Drug resistance in epilepsy.

Drug resistance is estimated to affect about a third of individuals with epilepsy, but its prevalence differs in relation to the epilepsy syndrome, the cause of epilepsy, and other factors such as age of seizure onset and presence of associated neurological deficits. Although drug-resistant epilepsy is not synonymous with unresponsiveness to any drug treatment, the probability of achieving seizure freedom on a newly tried medication decreases with increasing number of previously failed treatments. After two appropriately used antiseizure medications have failed to control seizures, individuals should be referred whenever possible to a comprehensive epilepsy centre for diagnostic re-evaluation and targeted management. The feasibility of epilepsy surgery and other treatments, including those targeting the cause of epilepsy, should be considered early after diagnosis. Substantial evidence indicates that a delay in identifying an effective treatment can adversely affect ultimate outcome and carry an increased risk of cognitive disability, other comorbidities, and premature mortality. Research on mechanisms of drug resistance and novel therapeutics is progressing rapidly, and potentially improved treatments, including those targeting disease modification, are on the horizon.

Temporal Encephalocele: A Treatable Etiology of Drug-Resistant Pediatric Temporal Lobe Epilepsy.

BACKGROUND: Temporal lobe encephaloceles (TEs) are a rare cause of drug-resistant temporal lobe epilepsy (DR-TLE), with head trauma and obesity identified as risk factors in adults. This study evaluated the clinical characteristics of childhood-onset DR-TLE due to TE. METHODS: This is a single-institution retrospective review of childhood-onset DR-TLE with radiographic TE identified between 2008 and 2020. The epilepsy history, brain imaging features, and surgical outcomes were collected. RESULTS: Eleven children with DR-TLE due to TE were included (median age at epilepsy onset was 11 years, interquartile range 8.5 to 13.5 years). Median latency between epilepsy diagnosis and TE detection was 3 years (range of 0 to 13 years). None had history of head trauma. Body mass index greater than 85 percentile for age and sex was seen in 36% of the children. No patient had bilateral TE identified. TEs were diagnosed based on epilepsy surgery conference re-review of imaging in 36% of cases. All herniations were contained defects without osseous dehiscence. Regional fluorodeoxyglucose (FDG) hypometabolism ipsilateral to the encephalocele was seen in all children who had FDG-positron emission tomography (PET) of the brain. Of the children who had surgery, 70% were seizure free or had nondisabling seizures at last follow-up (mean follow-up 52 months). CONCLUSIONS: TE is a surgically remediable etiology of DR-TLE in childhood. TEs are often overlooked at pediatric epilepsy diagnosis, calling for the need to increase awareness of this entity. FDG-PET temporal hypometabolism in children with presumed nonlesional DR-TLE should be carefully examined for occult TEs.

Autism Spectrum Disorder and Epilepsy.

Autism spectrum disorder (ASD), was first described in 1943 as a disorder consisting of a triad of qualitative impairments of social interaction, communication and restricted repetitive patterns of behavior, interests, and activities. The relationship between ASD and epilepsy is well documented. Patients with ASD have an increased risk of epilepsy, while those with epilepsy have a higher risk of ASD, as compared with the general population. Diagnosing epilepsy in those with ASD can be challenging. For example, stereotyped behaviors could be mistaken as ASD stereotypies, when in fact, they may be due to seizures. Fortunately, in recent years, we have gained a better understanding of the best antiseizure medications (ASMs) to use in this vulnerable population. However, more studies are needed to understand how best to screen for ASD in epilepsy, what the various ASD phenotypes are in people with epilepsy, especially those due to de novo genes/mutations, as well as factors influencing the fluctuating nature of ASD symptoms (eg, seizure type, frequency, syndromes, ASMs)..

Safety and efficacy of responsive neurostimulation in the pediatric population: Evidence from institutional review and patient-level meta-analysis.

BACKGROUND: Responsive neurostimulation (RNS) is a novel technology for drug-resistant epilepsy rising from bilateral hemispheres or eloquent cortex. Although recently approved for adults, its safety and efficacy for pediatric patients is under investigation. METHODS: A comprehensive literature search (Pubmed/Medline, Scopus, Cochrane) was conducted for studies on RNS for pediatric epilepsy (<18 y/o) and supplemented by our institutional series (4 cases). Reduction in seizure frequency at last follow-up compared to preoperative baseline comprised the primary endpoint. RESULTS: A total of 8 studies (49 patients) were analyzed. Median age at implant was 15 years (interquartile range [IQR] 12-17) and 63% were males. A lesional MRI was noted in 64% (14/22). Prior invasive EEG recording was performed in the majority of patients (90%) and the most common modality was stereoelectroencephalography (57%). The most common implant location (total of 94 RNS leads) was the frontal lobe (27%), followed by mesial temporal structures (23%) and thalamus (17%). At a median follow-up of 22 months, median seizure frequency reduction was 75% (IQR: 50-88%) and 80% were responders (>50% seizure reduction). Responses ranged from 50% for temporal lobe epilepsy to 81-93% for frontal, parietal, and multilobar epilepsy. Four infections were observed (8%) and there were no hematomas or postoperative neurological deficits. CONCLUSION: Current evidence, albeit limited by potential publication bias, supports the promising safety and efficacy profile of RNS for medically refractory pediatric epilepsy. Randomized controlled trial data are needed to further establish the role of this intervention in preoperative discussions with patients and their families.

Monogenic Epilepsies: Disease Mechanisms, Clinical Phenotypes, and Targeted Therapies.

A monogenic etiology can be identified in up to 40% of people with severe epilepsy. To address earlier and more appropriate treatment strategies, clinicians are required to know the implications that specific genetic causes might have on pathophysiology, natural history, comorbidities, and treatment choices. In this narrative review, we summarize concepts on the genetic epilepsies based on the underlying pathophysiologic mechanisms and present the current knowledge on treatment options based on evidence provided by controlled trials or studies with lower classification of evidence. Overall, evidence robust enough to guide antiseizure medication (ASM) choices in genetic epilepsies remains limited to the more frequent conditions for which controlled trials and observational studies have been possible. Most monogenic disorders are very rare and ASM choices for them are still based on inferences drawn from observational studies and early, often anecdotal, experiences with precision therapies. Precision medicine remains applicable to only a narrow number of patients with monogenic epilepsies and may target only part of the actual functional defects. Phenotypic heterogeneity is remarkable, and some genetic mutations activate epileptogenesis through their developmental effects, which may not be reversed postnatally. Other genes seem to have pure functional consequences on excitability, acting through either loss- or gain-of-function effects, and these may have opposite treatment implications. In addition, the functional consequences of missense mutations may be difficult to predict, making precision treatment approaches considerably more complex than estimated by deterministic interpretations. Knowledge of genetic etiologies can influence the approach to surgical treatment of focal epilepsies. Identification of germline mutations in specific genes contraindicates surgery while mutations in other genes do not. Identification, quantification, and functional characterization of specific somatic mutations before surgery using CSF liquid biopsy or after surgery in brain specimens will likely be integrated in planning surgical strategies and reintervention after a first unsuccessful surgery as initial evidence suggests that mutational load may correlate with the epileptogenic zone. Promising future directions include gene manipulation by DNA or mRNA targeting; although most are still far from clinical use, some are in early phase clinical development.

Management of CLN1 Disease: International Clinical Consensus.

BACKGROUND: CLN1 disease (neuronal ceroid lipofuscinosis type 1) is a rare, genetic, neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase 1 (PPT1) enzyme deficiency. Clinical features include developmental delay, psychomotor regression, seizures, ataxia, movement disorders, visual impairment, and early death. In general, the later the age at symptom onset, the more protracted the disease course. We sought to evaluate current evidence and to develop expert practice consensus to support clinicians who have not previously encountered patients with this rare disease. METHODS: We searched the literature for guidelines and evidence to support clinical practice recommendations. We surveyed CLN1 disease experts and caregivers regarding their experiences and recommendations, and a meeting of experts was conducted to ascertain points of consensus and clinical practice differences. RESULTS: We found a limited evidence base for treatment and no clinical management guidelines specific to CLN1 disease. Fifteen CLN1 disease experts and 39 caregivers responded to the surveys, and 14 experts met to develop consensus-based recommendations. The resulting management recommendations are uniquely informed by family perspectives, due to the inclusion of caregiver and advocate perspectives. A family-centered approach is supported, and individualized, multidisciplinary care is emphasized in the recommendations. Ascertainment of the specific CLN1 disease phenotype (infantile-, late infantile-, juvenile-, or adult-onset) is of key importance in informing the anticipated clinical course, prognosis, and care needs. Goals and strategies should be periodically reevaluated and adapted to patients' current needs, with a primary aim of optimizing patient and family quality of life.

Care Delivery for Children With Epilepsy During the COVID-19 Pandemic: An International Survey of Clinicians.

OBJECTIVE: To evaluate the effect of the COVID-19 pandemic on global access to care and practice patterns for children with epilepsy. METHODS: We conducted a cross-sectional, online survey of pediatric neurologists across the world affiliated with the International Child Neurology Association, the Chinese Child Neurology Society, the Child Neurology Society, and the Pediatric Epilepsy Research Consortium. Results were analyzed in relation to regional burden of COVID-19 disease. RESULTS: From April 10 to 24, 2020, a sample of 212 respondents from 49 countries indicated that the COVID-19 pandemic has dramatically changed many aspects of pediatric epilepsy care, with 91.5% reporting changes to outpatient care, 90.6% with reduced access to electroencephalography (EEG), 37.4% with altered management of infantile spasms, 92.3% with restrictions in ketogenic diet initiation, 93.4% with closed or severely limited epilepsy monitoring units, and 91.3% with canceled or limited epilepsy surgery. Telehealth use had increased, with 24.7% seeing patients exclusively via telehealth. Changes in practice were related both to COVID-19 burden and location. CONCLUSIONS: In response to COVID-19, pediatric epilepsy programs have implemented crisis standards of care that include increased telemedicine, decreased EEG use, changes in treatments of infantile spasms, and cessation of epilepsy surgery. The long-term impact of these abrupt changes merit careful study.

LGI1 and CASPR2 neurological autoimmunity in children.

The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated proteinlike 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for voltage-gated potassium channel-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for LGI1-IgG (n = 7), CASPR2-IgG (n = 3), or both (n = 3). This is significantly less than in adults. Encephalopathy, seizures, and peripheral nerve hyperexcitability were common, as was coexisting autoimmunity. No faciobrachial dystonic seizures or cancers were identified. Functional neurologic disorders were frequently the initial diagnosis, and immunotherapy appeared beneficial. Ann Neurol 2018;84:473-480.

Stiripentol in the Management of Epilepsy.

Stiripentol is a structurally unique antiepileptic drug that has several possible mechanisms of action, including diverse effects on the gamma-aminobutyric acid (GABA)-A receptor and novel inhibition of lactate dehydrogenase. Because of its inhibition of several cytochrome P450 enzymes, it has extensive pharmacokinetic interactions, which often necessitates reduction in doses of certain co-therapies, particularly clobazam. Stiripentol also has a neuroprotective action, by reducing calcium-mediated neurotoxicity. Evidence of its efficacy is most robust for Dravet syndrome, where stiripentol added to clobazam and valproic acid reduces seizure frequency and severity in the majority of cases. Small case series have also suggested benefit for malignant migrating partial seizures in infancy, super-refractory status epilepticus, and intractable focal epilepsy, although larger prospective studies are needed in these disorders.

Usefulness of repeat review of head magnetic resonance images during presurgical epilepsy conferences.

Surgical epilepsy conferences are an important part of the process of determining whether a patient is a candidate for resective epilepsy surgery. At these conferences, repeat review (re-review) of the magnetic resonance images (MRIs) of the patient's head often occurs. This study assessed how often radiologic re-review at a presurgical epilepsy conference resulted in a changed interpretation of the head MRI. Charts were reviewed for 239 patients who had been presented at presurgical epilepsy conferences between 2008 and 2012. Of the 233 patients whose MRIs were re-reviewed, resective surgery was performed in 94 patients (40.3%). Forty-one patients (17.6%) had a previously undiagnosed finding, and 18 of the 41 (43.9%) underwent resective surgery. For 4 of the 41 patients (9.8%) with a previously undiagnosed pertinent finding, re-review detected abnormalities that were not amenable to surgical resection (autoimmunity or significant bilateral pathology).

Seizure Freedom in Children With Pathology-Confirmed Focal Cortical Dysplasia.

OBJECTIVE: We evaluated the temporal course of seizure outcome in children with pathology-confirmed focal cortical dysplasia and explored predictors of sustained seizure freedom. METHODS: We performed a single-center retrospective study of children ≤ 18 years who underwent resective surgery from January 1, 2000 through December 31, 2012 and had pathology-proven focal cortical dysplasia. Surgical outcome was classified as seizure freedom (Engel class I) or seizure recurrence (Engel classes II-IV). Fisher exact and nonparametric Wilcoxon ranksum tests were used, as appropriate. Survival analysis was based on seizure-free outcome. Patients were censored at the time of seizure recurrence or seizure freedom at last follow-up. RESULTS: Thirty-eight patients were identified (median age at surgery, 6.5 years; median duration of epilepsy, 3.3 years). Median time to last follow-up was 13.5 months (interquartile range, 7-41 months). Twenty patients (53%) were seizure free and 26 patients (68%) attained seizure freedom for a minimum of 3 months. Median time to seizure recurrence was 38 months (95% confidence interval, 6-109 months), and the cumulative seizure-free rate was 60% at 12 months (95% confidence interval, 43%-77%). Clinical features associated with seizure freedom at last follow-up included older age at seizure onset (P = .02), older age at surgery (P = .04), absent to mild intellectual disability before surgery (P = .05), and seizure freedom for a minimum of 3 months (P < .001). CONCLUSION: Favorable clinical features associated with sustained seizure freedom included older age at seizure onset, older age at surgery, absent or mild intellectual disability at baseline, and seizure freedom for a minimum of 3 months.

Yield and Predictors of Epilepsy Surgery Candidacy in Children Admitted for Surgical Evaluation.

OBJECTIVE: The aim of this study was to identify preadmission variables that are prognostic of epilepsy surgical candidacy for children admitted into an epilepsy-monitoring unit. METHODS: This study is a retrospective review of patients 0-18 years who were admitted into the pediatric epilepsy-monitoring unit at Mayo Clinic between November 2010 and December 2013 to assess for surgery candidacy for medically intractable epilepsy. Demographic data, epilepsy details, treatments, electroencephalograph and imaging results, and the consensus notes of the epilepsy surgery conferences were collected. RESULTS: One hundred and forty eight children underwent inpatient, prolonged video-electroencephalograph monitoring for presurgical evaluation, of which 136 had their typical events recorded. Five recommended for callosotomy alone were excluded and 131 composed the study group. Of these 131, the epilepsy surgery conference consensus deemed that 69 were surgical candidates, of which 45 (65%) underwent resective surgery. Chi-square analysis found seven preadmission predictors of surgical candidacy: single semiology at seizure onset (P < 0.001), structural etiology (P < 0.001), one or more interictal foci all in the same hemisphere (P < 0.004), focal background electroencephalograph slowing (P < 0.001), focal or hemispheric abnormality on magnetic resonance imaging (P < 0.001), male sex (P = 0.02), and normal development (P = 0.04). CONCLUSIONS: The presence of fewer than four predictors was suggestive of low likelihood of candidacy (<31%), whereas if more than four factors were present, 91% were found to be surgical candidates. These findings facilitate clinical decision-making for providers in a cost-effective manner and provide realistic expectations for families.

Repeat resective surgery in complex pediatric refractory epilepsy: lessons learned.

OBJECT Resection can sometimes offer the best chance of meaningful seizure reduction in children with medically intractable epilepsy. However, when surgery fails to achieve the desired outcome, reoperation may be an option. The authors sought to investigate outcomes following resective reoperation in pediatric patients with refractory epilepsy, excluding tumoral epilepsies. Differences in preoperative workup between surgeries are analyzed to identify factors influencing outcomes and complications in this complex group. METHODS Medical records were reviewed for all pediatric patients undergoing a repeat resective surgery for refractory epilepsy at the authors' institution between 2005 and 2012. Tumor and vascular etiologies were excluded. Preoperative evaluation and outcomes were analyzed for each surgery and compared. RESULTS Ten patients met all inclusion criteria. The median age at seizure onset was 4.5 months. Preoperative MRI revealed no lesion in 30%. Nonspecific gliosis and cortical dysplasia were the most common pathologies. The majority of preoperative workups included MRI, video-electroencephalography (EEG), and SISCOM. Intracranial EEG was performed for 60% for the first presurgical evaluation and 70% for the second evaluation. The goal of surgery was palliative in 4 patients with widespread cortical dysplasia. The final Engel outcome was Class I in 50%. The rate of favorable outcome (Engel Class I-II) was 70%. The complication rate for the initial surgery was 10%. However, the rate increased to 50% with the second surgery, and 3 of these 5 complications were pseudomeningoceles requiring shunt placement (2 of the 3 patients underwent hemispherotomy). CONCLUSIONS Resective reoperation for pediatric refractory epilepsy has a high rate of favorable outcome and should be considered in appropriate candidates, even as a palliative measure. Intracranial EEG monitoring should be considered on initial workup in cases where the results of imaging or EEG studies are ambiguous or conflicting. Epilepsy secondary to cortical dysplasia, especially if the dysplasia is not seen clearly on MRI, can be difficult to cure surgically. Therefore, in these cases, as large a resection as can be safely accomplished should be done, particularly when the goal is palliative. The rate of complications, particularly pseudomeningocele ultimately requiring shunt placement, is much higher following reoperation, and patients should be counseled accordingly.

DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients.

OBJECTIVE: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. METHODS: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. RESULTS: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. CONCLUSIONS: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

Factors contributing to the yield of asymmetric bilateral implantation of intracranial electrodes.

OBJECTIVE: To determine the outcome of implanting fewer electrodes over the hemisphere with less supporting presurgical localizing data. METHODS: We retrospectively reviewed our epilepsy surgery database at Mayo Clinic, Rochester, Minnesota, between January 1, 1999, and December 31, 2011, to identify patients who had an asymmetric number of electrode contacts implanted in each hemisphere for seizure localization. We scored each presurgical noninvasive data point (0, 0.5, or 1) to predict the likelihood of identifying seizure onset in the hemisphere with fewer intracranial electrode contacts (HFEC). An aggregate score was obtained for each patient. RESULTS: Thirteen (37%) of 35 patients had HFEC-onset seizures on intracranial electroencephalography (iEEG). The following factors predicted HFEC-onset seizures: (1) temporal lobe epilepsy (p = 0.02); (2) interictal scalp electroencephalographic discharges at the HFEC (p = 0.04); and (3) both interictal and ictal scalp EEG discharges at the HFEC (p = 0.01). The median (range) aggregate score was 2 (1-3) for patients with HFEC-onset seizures recorded on iEEG and 1 (0-3) for patients without HFEC-onset seizures (p = 0.001). Using this scoring model, the odds ratio of identifying HFEC-onset seizures on iEEG was 6.4 for each one-point increment in the aggregate score. The area under the receiver operating characteristic curve for this model was 0.84, suggesting excellent ability of the aggregate score to discriminate between patients with and without HFEC-onset seizures on iEEG. SIGNIFICANCE: Implanting electrodes on the basis of limited supporting presurgical data may be useful in selected patients, especially those with temporal lobe epilepsy, interictal scalp discharges involving the HFEC, or both interictal and ictal scalp discharges involving the HFEC. In addition, our proposed scoring system may be helpful in selecting patients with complicated epilepsy for implantation of an asymmetric number of intracranial electrodes in the hemispheres.

Diagnostic outcome of surgical revision of intracranial electrode placements for seizure localization.

PURPOSE: We aimed to determine the yield of revising intracranially implanted electrodes and the factors contributing to the yield. METHODS: Patients were identified from the Mayo Clinic Epilepsy Surgery Database between 1997 and 2010. Twenty patients had revision of intracranial electrode placements because initial implantation did not localize seizure onset adequately. RESULTS: Seizures were captured in 18 of 20 patients who underwent intracranial electrode revision, of which 10 (55.6%) showed localized seizure onset that led to a surgical resection. Seizures were improved in 9 of 10 patients who underwent resection; of these, five were seizure free. The only factors found to be statistically significant in localizing ictal onset zone after revised implantation were prior focal scalp interictal discharges and an initial intracranial EEG showing ictal onset at the edge of the electrode grid. No permanent complication was associated with revised implantation, but one patient had transient apraxia of the right foot. CONCLUSIONS: Revised implantation could be useful in selected patients with inadequate seizure localization on initial intracranial EEG. Resective surgery was performed in 50% of patients who underwent revision of intracranial electrodes with the majority of these patients experiencing an improvement in seizure control.

Seizure outcome after AED failure in pediatric focal epilepsy: impact of underlying etiology.

OBJECTIVE: This study aimed to identify long-term seizure outcome in pediatric nonsyndromic focal epilepsy after failure of serial antiepileptic drugs (AEDs) due to lack of efficacy. METHODS: Children (1 month-17 years) with new-onset focal epilepsy not meeting the criteria for a defined electroclinical syndrome diagnosed between 1980 and 2009 while residing in Olmsted County, MN, were retrospectively identified. Medical records of those followed for ≥2 years were reviewed to assess etiology, the number of AEDs that failed due to lack of efficacy, and seizure outcome at final follow-up. Etiology was classified into structural/metabolic, genetic, or unknown. Favorable outcome was defined as seizure freedom ≥1 year, on or off AEDs, without prior epilepsy surgery. Poor outcome was defined as ongoing seizures in the preceding year or having undergone prior epilepsy surgery. RESULTS: Nonsyndromic focal epilepsy accounted for 275/468 (59%) of all patients with newly diagnosed epilepsy--of these, 256 (93%) were followed for a minimum of two years and were included in the study. Median duration of follow-up was 10.0 years. At least one AED had failed due to lack of efficacy in 100 (39.1%) children. Favorable outcomes occurred in 149/156 (95.5%) children with no AED failure, 16/30 (53.3%) with one AED failure, 8/25 (32%) with two AED failures, and only 2/45 (4.4%) with three AED failures. After two AED failures, the seizures of nearly one-quarter of children who had epilepsy with an unknown cause responded favorably to the third AED compared with only 7.8% of the cohort that had epilepsy with a structural/metabolic cause. Children with a remote brain insult had a significantly higher likelihood of favorable outcome with serial AEDs than those with other structural abnormalities. SIGNIFICANCE: Etiology is an important determinant of pharmacoresistance in nonsyndromic focal epilepsy. Surgical evaluation should be considered after failure of 1-2 AEDs in those who have epilepsy with structural causes, excluding remote brain insults. Conversely, as surgical success is lower with normal MRI or more diffuse brain insults, it appears reasonable to hold off surgical evaluation until 2-3 AEDs have failed in such children.

Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy.

We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data.

Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex.

Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long-term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality.

Predicting pharmacoresistance in pediatric epilepsy.

Approximately 20% of children with epilepsy will be pharmacoresistant. The impact of intractable epilepsy extends far beyond just the seizures to result in intellectual disability, psychiatric comorbidity, physical injury, sudden unexpected death in epilepsy (SUDEP), and poor quality of life. Various predictors of pharmacoresistance have been identified; however, accurate prediction is still challenging. Population-based epidemiologic studies show that the majority of children who develop pharmacoresistance do so relatively early in the course of their epilepsy. However, approximately one third of children who initially appear pharmacoresistant in the first few years after epilepsy onset will ultimately achieve seizure freedom without surgery. The most significant predictor that early pharmacoresistance will not remit is the presence of a neuroimaging abnormality. Such children should be strongly considered for surgical evaluation.