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Summary Purpose: We present two methods of implantation for the investigation of suspected insular and perisylvian epilepsy that combine depth and subdural electrodes to capitalize on the advantages of each technique. Methods: Retrospective study of all intracranial EEG studies that included insular electrodes from 2004–2010. Patients were divided according to the implantation scheme. The first method (type 1) consisted of a craniotomy, insertion of insular electrodes after microdissection of the sylvian fissure, orthogonal implantation of mesiotemporal structures with neuronavigation, and coverage of the adjacent lobes with subdural electrodes. The second method (type 2) consisted of magnetic resonance imaging (MRI)–stereotactic frame-guided depth electrode implantation into insula and hippocampus using sagittal axes, and insertion of subdural electrodes through burr holes to cover the adjacent lobes. The combined implantations were developed and performed by one neurosurgeon (AB). Key Findings: Nineteen patients had an intracranial study that sampled the insula, among other regions. Sixteen patients were implanted using the first method, which allowed a mean of 4, 5, 20, 15, and 42 contacts per patient to be positioned into/over the insular, mesial temporal, neocortical temporal, parietal, and frontal areas, respectively. The second method (three patients) allowed a mean of 8, 7, 16, 6, and 9 contacts per patient to sample the same areas, respectively. The four patients in whom transient neurologic deficits occurred were investigated with use of type 1 implantation. Significance: Combined depth and subdural electrodes can be used safely to investigate complex insular/perisylvian refractory epilepsy. Choice of implantation scheme should be individualized according to presurgical data and the need for functional localization.

Tuberous sclerosis complex (TSC) is associated with the potential development of benign hamartomas, including subependymal giant cell astrocytomas (SEGAs). Intracranial hypertension can be caused by SEGAs due to their propensity to block the foramen of Monro. The traditional management approach is to monitor SEGAs with periodic neuroimaging and to resect those that exhibit serial growth and/or cause clinical signs of intracranial hypertension. Recent observations suggest that rapamycin therapy may induce partial regression of SEGAs, therefore providing a potential alternative to resection. The authors present the case of an 8-year-old girl with bilateral SEGAs that led to progressive hydrocephaly and incipient signs of papilledema. Three months after initiating rapamycin therapy, the SEGAs exhibited significant reduction in size (82.6% on the left and 46.7% on the right), and the lesions remained stable 5 months later. Compared with previous case reports, similar or even greater antitumor efficacy was achieved with much lower trough levels of rapamycin (10–15 compared with 3.3–4.5 ng/ml, respectively). The authors discuss various aspects of rapamycin therapy and address unresolved issues that highlight the need for further prospective clinical trials.

Background Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease.

Summary Nearly 90% of patients with tuberous sclerosis complex (TSC) develop epilepsy; however the mechanisms of epileptogenesis remain unclear. Some cortical tubers are thought to be epileptogenic while others are not. This study aimed to evaluate whether tuber burden, size or type seen on magnetic resonance imaging (MRI) co-registers with interictal epileptiform discharges on electroencephalogram (EEG). EEG and MRI data from 69 patients with TSC were reviewed by dividing the cerebrum into four quadrants. Quadrants containing greatest tuber burden, largest tuber, calcified tubers, cyst-like tubers, and no tubers were identified on MRI. For EEG analysis, spikes and sharp waves were counted and averaged to a value per minute, and each quadrant was assigned a score. MRI and EEG findings were compared in each patient. The presence of a cyst-like tuber in a quadrant correlated with a higher incidence of epileptiform activity in the same quadrant ( p =0.002). This finding supports the notion that cyst-like cortical tubers may contribute to the more severe epilepsy profile seen in TSC patients with these lesions. Quadrants containing greatest tuber burden, largest tubers, and calcified tubers were not predictive of regional interictal epileptiform activity. Furthermore, quadrants without any apparent tuber co-registered with interictal epileptiform discharges in two patients, suggesting a multifactorial component of epileptogenicity in TSC.

Background: Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of hamartomatous lesions in multiple organs, including tubers in the brain. The majority of patients with TSC have epilepsy. Some cortical tubers are epileptic foci, while others appear to be physiologically quiescent. It is unknown whether variations in tuber morphology may account for this difference. The objectives of this study were to determine the frequency of cyst-like tubers in patients with TSC, whether cyst-like tubers correlate with TSC genotype, and whether cyst-like cortical tubers are associated with a history of infantile spasms, epilepsy, or refractory epilepsy. Methods: A retrospective chart review was performed of 173 patients with TSC. MRI images were evaluated for the presence of at least one cyst-like cortical tuber. Patient charts were then reviewed for genetic mutation, a history of infantile spasms, epilepsy, and epilepsy refractory to more than three medications. Results: A total of 46% of patients had at least one cyst-like cortical tuber present on neuroimaging. Patients with a TSC2 mutation were more likely to have a cyst-like tuber than patients with TSC1 mutation (p = 0.002) or patients with no mutation identified (p = 0.039). Patients with at least one cyst-like cortical tuber were more likely to have a history of infantile spasms (p = 0.00005), epilepsy (p = 0.0038), and refractory epilepsy (p = 0.0007) than patients without a cyst-like cortical tuber. Conclusion: Cyst-like cortical tubers are strongly associated with TSC2 gene mutation and a more aggressive seizure phenotype in patients with tuberous sclerosis complex.

Object Ischemic cerebral vascular accidents (CVAs) in children result in epilepsy in 25% of patients, which is refractory in 7% of cases. Repeated seizures worsen the global and cognitive prognosis of these patients. To evaluate the prognosis of epilepsy and cognitive development in children with refractory seizures following a CVA, the authors retrospectively studied the effectiveness of periinsular hemispherotomy in the treatment of these patients. Methods Between March 1995 and November 2007, 8 children who suffered from stroke-induced refractory epilepsy underwent a periinsular hemispherotomy. All patients' charts were reviewed in a retrospective manner. Age at the time of the CVA, imaging studies, cause of the ischemic event, onset of the first seizure, patient's handedness, the extent of the parenchymal damage, electroencephalography findings, type of epileptic seizures, number of seizures per day, number of antiepileptic medications, preoperative neuropsychological evaluation, and surgical outcome with regard to the patient's seizure activity were analyzed. Results There were 7 boys and 1 girl in this study. The mean age at stroke was 23 months (range birth–5 years). The mean age at onset of epilepsy was 22 months (range 0–60 months). The mean age at the time of the hemispherotomy was 7 years (range 54–130 months). The average delay prior to the hemispherotomy was 5 years and 3 months (range 23–115 months). Prior to surgery, the average number of seizures per day was 35 (range 5–100). The average number of antiepileptic medications introduced before the hemispherotomy was 8 (range 6–12). Six patients required only 1 surgical intervention and 2 necessitated 2 separate operations:1 underwent a 2-staged hemispherotomy and the other underwent a prior callosotomy. There were no reported surgical complications in this series. Seven children are seizure free. However, the remaining child, after a 3.5-year disease-free interval, has recently started having seizures. No child demonstrated an improvement in neuropsychological evaluation. Conclusions The periinsular hemispherotomy must be considered an alternative in the therapeutic approach to stroke-induced pediatric refractory epilepsy. It is effective in controlling seizure activity. The authors believe the delay before hemispherotomy must be shortened in children with post-CVA refractory epilepsy.

Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC and determined possible associations with SIB. We found a 10% frequency of SIB in our TSC population. When compared with patients without psychiatric symptoms, we identified a significantly higher rate of electroencephalographic interictal spikes in the left frontal lobe and a significantly lower number of tubers in the left occipital, parietal, and posterior temporal lobes. We also found that frequency of TSC2 mutation, history of infantile spasms, history of seizures, mental retardation, and autism are significantly associated with SIB.

The aim of the study described here was to characterize the efficacy and safety of vagus nerve stimulation in a population of patients with tuberous sclerosis complex (TSC) and intractable epilepsy.This retrospective study comprised 16 patients with TSC who underwent implantation of a vagus nerve stimulator for treatment of intractable epilepsy.The average age at vagus nerve stimulator implantation was 15 years (range: 2-44, SD: 12.5) and the average duration of follow-up on VNS was 4 years (range: 0.5-8.6, SD: 2.3). Outcome was rated class I (80% seizure frequency reduction) in 3 (19%), class II (50-79% reduction) in 5 (31%), class III (50% reduction) in 2 (13%), class IV (magnet benefit only) in 1 (6%), and class V (no improvement) in 5 (31%) patients. Intermittent magnet use was effective in aborting seizures in 8 (50%). Five (31%) patients reported an improved level of functioning.The findings suggest that the vagus nerve stimulation can be an effective and safe therapy for patients with TSC with intractable epilepsy.

To review the efficacy, cognitive outcome and safety profile in children treated with vigabatrin (VGB) for infantile spasms (IS) and partial epilepsies related to tuberous sclerosis complex (TSC) and other etiologies.Retrospective review of children followed in the Pediatric Epilepsy Program of Massachusetts General Hospital for Children between May 2001 and March 2006 who were treated with VGB.Eighty-four children were treated with VGB, 68 of them were treated for IS, and 59 were treated for partial seizures (PS). Etiology (TSC or other) was the only predictive factor for IS control with VGB (p0.0003). IS control was achieved in 73% of children with TSC and 27% of children with other etiologies (combined 56%). Partial onset seizures were controlled in 34% of all children, (17% seizure free,17%reduction in seizure frequency50%) and no predictive factor was found. Shorter time from seizure onset to VGB treatment (p0.027) and longer total time on VGB (p0.045) was associated with better IQ-developmental quotient (DQ) outcome in children treated for IS, but not with IS control. Adverse events were seen in 13%. Electroretinogram and/or behavioral visual field (VF) testing was done in 52%. VGB was discontinued in one case due to abnormal electroretinogram (ERG) findings.We confirm the efficacy of VGB in the treatment of IS and PS in an American population. VGB may improve cognitive outcome in the absence of complete IS control, but this finding is of uncertain clinical significance. VGB was well tolerated, and ophthalmologic side effects were uncommon.

1. Philippe Major, MD* 2. Elizabeth A. Thiele, MD, PhD* 1. *Department of Neurology, Massachusetts General Hospital, Boston, Mass After completing this article, readers should be able to: 1. Formulate an appropriate diagnostic plan for a child who has seizures. 2. Discuss the management of epilepsy. The initial article on seizures in childhood (October 2007) focused on the diagnosis and classification of seizures in children. This second article reviews investigational tools and management. The evaluation of a child who has a seizure disorder must be tailored to the findings on history and physical examination. The electroencephalogram (EEG) is the primary electrophysiologic tool; brain neuroimaging is the primary modality for evaluating neuroanatomic and functional features. The EEG can help confirm the clinical diagnosis of epilepsy, classify the type of epilepsy, localize the epileptic focus, and help determine if treatment can be discontinued safely. In general, 21 electrodes placed on specific locations on the patient's scalp measure voltage fluctuations of superficial neurons in relation to time. Figure 1 shows the position and labeling of the scalp electrodes; Figures 2through ⇓⇓⇓6 show examples of typical EEG tracings. Generalized epileptic syndromes are characterized by discharges recorded simultaneously at each electrode; partial epilepsy syndromes show localized spikes or slowing in the epileptogenic region. Epilepsy is a clinical diagnosis that cannot be made on the basis of abnormal EEG findings. In fact, EEG abnormalities can be found in 5% of children who have no history of seizures. Figure 1. Scalp electrode positions for EEG. By convention, electrodes labeled with an even number are placed over the right hemisphere, and odd-numbered electrodes are placed over the left hemisphere. Fp=frontopolar, F=frontal, T=temporal, C=central, P=parietal, O=occipital, z=midline Figure 2. Normal EEG tracing showing a reactive posterior alpha (9-Hz) rhythm in an 8-year-old boy who has no history of seizures. The slow waves observed in the frontal areas are associated with eye movements. Figure 3. EEG tracing showing frequent independent left and right …

1. Philippe Major, MD* 2. Elizabeth A. Thiele, MD, PhD* 1. *Department of Neurology, Massachusetts General Hospital, Boston, Mass After completing this article, readers should be able to: 1. Classify the different seizure types. 2. Distinguish seizures from other paroxysmal phenomena. 3. List the possible causes of seizures according to age and mode of presentation. Seizures are among the most common pediatric neurologic disorders. The overall prevalence of epilepsy is approximately 1%, and as many as 5% of all children experience febrile seizures before the age of 6 years. Seizures are caused by an abnormal and excessive discharge of neurons, usually accompanied by behavioral or sensorimotor manifestations. Epilepsy is defined classically as the occurrence of two or more unprovoked seizures. A seizure can be viewed as a symptom of an underlying central nervous system disorder that requires thorough evaluation and specific treatment. In addition to the consequences of the seizures, 50% of those who have epilepsy experience learning difficulties, and 30% to 50% have mental health and behavioral issues. In this first of two articles on seizures in children, we review the diagnosis and classification of seizures as well as possible causes of seizures in childhood. The second article, to be published in the November 2007 issue of Pediatrics in Review , focuses on the laboratory diagnosis and management of seizure disorders. The diagnosis of epilepsy and classification of specific seizure types are essential to determining a prognosis and choosing an appropriate treatment. The investigation of a child experiencing seizures begins with a medical history and physical examination. Although significant technologic advances have been made in electrophysiology and neuroimaging, the diagnosis of seizures and epilepsy remains largely clinical. Table 1 lists key features of the medical history and physical examination of a child presenting with paroxysmal events. | Questionnaire | || |

Background There are no established variables that predict the success of curative resective epilepsy surgery in children with tuberous sclerosis complex (TSC). Objective We performed a multicenter observational study to identify preoperative factors associated with seizure outcome in children with TSC undergoing resective epilepsy surgery. Methods A retrospective chart review was performed in eligible children at New York Medical Center, Miami Children's Hospital, Cleveland Clinic Foundation, BC Children's Hospital, Hospital for Sick Children, and Sainte-Justine Hospital between January 2005 and December 2013. A time-to-event analysis was performed. The "event" was defined as seizures after resective epilepsy surgery. Results Seventy-four patients (41 male) were included. The median age of the patients at the time of surgery was 120 months (range, 3-216 months). The median time to seizure recurrence was 24.0 ± 12.7 months. Engel Class I outcome was achieved in 48 (65%) and 37 (50%) patients at 1- and 2-year follow-up, respectively. On univariate analyses, younger age at seizure onset (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.03-4.00, P = .04), larger size of predominant tuber (HR: 1.03, 95% CI: 0.99-1.06, P = .12), and resection larger than a tuberectomy (HR: 1.86, 95% CI: 0.92-3.74, P = .084) were associated with a longer duration of seizure freedom. In multivariate analyses, resection larger than a tuberectomy (HR: 2.90, 95% CI: 1.17-7.18, P = .022) was independently associated with a longer duration of seizure freedom. Conclusion In this large consecutive cohort of children with TSC and medically intractable epilepsy, a greater extent of resection (more than just the tuber) is associated with a greater probability of seizure freedom. This suggests that the epileptogenic zone may include the cortex surrounding the presumed offending tuber.

Lymphangioleiomyomatosis (LAM) is a manifestation of tuberous sclerosis complex (TSC) that causes destruction of the lung and chronic respiratory failure. Population-based estimates of demographics, clinical outcomes, and health-care utilization are lacking for TSC and LAM.Data on demographics, clinical outcomes, and health-care utilization in the Quebec ministerial provincial health-care database were analyzed for their association with TSC and LAM.A total of 1,004 subjects with TSC were identified using International Classification of Diseases, Ninth and 10th Revisions, codes for a prevalence of one in 7,872 people. There were 38 subjects with LAM, nine of whom also had TSC. Mean ages as well as the mean age at death were lower in the LAM and TSC group than in the control group. Mortality rates were higher in subjects with LAM than in those with TSC or in control subjects. Subjects with LAM experienced more medical visits and hospitalizations than did those with TSC and control subjects; these were associated with higher health-care costs. Frequently prescribed drugs in TSC or LAM included anticonvulsants, antidepressants, and sedatives; the use of mammalian target of rapamycin inhibitors was uncommon.The prevalence of TSC in Quebec, Canada, is similar to estimates from previously published surveys. LAM is likely underreported, perhaps due to suboptimal case identification or referral. Health-care utilization and mortality for LAM are high, suggesting that timely diagnosis and therapy could be beneficial. Mental health disorders may be an unrecognized clinical feature of LAM. These results provide a population-based background for policymakers and researchers to better address the needs of patients with TSC and LAM.

Background Tuberous sclerosis complex is characterized by the growth of benign tumors in multiple organs, caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. mTOR inhibitors, such as everolimus, are used in patients with tuberous sclerosis complex, mainly to reduce the size of renal angiomyolipomas and subependymal giant cell astrocytomas. There are minimal data available regarding its use during the neonatal period. Methods We report clinical and pharmacological data of three neonates treated with the mTOR inhibitor everolimus (two hemodynamically significant cardiac rhabdomyomas and one voluminous subependymal giant cell astrocytoma). Results Beneficial clinical responses were observed in all three patients and the medication was generally well-tolerated. Optimal dose was 0.1 mg orally once daily and was confirmed with therapeutic drug monitoring. Conclusion Everolimus is a promising pharmacological approach to treat clinically significant inoperable cardiac rhabdomyomas or subependymal giant cell astrocytoma associated with tuberous sclerosis complex during the neonatal period.

Background: Planning for neurology training necessitated a reflection on the experience of graduates. We explored practice characteristics, and training experience of recent graduates. Methods: Graduates from 2010-2014 completed a survey. Results: Response rate was 37% of 211. 56% were female. 91% were adult neurologists. 65% practiced in an outpatient setting. 63% worked in academics. 85% completed subspecialty training (median 1 year). 36% work 3 days a week or less. 82% took general call (median 1 night weekly). Role preparation was considered very good or excellent for most; however poor or fair ratings were 17% in advocacy and 8% in leadership. Training feedback was at least “good” for 87%. Burnout a few times a week or more was noted by 5% (6% during residency, particularly PGY1 and 5). 64% felt overly burdened by paperwork. Although most felt training was adequate, it was poor or fair at preparing for practice management (85%) and personal balance (55%). Most conditions were under-observed in training environment. Many noted a need for more independent practice development and community neurology. Conclusions: Although our training was found to be very good, some identified needs included advocacy training, and more training in general neurology in the longitudinal outpatient/community settings.

Rapamycin inhibits the mTOR (target of rapamycin) pathway and extends lifespan in multiple species. The tuberous sclerosis complex (TSC) protein is a negative regulator of mTOR. In humans, loss of the TSC protein results in a disorder characterized clinically by the growth of benign tumors in multiple organs, due to overactivation of mTOR inhibition. Subependymal giant cell astrocytomas (SEGAs) are benign brain tumors associated with TSC that have traditionally been treated by surgery, but for which mTOR inhibitors have recently been suggested as potential alternative treatments. The duration of mTOR treatment for SEGAs might have to be prolonged, probably lifelong, because SEGAs usually grow back after treatment is stopped. This cohort of patients who will experience prolonged exposure to mTOR inhibitors should be carefully followed longitudinally to better document long term side effects, but also to compare their longevity with the one of similar patients with TSC. These patients represent a unique opportunity to study the potential anti-aging properties of mTOR inhibitors in humans.

Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ∼40% of patients. We hypothesized that unexplained IS cases represent a large collection of rare single-gene disorders. We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n = 44) followed by targeted sequencing of 35 known epilepsy genes (n = 8) or whole-exome sequencing (WES) of familial trios (n = 18) to search for rare inherited or de novo mutations. aCGH analysis revealed de novo variants in 7% of patients (n = 3/44), including a distal 16p11.2 duplication, a 15q11.1q13.1 tetrasomy and a 2q21.3-q22.2 deletion. Furthermore, it identified a pathogenic maternally inherited Xp11.2 duplication. Targeted sequencing was informative for ARX (n = 1/14) and STXBP1 (n = 1/8). In contrast, sequencing of a panel of 35 known epileptic encephalopathy genes (n = 8) did not identify further mutations. Finally, WES (n = 18) was very informative, with an excess of de novo mutations identified in genes predicted to be involved in neurodevelopmental processes and/or known to be intolerant to functional variations. Several pathogenic mutations were identified, including de novo mutations in STXBP1, CASK and ALG13, as well as recessive mutations in PNPO and ADSL, together explaining 28% of cases (5/18). In addition, WES identified 1-3 de novo variants in 64% of remaining probands, pointing to several interesting candidate genes. Our results indicate that IS are genetically heterogeneous with a major contribution of de novo mutations and that WES is significantly superior to targeted re-sequencing in identifying detrimental genetic variants involved in IS.

Behavioral side effects related to the use of levetiracetam (LEV) in epilepsy are increasingly being recognized. Patients followed in our center have reported improvement of these side effects after starting pyridoxine (vitamin B(6)) supplements. Using mailed questionnaires, retrospective chart reviews, and phone call follow-ups, we analyzed 42 pediatric patients who had been treated with LEV and pyridoxine. Twenty-two patients started pyridoxine after being on LEV, and significant behavioral improvement was observed in nine (41%), no effect in eight (36%), deterioration in four (18%), and an uncertain effect in one. The effects of pyridoxine supplementation were observed during the first week. The remaining patients (20) were already on pyridoxine before LEV was started, started pyridoxine and LEV at the same time, or took pyridoxine intermittently. Pyridoxine is an easily available, inexpensive, and safe therapeutic option. Given these preliminary results, we plan to conduct a placebo-controlled cross-over study to better characterize these observations.

Seizures are common and worsen the outcome in critically ill neonates. Predicting seizure recurrence could allow individualizing antiepileptic treatment and improving the outcome. To identify EEG signatures of seizure recurrence, we investigated periictal spectral power and electrographic characteristics of seizures in five consecutive asphyxiated neonates under continuous EEG monitoring. All patients had high seizure burden while undergoing hypothermic neuroprotection. Two neonates had recurrence of seizures on rewarming. Spectral power analysis of fifteen artifact-free consecutive ictal events demonstrated, in all neonates, a significant increase in overall spectral power from the interictal to preictal and ictal periods ( p

Background: Sturge Weber Syndrome (SWS) patients at risk of epilepsy are often not identified before their first seizure which leads to unnecessary follow up of many patients with facial angioma. Methods: The medical photography database of our institution has been reviewed to identify SWS patients followed between 1993 and 2013. Patients with isolated glaucoma were compared to patients with epilepsy regarding the location of the facial angioma, the presence of asymmetrical background activity on EEG done prior epilepsy onset and cerebral imaging. Logistical regression tests and a p-value of 0.05 were used. Results: 21 patients with SWS have been identified. No significant difference was noted when patients were compared based on the laterality of the lesion (p=0.169), or the location of the facial angioma (p = 0.314 to 0.999). Only 2 epileptic patients had digital EEG done prior the onset of epilepsy and only 2 patients with glaucoma had digital EEG done during their follow up. No significant difference was noted between EEG background activities in the two groups (p= 0.514). The presence of venous drainage anomalies (VDA) predicted (p = 0.004) the onset of epilepsy. Conclusions: Cerebral VDA increases the risk of epilepsy in SWS patients. Since they can be detected at birth, they might guide the management.

Background Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present with many disabling neurological disorders, the most common being epilepsy. Although it is a chronic multi-system disease, healthcare utilization and long-term outcome of subjects with TSC are not yet well defined. The goal of this study was to evaluate the direct cost and long-term outcome of TSC in the province of Quebec, compared to other forms of epilepsy and healthy controls. Methods Our provincial health care database was interrogated to determine use of medical services by patients with TSC, epilepsy and healthy controls from 1996 to 2011. Data on demographics, outcomes and health care utilization were analyzed. Results 1004 TSC, 41,934 with epilepsy and 41,934 controls were identified. The prevalence of TSC was 1/7872 compared to 1/189 for epilepsy. TSC experienced more hospitalizations, medical visits and prescription drug use. Their most common admission diagnosis was seizures and age at death was significantly lower: 61.3 years old for TSC vs 69.6 and 76.6 years old for epilepsy and controls ( p 0.001 ). Conclusions TSC subjects have a significantly higher burden of disease than other subjects with epilepsy. These results stress the need for specialized services in this population through the lifespan.

A 14-year-old girl presented with a prolonged migraine visual aura of several weeks' duration. Symptoms gradually resolved over a 6-week period, with no recurrence of visual aura over a 20-month follow-up period. Although there is significant overlap between the features of stereotypical and persistent migraine auras, or "visual snow," the latter tend to be unformed and can occupy the entire visual field of both eyes. To our knowledge, this phenomenon has been reported only twice before in children. Recognition of its features will allow the pediatric ophthalmologist to differentiate persistent visual aura from visual hallucinations.

The phenotypic and etiologic spectrum in adults with nodular heterotopias (NHs) has been well characterized. However, there are no large pediatric case series. We, therefore, wanted to review the clinical features of NHs in our population.Hospital records of 31 patients with pathology or imaging-confirmed NHs were reviewed. Two-sided Fisher's exact t-test was used to assess associations between distribution of NHs and specific clinical features.NHs were distributed as follows: 8 (26%) unilateral focal subependymal, 3 (10%) unilateral diffuse subependymal, 5 (16%) bilateral focal subependymal, 12 (39%) bilateral diffuse subependymal, and 3 (10%) isolated subcortical. The phenotypic spectrum in our population differs from that described in adults. Significant morbidity and mortality are associated with presentation in childhood. Twenty-two of 31 patients (71%) died in the neonatal period or in childhood. Additional cerebral malformations were found in 80% and systemic malformations in 74%. The majority of patients had developmental delay, intellectual deficit, and intractable epilepsy. Patients with unilateral focal NHs were more likely to have ventriculomegaly (p = 0.027), and those with bilateral diffuse NHs more likely to have cerebellar abnormalities (p = 0.007). Isolated subcortical NHs were associated with multiple malformations (p = 0.049) and cardiac abnormalities (p = 0.027). Underlying etiology was heterogeneous and determined in only six cases (19%): del chr 1p36, del chr 15q11, pyruvate dehydrogenase deficiency, sialic acidosis type 1, Aicardi syndrome, and FLNA mutation.NHs are present in childhood as part of multiple cerebral and systemic malformations; developmental delay and refractory seizures are the rule rather than the exception. Milder forms go unrecognized until seizure onset in adulthood.

We present two methods of implantation for the investigation of suspected insular and perisylvian epilepsy that combine depth and subdural electrodes to capitalize on the advantages of each technique.Retrospective study of all intracranial EEG studies that included insular electrodes from 2004-2010. Patients were divided according to the implantation scheme. The first method (type 1) consisted of a craniotomy, insertion of insular electrodes after microdissection of the sylvian fissure, orthogonal implantation of mesiotemporal structures with neuronavigation, and coverage of the adjacent lobes with subdural electrodes. The second method (type 2) consisted of magnetic resonance imaging (MRI)-stereotactic frame-guided depth electrode implantation into insula and hippocampus using sagittal axes, and insertion of subdural electrodes through burr holes to cover the adjacent lobes. The combined implantations were developed and performed by one neurosurgeon (AB).Nineteen patients had an intracranial study that sampled the insula, among other regions. Sixteen patients were implanted using the first method, which allowed a mean of 4, 5, 20, 15, and 42 contacts per patient to be positioned into/over the insular, mesial temporal, neocortical temporal, parietal, and frontal areas, respectively. The second method (three patients) allowed a mean of 8, 7, 16, 6, and 9 contacts per patient to sample the same areas, respectively. The four patients in whom transient neurologic deficits occurred were investigated with use of type 1 implantation.Combined depth and subdural electrodes can be used safely to investigate complex insular/perisylvian refractory epilepsy. Choice of implantation scheme should be individualized according to presurgical data and the need for functional localization.

Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease.A retrospective chart review of all patients with TSC seen between January 2002 and October 2008. Charts were reviewed for a history of infantile spasms (IS), seizure other than IS, refractory epilepsy, Lennox-Gastaut syndrome (LGS), anticonvulsant medication use, ages of seizure onset, last seizure, last clinic visit, clinical seizure phenotype(s), cognitive impairment, and genetic mutation.Two hundred ninety-one patients were included. Among these patients, 37.8% had a history of IS; 85.2% had a history of seizure; 54.1% developed multiple seizure types, not including IS; 63.2% had seizure onset in the first year of life; and 12.1% of adults without a seizure history developed epilepsy. Of epilepsy patients, 62.5% developed refractory epilepsy and 33.5% achieved epilepsy remission; 37.5% of these patients achieved medication freedom. IS was a risk factor for refractory epilepsy (p0.0001) and LGS (p0.0001). History of seizure, IS, age at seizure onset, and refractory epilepsy each correlated with poor cognitive outcome (p0.0001). Epilepsy remission correlated with better cognitive outcome (p0.0001). TSC2 was a risk factor for IS and epilepsy; patients without an identified mutation were more likely to achieve remission.Most patients with TSC develop epilepsy and most develop multiple seizure types. Onset typically occurs in the first year of life; however, adults remain at risk. Although refractory epilepsy is common, many patients achieve seizure control. Many features of seizure history are predictive of cognitive and epilepsy outcome.

The purpose of this study was to characterize the epileptogenicity of tubers and surrounding cortex in patients with tuberous sclerosis complex (TSC). Three pediatric patients with TSC and intractable epilepsy underwent surgical resection of tubers associated with epileptogenic foci. In all patients, presurgical imaging revealed a prominent tuber that correlated on electroencephalography (EEG) with frequent interictal epileptiform discharges and electrographic seizures. Intracranial electrocorticography (ECoG) was performed using subdural grids placed over the tuber and surrounding cortex and depth electrodes positioned directly within the tuber. In all three patients, the depth electrode within the tuber was electrographically silent, whereas the surrounding cortical tissue showed significant epileptiform activity. The tuber and the electrically active adjacent cortex were resected. The patients experienced a drastic reduction in seizure frequency postsurgery. Epileptogenicity of cortical tubers may derive not from the lesion itself, but rather from the perturbation or abnormal development of the surrounding cortex.

Background: Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present with many disabling neurological symptoms, the most common being seizures. Although it is a chronic systemic syndrome, healthcare utilization and long-term outcome of subjects with TSC are not well defined. The goal of this study was to evaluate the direct cost and long-term outcome of TSC compared to other forms of epilepsy and healthy controls. Methods: Our provincial health care database was interrogated to determine use of medical services by patients with TSC, epilepsy and healthy controls from 1996-2011. Data on demographics, outcomes and health care utilization were analyzed. Results: 1004 TSC, 41,934 with epilepsy and 41,934 controls were identified. The prevalence of TSC was 1/7,872 compared to 1/189 for epilepsy. TSC experienced more hospitalizations, medical visits and prescription drug use, resulting in higher total health care costs. Their most common admission diagnosis was seizures and age at death was significantly lower: 61,3 years old for TSC vs 69,6 and 76,6 years old for epilepsy and controls, (pConclusions: TSC subjects have a significantly higher burden of disease than other subjects with epilepsy. These results stress the need for specialized services in this population through the lifespan.

Background: Debate persists in Canada about the cost and benefit of vagal nerve stimulation in patients with refractory epilepsy. The aim of our study was to evaluate the impact of a vagal nerve stimulator on the seizure frequency and the admission rate of children with refractory epilepsies over five years of follow-up. Methods: 52 patients were implanted between 2000-2013. Of these, 37 were followed at CHU Sainte-Justine and 21 kept seizure diaries. Seizure frequency was compared to the baseline at 6 months, 12 months, 24 months and 60 months of follow up using a multivariate ANOVA analysis. The hospitalization rate was calculated as the mean difference between the number of hospitalizations prior to and after the implantation. Results: Seizure frequency decreased by 58% at 6 months, by 61% at 12 months, by 53% at 24 months and by 63% at 60 months of follow up respectively compared to the baseline (pConclusion: In our population, vagal nerve stimulation has a sustained impact on seizure frequency and hospitalization rates. This supports previous data from our group and others on cost-effectiveness of the technique in children with refractory epilepsy.

This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical presentation than patients with mesial temporal sclerosis. Genetic studies of these mostly French Canadian families should help confirm the existence of a distinct syndrome.