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Access to paediatric neurology care is complex, resulting in significant wait times and negative patient outcomes. The goal of the American Academy of Pediatrics National Coordinating Center for Epilepsy's project, Access Improvement and Management of Epilepsy with Telehealth (AIM-ET), was to identify access and management challenges in the deployment of telehealth technology. AIM-ET organised four paediatric neurology teams to partner with primary-care providers (PCP) and their multidisciplinary teams. Telehealth visits were conducted for paediatric epilepsy patients. A post-visit survey assessed access and satisfaction with the telehealth visit compared to an in-person visit. Pre/post surveys completed by PCPs and neurologists captured telehealth visit feasibility, functionality and provider satisfaction. A provider focus group assessed facilitators and barriers to telehealth. Sixty-one unique patients completed 75 telehealth visits. Paired t-test analysis demonstrated that telehealth enhanced access to epilepsy care. It reduced self-reported out-of-pocket costs ( p

Tuberous sclerosis complex (TSC) is a multisystem disorder with increased prevalence of autism spectrum disorders (ASDs). This project aimed to characterize the autism phenotype of TSC and identify biomarkers of risk for ASD. Because abnormalities of EEG during sleep are tied to neurodevelopment in children, we compared electroencephalographic (EEG) measures during Stage II sleep in TSC children who either did (ASD+) or did not (ASD-) exhibit symptoms of ASD over 36-month follow up. Relative alpha band power was significantly elevated in the ASD+ group at 24 months of age with smaller differences at younger ages, suggesting this may arise from differences in brain development. These findings suggest that EEG features could enhance the detection of risk for ASD.

Objective To determine if routine electroencephalography (EEG) in seizure‐naive infants with tuberous sclerosis complex (TSC) can predict epilepsy and subsequent neurocognitive outcomes. Methods Forty infants 7 months of age or younger and meeting the genetic or clinical diagnostic criteria for tuberous sclerosis were enrolled. Exclusion criteria included prior history of seizures or treatment with antiseizure medications. At each visit, seizure history and 1‐hour awake and asleep video‐EEG, standardized across all sites, were obtained until 2 years of age. Developmental assessments (Mullen and Vineland‐II) were completed at 6, 12, and 24 months of age. Results Of 40 infants enrolled (mean age of 82.4 days), 32 completed the study. Two were lost to follow‐up and six were treated with antiepileptic drugs (AEDs) due to electrographic seizures and/or interictal epileptiform discharges (IEDs) on their EEG studies prior to the onset of clinical seizures. Seventeen of the 32 remaining children developed epilepsy at a mean age of 7.5 months (standard deviation [SD] = 4.4). Generalized/focal slowing, hypsarrhythmia, and generalized/focal attenuation were not predictive for the development of clinical seizures. Presence of IEDs had a 77.3% positive predictive value and absence a 70% negative predictive value for developing seizures by 2 years of age. IEDs preceded clinical seizure onset by 3.6 months (mean). Developmental testing showed significant decline, only in infants with ongoing seizures, but not infants who never developed seizures or whose seizures came under control. Significance IEDs identify impending epilepsy in the majority (77%) of seizure‐naive infants with TSC. The use of a 1‐hour awake and asleep EEG can be used as a biomarker for ongoing epileptogenesis in most, but not all, infants with TSC. Persistent seizures, but not history of interictal epileptiform activity or history of well‐controlled seizures, correlated with low scores on the Vineland and Mullen tests at 2 years of age.

After initially successful treatment of infantile spasms, the long-term cumulative risk of relapse approaches 50%, and there is no established protocol to mitigate this risk. Although vigabatrin may be an effective means to prevent relapse, there is little guidance as to ideal duration and dosage. Using a cohort of children with infantile spasms and tuberous sclerosis complex (TSC), we evaluated the potential association of post-response VGB treatment and the rate of infantile spasms relapse. Patients with infantile spasms and clinical response to vigabatrin were identified among a multicenter prospective observational cohort of children with TSC. For each patient we recorded dates of infantile spasms onset, response to vigabatrin, relapse (if any), and quantified duration and dosage of vigabatrin after response. Time to relapse as a function of vigabatrin exposure was evaluated using survival analyses. We identified 50 children who responded to VGB. During a median follow-up of 16.6 months (IQR 10.3–22.9), 12 (24%) patients subsequently relapsed after a median of 7.8 months (IQR 3.1–9.6). Relapse occurred after VGB discontinuation in four patients, and during continued VGB treatment in the remaining eight cases. In survival analyses, risk of relapse was unaffected by the presence or absence of VGB treatment (HR 0.31, 95%CI 0.01–28.4, P = 0.61), but weighted-average dosage was associated with marked reduction in relapse risk: Each 50 mg/kg/d increment in dosage was associated with 61% reduction in risk (HR 0.39, 95%CI 0.17 – 0.90, P = 0.026). This study suggests that the risk of infantile spasms relapse in TSC may be reduced by high-dose vigabatrin treatment.

Background To determine if early epilepsy surgery mitigates detrimental effects of refractory epilepsy on development, we investigated surgical and neurodevelopmental outcomes in children with tuberous sclerosis complex who underwent surgery before age two years. Methods Prospective multicenter observational study of 160 children with tuberous sclerosis complex. Surgical outcome was determined for the seizure type targeted by surgery. We obtained Vineland Adaptive Behavior Scales, Second Edition (Vineland-II); Mullen Scales of Early Learning; and Preschool Language Scales, Fifth Edition, at age three, six, nine, 12, 18, 24, and 36 months. Surgical cases were compared with children without seizures, with controlled seizures, and with medically refractory seizures. Results Nineteen children underwent surgery (median age 17 months, range 3.7 to 21.3), and mean follow-up was 22.8 months (range 12 to 48). Surgical outcomes were favorable in 12 (63%, Engel I-II) and poor in seven (37%, Engel III-IV). Nine (47%) had new or ongoing seizures distinct from those surgically targeted. All children with seizures demonstrated longitudinal decline or attenuated gains in neurodevelopment, the surgical group scoring the lowest. Favorable surgical outcome was associated with increased Mullen Scales of Early Learning receptive and expressive language subscores compared with the medically refractory seizure group. A nonsignificant but consistent pattern of improvement with surgery was seen in all tested domains. Conclusions These pilot data show neurodevelopmental gains in some domains following epilepsy surgery. A properly powered, prospective multicenter observational study of early epilepsy surgery is needed, using both surgical and developmental outcome metrics.

OBJECTIVEThe goal of this study was to evaluate the predictive value and relative contribution of noninvasive presurgical functional imaging modalities based on the authors’ institutional experience in pursuing seizure-free surgical outcomes in children with medically refractory epilepsy.METHODSThis was a retrospective, single-institution, observational cohort study of pediatric patients who underwent evaluation and surgical treatment for medically refractory partial epilepsy between December 2003 and June 2016. During this interval, 108 children with medically refractory partial epilepsy underwent evaluation for localization and resective epilepsy surgery. Different noninvasive functional imaging modalities, including ictal SPECT, FDG-PET, and magnetoencephalography–magnetic source imaging, were utilized to augment a standardized paradigm (electroencephalography/semiology, MRI, and neuropsychology findings) for localization. Outcomes were evaluated at a minimum of 2 years (mean 7.5 years) utilizing area under the receiver operating characteristic curve analysis. Localizing modalities and other clinical covariates were examined in relation to long-term surgical outcomes.RESULTSThere was variation in the contribution of each test, and no single presurgical workup modality could singularly and reliably predict a seizure-free outcome. However, concordance of presurgical modalities yielded a high predictive value. No difference in long-term outcomes between inconclusive (normal or diffusely abnormal) and abnormal focal MRI results were found. Long-term survival analyses revealed a statistically significant association between seizure freedom and patients with focal ictal EEG, early surgical intervention, and no history of generalized convulsions.CONCLUSIONSComprehensive preoperative evaluation utilizing multiple noninvasive functional imaging modalities is not redundant and can improve pediatric epilepsy surgical outcomes.

Background We assessed the clinical utility of routine electroencephalography (EEG) in the prediction of epilepsy onset in asymptomatic infants with tuberous sclerosis complex. Methods This multicenter prospective observational study recruited infants younger than 7 months, seizure-free and on no antiepileptic drugs at enrollment, who all underwent serial physical examinations and video EEGs throughout the study. Parental education on seizure recognition was completed at the time of initial enrollment. Once seizure onset occurred, standard of care was applied, and subjects were followed up until 24 months. Results Forty patients were enrolled, 28 older than 12 months with completed EEG evaluation at the time of this interim analysis. Of those, 19 (67.8%) developed seizures. Epileptic spasms occurred in 10 (52.6%), focal seizures in five (26.3%), generalized tonic-clonic seizure in one (5.3%), and a combination of epileptic spasms and focal seizures in three (15.7%). Fourteen infants (73.6%) had the first emergence of epileptiform abnormalities on EEG at an average age 4.2 months, preceding seizure onset by a median of 1.9 months. Hypsarrhythmia or modified hypsarrhythmia was not found in any infant before onset of epileptic spasms. All children with epileptiform discharges subsequently developed epilepsy (100% positive predictive value), and the negative predictive value for not developing epilepsy after a normal EEG was 64%. Conclusions Serial routine EEGs in infants with tuberous sclerosis complex is a feasible strategy to identify individuals at high risk for epilepsy. The most frequent clinical presentation was epileptic spasms followed by focal seizures, and then a combination of both seizure types.

Background Children with tuberous sclerosis complex (TSC), caused by pathogenic variants in TSC1/TSC2, are at risk for intellectual disability. TSC2 pathogenic variants appear to increase the risk, compared with TSC1. However, the effect of TSC2 pathogenic variants on early and specific domains of development hasn't been studied. Using an extensively phenotyped group, we aimed to characterize differences in early intellectual development between genotypes. Methods The study group (n = 92) included participants with TSC enrolled in a multicenter study involving genetic testing and detailed prospective phenotyping including the Mullen Scales of Early Learning, a validated measure of cognition, language, and motor development in babies and preschool children. Mean T-scores at 24 months for each Mullen Scales of Early Learning domain were calculated for children with, versus without, a TSC2 pathogenic variant. Multivariable linear regression models were used to compare the groups, adjusting for seizures. Results T-scores on every Mullen Scales of Early Learning domain were significantly worse in the TSC2 group. Below average composite scores were present in three-fourths of the TSC2 group, compared with one-fourth of those without TSC2. Having a TSC2 pathogenic variant was associated with lower composite Mullen Scales of Early Learning scores, even when corrected for seizures. Conclusions In a well-characterized patient population with standardized assessment of multiple aspects of development, we found that having a TSC2 pathogenic variant was associated with significantly lower Mullen Scales of Early Learning scores at age 24 months, independent of seizures. These data suggest that a baby with a TSC2 pathogenic variant is at high risk for significant developmental delays by 24 months.

Epilepsy surgery in frontal lobe epilepsy (FLE) has less favorable seizure-free outcomes than temporal lobe epilepsies. Possible contributing factors include fast propagation patterns and large clinically silent areas which are characteristics of the frontal lobes. Bilateral frontal lobe abnormalities on MRI are another relative contraindication to epilepsy surgery. For example, bilateral encephalomalacia may be a presupposition to bilateral or multifocal epilepsy. The possibility of potential disinhibition with already poor reserves may be another deterrent to consideration for resective epilepsy surgery. As such, conventional surgical approaches to intractable epilepsy with bilateral frontal injury may be limited to palliative procedures like vagus nerve stimulation and corpus callosotomy. We present a case in which the epileptogenic zone was a subset of the acquired, bilateral, cystic encephalomalacia. This iatrogenic injury resulted from two prior craniotomies for excision of craniopharyngioma and its recurrence.Following the initial bilateral and subsequent unilateral, subdural grid- and depth electrode-based localization and resection, our patient has remained seizure-free 2years after epilepsy surgery with marked improvement in her quality of life, as corroborated by her neuropsychological test scores. Our patient's clinical course is testament to the potential role for resective strategies in selected cases of intractable epilepsy associated with bifrontal injury. Reversal of behavioral deficits with frontal lobe epilepsy surgery such as in this patient provides a unique opportunity to further our understanding of the complex nature of frontal lobe function.

Epilepsy associated with preterm birth is often refractory to anticonvulsants. Children who are born preterm are also prone to cognitive delay and behavioral problems. Brains from these children often show diffuse abnormalities in cerebral circuitry that is likely caused by disrupted development during critical stages of cortical formation. To test the hypothesis that prenatal injury impairs the developmental switch of gamma-amino butyric acid (GABA)ergic synapses from excitatory to inhibitory, thereby disrupting cortical circuit formation and predisposing to epilepsy, we used immunohistochemistry to compare the expression of cation-chloride transporters that developmentally regulate postsynaptic GABAergic discharges in postmortem cerebral samples from infants born preterm with known white matter injury (n = 11) with that of controls with minimal white matter gliosis (n = 7). Controls showed the expected developmental expression of cation-chloride transporters NKCC1 and KCC2 and ofcalretinin, a marker of a GABAergic neuronal subpopulation. Samples from infants with white matter damage showed a significant loss of expression of both NKCC1 and KCC2 in subplate and white matter. By contrast, there were no significant differences in total cell number or glutamate transporter VGLUT1 expression. Together, these novel findings suggest a molecular mechanism involved in the disruption of a critical stage of cerebral circuit development after brain injury from preterm birth that may predispose to epilepsy.

Summary: Purpose: Many children with refractory epilepsy can achieve better seizure control with surgical therapy. An abnormality on magnetic resonance imaging (MRI), along with corroborating localization by other modalities, markedly increases chances of successful surgical outcome. We studied the impact of high-resolution MRI on the surgical outcome of intractable epilepsy. Methods: High-resolution MRI using four-coil phased surface array was obtained as part of the comprehensive presurgical protocol for children with focal onset intractable seizures evaluated by our epilepsy center during the first half of 2002. Results: Thirteen consecutive children, ages 5 to 18 years, entered this prospective study. For four patients with a lesion on a recent MRI examination with a standard head coil, management did not change with high-resolution MRI. Standard MRI in the other nine patients did not identify a lesion. However, high-resolution MRI with the phased-array surface coil found previously undiagnosed focal abnormalities in five of nine patients. These abnormalities included hippocampal dysplasia, hippocampal atrophy, and dual pathology with frontal cortical dysplasia. In four of nine patients, no identifiable lesion was identified on the high-resolution MRI. All patients underwent invasive monitoring. In three of five patients, newly diagnosed lesions correlated with EEG abnormalities, and resection was performed. Conclusions: In our center, high-resolution MRI identified lesions not detected by standard MRI in more than half the children (56%). Technical advances such as four-coil phased surface array MRI can help identify and better delineate lesions, improving the diagnosis of patients who are candidates for surgical treatment of refractory epilepsy.

Summary: Purpose: Although seizures are relatively common in acute childhood leukemias, evolution into epilepsy is rare. Methods: We describe three patients with acute leukemias who received chemotherapy. One patient also received cranial irradiation. Results: All three developed recurrent complex partial seizures after initiation of chemotherapy. Initial neuroimaging performed in two patients was normal. Subsequent neuroimaging in all three revealed mesial temporal sclerosis. Conclusions: The association of mesial temporal sclerosis in acute childhood leukemias has not been previously described and may be secondary to antileukemic treatment and recurrent seizures.

The association of psychiatric disorders and pediatric epilepsy is under appreciated by clinicians. Behavioral disorders, especially depression, are often perceived as "reactionary" processes. In fact, these comorbid disorders can be more disabling than the epilepsy itself. This review discusses the common behavioral comorbidities associated with epilepsy including autistic spectrum disorders, psychosis, attention deficit hyperactivity disorders, and mood disorders.

The aim of epilepsy surgery in children is not only to control seizures but also to curtail future adverse neurological sequelae and improve quality of life. If presurgical evaluation demonstrates discordant or multifocal disease, intracranial surgery may be denied as a viable treatment option. When surgical therapy is offered not just as curative but also as palliative therapy, many children not considered optimal surgical candidates may benefit. From a consecutive series of 57 cases involving children who underwent intracranial epilepsy surgery at Rainbow Babies and Children's Hospital during 2001–2005, the authors present in detail 3 cases involving children who benefited significantly from such an aggressive approach. Marked improvement occurred not only in seizure control, but also in developmental and social functioning.