Mortality in infantile spasms: A hospital-based study.

OBJECTIVE: To determine risk factors and causes for mortality during childhood in patients with infantile spasms (IS). We describe the overall goals of care for those who died. METHODS: This is a retrospective chart review of IS patients born between 2000 and 2011. We examined potential risk factors for mortality, including etiology, neurologic impairment, medication use, persistence of epileptic spasms, and comorbid systemic involvement (requirement for G-tube feedings, respiratory interventions). For patients who died, we describe cause of death and resuscitation status or end-of-life care measures. RESULTS: We identified 150 IS patients with median follow-up of 12 years. During the study period, 25 (17%) patients died, 13 before 5 years of age. Univariate analysis demonstrated that developmental delay, identifiable etiology, hormonal use for IS, persistence of epileptic spasms, polypharmacy with antiseizure medications, refractory epilepsy, respiratory system comorbidity, and the need for a G-tube were significant risk factors for mortality. In a multivariate analysis, mortality was predicted by persistence of epileptic spasms (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 1.11-16.67, P = .035) and significant respiratory system comorbidity (OR = 12.75, 95% CI = 2.88-56.32, P = .001). Mortality was epilepsy-related in one-third of patients who died with sudden unexpected death in epilepsy (SUDEP), accounting for 88% of epilepsy-related deaths. Most deaths before age 5 years were related to respiratory failure, and SUDEP was less common (17%) whereas SUDEP was more common (45%) with deaths after 5 years. For the majority (67%) of patients with early mortality, an end-of-life care plan was in place (based on documentation of resuscitation status, comfort measures, or decision not to escalate medical care). SIGNIFICANCE: Mortality at our single-center IS cohort was 17%, and persistence of epileptic spasms and comorbid respiratory system disorders were the most important determinants of mortality. Early deaths were related to neurological impairments/comorbidities. SUDEP was more common in children who died after 5 years of age than in those who died younger than 5 years.

Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression.

OBJECTIVE: We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and early myoclonic encephalopathy) and evaluate genotype-phenotype correlations. METHODS: We enrolled 33 patients with a referral diagnosis of Ohtahara syndrome or early myoclonic encephalopathy without malformations of cortical development. We performed detailed phenotypic assessment including seizure presentation, electroencephalography, and magnetic resonance imaging. We confirmed burst suppression in 28 of 33 patients. Research-based exome sequencing was performed for patients without a previously identified molecular diagnosis from clinical evaluation or a research-based epilepsy gene panel. RESULTS: In 17 of 28 (61%) patients with confirmed early burst suppression, we identified variants predicted to be pathogenic in KCNQ2 (n = 10), STXBP1 (n = 2), SCN2A (n = 2), PNPO (n = 1), PIGA (n = 1), and SEPSECS (n = 1). In 3 of 5 (60%) patients without confirmed early burst suppression, we identified variants predicted to be pathogenic in STXBP1 (n = 2) and SCN2A (n = 1). The patient with the homozygous PNPO variant had a low cerebrospinal fluid pyridoxal-5-phosphate level. Otherwise, no early laboratory or clinical features distinguished the cases associated with pathogenic variants in specific genes from each other or from those with no prior genetic cause identified. INTERPRETATION: We characterize the genetic landscape of epileptic encephalopathy with burst suppression, without brain malformations, and demonstrate feasibility of genetic diagnosis with clinically available testing in >60% of our cohort, with KCNQ2 implicated in one-third. This electroclinical syndrome is associated with pathogenic variation in SEPSECS. Ann Neurol 2017;81:419-429.

Response to clobazam in continuous spike-wave during sleep.

AIM: To evaluate the efficacy of clobazam treatment in reducing epileptiform discharges and modifying neuropsychological function in continuous spike-wave during slow wave sleep. METHOD: We performed a prospective clinical trial in patients with continuous spike-wave during sleep aged 4 to 10 years. Patients underwent neuropsychological assessment and overnight electroencephalographic monitoring before treatment, and subsequent repeat assessment and overnight electroencephalographic monitoring 3 months after treatment. Treatment consisted of 1mg/kg clobazam up to a maximum dose of 30mg during the first night, followed by 0.5mg/kg nightly for 3 months. RESULTS: Nine patients completed the study and had pre- and post-neuropsychological evaluation. There was a qualitative reduction in median (p25 -p75 ) spike percentage after 3 months (72.2 [68.0-75.8] vs 32.7 [4.7-81.7]). There were no marked changes in median (p25 -p75 ) IQ comparing pre- and post-clobazam treatment (80.0 [74.0-88.0] vs 80.0 [67.0-89.0]). There was a qualitative increase in Verbal IQ (83.0 [69.0-92.0] vs 95.0 [83.0-99.0]) and a qualitative decrease in Non-verbal IQ (84.0 [74.0-87.0] vs 71.0 [60.0-84.0]). INTERPRETATION: Qualitative improvements in epileptiform activity and cognition occurred in patients treated with clobazam for 3 months and the relationship between epileptiform activity and cognitive outcome should be studied in larger studies. WHAT THIS PAPER ADDS: Verbal IQ in patients with continuous spike-wave during sleep improved following short-term treatment with clobazam. Other neuropsychological improvements were observed, but varied by patient. Cognitive improvement was observed despite some worsening of epileptiform discharges.

Copy number variation plays an important role in clinical epilepsy.

OBJECTIVE: To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. METHODS: We identified patients with International Classification of Diseases, ninth revision (ICD-9) codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children's Hospital. We reviewed medical records and included patients who met criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. RESULTS: Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1-4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18kb to 142Mb, and 34% were >500kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or "hotspots." We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. INTERPRETATION: Copy number abnormalities play an important role in patients with epilepsy. Because the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy.

Utility of initial EEG in first complex febrile seizure.

OBJECTIVE: The risk of developing epilepsy following febrile seizures (FS) varies between 2% and 10%, with complex febrile seizures (CFS) having a higher risk. We examined the utility of detected epileptiform abnormalities on the initial EEG following a first CFS in predicting subsequent epilepsy. METHODS: This was a retrospective study of consecutive patients (ages 6-60 months) who were neurologically healthy or mildly delayed, seen in the ED following a first CFS and had both an EEG and minimum of 2-year follow-up. Data regarding clinical characteristics, EEG report, development of subsequent epilepsy, and type of epilepsy were collected. Established clinical predictors for subsequent epilepsy in children with FS and EEG status were evaluated for potential correlation with the development of subsequent epilepsy. Sensitivity, specificity, and positive and negative predictive values of an abnormal EEG (epileptiform EEG) were calculated. RESULTS: A group of 154 children met our inclusion criteria. Overall, 20 (13%) children developed epilepsy. The prevalence of epilepsy was 13% (CI 8.3-19.6%). Epileptiform abnormalities were noted in 21 patients (13.6%), EEG slowing in 23 patients (14.9%), and focal asymmetry in six (3.8%). Epileptiform EEGs were noted in 20% (4/20) of patients with epilepsy and 13% (17/134) of patients without epilepsy (p=0.48). At an estimated risk of subsequent epilepsy of 10% (from population-based studies of children with FS), we determined that the PPV of an epileptiform EEG for subsequent epilepsy was 15%. None of the clinical variables (presence of more than 1 complex feature, family history of epilepsy, or status epilepticus) predicted epilepsy. CONCLUSIONS: An epileptiform EEG was not a sensitive measure and had a poor positive predictive value for the development of epilepsy among neurologically healthy or mildly delayed children with a first complex febrile seizure. The practice of obtaining routine EEG for predicting epilepsy after the first CFS needs clarification by well-defined prospective studies.

Safety and retention rate of rufinamide in 300 patients: a single pediatric epilepsy center experience.

OBJECTIVE: Reports of studies evaluating rufinamide as an add-on therapy in children and adolescents with refractory epilepsy are restricted to a few publications. Prospective multicenter studies including children and adults have yielded important information about several types of epilepsies and syndromes. We evaluated the use of rufinamide in a single pediatric center with a large cohort and long-term follow-up period. METHODS: We retrospectively included patients taking rufinamide from November 2008 to March 2013. Response was defined by a seizure reduction of ≥50% compared to baseline. RESULTS: Three hundred patients with a median age of 9.1 years (range 0.4-29.6 years) were reviewed. Median follow-up was 9 months (range 1-37 months). Epilepsy etiology was classified as genetic (23.7%), structural/metabolic (41%), and unknown cause (35.3%). Overall, rufinamide treatment led to a median seizure frequency reduction of 59.2% from responders to baseline. Seizure reduction was greater in patients with genetic etiology compared to structural/metabolic (66.2% vs. 45.5% responders, p = 0.005). Rufinamide was discontinued in 110 (36.7%) of 300 patients: 63 (21%) due to unsatisfactory response, 47 (15.7%) due to side effects, and in 18 (6%) of those due to both. Most common adverse effects were sleepiness, vomiting, mood changes, nausea, and loss of appetite. Median time to loss of efficacy was 11.6 months (range 3-28 months). SIGNIFICANCE: Rufinamide provides satisfactory seizure reduction as an adjunctive treatment in refractory epilepsy. Results need to be interpreted in the setting of data acquisition, including inherent biases of retrospective studies. Patients with a known genetic etiology may have better responses than patients with structural/metabolic etiology.

Variation in neuroimaging and outcomes in patients with Sturge Weber syndrome Type III.

OBJECTIVES: Sturge Weber syndrome (SWS) is a neurovascular condition with an estimated incidence of 1 in 20,000 to 50,000 live births. SWS Types I and II involve cutaneous and ophthalmological findings, with neurological involvement in Type I. SWS Type III is exclusive to brain stigmata. Our study aims to describe the characteristics of brain MRI findings and report neuroradiological features with seizure and cognitive outcomes in patients with SWS Type III. METHODS: This is a retrospective case series examining the clinical, radiological, and cognitive characteristics of patients with SWS Type III referred to the SWS Clinic at Boston Children's Hospital. We analyzed brain MRI findings based on vascular and parenchymal features. Clinical and cognitive outcomes were based on a validated assessment tool in this population (Neuroscore). RESULTS: This dedicated case series of patients with Type III SWS from a single center identified ten patients. All patients had classic stigmata indicative of SWS. Two distinct radiological phenotypes were found, one characterized by more pronounced deep venous enlargement, and the other, with more pronounced parenchymal abnormalities. There was heterogeneity in seizure presentation and outcome. Earlier age of onset and seizures predict more severe outcomes, as seen in classic SWS. CONCLUSION: We could not find significant divergence in outcomes between patients with differing neuroimaging phenotypes. These results raise the question of whether the two distinct radiological phenotypes found in SWS Type III are reflective of different disease entities, with underlying genetic heterogeneity. These results suggest the need for larger, multi-center natural history studies.

Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep.

PURPOSE: Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS. METHODS: We enrolled patients from our video-electroencephalography (EEG) monitoring unit with CSWS and with overnight EEG studies with at least one overnight assessment per year over a minimum period of 3 years. We studied clinical presentation and electroencephalographic features. We calculated the (1) spike-wave percentage (SWP) as the percentage of 1-s bins containing at least one spike-wave complex and (2) spike frequency (SF) as the number of spikes per 100 s. KEY FINDINGS: Nine children (six boys) met the inclusion criteria during a 15-year period. Seven (78%) had an abnormal development prior to the epilepsy onset, and in two (22%) seizures were the only presenting symptom. Median age at epilepsy onset was 2 years (range 2 days to 4 years), at neuropsychological regression 5.1 years (4-7.7 years), and at seizure freedom 8.6 years (6.5-11.4 years). Median duration and range of clinically relevant stages were as follows: dormant stage (birth-epilepsy onset median 2 years, range 2 days-4 years), prodromal stage (epilepsy onset-neuropsychological regression 3.9 years, range 0.9-7.7 years), acute stage (neuropsychological regression-seizure freedom 2.9 years, range 2.1-6.6 years), and residual stage (after seizure freedom). Seven patients (78%) had a structural lesion on neuroimaging. At last follow-up (median 11.4 years, range 7.2-20.3 years), eight patients (89%) were receiving antiepileptic treatment, and all patients had residual neurocognitive deficits. During the acute stage, SWP was <85% in 13 (42%) of 31 assessments, and after seizure freedom, 3 of 5 patients (60%) had SWP >85%. Evolution of electroencephalographic patterns included increasing-decreasing, continuously elevated, and fluctuating patterns (33.3% each). There was good correlation between SWP and SF (Spearman correlation-coefficient = 0.942; p < 0.0001). SF, which can exceed 100%, reflected changes in electroencephalography pattern in more detail than SWP, which cannot exceed 100% and therefore has a ceiling effect. SIGNIFICANCE: Our series systematically studied the age of occurrence of the significant clinical events. These may assist in defining clinical stages, which can provide a useful framework for future clinical trials in patients with CSWS. The severity of the epileptiform discharges on EEG did not always correlate with seizure frequency and severity; epileptiform discharges could be prominent after seizure freedom and fluctuated along the course of the disease. The values of SWP and SF correlated well, but SWP based on 1-s bins has the potential disadvantage of a ceiling effect.

Interictal Connectivity Revealed by Granger Analysis of Stereoelectroencephalography: Association With Ictal Onset Zone, Resection, and Outcome.

BACKGROUND: Stereoelectroencephalography (sEEG) facilitates electrical sampling and evaluation of complex deep-seated, dispersed, and multifocal locations. Granger causality (GC), previously used to study seizure networks using interictal data from subdural grids, may help identify the seizure-onset zone from interictal sEEG recordings. OBJECTIVE: To examine whether statistical analysis of interictal sEEG helps identify surgical target sites and whether surgical resection of highly ranked nodes correspond to favorable outcomes. METHODS: Ten minutes of extraoperative recordings from sequential patients who underwent sEEG evaluation were analyzed (n = 20). GC maps were compared with clinically defined surgical targets using rank order statistics. Outcomes of patients with focal resection/ablation with median follow-up of 3.6 years were classified as favorable (Engel 1, 2) or poor (Engel 3, 4) to assess their relationship with the removal of highly ranked nodes using the Wilcoxon rank-sum test. RESULTS: In 12 of 20 cases, the rankings of contacts (based on the sum of outward connection weights) mapped to the seizure-onset zone showed higher causal node connectivity than predicted by chance ( P ≤ .02). A very low aggregate probability ( P < 10 -18 , n = 20) suggests that causal node connectivity predicts seizure networks. In 8 of 16 with outcome data, causal connectivity in the resection was significantly greater than in the remaining contacts ( P ≤ .05). We found a significant association between favorable outcome and the presence of highly ranked nodes in the resection ( P < .05). CONCLUSION: Granger analysis can identify seizure foci from interictal sEEG and correlates highly ranked nodes with favorable outcome, potentially informing surgical decision-making without reliance on ictal recordings.

A novel mutation in the aristaless domain of the ARX gene leads to Ohtahara syndrome, global developmental delay, and ambiguous genitalia in males and neuropsychiatric disorders in females.

PURPOSE: ARX, the aristaless-related homeobox gene, is implicated in cerebral, testicular, and pancreatic development. ARX mutations are associated with various forms of epilepsy, developmental delay, and ambiguous genitalia in humans. A mouse model that recapitulates X-linked lissencephaly with ambiguous genitalia (XLAG) is far from elucidating the substrate for phenotypes that different ARX mutations cause. Moreover, despite phenotypic pleomorphism associated with X-linked dominant ARX mutations, heterozygous female carriers have not been thoroughly studied. Reviewing records of patients with ARX mutations, infantile epilepsies, and psychomotor retardation, we analyzed a family harboring a novel ARX mutation with different phenotypes in males and females, including Ohtahara syndrome. METHODS: Children's Hospital Boston patient records were retrospectively screened for patients with infantile epileptic encephalopathies who underwent ARX sequencing based on clinical suspicion. Identified families were analyzed for genetic and neuropsychiatric phenomena. KEY FINDINGS: The proband was a male with Ohtahara syndrome, ambiguous genitalia, psychomotor delay, and central nervous system dysgenesis due to a novel ARX mutation in exon 5, causing a frameshift in the aristaless domain. Heterozygous females demonstrated neurocognitive/psychiatric phenomena including learning difficulties, anxiety, depression, and schizophrenia. SIGNIFICANCE: This is the first reported case of Ohtahara syndrome with abnormal genital and psychomotor development in the setting of this novel ARX mutation in exon 5. Based on the unique phenotype of the proband and on the presence of heterozygous females with neurocognitive/psychiatric ailments, this study describes the potential roles for ARX mutations in epilepsy and neuropsychiatric disease, underscoring the importance of ARX in interneuron development, cerebral electrical activity, cognition, and behavior.

Electroencephalography in clinical epilepsy research.

Electroencephalography (EEG) remains central to the investigation of epilepsy. This review discusses two clinical problems at the temporal extremes of neurophysiologic recording: evaluation of the clinical significance of individual spike discharges in benign epilepsy of childhood with centrotemporal spikes (BECTS), and prolonged (several days) continuous EEG monitoring in the ICU. BECTS is misdiagnosed often, and probably mis-treated often as well. Though the long-term outcome is usually excellent, it remains unclear whether the individual epileptiform discharges have a clinical effect. Answering this question is difficult, in part because of the natural evolution of the epilepsy and its different appearance depending on wakefulness or sleep state, and also due to substantial methodologic problems in measuring short and long-term cognitive effects. Continuous EEG (CEEG) recording has grown remarkably over the last 10 years. It has proved crucial in the diagnosis of nonconvulsive status epilepticus (NCSE), especially in the ICU, given the usual lack of obvious clinical signs of seizures in most of these patients, many of whom are critically ill. Much progress has been made in agreeing on terminology for the EEG findings, but diagnosis is still complicated. More efficient and reliable technology is being developed to help process the massive amount of data captured by CEEG and make it more useful (and in a timely fashion) clinically. Still, it is not completely clear which patients should be monitored, for how long, and what is the best role for CEEG in assessing and adjusting treatment once the diagnosis has been made. Investigators are using CEEG to study "seizure burden," to help determine what are the long-term effects of nonconvulsive seizures and NCSE, and to help guide treatment and improve outcome.

Benign rolandic epileptiform discharges are associated with mood and behavior problems.

Children with benign rolandic epilepsy (BRE) experience elevated rates of cognitive, behavioral, and affective problems. Frequent epileptiform spike discharges may impair behavioral functioning. To elucidate this relationship, we evaluated associations between the EEG spike frequency index (SI) and parental ratings of psychosocial adjustment and executive functioning in school-aged children with EEGs typical of BRE. Twenty-one children (6-12 years) participated. Parents completed validated questionnaires at a median of 5 months (range: 1-8) after a routine outpatient EEG. The EEG SI was calculated for wakefulness and sleep. The strength of association between the SI and behavioral variables was evaluated by simple and multivariate correlation. Higher awake and sleep SIs were associated with more symptoms of depression (P<0.001), aggression and conduct problems (P<0.01). Higher sleep SI was associated with executive dysfunction and anxiety (P<0.05). Symptoms of hyperactivity and inattention had no correlation. Increased epileptiform activity in children with BRE may predict higher rates of mood and behavioral problems.

Infantile Hemiconvulsion-Hemiplegia and Epilepsy (IHHE) in a boy with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease due to pathogenic variants in TSC1 or TSC2 genes. In the brain, TSC is associated with multiple cortical and subcortical malformations including tubers and abnormalities of radial neuronal migration. Approximately 80% of patients develop epilepsy in the first two years of life, most often focal seizures and infantile spasms. As with all seizure disorders, systemic illness and fever can trigger a seizure, and result in status epilepticus or even refractory status epilepticus. Infantile Hemiconvulsion-Hemiplegia and Epilepsy (IHHE) is considered a subcategory of new-onset refractory status epilepticus (NORSE) and presents with hemiclonic seizures in the setting of fever, unihemispheric brain imaging abnormality and hemiparesis. Here, we present an 18-month-old boy with TSC who developed IHHE. His extensive brain malformations and neuronal hyperexcitability in peri-tuberal tissue could have predisposed him to IHHE. In addition to these factors, we postulate that another prerequisite for IHHE is likely a genetic predisposition for an excessive inflammatory response that is yet to be elucidated.

High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy.

We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.

Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive focal brain stimulation by which small intracranial electrical currents are generated by a fluctuating extracranial magnetic field. In clinical epilepsy, rTMS has been applied most often interictally to reduce seizure frequency. Less often, rTMS has been used to terminate ongoing seizures, as in instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective and safe in the treatment of EPC has not been extensively studied. Here, we describe our recent experience with rTMS in the treatment of EPC, as an early step toward evaluating the safety and efficacy of rTMS in the treatment of intractable ongoing focal seizures. METHODS: Seven patients with EPC of mixed etiologies were treated with rTMS applied over the seizure. rTMS was delivered in high-frequency (20-100 Hz) bursts or as prolonged low-frequency (1 Hz) trains. The EEG was recorded for three of the seven patients. RESULTS: rTMS resulted in a brief (20-30 min) pause in seizures in three of seven patients and a lasting (>or=1 day) pause in two of seven. A literature search identified six additional reports of EPC treated with rTMS where seizures were suppressed in three of six. Seizures were not exacerbated by rTMS in any patient. Generally mild side effects included transient head and limb pain, and limb stiffening during high-frequency rTMS trains. CONCLUSIONS: Our clinical observations in a small number of patients suggest that rTMS may be safe and effective in suppressing ongoing seizures associated with EPC. However, a controlled trial is needed to assess the safety and anticonvulsive efficacy of rTMS in the treatment of EPC.

Neuroimaging in Pediatric Epilepsy.

Pediatric epilepsy presents with various diagnostic challenges. Recent advances in neuroimaging play an important role in the diagnosis, management and in guiding the treatment of pediatric epilepsy. Structural neuroimaging techniques such as CT and MRI can identify underlying structural abnormalities associated with epileptic focus. Functional neuroimaging provides further information and may show abnormalities even in cases where MRI was normal, thus further helping in the localization of the epileptogenic foci and guiding the possible surgical management of intractable/refractory epilepsy when indicated. A multi-modal imaging approach helps in the diagnosis of refractory epilepsy. In this review, we will discuss various imaging techniques, as well as aspects of structural and functional neuroimaging and their application in the management of pediatric epilepsy.

Yield of Emergent Neuroimaging in Patients With Sturge-Weber Syndrome Presenting With Acute Neurologic Symptoms.

BACKGROUND/AIMS: Seizures, strokelike episodes, and headaches are common complications in patients with Sturge-Weber syndrome. Based on our experience, we hypothesized that patients with Sturge-Weber syndrome have frequent urgent neuroimaging studies when presenting acutely to the emergency department. In this study, we aimed to determine the incidence of acute imaging studies in this patient population and to evaluate the prevalence of findings such as acute intracranial hemorrhagic or ischemic strokes. METHODS: To determine the frequency and yield of brain imaging, we conducted a retrospective chart analysis in patients with Sturge-Weber syndrome who presented to Boston Children's Hospital with acute neurologic symptoms between 1996 and 2016. RESULTS: We reviewed 136 encounters of patients with Sturge-Weber syndrome. In 73 of 136 encounters (53.7%), patients underwent a total of 89 imaging studies, consisting of 47 head computed tomographies (CTs) and 42 brain magnetic resonance images (MRIs). Twenty-two percent of patients imaged underwent both CT and MRI scanning of the brain. Patients with strokelike episodes or headaches were more likely to be imaged compared to patients presenting with seizures (89.7% and 100% vs 34.4%, respectively). None of the neuroimaging studies showed acute hemorrhagic or ischemic strokes. CONCLUSIONS: Acute neurologic manifestations of Sturge-Weber syndrome frequently lead to urgent neuroimaging. In our cohort, there was no imaging evidence of acute hemorrhagic or ischemic strokes. In addition, emergent imaging in patients presenting with breakthrough seizures did not result in meaningful changes in management.

Compound heterozygosity with PRRT2: Pushing the phenotypic envelope in genetic epilepsies.

PRRT2 pathogenic variants have been described in benign familial infantile epilepsy, episodic ataxia, paroxysmal kinesigenic dyskinesia, and hemiplegic migraines. We describe a patient with compound heterozygous variants, infantile epilepsy with status epilepticus, paroxysmal dyskinesia and episodic ataxia. Testing revealed a pathogenic PRRT2 duplication (c.649dupC), and a likely pathogenic missense variant (c.916G>A). His presentation meets the severe phenotypic category with a combination of at least 3 neurological symptoms: seizures and status epilepticus, prolonged episodic ataxia, and paroxysmal dyskinesia. This further expands the clinical findings related to PRRT2, and suggests that compound heterozygous variants could confer a severe phenotype.

Present status of surgical intervention for children with intractable seizures.

We present a discussion of recent relevant publications in pediatric epilepsy surgery. In 1998, the Commission on Neurosurgery of the International League Against Epilepsy formed the Subcommission for Pediatric Epilepsy Surgery. Their proposed recommendations are included here. We also discuss updates on identification and selection of children with severe refractory epilepsy. Functional imaging has advanced in recent years as an important adjunct in identifying the epileptogenic zone during the preoperative evaluation. The newer imaging modalities are summarized. Routine positron emission tomography, positron emission tomography with special tracers, and single photon emission computed tomography have proven to be beneficial. Other newer investigative techniques await validation. A number of studies on postoperative outcomes over the past few years have demonstrated the benefits of early surgical treatment for selected children.

Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen's encephalitis.

Repetitive transcranial magnetic stimulation (rTMS) has been applied with variable success to terminate the seizures of epilepsia partialis continua. The rationale for using this technique to suppress ongoing seizures is the capacity of rTMS to interrupt ongoing neuronal activity, and to produce a lasting decrease in cortical excitability with low-frequency (1 Hz) stimulation. We report a case of epilepsia partialis continua in a child with Rasmussen's encephalitis, in whom seizures were transiently suppressed by 1-Hz rTMS delivered in nine daily 30-minute sessions. In this case, total ictal time was significantly reduced during stimulation, but the daily baseline seizure rate remained unchanged. Notably, the detection and quantification of this short-lived improvement were enabled by recording EEG continuously during the rTMS session. Thus, we present this case to illustrate a potential utility of combined continuous EEG recording and rTMS in seizure treatment.