treatment and to identify the subgroups of patients which will benefit the most.

[Epilepsy centers: classification and basic requirements]. / Centros especializados en epilepsia: clasificación y requisitos básicos.

Over the last two decades the surgical treatment of epilepsies has become a commonly used and effective method for the treatment of intractable epilepsy. However, because of its wide use in various types of centers throughout the world the methodology involved varies significantly throughout the centers. With this article we propose the bases from which a multidisciplinary team of numerous centers can eventually develop an effective and acceptable international protocol for the surgical treatment of the epilepsies and the classifications of the centers.

Epilepsy surgery in the first three years of life.

PURPOSE: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes. METHODS: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery. RESULTS: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment. CONCLUSIONS: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and lesion are removed.

[Neuropathology of refractory epilepsy in children]. / Neuropatología de la epilepsia refractaria en niños.

INTRODUCTION AND OBJECTIVES: The pathological findings in surgical material from children with refractory epilepsy has not offered yet a clear understanding of its role in this condition. The objective of this paper is to report our findings to further expand our knowledge about refractory epilepsy in children. MATERIAL AND METHODS: Results of microscopic examination of the surgical specimen obtained from 80 children, ages 12 or younger, who had surgery for intractable epilepsy at Miami Children's Hospital between 1990 and 1996 were reviewed. RESULTS: Examination was normal only in one. The rest revealed ectopic neurons (1), dysplastic cells with ectopic neurons (2), dyslamination with large neurons (7), dyslamination with ectopic neurons (18), dyslamination with dysplastic cells (10), pachygyria (2), encephalomalacia (9), gliosis with ectopic neurons (10), gliosis without ectopic neurons (3), developmental ectodermal tumor (6), ganglioglioma (2), tumors (3), and Rasmussen encephalitis (4). Lesions were located to the temporal lobe in 34 children. CONCLUSIONS. Extratemporal lesions are more frequent than temporal one, including hyppocampal sclerosis. Ectopic neurons, the most frequent pathological findings, rather than a cause of seizure may be a marker other highly epileptogenic cortical malformations.

Results and complications after reoperation for failed epilepsy surgery in children.

The seizure outcome and neurological outcome in children who undergo reoperation for failed epilepsy surgery have not been well documented. This retrospective study evaluated 20 children who underwent a second resective surgery for recurrent seizures. Four categories of patients were identified: (1) extension of the initial resection was performed in 8 patients; (2) 5 patients underwent lobectomy or corticectomy in a region remote from the original surgical site; (3) multilobar resection which may have included further resection of the initial procedure was accomplished in 4 patients; (4) hemispherectomy was performed in 3 patients. Patients with reoperation in the same lobe as the first procedure (group 1) had a 62% seizure-free rate, while 44% of patients in groups 2 and 3 were free from seizures at follow-up evaluation. Patients undergoing hemispherectomy had a 67% seizure-free rate. Significant unexpected neurological deficits occurred in 3 patients who underwent multilobar resection at reoperation. Complications included motor and language deficits. Reoperation for intractable partial epilepsy is beneficial in selected children. Patients who require multilobar resections may have higher risk of postoperative neurological deficit than those patients with reoperation in one lobe. These factors may be useful in counseling parents of children considering reoperation for recurrent epilepsy.